June 2018 Classics Revisits Sci. Med. 2018; 5(1)
ISSN: 0796-191X Classics and Revisits in Scientific Medicine Jun 2018 Vol 5 Issue No 1
Table of contents———————————————————————————–
Back ground and Purpose———————————————————————–
Editorial Policy for Classics Revisits Sci. Med.———————————————
Editorial for Classics Revisits Sci. Med. 2018; 5(1) ————————————–
Exploratory OBSERVATIONAL and Problem Solving PRE- Experimental Study. On Achieving The Diagnosis of Probable Congenital Nephrotic Syndrome or Congenital Nephritic Syndrome Through A Retrospective Historical Charting and Chronicles OF the Earliest Timing OF the Onset OF Symptomatologies OF Oedema In Infant Children with The Triad OF Hypoalbuminaemia, Proteinurias And Oedema. (Especially Those Subsets with Steroid –Non Responsive or recidivist Oedema and Proteinuria) Is Prognostically And Prophylactically Rewarding Since Their Specific Diagnostic And Therapeutic Interventions Remarkably Differs.——————————————————————————–
A Combined evaluative Explanatory Survey With Meta-Content Analysis For Several Subsets of Periodic Paralysis. On The Occasional Very Deleterious Impact Of Transient Periodic Paralysis Overlapping With Unclassifiable Paroxysmal Events OR Chronic Fatigue Syndrome (Fibromyalgia) Supports The Use Of An Indepth Clinical Pathological Electrophysiological Evaluations Of Cases With Thyroid Dysfunctions, Migrainous Cephalgias with or without Neurological Sequelae For Compatible Features.————————————————————————-
An informative mix of education and novel Data.
Naturalistic Inquiry, Participant Observation, structured Interviews And Documentary Content Analysis in addition to Media analysis for the
Illustrative instructive Epitomes of the range/and impact of electric shock related injuries. The age gender and seasonal differential variations in the pathophysiological effects of different intensities of electric current suggests the role of environmental genetic, humoral, hormonal, metabolic, constitutional idiosyncratic factors and pathological states in the diathestic predispositions to electrical injuries and electrocutions.
Acknowledgements——————————————————————————-
CLASSICS REVISITS SCI. MED. JUNE 2018
ISSN: 0796-191X CRS [Med.] June 2018 Volume 5 Issue Number 1
The section Classics and Revisits in Scientific Medicine [CRSM] Volume 5 NO. 1 June 2018.
Classics and Revisits in Scientific Medicine
Back ground
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The intent is that CRS [Med.] could provide a fairly well effective reciprocal communicative pathway for continuing medical education development in Scientific Medicine.
The text delivers the details of good basic and clinical dermatology practice clearly and concisely .It is a unique contribution to medical specialty practice development nationally, regionally and globally, in the context of ongoing health trends. Although the current directions in health care developments were highlighted, an unpretentious emphasis to quite often unavailable advanced technological innovations and models were reasonably weighted.
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June 2018 Classics and Revisits in Scientific Medicine. Volume One.
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December 2018 5(1) Classics and Revisits in Scientific Medicine.
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June 2018 Volume One Classics and Revisits in Scientific Medicine.
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June 2018 Volume 5 Issue (1) Classics and Revisits in Scientific Medicine.
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Editorial
The role of the Scientific Editor as a gate keeper and umpire.
Scientific Editors have the most challenging, difficult and occasionally impossible jobs.
What made their work awkward are the expectations of some contributors.
This attitude was epitomized by the opinion of an unwary contributor, who when asked what do you expect from editors, said that not only do I expect all the editors to accept all my papers, accept them as they were submitted, and publish them promptly, but I also expect them to scrutinize all the other papers with the utmost care, especially those of my competitors.
Someone once said, Scientific Editors are in my opinion a lowly form of life, and with regards to belligerence were inferior to the viruses and only slightly superior to the academic deans. And then there is the story about the legendary celebrity and the Scientific Editor who lived contemporaneously and arrived to an occasion simultaneously. They were subjected to the usual initial processing and thereafter were assigned their ceremonial quarters. The legendary celebrity looked around his apartment and found it to be spartan indeed.
The Scientific Editor on the other hand, was assigned to magnificent apartment, with plush furnishings, deep pile carpets and superb appointments.
When the Legendary celebrity saw this, he went to the master of ceremony and said, perhaps there has been a mistake .I am a celebrated legend very popular and admired by all, I delayed and deferred every other engagement and invitations to attend your ceremony,
I have been assigned to a shabby quarters, whereas this lowly scientific editor has been assigned to a lovely apartment. Then the master of the ceremony answered.
Well in my opinion there isn’t anything very special about you. We have admitted over two hundred legendary celebrities in the last two years, but this is the very first scientific editor who ever made it to our ceremonial events. So we see that a scientific editor should have a hermit as a brother so that he should have somebody to look up to. It has been said that the role of the scientific editor is to separate the wheat from the chaff and then make sure that the chaff gets printed.
Besides which, the contributors should never be afraid to talk to scientific editors.
With very rare exceptions, scientific editors are overall generally nice people. Never consider them adversaries; they are on your side as a contributor. Their only goal as scientific editors , academic goal keepers and umpires is to see that the articles are well reviewed and refereed, so as to ensure that only good science gets published in an understandable language.
However, if that is not your goal as a good willed bona-fide scientific contributor, then you will be dealing with a deadly adversary indeed, whereas if you share the same goal, you will find the scientific editor to be a resolute ally, then you will be likely to receive advice that you could not possibly buy. Perhaps, the most important point to remember when dealing with scientific editors is that the scientific editor is a mediator between the contributor and the reviewers. If the contributor corresponds with the scientific editor academically and could defend their work scientifically then their chances of getting published will be considerably enhanced.
The scientific editors and the reviewers are usually on the side of the contributors, their primary function is to assist the contributors to express themselves effectively, and provide them with the assessment of the science involved. What scientific editors aim to achieve is that of ensuring that only good science gets published and will be available to the scientific world. It will be worthwhile for the contributors, if they aim to follow their guidelines as much as will be achievable. The possible outcomes of the scientific editorial process could be neatly described as declined, modify or accept. The modern metaphor for scientific editing would be a car wash through which all cars headed for a goal must pass. Very dirty cars were turned away, dirty cars emerge much cleaner, whilst clean cars were little changed.
Having spent the proverbial more years than I could remember as a contributor, and an associate scientific editor and scientific editor to several notable and visible mainstream, newsletters, Journals and the Grey Medical Literature. I am totally convinced that, were it not for the goal keeper or umpire role so valiantly maintained by scientific editors, that our scientific journals would soon be reduced to unintelligible gibberish garbage.
No matter how unkindly or unthoughtfully you think that you were treated by the scientific editors, try somehow to maintain a bit of sympathy for members of that benighted profession.
I recall with nostalgia, when a couple of years ago I wrote one of my favorite literary mentors equally a scientific editor in chief of a notable medical scientific journal and informed him of my flair, wish and desire to oversee the editing of a multispecialty medical scientific journal, he replied and wrote me a letter dated 15th June 2012, Dear Scientific Editor in Chief to be, I note what you say about your aspiration to edit a scientific medical Journal.
I am sending you by this mail an imaginary twelve multi-chambered revolver, load it and fire every one shot into your head. You will thank me very profusely after you get to life beyond and learn from other editors how dreadful their job was whilst they were on earth.
I must say that I do not have all the answers, I thought I did when I was a bit younger and inexperienced. Perhaps I could trace my character developments, and reciprocal attitudes in the two way communicative pathways with contributors several years ago, when one Dr. Perseverance a veteran repeater contributor submitted to one of the associated Medical Scientific Journals I worked with a surprisingly and an unexpectedly well-written and well prepared manuscripts, his previous manuscripts were poorly written and badly organized messes. After a review of his new manuscript, the chief-editor replied and wrote, Dear Dr, Perseverance, we are happy to accept your superbly written paper for publication, in our Journal, however, before we move on and complete the publication process, I just couldn’t help adding, please could you tell me, who wrote it for you?
Dr.Perseverance replied and answered, Dear Editor-in- Chief, I am delighted that you found my, manuscript acceptable, this time, and that its publication will soon be underway, but before I go on to celebrate with my associates, I eagerly wish, that you could tell me, who read it for you this time? [1]-
This issue of the classics and revisits in scientific medicine proffers several Collegiate Academic Transactions. Through serial Editorial Symposia:
An Editorial for congenital nephrotic syndrome in the Classics and Revisits in Scientific Nephrology dissects the seminal aspects of Congenital Nephrotic Syndrome entitled an
Exploratory OBSERVATIONAL and Problem Solving PRE- Experimental Study. On Achieving The Diagnosis of Probable Congenital Nephrotic Syndrome or Congenital Nephritic Syndrome Through A Retrospective Historical Charting and Chronicles OF the Earliest Timing OF the Onset OF Symptomatologies OF placentomegaly and effusive disease in neonates and Infant Children with The Triad OF Hypoalbuminaemia, Proteinurias And Oedema. (Especially Those Subsets with Steroid –Non Responsive or recidivist disease) Is Prognostically And Prophylactically Rewarding Since Their Specific Diagnostic And Therapeutic Interventions Remarkably Differs. ————————————————————–
CNS which implies Nephrotic syndrome in the first three months of life, is most common in the Nordic region especially Finland, where the pathology is described as microcystic disease. A nephrotic syndrome is called congenital if it presents within the first three months of life, this definition is based on the natural history of the Finnish type, the most common type of nephrotic syndrome in new born infants. Congenial nephrotic syndrome is a rare uniformly fatal renal disorder which is often observed in multiple siblings in a single family.An autosomal recessive inheritance has been suggested on the basis of the 1973 article on this theme by Burke & Others, on Familial nephrotic syndrome.
Other types with minimal lesion histology, diffuse Mesangial sclerosis or related to the tubulo-interstitial nephritis of congenital syphilis were occasionally described and reported sporadically in the global medical literature.
These Finnish types are now more frequently seen in the descendants of other Caucasian ancestry and the condition is inherited in an autosomal recessive fashion.
Oedema is noted in the first weeks of life with placentomegaly and prematurity being common precursors. There is no specific treatment but transplantation could be considered if survival is longer than eighteen months to twenty four months.
Elevated amniotic fluid alpha fetoprotein, if the fetus is affected, allows prenatal diagnosis.
Reviews on the Aetiopathogenesis of Congenital Nephrosis suggests that
For a long time Its precise pathogenesis was unknown .A fundamental immunologic incompatibility between the mother and her affected infant is perhaps responsible, since mothers reject skin grafts of these nephrotic infants more rapidly than control mothers reject grafts of normal infants. Evidence of the immune injuries to the kidneys relates to the finding of gammaglobulin and complement components on the glomerular loops. This was buttressed by the 1972 data from the genetic and immunological studies in congenital nephrosis by Conwald and McIntoch.
With regards to the Finnish Type of Congenital Nephrotic Syndrome, the Clinical Presentation and Laboratory Findings for The Congenital Nephrotic Syndrome Finnish Type (CNF) infers that the incidence of congenital nephrotic syndrome was estimated at about 1.2 per 10,000 births in Finland. Epidemiological data on this theme was provided by Huttunen from his scholarship on congenital nephrotic syndrome of Finnish type following a study of 75 patients in 1976.
Low birth weight with an obstetrics history of large placenta, wide cranial sutures, delayed ossification, and oedema are commonly noted at birth .The edema, however, may be apparent only after the first few weeks or months of life.Anarsarca follows, and the abdomen is distended by ascites .
Congenital Nephrotic Syndrome should be suspected if there is a history of Congenital Nephrotic Syndrome in a sibling, hydrops fetalis or oedema of the placenta (i.e a placental weight of more than twenty five percent) birth weight or an elevated alpha-fetoprotein or total protein concentration in the amniotic fluid.
Huttunen in 1976, remarked that since the disease begins in utero in all patients, an increased alpha-fetoprotein more than ten standard deviations above the mean amniotic fluid concentration during the second trimester) is a reliable indicator of the disease.
The natural history of the disease is based on experience before the availability of renal transplantation in young patients. Histriographically, several natural history data on CNF exists, Huttunen in 1976, Huttunen, Vehaskari, Vihikari et al in 1980 and Norio and Rapola’s scholarships data on .Congenital and infantile nephrotic syndromes in the .Genetics of kidney disorders by Bartsocas in 1989.
The mean gestational age was thirty six and half weeks +-(one and half weeks) weeks (mean +-SD) and about three in five of the infants were premature of less than thirty seven completed gestational age.
Many of the infants were small for gestational age (SGA), especially those that attained a gestational age of or above thirty seven completed gestational age.
Massive proteinuria associated with typical nephrotic serum protein electrophoresis and hyperlipidaemia is the rule.Haematuria is not uncommon.
If the patient lives long enough, progressive renal failure occurs. Most affected infants succumb to infections at the age of a few months.
In some patients, the typical signs of nephrotic syndrome such as oedema, proteinuria, and hypoalbuminaemia did not develop until the third month of life.
The evolution of the disease was not affected by the administration of steroids or cytotoxic medications. Complications included severe failure to thrive and ascites in all patients, severe bacterial infections in about four out of five cases, pyloric stenosis in one in eight cases, and thrombotic events in about one of ten cases. .An increase in P-creatinine or Blood Urea Nitrogen (BUN) was observed in approximately one of five of the patients, but none had frank ureamia.
One-half of the patients died by the age of six months, and all of them by four years of age. The immediate cause of death appeared to be infection in one three cases
Autopsy revealed thrombi in large vessels in about one in five cases .However the survival rates appears to be getting more and more better because of intensive interventions.
The Laboratory Features For The Congenital Nephrotic Syndrome Finnish Type (CNF)Indicates that the proteinuria which was initially very selective and usually almost entirely albumin as a result of increased permeability of the glomerulus only for small proteins, increases progressively and becomes nonselective, corresponding to an increased filtration and sieving co-efficients and to tubular damage.
In 1980, Proteinuria in congenital nephrotic syndrome of the Finnish type was tackled by Huttunen , Vehaskari and Vihikari et al. Data from previous and ongoing studies depict that the chemical pathological profile is significant for low serum albumin concentration and total thyroxine concentration as a result of low thyroxine binding globulin, a normal or mildly elevated P creatinine and hyperlipidaemia.
Ultrasonography reveals enlarged kidneys, increased echogenicities of the renal cortex compared to the liver and the spleen, decreased differentiation between the renal cortex and the renal medulla, and poor visualization of the pyramids.
The ultrasonic features of the congenital nephrotic syndrome of the Finnish type. Was discussed in 1989 by Lanning, Uhari and Kolivanen K, et al.
Tubular dilatations may be misinterpreted as due to other causes of cystic disease, including Autosomal Recessive Polycystic Kidney Disease. [ARPKD]
In addition to other scholarship endvours by Bratton, Ellis and Seibert on the Ultrasonic findings in congenital nephrotic syndrome in 1990.
The diagnosis is confirmed at renal biopsy.
The Histopathological Findings in Congenital Nephrotic Syndrome. Finnish Type (CNF) demonstrates that The kidneys are pale and large and may show microcystic dilatations of the proximal tubules and glomerular changes. The latter consists of proliferation, crescent formation, and thickening of capillary walls.
Although the basic defect in congenital nephrotic syndrome is unknown, the pathologic findings are characteristic and pathognomonic.
Glomerular changes were seen by scanning electron microscopy in human fetuses at thirteen to twenty four weeks. of gestational age. In 1983 Atiuo-Harmainen and Rapola seminally discussed and disseminated their data on the thickness of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type.
Renal biopsy in infancy reveals irregularities of the glomerular basement membranes and thinning of the lamina densa. According to this data of Atiuo-Harmainen and Rapola followed by fusion of the epithelial cells foot processes, all of which were similar to the findings in minimal- change, steroid-sensitive nephrotic syndrome.
On light microscopy, the mature glomeruli initially typically show only minimal abnormalities, including mild mesangial hyper-cellularity and an increase in mesangial matrix.
Immature-appearing glomeruli demonstrates a dilated urinary space surrounding a small glomerular tuft .Progressive changes include obliteration of capillary loops ,and glomerlar hyalinization .Immune deposits become visible by electron microscopy within the mesangium only at late stages of the disease.
Except in the early stages, the biopsy frequently shows dilated tubules from both proximal and distal origin, such as was seen in microcystic disease .Although these cystic changes were used by some neonatologists as diagnostic criterion, they were not pathognomonic and have caused some confusion in the differential diagnosis.
Although the aetiology of the tubular dilatation is unknown, it has been attributed to heavy proteinuria.
Following the immnohistochemical and ultra structural studies of Rapola, Sariola and Ekblom on the .Pathology of fetal congenital nephrosis: in 1984.
Progressive interstitial fibrosis and tubular atrophy develop, the latter is well correlated with increasing proteinuria.
This aspect was confirmed by Huttunen in his 1976 scholarship entitled congenital nephrotic syndrome of Finnish type: study of 75 patients.
On the Treatment and Prognosis for the Congenital Nephrotic Syndrome Finnish Type (CNF)
Although supposedly, routine therapeutic interventions for nephrosis has nothing to offer. Prevention and effective management of urinary tract infections are important, immunosuppressives such as cyclosporine A appeared to extend renal function for a period.
Infants with congenital nephrotic syndrome require intensive management, which includes repetitive administration of albumin and diuretics for ascites, oral and parenteral hyper- alimentation and the treatment of multiple complications. Chronic renal insufficiency develops between the sixth and the twenty third months of life
As a consequence most patients eventually receive dialysis whilst awaiting transplantation.
All reported infants treated before the availability of renal transplantation died, mostly of infection.In one report, of the patients who received renal transplantation, the twenty four months patient and graft survival rates were eight in ten and seven in ten respectively.
Recurrence of nephrotic syndrome was not observed after transplantation. Most infants had a normal or accelerated growth, although the mean height remained significantly lower than normal. Although well over ninety percent had delayed psychomotor development at the time of transplantation, marked improvement was evident twelve months after, and about eighty percent of the surviving children had normal school and social performance.
Disappointingly, even though some infants with congenital nephrotic syndrome were found to have minimal change disease on biopsy, the application of corticosteroid and cyclosporine A therapy proved unrewarding.
However, thereafter pharmacotherapeutic interventions with Indomethacin and Captopril .in addition to other prototypes ACE inhibitors were tried with noteworthy success, in this way the disease progressions were thought to be attenuated and several candidates were assisted from progression to renal transplantation.
The exposition on the other causes of congenital nephrotic syndrome and its differential diagnostic considerations other than Congenital Nephrotic Syndrome of the Finnish Type. (CNF) depicts that several pathological and syndromic entities were associated with congenital nephrotic syndromes. An increase in alpha fetoprotein may be observed in these conditions, but this is far less consistent than that which was observed in frank Idiopathic congenital nephrotic syndrome.
Although therapy with corticosteroids and cytotoxic agents invariably has proven ineffective, specific therapy may be available for some subsets such as those related to the congenital TORCHES Complex infections. Classification of a patient into one of the major entities on the basis of aetiology or idiopathy may not be possible, hence such cases were denoted as unclassifiable or unclassified. If the Congenital Nephrotic Syndrome tantamount to Diffuse Mesangial Sclerosis and Its Other Differentials of The Congenital Nephrotic Syndrome Finnish Type (CNF) and The Drash Syndrome related Congenital Nephrotic Syndrome were Compared and Contrasted. It could be appreciated that Congenital Nephrotic Syndrome tantamount to Diffuse Mesangial Sclerosis is the second most common cause of congenital nephrotic syndrome, and it appears to be a heterogeneous group.
According to the 1989 data of Norio and Rapola on Congenital and infantile nephrotic syndrome edited by Bartsocas as book chapters of Genetics of kidney disorders, the onset may be as late as one year of life. In contrast to Congenital Nephrotic syndrome of the Finnish type, Chronic Renal Failure (CRF) develops rapidly in these patients, and is the major cause of demise in the absence of renal replacement therapy or renal transplantation.
Renal venous thrombosis is a frequent complication .In other instances, in most families, diffuse
Mesangial sclerosis was genomically determined and was transmitted as an autosomal recessive trait.
Histologic examination of the glomeruli demonstrates mesangial cells embedded in a periodic acid Schiff positive and silver-positive fibrillar network occluding the capillaries.
Although the associated renal tubular changes for this subset were similar to those in the CNFHowever, the accompanying renal interstitial fibrosis for this subset were more pronounced than that encountered in CNF.
The Drash Syndrome related Congenital Nephrotic Syndrome was described following the observation that in some infants, diffuse mesangial sclerosis is part of a Drash syndrome, which also includes ambiguous genitalia, most often male pseudo-haemophrodism (i.e. 46XY karyotype) and Wilms tumour.
A detailed review on the nephropathy associated with male pseudohaemophroditism and Wilms tumour (Drash syndrome) as a distinctive glomerular lesion with report of ten cases was provided by Habib, Sariola and Gubler et al in 1985.
Patients with the Drash syndrome present between two weeks to thirty-three months of age with or without nephrotic syndrome, sometimes haematuria, often arterial hypertension and progressive Chronic Renal Failure leading to End Stage Renal Disease within a few months to two years from the onset. Several patients have presented with incomplete forms of Drash-Syndrome (i.e. only two of the three signs of the triad. In some Dennis-Drash Syndrome, CNF presents in the setting of a child with Wilms’ tumour and hemi hypotrophy without pseudo-haemophroditism.
With regards to Congenital Nephrotic Syndrome related to Congenital Infections,
Several authors inferred that nephrotic syndrome due to congenital infection was most commonly seen in congenital syphilis. Several histriographic data on this theme exists,
In 1961, Papaioannou , Asrow and Schuknell implicated .Nephrotic syndrome in early infancy as a manifestation of congenital syphilis. .
Where as in 1973, Wiggelinkhuzen, Kaschula and Uys et al approached congenital syphilis and glomerulonephritis with evidence for immune pathogenesis.
In which case the lesion was characterized by epimembranous or proliferative glomerlopathy, with diffuse deposits of gamma-immunoglobulin and treponemal antigen along the glomerlar capillaries and sub-epithelial electron dense deposits.
The condition responds remarkably well to the application of the penicillomic acid derivatives. The congenital nephrotic syndrome associated with congenital toxoplasmosis is also possible but less common than that tantamount to congenital syphilitic leutic disease.
.Classic data on .Congenital nephrotic syndrome associated with congenital toxoplasmosis was presented by Shahin, Papadopoupou and Jenis in 1974.
A Parisian scholarship by Couvreur ,Allison and Coccon-Gibod L,et al. Investigated and discussed the Kidneys and toxoplasmosis in 1984.Entiltled « Rein et toxoplasmose. », the lesion is characterized by the deposition in the glomeruli of immunoglobulins, complement and Toxoplasma gondi antigen and antibody complexes. It may respond to the administration of pyrimethamine, sulfadiazine and steroids.
Although case reports of congenital nephrotic syndrome in association with congenital cytomegalovirus infection exists, it was inconclusive whether or not the nephrotic process was mediated by or related to the infection, incidentally, co-incidentally, epiphenomenally or not.
In 1986, Neonatal cytomegalovirus infection with pancreatic cystadenoma and nephrotic syndrome was reported and discussed by Amir, Hurvitz and Neeman et al.
Also, Congenital Nephrotic Syndrome related to other miscellaneous aetiological Factors have been described,
Some cases of syndromic and non-syndromic dysmorphisms were associated with congenital nephrotic syndromes, such dysmorphic features included, primary microcephalies related to Cornelia de Lange Syndromes, The Carpenters syndrome,etc, bupthalmos(congenital glaucoma) or disturbances of neuronal neuroblasts migrations including but not confined to lissenencephaly, cortical dysplasias and the pachygyrias
Congenital microcephaly, hiatus hernia and nephrotic syndrome in an autosomal recessive syndrome was reported as Birth defects in 1976 by Shapin, Duncan and Fansworth et al.
Robain and Deonna in 1983 included Pachygyria and congenital nephrosis as an association of disorders of migration and neuronal orientation.
This associational entity was further strengthened in 1986 by the scholarship investigations of Palm, Hagerstrand and Kristofferson et al on the theme entitled the Nephrogenesis and disturbances of neuronal migration in male siblings as a new hereditary disorder.
Transient cases of congenital nephrotic syndrome have been described related to maternal transmission.
Lagrue , Braneller and Niauder et al in 1991,dwelt on the Transmission of nephrotic syndrome to two neonates and its spontaneous regression.
CNS was also related to mercury intoxications (minimata disease.) or the yellow nail patella syndrome associated with lymphoedema congenita.
In 1970; Simila, Vesa and Wasz-Hockert discussed the Hereditary onycho-osteodysplasis (the nail-patella syndrome) with nephrosis- like renal disease in a new born boy.
Case reports of one three month old infant with infantile SLE who reportedly had steroid-responsive membranous glomerulopathy and other instructive cases were available.
In 1979, Ty and Fine presented Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities.
The interventions for these secondary Nephrotic syndromes will be contingent on managing the associated primary pathological processes.
Exponentially, several informative novel genetic data on CNS are getting increasingly more and more available. [2]-
The Classics and Revisits in Scientific Neurology presents
A Combined evaluative Explanatory Survey With meta-Content Analysis for several Subsets of Periodic Paralysis on the Occasional Very Deleterious Impact of Transient Periodic Paralysis Overlapping With Unclassifiable Paroxysmal Events Or Chronic Fatigue Syndrome (Fibromyalgia) Supports The Use Of An Indepth Clinical Pathological Electrophysiological Evaluations Of Cases With Thyroid Dysfunctions ,migranous cephalgias with or without neurological sequelae for Compatible Features.
and secondarily aims to analyse the Research question, hypothesis and paradigm of achieving a distinction for the conundrum and continuum from hypokalaemic through normokalaemia to hyperkalemic Periodic Paralysis, suggests the need to consider normokalaemic periodic paralysis as an intermediate mosaic of the two extremes, which implies that serum potassium levels should not be the sole criteria for inclusion or exclusion of compatible cases.
Traditionally, periodic paralysis (PP) is a rare autosomally inherited genetic disease leading to muscle weakness ,paresis or paralysis .Its clinical impact is spectral ranging from non-incapacitating occasional muscle weakness with ambulatory difficulties to permanent muscle decimation leading to a fatal respiratory muscle paralysis. It usually presents following common triggers such as cold, heat, unduly high carbohydrate meals, fasting state related hypoglycaemia, stress, emotional activities, excitement in addition to unduly vigorous activities.
At the molecular level, the underlying defects were skeletal muscle cell membranes ion channels malfunctions allowing electrically charged ions to leak in and out of the muscle cell, causing them to depolarize and become excited( a form of channelopathy) It could be hyperthyroidism related or associated (thyrotoxic (PP)
In hypokalaemic (PP) Potassium leaks into the muscle cells from the blood stream, it could interact with a co-existing or epiphenomenal genetically inherent abnormalities in calcium channels in muscle cells, occasionally with sodium /potassium channels.
In hyperkalaemic Periodic Paralysis (PP) (Adynamia Episodica Hereditaria) potassium leaks out of the cells into the blood stream and interacts with genetically determined abnormalities in sodium channels.This form is usually accompanied by Paramyotonia congenita, the primary symptom of Paramytonia is muscle contractures which develops during activities .Also similarly Paramyotonia congenita attacks may also be triggered off by hypokalaemia.
Usually, it manifests as sudden collapse following prolonged standing, in public places, or it may be occupationally related.
The diagnosis of periodic paralysis were unusually difficult, with parents often reporting many futile efforts of several years with misdiagnosis and interventions with worsening symptomatologies.Part of this may be due to the fact that unclassifiable paroxysmal events were present in up to half of the cases with overlapping symptomatologies such as migranous cephalgias, speech difficulties, visual, auditory tactile and multisensory auras .Diagnostic accuracy was confounded and compounded by the facts that DNAs testings were available and achievable for only some common gene mutations
EMG results were normal except during attacks, however a properly performed exercise –EMG (compound Muscle Test) in the appropriate clinical setting could provide an accurate diagnosis in most instances. Most cases will function fairly well with appropriate pharmacotherapy, environmental manipulations and lifestyle modifications.
The onset of hyperkalaemic periodic paralysis is in childhood, whereas the ones of the hypokalaemic type is in early childhood to adulthood (one to twenty five years of age),although this anecdotal concept has been challenged, the serum potassium levels do not necessarily have to range outside the normal limits to cause serious life threatening paralysis .Indeed against its classification schemes, these clinical features do not usually fit in neatly into hyperkalaemia or hypokalaemia and as such, they should not be managed categorically.
In both these cases, the total body potassium is usually normal, but it just in the wrong place .The gene mutation, the ion channel affected and the amount of genetic change or expression could have significant impact on disability and therapeutic interventions.The progression of the hyperkalaemic Periodic Paralysis somewhat slows down towards middle age, whereas that of hypokalaemic periodic paralysis could be quite progressive and deleterious.
The hypokalaemic Periodic Paralysis were more common in males. Electrocardiographic features compatible with hypokalaemia or hyperkalaemia were more indicative of the total body potassium compared to the serum/blood potassium levels .The changes of the blood potassium levels in the secondary forms were always marked, but this was not the case in the primary forms.
Also hypermagnesaemia of any cause could be a cause of periodic paralysis.
Furthermore some genetic forms of Periodic Paralysis were associated with significant rhythm dysfunctions .Carbonic anhydrase inhibitors such as acetozolamide and dichlorophenamide were initially tried in patients with Periodic Paralysis on the basis of their kaliuretic effect for hyperkalaemic periodic paralysis and then based on serendipitously made observations, and probably because of its induction of alkalosis in hypokalaemic Periodic Paralysis. On the basis of our experience, for us Acetozolamide is probably a wonder drug. In the management of Periodic Paralysis of several aetiologies because of its modifying effects on channelopathies. It was found to increase extracellular proton concentrations which strongly inhibit ionic permeations through open calcium channels .They could also equally function by activating potassium calcium channels thereby modifying their myogenic pace setting activities.
On the essence and objective of this paper, Since we have previously identified, presented, reported and discussed other domains of primary idiopathic myopathies in addition to acquired secondary systemic paralytic myoneuropathies.This paper aims to further report unusual and severe cases of presumptive primary idiopathic Periodic Paralysis in adolescent and adult males and females managed successfully by the authors.
The employed methodology involves Case Studies with Triangulated Analytical Techniques and Methodological approach with Analysis of Empirical observations of Presentations and Document Research through the use of Structured Qualitative and Quantitative independent content analysis, of Nominal and Ordinal data from the mainstream Journals and the Grey Medical Literature.
The investigators experience with periodic paralysis in childhood were highlighted with extremely severe cases of non-familial possibly dyskalaemic, normokalaemic, normocalcaemic normonatriemic, non-diurnal idiopathic periodic paralysis cases in previously healthy females with unclassifiable paroxysmal events initially inferred as convulsive equivalents associated with non-diurnal non myotonic tachycardiac recurrent episodic severely frank tetraparetic paralytic events lasting for about twenty four hours in each instance ,
And subsets of adolescent males with a new onset recurrent episodic prolonged paraparesis with visual difficulties occasionally lasting up to a week in some instances none of the parents were consanguineously married. Good outcome measures were achieved with appropriate conventional interventions in all instances with acetozolamide, environmental and life style modifications in addition to physical therapies
The global regional literature were examined to buttress the import of achieving the diagnosis at the milder and earlier spectra of the defect, plausible diagnostic, therapeutic and prophylactic options were proffered and discussed.
This paper highlights cases at the upper range of the defect, given the spectral nature of the defect, it is likely that there are still many defects out there at the milder spectrum with minimal expressivities which could be therapeutically
amenable at this stage compared to when progressed to decimated myopathic paralysis. This is one aspect where basic evaluations with in-depth comprehensive historical and clinical evaluation, applying commonly available inclusive biochemical profile, electrocardiogram and exclusive neuroimaging a tentative diagnosis could be achieved, fortunately this condition is amenable to commonly available diuretics/salts ,medical interventions and specific/generic deterrent options .
A review of the literature compares these cases with others described previously in the global medical literature and offers a systematic and standardized diagnostic and therapeutic approach and strategies for the more enigmatic and difficult cases.
The Transient and Periodic Paralysis as a group of neuromuscular disorders is characterized by attacks of acutely developing paralysis, which spontaneously recover to complete normality, usually within a few hours. These conditions the periodic paralysis cause recurrent attacks which are usually associated with alterations of serum potassium concentrations .The clinical features like its inherited nature achieves the distinction between these forms from the acute and subacute monophasic conditions where the recovery is much slower such as the inflammatory, immune or neoplastic related dermatomyositis -polymyositis syndromes and electrolyte imbalance related paralysis or paresis including the other forms of potassium related disturbances in itself. They also differ from the disorders of neuromuscular transmission where there is increased weakness with superadded exercise-induced fatigue.
They differ from the numerous central nervous system causes of transient loss of muscle power, which include syncope, .seizures, transient ischaemic attacks of the brain, cataplexy, hydrocephalic attacks, and idiopathic drop attacks .It is most important to realize that any cause of excessively high or low serum potassium will produce diffuse muscle paresis by an effect on the resting sarcolemmal membrane potential .Hyperkalaemia causes hyperpolarisation, preventing the end-plate potential from reaching the critical depolarization potential required to fire the muscle fibre. Hypokalaemia produces depolarization, which produces depolarization inactivation (closure of the off-gate) of sodium channels in the sarcolemmal .Conditions such as excessive potassium administration and renal failure cause hyperkalaemia; and primary hyperaldosteronism (Conn’s syndrome) and diuretic (kaliuretic) and corticosteroids therapy may cause hypokalaemia.
In contrast, the familial periodic paralysis cause attacks of considerably greater muscle weakness than expected from the change in serum potassium. In fact, some patients have paralytic attacks without change in the serum potassium concentration .These observations suggest that the serum potassium changes may be secondary to some basic abnormality in the sarcolemmal.
At least five different syndromes of transient muscle weakness have now been identified these are:[I]-Familial hypokalaemic periodic paralysis.[II]-Hyperthyroidism with hypokalaemic periodic paralysis.[III]-Familial hyperkalaemic periodic paralysis (adynamia episodica hereditaria of Gamstorp)[Iv]-Paramyotonia congenita of von Eulenberg.[v]-Normokalaemic Periodic Paralysis.
In each of these conditions, over a period of a few minutes or hours the patient develops a disorder of skeletal muscle which may vary from mild weakness of limb muscles to total paralysis and which subsides and disappears completely after a few hours or days. There are a few clinical features which suggest the exact type of periodic paralysis that is present, but generally, the diagnosis rests on determining the serum potassium level in an attack and on tests which attempt to precipitate paralytic attacks either by increasing or decreasing the serum potassium concentration. [3]-
Finally, the Classics and Revisits In Interdisciplinary Medical Themes presents An informative mix of education and novel Data from
Naturalistic Inquiry, Participant Observation, structured Interviews And Documentary Content Analysis in addition to Media analysis on Illustrative instructive Epitomes of the range/and impact of electric shock related injuries .
The environmental, age and gender differential variations in the pathophysiological effects of different intensities of electric current suggests the role of environmental,genetic,humoral,hormonal ,metabolic , constitutional idiosyncratic factors and pathological states in the diathesistic predispositions to electrical injuries and electrocutions.
This article is an informative mix of education and novel Data. On Electrical Injuries achieved through
Pre-experimental studies with Triangulated Research Methodological Approach comprising an employ of Naturalistic Inquiry, Participant Observation, structured Interviews and Documentary Content Analysis in addition to
Media analysis (news papers, magazines) films (movies) Radio, television (advertisements, news and broadcasts) and other acquired documentary informative data.
Descriptive systems for the evaluation and creation of distinctions for lightning and electric current related events were still unharmonised.there appears to be no records of adverse cardiopulmonary and cerebrovascular or myogenic events and vital end organ dysfunctions following frank, bur especially with subtle lightning events. Global demographics are lacking for policy and decision making.
This article equally aims to propose the evaluation of the following hypothesis, research questions and Paradigms and proffer complimentary mitigating measures that, Firstly, the seasonality and additive effect in electric and lightning current related injuries warrants temporal differential deterrent preventive options, slanted and weighted to the wet seasons.
Secondly, although previously electrical injuries used to be an urban cosmopolitan phenomenon, but the additive impact of the availability of electricity and multiple bodies of water in the hinterlands warrants an augmented and directed electrical and lightning injuries educational and environmental modification deterrent and preventive options.
Thirdly, with regards to electrical and lightning injuries; a little overdose may matter in some individuals with certain genetic and acquired pathological conditions because of aneurysmal formation in those with connectivopathiies such as the Elans Danlos syndromes, Marfans syndromes or Osteogenesis Imperfecta, or acquired metabolic or infective defects such as cardiovascular syphilitic leutic diseases, metabolic syndromes etc Since aneurysms occur following prolonged coagulative coaliquative necrosis of the fibromuscular medial intima of the large blood vessels especially the aorta following electrical shock injuries. Aneurysms predisposes to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries, both could cause dizzy spells.
Also, since aneurysms predispose to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries with both presenting with dizzy spells such individuals with predisposing diathesis to aneurysmal formation will need at least a non-invasive survey for the evolution of the aneurysm such as trans thoraco-abdominal ultrasound in addition to haemoglobin estimation and complete blood counts.
Similarly individuals with arrythmogenic predisposing homeostatic metabolic or structural cardiopulmonary or neurogenic dysfunctional/ diathesis will need evaluation with ultrasound, ECG and if imperative EEG.
Fourthly, in addition, Electrical and lightning injuries by causing fatty tissue necrosis could predispose to cryptogenic acute, then subacute and chronic pancreatitis with calcific fibrosis leading to a fibrocalculous chronic pancreatitis with enzymic and hormonal insufficiencies.
Finally, the stress of electric shock could lead to an irreversible diabetogenic hormone release, the enhanced impact of electrical injury in pregnancy being grave may well be related to the exacerbated humoural endocrine factors at play in pregnancy.
This review explores the wider impact or connotations of electrical injuries through the following problem solving paradigm such as the case for the position of the elderly and certain metabolic vital organ dysfunctions associated cardiopulmonary difficulties and neuropathies in this scale may warrant an enhanced anti-electric shock measures for this subsets as a group.
Therefore electrically injured patients should receive a more comprehensive evaluation for renal injuries, neurological deficits; in addition to longer term ophthalmological follow ups for cataracts. As a group patients with electric shock injuries will need longer term and more diligent follow ups.
These aspects are prophylactically, diagnostically and therapeutically unexplored but crucial concepts.
Although electrical trauma, accidents or “shock” are very common and almost everyone has been exposed to these. Severe electrical injury is a relatively infrequent but potentially devastating form of multisystem injury with high morbidity and mortality. Most electrical injuries in adults are occupationally related, whereas children encounter these injuries in the domiciliary settings. Natural electrical injury is related to lightning events, with immense and utmost morbidity and mortality.
The severity of the injury depends on the intensity of the electrical current (determined by the voltage of the source and the resistance of the victim).the pathway it follows through the victims body and the duration of the contact with the source of the current .Immediate death may occur either from current-induced ventricular fibrillation or asystole or from respiratory arrest secondary to paralysis of the central respiratory control system or due to paralysis of the respiratory muscles. Presence of severe burns (common in high voltage electrical injury), myocardial necrosis, the level of central nervous system injury, and the secondary multiple system organ failure determines the subsequent morbidity and long term prognosis .There is no specific therapy for electrical injury, and the management is somewhat generic and symptomatic. Although advances in the intensive care unit, and especially in burn care, have improved the outcome, prevention remains the best way to minimize the prevalence and severity of electrical injury.
Although frequently categorized collectively as a single entity, electrical injuries were actually spectral ranging from mild as seen with low voltage outdoor electrical injuries, through high voltage occupational injuries to lightning injuries, however in younger children an occasional in door larger household electrical injury may be associated with very deleterious consequences.
Electrical injuries, although uncommon are inevitably encountered by most clinicians. Adult electrical injuries usually occur in occupational settings, whereas children are primarily injured in the domestic domiciliary settings. The spectrum of electrical injury is broad, ranging from minimal injury to severe multiorgan involvement to death.
Injuries could result from spontaneous atmospheric electricity (lightening injuries) or generated electricity, such as household or industrial electrical currents
(electrical injuries)
Reviews on the Principles of Electricity indicates that Electrical current passing through the body generates heat, which burns and destroys tissues .Burns can affect internal tissues as well as the skin. An electrical shock could short circuit the body’s own electrical circuitry systems, augmenting their impedance, thereby inhibiting neuronal impulse transmissions or make the body to transmit impulses in an unregulated erratically inconsistent manner. This anomalous and abnormal impulse transmission could affect the predominantly myogenic organs and systems, including the cardiac muscles inciting tetany or cardiac arrhythmias which could lead to falls or cardiac arrest. It could equally affect the central nervous system causing convulsive or non-convulsive seizures, loss of consciousness, in addition to multimodal sensory abnormalities. An electrical injury occurs when a current passes through the body, interfering with the function of an internal organ or sometimes burning tissues.
More often than not the main symptom is a skin burn, but not in all instances will there be conspicuously observable injuries.
In the initial evaluation, the patient should be assessed for abnormal cardiac rhythm, fractures, dislocations, spinal cord and other injuries.
The abnormal cardiac rhythms are observed, the burns are managed, and if the burn caused extensive internal damage, intravenous fluids are given.
Where as some electrical injuries such as low to high voltage electrical injuries were somewhat partly preventable, others such as severe thundering/lightening were not. Anecdotally, electric injuries were most frequent in young adults in the second to the fourth decades of their lives, probably due to more frequent occupationally related, domiciliary or outdoor exposures. Obtaining detailed information regarding the characteristics of the involved agents has major impact on workup, management, and outcome in cases.The relevant details will include the amount of current, whether it is low voltages (one hundred and twenty to four hundred and forty Volts), High Tension ;Voltage ( more than one thousand volts), type current (alternating current)(AC) or direct current(DC) ,path-of-current ( hand-to-hand) ,hand-to-foot ,foot-to-foot ),the length of contact ( tetany ,locked-on phenomenon ),and the- events-associated with the injury (falls-,burns, water contact ) On the basis of the conductivities /resistivties of various body tissues ,the consequences of the injuries could be inferred. The resistivity of the body is estimated to be between five hundred to one thousand ohms, with bones, tendons and fat providing the most resistant to electric current.
Nerves, blood vessels, mucus membranes and muscles were the best conductors. With regards to electrical burns, the cross sectional areas were inversely proportional to tissue damage. Therefore small areas such as ball and socked or hinge joints receive maximal injuries .The current pathways plays an important role in determining injury with a vertical being more dangerous than a horizontal hand to hand pathway. Skeletal muscles were usually stimulated into tetany by currents with frequencies of forty to one hundred and ten Hetz.Most low and high tension electrical currents are AC.AC produces tetany and the locked on phenomenon although tetany occurs in all muscles that are stimulated, the flexor muscle groups are usually strongly and more predominantly affected. As a result an individual’s grasp is uncontrollably locked onto an object, which could increase the length of time that the current passes through the body and may result in greater injury. In contrast, DC current tends to produce a single large muscular contraction that often throws the child away from the source, they often involve adventurous outdoor cases as demonstrated in our editorial cases.Cardipulmonary arrests and comas were very rare, if ever observed. At low voltages AC injuries had three times the morbidity and mortality rates as DC current injuries. However, at high voltages both AC/DC produce similar effects. Electrocutions by lightening injuries were not accurately reported injuries and as such accurate statistics were lacking .Occasionally, the presentations were so subtle that the correct diagnosis may be missed entirely. Low voltage electric injuries without loss of consciousness and/or arrest were the injury patterns most described for infants and young children who bite into electrical cords of common household domestic appliances or in older children during the repair of household appliances, neurological sequelae such as global comatose encephalopathies, transverse myelitis and peripheral neuritis were the most frequently encountered defects in most cases ,cardiac arrhythmias ,myoglobunuria ,hyperkalaemia ,renal cortical, renal tubular necrosis and renal insufficiencies were commonly associated complications. Electrical energy is perceptible to the touch at a current as low as 12 mA. A narrow range exists between perceptible current and the “let go” current:, the maximum current at which a person can grasp and then release the current before muscle tetany makes it impossible to let go.The symptomatologies associated with the physico-chemical effects of electrical currents of different strengths, yields, interesting diagnostic, prophylactic and therapeutic data.
Pins, needles and Tingling sensations occur at a current between one to four milliamperes.The “let go” current for the average child is three to five Milliamperes, this is well below the fifteen to thirty Amperes of common household circuit breakers .For adults, the “let go” current is six to nine milli-Amperes, slightly higher for men than for women at a Let-go current- for women of six to eight milli-Amperes. And a Let-go current for Men of seven to nine milli-Amperes, skeletal muscle tetany occurs at sixteen to twenty milliamperes. Respiratory muscle paralysis occurs between twenty to fifty milli-amperes and ventricular fibrillation can occur at currents of fifty to one hundred and twenty milli-Amperes. These clinico-pathophysiologic correlative aspects of electrical injuries were illuminated upon in 2002. by Koumbouris in his scholarships on electrical injuries.
So in conclusion, this article is of prospective health importance, given the occasional covert presentations of some cases of electrical injuries, electrical circuitry related catastrophes must be excluded in all cases of sudden syncope and sudden cardiac arrest, especially when preceded by a scream due to involuntary contraction of the chest muscles.
Though this presumption is achieved with a case series, if these speculations were extrapolated further, it seems that there is a tendency that most cases of severe electrical injuries in teenagers and adults could lead to cardiac dysfunctions where as in children a global cerebral dysfunction may be the rule
A lot of cases could have been unreported or managed peripherally either by orthodox means or otherwise detailed information regarding the specifics of the associated injuries which has major impacts on the work ups, management and outcomes were vitally important factors in determining the outcome of these cases.
Given the occasionally hypothetical or proven paradoxical outcomes of some cases of electrical injuries a basic evaluation of all cases which could very easily be proposed in most settings is warranted which could imply the application of a long strip twelve lead electrocardiogram (ECG) or rhythm strip, complete blood counts (CBCs). In addition to biochemical profiles and muscle enzymologies .Urine examination and urinalysis for haemoglobunurias, myoglobunurias as a minimum investigative workup, because deaths from ARF were known to occur even with supposedly minor voltage incidents, also age specific deterrent options should be proffered.. [4]
This is all aimed towards the preservation and perfection of the artistic and scientific medical knowledge through the advancement of fellowship of Medicine.
With this notes we welcome you to this edition of Classics and Revisits in Scientific Medicine.
Dr.Emmnauel Onyekwelu.
Honorary Editor in Chief &Publisher.
Classics and Revisits in Scientific Medicine.
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References
[1]-Editorial for Classics Revisits Sci. Med. 2018; 5(1) ———————————–
[2]-An Exploratory OBSERVATIONAL and Problem Solving PRE- Experimental Study. On Achieving The Diagnosis Of Probable Congenital Nephrotic Syndrome or Congenital Nephritic Syndrome Through A Retrospective Historical Charting And Chronicles OF the Earliest Timing Of the Onset OF Symptomatologies OF placentomegaly, effusive disease in neonates, Infants or Children with The Triad OF Hypoalbuminaemia, Proteinurias And Oedema. (Especially Those Subsets With Steroid –Non Responsive or recidivist Oedema And Proteinuria) Is Prognostically And Prophylactically Rewarding Since Their Specific Diagnostic And Therapeutic Interventions Remarkably Differs. ——————————————————————————-
[3]-A Combined evaluative Explanatory Survey With Meta-Content Analysis For Several Subsets of Periodic Paralysis. On The Occasional Very Deleterious Impact Of Transient Periodic Paralysis Overlapping With Unclassifiable Paroxysmal Events OR Chronic Fatigue Syndrome (Fibromyalgia) Supports The Use Of An Indepth Clinical Pathological Electrophysiological Evaluations Of Cases With Thyroid Dysfunctions, Migranous Cephalgias with or without Neurological Sequelae For Compatible Features.——————————————
[4]-An informative mix of education and novel Data from
Naturalistic Inquiry, Participant Observation, structured Interviews And Documentary Content Analysis in addition to Media analysis on
Illustrative instructive Epitomes of the range/and impact of electric shock related injuries. The age gender and seasonal differential variations in the pathophysiological effects of different intensities of electric current suggests the role of environmental ,genetic, humoral, hormonal, metabolic, constitutional idiosyncratic factors and pathological states in the diathestic predispositions to electrical injuries and electrocutions.———————————————————–
ISSN: 0796-191X Classics Rev. Sci. Med. Neonatology.Vol 5, No,1
The Classics and Revisits in Scientific Nephrology VOLUME 5 ISSUE 1
Original Action Document Research and OBSERVATIONAL PRE- Experimental Studies.
Exploratory Observational and Problem Solving Pre- Experimental Study. On Achieving The Diagnosis Of Probable Congenital Nephrotic Syndrome or Congenital Nephritic Syndrome Through A Retrospective Historical Charting And Chronicles Of the Earliest Timing Of the Onset Of Symptomatologies Of Placentomegaly ,Oedema In Infant Children with The Triad Of Hypoalbuminaemia, Proteinurias And Oedema. (Especially Those Subsets With Steroid –Non Responsive or recidivist disease) Is Prognostically And Prophylactically Rewarding Since Their Specific Diagnostic And Therapeutic Interventions Remarkably Differs.
ABSTRACT
Introduction:
Congenital nephrotic syndrome is a disorder of autosomal recessive trait characterized by the development of nephrotic syndrome at the time of or shortly after birth. It occurs with highest frequency in families of Finnish ancestry or extraction Affected individuals have gross placentomegaly, low birth weight, anasarca, polycytheamia, and an initially normal GFR.Alpha fetoprotein levels are increased in amniotic fluid and maternal serum. Proteinuria is usually very heavy and very unselective.Nephrotic syndrome appearing several months after birth is usually due to other causes, especially minimal change disease or focal glomerular sclerosis. Congenital TORCHES infections spectrum could produce similar syndrome and should be excluded.Pathologically, microcystic transformation of the cortical nephrons, due to proximal tubular dilatation is found.Glomerular changes are nonspecific .Extensive effacement of the focal foot processes and sclerosis of the glomerular tufts are seen by electron microscopy.Immunoflouresence findings are either negative or nonspecific.
The course is progressive, and few patients survive the first year of life. Death is usually due to inanition, infection, or renal failure. All forms of treatment have been ineffective. A few patients may survive long enough to be considered for renal transplantation.
Methodology:
Original Action Document Research and Observational Pre- Experimental Studies.
Results:
Although previously, a lot of the pathogenesis of CNS were Enigmatic speculative and its diagnostic and therapeutic interventions empirical
Exponentially, several informative novel diagnostic and therapeutic directing genetic data on CNS are getting increasingly more and more available, globally,
However, it may take some time before this is widely available in several settings and circumstances.The need to circumvent rapid progression to end stage renal insufficiency makes the employ and application of an appropriate index of suspicion with diagnostic and therapeutic directing focused selective historical, clinical and prophylactic interventions expedient in most circumstances and settings.
Discussion:
Although Congenital Nephrotic Syndrome which implies nephrotic syndrome in the first three months of life is most common in the Nordic region especially Finland, where the pathology is described as microcystic disease,however,other types with minimal lesion histology, diffuse mesangial sclerosis or related to the tubulo-interstitial nephritis congenital syphilis were occasionally seen, described and reported sporadically in the global medical literature.These Finnish types are now more frequently seen in the descendants of other European communities and the condition is inherited in an autosomal recessive fashion.
Oedema is noted in the first weeks of life with placentomegaly and prematurity being common precursors. There is no specific treatment but transplantation could be considered if survival is longer than eighteen months to twenty four months. Elevated amniotic fluid alpha fetoprotein, if the fetus is affected, allows prenatal diagnosis.
Nephrotic syndrome is defined by the association of marked proteinuria less than one grammes per metre squared per day associated with a hypoalbuminaemia of less than two and a half grammes per deciliters. A nephrotic syndrome is called congenital if it presents within the first three months of life, this definition is based on the natural history of the Finnish type, the most common type of nephrotic syndrome in new born infants. Previously, congenial nephrotic syndrome is a rare uniformly fatal renal disorder which is often observed in multiple siblings in a single family.An autosomal recessive inheritance has been suggested on the basis of the 1973 article on this theme by Burke & Others, on Familial nephrotic syndrome. Reviews on the Aetiopathogenesis of Congenital Nephrosis suggests that.the pathogenesis is unknown .A fundamental immunologic incompatibility between the mother and the infant is perhaps responsible, since mothers reject skin grafts of these nephrotic infants more rapidly than control mothers reject grafts of normal infants. Evidence of the immune injuries to the kidneys relates to the finding of gammaglobulin and complement components on the glomerular loops. This was buttressed by the 1972 data from the genetic and immunological studies in congenital nephrosis by Conwald and McIntoch.
On the Finnish Type of Congenital Nephrotic Syndrome, the Clinical Presentation and Laboratory Findings for The Congenital Nephrotic Syndrome Finnish Type (CNF) infers the incidence of congenital nephrotic syndrome was estimated at about one and one fifth of ten thousand births in Finland. Epidemiological data on this theme was provided by Huttunen from his scholarship on congenital nephrotic syndrome of Finnish type following a study of about seventy five patients in 1976.
Low birth weight with an obstetrics history of large placenta, wide cranial sutures, delayed ossification, and oedema are commonly noted at birth .The edema, however, may be apparent only after the first few weeks or months of life.Anarsarca follows, and the abdomen is distended by ascites .
Congenital Nephrotic Syndrome should be suspected if there is a history of Congenital Nephrotic Syndrome in a sibling, hydrops fetalis or oedema of the placenta (i.e a placental weight of more than twenty five percent) birth weight or an elevated alpha-fetoprotein or total protein concentration in the amniotic fluid.
Huttunen in 1976, remarked that since the disease begins in utero in all patients, an increased alpha-fetoprotein more than 10 standard deviations above the mean amniotic fluid concentration during the second trimester) is a reliable indicator of the disease. The natural history of the disease is based on experience before the availability of renal transplantation in young patients. Histriographically, several natural history data on CNF exists, Huttunen in 1976,
Huttunen, Vehaskari, Vihikari et al in 1980
and Norio and Rapola scholarships data on .Congenital and infantile nephrotic syndromes in the .Genetics of kidney disorders by Bartsocas in 1989.
The mean gestational age was about thirty five to thirty seven completed weeks and two of five of the infants were premature of less than thirty seven completed gestational age.
Many of the infants were of small for gestational age (SGA), especially those that attained a gestational age of or above thirty seven completed gestational age.
Massive proteinuria associated with typical nephrotic serum protein electrophoresis and hyperlipidaemia is the rule.Haematuria is not uncommon.
If the patient lives long enough, progressive renal failure occurs. Most affected infants succumb to infections at the age of a few months.
In some patients, the typical signs of nephrotic syndrome such as oedema, proteinuria, and hypoalbuminaemia did not develop until the third month of life.
The evolution of the disease was not affected by the administration of steroids or cytotoxic medications.
Complications included severe failure to thrive and ascites in all patients, severe bacterial infections in eighty five percent, pyloric stenosis in twelve percent, and thrombotic events in ten percent. .An increase in P-creatinine or Blood Urea Nitrogen (BUN) was observed in approximately twenty percent of the patients, but none had frank ureamia. One-half of the patients died by the age of six months, and all of them by four years of age. The immediate cause of death appeared to be infection in one third.
Autopsy revealed thrombi in large vessels in about nineteen percent .Since this early report aggressive management has considerably improved the survival rate.
The Laboratory Features For The Congenital Nephrotic Syndrome Finnish Type (CNF)Indicates that the proteinuria which was initially very selective and usually almost entirely albumin as a result of increased permeability of the glomerulus only for small proteins, increases progressively and becomes nonselective, corresponding to an increased filtration and sieving co-efficients and to tubular damage.
In 1980, Proteinuria in congenital nephrotic syndrome of the Finnish type was tackled by Huttunen, Vehaskari and Vihikari et al.
The chemical pathological profile is significant for low serum albumin concentration and total thyroxine concentration as a result of low thyroxine binding globulin, a normal or mildly elevated P creatinine and hyperlipidaemia.
Ultrasonography reveals enlarged kidneys, increased echogenicities of the renal cortex compared to the liver and the spleen, decreased differentiation between the renal cortex and the renal medulla, and poor visualization of the pyramids.
The ultrasonic features of the congenital nephrotic syndrome of the Finnish type. Was discussed in 1989 by Lanning, Uhari and Kolivanen K, et al.
Tubular dilatations may be misinterpreted as other causes of cystic disease, including Autosomal Recessive Polycystic Kidney Disease. [ARPKD]
In addition to other scholarship endvours by Bratton, Ellis and Seibert on the Ultrasonic findings in congenital nephrotic syndrome in 1990.
The diagnosis is confirmed at renal biopsy.
The Histopathological Findings in Congenital Nephrotic Syndrome. Finnish Type (CNF)
The kidneys are pale and large and may show microcystic dilatations of the proximal tubules and glomerular changes.
The latter consist of proliferation, crescent formation, and thickening of capillary walls.
Although the basic defect in congenital nephrotic syndrome is unknown, the pathologic findings are characteristic and pathognomonic.
Glomerular changes were seen by scanning electron microscopy in human fetuses at thirteen to twenty four weeks. of gestational age. In 1983 Atiuo-Harmainen and Rapola seminally discussed and disseminated their data on the thickness of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type.
Renal biopsy in infancy reveals irregularities of the glomerular basement membranes and thinning of the lamina densa. According to this data of Atiuo-Harmainen and Rapola
followed by fusion of the epithelia; cells foot processes, all of which were similar to the findings in minimal- change, steroid-sensitive nephrotic syndrome.
On light microscopy, the mature glomeruli initially typically show only minimal abnormalities, including mild mesangial hyper-cellularity and an increase in mesangial matrix.
Immature-appearing glomeruli demonstrates a dilated urinary space surrounding a small glomerular tuft .Progressive changes include obliteration of capillary loops ,and glomerlar hyalinization .Immune deposits become visible by electron microscopy within the mesangium only at late stages of the disease.
Except in the early stages, the biopsy frequently shows dilated tubules from both proximal and distal origin, such as was seen in microcystic disease .Although these cystic changes were used by some neonatologists as diagnostic criterion, they were not pathognomonic and have caused some confusion in the differential diagnosis.
Although the aetiology of the tubular dilatation is unknown, it has been attributed to heavy proteinuria.
Following the immnohistochemical and ultra structural studies of Rapola, Sariola and Ekblom on the .Pathology of fetal congenital nephrosis: in 1984.
Progressive interstitial fibrosis and tubular atrophy develop, the latter is well correlated with increasing proteinuria.
This aspect was confirmed by Huttunen in his 1976 scholarship entitled congenital nephrotic syndrome of Finnish type: study of seventy five patients.
On the Treatment and Prognosis for the Congenital Nephrotic Syndrome Finnish Type (CNF)
Although supposedly, routine therapeutic interventions for nephrosis has nothing to offer. Prevention and effective management of urinary tract infections are important immunosuppressive such as cyclosporine A appeared to extend renal function for a period.
Infants with congenital nephrotic syndrome require intensive management, which includes repetitive administration of albumin and diuretics for ascites, oral and parenteral hyper- alimentation and the treatment of multiple complications. Chronic renal insufficiency develops between the sixth and the twenty third months of age.
As a consequence most patients eventually receive dialysis whilst waiting for transplantation.
All reported infants treated before the availability of renal transplantation died, mostly of infections.
In one report, of the seventeen patients who received renal transplantation, the two year patient and graft survival rates were eighty two percent and seventy one percent respectively.
Recurrence of nephrotic syndrome was not observed after transplantation. Most infants had a normal or accelerated growth, although the mean height remained significantly lower than normal. Although sixteen of seventeen had delayed psychomotor development at the time of transplantation, marked improvement was evident one year later, and twelve of fifteen surviving children had normal school and social performance for children ranged from early preschool age to late adolescent period.
Disappointingly, even though some infants with congenital nephrotic syndrome were found to have minimal change disease on biopsy, the application of corticosteroid and cyclophosphamide therapy proved unrewarding.
However, thereafter pharmacotherapeutic interventions with Indomethacin and Captopril were tried with noteworthy success, in this way the disease progressions were thought to be attenuated and several candidates were assisted from progression to renal transplantation.
Other causes of congenital nephrotic syndrome and differential diagnostic considerations other than Congenital Nephrotic Syndrome of the Finnish Type. (CNF)
Several pathological and syndromic entities were associated with congenital nephrotic syndromes. An increase in alpha fetoprotein may be observed in these conditions, but this is far less consistent than that which was observed in frank Idiopathic congenital nephrotic syndrome.
Although therapy with corticosteroids and cytotoxic agents invariably has proven ineffective, specific therapy may be available for some subsets such as those related to the congenital TORCHES Complex infections. Classification of a patient into one of the major entities on the basis of aetiology or idiopathy may not be possible, hence such cases were denoted as unclassifiable or unclassified. Congenital Nephrotic Syndrome tantamount to Diffuse Mesangial Sclerosis and Its Other Differentials of The Congenital Nephrotic Syndrome Finnish Type (CNF) and The Drash Syndrome related Congenital Nephrotic Syndrome Compared and Contrasted.
Congenital Nephrotic Syndrome tantamount to Diffuse Mesangial Sclerosis
The second most common cause of congenital nephrotic syndrome is diffuse mesangial sclerosis which appears to be a heterogeneous group.
According to the 1989 data of Norio and Rapola on Congenital and infantile nephrotic syndrome edited by Bartsocas as book chapters of Genetics of kidney disorders the onset may be as late as one year of life. In contrast to Congenital Nephrotic syndrome of the Finnish type, Chronic Renal Failure (CRF) develops rapidly in these patients, and is the major cause of demise in the absence of renal replacement therapy or renal transplantation.
Renal venous thrombosis is a frequent complication .In other instances, in most families, diffuse
Mesangial sclerosis was genomically determined and was transmitted as an autosomal recessive trait.
Histologic examination of the glomeruli demonstrates mesangial cells embedded in a periodic acid Schiff positive and silver-positive fibrillar network occluding the capillaries.
Although the associated renal tubular changes for this subset were similar to those in the CNFHowever, the accompanying renal interstitial fibrosis for this subset were more pronounced than that encountered in CNF.
The Drash Syndrome related Congenital Nephrotic Syndrome
In some infants, diffuse mesangial sclerosis is part of a Drash syndrome, which also includes ambiguous genitalia, most often male pseudo-haemophrodism (i.e. 46XY karyotype) and Wilms tumour.
A detailed review on the nephropathy associated with male pseudohaemophroditism and Wilms tumour (Drash syndrome): a distinctive glomerular lesion –report of ten cases. Was provided by Habib, Sariola and Gubler et al in 1985.
Patients present between two weeks to thirty-three months of age with or without nephrotic syndrome, sometimes haematuria, often arterial hypertension and progressive CRF leading to ESRD within a few months to two years from the onset. Several patients have presented with incomplete forms of Drash-Syndrome (i.e. only two of the three signs of the triad. In some Dennis-Drash Syndrome, CNF presents in the setting of a child with Wilms’ tumour and hemi hypotrophy without pseudo-haemophroditism.
Congenital Nephrotic Syndrome related to Congenital Infections.
Several authors inferred that nephrotic syndrome due to congenital infection was most commonly seen in congenital syphilis.Histriographic data on this theme exists,
In 1961, Papaioannou, Asrow and Schuknell implicated .Nephrotic syndrome in early infancy as a manifestation of congenital syphilis. .
Where as in 1973, Wiggelinkhuzen, Kaschula and Uys et al approached congenital syphilis and glomerulonephritis with evidence for immune pathogenesis.
in which case the lesion was characterized by epimembranous or proliferative glomerlopathy, with diffuse deposits of gamma-immunoglobulin and treponemal antigen along the glomerlar capillaries and sub-epithelial electron dense deposits.
The condition responds remarkably well to the application of the penicillomic acid derivatives. The congenital nephrotic syndrome associated with congenital toxoplasmosis is also possible but less common than that tantamount to congenital syphilitic leutic disease.
Classic data on .Congenital nephrotic syndrome associated with congenital toxoplasmosis was presented by Shahin, Papadopoupou and Jenis in 1974.
A Parisian scholarship by Couvreur J,Allison F,Coccon-Gibod L,et al. Investigated and discussed the Kidneys and toxoplasmosis in 1984.Entiltled « Rein et toxoplasmose. », the lesion is characterized by the deposition in the glomeruli of immunoglobulins, complement and Toxoplasma gondi antigen and antibody complexes. It may respond to the administration of pyrimethamine, sulfadiazine and steroids.
Although case reports of congenital nephrotic syndrome in association with congenital cytomegalovirus infection exists, it was inconclusive whether or not the nephrotic process was mediated by or related to the infection, incidentally, co-incidentally, epiphenomenally or not.
In 1986, Neonatal cytomegalovirus infection with pancreatic cystadenoma and nephrotic syndrome was reported and discussed by Amir, Hurvitz and Neeman et al.
Congenital Nephrotic Syndrome related to other miscellaneous aetiological Factors.
Some cases of syndromic and non-syndromic dysmorphisms were associated with congenital nephrotic syndromes, such dysmorphic features included, primary microcephalies related to Cornelia de Lange Syndromes, The Carpenters syndrome,etc, bupthalmos(congenital glaucoma) or disturbances of neuronal neuroblasts migrations including but not confined lissenencephaly, cortical dysplasias and the pachygyrias
Congenital microcephaly, hiatus hernia and nephrotic syndrome: an autosomal recessive syndrome was reported as Birth defects in 1976 by Shapin, Duncan and Fansworth et al.
Robain and Deonna in 1983 included Pachygyria and congenital nephrosis as an association of disorders of migration and neuronal orientation.
This associational entity was further strengthened in 1986 by the scholarship investigations of Palm, Hagerstrand and Kristofferson et al on the theme entitled the Nephrogenesis and disturbances of neuronal migration in male siblings: a new hereditary disorder. Transient cases of congenital nephrotic syndrome have been described related to maternal transmission.
Lagrue , Braneller and Niauder et al in 1991,dwelt on the Transmission of nephrotic syndrome to two neonates and its spontaneous regression.
CNS was also related to mercury intoxications (minimata disease.) or the yellow nail patella syndrome associated with lymphoedema congenita.
In 1970; Simila, Vesa and Wasz-Hockert discussed the Hereditary onycho-osteodysplasis (the nail-patella syndrome) with nephrosis- like renal disease in a new born boy.
Reports of one three month old infant with infantile SLE who reportedly had steroid-responsive membranous glomerulopathy and other instructive cases were available.
In 1979, Ty and Fine presented Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities.
The interventions for these secondary Nephrotic syndromes will be contingent on managing the associated pathological process.
Conclusions:
At the present, the main challenge in CNS is to identify the cause of disease for individual patients. To make a definitive diagnosis, with the exclusion of infection related CNS and maternal associated disorders, pathology, family history, inheritance mode, and other accompanying congenital malformations are sometimes, but not always useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients, however, there are still some challenges with next generation sequencing that need to be resolved in the future.
Unexplained prolonged ill heath in infants with features of renal impairment should be explored for CNS, especially those subsets with recidivists or resistant proteinuria, even if selective given the considerable overlap between the clinicopathological features of CNS and the minimal change disease, as much as would be achievable cases of unexplained sudden infant deaths should have a histopathological examination of vital end organs ,but especially the kidneys for features suggestive of CNS.
The authors propose that to circumvent ambiguity, and to improve diagnostic accuracy, although not absolutely pathognomonic,that the nosological histopathological nomenclature of microcystic disease and mesangial glomerular sclerosis should be borne in mind in the evaluation of these subsets since this is diagnostically, prognostically, prophylactically and therapeutically more encompassing and rewarding compared to a chronologically temporal one of congenital nephrotic syndrome which might implicate other nephrotic glomerulopathy such as allergic nephritis or Alports nephritis occurring equally within this period ,but without microcystic tubular dilatations.
This shortcoming warrants retrospective historical inquiry that could offer clues to the earliest onset of oedema ( especially with facial puffiness or pedal oedema which is the most clinically overt of the triad of hypoalbunaemia ,proteinuria and oedema ,this will imply reviews of child’s infant welfare health cards ,weight charts for sudden unexplained earlier weight gains and urinary colour ,frequency and volume.
Also children with nephrotic syndrome commonly present with abdominal pains which as a result of intestinal bowel oedema, ascites or SBP and respiratory difficulty due to significant pleural effusions, in addition, as a group nephrotic children are prone to a miscellaneous subset of infectious diseases especially respiratory tract and renal parenchymal infections disease spectrum which may point to a covert CNS, These aspects should be retrospectively enquired and reviewed in all children presently overtly with supposedly innocuous minimal change nephrotic syndrome.
In utero Nuchal translucency as a pointer to congenital lymphoedema and in all those cases should be evaluated for, and all cases where this is demonstrated, a search, determination and follow up for other features of congenital nephrotic syndrome should be aimed for, radiologically, pathologically and genetically.
The performance of a renal biopsy, at least amongst adults is required for the accurate diagnosis of recidivist nephrotic syndromes and for the formulation of a rational therapeutic interventional plan, however the situation is different for children who need not always be subjected to renal biopsy since careful clinical and non invasive laboratory studies could achieve diagnostic accuracy in several instances of congenital nephrotic or congenital nephritic syndrome.
Since considerations for the possibility of congenital nephritic syndrome has been under appreciated.
Blood pressure measurements, blood urea nitrogen .urinalysis and twenty four hour urinary outputs if routinely undertaken in this age group would identify those cases in the nephritic range of this congenital glomerulopathy with the opportunity for earlier intervention and the probability of a more favourable prognosis.
MAIN TEXT
The Classics and Revisits in Scientific Nephrology VOLUME 3 ISSUE 3
MAIN TEXT:
Exploratory OBSERVATIONAL and Problem Solving PRE- Experimental Study on Achieving The Diagnosis Of Probable Congenital Nephrotic Syndrome or Congenital Nephritic Syndrome Through A Retrospective Historical Charting AND Chronicles OF the Earliest Timing OF the Onset OF Symptomatologies OF placentomegaly and effusive disease in neonates, infants or Children with The Triad OF Hypoalbuminaemia, Proteinurias And Oedema. (Especially Those Subsets With Steroid –Non Responsive or recidivist disease is Prognostically And Prophylactically Rewarding Since Their Specific Diagnostic And Therapeutic Interventions Remarkably Differs.
Background, Introduction and Nomenclature:
Congenital Nephrotic Syndrome which Implies Nephrotic syndrome in the first three months of life is most common in the Nordic region especially Finland, where the pathology is described as microcystic disease. Other types with minimal lesion histology, diffuse mesangial sclerosis or related to the tubulo-interstitial nephritis and congenital syphilis were occasionally seen, described and reported sporadically in the global medical literature. These Finnish types are now more frequently seen in the descendants of other Caucasian communities and the condition is inherited in an autosomal recessive trait pattern, with a gene frequency of one in two hundred.Histriographic molecular genetic data on the heredity in congenital nephrotic syndrome produced by Norio has been in existence since 1966. [1]
The Problematic Statement and the Purpose of the Study:
The astonishing overlap, association and intertwined complications course between CNF, Congenital Lymphoedema(Milroy’s Syndrome) ,Turners Syndrome,Hypothyrodism and the Aneuploidy Trisomys,and CNS ,TORCHES complex infectious spectrum, Infantile Beriberi, Oedematous Protein Energy Malnutrition, Congenital Cardiac Defects, Myocarditis or Congenital infantile Anaemias Related Heart Failures and Malabsorptive Intestinal Failures , weights the overall diagnostic and therapeutic intents towards a high index of suspicion for an early timely specific intervention for Renal Insufficiency in those cases of CNS which could present covertly as these pathological associational entity or the congenital nephritic syndrome.
.
Methodology:
Original Action Document Research and Observational Pre- Experimental Studies.
Reviews on the Aetiopathogenesis of Congenital Nephrosis suggests that
Infections, such as congenital syphilis and toxoplasmosis are possible pathogenic agents, especially for those infants conceived and delivered in the regions between the Tropics of Cancer and Capricorn. Infection should be excluded as the cause of CNS before instituting the investigations for genetic CNS, because it is important for selecting an apposite therapeutic strategy and for long term prognosis in most cases. In the opinion of several investigators, the current main challenge for CNS is how to identify the aetiology of CNS in the individual patient. Establishing a therapeutic strategy is also another major challenge, but it is not the primary difficulty, because it depends on the cause of CNS.For this reason, the objective of most diagnostic and therapeutic protocols will be to compile a list of the possible causes of CNS in a given setting, and to identify the aetiological factors in their index cases, before the commencement of specific therapeutic interventions, and also to exclude infectious causes for CNS, such as the TORCHES infections in some patients, before the initiation of therapy.
Results and Discussions.
Congenital nephrotic syndrome (CNS), presents with heavy proteinuria, hypoalbuminaemia, hyperlipidaemia and edema with presentations in the first three months of life, besides the genetic and the idiopathic cryptogenic forms it may be caused by, associated with or related to congenital syphilis, toxoplasmosis or congenital viral infections (such as cytomegalovirus).However, overall, the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular filtration barrier in the kidneys. Congenital nephrotic syndrome as a thematic concept was approached by Jalanko in 2009.
[2]
Whereas, congenital nephrotic syndrome (CNS) defined as nephrotic syndrome (NS) presenting in the first three months of life, is a relatively rare glomerular disease globally compared with infantile nephrotic syndrome (those NS appearing between four to twelve months after birth) Nephrotic syndrome manifesting after three months of age is called childhood nephrotic syndrome.The rationale for this classification is based on the difference in aetiology.Primary nephrotic syndrome, described as the tetralogy of massive proteinuria, hypoalbuminaemia, hyperlipidaemia and oedema, is the most common glomerular disorder in children, with an incidence of approximately one to three per one hundred thousand children less than sixteen years of age.
Though a great deal of published evidence has suggested that massive proteinuria by a particular gene defect or pathogen can manifest at various ages through out the life span of individuals, the clinical features and therapeutic strategies between CNS and later-onset Nephrotic Syndrome (NS) remarkably differs. The approach of the investigators was to explore the possibility of this diagnosis in those cases of compatible congenital nephrotic syndrome on the basis of chronological age of onet,of the symptomatologies, after having excluded the differentials ,complications,comorbidities or epiphenomenal incidental, accidental or co-incidental pathologies of congenital lymphoedema(Milroy’s Syndrome) ,Turners Syndrome, Beriberi, Oedematous Protein Energy Malnutrition, Congenital Cardiac, defects ,Myocarditis or Anaemia Related Heart Failures, in addition to Malabsorptive Intestinal Failures and Hypothyrodism or Trisomy 21.
Demographic Research and the Geographical and Molecular Genetic Epidemiology of CNF of the Congenital Nephrotic Syndrome.
The aetiology of CNS is heterogeneous, although genetic defects account for the vast majority of CNS cases.
Cil, Besbas, Duzova, TOPAloglu, Peco-Antic, Korkmaz, et al.discussed the Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome in 2015. [3]
Employing an Australasian cohort In 2007, Wong characterized the biological behavioural aspects of nephrotic syndrome in children through a study and analysis of its demographic, clinical features, initial management and outcome after twelve-month follow up as part of the results of a three-year national surveillance study. [4]
Since 1998, an increasing number of genetic defects have been identified and implicated for their involvements in the pathogenesis of CNS, including but not confined to genetic mutations of NPHS1(Nephrin),
Kestila, Lenkerri, Mannikko, Lamerdin, McCready, Putaala et al in 1998 hypothesized, studied and discussed that positionally cloned gene for a novel glomerular protein –nephrin-is mutated in congenital nephrotic syndrome. [5]
The role of NPHS1 (Nephrin) mutations in the aetiopathogenesis of childhood onset nephrotic syndrome as was elucidated and discussed by Philippe, Nevo, Esquivel, Reklaityte, Gribouval, Tete, et al.that Nephrin mutations can cause childhood onset steroid-resistant nephrotic syndrome in 2008 was employed to reaffirm this stance,[6]
Geographical and Molecular Genetic Epidemiology of CNF of the Congenital Nephrotic Syndrome.
With regards to NPHS2 (Podocin) mutations in CNS, Maruyama, Iijima, Ikeda, Kitamura, Tsukaguchi and Yoshiya et al implicated .NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children in their investigations on this theme of 2003.[7]
In a similar endevour on this theme, in 2004, Weber, Gribouval, Esquivel, Moriniere, Tete, Legendre et al argued and proposed that .NPHS2 mutation analysis demonstrates genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. [8]And several molecular epidemiological scholarships on this theme exist.
In 2005,Sako , Nakanishi ,Obana ,Yata ,Hoshii ,Takahashi , et al presented and discussed the Analysis of NPHS1,NPHS2,ACTN4,and WT1 in Japanese patients with congenital nephrotic syndrome . [9]
Lipska, Balasz-Chmielewska, Wasielewski, Vetter, Borzecka, et al. approached Mutational analysis in Podocin associated hereditary nephrotic syndrome in Polish patients with a founder effect in the Kashubian population in 2013. [10]
Previous epidemiological scholarships by Mao, Zhang, Du, Dai, Gu, Liu et al identified and dissected NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome in 2007. [11]
In 2008, Hinkes, Vlangos, Heeringa, Mucha, Gbadegesin, Liu, et al hypothesized and demonstrated that .Specific Podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. [12]
At the experimental molecular level, Roselli, Heidet, Sich, Henger, Kretzler, Gubler et al demonstrated early Glomerular Filtration Defect and severe renal disease in Podocin –deficient mice in 2004. [13]
Previous investigations by Schwarz ,Simons ,Reiser ,Saleem ,Faul and Kriz et al in 2001.proposed that Podocin a raft-associated component of the glomerular slit diaphragm ,interacts with CD2AP and nephrin. [14]
With regards to the WT1, PLCE1 (NPHS3) and LAMB2 (Laminin-B2) genetic entities.Togawa, Nakanishi, Mukaiyama, Hama, Shima, Nakano, et al. reported and discussed the First Japanese case of Pierson syndrome with mutations in LAMB2.in 2013. [15]
The functional diversity of the laminins was approached by Domogatskaya, Rodin, and Tryggvason in 2012. [16]
Dietrich, Matejas, Bitzan, Hasmi, Kiraly-Borri, Lin, et al. tackled the Analysis of genes encoding laminin beta2 and related proteins in patients with Galloway-MOWAT syndrome.in 2008. [17]
In 2006, Hasselbacher, Wiggins, Matejas, Hinkes, Mucha and, Hoskins et al proposed and discussed that recessive missense mutations in LAMB 2 expand the clinical spectrum of LAMB 2-associated disorders. [18]
Also, thereafter, in 2007,Hinkes ,Mucha ,Vlangos , Gbadegesin ,Liu ,Hasselbacher ,et al.hypothesised that pertaining to Nephrotic syndrome in the first year of life that two thirds of cases were caused by mutations in 4 genes(NPHS1,NPHS2,WT1,and LAMB2) [19]
Other scholarships by Chen, Kikkawa and Miner in 2011 proposed that .A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion. [20]
Where as Debiec ,Nauta ,Coulet ,van der Burg ,Guigonis ,Shurmans , et al seminally analysed and presented the role of truncating mutations in MME gene in Fetomaternal alloimmunisation and antenatal glomerulonephritis.in 2004;.[21]
Denamur, Bocquet, Mougenot, Da Silva, Martinat, Loirat, et al demonstrated and published that Mother to-child transmitted WT1 splice-site mutation is responsible for distinct glomerular diseases. [22]Whereas ,Zenker ,Aigner ,Wendler ,Tralau , Mintefering and Fenski ,et al. reported and discussed Human Laminin beta 2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities in 2004.[23]
Other forms of CNS have been associated with maternal systemic lupus erythematosus, mercury poisoning, renal vein thrombosis, and neonatal alloimmunisation against neutral endopeptidase.In 2002, Debeic, Guigonis, Mougenot, Decobert, Haymann, Bensman, et al approached antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.
[24]
Also, Congenital nephrotic syndrome: a novel phenotype of type I carbohydrate –deficient glycoprotein syndrome was introduced and discussed in 1996 by
van der Knaap, Wevers, Monnens, Jacobs, Jaeken .Van Wijk. [25]
Geographical and Molecular Genetic Epidemiology of CNF of the Congenital Nephrotic Syndrome.
Although the Finnish congenital nephrotic syndrome is a rare disease ,it could have been because it was underreported, but for the other forms of congenital nephrotic syndrome which are geographically more widespread globally ,the confounding effect of its other differential diagnosis ,in the setting of infections and shared features with other more commonly occurring childhood pathologies weights diagnostic policies towards its utmost consideration with a high index of suspicion to facilitate earlier diagnosis with a more overall positive outcome implications.
Huttunen from his scholarship on congenital nephrotic syndrome of Finnish type following a study of seventy five patients in 1976 provided an epidemiological data on this theme which infers that the incidence of congenital nephrotic syndrome was estimated at about one and a fifth per ten thousand births in Finland. [26]
Until recently, the biochemical defect in this disease was unknown, but in view of the heavy proteinuria, abnormalities in the glomerular filtration barrier have been suggested. In 1994, using a candidate gene approach to linkage analysis Kestila, Mannikko, and Holmberg et al excluded defects in the genes encoding the type IV collagen chains alpha1-alpha 4; BLe, B2e, and B2t chains of laminin; and the perlecan gene, summarizing and publishing their results as the exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. [27]
In a closely related experimental endevour, in the same year of 1994, using a random mapping approach to linkage analysis, the same group of Kestila et al assigned the gene responsible for Finnish congenital nephrotic syndrome (the CFN gene) to the long arm of chromosome 19 and disseminated a conclusive result that congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome nineteen. [28]
Furthermore, linkage disequilibrium was demonstrated, suggesting a founder effect owing to a common ancestral mutation in this population.In 1998, Kestilas, Lenkkeri and Mannikko et al as a group identified a gene on which four different mutations segregate with the disease. [5]
The gene encodes a 1241 amino acid transmembrane protein called nephrin, whose function remains unclear.
Genetic linkage analysis undertaken in several families other than Finland or the other Nordic regions in whom DNA extraction from their blood samples were achieved resulted in the locus being mapped to the same region on chromosome 19 as in the Finnish families, suggesting that these non Nordic families share the same disease locus as the Finnish and the other Nordic subsets.Infact the disease was not exclusive to the Scandinavia or those of Irish ancestry, but has been described globally, in other reported cases of CNF from apparently non endogamous or non-consanguineous families; there were no evidence of consanguinity or Finnish ancestry in any of these families.
Lenkkeri, Mannikko, McCready, Lamerdin ,Gribouval, Niaudet et al. analysed and discussed the Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and proffered a characterization of its associated mutations in 1999.[29]
The elevated amniotic fluid alpha fetoprotein, in an affected, fetus allows prenatal diagnosis.Nephrotic syndrome is defined by the association of marked proteinuria less than one grammes per metre squared per day associated with a hypoalbuminaemia of less than two and a half grammes per deciliters. A nephrotic syndrome is called congenital if it presents within the first three months of life, this definition is based on the natural history of the Finnish type, the most common type of nephrotic syndrome in new born infants. Congenial nephrotic syndrome is a rare uniformly fatal renal disorder which is often observed in multiple siblings in a single family.An autosomal recessive inheritance has been suggested on the basis of the 1973 article on this theme by Burke & Others, on Familial nephrotic syndrome. [30]
Oedema is noted in the initial weeks of life, with placentomegaly and prematurity being common precursors. There is no specific therapeutic interventions for CNS, but transplantation could be considered if survival is longer than eighteen months to twenty four months. Previous reviews summarized the current knowledge of genetic and non-genetic causality factors for CNS, the rational scheme for molecular sequencing and the current difficulties and challenges. [3]
At the moment, the main challenge of Congenital Nephrotic Syndrome (CNS) is to identify the cause of disease for individual patients. To make a definitive diagnosis, with the exclusion of infection-related CNS and maternal-associated disorders, pathology, family history, inheritance mode, and other accompanying congenital malformations are sometimes, but not always useful indicators for diagnosing genetic CNS.
Next generation sequencing would be a more effective method for diagnosing genetic CNS in some patients, however, there are still some challenges with next-generation sequencing that need to be resolved in future.
The pathogenesis is unknown .A fundamental immunologic incompatibility between the mother and the infant is perhaps responsible, since mothers reject skin grafts of these nephrotic infants more rapidly than control mothers reject grafts of normal infants. Evidence of the immune injuries to the kidneys relates to the finding of gammaglobulin and complement components on the glomerular loops. This immunopathology was buttressed by the 1972 data from the genetic and immunological studies in congenital nephrosis by Conwald and McIntoch. [31]
The Congenital Nephrotic Syndrome Finnish Type [CNF]
On the Clinical Presentation of the Finnish Type of Congenital Nephrotic Syndrome,
The relative rarity of the classically typical CNF, both within the Nordic regions and elsewhere infers that there would be paucity of data regarding this pathological entity, as investigations were confined to case series compromising statistical power.
Most infants with CNF will present within the first five weeks of life, most at birth Details of the pregnancy, may be available in up to one half of cases, in about one third of the cases, the course of the pregnancy would be entirely innocuous. In about one of twenty, prenatal isolated frank proteinuria was present in the very terminal period of the pregnancy, in another one of twenty, microscopic and frank haematuria, and proteinuria in addition to hypertensive disease in pregnancy were associated features towards term.
The mean gestational age was usually about thirty six completed weeks (ranging from twenty nine and half to forty one and half weeks of gestation) and the mean birth weight was two and four fifths kilogrammes with a range of one and two thirds to three and four fifths kilogrammes about one in five of the cases will have a low birth weight of less than two and half kilogrammes. The placentas will reveal pronounced placentomegaly with placental weight of about one thousand grammes or more, with relatively pronounced placentomegaly of between thirty nine to fifty percent of the newborns total birth weight.
The natural history of the disease is based on experience before the availability of renal transplantation in young patients. Histriographically, several natural history data on CNF exists, Huttunen in 1976, [26]
Huttunen, Vehaskari, Vihikari et al in 1980. [32] and Norio and Rapola scholarships data on .Congenital and infantile nephrotic syndromes in the .Genetics of kidney disorders by Bartsocas in 1989. [33]
The mean gestational age was about two fifty six days and two of five of the infants were premature of less than thirty seven completed gestational age.Many of the infants were of small for gestational age (SGA), especially those that attained a gestational age of or above thirty seven completed gestational age.
Affected infants are usually born early (at about thirty five to thirty eight weeks), showing signs of fetal distress, and are below gestational weight for age. Low birth weight with an obstetrics history of placentomegaly (which accounts for more than a quarter of the babies weight, low bridged nose, widely separated cranial sutures, delayed ossification, with large widely spaced anterior and posterior fontanel’s and oedema are commonly noted characteristics features at birth of CNF infants.
Morgan, Postlethwaite and Savage in 1981 detailed on the congenital structural abnormalities, stigmata and dysmorphology in children with congenital nephrotic syndrome (Finnish Form) [34]
Most cases are oedematous at birth or develop typical features within the first week .Some form of dropsy of any recognized clinical character was the most frequent presenting feature.
Clinical Pathological Correlates for The Congenital Nephrotic Syndrome Finnish Type (CNF)
Congenital Nephrotic Syndrome should be suspected if there is a history of Congenital Nephrotic Syndrome in a sibling, hydrops fetalis or oedema of the placenta (i.e a placental weight of more than one in four of the infant’s birth weight or an elevated alpha-fetoprotein or total protein concentration in the amniotic fluid.
Huttunen in 1976, remarked that since the disease begins in utero in all patients, an increased alpha-fetoprotein more than ten standard deviations above the mean amniotic fluid concentration during the second trimester) is a reliable indicator of the disease. [26]
Since, the Finnish congenital nephrotic syndrome is an extremely severe disease of early childhood, prenatal diagnosis is often requested by families who have previously had an affected child .A raised alpha fetoprotein concentration in the amniotic fluid caused by fetal proteinuria has been used to identify those at risk, but this is not a test for a specific marker, and could only be performed after the fifteenth week.
An increase in maternal serum alpha fetoprotein could also be used as a less sensitive general screening method. In 1993, Ryynanen, Seppala, Kuusela, et al discussed prenatal screening for congenital nephrosis in Finland by maternal serum alpha-fetoprotein. [35]
For a comprehensive overview see the seminally disseminated classic scholarships of Seppala, Rapola, and Huttenen et al.of 1976 on congenital nephrotic syndrome: prenatal diagnosis and genetic counselling by the estimation of the amniotic fluid and maternal alpha-fetoprotein. [36]
On the basis of the 1997 scholarships of Mannikko, Kestila and Lenkkerri et al,
Improved prenatal diagnosis of Finnish congenital nephrotic syndrome, based on DNA analysis of chorionic villus tissue, is now achievable. [37]
Results of subsequent linkage and haplotype analyses can reduce the risk of false positive diagnosis based on alpha fetoprotein concentrations alone.
The identification of the mutated gene in congenital nephrotic syndrome of the Finnish type will allow for accurate prenatal and carrier detection in those at risk without the need for unduly undirected family studies and will provide valuable insights into the mechanisms of proteinuria and glomerular function. Common haplotypes of markers have been described in both Finnish and the non-Finnish affected families suggesting that one or two ancestral mutations account for most cases of the Finnish congenital nephrotic syndrome. Currently, there are several studies examining additional markers in the non-Scandinavian families in an attempt to define a common haplotype in these families, which might further narrow down the region of interest and accelerate the cloning of the CNF gene.
Although the renal function of the affected infants on presentation is usually normal or mildly impaired for the first six months, but the babies fail to thrive and are particularly prone to infection and thromboembolism.The florid features of nephrotic syndrome commonly predominate and appears early, proteinuria is typically severe at about more than twenty grammes per litre, when the serum albumin is corrected to more than fifteen grammes per litre and associated with pronounced hypoalbuminaemia at less than ten grammes per litre at presentation. The edema, however, may be apparent only after the first few weeks or months of life.Anarsarca follows, and the abdomen is distended by ascites.These clinicopathological aspects were eloquently discussed by
Holmberg, Laine, Ronnholm, et al in their scholarships on the congenital nephrotic syndrome. [38]
Massive proteinuria associated with typical nephrotic serum protein electrophoresis and hyperlipidaemia is the rule. Up to thirty nine grammes per twenty four hours has been recorded .The minimal range being about two grammes per twenty four hours, which was also invariably associated with severe oedema and ascites and reflected a low serum albumin level.Haematuria, is not uncommon. If the patient lives long enough, progressive renal failure occurs. Most affected infants succumb to infections at the age of a few months. In some patients, the typical signs of nephrotic syndrome such as oedema, proteinuria, and hypoalbuminaemia did not develop until the third month of life.The evolution of the disease was not affected by the administration of steroids or cytotoxic medications. Other recognized features include hypothyroidism, seizures, umbilical hernia. bony deformities and developmental delays.
The Laboratory Features For The Congenital Nephrotic Syndrome Finnish Type (CNF)
This indicates that the proteinuria which was initially very selective and usually almost entirely albumin as a result of increased permeability of the glomerulus only for small proteins, increases progressively and becomes nonselective, corresponding to an increased glomerular filtration co-efficients in addition to tubular damage. In 1980, Proteinuria in congenital nephrotic syndrome of the Finnish type was tackled by Huttunen, Vehaskari and Vihikari et al. [3D]
The chemical pathological profile is significant for low serum albumin concentration and total thyroxine concentration as a result of low thyroxine binding globulin, a normal or mildly elevated P creatinine and hyperlipidaemia.Since infection is a common complication, blood cultures and latex particle agglutinations tests if antimicrobials have been employed, in addition to other advanced electronic pathogen detection techniques should be applied in a rigorous algorithm , some series have reported an incidence of one in twenty of streptococcal pneumoniae spontaneous bacterial peritonitis, Haemophilus influenzae meningitis and pseudomonas septicaemia in addition to other polymicrobial septicaemic processes.Hypothyrodism related to urinary loss of thyroid binding globulin in the urine may warrant thyroid replacement therapy.
An increase in P-creatinine or Blood Urea Nitrogen (BUN) was observed in approximately one in five of the patients, but none may have frank ureamia.
Children, who survive this early complications progress to renal failure and, without treatment, die in their early childhoods.Hallman, Norio, Kouvalainen in 1976 highlighted the classically typical salient features and clinical course of the congenital nephrotic syndrome Finnish type. [39]
Ultrasonography:
The scholarship endvours by Bratton, Ellis and Seibert on the Ultrasonic findings in congenital nephrotic syndrome in 1990.[39]suggests that ultrasonography reveals enlarged echogenic kidneys, increased echogenicities of the renal cortex compared to the liver and the spleen, decreased differentiation between the renal cortex and the renal medulla (with loss of corticomedullary distinction), and poor visualization of the pyramids. As a seminal data, the ultrasonic features of the congenital nephrotic syndrome of the Finnish type was previously presented and discussed in 1989 by Lanning, Uhari and Kolivanen K, et al. [40]
The diagnosis of CNF could be reaffirmed at renal biopsy demonstrating the characteristic irregular dilatation of proximal convoluted tubules (microcystic disease)
Tubular dilatations may be misinterpreted as a sequelae of other causes of cystic disease, including Autosomal Recessive Polycystic Kidney Disease. [ARPKD]
Although the aetiology of the tubular dilatation is idiopathic- cryptogenic, it has been attributed to heavy proteinuria. On the basis of the data from the immnohistochemical and ultra structural studies of Rapola, Sariola and Ekblom on the .Pathology of fetal congenital nephrosis: in 1984. [41]
Progressive interstitial fibrosis and tubular atrophy develop, the latter is well correlated with increasing proteinuria. These aspects were confirmed by Huttunen in his 1976 scholarship entitled congenital nephrotic syndrome of Finnish type a study of 75 patients. [26]
Findings in Congenital Nephrotic Syndrome. Finnish Type (CNF)
In CNF, there is usually pallid nephromegaly, which may be accompanied by proximal tubular microcystic dilatations and glomerulopathy. There is proliferation of the glomerulus, crescent formation, and thickening of the capillary walls. For a long time, although the basic defect in congenital nephrotic syndrome is somewhat elusive, the pathologic findings are characteristic and almost pathognomonic. Glomerulopathy could be demonsrated by scanning electron microscopy in human fetuses as early as thirteen to twenty four weeks. of gestational age. In 1983 Atiuo-Harmainen and Rapola seminally discussed and disseminated their data on the thickness of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type. [42]
According to this data of Atiuo-Harmainen and Rapola, renal biopsy in infancy reveals irregularities of the glomerular basement membranes and thinning of the lamina densa. Followed by fusion of the epithelia cells of the foot processes, all of which were similar to the findings in minimal- change, steroid-responsive nephrotic syndrome. On light microscopy, the mature glomeruli initially typically show only minimal abnormalities, including mild mesangial hyper-cellularity and an increase in mesangial matrix.
Immature-appearing glomeruli demonstrates a dilated urinary space surrounding a small glomerular tuft .Progressive changes include obliteration of capillary loops ,and glomerlar hyalinization .Immune deposits become visible by electron microscopy within the mesangium only at the later stages of the disease. Except in the early stages, the biopsy frequently shows dilated tubules of both proximal and distal origin, such as was seen in microcystic disease .Although these cystic changes were used by some neonatologists as diagnostic criterion, they were not pathognomonic and have been contentiously discussed with regards to its other diagnostic differentials.[42]
THE MOLECULAR GENETIC STUDIES FOR CONGENITAL NEPHROTIC SYNDROME FINNISH TYPE.
GENETIC LINKAGE ANALYSIS:
The advent of specific genomic data for CNF has revolutionized its diagnostic accuracy and precision.
Many of the hereditary diseases that have recently been analysed at a molecular level have revealed genetic heterogeneity. At least two loci have been identified for adult polycystic kidney disease (PKD1 and PKD2) and Alport syndrome (COL4A5, COL4A3, and COL4A4) In the Nordic families, the CNF locus was mapped to chromosome 19q13.113. Fairly more recent data on this theme has emerged. In 1996, Mannikko, Lenkerri and Kashtan et al undertook a haplotype analysis of congenital nephrotic syndrome of the Finnish type in non-Finnish families and eminently disseminated their results. [43]
Ideally, the genetic linkage analysis for Congenital Nephrotic Syndrome Finnish Type were apposite in those families with one affected index case and one unaffected family member to be employed as a control, however occasionally, some of the affected children may not have an unaffected sibling, or in other instances, the index case may not have a living sibling at all, making achieving rigorous results of genetic analysis of inheritance of chromosome nineteen markers flanking known in CNF locus seven daunting. Several research genetic laboratories could proffer flanking microsatellite oligoprimers .Polymerase chain reaction (PCR) could be employed to amplify the polymeric region in a reaction volume of ten microlitres containing twenty five nano grammes DeoxyRiboNucleic Acid, The Polymerase Chain Reaction products could be separated by electrophoresis in a six percent denaturing polyacrylamide gel and visualized by autoradiography.
This localization and focalization of the CNF gene to chromosome nineteen has also been confirmed recently in populations of non-Finnish ancestry.
Fuchshuber, Niaudet and Gribouval et al in 1996 demonstrated and discussed congenital nephrotic syndrome of the Finnish type and its linkage to the locus in a non-Finnish population. [44]
The Computation of Lod Scores
Genetic heterogeneity in the Nordic families could be searched for by the performance of linkage analysis using microsatellite markers on chromosome 19.Because linkage disequilibrium had been demonstrated in the Nordic families with the markers D19S220 and D19S224, recombination events with these markers in any of the Nordic families would suggest heterogeneity. Using five polymorphic microsatellite markers in this region, the disease gene could be mapped to the same area on chromosome 19 as in the Nordic families, with a maximum Lod score of 2.6.This demonstrates a further non-Nordic population in whom the disease has been mapped to chromosome 19 consistent with locus homogeneity.
Lod scores and Alleles scores could be calculated using the MLINK program from the computer package LINKAGE. An achievement of a positive Lod scores with all the five markers using two point linkage analysis would raise the Lod score up to 2.60 between the markers D19S224 and D19S422.
For a user friendly programme see the Easy calculations of lod scores and genetic risks on small computers by Lathrop and Lalouel of 1984. [45]
There may be no evidence of a common haplotype with these markers to indicate linkage disequilibrium. Family pedigrees could demonstrate haplotypes for markers D19S416, D19S224, D19S220, D19S422 and D19S223.
For interpretative clarity, the two point linkage analysis between disease gene and chromosome 19 markers could be depicted in an illustrative tabular form.
Fairly recently in 2013, Gbadegesin, Winn and Smoyer presented and discussed .as a seminal theme, the genetic testing in nephrotic syndrome with its overall challenges and opportunities. [46]
Complications of the Congenital Nephrotic Syndrome (Finnish Type)
Complications of CNF included severe to profound failure to thrive and universal ascites, severe bacterial infections in about eight to nine of ten instances, hypertrophic obstructive pyloric stenosis in one of eight instances, and thrombotic events in one of ten cases in addition to cerebral palsy, hemiplegia and seizures in about one of twenty instances respectively. Thrombotic complications were particularly common, troublesome and affect a large number of children with CNF, in most series advanced neuroimaging of the cerebral cytoarchitechtonics revealed and identified evidence of intracerebral lesions shortly after birth, suggesting intrauterine cerebral thrombosis. Neurological complications were most prominent topographically as eloquent spastic cerebral palsy, unilateral hemiplegia and polygraphic seizures. Also asymptomatic pelvic veins thrombosis demonstrated at the point of transplantation, in addition to principal tributary venous system thrombosis related to venous catheterizations in about one of twenty cases respectively were associated pathologies of concern It is becoming more and more popular and acceptable that these sets as a group should receive anticoagulation, preferably heparanisation during the neonatal period and warfarinization thereafter. Other complications worthy of consideration in CNS were related to transplantation, especially hypercouagulability, adult type acute respiratory distress syndrome, primary aspiration pneumonitis and host versus graft disease in addition to the multisystemic pathological impact of transplantation related immunosuppression.
Differential Diagnostic Considerations for Congenital Nephrotic Syndrome.
Congenital Lymphoedema ,Milroy’s Disease, Turners and Noonans Syndrome, Hypothyrodism (cretinism) and the aneuploidy Trisomys are differential diagnostic pathological entities of CNF worthy of exploring to exclude CNF.
The myxoedema of Cretinism and its anthropometrical stigmata mimics those of CNF and in itself, cretinism could present with congenital nephrotic syndrome.
When Trisomys 21, Turners and Noonans syndromes are associated with Congenital structural cardiac defects they could be complicated by biventricular congestive cardiac failures with dropsy and mimics very closely the CNS/CNF.
The umbilical hernias and other dysmorphology of Trisomy 21 very easily parallel those of CNS and CNF.
On the Therapeutic Interventions and Prognosis for the Congenital Nephrotic Syndrome Finnish Type (CNF)
Although supposedly, routine therapeutic interventions for nephrosis has very little to offer. Prevention and effective management of urinary tract infections are important prophylactic therapeutic considerations.Disease modifying Immunosuppressives such as cyclosporine A appeared to extend renal function for a period. Infants with congenital nephrotic syndrome require intensive management, which includes early repetitive administration of albumin supplementation to replace the renal losses, and diuretics for ascites, nutritional support with enteral and parenteral hyper- alimentation, multiple essential multivitamin and micronutrients, thyroxine replacement and the treatment of multiple complications especially related to infective and thrombo-embolic pathological factors will encourage the achievement of a steady state at the first instance..
The application of a twenty percent albumin solution to deliver three to four kilogrammes of albumin intravenously, initially in two divided doses of three to four hours duration ,and later as a single overnight infusion over six to eight weeks .A loop diuretic such as frusemide is usually given at a dose of one half milligrammes per deciliter with the albumin infusion .Nutrition is supplemented with nasogastric or gastrotomy tube feeding delivering one half milliliters per Kilogrammes of four grammes per kilogrammes protein each day and dietary fat manipulation ,this regimen is followed by bilateral nephrectomy at the age of six to ten months , and peritoneal dialysis leading to improvements in feeding and growth ,which allow the child to reach a weight and body size( usually eight to ten kilogrammes) at which renal transplantation can be successful .Angiotensin converting enzyme inhibitors such as captopril and Indomethacin to diminish urinary protein loss has been a successful alternative to bilateral nephrectomy in a few selected series.
The aim of the generic interventional approach is to sustain nutrition and growth so that children can tolerate bilateral nephrectomy at twelve months of age, with the sequential management of renal failure with cycling peritoneal dialysis until a suitable weight and size for renal transplantation is achieved.
In 1995, Pomeranz, Wolach, Korzets and Bernhiem following their therapeutic trial reported and discussed the successful management of Finnish congenital nephrotic syndrome with Captopril and Indomethacin. [47]
Chronic renal insufficiency develops between the sixth and the twenty third months of life. On this basis, most candidates will eventually receive dialysis whilst waiting for transplantation. All reported infants treated before the availability of renal transplantation died, mostly of infectious complications. In one report, of the patients who received renal transplantation, the twenty four months patient and graft survival rates were eight to nine of ten and three of four cases respectively.
Recurrence of nephrotic syndrome was not observed after transplantation. Most infants had a normal or accelerated growth, although the mean height remained significantly lower than normal. Although sixteen of seventeen had delayed psychomotor development at the time of transplantation, marked improvement was evident twenty four months after, and twelve of fifteen surviving children had normal school and social performance (range thirty months to eighty four months of age)
Discouragingly, even though some infants with congenital nephrotic syndrome were found to have minimal change disease on histopathology, the application of corticosteroids or disease modifying drugs such as cyclophosphamide or cyclosporine A therapy proved unrewarding.
However, thereafter pharmacotherapeutic interventions with Indomethacin and Captopril were tried with noteworthy success, in this way the disease progressions were thought to be attenuated and several candidates were assisted from progression to the need for a renal transplantation.
Most children surviving within the initial six to twelve months would have undergone bilateral nephrectomy before eighteen months. Although staged nephrectomy was initially very fashionable and popular there appears to be no evidential proof of its superior benefit. In most series about one of seven of the cases overall may meet the specific criteria to progress to renal transplantation through bilateral nephrectomy.In most dedicated renal transplantation units, the twelve month graft survival following renal transplantation was computed at about three of four to eight to nine of ten cases, however these figures appears to be improving with the perfection of the selection criteria of the appropriate transplantation candidates, in addition to operative and postoperative immunosuppressive techniques.Peri-operative deaths were estimated at about one in ten cases. With improvements in immunosuppressive approach, graft rejection was negligible at about one in twenty cases and this figure appears to be getting more and more diminutive with an enhanced lucid comprehension of the immunopathology of transplantation rejection. With the recent improvement in the comprehension of the immunopathology of transplantation related rejection, more and more children with CNF are sustaining the first and repeat transplantations from donor siblings and recidivist renal transplantations rejections are getting less frequent to being a thing of the past.
Denovo infective and immune related nephrotic syndrome of a disparate and divergent aetiopathological entity of undetermined prognostic significance which were occasionally reported perturbations in the grafted kidney were commonly reported as relating to a post transplantation upper respiratory tract infection, in these instances,masangial proliferative glomerulonephritis rather than evidence of recurrent disease of mesangial sclerosis were the most commonly demonstrated histopathological phenomenon at renal biopsy.
Fortunately, these cases were satisfactorily responsive to renal replacement therapy, with encouraging graft response. Even massive proteinurias more than two and half grammes per twenty four hours several months after transplantation resolved satisfactorily with an augmentation of the steroid or disease modifying drugs pharmacotherapeutic regimens including Cyclosporine A with no relapse at follow ups.
Other causes of congenital nephrotic syndrome and differential diagnostic considerations other than Congenital Nephrotic Syndrome of the Finnish Type. (CNF)
Several pathological and syndromic entities were associated with congenital nephrotic syndromes. An increase in alpha fetoprotein may be observed in these conditions, but this is far less consistent than that which was observed in frank Idiopathic congenital nephrotic syndrome. Although therapy with corticosteroids and cytotoxic agents invariably has proven ineffective, specific therapy may be available for some subsets such as those related to the congenital TORCHES Complex infections. Classification of a patient into one of the major entities on the basis of aetiology or idiopathy may not be possible, hence some of such cases were denoted as unclassifiable or unclassified.
A reasonably recent data on the clinicopathological correlations of congenital and infantile nephrotic syndrome over two decades was achieved by Kari, Montini, Bockenhauer, Brennan, Rees and Trmpter et al in 2014. [48]
Congenital Nephrotic Syndrome tantamount to Diffuse Mesangial Sclerosis and Its Other Differentials of The Congenital Nephrotic Syndrome Finnish Type (CNF) and The Drash Syndrome related Congenital Nephrotic Syndrome Compared and Contrasted.
Congenital Nephrotic Syndrome (Tantamount to Diffuse Mesangial Sclerosis.
The second most common cause of congenital nephrotic syndrome is Idiopathic Cryptogenic diffuse mesangial sclerosis which appears to be a heterogeneous histopathological group.
According to the 1989 data from the book chapters of Norio and Rapola on Congenital and infantile nephrotic syndrome edited by Bartsocas in the book Genetics of kidney disorders the onset CNS may be as late as twelve months of life. In contrast to Congenital Nephrotic syndrome of the Finnish type, Chronic Renal Failure (CRF) develops rapidly in these patients, and is usually the major cause of demise in the absence of renal replacement therapy or renal transplantation. Renal venous thrombosis is also another frequent complication In other instances, in most families, diffuse mesangial sclerosis was genomically determined and was transmitted as an autosomal recessive trait.
Histologic examination of the glomeruli demonstrates mesangial cells embedded in a periodic acid Schiff positive and silver-positive fibrillar network occluding the capillaries.
Although the associated renal tubular changes for this subset of CNS were similar to those in the CNF with regards to dilatations and microcystic deformations, However, the accompanying renal interstitial fibrosis for this subset were more eloquent and florid than that encountered in CNF.These aspects were further analysed in the book chapters of Norio and Rapola on Congenital and infantile nephrotic syndromes in the book Genetics of kidney disorders edited by Bartsocas and published. by Alan Liss in 1989. [33]
In addition to the scholarships of Habib, Gubler, Antignac and Gagnadoux on Diffuse mesangial sclerosis as a congenital glomerulopathy with nephrotic syndrome of 1993. [49]
The performance of a renal biopsy, at least amongst adults is required for the accurate diagnosis of resistant or recidivist nephrotic syndromes and for the formulation of a rational therapeutic interventional plan, however the situation is different for children who need not always be subjected to renal biopsy since careful historical, clinical and non invasive laboratory studies could lead to accurate diagnosis in several instances,
The Differential Diagnostic Considerations worthy of inclusion for the Congenital Nephrotic Syndrome Tantamount to Diffuse Mesangial Sclerosis.
Since in CNS, pathlogically, microcystic transformation of the cortical nephrons due to proximal tubular dilatation is demonstrated, and the glomerular changes nonspecific, the extensive effacement of the podocytes and sclerosis of the glomerular tufts demonstrated by electron microscopy non pathognomonic,in addition to the negative or non-specific immunological findings makes the probable differential diagnostic considerations in CNS extensive.
Given this clinico-pathological conundrum, other causes of primary and secondary nephrotic syndrome should be considered, in the appropriate clinicopathological settings such as, but not confined to:
[I]-The histopathological features of Nephrotic syndromes from Primary glomerular Diseases.
+Minimal change diseases (could also be associated with allergy.
+Mesangial proliferative glomerulonephritis (including Berger’s Disease (IgA nephropathy).
+Focal and segmental glomerulosclerosis.
+Membranous proliferative glomerulosclerosis.
+Membrano-proliferative glomerulonephritis.Types I, II & III.
+Other uncommon lesions such as Crescentic glomerulonephritis, Focal, segmental and other unclassifiable lesions.
+Also worthy of differential diagnostic considerations will be the nephrotic syndrome secondary to other diseases such as The Post Streptococcal Glomerulonephritis, endocarditis shunt nephritis, secondary syphilis, leprosy, hepatitis B, infectious mononucleosis ,malaria,schistosomiasis and filiariasis.
+Drugs use in mother or infant such as organic gold, inorganic and elemental mercury, penicillamine, street heroin, probenecid, captopril, tridione ,mesantoin,perchlorate,antivenom ,antitoxins and contrast media are equally worthy of consideration from the aetiological points of views.
+Neoplastic conditions such as Hodgkin’s disease, lymphomas, leukaemias, carcinomas, melanomas and Wilms tumour should be considered in the infantile periods.
+Multisystemic Disorders:
Systemic lupus erythromatosus, Honech-Scholein purpura, vasculitis, Good pastures syndrome, dermatomyositis, dermatitis, herpetiformis, amyloidosis, sarcoidosis Sjogrens syndrome and rheumatoid arthritis.
+Heredofamilial diseases such as Diabetes mellitus, Alports syndrome, sickle cell disease, Fabrys disease, nail-patella syndrome, lipodystrophy in addition to congenital nephrotic syndrome itself.
Miscellaneous :
Cor Pulmonale, neonatal and infantile thyroiditis, cretinism, malignant infantile obesity, renovascular hypertension, chronic interstitial nephritis with vesicoureteric reflux, allograft rejections and bee stings.
The Dennis-Drash Syndrome related Congenital Nephrotic Syndrome.
In some infants, diffuse mesangial sclerosis is part of a Drash syndrome, which also includes ambiguous genitalia, most often male pseudo-haemophrodism (i.e. 46XY karyotype) and Wilms tumour.A detailed review on the nephropathy associated with male pseudohaemophroditism and Wilms tumour (Drash syndrome) as a distinctive glomerular lesion and a report of ten cases was provided by Habib, Sariola and Gubler et al in 1985. [50]
Commonly, patients present between two weeks to thirty-three months of age with or without nephrotic syndrome, sometimes haematuria, often arterial hypertension and progressive CRF leading to ESRD within a few months to two years from the onset. Several patients have presented with incomplete forms of Drash-Syndrome (i.e. only two of the three signs of the triad. In some Dennis-Drash Syndrome, CNS presents in the setting of a child with Wilms’ tumour and hemi hypertrophy without pseudo-haemophroditism.
Frasier syndrome showing splice mutations in Wilms tumor gene (WT1) Intron. .
Eminent data from Fujita, Sugimoto, Miyazawa, Yanagida, Tabata and Okada, et al. in 2010 reported and discussed a female infant with Frasier syndrome showing splice mutations in Wilms tumor gene (WT1) Intron. . [51]
Congenital nephrotic syndrome in epidermolysis bullosa congenita.
Another association worthy of consideration and discussion is that between congenital nephrotic syndrome and epidermolysis bullosa congenita.
In the year 2000, Kambham, Tanji, Seigle, Markowitz, Pulkkinen and Uitto et al demonstrated, reported and discussed congenital focal segmental glomerulosclerosis associated with beta 4 integrin mutations and epidermolysis bullosa. [52]
Thereafter, Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes in an infant with Herlitz junctional epidermolysis bullosa was presented and reviewed by Hata, Miyazaki, Seto, Kadota, Muso, Takasu, et al.in 2005.[53]
The respiratory chain deficiency related congenital nephrotic syndrome.
Also the respiratory chain deficiency could present as congenital nephrotic syndrome. A case study of respiratory chain deficiency presenting as congenital nephrotic syndrome was demonstrated , reported and discussed by Goldenberg, Ngoc, Thouret, Cormier-Daire, Gagnadoux, Chretien, et al. in 2005.[54]
Fairly recently in 2010, Machuca, Benoit, Nevo, Tete, Gribouval, Pawtowski, et al. analysed and discussed the genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. [55]
Congenital Nephrotic Syndrome related to Congenital Infections.
Reviews on the Aetiopathogenesis of Congenital Nephrosis suggests that
infections, such as congenital syphilis and toxoplasmosis are possible pathogenic agents, especially for those infants conceived and delivered in the regions between the Tropics of Cancer and Capricorn. Infection should be excluded as the cause of CNS before instituting the investigations for genetic CNS, because it is important for selecting an apposite therapeutic strategy and for long term prognosis in most cases. In the opinion of several authors, the current main challenge for CNS is how to identify the aetiology of CNS in the individual patient. Establishing a therapeutic strategy is also another major challenge, but it is not the primary difficulty, because it depends on the cause of CNS.For this reason, the objective of most diagnostic and therapeutic protocols will be to compile a list of the possible causes of CNS in a given setting, and circumstance, to identify the aetiological factors in their index cases, before the commencement of specific therapeutic interventions, and also to exclude infectious causes for CNS, such as the TORCHES infections in some patients, before the initiation of therapy.
Syphilitic (Luetic Disease)
Anecdotally, for a long time congenital syphilis has been implicated as a causative factor for CNS. Several Asiatic epidemiological surveys on these themes exists, but this is probably lacking in several other emerging settings. Although, syphilitic (leutic disease) is a commonly occurring pathological entity in several tropical settings. Way back in 1993, Niemsiri undertook an epidemiological field survey on congenital syphilitic nephrosis and there after reported and seminally disseminated his results. [56]
Several authors inferred that nephrotic syndrome due to congenital infection was most commonly seen with congenital syphilis.Histriographic data on this theme exists, In 1961, Papaioannou, Asrow and Schuknell implicated nephrotic syndrome in early infancy as a manifestation of congenital syphilis. [57]-
In a very closely related academic endevour several decades after in 2005, Vachvanichsanong, Mitarnun, Tungsinmunkong and Dissaneewate studied and discussed congenital and infantile nephrotic syndrome in Thai infants and implicated congenital syphilitic leutic disease as a causative factor.[58]
Where as in 1973, Wiggelinkhuzen, Kaschula and Uys et al approached congenital syphilis and glomerulonephritis with evidence for immune pathogenesis in which case the lesion was characterized by epimembranous or proliferative glomerlopathy, with diffuse deposits of gamma-immunoglobulin and treponemal antigen aligned along the glomerlar capillaries and sub-epithelial electron dense deposits. The condition responds remarkably well to the application of the penicillomic acid derivatives.Histriographically, several data on this aetiological associational entity exists notably but not confined to those of Kaplan, Wiglesworth, Marks and Drummond of 1972 on the glomerulopathy of congenital syphilis as an immune deposit disease. [59]
In another related scholarship, in 1973.Wiggelinkhuzen, Kaschula and Uys et al studied and discussed congenital syphilis and glomerulonephritis with evidence for immune pathogenesis in its aetiology.Further epidemiological surveys by Lago and Garcia on Congenital syphilis as an emerging emergency also in Brazil in the year 2000 infers that Nephrotic syndrome in congenital syphilis generally appears between two to three months of age. [60]
Corroborating the age of incidence range proposed by the previous epidemiological surveys of Niemsiri et al on this pathological associational entity. [56]
In addition to the 1973 data of Wiggelinkhuzen, Kaschula and Uys et al on congenital syphilis and glomerulonephritis with an evidence for immune pathogenesis. [61]
Paraphrasing the excerpts from the histriographic data of Suskind, Winkelstein and Spear of 1973 on. Nephrotic syndrome in congenital syphilis, the extent of clinical renal involvement may vary from microscopic haematuria through nephritic syndrome to more significant features, such as frank nephrotic syndrome. [62]
Vachvanichsanong, Mitarnun, Tungsinmunkong and Dissaneewate on their scholarship on congenital and infantile nephrotic syndrome in Thai infants of 2005 reported a two and half percent prevalence of congenital syphilis that caused congenital nephrotic syndrome amongst four hundred and fifty five neonates or infants in Thailand. [58]
Lago and Garcia on the basis of their scholarship on congenital syphilis as an emerging emergency also in Brazil of the year 2000 demonstrated that
Membranous nephropathy is a common histopathological feature in renal biopsy, with immune deposits in the region of the glomerular basement membrane, this observation implicates the immune system in the pathogenesis of syphilis-associated CNS. [60]
If the diagnosis was made early, the prognosis is good because antimicrobial therapy, usually penicillomic acid derivatives, is curative, provided that irreversible renal lesions have not developed. Neonates with congenital syphilis may present with fever, hepatosplenomegaly, persistent rhinitis, neurosyphilis, hepatitis, anaemia, erythematous patches with superficial bullae or desquamations. These could co-exist with the CNS. Timely therapeutic interventions with penicillomic acid derivatives could be curative in several forms of syphilitic leutic disease including CNS as a group.
Toxoplasmosis:
Congenital nephrotic syndrome associated with congenital toxoplasmosis is also possible but less common than that tantamount to congenital syphilitic leutic disease.Beale ,Strayer ,Kissane and Robson reported .Congenital glomerulosclerosis and nephrotic syndrome in two infants and discussed its Speculations and pathegenesis in 1979 .These infants who had extensive glomerulosclerosis manifested by nephrotic syndrome ,severe oliguria, and progressive renal failure.Both patients had intrauterine infections.Therefore the screening for congenital toxoplasmosis infection is necessary for high-risk CNS infections.[63]
Fan ,Zhang and Wang et al presented and reported one case of congenital nephrotic syndrome secondary to congenital toxoplasmosis in 2005 ,this case was that oa 3-month-old girl presented with massive proteinuria ,anarsarca ,hypoalbumnaemia and positive serum antibody IgM for toxoplasmosis .Her mother also presented with positive serum IgM antibody to toxoplasmosis.After treatment with spiramycin for three weeks ,the patient became negative for proteinuria,and serum toxoplasmosis IgM antibody titre will vanish simultaneously .[64]
Classic histriographic data on this theme of congenital nephrotic syndrome associated with congenital toxoplasmosis was provided in 1974 by Shahin ,Papadopoulou and Jenis.[65]
A Parisian scholarship by Couvreur ,Allison ,Coccon-Gibod ,et al. Investigated and discussed the implication of the kidneys in toxoplasmosis in 1984.Entiltled « Rein et toxoplasmose. », the renal lesion is characterized by the deposition in the glomeruli of immunoglobulins, complement and Toxoplasma gondi antigen and antibody complexes. It may respond to the administration of pyrimethamine, sulfadiazine and steroids. [66]
This reported was corroborated by other future reports by Roussel ,Pinon ,Birembaut ,Rullier and Pennaforte et al in 1987 on Congenital nephrotic syndrome associated with congenital toxoplasmosis,which was that of a one month old infant presenting with congenital toxoplasmosis associated with nephrotic syndrome and microscopic hemmaturia,in this case percutaneous renal biopsy demonstrated a diffuse mild increase in mesangial cells and matrix,but immunoflorescence was negative.[67]
So toxoplasmosis is a possible cause of nephrotic syndrome ,with the majority of cases being associated with congenital infection. Haskell ,Fusco ,Ares and Sublay reported and discussed disseminated toxoplasmosis presenting as symptomatic orchitis and nephrotic syndrome.in 1989 .[68]
Cytomegalovirus Inclusion Disease:
Although previous histriographic case reports of congenital nephrotic syndrome in association with congenital cytomegalovirus infection exists, it was inconclusive whether or not the nephrotic process was mediated by or related to the infection, incidentally, co-incidentally, epiphenomenally or not as was epitomized by the reports of the observations of Frishberg, Rinat, Feinstein, Becker-Cohen, Megged, Schlesinger on Mutated Podocin manifesting as CMV-associated congenital nephrotic syndrome of 2003.[69]
However, several sporadic associations of neonatal cytomegalovirus (CMV) infection and CNS that were also reported lends weight to the causality of this associational entity. In many cases, diffuse mesangial sclerosis (DMS) in histology is often found and the patients clearly respond to gangiclovir therapy.
Besbas, Bayrakci, Kale, Cengiz, Akcoren, Akinci, et al.presented and discussed Cytomegalovirus-related congenital nephrotic syndrome with diffuse mesangial sclerosis in 2006. This report described CNS associated with cytomegalovirus infection in a 2-month -old girl.
Histopathological examination on her renal biopsy demonstrated diffuse mesangial sclerosis and cytomegalovirus inclusion bodies in the tubular cells and in some glomeruli.Cytomegalovirus (CMV) Polymerase Chain Reaction (PCR) titer in the serum was high .Remission of pulmonary and renal symptoms was achieved with gangiclovir in three weeks. No recurrence of proteinuria was observed during the fourteen month follow up period. Their findings suggested a causal relationship between congenital nephrotic syndrome and CMV infection.
[70]
In 1986, Neonatal cytomegalovirus infection with pancreatic cystadenoma and nephrotic syndrome was reported and discussed by Amir, Hurvitz and Neeman et al. [71]
However, thereafter, fairly more recent data was provided in 1993 by
Batisky, Roy and Gaber which reaffirmed congenital nephrotic syndrome and neonatal cytomegalovirus infection as a clinico-pathological association.
[72]
Nevertheless, however, Frishberg et als report of this girl with CNS associated with CMV infection; and histological findings on renal biopsy suggested a causal relationship between CNS and CMV infections.However, since she was subsequently found to be a homozygous for a nonsense mutation in the NPHS2 gene encoding Podocin (R138X), which is the true cause of her CNS.So when specific antiviral treatment is not effective in the patient with cytomegalovirus infection and CNS, one should consider other causes of CNS, especially the genetic factors.[73]
Other infectious Pathogens.
Congenital Rubella
Also, furthermore; rare infants with CNS associated with congenital rubella have been described. Histriographic classic scholraship on this associational pathological entity was proffered by Esterly and Oppenheirmer in 1969 on the pathological lesions due to congenital rubella. [74]
In a similar research endevour, Menser, Robertson, Dorman, Gillespie and Murphy in their 1967 scholarship with compilation, itemization, enumeration and annotated discussions dissected the renal lesions in congenital rubella. [75]
Human Immunodeficiency Virus:
So also the Human Immunodeficiency virus could present with congenital nephrotic syndrome. About two of five of all HIV infected children in the North America present with renal complications. Massive proteinuria and nephrotic syndrome usually appear in children older than one year of age, some affected infants have been reported.In 1998, Attolou, Bigot, Ayivi and Gninafon presented and discussed the renal complications associated with human acquired immunodeficiency virus infection in a population of hospital patients at the Hospital and University Centre in Cotonou. Benin Republic. [76]
Bhimma, Purswani and Kala on the basis of their observational results on the investigations of Kidney disease in children and adolescents with perinatal HIV-1 infection.in 2013 proposed that severe proteinuria is more prevalent in African children. [77]
Where as the 2012 scholarships of Ramsuran, Bhimma, Ramdial, Naicker, Adhikari and Deonarain, et al approached the spectrum of HIV-related nephropathy in children. [78]
Although ,anecdotally, frank CNS cases caused by HIV infection is rather presumptive, however it is axiomatic that bye and large that this associational entity remains a very plausible diagnostic consideration in newborns and young infants within this age range.This pathological associational link could be a possibility on the basis of the extrapolations from the inferences of the scholarships of Attolou, Bigot, Ayivi and Gninafon on the renal complications associated with human acquired immunodeficiency virus infection in a population of hospital patients at the Hospital and University Centre in Cotonou.of 1998.
[79]
In addition to those of Glacomet, Erba, Di Nello, Colett, Vigano and Zuccotti on proteinuria in paediatric patients with human immunodeficiency virus infection.of 2013. [80]
And the 1987 collective approach to the types of renal disease in the acquired immunodeficiency syndrome by Rao, Friedman and Nicastri. [81]
In addition, several other scholarships on this associational pathological entity are becoming increasingly more and more available.
Hepatitis B Virus.
Although more common in children, Hepatitis B virus-related nephropathy could occur at any age including the neonatal period. Already, there are several existing scholarships on this aetiopathological associational theme.Appel presented viral infections and the kidney with relevance to HIV, hepatitis B, and hepatitis in 2007. [82]
Where as fairly recent literature on an International Data Analysis in Hepatitis B virus-associated nephropathy was achieved by Khedmat and Taheri in 2010. [83]
Differential Diagnostic Considerations for the Parainfectious or Post infectious Nephrotic Syndromes.
Infantile Beriberi, Oedematous Protein Energy Malnutrition, Congenital Cardiac Defects, Myocarditis or Congenital and Infantile Anaemia Related Heart Failures and Malabsorptive Intestinal Failures are important considerations for the infectious related congenital nephrotic syndrome,the consideration of other commonly occurring infections and infestations are of utmost importance in tropical countries especially in helminthic and malaria endemic regions, with the possibility of congenital and infantile malaria complicated by anaemic heart failure and glomerulonephropathy.
The congenital nephrotic syndrome is a recognized complication of Plasmodium malariae infestation, (here the histopathological feature is an intermediate dimorphism between a membranous glomerulonephritis and a glomerulosclerosis) where as congenital nephritic syndrome is a probability in acute Plasmodium falciparium infection. (here the histopathological finding is that of a (membranoproliferative glomerulonephritis)
Also helminthic hookworms infestations with (Strongyloides stercoralis, Necator americanus and Ancylostoma deudenale) which cause severe anaemia, and intense dropsy through continual blood and albumin dissipation with heavy worm load will be other major differential diagnostic concerns with those children with historical notes of dropsy.
The case for application of steroids for the management of congenital nephrotic syndrome in affected children with Strongyloides stercoralis infection is one of major concern, since this has been known to be associated with disseminated strongyliodiasis which is known to translocate bacterial pathogens systemically.
Dropsy is a constant feature of the micronutrient and macronutrient deficiency of oedematous protein energy malnutrition (Kwashiorkor and marasmic kwashiorkor) and the micronutrient deficiency of wet cardiac decompensated Beriberi (thiamine-vitamin B1 deficiency) Both the cyanotic and the acyanotic congenital cardiac defects and congenital and infantile anaemias of diverse aetiological origins could be complicated by dropsy related to cardiac insufficiency or albumin loss mimicking CNS.
Current Challenges for infection-related CNS.
However using the present diagnostic procedure of temporal coincidental, incidental or epiphenomenal approach, to the diagnosis of infection related CNS, the incidence of infection-related CNS may be over-estimated. Cytomegalovirus as a probable pathogen implicated in the pathogenesis of congenital nephrotic syndrome was discussed by Besbas, Bayrakci, Kale, Cengiz, Akcoren and Akinci, et al in their reports on Cytomegalovirus-related congenital nephrotic syndrome with diffuse mesangial sclerosis in 2006.[70]
Congenital Nephrotic Syndrome related to other miscellaneous aetiological Factors.
Syndromic and non-syndromic dysmorphisms were associated with congenital nephrotic syndromes,
Some cases of syndromic and non-syndromic dysmorphisms were associated with congenital nephrotic syndromes, such dysmorphic features included, primary microcephalies related to Cornelia de Lange Syndromes, The Carpenters syndrome,etc, bupthalmos(congenital glaucoma) or disturbances of neuronal neuroblasts migrations including but not confined to lissenencephaly, cortical dysplasias and the pachygyrias.Congenital microcephaly, hiatus hernia and nephrotic syndrome as an autosomal recessive syndrome were reported as birth defects in 1976 by Shapin, Duncan and Fansworth et al.[84]
Robain and Deonna in 1983 included Pachygyria and congenital nephrosis as an association of disorders of migration and neuronal orientation in their annotated compilation. [85]
This associational entity was further strengthened in 1986 by the scholarship investigations of Palm, Hagerstrand and Kristofferson et al on the theme entitled the nephrogenesis and disturbances of neuronal migration in male siblings: a new hereditary disorder. [86]
Transient cases of congenital nephrotic syndrome have been described related to maternal transmission.Lagrue, Braneller and Niauder et al in 1991, detailed on the Transmission of nephrotic syndrome to two neonates and its spontaneous regression.[87]
Mercury intoxications (minimata disease.)
Anecdotally, CNS was also related to mercury intoxications (minimata disease.) [88]
The nail patella syndrome
Or the yellow nail patella syndrome associated with lymphoedema congenita.
In 1970; Simila, Vesa and Wasz-Hockert discussed the Hereditary onycho-osteodysplasis (the nail-patella syndrome) with nephrosis- like renal disease in a new born boy. [89]
The nail patella syndrome is an autosomal dominant disorder .linked to the ABO blood groups and characterized by dystrophic nails, absence of one of patellae, iliac horns and renal disease. Previously recognized renal manifestations of the nail patellae syndrome includes, isolated proteinuria and haematuria and the congenital nephrotic syndrome. Progressive renal failure is relatively uncommon .Glomerular lesions by light microscopy are non-specific, but electron microscopy reveals a characteristic moth-eaten appearance of the glomerular basement membrane associated with intramembranous collagen fibrils. The prognosis is generally favourable .No treatment is known to be effective as such.
Further reviews on the nephropathy of the nail-patella syndrome was proffered by Bongers , Gubler , Knoers scholarships on Nail-Patella Syndrome an Overview on clinical and molecular findings of 2002.[90]
The association of the nail-patella syndrome with the congenital nephrotic syndrome lends weight to the need to explore the all cases of suspected CNS for abnormal dermatoglyphics features.
Systemic lupus erythematosus associated with chromosomal abnormalities.
Case reports of one three month old infant with infantile SLE who reportedly had steroid-responsive membranous glomerulopathy and other instructive cases were available. In 1979, Ty and Fine presented Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities. [91]
Renal vein thrombosis
Histriographically, renal vein thrombosis was proposed as an aetiological factor for congenital nephrotic syndrome [92]
In 1971, Alexander, and Campbell approached and discussed congenital nephrotic syndrome and renal vein thrombosis in infancy. Axiomatically, just like it is a known aetiological factor for neonatal, earlier infancy, later infancy, childhood and adult nephrotic syndromes. As a seminal investigational topic, the nephrotic syndrome and renal vein thrombosis. Was tackled by Kaplan, Chesney and Drummond in 1978. [93]
Previous PROGNOSIS for CNF.
In early years, the prognosis of CNF was poor, with most children dying within the first year of life, predominantly from sepsis.
One-half of the patients died by the age of six months, and all of them by four years of age. The immediate cause of death appeared to be infection in one third. Autopsy revealed thrombi in large vessels in about one in five instances.
Since this early report aggressive management has considerably improved the survival rate.
Historically, all children died, usually within the first six months of life, but now with aggressive treatment an extended survival can be achieved.
This chronologically progressively increasing positive outlook for these groups of children was presented and discussed by Holmberg, Antikainen Ronnholom, Ala-Houhala and Jalanko in 1995 in their scholarships on the management of congenital nephrotic syndrome of the Finnish type.[94]
Current Medical interventions have positive Implications on Prognosis.
All children are now treated initially with daily intravenous albumin infusions. Nutrition is supplemented with nasogastric or gastorostomy tube feeds high in energy and protein. All children are anticougulated routinely with warfarin after the neonatal period. Early bilateral nephrectomy is used to prevent the massive urinary protein losses. After dialysis and subsequent renal transplantation many of these children have now achieved an excellent quality of life and good long term prognosis. However, more and more reports of successful management of congenital nephrotic syndrome with prolonged survival without renal replacement therapy are becoming more and more available. Fairly recent reports on this promising outlook was achieved by Wong, Morris and Kara on Congenital nephrotic syndrome with prolonged renal survival without renal replacement therapy of 2013. [95]
The interventions for these secondary Nephrotic syndromes will be contingent on managing the associated pathological process.
Of equal importance in the management of these patients is the screening and intervention for infective complications, which complicates the clinical course and the therapeutic responsiveness of both CNF and CNS, by inciting an exacerbating additional immunopathological pathway in addition to a prolonged proteinuria resolution time.In the authors experience the presence of infections in general, but specifically especially urinary tract infections confounds the interventions for this subsets in several ways, besides the delayed the proteinuria resolution time until these infections were managed with the appropriate antimicrobial therapy,urinary tract infections confounds the accurate estimations of the urine dipstick examinations for proteinuria ,erythrocyturias and glycosurias.Equally,during infective events, the serum protein levels and the urinary selectivity ratios and coefficients are disturbed through the liberation of increased amounts of gamma globulins ,complements and specific and non-specific acute phased proteins associated with infectious,parainfectious or postinfectious events.
Also, the several complications of infections and septicemias yielded end vital organs and blood haemostatic disturbances which retarded the stabilization of these patients towards complete recovery.
CONCLUSIVE REMARKS&Recommendations.
At the present, the main challenge in CNS is to identify the cause of disease for individual patients. To make a definitive diagnosis, with the exclusion of infection related CNS and maternal associated disorders, pathology, family history, inheritance mode, and other accompanying congenital malformations are sometimes, but not always useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients, however, there are still some challenges with next generation sequencing that need to be resolved in the future.
Unexplained prolonged ill heath in infants with features of renal impairment should be explored for CNS, especially those subsets with recidivists or resistant proteinuria, even if selective given the considerable overlap between the clinicopathological features of CNS and the minimal change disease, as much as would be achievable cases of unexplained sudden infant deaths should have a histopathological examination of vital end organs ,but especially the kidneys for features suggestive of CNS.
The nosological histopathological nomenclature of microcystic disease should be borne in mind in the evaluation of these subsets since this is diagnostically, prognostically, prophylactically and therapeutically more encompassing and rewarding compared to a chronologically temporal one of congenital nephrotic syndrome which might implicate other nephrotic glomerulopathy such as allergic nephritis or Alports nephritis occurring equally within this period ,but without microcystic tubular dilatations.
This shortcoming warrants retrospective historical inquiry that could offer clues to the earliest onset of oedema (such as placentomegaly ,but especially with facial puffiness or pedal oedema which is the most clinically overt of the triad of hypoalbunaemia ,proteinuria and oedema ,this will imply reviews of child’s infant welfare health cards ,weight charts for sudden unexplained earlier weight gains and urinary colour ,frequency and volume.
Also children with nephrotic syndrome commonly present with abdominal pains which as a result of intestinal bowel oedema, ascites or SBP and respiratory difficulty due to significant pleural effusions, in addition, as a group nephrotic children are prone to a miscellaneous subset of infectious diseases especially respiratory tract and renal parenchymal infections disease spectrum which may point to a covert CNS, these aspects should be retrospectively enquired and reviewed in all children presently overtly with supposedly innocuous minimal change nephrotic syndrome.In utero Nuchal translucency at gestational ultrasound is a pointer to congenital lymphoedema and in all those cases should be evaluated for, and all cases where this is demonstrated, a search, determination and follow up for other features of congenital nephrotic syndrome should be aimed for, radiologically, pathologically and genetically.
The performance of a renal biopsy, at least amongst adults is required for the accurate diagnosis of recidivist nephrotic syndromes and for the formulation of a rational therapeutic interventional plan, however the situation is different for children who need not always be subjected to renal biopsy since careful historical, clinical and non invasive laboratory studies could lead to an accurate diagnosis in several instances,
Since considerations for the possibility of congenital nephritic syndrome has been under appreciated.
Blood pressure measurements, blood urea nitrogen .urinalysis and twenty four hour urinary outputs if routinely undertaken in this age group would identify those cases in the nephritic range of this congenital glomerulopathy with the opportunity for earlier intervention and the probability of a more favourable prognosis compared to the nephrotic phases.
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CLASSICS AND REVISITS IN SCIENTIFIC NEUROLOGY. Volume 5 Issue 2
Editorial Symposium from Collegiate Academic Transactions.
TITLE:
A Combined evaluative Explanatory Survey With Meta-Content Analysis For Several Subsets of Periodic Paralysis. On The Occasional Very Deleterious Impact Of Transient Periodic Paralysis Overlapping With Unclassifiable Paroxysmal Events OR Chronic Fatigue Syndrome (Fibromyalgia) Supports The Use Of An Indepth Clinical Pathological Electrophysiological Evaluations Of Cases With Thyroid Dysfunctions, Migranous Cephalgias with or without Neurological Sequelae For Compatible Features.
Research question, hypothesis and paradigm:
[II]-The need to achieve a distinction for the conundrum and continuum from hypokalaemic through normokalaemia to hyperkalemic Periodic Paralysis, suggests the need to consider normokalaemic periodic paralysis as an intermediate mosaic of the two extremes implying that serum potassium levels should not be the sole criteria for inclusion or exclusion of compatible cases.
Abstract:
Context, Conceptual Framework & Theory Literature.
Traditionally, periodic paralysis (PP) is a rare autosomally inherited genetic disease leading to muscle weakness, paresis or paralysis .Its clinical impact is spectral ranging from non-incapacitating occasional muscle weakness with ambulatory difficulties to permanent muscle decimation leading to a fatal respiratory muscle paralysis. It usually presents following common triggers such as cold, heat, unduly high carbohydrate meals, fasting state related hypoglycaemia, stress, emotional activities /excitement in addition to unduly vigorous activities.
At the molecular level, the underlying defects were skeletal muscle cell membranes ion channels malfunctions allowing an unregulated sarcolemmal influx or efflux of electrically charged ions, leading to depolarization and excitation (it is a form of channelopathy). It could be hyperthyroidism related or associated (thyrotoxic (PP)
In hypokalaemic (PP) Potassium leaks into the muscle cells from the blood stream, it could interact with a co-existing or epiphenomenal genetically inherent abnormalities in calcium channels in muscle cells, occasionally with sodium or potassium channels.
In hyperkalaemic Periodic Paralysis (PP) (Adynamia Episodica Hereditaria) potassium leaks out of the cells into the blood stream and interacts with genetically determined abnormalities in sodium channels.This form is usually accompanied by Paramytonia Congenita, the primary symptom of Paramytonia is muscle contractures, which develops during activities .Also similarly Paramyotonia Congenita attacks may also be triggered off by hypokalaemia.
Usually as sudden collapse following prolonged standing, in public places, or it may be occupationally related.
The diagnosis of periodic paralysis were unusually difficult with parents often reporting many futile efforts of several years with misdiagnosis and interventions with worsening symptomatologies.Part of this may be due to the fact that unclassifiable paroxysmal events were present in up to half of the cases with overlapping symptomatologies such as migranous cephalgias, speech difficulties, visual, auditory tactile and multisensory auras .Diagnostic accuracy was confounded and compounded by the facts that DNAs testings were available and achievable for only some common gene mutations
EMG results were normal except during attacks, however a properly performed exercise –EMG (compound Muscle Test) in the appropriate clinical setting could provide an accurate diagnosis in most instances. Most children will function fairly well with appropriate pharmacotherapy, environmental manipulations and lifestyle modifications.
The onset of hyperkalaemic periodic paralysis is in childhood, whereas the ones of the hypokalaemic type is in early childhood to adulthood (one to twenty five years of age),although this anecdotal concept has been challenged, the serum potassium levels do not necessarily have to range outside the normal limits to cause serious life threatening paralysis .Indeed against its classification schemes, these clinical features do not usually fit in neatly into hyperkalaemia or hypokalaemia and they should not be managed categorically. .In both these cases, the total body potassium is usually normal, but it just in the wrong place .The gene mutation, the ion channel affected and the amount of genetic change or expression could have significant impact on disability and therapeutic interventions.The progression of the hyperkalaemic Periodic Paralysis somewhat slows down towards middle age, whereas that of hypokalaemic periodic paralysis could be quite progressive and deleterious.
The hypokalaemic Periodic Paralysis were more common in boys. Electrocardiographic features compatible with hypokalaemia or hyperkalaemia were more indicative of the total body potassium compared to the serum/blood potassium levels .The changes of the blood potassium levels in the secondary forms were always marked, but this was not the case in the primary forms. Also hypermagnesaemia of any cause could be a cause of periodic paralysis.
Furthermore some genetic forms of Periodic Paralysis were associated with significant rhythm dysfunctions .Carbonic anhydrase inhibitors such as acetozolamide and dichlorophenamide were initially tried in patients with Periodic Paralysis on the basis of their kaliuretic effect for hyperkalaemic periodic paralysis and then based on serendipitously made observations, and probably because of its induction of alkalosis in hypokalaemic Periodic Paralysis. On the basis of our experience, for us Acetozolamide is probably a wonder drug. In the management of Periodic Paralysis of several aetiologies because of its modifying effects on channelopathies. It was found to increase extracellular proton concentrations which strongly inhibit ionic permeations through open calcium channels .They could also equally function by activating potassium calcium channels thereby modifying their pace making activities.
ESSENCE&OBJECTIVE
We have previously identified, presented, reported and discussed other domains of primary idiopathic myopathies in addition to acquired secondary systemic paralytic myoneuropathies.This paper aims to further report unusual and severe cases of presumptive primary idiopathic Periodic Paralysis in adolescent and adult males and females managed successfully by the authors.
Methodology:
Case Study with Triangulated Analytical Techniques and Methodological approach with Analysis of Empirical observations of Compatible Cases and Document Research through the use of Structured Qualitative and Quantitative independent content analysis, of Nominal and Ordinal data from the mainstream Journals and the Grey Medical Literature.
Case Study with Comprehensive Literature Reviews
The authors experience with periodic paralysis in childhood were highlighted with extremely severe cases of non-familial possibly dyskalaemic, normokalaemic, normocalcaemic normonatriemic, non-diurnal idiopathic periodic paralysis cases in previously healthy females with unclassifiable paroxysmal events initially inferred as convulsive equivalents associated with non-diurnal non myotonic tachycardiac recurrent episodic severely frank tetraparetic paralytic events lasting for about 24 hours in each instance ,and subsets of adolescent males with a new onset recurrent episodic prolonged paraparesis with visual difficulties occasionally lasting up to a week in some instances None of the parents were consanguineously married. Good outcome measures were achieved with appropriate conventional interventions in all instances with acetozolamide, environmental and life style modifications in addition to physical therapies. The global regional literature was briefly examined to buttress the import of achieving the diagnosis at the milder and earlier spectra of the defect, plausible diagnostic, therapeutic and prophylactic options were proffered and discussed.
CONCLUSIONS& SIGNIFICANCE.
This paper highlights cases at the upper range of the defect, given the spectral nature of the defect, it is likely that there are still many defects out there at the milder spectrum with minimal expressivities which could be therapeutically
Amenable at this stage compared to when it has progressed to decimated myopathic paralysis. This is one aspect where basic evaluations with in-depth comprehensive evaluation, applying commonly available inclusive biochemical profile, electrocardiogram and exclusive neuroimaging a tentative diagnosis could be achieved, fortunately this condition is amenable to commonly available diuretics/salts ,medical interventions and specific/generic deterrent options .
A review of the literature compares these cases with others described previously in the global medical literature and offers a systematic and standardized diagnostic and therapeutic approach/strategies for the more enigmatic and difficult cases.
MAIN TEXT:
INTRODUCTION
BACKGROUND, CONTEXT NOMENCLATURE& NOSOLOGY
THE TRANSIENT AND PERIODIC PARALYSIS:
This group of neuromuscular disorders is characterized by attacks of acutely developing paralysis, which spontaneously recover to complete normality, usually within a few hours. These conditions the periodic paralysis cause recurrent attacks which are usually associated with alterations of serum potassium concentrations .The clinical features like its inherited nature achieves the distinction between these forms from the acute and subacute monophasic conditions where the recovery is much slower such as the inflammatory, immune or neoplastic related dermatomyositis -polymyositis syndromes and electrolyte imbalance related paralysis or paresis including the other forms of potassium related disturbances in itself. They also differ from the disorders of neuromuscular transmission where there is increased weakness with superadded exercise-induced fatigue.
They differ from the numerous central nervous system causes of transient loss of muscle power, which include syncope, .seizures, transient ischaemic attacks of the brain, cataplexy, hydrocephalic attacks, and idiopathic drop attacks .It is most important to realize that any cause of excessively high or low serum potassium will produce diffuse muscle paresis by an effect on the resting sarcolemmal membrane potential .Hyperkalaemia causes hyperpolarisation, preventing the end-plate potential from reaching the critical depolarization potential required to fire the muscle fibre. Hypokalaemia produces depolarization, which produces depolarization inactivation (closure of the off-gate) of sodium channels in the sarcolemmal .Conditions such as excessive potassium administration and renal failure cause hyperkalaemia; and primary hyperaldosteronism (Conn’s syndrome) and diuretic (kaliuretic) and corticosteroids therapy may cause hypokalaemia.
In contrast, the familial periodic paralysis cause attacks of considerably greater muscle weakness than expected from the change in serum potassium. In fact, some patients have paralytic attacks without change in the serum potassium concentration .These observations suggest that the serum potassium changes may be secondary to some basic abnormality in the sarcolemmal.
At least five different syndromes of transient muscle weakness have now been identified these are:
[I]-Familial hypokalaemic periodic paralysis.
[II]-Hyperthyroidism with hypokalaemic periodic paralysis.
[III]-Familial hyperkalaemic periodic paralysis (adynamia episodica hereditaria of Gamstorp)
[Iv]-Paramyotonia congenita of von Eulenberg.
[v]-Normokalaemic Periodic Paralysis.
In each of these conditions, over a period of a few minutes or hours the patient develops a disorder of skeletal muscle which may vary from mild weakness of limb muscles to total paralysis and which subsides and disappears completely after a few hours or days. There are a few clinical features which suggest the exact type of periodic paralysis that is present, but generally, the diagnosis rests on determining the serum potassium level in an attack and on tests which attempt precipitate paralytic attacks either by increasing or decreasing the serum potassium concentration.
FAMILIAL HYPOKALAEMIC PERIODIC PARALYSIS.
Primary Hypokalaemic Periodic Paralysis:
This condition is inherited as an autosomal dominant trait, with decreased occurrence in females, but it may appear sporadically. A family history of migraine is often present. The onset is usually about the end of the first decade of life.The proximal muscles are affected first .The muscles innervated by the cranial nerves are spared such as the extraocular muscles ,the muscles of facial expression ,mastication ,and swallowing ,and the tongue muscles .
The diaphragm, is usually spared because its embryologic origin is from the bulbar territory, offering it a different neuronal impulsations.Attacks of weaknesses could be precipitated by rest after exercise, exposure to cold, emotional stress, high dietary intake of carbohydrates and sodium ,and administration of corticosteroids.
Attacks may last for days, but may be aborted by minimal non-physically demanding activities. These attacks may progress to a chronic form of weakness and atrophy, but in general attacks are less frequent after middle age.The serum potassium is low during an attack exposure to cold should be avoided. The disorder is consistent with a normative life expectancy
Familial hypokalaemic periodic paralysis is probably the most common of the periodic paralysis, though it is still a rare disorder. It is usually inherited as a Mendalian Dominant Trait. The patients have a normal strength except during well-demarcated episodes in which intense weakness or complete paralysis of limb and trunk muscles develops .The attacks begin in the second decade and are more frequent in adolescence or early adult years. A single attack may last from a few minutes to several days, the average duration being from half a day to about two days. The attacks seldom occur more frequently than every one month to one and half months. During the episode, marked hypotonia of the affected muscles and hyporreflexia are encountered, during the paralytic attacks, the affected muscles are refractory to electrical stimulation. The facial, pharyngeal, thoracic, and diaphragmatic muscles are rarely affected, however respiratory embarrassments and death have been reported. Although, the cardiac muscles are not directly involved, but there may be ECG changes related to the hypokalaemia.
The attacks are precipitated by several factors, such as rest after exercise, ingestion of sodium chloride or a large carbohydrate meal. Attacks commonly begin during sleep and are present upon awakening. Profuse diaphoresis may precede the attack .Often no precipitating cause can be discovered. Patients can often abort an attack by gentle exercise as soon as the first symptomatologies are perceived. On the average patient, there is no evidence of progressive muscular disease, and physical examination between attacks frequently demonstrates no abnormality .Rarely, there may be eyelid myotonia exacerbated by cold. Exceptionally, some degree of weakness, usually mild, persists after the termination of the attack and is cumulative in successive attacks. This sometimes causes a slowly progressive vacuolar myopathy of pelvi-femoral muscles during middle and late adult life (Gold flam)
Pathology:
Despite the striking paralysis, muscle biopsies often are normal, even in an acute paralytic attack .At other times, there is a significant vacuolization of muscle fibers. The vacuoles are filled with clear fluid, but in glycogen stains a few positive-reacting granules may be seen. Under the electron microscope the vacuoles appear to originate from the dilatation of the longitudinal endoplasmic reticulum. In the chronic state, the vacuoles probably communicate with the extracellular space.
Pathogenesis:
During the attack, the serum potassium level drops sharply .though rarely to very low values. This apparently results from the sudden passage of potassium into the cells of the body since the urinary excretion of potassium diminishes at the same time. The intracellular potassium levels of muscles have been demonstrated to rise during the attacks. According to the scholarships of Layzer on this theme. [1]
The resting membrane potential of the sarcolemmal is decreased both in the interactal period or to a greater extent during the attack. The primary abnormality in familial hypokalaemic periodic paralysis is not known but may be of one or more of the ion channels and ion pumps in the sarcolemma.As was stated above, the entry of potassium into the muscle may be a secondary process.
The relation to excess carbohydrate intake is probably connected with the fall in serum potassium level and rise in intracellular levels of potassium in muscle and liver which occur during rapid glycogen storage.However, the timing of these two events differs. The initial potassium changes occur during the first few hours after carbohydrate ingestion, while the attack of periodic paralysis is frequently delayed for about eight to twelve hours.
DIAGNOSTIC ASPECTS OF HYPOKALAEMIC PERIODIC PARALYSIS.
This rests on the finding of a low potassium concentration in a spontaneous attack .The diagnosis can be confirmed by the precipitation of a paralytic attack by the intravenous infusion of glucose at two grammes per kilogram body weight, followed ten minutes later by the intravenous injection of ten to twenty units of soluble insulin. Provocative tests which induce weakness and thus confirm the diagnosis include [I]-Exercise and [II] giving insulin, a quarter units per kilogrammes subcutaneously, simultaneously with glucose four fifths grammes per .kilogrammes orally.
Therapeutic interventional aspects for Hypokalaemic periodic paralysis.
Episodes of familial hypokalaemic periodic paralysis are treated by the oral administration of potassium salts in doses of 30 to 120 mEq until the attack is relieved.In the rare instances where acute respiratory or pharyngeal paralysis appears, it may be necessary to give potassium intravenously though great care should be taken with this route of administration
Apposite therapeutic interventions and its maintenance imply giving potassium chloride, two to ten grammes orally, to terminate an, attack, and two to ten grammes at bedtime in between attacks. The patient should be encouraged to eat a low-carbohydrate, low-sodium diet Thiamine may abort the effects of carbohydrates, and unnecessary
The serum potassium concentration, ECG, and muscle strength should be followed at fifteen minutes intervals, the attack usually begins within one and half hours and may be aborted by oral or if necessary intravenous potassium .Patients do not develop a paralytic attack when given thirty to fifty milliequivalence of potassium orally, unlike the reaction seen in the hyperkalaemic form of periodic paralysis.
In patients with frequent attacks of familial hypokalaemic periodic paralysis, sixty to one hundred and twenty milli equivalence of potassium per day by mouth in divided doses and avoidance of meals high in carbohydrate are helpful in preventing attacks .Acetozolamide (Diamox), up to two grammes per day in divided doses may also prevent paralytic attacks. This serendipitous effect is paradoxical, since this carbonic anhydrase inhibitory diuretic is mildly kaliuretic, and the presumptive action appears to rest on the alkalosis which it induces.
HYPERTHYROIDISM WITH HYPOKALAEMIC PERIODIC PARALYSIS.
Attacks of hypokalaemic periodic paralysis are frequently due to thyrotoxicosis particularly in Orientals, but also in the Occidentals .These attacks are identical to those in the familial condition, but patients generally do not have a positive family history.The pathogenesis of this condition is not clearly understood, but the attacks disappear with the correction of the hyperthyroidism.
FAMILIAL HYPERKALAEMIC PERIODIC PARALYSIS (ADYNAMIA EPISODICA HEREDATARIA OF GARMSTORP)
This is also a Mendelian dominant condition and is characterized by periods of weakness or paralysis of skeletal muscle not unlike those of familial hypokalaemic periodic paralysis. The onset is between the ages of five and ten years .The attacks are frequent and may last for one to many hours and then tend to occur during rest after physical exertion, particularly if the patient is wet, cold or hungry. Tingling of the lips, fingers or toes may occur at the onset of attack .Weakness varies in degree. Respiratory embarrassment is virtually never seen, between attacks, the patient is symptom free, though in some cases mild weakness persists for days or weeks at a time. Some patients have clinical and electromyographic myotonia.
The diagnosis rests on the finding of a serum potassium concentration that rises transiently in the attack. Paralysis may be present with a serum potassium concentration of five to six milli-equivalents per litre.The diagnosis can be confirmed by the precipitation of an attack by the oral administration of thirty to one hundred and fifty milli-equivalence of potassium. The ECG, muscle strength and serum potassium should be monitored every fifteen minutes. This test should be avoided if there is renal or cardiac insufficiency and the patient should have an intravenous route for the administration of glucose and insulin if reversal of the hyperkalaemia or paralysis is imperative. Muscle biopsy is usually normal, and electromyography shows electrical silence in the paralysed muscles.
The pathogenesis of familial hyperkalaemic periodic paralysis is uncertain but probably due to some abnormality of sarcolemmal ion channels or ion pumps.
An increased sodium permeability has been suggested as an explanation of the observed partial depolarization of the sarcolemmal membrane during the interactal period and the greater depolarization during the attack. If correct, the release of potassium from muscle into the serum is a compensatory flux tending to repolarise the sarcolemma.The acute attacks should be treated by oral glucose, a kaliuretic diuretic such as the thiazides prevents attacks in some patients. However, the latter agents may exacerbate the myotonia in patients where this is prominent.Acetazolomide up to 2g per day in divided doses, is often effective in preventing attacks.
PARAMYOTONIA CONGENITA OF VON EULENBERG.
The principal feature of this disease is stiffness (myotonia) and weakness or paralysis following exposure to cold .It is inherited in a Mendelian dominant trait.
The myotonic features of this disease are usually the most prominent, though in some cases there are rare attacks of weakness similar to those of periodic paralysis which may or may not be related to cold. The serum potassium concentration may rise in attacks, and the administration of potassium may induce an attack the resting membrane potential of muscle fibers during the attack is reduced. The myotonia in this syndrome may be limited to the eyelids or tongue. Muscle biopsy reveals no abnormality, vacuolization is seldom seen.
Normokalaemic PERIODIC PARALYSIS
Although, previous few reports of patients having attacks of periodic paralysis without changes in the serum potassium concentration exists, however more and more reports on this theme are increasingly becoming available ,some of these attacks respond to the intravenous infusion of sodium chloride ,attacks may be precipitated by oral potassium administration ,and not by intravenous glucose and insulin. Thus there are features linking this condition to familial hyperkalaemic periodic paralysis, but its nosological position remains to be clarified.
Methodological Issues:
Case Studies with Triangulated Analytical Techniques and Methodological approach with Analysis of Empirical observations of Compatible Cases and Document Research through the use of Structured Qualitative and Quantitative independent content analysis, of Nominal and Ordinal data from the mainstream Journals and the Grey Medical Literature. The global regional literature was examined to buttress the import of achieving the diagnosis at the milder and earlier spectra of the defect, plausible diagnostic, therapeutic and prophylactic options were proffered and discussed.
Results, Literature Reviews and Discussions:
Histriographic Background & Archival Historical Research:
Primary Hyperkalemic Periodic Paralysis. (Adynamia Episodica Hereditaria of Gamstrorp.) or Hyperkalaemic Periodic Paralysis:
Hyperkalaemic PP was originally described in 1951 by Tyler et al
In their original classic article, Tyler, Stephens, Gunn and Perkoff detailed on the Studies in disorders of muscle.VII.Clinical manifestations and inheritance of a type of periodic paralysis without hypopotassemia.and seminally disseminated their results. [2]
Hyperkalaemic PP was further extensively investigated by Gamstrop in 1957, who attached the nomenclature adynamia episodica hereditaria. (of Gamstorp) to it. [3]
The term was later changed to hyperkalaemic periodic paralysis on the basis of the provocative impacts of acute potassium intake, in addition to the rise in serum potassium levels associated with its episodic, instantaneous and spontaneous attacks.Hyperkalaemic PP is an autosomal dominant myogenic channelopathy with an almost absolute complete penetrance.it is occasionally associated with nondystrophic myotonias.These aspects were further characterized by Lehmann-Horn, Rudel and Jurkat-Rott et al in their book chapters on Nondystrophic myotonias and periodic paralysis.In the book on Myology edited by Engel and, Franzini-Armstrong published by NcGraw-Hill Professionals.[4]
This form of periodic paralysis which has its onset in the first decade of life, is usually detected in infancy because of “starring eyes” (myotonic form of lid lag), or the mother may note that the infant has a very feeble cry, especially on waking. It is inherited in an autosomal dominant form .Pseudohypertrophy of the calf muscles is often present. There is in increased incidence of diabetes mellitus
The attacks are relatively short, lasting about thirty minutes to two hours and may be precipitated by rest after exercise, cold and fatigue .Attacks usually occur in school age children and then abates. The serum potassium rises during attacks. The EMG may demonstrate myotonia of the external ocular and facial muscles. Treatment is with hydrochlorothiazide fifty milligrammes orally daily, or acetozolamide (Diamox) two hundred and fifty milligrammes orally daily .Dichlorophenamide (Daranide), fifty milligrammes orally daily, has also been recommended. The dose must be adjusted for each case. The disorder is consistent with a normal life span.
Normokalaemic Periodic Paralysis.
In this disorder, the onset is in the first decade of life. It is inherited in an autosomal dominant fashion. Attacks come on during rest after exercise, with cold, following ingestion of foods high in potassium (such as many fruit juices), and following ingestion of alcohol .The attacks may last for days.
In normokalaemic paralysis, serum electrolytes do not change during attacks. Muscle biopsy may demonstrate vacuolar myiopathy.Treatment consists of increased salt intake; acetozolamide (Diamox|), two hundred and fifty milligrammes daily orally, with dosages adjusted for each case; and fludrocortisones one tenth milligrammes daily orally. The overall prognosis is generally good. In 1964.Pearson classically discussed the periodic paralysis its differential features and pathological observations in permanent myopathic weakness. [5]
A Comparative overview of the different forms of Periodic Paralysis:
Nosology, Literature &Theory.
Periodic paralysis is a rare neuromuscular disorder, related to a defect in muscle ion channels, characterized by episodes of painless muscle weakness, which may be precipitated by vigorous exercise, fasting or high carbohydrate meals.
Periodic paralysis (PP) is classified as hypokalaemic when episodes occur in association with low potassium, or high- carbohydrate meals.
Periodic Paralysis (PP) is classified as normokalaemic when episodes occur in association with normal potassium blood levels or as hyperkalaemic when episodes can be induced by elevated potassium levels.
Where as the patients suffering from type 1 hypokalaemic periodic paralysis (Hypo PP1) experience attacks of muscle paralysis associated with hypokalaemia.
Hypokalaemic periodic paralysis arises from missense mutations in the genes encoding the gated myogenic ion channels. Fairly recent data on this theme by Allard and Fuster of 2018 suggests that: insights into the pathophysiology of type 1 hypokaelemic periodic paralysis could be deciphered when muscle Ca2+ channels carry monovalent cations through gating pores is appreciated.[6]
For a fairly long time it has been axiomatic that most cases of hypokalaemic PP are hereditary, usually with an autosomal dominant inheritance pattern. This concept has stood the test of time and has been reaffirmed by the inferential scholarships of Ober in 1992 [7] and reaffirmed by those of Fontaine, Lapie and Plassart of 1996. [8]
Aggregating the data from the 2006 studies of Venance, Cannon and Fialho, et al.The primary periodic paralysis, diagnosis, pathogenesis and treatment proposes that .however in approximately thirty three percent of cases, of hypokalaemic PP, the inheritance pattern is consistent with new mutations, thereby distorting the inheritance pedigree pattern anticipated from an autosomal dominant pattern.[9]
This concept on new mutations is corroborated by previous data from the 2004 investigations of Miller, Dias da Silva and Miller et al on the Correlation of the phenotype and genotype in the periodic paralysis. [10]
Also, in the same vein, although Hyperkalaemic PP is typically hereditary in an autosomal dominant fashion, de novo new mutations have also been equally described and reported. An indepth scholarship on the genetics and hereditary aspects of hyperkalaemic PP was proffered by Schpira and Griggs in the book chapters on Muscle disease provided in the blue books of practical neurology. And published by Elsevier in 1991. [11]
Acquired cases of hypokalaemic PP have been described in association with hyperthyroidism. Thyrotoxic periodic paralysis (TPP) Belongs To A Group of Muscle Diseases called channelopathies, which present with painless generalized muscle weakness without exertion. Very recent report on the consistency of this specific endocrinological myopathic association with the iatrogenic impact of its therapeutics has been provided by Ahamed, McCalley and Sule on their observational annotation that Steroids and Thyrotoxicosis Precipitate Periodic Paralysis of 2018. [12]
And several previous inferences of the consonance of this specific hypokalaemic endocrinological myopathological linkage exists.Kung in 2006, highlighted and discussed this causality in his Clinical review. On Thyrotoxic paralysis: as a diagnostic challenge. [13]As did Lin in his annotations and discussions on Thyrotoxic periodic paralysis of 2005. [14]
And also Ko, Chow and Yeung et al alluded to this hypokalaemic Thyrotoxic periodic paralysis in a Chinese population.in 1996. [15]
In addition to the data results on the vivo and invitro sodium pump activity in subjects with thyrotoxic periodic paralysis proffered by Chan, Shinde and Chow et al of 1991. [16]
And chronologically more and more data buttressing the strength of the implication of thyrotoxicosis in periodic paralysis are increasingly being made available by several authors.
Anderson’s disease.
Anderson’s disease could be associated with Periodic Paralysis (PP)
Tawil, Ptacek, and Pavlakis, et al in 1994 proposed Andersen’s syndrome as a potassium sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. [17] And this proposition was corroborated by the 1997 scholarships of Sansone, Griggs and Meola et al on this multifaceted pathological associational entity in Andersen’s Syndrome. [18]
Large comparative clinical, laboratory, electrophysiological and genetic studies on Periodic Paralysis are lacking, making the aggregation of available data crucial for a more lucid and encompassing dissection of its character especially the elusive, paradoxical and obscure aspects of its pathobiophysiology and therapeutics.
Data from Previous Epidemiological & Demographic Research.
Fontaine in his concerted scholarship of 2008 on this theme proposed that Hypokalaemic Periodic Paralysis (PP) is the most common of the periodic paralysis, but is still relatively quite rare, with an estimated prevalence of one in a hundred thousand.However,It is twice as common as the hyperkalaemic form of PP.[19]- Several epidemiological studies on hypokalaemic periodic paralysis exists. Phakdeekitcharoen, Ruangraska and Radinahamed in 2004 rigorously approached Hypokalaemia and paralysis in the Thai population and eminently disseminated the results of their research. [20]
Whereas according to the scholarships of Lehmann-Horn, Rudel, Jurkat-Rott et al of 2004, the Hyperkalaemic PP affects approximately one in every two hundred thousand individuals. [4]
Overall myotonia and paramyotonia appear to affect a larger proportion of individuals with hyperkalaemic Periodic Paralysis than was previously recognized.
The Genetic Inheritance Pattern of Periodic Paralysis.
Results of fairly recent scholarships by Vicart of 2010 asserts that in hyperkalaemic PP, Point mutations in the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Navl 4 lead to defective channel function.This disrupts the normal exchange of ions in skeletal muscles, consequently reducing their ability to contract and resulting in attacks of muscle weakness or paralysis. [21] And there after other corroborative resources emerged. [22]
In Hyperkalaemic PP, the same mutations can have variable expressivity within and between families, with the severity of the attacks quite erratic or spectral. [21]
Whereas phenotypically, the disorder of hypokalaemic periodic paralysis (PP) is more eloquent and symptomatologically expressed in the male gender with a male to female ratio of about seven is to two, probably because, clinical penetrance is often incomplete in the feminine gender. These Gender differences in penetrance and phenotype in hypokalaemic periodic paralysis was highlighted and speculated upon by Ke, Luo, Qi, et al in 2013, [23] as did the previous familial molecular epidemiological reviews of Elbaz, Vale-Santos, Jurkat-Rott, et al on Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL 1A3) with genotype and phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 Caucasian families of 1995. [24]
In most investigations, the genetic diagnosis of Periodic paralysis is focused specifically to those cases with mutations such as : A499T,El702K,F1311V,G1306A,G1456E,I1160V,I1495T,I693T,L1436P,L1489H,L433R,M1360V,M1592V,R1448C,R1448H,S804F,T1313M,T704M,and V12931 with the occasional mention of the other identified but unreported candidate mutations.
In at least one of eight to one of nine instances there is a report of an affected relative with hyperkalaemic Periodic Paralysis, in those instances without a family member diagnosed with Hyperkalaemic Periodic Paralysis, several reported a
Family history of multiple relatives with Paramyotonia Congenita (PMC), but without associated hyperkalaemic Periodic Paralysis events. In such instances, those index cases without associated hyperkalaemic Periodic Paralysis or Paramyotonia Congenita (PMC) apparently were related to de novo mutations.
Familial cases tend to have a predilection for the same shared symptomatologies for the paramyotonia and myotonia respectively.
An Asian Chinese familial molecular epidemiological study of 2005.on the genetics of hypokalaemic periodic paralysis was proffered by Wang, Liu, Xu, et al.on Novel CACNA1S mutation causes autosomal dominant hypokalaemic periodic paralysis in a Chinese family. [25]And another familial Asian Korean genetic study of 2005.by Kim, Lee and Hur on A Korean family of hypokalaemic Periodic Paralysis with Mutation in a voltage-gated calcium channel (R1239g) is available. [26]
A Scandinavian familial molecular epidemiological study of 1997 by Sillen, Sorensen T, Kantola I, et al on the Identification of mutations in the CACNL 1A3 gene in thirteen families of Scandinavian origin having hypokalaemic periodic paralysis and evidence of a founder effect in Danish families dissected the genetics of the familial hypokalaemic periodic paralysis and seminally discussed their results. [27]And several other genetic studies exist.
Morrill, Brown Jr Cannon approached the Gating of the L-type Ca channel in human skeletal myotubes as an activation defect caused by the hypokalaemic periodic paralysis mutation R528H in 1998. [28]
In 1999, a novel sodium channel mutation in a family with hypokalaemic periodic paralysis was the topic of interest of Bulman, Scoggan and van Oene et al. [29]
In addition to the 2001 scholarship of Sternberg, Maisonabe and Jurkat-Rott, et al on Hypokalaemic periodic paralysis type 2 caused mutations at codon 672 in the muscle sodium channel gene SCN4A. [30]
Previously in 1996,Lapie , Goudet and Nargeot et al.studied and discussed the electrophysiological properties of the hypokalaemic periodic paralyses mutation(R528H) of the skeletal muscle alpha 1 S subunit as expressed in mouse l cells . [31]
The Genetic defects in Andersen’s syndrome has been deciphered
Tristani-Firouzi, Jensen and, Donaldson et al. researched, reviewed and discussed the Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen’s syndrome) in 2002. [32]
Whereas Davies, Imbrici, and Fialho et al analysed, discussed and seminally dissected Andersen-Tawl syndrome as new potassium channel mutations and possible phenotypic variation in 2005. [33]
Fairly recently, Belus, Rogers and Bats experimentally demonstrated that EA Kir 2.1 is important for efficient BMP signaling in mammalian face development. And concluded that Mutations that disrupt the inwardly rectifying potassium channel Kir 2.1 lead to Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmias, cognitive deficits and craniofacial dysmorphology. [34]
Although the symptomatologies and expressivities could be greatly attenuated in some subsets of familial periodic paralysis with incomplete penetrance, other subsets with florid and markedly severe extensive disease has been described in several large families.Caciotti, Morrone and Domenici, et al in 2003 demonstrated and identified a severe prognosis in a large family with hypokalaemic periodic paralysis. [35]
Aetiology, inciting and risk factors associated with Periodic Paralysis.
Perturbations in the sodium-potassium ATPase gated channel pump has been proposed by several authors as the implicated factor in both the hypokalaemic and hyperkalaemic periodic paralysis. Chronologically, in 1982 Layzer tackled and reconciled the periodic paralysis and the sodium-potassium pump as a thematic concept. [1]
Tanabe, Beam, Powell and Numa demonstrated, dissected and eminently disseminated the restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA in 1988.[36] In 1999, Ruff demonstrated and reiterated that Insulin acts in hypokalaemic periodic paralysis by reducing inward rectifier K+ current.[37]
The impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalaemic periodic paralysis was studied and discussed by Tricarico, Servidel and Tonali et al in 1999. [38]
As a seminal and emerging concept, gating pore current in an inherited ion channelopathy was tackled and dissected by Sokolov, Scheuer and Catherall in 2007. [39]
Whereas in 2009, Matthews, Labrum and Sweeney et al.hypothesised and demonstrated that voltage sensor charge loss accounts for most cases of hypokalaemic periodic paralysis. [40] In addition to the, discoveries of Leaky sodium channels from voltage sensor mutations in periodic paralysis.but not paramyotonia by Francis, Rybalchenko, Strucyk and Cannon of 2011. [41]
Paralytic attacks in hyperkalaemic periodic paralysis could be incited or precipitated by the restive state following a rigorous exercise.
Hyperkalaemic periodic paralysis could be provoked by or worsened by anaesthesia, potassium replete crystalloids infusion, relative hypothermias in chilly environments, a famish state, psychogenically challenging emotive dysthymic dispositions, corticosteroids use ,in addition to the gestational state.
For further reviews on the inciting agents of hyperkalemic periodic paralysis See the 2010 scholarships on this theme by Vicart. [21]
During pregnancy, about one nine in of the women reported an increase in the attack frequency, however a total of one in eight reported an improvement in muscle weakness during attacks, where as three quarters to four in five reported worsening of stiffness, a quarter suggested some improvement in muscle stiffness during pregnancy. So overall, on the average the general impression during pregnancy happens to be increased attack frequency, improved muscle weakness during attacks, and worsened muscle stiffness during attacks.
Common pathological associations and phenomenological risk factors linked and related to Familial Periodic Paralysis include thyroid abnormalities, cardiac arrythmias, migranous cephalgias and hyperlipidaemias (hypercholesterolaemia and hypertriglyceridaemias)
Although more commonly associated with hypokalaemic periodic paralysis, however,anecdotally thyroid dysfunctions were computed to affect about one in five of the hyperkalaemic Periodic Paralysis cases, putting them at a relative risk(RR) of three to four compared to the general population and this achieved both statistical and clinical significance (p<0.0001)These aspects of thyroid dysfunction periodic paralysis were addressed by Bjoro, Holmen, Kruger, Midthjell, Hunstad, Schreiner, Sandnes and Brochmann on their scholarship on the Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population (The Health Study of Nord-Trondelag (HUNT) of the year 2000.[42]
Where as Cardiac arrhythmias were reported in about one in ten by several population studies, which though not statistically significant compared to the general population (p=0.04) statistical significance requires a p value of (0.005), was clinically significant
Electrcardiographic changes suggestive of hyperkalaemia or hypokalaemia could be demonstrated in these subsets of periodic paralysis, although this is not invariable. These aspects were comprehensively dealt with elsewhere by Rose and Post on their scholarship on the Clinical Physiology of Acid-Base and Electrolyte Disorders of 2001. [43]
However, neither the prevalence of migranous cephalgias nor of hyperlipidaemias is exacerbated in Familial Periodic Paralysis compared to the general population. Prior to achieving the diagnosis of hyperkalaemic Periodic Paralysis, subjects were misdiagnosed with pathologies such as malingering, conversion disorders, hypokalaemic Periodic Paralysis, Paramyotonia congenita and depressive or dysthymic symptomatologies.
Suggested attack inducers that exist for hyperkalaemic Periodic Paralysis are quote diverse and on a continual basis, new inciters are being added to those previously reported As many as one in seven have reported chilly cold environments as a precipitant of symptomatologies for both the hyperkalaemic and the hypokalaemic subsets. This diathesis to cold induced susceptibility is more common in mutant SCN4A, as was highlighted by Sugura, Makita and Li et al in their scholarship of 2003,that Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalaemic periodic paralysis [44]
Rest after exercise in one half, stress or fatigue in one half, alcoholic beverages in about two in five cases, hunger in about two in five cases ,marked alteration in the rate of physical activities normally undertaken by the individual in a third ,potassium in the food ingested by the individual in a third, identified specific beverages or foods in a third, alterations in the humidity in a third, excessive sleeping in the afternoons in a quarter, pregnancy in a third ,uncharacterized ill health in about one fifth, menstruation in about one sixth, medications in one sixth and one seventh potassium supplements.
Sleep is comparable to a restive state following a vigorous activity in inciting or inducing attacks of hyperkalaemic periodic paralysis.
As for hypokalaemic periodic paralysis several associated factors have been determined notably but not confined to: syndromic associations such as Gitelman syndrome.Ng, Lin and Hsu et al in 2006 undertook a familial case study of Hypokalaemic paralysis due to Gitelman syndrome: [45]
Associations of Periodic Paralysis with Autoimmune disorders:
Previous reports of presentations unusually in association with Sjogrens syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest exists. Primary Sjogrens syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest, was reported and discussed by Fujimoto, Shiiki, Takahi and Dohi in 2001. [46]
Myasthenic symptoms in both the hereditary and acquired forms of Myasthenic gravis overlap with those of periodic paralysis especially those of hypothyroidism with shared associations between MG and PP.
Pharmacotherapeutic agents as precipitants of Periodic Paralysis.
Tucker and Villanueva on the basis of their observational scholarships of 2013 on this theme intimated that attacks of acute hypokalaemic periodic paralysis could possibly be precipitated by albuterol. [47]
Malignancies as aetiological Factor for Periodic Paralysis:
Malignancies such as prostatic carcinomas was implicated as a covert and insidious cause of hypokalaemic paralysis in a patient with prostate cancer by Cheng, Chen, Chau and Lin in 2004. [48]
Autoimmune Endocrinopathies and Metabolic Conditions:
Thyrotoxicosis:
Agarawol, Wadwa and Wali reiterated the axiom that Hypokalaemic periodic paralysis is associated with thyrotoxicosis in 1994. [49]
This was corroborated by the 1999 scholarship of Manoukian, Foote and Crapo on the Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes [50]
Diabetes Ketoacidosis with Hypophosphataemia.
Liu and Jeng reported severe hypophosphataemia in a patient with diabetic ketoacidosis and acute respiratory failure as a form of acquired acute periodic paralysis in 2004. [51]
This illustrative and instructive case study with literature reviews describes the authors experience with compatible cases of periodic paralysis .Study objectives include to buttress and reiterate previously reported descriptions of the disease, to decipher new and previously undescribed and unreported features and associations, and to provide a more lucid comprehension of the experience of patients with periodic paralysis. It also summarizes the position statements and evidence on the Periodic Paralysis to date, and critically appraises and evaluates some of the concepts and data in the literature.
With the employ of independent research document content analysis, the extant, modern and current global medical literature were rigorously examined to characterize the epidemiology, symptomatologies, diagnostic ,therapeutic and prophylactic options and unusual associations of hyperkalaemic periodic paralysis. This applied to cases with specific and definite genetic mutation data, in addition to severe amino acid substitutions in typical and classical hyperkalaemic periodic paralysis.
THE NATURAL HISTORICAL, CLINICAL AND ELECTROPHYSIOLOGICAL (EMG, EEG.ECG)
PHENOMENOLOGIES OF PERIODIC PARALYSIS.
The clinical presentation of hyperkalaemic periodic paralysis could be very covert and indeed elusive especially to the unwary, because in between attacks lid lag secondary to eyelid myotonia may be the only clinical sign present
This occasional diagnostic clinical conundrum was fairly recently highlighted and discussed by.Jurkat-Rott and, Lehmann-Horn in their 2011 Hyperkalaemic periodic paralysis type 1.Gene Reviews. [52]
And previous scholarships on this theme by Amato and Russell are available in their eminently published and disseminated work on the neuromuscular disorders. [53]
,in this way of unusual presentation with lid lag, familial hyperkalaemic periodic paralysis could mimic hyperthyroidism unassociated or uncomplicated with periodic paralysis in its myotonic phase ,but also hyperthyroidism associated or complicated by periodic paralysis in its paretic or paralytic form,in the absence of an overt orthotopic goiter this makes the consideration of an ectopic proximate retrosternal or lingual thyroid or a distant metastatic teratomatous ovarian tissue ( struma ovarii )imperative in such cases ,other differential diagnostic considerations will include the Myasthenia gravis denovo or thyroiditis related myasthenia in addition to the Eaton Lamberts syndrome in association with Oat cell carcinoma of the Lungs in an appropriate clinical and pathological setting,
Previous experience of the author on childhood and adolescent myasthenia gravis and periodic paraluysis included hyperthyroidism. [54]
The term periodic paralysis is a misnomer,
The term periodic paralysis is a misnomer, especially when applied in the context of Hyperkalaemic PP which is characterized by attacks of flaccid muscle weakness that are infact episodic, paroxysmal ,rather than periodic in character as is implied by its nomenclature. Although it was not entirely explored previously, on the average, the fact that attacks of Periodic Paralysis typically commences in infancy to later childhood, before adolescence and pubertal period, its relationship to endocrinopathies especially hyperthyroidism and its response to acetozolamide may well suggest the role of hormonal, in addition to other humoural factors such as prostaglandins in its aetiopathophogenesis.
In Hyperkalaemic PP, Bouts of paralysis typically commences in the first ten years of life, with increasing events cumulatively until it finally climaxes in the late adolescence age. Fortunately in some cases, the hyperkalaemic PP event gets considerably more seldom in midlife .This was previously remarked upon and annotated on by the fairly recent contributions of Jurkat-Rott and Lehmann-Horn of (2011) on Hyperkalaemic periodic paralysis type 1.Gene Reviews. [52]
Jurkat-Rott et al opined that however the persistence of symptomatologies of hyperkalaemic periodic paralysis does not augur well with a favourable outlook, because prognostically these subsets have been noted to suffer attacks of chronic progressive myopathy that can cause permanent muscle decimation and weakness. [52] As did Lehmann-Horn and Jurkat-Rott in their scholarships and reviews on Genotype-phenotype correlation and therapeutic rationale in hyperkalaemic periodic paralysis neurotherapeutics of 2007. [55]
In hyperkalaemic PP, paralytic attacks demonstrates no diurnal variation as such,
Although hyperkalaemic PP, paralytic attacks may occur at any time, anecdotally and evidentially, they frequently occurs in the morning before the first meal of the day in about three fifths of the cases, However, more recent reports have given more weight to sleeping offering a figure of about one half and other series proffered a figure of two in five in the awakening post hypognonomic state ,where as the afternoon (post cibal period) and the evening periods were reported in one in five to one third of the cases in other series respectively.
Typically, these attacks may last for up to sixty minutes or more with an undertermined, erratic and staggered recovery temporal course.
For excellent reviews on the thematic aspects of the natural history of Periodic Paralysis see the fairly recent reviews of 2012 on this theme by Dugdale, Lin and, Zieve on Hyperkalaemic periodic paralysis abstracted, catalogued and indexed at the U.S.National Library of Medicine. [56]
In addition to the re-echos of these of aspects by Jurkat-Rott and Lehmann-Horn and Amato and Russell in 2011 and 2008.respectively. [52] [53]
In other instances, attacks could last anywhere from thirty minutes to several hours
Data from the clinical trials of Venance ,Cannon ,Fialho ,Fontaine ,Hanna ,Ptacek ,Tristani-Firouzi ,Twill and,Griggs et al on behalf of the ,CINCH investigators. on The primary periodic paralysis; diagnosis, pathogenesis and treatment. Of 2006; infers that exceptionally, with progressive disease, attacks have been prolonged for several days continually. [57]
Whereas those with hypokalaemic periodic paralysis experience generalized flaccid paralysis, those with hyperkalaemic periodic paralysis seldom, experience a global flaccid paralysis.
Hyperkalaemic periodic paralysis cases seldom, experience widespread flaccid paralysis but rather are inclined towards focal muscular weaknesses, especially implicating the thigh and calf muscles Also, in addition the muscular dysnergia and hypotonia in hyperkalaemic periodic paralysis subsets tends to be [i]-exclusive of myotonia in one subset ,[ii]-associated with ,inclusive of or existing incidentally with a clinically overt myotonia in another or [ii] co-existing epiphenomenally with a coincidentally clinically covert but electromyographically(EMG) demonstrated Myotonia or in the setting of a [iv]- myogenic dysnergia expressed synonymously with a denovo paramyotonia congenita(PMC)
These aspects were thematically illustrated by Canon and George in their book chapters on the Pathophysiology of myotonia and periodic paralysis .In the book the Diseases of the Nervous System, edited by Asbury, McKhann and McDonald WI, et al in 2002. [58]
In some instances of hyperkalaemic Periodic Paralysis, the co-existence of myotonia or paramyotonia may not be conclusively established because even after a life or video assisted illustration, most subjects could not confidently assert that they has these phenomenologies.Between 2007 and 2008, Lehmann-Horn, Jurkat-Rott, Amato and Russell comtemperonously but independently proposed that the clinical pattern of the paralytic attacks is uninfluenced by the .subtype of myotonia. [55] [53]
During the paralytic attacks, the superficial abdominal and the deep tendon reflexes during an attack may be absent or diminished, and exceptionally, there may be dysphonia, dysphagia and dyspnoea related to bulbar and respiratory muscle pathological implications.
Amato and Russell opines that Although, normally, since hyperkalaemic periodic paralysis is a motor myogenic pathology, the sensations to the stimuli modalities of touch, pain, temperature, vibration, kineasthology, pressure were not ordinarily implicated, but perturbations of sensations reported during bouts of hyperkalaemic PP attacks included but were not confined to: prodromes and aura of myogenic paraesthesias, tingling, needles and pins sensations and variable degrees of relative rather than absolute numbness.
Furthermore, also several other subjects reported focal muscular tenderness, several myogenic nociceptive or unpleasant and discomforting sensations of some disabling or dysfunctional character, [53]
Observational follow up studies by Jurkat-Rott and Lehmann-Horn in 2011 opines that However normally overall, most attacks in affected subjects were not usually complicated by arrythmogenic cardiomyogenic events or cardiopulmonary insufficiency of any suspicious flair or deleterious character.
[52]
In the other outstanding instances, in between attacks individual cases with known hyperkalaemic periodic paralysis will have normal sensation, normal muscle stretch reflexes and muscle length. In 2008,Amato and Russell observed that although, certain individuals may experience myotonia in between paretic or paralytic events in hyperkalaemic periodic paralysis, however overall, the myotonia is often mild ,could be precipitated and aggravated with muscular groups activations through tapping or manoeuvres involving the facial, the lingual ,the forearm muscles and the thenar eminence. It does not generally hinder voluntary motions, and myotonia is usually ameliorated by repetitive muscular activities.The emphasis is on myotonia (i.e., defined by Dorland’s as repetitive but non-tetanic myogenic spasms) [59]
Since the normal course of myotonia in association with hyperkalaemic periodic paralysis in innocuous, with regards to achieving a distinction between these subsets and other subsets of periodic paralysis, though of clinical and therapeutic relevance in exceptional instances, overall this distinctiveness is more of an academic activity. [53]
The only exception to the benign course of the myotonia in hyperkalaemic periodic paralysis appears to be those subsets with paramyotonia congenita (PMC), who experience muscular rigidity and stiffness which increases instead of decreases with continued activities, in addition to cold induced exacerbations of its symptomatologies.An elegant overview on this clinicopathological overview and its nosological characterization has been achieved in the Myology Monograph of 2004 authored by Lehmann-Horn, Rudel and Jurkat-Rott on Nondystrophic myotonias and periodic paralysis.and edited by: Engel, Franzini-Armstrong.[4]
Prevalence studies of myotonia and paramyotonia in individuals with hyperkalaemic Periodic Paralysis computed an approximate ratio of one in two for paramyotonia, in addition to a myotonia occurrence in one in two of these paramyotonic subsets.
Also Myotonia could confound threatening miscarriage or premature onset of labour because of its occasional exacerbations during pregnancy, making the abdominal and uterine muscles to contract continually.
Since menstrual cycle and pregnancy were implicated as inciting factors several authors propose the implication of oestrogenic hormones in its aetiopathogenic causal pathways.
Pertaining to the prodromal symptoms, the affected individuals with Hyperkalaemic Periodic Paralysis complained of experiencing prodromal symptomatologies before the onset of a florid paralysis attack, the prodromal symptomatologies range from fatigue, lethargy, lassitude weakness, irritability, and/or restlessness.
Immediately preceeding an attack most of the subjects complained of hyperhydrosis, myalgias, stiffening, rigidity, weakness, restlessness, tingling and/or numbness. The attack interval from these prodromal symptomatologies range from a third of an hour to several hours, however interestingly this interval is not predictably constant for any particular individual. Many subjects reported being melancholic, dysthymic, irritable and depressed pre, peri and post periodic paralytic events. Although this is not invariable, but overall most subjects reported an alteration of the muscular sensation and hyperhydrosis.
However, some subjects reported that their attacks happen more commonly than they will otherwise would as they are now medically controlled. Attack frequency ranged from one to three attacks per month in a third, to once a week in one fifth and to about two to six in a quarter. Although previous literature described attacks of Periodic paralysis as lasting for about sixty minutes to one twenty minutes, in duration, and seldom lasting for days, other series have reported a duration of more than twenty four hours in a fifth of their subjects, and a fifth reported typical attacks lasting an hour and another one eight reported attacks lasting about a quarter of an hour to half an hours.In a fifth of the patients their longest attack was reported to be over a week.
Pertaining to the topographical involvement of the appendicular skeleton .most subjects could report those areas of the body affected most during attacks.
The arms and hands are just as frequently affected during attacks as do the thighs and calves. However, it is of much concern that the facial and the respiratory musculature are affected during attacks in a significant number of individuals.
Several emerging and ongoing data are divergent from previous reports in the literature which stated that lid lag secondary to eyelid myotonia may be the only clinical sign present between attacks.
The reported severity of attacks varied greatly between individuals, with the largest subsets, two fifths of the respondents described the majority of
their attacks as mild (defined as having some perceptible limitations on motion, About one sixth reported their attacks as severe (because it is accompanied by aphasia or functionally disabling dysphasia) in more recent series, the majority of individuals reported mild or no symptoms between attacks However, one eight reported severe symptomatologies in between attacks that impair their functional professional and domiciliary capabilities. Previous data on these themes achieved by Jurkat-Rott and Lehmann-Horn in (2011) [52] And Amato and, Russell of 2008 respectively. [53] Are in consonance.
Following attacks, previous series reported myalgia in about two fifths pre and post attack, where as one fifth denied any associated myalgia.
However, more recent series includes other more or less eloquent or vague symptomatologies such as malaise, clumsiness, extreme fatigability, unexplained tiredness, listlessness, lethargy, weakness, and/or irritability, frightening symptomatologies reported include dyspnoea and palpitations.
An evaluation of the natural history of periodic paralysis yielded some interesting data, with regards to the manner in which their symptomatologies have altered chronologically, it was reported that attacks typically increased in frequency during childhood in nine of ten cases, where as in four of every five cases, during the adolescence and teenage years. From the second decade to well into the third decade, the pattern was heterogeneous with one half reporting increasing attack frequencies and a third reporting no change in the attack frequencies and one sixth reporting a decrease in the attack frequency. .From the fourth decade to well into the sixth decade, about three fifths of the subjects reported an increased frequency of the attacks, whereas one fifth reported that the symptoms stayed as the same, and the other one fifth diminished in attack frequency.
Overall several subjects commented that their attack frequency has remained the same throughout their lives.
Regarding changes in the severity of muscle weakness during attacks, in individuals within the first two decades of life, there were no observable pattern and the changes were erratic, unpredictable and more or less characterless. Between the second decade and well into the third decades of life, about three fifths reported improvement in the periodic paralysis symptomatologies, and between the fourth and well into the sixth decade of life, about one half reported improvement in their symptomatologies where as two fifths reported worsening symptomatologies.
With regards to changes in muscle stiffness during attacks over time, several subjects frequently reported worsening stiffness during childhood in about eight to nine of ten instances and in seven of ten cases of the pubertal, adolescence or teenage age groups. From the second decade of life to well into the third decade, a third of the subjects reported no alteration in the muscle stiffness, a worsening of muscle stiffness and improvement in muscle stiffness respectively respectively. From the fourth decade to well into the sixth decade, about one half reported worsening and one fifth reported improvements in muscle stiffness
The majority of the subjects noted progressive permanent muscle wellness during childhood in seven of ten cases, whilst only a one third minority of individuals reported such changes during the teenage years and from the second into well the third decades respectively. This is in marked contrast to the opinion of the previous literature that reported that permanent muscle weakness to be the problem of older adults principally.
This chronologically dependent clinico-pathological association was inferentially buttressed by nuclear magnetic resonance spectroscopic imaging data by Amarteifo, Nagal, Weber, Jurkat-Rott and Lehmann-Hom on Hyperkalemic periodic paralysis and permanent weakness: 3-T MR imaging depicts intracellular 23 Na overload-initial results of .2012. [60]
As did the re-echos of the contemporaneous reviews of Jurkat-Rott and Lehmann-Horn on Hyperkalaemic periodic paralysis type 1.Gene Reviews. [52]
However most studies concur with previous studies that in eight to nine of every ten cases, that cases aged from their fourth decades onwards, reported permanent muscle weakness thereafter.
Overall, in summary, the general trend in most series is that of a chronologically increasing attack frequency, which is especially prevalent during childhood and adolescence, improving muscle weakness during attacks from young adulthood onwards ,worsening muscle stiffness during attacks prior to adulthood, and progressive permanent muscle weakness during childhood and after the fourth decade. Permanent muscle weakness is equally a feature of hypokalaemic periodic paralysis. as was indicated by Links, Zwarts and, Wilmink et al on their scholarships on Permanent muscle weakness in familial hypokalaemic periodic paralysis .Clinical, radiological and pathological aspects of 1990.[61]
The degree of incapacitation caused by hyperkalaemic Periodic Paralysis is quite variable, with some being intervally dependent on their next of kins during attacks for their domestic needs ,to instances of being bedridden and confined to a hospital bed. In several instances, participants reported their initial attack of hyperkalaemic periodic paralysis in the second decade of life, in contrast to the accepted notion that attacks usually commences in the first ten years of life. (Jurkat-Rott K, Lehmann-Horn F (2011) Hyperkalaemic periodic paralysis type 1.Gene Reviews.)[52]
Compared to the Index case in an affected family, the diagnosis of Periodic Paralysis is usually more rapidly achieved in the subsequent subjects,
Diagnostic delay could be as long as the index cases life span, because of several confounding variables, unusual, or atypical presentation, leading to low suspicion index, in addition to restricted diagnostic options. Following diagnosed index cases, familial screening and education diagnosis has been very rapid in the other affected members because of a heightened suspicion index. An average diagnostic delay time of about two decades was reported by the earlier series. The other area of interest is the identification of Familial Periodic Paralysis with certain medical specialty from the diagnostic accuracy point of view such as but not confined to acute neurology most commonly, but also a genetist, a Paediatrician or an internist. Although overall, the epidemiological, familial, genetic, clinicopathoradiological and social aspects of Familial Periodic Paralysis had a multidisciplinary and interdisciplinary intent, but however on the average the utmost diagnosis was usually achieved within the Neurology and Neurosciences domain. Interestingly ongoing and conclusive reports have suggested a higher incidence of myotonia more than the previous reports of one case in five instances.
(Venance ,Cannon ,Fialho ,Fontaine ,Hanna ,Ptacek ,Tristani-Firouzi ,Twil and Griggs on behalf of CINCH investigators.The primary periodic paralysis;diagnosis,pathogenesis and treatment. (2006)[57]
In addition to the physical effects of their disease, subjects reported other associated difficulties. Especially, subjects reported their condition having negative impacts on their vocation in about seven of ten instances, an undermining Factor to their overall physical health ,in addition to their academic, didantic activity in three of five instances respectively, as well as their nuclear and extended familial and domiciliary undertakings in four of ten cases, some of the affected subjects thought that periodic paralysis compromised their global and holistic psychosocial well being in a third of cases and perturbations of social relationships and networking was reported in a quarter of cases.
The effects on the overall physical health reported include weight gain, inability to exercise, and cardiac dysarrythmias.
Severe attacks have made punctuality and attendance at school and work burdensome if not impossible increasing the rates of absenteeism and sick leave off days. Moderate attacks are equally incapacitating through making activities more demanding, uncomfortable, painful, tardy. exhaustive and tiring. Domiciliary familial life is particularly undermined by the limited range of activities permissible for the affected cases, especially their children or wards.
Also the progressive myopathy with muscle dysfunction encountered in about a third of subjects contributes to such limitations.
The age aggregate of those reporting limitations of activity range from the end of the first two decades of life to mid seventies, with a median age of mid forties.
Overall, on the basis of the complaints of cases of hyperkalaemic periodic paralysis, the overall impact of periodic paralysis extend far beyond the chronological boundaries of acute paralytic episodes.Interestingly, with regards to their overall emotional and mental well-being, in thinking about their lives with periodic paralysis, most affected cases perceived their overall psych-social well-being as complacent, delightful, accomplished or non despondent. Whereas a simple minority described their state as being dysthymic, melancholic, despondent and sober.
Several subjects narrated their grave difficulties in life tantamount to their hyperkalaemic periodic paralysis, such experiences include but not confined to falls whilst outdoors and being trampled upon whilst lying in a crowdy environment following an attack, apprehensions from occasional and festive phobias because of the possibility of a periodic paralysis event and lack of independence especially having to rely on unknown strangers for support following attacks , in addition to perceptions of empathy from unfamiliar attack witnesses.
The recommendations offered by subjects with hyperkalaemic Periodic Paralysis, to others with similar symptomatologies include but not confined to getting educated on the natural history, diagnostic therapeutic and prophylactic interventions for periodic paralysis and seek prompt support.
Lifestyle modification with regards to dietetics, physical activities, and knowledge on medications needed to manage the paralytic events. In addition to enrollment into Periodic Paralysis support groups for experiences sharing and obtaining educative information from other PP subjects.
Other proffered recommendations include counseling others about the disorder, with honest nonjudgmental probity, whilst acknowledging the individualities in the required therapeutics and divergence in the degrees of attack severities.
Affected individuals and their families were equally counseled to undertake in positive health seeking activities which they consider worthwhile in giving meaning to their lives, whilst not forgetting to take their medications,
prophylactic options should aim as much as possible to eschew thoughts dwelling on the condition as much as will be achievable.
THE DIAGNOSTIC ASPECTS AND FEATURES OF HYPERKALAEMIC PERIODIC PARALYSIS.
The diagnosis of hyperkalaemic periodic paralysis is based on clinical grounds, sometimes with the use of provocative tests in cases of diagnostic ambiguity and uncertainty. Fairly recent reviews by Jurkat-Rott and Lehmann-Horn of (2011) on Hyperkalaemic periodic paralysis type 1.Gene Reviews dissected these diagnostic modalities. [52]
The diagnosis is suggested by historical notes of attacks of weakness or paralysis, a positive family history, and the presence of myotonia or paramyotonia.
Serum creatinine (CK) values may be elevated, and some individuals exhibit calf muscle hypertrophy. On the average, the muscles are typically well-developed. Excellent updates on the myogenic and neuro-myogenic aspects of periodic paralysis were achieved by the independent collective efforts of the groups of Schpira and Griggs and that of Amato and Russell in 1991 and 2008 respectively. [11], [53]
However, a large proportion of individuals with hyperkalaemic periodic paralysis develop a chronic progressive decimating proximal myopathy as they advance chronologically.
In their 2012 scholarship Amarteifo, Nagal, Weber, Jurkat-Rott and Lehmann-Hom .demonstrated that in Hyperkalemic periodic paralysis with permanent weakness that 3-T Magnetic Resonance Spectroscopic imaging depicts intracellular 23- Na overload-initial results . It was speculative that this might connote predisposition for these groups of myogenic cells to cytotoxic and osmotic injury with hydropic vacoulative degeneration. [60]
Previous reports from other experimental studies by Venance ,Cannon ,Fialho ,Fontaine ,Hanna ,Ptacek ,Tristani-Firouzi ,Twil and ,Griggs on behalf of the ,CINCH investigators. On the primary periodic paralysis; diagnosis, pathogenesis and treatment in 2006 highlighted on the nonreversible chronological down hill course of some cases of periodic paralysis. [57]
Although more modern literature refutes this notion, previous reviews indicate that paradoxically, individuals without interactal myotonia are much more susceptible to developing this progressive myopathy than are individuals with myotonia. Reviews of Jurkat-Rott and Lehmann-Horn et al dissected these aspects lucidly. [52], [4]
Muscle biopsy though non-specific, will frequently reveal muscle fibre atrophy with vacuolopathy.
In 1992, on the basis of a diligently studied case report and comprehensive literature reviews, Gold and Reichmann proposed that muscle pathology correlates with permanent muscle weakness in hypokalaemic periodic paralysis.
[62]
The histopathological features of the myopathy of periodic paralysis were equally analysed and presented by Amato and Russell and Vicart in 2008 and 2912 respectively [53], [21]
Genetic testing is positive in approximately sixty percent of individuals who meet clinical diagnostic inclusion criteria.
THE LABORATORY FEATURES OF PERIODIC PARALYSIS.
During attacks, individuals may be hyperkalaemic or normokaelemic. [22]
Scholarships and reviews by Schpira and Griggs suggests that the simultaneous, synchronous or contemporaneous elevation of the serum potassium levels may spectrally range from upper normal values to figures in the cardiomyogenic arrythmogenic inciting ranges [11] However, on the basis of their meticulous study on the theme, Genotype-phenotype correlation and therapeutic rationale in hyperkalaemic periodic paralysis. Lehmann-Horn and Jurkat-Rott in 2007 pointed out that following an episode of hyperkalaemic periodic paralysis, serum potassium may be paradoxically temporarily diminutive due to rapid renal clearance of potassium in addition to enhanced cellular myogenic potassium reuptake. [55] On the average in the interval between paralytic attacks, in the hyperkalaemic PPs, most affected subjects will have a normal serum potassium level.
Regarding the association between serum potassium and attack characteristics, no specific trends were noted. Of those who had their serum potassium measured during attacks, the majority reported being hyperkalemic, although several reported normokalaemic and in occasional instances being hypokalaemic was reported.However, overall regardless of the serum potassium levels, most subjects reported feeling stiff and weak during attacks.There is no existing report or data on specific potassium level threshold at which attacks would occur,Curiously, in one of eight instances, episodes of weakness that improved with potassium intake was paradoxically reported by the affected subjects with supposedly known hyperkalaemic PP.
ELECTROPHYSIOLOGICAL STUDIES IN HYPERKALAEMIC PERIODIC PARALYSIS.
In hypokalaemic periodic paralysis, these electrophysiological tests are largely reversible. In 2014 an Indian Asian Study by Sharma, Nath and Parekh discussed reversible electrophysiological abnormalities in hypokalaemic paralysis: and reported two cases. [63]
An EMG may show myotonic risks to the patient but may be done to support the diagnosis, although approximately half of those with the most common mutations show no such signs. Several aspects of clinico-genetic electrophysiological correlations in periodic paralysis were discussed by Jurkat-Rott and Lehmann-Horn in 2011 in the theme Hyperkalaemic periodic paralysis type 1.Gene Reviews. [52]
Venance et al on behalf of the CINCH Investigators indicated that electrical myotonia could be demonstrated on EMG in about one half to three quarters of patients with hyperkalaemic PP, while less than one fifth were symptomatologically overt. [57]
THE DIAGNOSTIC ASPECTS OF HYPOKALEMIC PERIODIC PARALYSIS:
EXERCISE TESTS.
Previous data on the exercise test in periodic paralysis by McManis, Lambert and Daube of 1986 infers that the exercise tests could be applied to achieve the diagnosis of hypokaelemic periodic paralysis. [64] Or For the monitoring of the progress of the disease activity or in response to pharmacotherapeutic interventions as was proposed comtemperonously in 2004 by Fournier, Arzel and Sternberg, et al in their investigative scholarships that electromyography guides toward subgroups of mutations in muscle channelopathies.[65]And The exercise test as a monitor of disease status in hypokalaemic periodic paralysis by Tengan, Antunes, Gabbal and Manzano.[66]In addition to the previous data on this theme in 2000 by Kuntzer, Flocard and Vial et al which discussed .exercise test in muscle channelopathies and other muscle disorders. [67]
Provocative tests such as the potassium challenge test pose obvious risks to the patient but may be done to support the diagnosis, although approximately half of those with the most common mutation show no such signs. The limitations and shortcomings of these provocative tests have been provided and discussed by several authors (Jurkat-Rott and Lehmann-Horn (2011) [52] (Amato and Russell (2008) [53] and (Vicart (2010) [21]
Previous scholarships by Streeten, Speller and Fellerman of 1993 demonstrated and discussed the use of corticotrophin-induced potassium changes in the diagnosis of both hypo- and hyperkalemic periodic paralysis. [68]
However, the availability of genetic testing and elctrophysiologic studies largely undermines the need for such cautious diagnostic approaches.
Differential Diagnostic challenges:
A majority of the misdiagnosis for Familial Periodic Paralysis implicates the psychiatric and psychosomatic conditions. In cases of hyperkalaemic periodic paralysis with overwhelming myotonia other diagnostic considerations will include Schwartz-Jampel syndrome (SJS) which according to the scholarships and reviews of Godai of 2017 is a rare syndrome characterized by myotonia and skeletal abnormalities .Most reports regarding SJS have stated that patients with this condition have symptomatologies mimicking ParaMyotonia Congenita. (PMC) [69]
On the basis of their recent scholarships of 2017 on the Analysis of Clinical and Metabolic Profile of Acute Neuromuscular Weaknesses Related to Hypokalaemia, Kumar Singh, Kumar MaURYA and Kumar Thacker suggested that other secondary causes of muscle weakness related to hypokalaemia ought to be considered before pursuing the establishment of the diagnosis of familial periodic paralysis. [70]
Complications
Non-anaesthetic related surgical complications were reported in one in five instances, and complete paralysis lasting several days up to a week has been recorded. Other complications encountered include malignant hyperthermia, hypernatreamia and respiratory difficulties these anaesthetic complications could be greatly ameliorated, if these cases are placed first on the operating list and their conditions discussed fully with the anesthesiologists in the pre-operative grand ward rounds so that no unsafe or contraindicated anaesthesia could be used on people with hyperkalaemic periodic paralysis. These aspects were detailed by (Lehmann-Horn et al (2004) [4]
Following local anaesthesia, about one in ten of the cases reported an untoward effect, specifically complete paralysis lasting several hours, respiratory depression, palpitations and muscle stiffness. The complication rate with general anaesthesia is higher at one of every three cases, which includes, but not confined to severe paralysis, involving the respiratory muscles, stiffness weakness ,hyperthermia and especially with propofol,a propofol induced heavy weakness, Although the anesthetic agents or implicated surgical procedures were noncategorically identified by the subjects,however,overall individuals with hyperkalaemic periodic paralysis are clearly at risk for complications from surgery and anaesthetics.
Management with GENERIC PREVENTIVE MEASURES.
Gleanings from classic histriographic data of 1968 by Resnick, Engel, Griggs and Stam suggests that Acetozolamide prophylaxis has been proposed by several authors, especially for the hypokalaemic form of familial periodic paralysis. [71]
Prophylactic measures include eating frequent carbohydrate-rich meals and the continous use of diuretics that reduce potassium levels, such as thiazides or carbonic anhydrase inhibitors. Equally important is the avoidance of potassium rich foods, medications that raise the serum levels of potassium, fasting strenuous work, and exposure to cold.Mexileten is beneficial in the management of myotonia .Early in the course of an attack, abortive or attenuating measures include mild exercise, carbohydrate ingestion, and beta-adrenergic agonist inhalation. Severe attacks warrant treatment with intravenous glucose and insulin Calcium carbonate is used in cases of severe hyperkalaemia to stabilize the myocardium to prevent arrhythmias. This prophylactic therapeutic modality was highlighted and positively discussed by Jurkat-Rott and Lehmann-Horn (2011)
[52] (Amato and Russell (2008.)[53] And (Schpira and Griggs (1991). [11]
In their scholarships on periodic paralysis and qas specifically reechoed by Griggs, Resnik and, Engel in their investigation on Intravenous treatment of hypokalaemic periodic paralysis of 1983. [72]
Patients with hyperkalaemic periodic paralysis must avoid depolarizing anesthetics, such as suxamethonium and anticholinesterase agents, as they aggravate myotonia and can interfere with intubation and mechanical ventilation.
Histriographically, several discussions and reviews on this theme was provided
In 1970, Griggs .Engel and Resnick in discussing .Acetozolamide treatment of hypokalaemic periodic paralysis .Prevention of attacks and improvement of persistent weakness highlighted these anaesthetic complications. [73]
As did Links, Smit and Molenaar et al in their reviews of Familial hypokalaemic periodic paralysis with regards to its clinical, diagnostic and therapeutic aspects of 1994. [74]
And Dalakas and Engel in their discussions on the treatment of “permanent “muscle weakness in familial Hypokalaemic Periodic Paralysis of 1983. [75]
In addition to the fairly recent reviews of Jurkat-Rott and Lehmann-Horn F Hyperkalaemic periodic paralysis type 1.Gene of 2011. [52]
The therapeutic intervention for thyrotoxic periodic paralysis deserves special attention, especially with regards to the potassium replacement therapy for the hypokaelemic subsets. These aspects were illuminated up on by Loh, Hsu and Chiu et al in their scholarships on Thyrotoxic periodic paralysis complicated by near fatal ventricular arrhythmias of 2005.[76] And previous scholarships by Lu, Pinheiro and Ng. of 2004.highlighted these aspects on the effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis.
[77]
Therapeutic Environmental Manipulations for Periodic Paralysis.
Some candidates discussed realistic and innovative solutions that they have conceived and implemented to facilitate the modification of their domiciliary environment to factor in the demands of their periodic paralysis, such as making handy those materials that could ameliorate an attack, notably, but not confined to, magnesium, sugar cane, etc, or muscle strengthening exercise equipment.
In addition to wheel chairs, lavatory and bathrooms assistive devices.
Other proposed domiciliary or ergonomics assistive modifications such as high energy powered automated scooters, in addition to the adornment of an identification emergency alert bracelet or devices. In other instances, isotonic less rigorous or physically demanding exercises such as walking, biking and swimming were employed to avoid attacks. Inculcating these ideas and specifications into an individual’s domiciliary and routine itenary may augment safety and assist one to deal more effectively with PP disease associated limitations.
Therapeutic Interventions and Management.
The length of time required to achieve a fairly well satisfying apposite therapy was quite variable, with about one half suggesting about ten years or more, where as one fifth suggested that it took from about half a decade to a decade to find a psychologically and functionally satisfying therapeutic option.
A quarter proffered about twelve to sixty months as the interval for the period that elapsed between the sentinel symptomatology and encountering a beneficial management regimen.
In another one of twelfth cases a therapeutically useful intervention was achieved within the first twelve months, on the average overall it took about twelve years for a psychologically, socially and functionally rewarding therapeutic intervention to be achieved. However, dauntingly, several candidates of hyperkalaemic periodic paralysis commented that they are still searching to achieve the utmost and perfect therapeutic regimens for their symptomatologies.
In most instances about one half of the subjects think that their treatment somewhat needs some form of improvement, where as nine of twenty of the cases, perceives that their therapeutic interventions mostly controls the symptomatologies adequate enough to preclude attacks of periodic paralysis in most instances, whereas one in twenty considers their management to be optimal and utmost.
Interestingly, about one of six cases in the frequently controlled persons denied taking continual medications, where as three fifths of those describing their disease status as needing improvement denied taking continual medications.
Therefore those not taking medications have a relative risk of about two to three (p<0.0001) for experiencing inadequate disease control compared to those taking chronic medications. Therefore clinicians should be proactive in prescribing medications when appropriate.
The efficacy of these therapeutic modalities have been demonstrated at both the the clinical and experimental levels.On the basis of the results of their investigations on this theme,
Tricarico, Barbieri and Mele et al in 2004, demonstrated that Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+ deficient rodent models. [78]
In the author’s experience from his series, Acerazolomide is probably a wonder drug for PP of various aetiological origin.
Many participants reported some combination of medications and carbohydrate rich food as their primary therapeutic regimen. The majority of subjects consume medium-sized meals, and at least a quarter consume smaller sized meals.
Most subjects with hyperkalaemic periodic paralysis ingest three to five square meals a day and carbohydrate rich snacks every sixty to ninety minutes. Ingested carbohydrate sources reported include candy, sugar, bread, and pasta .Overall, most subjects with hyperkalaemic periodic paralysis will avoid alcoholic liquors , a whole lot of potassium enriched food substances ,diet soda, and cold foods and beverages.
Concerning those medications used by the frequently controlled cases, one fifth used hydrochlorothiazide and mexiletene respectively, where as one eight used fleicanide. Previously experimentally, local anaesthetics have been employed as candidate therapeutic options for hyperkalemic periodic paralysis.
In 1998, Sah et al examined the ability of local anaesthetics to correct altered inactivation properties of rat skeletal muscle Na+ channels containing the equine hyperkalaemic periodic paralysis (eq-HPP) mutation. [79]
Most affected individuals tend to use beta- 2 agonists or their routine continual medications in the acute setting. With regards to the maneuver that most subjects identified as effective for ameliorating acute attacks outside of their long-term treatment regimens.Common practices include doing gentle exercise, keeping warm, eating sweet foods, encouraging muscular relaxations and drinking water. However, dishearteningly in about two fifths instances aborting an attack with these maneuvers were unachievable or very occasionally useful.
With reference to the dietetics practices with utmost positive influence on Familial Periodic Paralysis, by terminating or ameliorating acute attacks of periodic paralysis a miscellaneous variety of specific food items and beverages which were replete in carbohydrate, although otherwise this seems to reflect personal taste rather than any nutritional trend. Food items of preference include chocolate bars, cookies, crackers, Coca-cola, Gatorade, and sugar.
The majority of subjects deny any difference between impact of solid versus liquid carbohydrates. Subjects reported carbohydrates take effect in anywhere from one fifth of a minute to about four to six hours, the majority reporting an effect within an hour. Subjects commented that it is also very important to drink a lot of fluids, such as water or tea, Carbohydrates and hydration appear to be a key part of nonmedical intervention for PP.
Some Speculations and observations on the Negative Impact of Acetozolamide on Periodic Paralysis:
Intriguingly, the role of acetozolamide was controversially discussed in the global medical literature, because several reports of acetozolamide inciting the exarcebation of familial hypokalaemic periodic paralysis exist.
In 2001, Bendahhou, Cumminis and Griggs et al. presented and discussed that Sodium channel inactivation defects are associated with acetozolamide-exacerbated hypokalaemic periodic paralysis. [80]
Earlier reviews by Tores, Griggs, Morley and Bender of 1981 on Hypokalaemic periodic paralysis exacerbated by acetozolamide alluded to this untoward iaotrogenic effect. [81]
In 2000, Tawil, McDermott and Brown et al.on behalf of the Working Group on Periodic Paralysis on the basis of their Randomized trials of dichlorophenamide in the periodic paralyses proposed the trial of dichlorophenamide another carbonic anhydrase inhibitor in those instances where the use of acetozolamide is precluded, unachievable or suspected to be exacerbating the symptomatologies of periodic paralysis. [82]
Several other therapeutic options have been proposed for familial periodic paralysis.Chronologically, In 1996 Ligtenberg, Van Haeften and Van Der Kolk et al presented and discussed normal insulin release during sustained hyperglycaemic periodic paralysis and the role of the potassium channel opener pinacidil in impaired muscle strength. [83]
Links, Arnoldus and Wintzen et al presented and discussed the specialized therapeutic role of the calcium channel blocker verapamil in hypokalaemic periodic paralysis .in 1998. [84]
In a similar therapeutic endevour, the role of topiramate in the treatment of hypokaelemic periodic paralysis was proposed and advanced by Fiore and Strober in 2011. [85]
A systematic review of the metaanalysis of several data from the global literature has been proffered by Sansone, Meola and Links, et al on the therapeutic aspects of periodic paralysis in 2008) [86]
Data on the predictive role of the genotype response to acetozolamide in familial periodic paralysis was provided by Mattews, Portaro and Ke et al following their investigative scholarships on Acetozolamide efficacy in hypokalaemic periodic paralysis and the predictive role of genotype of 2011. [87]
Discussions on what is known axiomatically of this topic relative to what the reviews introduces as a new knowledge or adds to an existing body of knowledge.
What is already known on this topic and a guide to the explanation of the patient and his family on what PP entails)
+Periodic Paralysis is an autosomal dominantly inherited disorder (only one affected parent is needed to pass the trait on to an offspring) that causes sudden attacks of weakness and paralysis. There are several forms.
Background & Essence:
+Muscles do not respond normally to stimulation, usually when the blood potassium is too low or high.
+Weakness is intermittent affecting mainly the limbs, and is often brought on by exercising or eating too much or too little carbohydrates.
+ The diagnosis is based on the symptoms and a check of the potassium level in the blood.
+Avoiding triggers that cause attacks and taking drugs can prevent attacks effectively.
During an attack of periodic paralysis .muscles do not respond to normal nerve impulses or even to artificial stimulation with an electronic instrument .The precise form that the disorder takes.
Symptomatologies and DIAGNOSTIC CONSIDERATIONS AXIOMS.
During an attack of weakness, the person remains completely awake and alert.
Muscles in the eyes and the face are not affected. Weakness may affect only certain muscles of all four limbs .In the hypokalaemic form attacks generally first appear before the age of sixteen, but may appear during the twenties and always by age thirty.
The attacks last up to twenty four hours ,occasionally even longer .Often the person awakens the day after vigorous exercise with an attack of weakness.However,eating meals rich in carbohydrates( sometimes hours or even the day after) can cause attacks.
Eating carbohydrates and exercising vigorously drive sugar into the cells .Potassium moves with the sugar, and the result is lowered potassium levels in the blood. In the hyperkalaemic form of the disorder, attacks often begin by age ten years, The attacks last fifteen minutes to sixty minutes. Weakness tends to be less severe than in the hypokalaemic form. Fasting, exercise, strenuous work, and exposure to cold may precipitate attacks.
A clinician’s best clue to the diagnosis is a person’s description of a typical attack. If possible, the clinician takes a blood sample while an attack is ongoing to verify if the of potassium level is abnormal, clinicians will usually undertake additional tests to be sure that the abnormal potassium levels are not from other causes. Occasionally, a physician may give the person intravenous drugs that increase or decrease the levels of potassium in the blood to see whether an attack results.
RECOGNISED PREVENTIVE AND THEREAPEUTIC OPTIONS FOR PERIODIC PARALYSIS:
Acetozolamide, a drug that alters the bloods acidity, may prevent attacks in all types of periodic paralysis. People with the hypokalaemic form can take potassium chloride in an unsweetened solution while an attack is in progress. Usually symptoms improve considerably within an hour. People with the hypokalaemic form should also avoid meals rich in carbohydrates and salt in addition to alcoholic beverages or strenuous exercise. People with the hyperkalaemic form can prevent attacks by eating frequent meals rich in carbohydrate and low in potassium and by avoiding fasting, strenuous activity, and exposure to cold. If an attack is severe or persistent, drugs (such as a thiazide diuretic or inhaled albuterol) can help lower the potassium level.
The potassium levels vary amongst different families .In some families, the paralysis is related to low levels of potassium in the blood (hypokalaemia) in a rare form potassium levels are normal during attacks.
CONCLUSIVE REMARKS and What this Study adds.
The periodic paralyses are a group of skeletal muscle channelopathies characterized by intermittent attacks of muscle weakness often associated with altered serum potassium levels. This definition has stood the test of time as was reaffirmed by Fialho, Griggs and Matthews on their recent scholarship on Periodic paralysis of 2018. [88]
The facts in more recent studies that add to the current body of knowledge or that counter scientific literature regarding hyperkalaemic periodic paralysis include but are not confined to the following points. Progressive myopathy affects approximately one-third of individuals regardless of the presence of concomitant myotonia.The relative risk of thyroid dysfunction in certain population studies could be as much as 3.6 compared to the general population. However, the trend toward an increased rate of cardiac arrhythmias although not statistically significant, but being statistically superior may be clinically significant and relevant.
About one in four of individuals experience their sentinel attack between the ages of twenty and thirty years. Symptomatic myotonia may be reported in three out of every five cases.
Alcoholic beverages, changes in humidity, sleep, illness, medications and menstruations may trigger off attacks of hyperkalaemic periodic paralysis.
Attacks may affect the facial and/or respiratory muscles; some subjects experience urinary or faecal incontinence. An average of one in eight of the subjects reported severe symptomatologies between attacks that impair their activities of daily living. Individuals may experience permanent muscle weakness starting from childhood.
Those with no routine continual treatment regimen have a relative risk (RR) of two to three for reporting relatively poorer disease control than those taking long-term medications. During acute attacks, over one in ten of the cases may note some improvement with potassium intake. Considerations of these factors will allow physicians to develop appropriate and patient specific management plans to best cater for each affected individuals.
In the female subjects who are supposedly more commonly affected by attacks, some cases could present covertly with symptomatologies mimicking chronic tension fatigue syndromes, fibromyalgia, hysteria, convulsive equivalents or unclassifiable paroxysmal events [89] and will therefore need to be evaluated indepth for periodic paralysis especially the normokalaemic subsets.
The Limitations of this review, include recall bias inherent in the resources where this review was derived from, over and under reporting of symptomatologies and the probability of an inadequate and non-uniform characterization of myotonia distinctively from PMC (Para myotonia congenita)
Also, the interview candidate’s ability to report peculiar symptomatologies de novo connotes that those responses would have been more widely reported, if they had been included amongst the several options interview questionnaires.
Several existing studies on hyperkalaemic periodic PP are not adequately powered enough for the utmost elucidation of the several possibilities in the hyperkalaemic periodic paralysis phenotype/genotype subsets. This study needs an intensive and sustained follow up for an ultimate elucidation of its natural history.
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CLASSICS AND REVISITS IN INTERDISCIPLINARY MEDICAL THEMES
An informative mix of education and novel Data through Naturalistic Inquiry, Participant Observation, structured Interviews And Documentary Content Analysis in addition to Media analysis for
Illustrative instructive Epitomes of the range/and impact of electric shock related injuries. The age ,gender and seasonal differential variations in the pathophysiological effects of different intensities of electric current suggests the role of environmental genetic, humoral, hormonal, metabolic, constitutional idiosyncratic factors and pathological states in the diathestic predispositions to electrical injuries and electrocutions.
Hypothesis, Paradigms& Research Questions:
Firstly, the seasonality and additive effect in electric and lightning current related injuries warrants temporal differential deterrent preventive options, slanted and weighted to the wet seasons.
Secondly, although previously electrical injuries used to be an urban cosmopolitan phenomenon, but the additive impact of the availability of electricity and multiple bodies of water in the hinterlands warrants an augmented and directed electrical and lightning injuries deterrent and preventive options.
Thirdly, with regards to electrical and lightning injuries; a little overdose may matter in some individuals with certain genetic and acquired pathological conditions because of innate aneurysmal formations in those with connectivopathiies, such as the Elans Danlos syndromes, Marfans syndromes or Osteogenesis Imperfecta, or acquired metabolic or infective defects such as cardiovascular syphilitic leutic diseases, metabolic syndromes etc Since aneurysms occur following prolonged coagulative coaliquative necrosis of the fibromuscular medial intima of the large blood vessels especially the aorta following electrical shock injuries. Aneurysms predisposes to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries, both could cause dizzy spells.
Also, since aneurysms predispose to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries with both presenting with dizzy spells such individuals with predisposing diathesis to aneurysmal formation will need at least a non-invasive survey for the evolution of the aneurysm such as trans thoraco-abdominal ultrasound in addition to haemoglobin estimation and complete blood counts.
Similarly individuals with arrythmogenic predisposing homeostatic metabolic or structural cardiopulmonary or neurogenic dysfunctional/ diathesis will need evaluation with ultrasound, ECG and if imperative EEG.
Fourthly, in addition, Electrical and lightning injuries by causing fatty tissue necrosis could predispose to cryptogenic acute, then subacute and chronic pancreatitis with calcific fibrosis leading to a fibrocalculous chronic pancreatitis with enzymic and hormonal insufficiencies.
Finally, the stress of electric shock could lead to an irreversible diabetogenic hormone release, the enhanced impact of electrical injury in pregnancy being grave may well be related to the exacerbated humoural endocrine factors at play in pregnancy.
This review explores the wider impact or connotations of electrical injuries through the following problem solving paradigm such as the case for the position of the elderly and certain metabolic vital organ dysfunctions associated cardiopulmonary difficulties and neuropathies in this scale may warrant an enhanced anti-electric shock measures for this subsets as a group.
Therefore electrically injured patients should receive a more comprehensive evaluation for renal injuries, neurological deficits; in addition to longer term ophthalmological follow ups for cataracts. As a group patients with electric shock injuries will need longer term and more diligent follow ups.
Pre-experimental studies Through document Content Analysis Research.
MAIN TEXT
ELECTRICAL INJURIES.
ABSTRACT:
Introduction & Background
Although electrical trauma, accidents or “shock” are very common and almost everyone has been exposed to these, severe electrical injury is a relatively infrequent but potentially devastating form of multisystem injury with high morbidity and mortality. Most electrical injuries in adults are occupationally related, whereas children encounter these injuries in the domiciliary settings. Natural electrical injury are related to lightning events, with immense and utmost morbidity and mortality .The severity of the injury depends on the intensity of the electrical current ( determined by the voltage of the source and the resistance of the victim).the pathway it follows through the victims body and the duration of the contact with the source of the current .Abrupt and rapid fatality may be related to either electric current-induced ventricular fibrillation or asystole or from respiratory arrest secondary to paralysis of the central respiratory control system or due to paralysis of the respiratory muscles. Presence of severe burns (common in high voltage electrical injury), myocardial necrosis, the level of central nervous system injury, and the secondary multiple system organ failure determines the subsequent morbidity and long term prognosis .There is no specific therapy for electrical injury, and the management is symptomatic. Although advances in the intensive care unit, and especially in burn care, have improved the outcome, preventive and prospective health options remains the best way to minimize the incidence, prevalence, impact and severity of electrical injury. Although frequently categorized collectively as a single entity, electrical injuries were actually spectral ranging from mild as seen with low voltage outdoor electrical injuries, through high voltage occupational injuries to lightening injuries, however in younger children an occasional in door larger household electrical injury may be associated with very deleterious consequences.
Electrical injuries, although uncommon are inevitably encountered by most clinicians. Adult electrical injuries usually occur in occupational settings, whereas children are primarily injured in the household settings. The spectrum of electrical injury is broad, ranging from minimal injury to severe multiorgan involvement to death.
Injuries could result from spontaneous atmospheric electricity (lightening injuries) or generated electricity, such as household or industrial electrical currents
(electrical injuries)
Electrical current passing through the body generates heat, which burns and destroys tissues .Burns can affect internal tissues as well as the skin.
An electrical shock can short circuit the body’s own electrical systems, causing nerves to stop transmitting impulses or to transmit impulses erratically .Abnormal impulse transmission can affect the muscles including the cardiac muscles inciting tetany or cardiac arrhythmias which could lead to falls or cardiac arrest.
It could equally affect the central nervous system causing convulsive or non-convulsive seizures, loss of consciousness, in addition to multimodal sensory abnormalities.
An electrical injury occurs when a current passes through the body, interfering with the function of an internal organ or sometimes burning tissues.
More often than not the main symptom is a skin burn, but not all the people have visible injuries.
In the initial evaluation, the patient should be checked for abnormal cardiac rhythm, fractures, dislocations, and spinal cord and other injuries.
The abnormal heart rhythms are monitored, burns are treated, and if the burn caused extensive internal damage, intravenous fluids are given.
Notes on Injuries Pattern:
Where as some electrical injuries such as low to high voltage electrical injuries were somewhat partly preventable others such as severe thundering/lightening were not. Anecdotally, electric injuries were most frequent in young adults aged in the second to the fourth decades of their lives probably due to more frequent exposures. Obtaining detailed information regarding the characteristics of the involved agents has major impact on workup, management, and outcome in cases.The relevant details will include the amount of current whether low voltages between one hundred and twenty to four hundred and forty Volts), High Tension Voltage (>more than one thousand volts), type current (alternating current)(AC) or direct current(DC) ,path-of-current ( hand-to-hand) ,hand-to-foot ,foot-to-foot ),the length of contact ( tetany ,locked-on phenomenon ),and the- events-associated with the injury (falls-,burns, water contact ) On the basis of the conductivities /resistivties of various body tissues ,the consequences of the injuries could be inferred. The resistivity of the body is estimated to be between five hundred to one thousand ohms, with bones, tendons and fat providing the most resistant to electric current.
Nerves blood vessels, mucus membranes and muscles were the best conductors. With regards to electrical burns, the cross sectional areas were inversely proportional to tissue damage. Therefore small areas such as joints receive maximal injuries .The current pathways plays an important role in determining injury with a vertical being more dangerous than a horizontal hand to hand pathway. Skeletal muscles were usually stimulated into tetany by currents with frequencies of forty to one hundred and ten Hetz.
Most low and high tension electrical currents are AC.AC produces tetany and the locked on phenomenon. Although tetany occurs in all muscles that are stimulated, the flexor muscle groups are usually stronger and predominant. As a result an individual’s grasp is uncontrollably locked onto an object, which could increase the length of time that the current passes through the body and may result in greater injury. In contrast, DC current tends to produce a single large muscular contraction that often throws the child away from the source, they often involve risk taking behaviours.Cardipulmonary arrests and comas were very rare, if ever observed. At low voltages AC injuries had three times the morbidity and mortality rates as DC current injuries. However, at high voltages both AC/DC produce similar effects. Electrocutions by lightening injuries were not reportable injuries and as such accurate statistics were lacking .occasionally, the presentations were so subtle that the correct diagnosis may be missed entirely. Low voltage electric injuries without loss of consciousness and/or arrest were the injury patterns most described for infants and young children who bite into electrical cords of common household domestic appliances or in older children during the repair of household appliances, neurological sequelae such as global comatose encephalopathies, transverse myelitis and peripheral neuritis were the most frequently encountered defects in most cases ,cardiac arrhythmias ,myoglobunuria ,hyperkalaemia ,renal cortical, renal tubular necrosis and renal insufficiencies were commonly associated complications.
Methodology:
Pre-experimental studies Through A Triangulated Research Methodological Approach.
Naturalistic Inquiry, Participant Observation, Interviews and Documentary Content Analysis. In addition to Media analysis (news papers, magazines) films (movies) Radio, television (advertisements, news and broadcasts) informative data.
Descriptive systems for the evaluation and creation of distinctions for lightning and electric current related events were still unharmonised.there appears to be no records of adverse cardiopulmonary and cerebrovascular or myogenic events and vital end organ dysfunctions following frank, bur especially with subtle lightning events. Global demographics are lacking for policy and decision making. This review explores the wider impact or connotations of electrical injuries through the following problem solving paradigm such as the case for the position of the elderly and certain metabolic vital organ dysfunctions associated cardiopulmonary difficulties and neuropathies in this scale may warrant an enhanced anti-electric shock measures for this subsets as a group.
Since, a little overdose may matter for electrical and lightning injuries in some individuals with certain genetic and acquired pathological conditions because of aneurysmal formation and arrythmogenic predisposing haemostatic metabolic and cardiopulmonary neurogenic dysfunctional structural diathesis. Electrically injured patients should receive a more comprehensive evaluation for renal injuries, neurological deficits; in addition to short, interval and longer term ophthalmological follow ups for cataracts and aneurysms formations.
Aneurysms occur following prolonged coagulative coaliquative necrosis of the fibromuscular medial intima of the large blood vessels especially the aorta following electrical shock injuries.
Aneurysms predisposes to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries both could cause dizzy spells.
Electrical and lightning injuries by causing fatty tissue necrosis could predispose to acute and chronic pancreatitis with calcification and fibrosis leading to a fibrocalculous chronic pancreatitis.
The stress of shock could lead to an irreversible diabetogenic hormone release, the effect of electrical injury in pregnancy being grave may well be related to the exacerbated humoural endocrine factors at play in pregnancy.
As a group patients with electric shock injuries will need longer term and more diligent follow ups.
These aspects are prophylactically, diagnostically and therapeutically unexplored but crucial concepts.
Results ,Case Studies and Discussions:
Extremely remarkable cases of severe electric current related injuries with unblemished favourable outcomes observed and managed by the authors were identified, itemized and analysed further for information gathered about the circumstances of the electric shock related injuries, the features on an indepth comprehensive physical examination ,cardiopulmonary, renal and vital end organs activities monitoring in addition to other presumably unforeseen or unseen injuries as epitomes of highlighting the range of plausible complications in childhood electric burn injuries and adolescence ,the pathophysiological mechanisms of several putative electrical related injuries were outlined extant and recent global literature concerned were reviewed, the diagnostic evaluations ,emergent and amenable prophylactic generic and specific deterrent options were proffered and discussed.
In one illustrative event a premorbidly healthy teenage male higher school leaver participating in an out door adventurous activity climbed unto a mango tree close to an electric pole, unintentionally placed his hands in contact with a high voltage overhead electric cable he was seen cyanosed, in hypertonus with cries and a firm sustained clenched titanic hand grip on an electric wire cable by passers by he was hinged down by rescuers with a wooden ladder.
When seen in the emergency department he was regaining normal muscle tone and control but was still cyanosed and hypothermic with poor capillary refill associated with bradycardia induced probably by dysystole or central apnea suggestive of a hand to hand flow of current across the heart. After an initial period of resuscitation he became tachycardiac, dysarrythmic and hypotensive .In this instance recovery was rapid and remarkable without sequelae following intensive prolonged cardiopulmonary resuscitations, the hearts automaticities restarted the heart to normal sinus rhythm.
On cutaneous examination, he had flash burns on both hands .On x-ray radiological surveys there were no associated musculoskeletal acute titanic, traumatic injuries or fractures, but he complained of dysasthesias, tingling, numbness and paresthesias especially of the upper limbs, there were no lenticular opacities or cataracts.
On otoscopy his tympanic membranes were intact. In another illustrative instance a six year old premorbidly healthy girl was seen after being rushed into the emergency department with a history consistent with being thrown to the floor after accidentally coming in contact with a household electrical appliance extension cord with recurrent convulsive seizures followed by progressive impairment of consciousness she was seen in convulsive status epilepticus with an arc and contact burns with a smaller more discreet entrance point at the upper trunk and a more pronounced blowout exit circuits in the right thigh in keeping with a prolonged severe direct contact energizing electrical current injuries with the possibility of immense internal injuries evoked.
She was oliguric with concentrated but non bloody, non haemoglobunuric or non myoglobunuric urine with an impaired consciousness level with a GCS of 12/15 Following an initial cardiopulmonary resuscitations, judicious fluid and electrolyte therapies, seizure control and impatient closer monitoring, hospitalizations and support with specific interventions, she recovered without sequelae, there were no lenticular opacities or cataracts on otoscopy her tympanic membranes were intact.
Conclusions & Importance:
Given the occasional covert presentations of some cases of electrical injuries, electrical circuitry related catastrophes must be excluded in all cases of sudden syncope and sudden arrest, especially when preceded by a scream due to involuntary contraction of the chest muscles. Though this presumption is achieved with a case series, if these presumptions were extrapolated elsewhere, it seems that there is a tendency that most cases of severe electrical injuries in teenagers and adults could lead to cardiac dysfunctions where as in children a global cerebral dysfunction may be the rule .A lot of cases could have been unreported or managed peripherally either by orthodox means or otherwise Detailed information regarding the specifics of the associated injuries which has major impacts on the work ups ,management and outcomes were vitally important factors in determining the outcome of these cases.
Given the occasionally hypothetical or proven paradoxical outcomes of some cases of electrocution injuries a basic evaluation of all cases which could very easily be proposed in most settings is warranted which could imply the application of a long strip 12 lead electrocardiogram (ECG) or rhythm strip, complete blood counts (CBCs) as a minimum investigative workup. In addition to biochemical profiles and muscle enzymologies .Urine examination and urinalysis for haemoglobunurias, myoglobunurias, because deaths from ARF were known to occur even with supposedly minor voltage incidents, also age specific deterrent options should be proffered.
MAIN TEXT:
Introduction
HISTORICAL PERSPECTIVE FROM ARCHIVAL RESEARCH:
Although electricity is a relatively recent invention, humans have always been exposed to electrical injuries caused by lightning. The catastrophic impact of the formidable effect of lightning was terrific and horrific. Perceived as non-amenable to any form of therapeutic intervention, it was accorded a punitive mystical origin and intent.Mythologically, Zeus, the ruler of the ancient Hellenic gods, was symbolically illustrated holding thunderbolts, which he used for cautionary and punitive purposes for disobedience to his ordinances. However, the invention and extensive employ of electricity in energy saving rapid machineries, improved ergonomics and the domiciliary settings in the mid-1800s some what partly demystified the mythological and diabolical concepts overwhelming electrical prowess, whilst comtemperonously introducing electrical injuries as a common problem at occupational or domiciliary settings.
The first reported and documented electrical fatality was recorded in a Parisian setting in 1879.The 1994 classics and eminent scholarships of Bernstein chronicled and reviewed the historical aspects of electrical injuries, it equally presented and discussed the electrical engineers perspective on this theme and proffered a position statement. [1]
Classifications of electrical injuries generally focus on the power source (lightning or electrical), voltage (high or low voltage), and the type of current (alternating or direct), each of which is associated with certain injury patterns.
Two modalities of electrical current has been recognized, the alternating current (AC) and the direct current (DC) .In the former, the electrons flow pattern is usually bidirectional (backwards and forwards) through a conductor in a cyclic pattern. This type of current is the most commonly used in households and offices, and it is standardized to a frequency of about sixty cycles per second (approximately sixty Hetz) in the later when the current is direct,(DC) the electrons flow only forward (unidirectionally).
This pattern of current motion is produced by various batteries and is used in certain medical equipment such as defibrillators, pacemakers, and electric scalpels.
Although AC is considered to be a far more efficient way of generating and distributing electricity, it is also more dangerous than DC (approximately three times) because it causes tetanic muscle contractions that prolong the contact of the victim with the source. In 1968, histriographic data on the pros and cons of either forms of current source (AC versus DC) was proffered by Taussig in his scholarship on the Death “from lightning and the possibility of living again. [2]
Whereas, Cooper presented and discussed the emergent care of lightning and electrical injuries.in 1995. [3]
On the basis of their scholarship on the pathophysiology of acute electric injuries of 1976 Hunt, Mason and Masterson et al. proposed that nerves and blood vessels, are the best conductors; the former because they are innately designed to carry electrical currents and the later due to their high water content. It has been suggested that these properties create the path of least resistance for current after it enters the body, thus affecting primarily the nerves and blood vessels. In reality it seems that internal tissues of the body act as a single resistor and not as a compendium of multiple resistors in themselves. [4]
And other previous reviews by -Stresser et al on .Lightning injuries of 1977 exists. [5]
This article proffers an explanatory survey of the historical aspects, demographics and pathophysiology, in addition to the diagnostic and therapeutic aspects of electrical injuries caused by manufactured electricity.
Methodology:
Pre-experimental studies Through A Triangulated Research Methodological Approach.
Naturalistic Inquiry, Participant Observation, Interviews and Documentary Content Analysis. In addition to Media analysis (news papers, magazines) films (movies) Radio, television (advertisements, news and broadcasts) informative data.
Descriptive systems for the evaluation and creation of distinctions for lightning and electric current related events were still unharmonised.there appears to be no records of adverse cardiopulmonary and cerebrovascular or myogenic events and vital end organ dysfunctions following frank, bur especially with subtle lightning events. Global demographics are lacking for policy and decision making. This review explores the wider impact or connotations of electrical injuries through the following problem solving paradigm such as the case for the position of the elderly and certain metabolic vital organ dysfunctions associated cardiopulmonary difficulties and neuropathies in this scale may warrant an enhanced anti-electric shock measures for this subsets as a group.
Since, a little overdose may matter for electrical and lightning injuries in some individuals with certain genetic and acquired pathological conditions because of aneurysmal formation and arrythmogenic predisposing haemostatic metabolic and cardiopulmonary neurogenic dysfunctional structural diathesis. Electrically injured patients should receive a more comprehensive evaluation for renal injuries, neurological deficits; in addition to short, interval and longer term ophthalmological follow ups for cataracts and aneurysms formations.
Aneurysms occur following prolonged coagulative coaliquative necrosis of the fibromuscular medial intima of the large blood vessels especially the aorta following electrical shock injuries.
Aneurysms predisposes to thrombo-embolic phenomenon as do the arrhythmias associated with electric shock injuries both could cause dizzy spells.
Electrical and lightning injuries by causing fatty tissue necrosis could predispose to acute and chronic pancreatitis with calcification and fibrosis leading to a fibrocalculous chronic pancreatitis.
The stress of shock could lead to an irreversible diabetogenic hormone release, the effect of electrical injury in pregnancy being grave may well be related to the exacerbated humoural endocrine factors at play in pregnancy.
As a group patients with electric shock injuries will need longer term and more diligent follow ups.
These aspects are prophylactically, diagnostically and therapeutically unexplored but crucial concepts.
Results and Literature Reviews:
Existing Epidemiological and Demographic Research Data for Electrical Injuries.
This review concerns electrical and lightning injuries. Approximately, about one thousand deaths per year are due to electrical injuries in the North America, with a mortality rate of about three to five percent. Electrical injuries have increasingly attracted a lot of interest following the report of the first human fatality from accidental electrocution in 1879.In several North American series, approximately one thousand deaths occur annually from electrical current related accidents, while another one hundred and fifty to two hundred and fifty persons die as a result of being struck by lightening .In addition, major electrical burns presently constitute nearly one in twenty of all admissions to burn centres on the average. Electrical injuries occur most commonly among utility pole linesmen and construction workers who come in contact with high tension current, but nearly a third result from accidents in the home or other settings including the hospital with its many electrically powered instruments and appliances. As a seminal concept the intensive care management of electrical injuries was approached by Koumbouris in 2002. [6] And corroborative data by Spies and Trohman on the .Narrative Review of Electrocution and life-threatening electrical injuries was produced in 2006.[7] Due to the nature of occupational hazards with electricity, electrical injuries represent the fourth leading cause of work related traumatic death (five to six percent of all workers deaths) No racial susceptibility to electrical burns exists. Occupational trends indicate that traces people in high-risk occupations to be disproportionately Caucasian; therefore, this group may be more likely than other races in the North America to experience occupation-related electrical injuries. An institutional report and position statement on the overview of electrical hazards in Worker Deaths by Electrocution which is a summary of NIOSH Surveillance and Investigative Findings of the Department of Health and Human Services (NIOSH) Washington, DC, USA was proffered by Casani in 1998. [8] Electrical injuries are responsible for about three to five percent of emergency department burn visits in the paediatric population. Rai, Jeschke, Barrow and Herndon on the basis of their thirty year review of electrical injuries of 1999 proposes that some evidence exists that the incidence of low-voltage injuries amongst children is declining, perhaps because of widespread use of ground fault circuit interrupters (GFCIs), but rates of high-voltage injuries usually involving power lines or rail sources, has remained steady.[9]
GENDER PREVALENCE:
Rates of childhood electrical injury are higher amongst boys than girls. And the incidence of adult injury are significantly higher in men than in women; likely because of occupational predisposition .Most series demonstrate that more than eighty percent of electrical injuries occur in men.[3]
AGE:
A bimodal distribution of electrical injuries exist amongst the very young
(Children less than six years of age) and amongst young and working-aged adults. Patterns of electrical injuries vary by age (e.g household low-voltage exposures amongst toddlers and high-voltage exposures amongst risk-taking adolescents and via occupational exposure. In 1976, Hunt, Mason and Masterson et al discussed and characterized the epidemiology, pathophysiology of acute electric injuries in the childhood population. [4] This was corroborated by the 1995, data of Cooper on the emergent care of lightning and electrical injuries. [3]
The most common mode of electrical injury in young children is from chewing or biting on electrical cords.Histriographic data on this theme was provided by Thomson, Juckes and Farmer in their reviews on electrical burns to the mouth in children of 1965. [10] In addition to the 1989 scholarships of Baker and Chiavello on Household electrical injuries in children with relevance to its epidemiology and identification of avoidable hazards. [11]
The Health Economics and Occupational Health Aspects of Electrical Injuries:
The health economic aspects of electrical injuries was of much historical interests when the case of protection against injuries over cost effectiveness became an overwhelming one in the era following the advent of electricity .Thomas Edison (who invented advanced and promoted DC) was at log aheads with George Westinghouse (who innovated and enhanced AC) To demonstrate the deleterious properties and effect of AC, Edison with persuasion and cohesion made the New York State legislature to apply AC for the first death penalty by electrocution ( coined as”Westing-housed”)
To date, electrocution is still used as a form of capital punishment in some circumstances. As a seminal theme, the combined topic of emergent care of lightning and electrical injuries was approached and dissected by Cooper in 1995, [3]
An institutional report and position statement on the overview of electrical hazards in Worker Deaths by Electrocution which is a summary of NIOSH Surveillance and Investigative Findings of the Department of Health and Human Services (NIOSH) Washington, DC, USA was proffered by Casani in 1998. [12]
Reviews by Kisner and Casini on the Epidemiology of electrocution Fatalities: 1998.In”Worker Deaths by Electrocution: A summary of NIOSH Surveillance and Investigative Findings .Washington D.C ,Department of Health and Human Services (NIOSH) proposes that ,despite significant improvements in product safety, electrical injury is still the cause of many fatalities and considerable morbidity. Electrical injuries (excluding lightning) are responsible for more than five hundred deaths per year in the USA.A little more than half of them occur in the workplace and constitute the fourth leading cause of work-related traumatic death(about five to six percent of all workers deaths) [13]
Electrocutions at home account for more than two hundred deaths per year, and they are mostly associated with malfunctioning or misapplication of consumer products [14]
Electrical injuries are also the cause of considerable morbidity .Electrical burns account for approximately two to three percent of all burns in children that require emergency department attention (more than two thousand cases per year) the vast majority of electrical burns in children take place at home and are associated with electrical and extension cords (in about sixty to seventy percent of the incidents) and with wall outlets, which account for another ten to fifteen percent of cases. As a topical concept of public health importance, Hiser on behalf of the Report Safety Commission, a Division of Hazard Analysis, and Directorate For Epidemiology, presented electrocution Associated with Consumer Products in 2001. [14]
As for the epidemiological figures for lightning related injuries, Lopez and Holle on the basis of their data on the demographics of lightning casualties of 1995 indicates that
Lightning is responsible for an average of ninety to one hundred deaths annually in the North America, whereas its associated morbidity is estimated to be between five to ten times higher than that due to other forms of electrical injury.
[15]
Because severe electrical injuries tend to occur primarily in the work place, they usually involve adults, and therefore, they account for a small percentage of the overall number of admissions to pediatric intensive care units (ICUs).However, considering that both the home and work environments are full of electrically powered devices, the potential of accidental injury is ever present, and it is necessary for the intensivist to know the characteristics and the principles of management of this type of injury. In the distant past, an interesting data on the changing concepts of the pattern of electrical injury was provided by Artz in 1974.
[16] Histriographically, other seminal data on the public and community health aspects of electrical injuries was provided by Lievens in 1970. [17]
Of particular importance is the possibility of iatrogenic electrical injury in the ICU (and in the operating room and electrophysiology suites), where several procedures are performed utilizing high-voltage energy for diagnostic and therapeutic purposes (e.g., defibrillators, Gibbs, Eisenberg and Damon reviewed and discussed dangers of defibrillation injuries to emergency personnel during patient resuscitation in 1990.[18] And in 1998, extensive pectoral muscle necrosis after defibrillation by nonthermal skeletal muscle damage caused by electroporation was highlighted and explored by Vogel, Wanner and Bultmann.
[19]Also, Gilbert, Shaffer and Matthews reported and discussed electrical shock by dislodged spark gap in bipolar electrosurgical device in 1991. [20]
In addition, a combined defibrillator and pacemaker injuries was highlighted by
Kim, Furman and Matos et al in their reports of automatic implantable cardioverter defibrillator inciting inadvertent discharges during permanent pacemaker magnet tests of 1987. [21]
Case Studies and Discussions:
Extremely remarkable cases of severe electric current related injuries with unblemished favourable outcomes observed and managed by the authors were identified, itemized and analysed further for information gathered about the circumstances of the electric shock related injuries, the features on an indepth comprehensive physical examination ,cardiopulmonary, renal and vital end organs activities monitoring in addition to other presumably unforeseen or unseen injuries as epitomes of highlighting the range of plausible complications in childhood electric burn injuries and adolescence ,the pathophysiological mechanisms of several putative electrical related injuries were outlined extant and recent global literature concerned were reviewed, the diagnostic evaluations ,emergent and amenable prophylactic generic and specific deterrent options were proffered and discussed.
In one illustrative event a premorbidly healthy teenage male higher school leaver participating in an out door adventurous activity climbed unto a mango tree close to an electric pole, unintentionally placed his hands in contact with a high voltage overhead electric cable he was seen cyanosed, in hypertonus with cries and a firm sustained clenched titanic hand grip on an electric wire cable by passers by he was hinged down by rescuers with a wooden ladder.
When seen in the emergency department he was regaining normal muscle tone and control but was still cyanosed and hypothermic with poor capillary refill associated with bradycardia induced probably by dysystole or central apnea suggestive of a hand to hand flow of current across the heart. After an initial period of resuscitation he became tachycardiac, dysarrythmic and hypotensive .In this instance recovery was rapid and remarkable without sequelae following intensive prolonged cardiopulmonary resuscitations, the hearts automaticities restarted the heart to normal sinus rhythm.
On cutaneous examination, he had flash burns on both hands .On x-ray radiological surveys there were no associated musculoskeletal acute titanic, traumatic injuries or fractures, but he complained of dysasthesias, tingling, numbness and paresthesias especially of the upper limbs, there were no lenticular opacities or cataracts.
On otoscopy his tympanic membranes were intact. In another illustrative instance a six year old premorbidly healthy girl was seen after being rushed into the emergency department with a history consistent with being thrown to the floor after accidentally coming in contact with a household electrical appliance extension cord with recurrent convulsive seizures followed by progressive impairment of consciousness she was seen in convulsive status epilepticus with an arc and contact burns with a smaller more discreet entrance point at the upper trunk and a more pronounced blowout exit circuits in the right thigh in keeping with a prolonged severe direct contact energizing electrical current injuries with the possibility of immense internal injuries evoked.
She was oliguric with concentrated but non bloody, non haemoglobunuric or non myoglobunuric urine with an impaired consciousness level with a GCS of 12/15 Following an initial cardiopulmonary resuscitations, judicious fluid and electrolyte therapies, seizure control and impatient closer monitoring, hospitalizations and support with specific interventions, she recovered without sequelae, there were no lenticular opacities or cataracts on otoscopy her tympanic membranes were intact.
The Physics of Electricity with the nosological aspects and Pathogenesis of electrical injuries.
Electricity is produced by the flow of electrons (the negatively charged outer particles of an atom) across a potential gradient from a high gradient to a low one through an electrical conductor. Any substance which accumulates electrons becomes negatively charged, and the efflux of electrons from this substance through an electrical conductor, creates an electric current, which is estimated in amperes.
The voltage, the propulsive drive to the flow of electrons, is estimated in volts.
Impedance of any character to the flow of electrons through an electrical conductor espouses an electrical resistance, which is gauged in ohms.
ELECTRIC SHOCK AND ELECTRIC BURNS:
The danger of injury from electric shock depends upon the voltage and the frequency. Alternating current is more dangerous than direct current. At a frequency of 25- 300 cycles, voltages below 230 volts can produce ventricular fibrillation .High voltages (which may be encountered in television circuits) produce respiratory failure .Faulty wiring of home appliances may lead to electric shock .In homes with young children, it is advisable to install occlusive safety outlets in the play area.
The Physics of Electricity with the Pathophysiology and the Determinants Of Electrical Injury.
Although the end result of the passage of an electric current through the human body is unpredictable in the individual case, many factors are known to influence the nature and severity of electrical injuries. Electrical injury involves both direct and indirect mechanisms. The direct damage is caused by the actual effect that the electric current has on various body tissues (such as the myocardium) or by the conversion of electrical to thermal energy that is responsible for various types of burns. Indirect injuries tend to be primarily the result of severe muscle contractions caused by electrical injury. In general, the type and extent of an electrical injury depends on the intensity (amperage) of the electric current.
Electrical injury may result from contact with faulty electrical appliances or machinery or inadvertent contact with household wiring or electrical power lines.
For adults getting shocked from touching an electrical outlet in the home or by a small appliance is rarely serious, but accidental exposure to high voltage causes about half a million deaths each year according to several North American series. However these figures are not directly applicable or extrapolateable to most other settings especially the developing units.
The severity of electrical injuries ranges from mild through severe to catastrophic and deadly. The severity of electrical injuries is contingent on the following factors.
[I]-The intensity of the voltage and the generated current.
[II]-The Form of the electrical current Circuit.
[III]-The pathway of the current through the body.
[iv]-The duration of exposure to the current.
[V]-The electrical resistance to the current.
THE VOLTAGE
The voltage (V) represents the magnitude of this potential difference and is usually determined by the electrical source. The type and extent of an electrical injury is determined by voltage, the strength of the current, the resistance to electrical flow, the duration of contact with the source of electricity, the pathway of flow, and the type of current (i.e direct or alternating).
In understanding the fundamental aspects of electrical current injuries, it is helpful to consider some electrical principles. For an electric current to flow, there must be a closed pathway or circuit, and a potential difference or voltage must exist between two points in a wholesome circuit.
Anecdotally, electrical injuries were traditionally and typically categorized into high-voltage or low-voltage injuries, using about five hundred or one thousand Volts as the cutoff.
On the basis of the narrative review on electrocution and life-threatening electrical injuries by Spies and Trohman of 2006, it could be inferred that in North America, typical household electricity provides about one hundred and ten volts for general use and two hundred and forty Volts for high-powered appliances, while industrial electrical and high-tension power lines can have more than one hundred thousand Volts. [7]
In 1997, High morbidity and mortality has been described in a six hundred voltage direct current injury associated with railroad “third rail” contact, by Rabban, Adler, Rosen, Blair and Sheridan in their scholarship on electrical injury from subway third rails with serious injuries associated with immediate voltage contact burns. [22]
Lightning is a form of Direct Current that occurs when the electrical difference between a thundercloud and the earthy sandy surface outstrips the insulating capabilities of the encircling atmospheric air. The current of a lightning strike rises to a peak in about 2Usec, and it lasts for only 1-2 msec.The voltage of a lightning strike is in excess of one million volts and it can generate currents of more than two hundred thousand amperes. Transformation of the electrical energy to heat can generate temperatures as high as 50,000 degrees Farenheight. However, the extremely short duration of lightning prevents struck objects from melting. Reviews on lightening related injuries were provided by Ghezzi in his scholarships on the unique treatment challenge of Lightning injuries of 1989.[23]And Fahmy, Brinsden and Smith et al.on Lightning the multisystem group injuries of 1999.[24]
Current:-The intensity of the current.
The intensity of the current is measured in volts and amperes .Ordinary household current in most installations is usually about one hundred and ten volts to two hundred and twenty voltages. Voltages above five hundred are considered to be high .High voltages can jump (arc) through the air anywhere from an inch up to several feet, depending on the voltage. Thus a person may be injured simply by coming too close to a high voltage line. High voltage causes more severe injuries than low voltages and is more likely to cause internal damages.
These aspects were dissected by Casani in his1998 overview of electrical hazards in Workers Deaths by Electrocution in A summary of NIOSH Surveillance and Investigative Findings. Washington, DC, Department of Health and Human Services (NIOSH) [12]
The volume of electrons flowing across a gradient is the current, which is represented in amperes (I); it is an estimate of the amount of energy that flows through a body.
[V]-The resistance and the conductivity of the electrical current by the body tissues.
The impedance to the flow of electrons across a gradient is the resistance® and varies depending on the electrolyte and water content of the body tissue through which electricity is being conducted. Blood vessels, muscles and nerves have high electrolyte and water content, and thus low resistance, and are good conductors of electricity –better than bone, fat, and skin.
Most of the body’s resistance is concentrated on the skin .The thicker the skin is, the greater is its resistance .A thick, callused palm or sole, for example, is much more resistant to electrical current than an area of thin skin, such as an inner arm, the skins resistance is compromised when there is a disruption or discontinuation of its integrity such as when it is punctured or scraped or when it is wet. If the skins resistance is augmented, more of the damage is circumscribed and localized, often only causing skin burns. If the skins resistance is compromised, more of the damage of electrical injuries affects the internal organs. Therefore, the damage is mostly, internal if people who are wet come in contact with electrical current, for example, when one attempts to work on an electric grinder after washing some vegetables or fruit or touching a high tension out door cable on a wet day.
RESISTANCE.
The flow of electrical currents is directly related to the voltage difference and inversely proportional to the electrical resistance between two points in the circuit (ohms law) High resistance paths allow relatively small currents to flow, while low resistance between two points permit larger currents to flow .When the voltage is very high, the flow of current will likewise be relatively great, unless the resistance is increased proportionally to the voltage; how-ever ,if the potential difference between the two points can be minimized ,the current flow can also be minimized regardless of resistance.
Body tissues vary considerably in their resistance to the flow of current, with conductivity being roughly proportional to water content. Bone and skin offer relatively high resistance, while blood, muscle, and nerve are good conductors. The resistance of normal skin can be lowered by moisture, and this factor alone can convert what might ordinarily be a mild injury to a fatal shock.
[II]-The type or Form of Electrical Current Circuit:
Electrical current is categorized as direct current (DC) or alternating current (AC).
Direct current, such as current generated by batteries, flows in the same direction constantly. Alternating currents such as currents available through household wall sockets, changes direction fifty to sixty times per second. Alternating current which is used in most households in North America and Europe is more dangerous than direct current. Direct current tends to cause a single muscle contraction often strong enough to force people away from the currents source, where as alternating current causes a continuing muscle contraction, often preventing people from releasing their grip on the currents source. As a result, exposure may be prolonged .Even a small amount of alternating current barely enough to be felt as a mild shock –may cause the grip to freeze, slightly more alternating current can cause the chest muscles to contract, making breathing impossible .Even more current can cause deadly abnormal heart rhythms( arrhythmias)
Types of Circuit:
Electrical current can flow in one of two types of circuits, the direct current (DC) in which the current flows linearly in a forward direction or alternating current (AC), in which the flow of electrons changes direction in rhythmic fashion or sinusoidal.pattern.AC is the most common type of electricity in homes and offices, standardized to a frequency of sixty cycles/second (Hetz).High-voltage DC often causes a large single muscle contraction that throws the victim away from the source, resulting in a brief duration of contact with the source flow.In contrast, AC of the same voltage is considered to be approximately three times more dangerous than DC, because the cyclic flow of electrons causes muscle tetany that prolongs victims exposure to the source.
Muscle tetany occurs when fibres are stimulated at forty to one hundred and ten Hetz; the standard sixty Hetz of household current is within the tetanic range. If the source contact point is the hand, when tetanic muscle contraction occurs the extremity flexors contract, causing the victim to grasp the current and resulting in prolonged contact with the source. An electrical injury will occur when a person comes into contact with the current produced by a source. This source could be an artificially made one (such as the power line of a utility company) or a natural one, such as lightning. [Casani1998,)[12]
Electrical power is generated and transmitted via a system of three conductors with the same voltage but with waveforms that reach their peak at a different phase. This three-phase system allows for a more efficient generation and transmission of power. Power lines used by utility companies are classified according to their voltage from phase to phase, and they range from “low” (when they carry more than six hundred volts) to “ultrahigh” (with voltage of more than one million volts) .Utility power lines with high voltages tend to be located in sparsely populated areas, and therefore, the possibility of an accidental contact with them is relatively limited for the general population. Through a succession of transformers, the voltage is gradually reduced, and the power lines that distribute electricity for homes, buildings, and the general industry carry low voltage, defined by the National Electrical Code as less than six hundred volts .Most houses in North America.)
Have a one hundred and twenty to two hundred and forty volts, single phase system that provides the two hundred and forty for the high-power appliances and the one-hundred and twenty volts for general use.The latter accounts for most of the accidental injuries .The household voltage in most other countries is usually higher (220V) Bernstein 1994 Electrical injury: Electrical engineers perspective and an historical review.)[1]
The pathophysiological effects of electrical currents of variable intensities generated by common household voltage is of interest because almost everyone has been implicated in this effect.In this way, this concept is of utmost public health importance.
At a current strength of one milliampere ,the probable effect is that of a tingling sensation which may almost be imperceptible by some individuals, a current of sixteen milli-Amperes is the maximum current that a person can grasp and let go, a current of seven to nine milli-Amperes is a let go current for an average man , a current of six to eight milli-Amperes is a let go current for an average woman ,a current of three to five milli-Amperes is a let go current for an average child ,at a current of sixteen to twenty milli-Amperes , there is tetany of the skeletal muscles ,at a current of twenty to fifty milli-Amperes there is paralysis of the respiratory muscles and respiratory arrest ,the current of fifty to one hundred and twenty milliamperes is the threshold for ventricular fibrillation ,and at current greater than two Amperes there could be asystole.
Most common house hold circuit breakers will have a current of between fifteen to thirty Amperes and the maximum intensity of house hold currents in the North America is about two hundred and forty Amperes. These clinico-pathophysiologic correlative aspects of electrical injuries were illuminated upon by Koumbouris in his scholarships on electrical injuries .in 2002. [6]
And by [Cooper (1995.Emergent care of lightning and electrical injuries.)[3]
Voltage is directly proportional to current and indirectly proportional to resistance as expressed by Ohms Law: V=I X R; where I= current, V= voltage, R= resistance.
THE RELATIONSHIP BETWEEN THE RESISTANCE AND RATE OF CURRENT FLOW:
Thus, exposure of different parts of the body to the same voltage will generate a different current (and by extrapolation, a different degree of damage) because resistance varies significantly between various tissues. The least resistance is found in nerves, blood, mucous membranes, and muscles, whereas the greatest resistance is found in bones, fatty tissues, and tendons with the skin having an intermediate resistance. These aspects were dissected by Cooper in his 1995 Scholarships on Emergent care of lightning and electrical injuries. [3]
From a practical point of view ,one could make a distinction between the external resistance ( represented by the skin ) and the internal resistance ( which includes all the other tissues) of the body .The skin is the primary resistor against the electrical current ,with a resistance ranging in adults between forty thousand and one hundred thousand ohms depending on its thickness ( i.e., the thicker the skin ,the higher is its resistance).Thus, the intensity of the electrical shock produced by a certain voltage will vary between victims of different gender and age.For,instance, exposure to the common household voltage of about one hundred and twenty volts of an adult Labourer with thick. calloused palms whose resistance may be in excess of one hundred thousand ohms will create a current of approximately one milliamperes, which is barely perceptible.
In contrast, the same exposure on a new-born infant whose skin is very thin and has a high water content (which markedly lowers its resistance) will probably cause significant injury. Even more important than the thickness is the moisture of the skin. Several existing scholarships dwelt on these physico-electro-mechanistic aspects, of water molecules on propagating the impact of electrical injuries. Fish in his scholarships on electric Shock: Part 1.Physics and Pathophysiology of 1993 discussed the intricacies and peculiarities of the individual or idiosyncratic factors influencing the propagation or the protection against electric shock injuries. [25]As did the grounded independent reviews of Cooper and Casani et al of 1995 and 1998 respectively. [12] [3]
The presence of a sweaty skin may decrease the resistance of the skin to as low as less than one thousand ohms. Wet skin (e.g .electrocution of a person in a bathtub or in a swimming pool) offers almost no resistance at all, thus generating the maximal intensity of current that the voltage can generate. This compounding synergistic impact of the deleterious impact of swimming during rains with lightning events is of utmost importance to children who swim in pools and body of accumulated water during rains, even mere wading or walking through bodies of water or wet clothing’s during rains could have the same compounding impact of water or wet clothing diminishing the resistance, some cases of near drowning or drowning during rains ,snow storms or hail stones could have been related to subtle and covert lightning related electrical injuries or electrocutions of some sort .Deaths from near drownings in accumulated bodies of water during rains have been reported and reviewed previously.
[26] [27]
The impact of subtle lightning related events during rains in causing perturbations of consciousness and multiple organ dysfunction syndromes have not been examined previously. Since moist mucus membranes also have negligible electrical resistance, thus maximizing any current with which they come into contact. This causes significant orofacial injury to infants and toddlers who tend to put live wires in their mouths. This enhanced conductivity may have implications for subtle but deleterious perturbations of cardiopulomany or CNS regulatory centres related to electrical injuries from electrocautrey surgeries especially in the anaesthetized patients.
The internal resistance of the body comprises all the other tissues and is estimated to be between 500 and 1000 ohms.Although bones, tendons, and fat offer the most resistance to electric current, they are not likely to be contact points. When exposed to electric current, they tend to heat up and coagulate before conducting the current. [Cooper 1995][3]
Of importance, at the time of contact is grounding which if effective can minimize the voltage difference between two points in the electrical circuit and lower the intensity of the current passing through the body. The pathway of the current through the body is crucial. An accident involving the passage of a current between a point of contact of the leg and the ground is likely to be injurious than one between the head and the foot, in which the heart lies between the two poles of the circuit. Similarly, a small current leak, which would be innocuous when applied to the surface of the intact body, may result in a fatal arrhythmia when conducted directly to the heart via a low-resistance intracardiac catheter. Heavily calloused areas of skin are excellent resistors, whereas a moderate amount of water or sweat on the skin surface can decrease its resistance significantly.
[III]-The pathway of the current through the body.
The path that the electricity takes through the body tends to determine which tissues are affected .Because alternating current continually reverses the direction .The commonly used terms “entry “and “exit “ are inappropriate .The terms “source” and “ground” are more precise. The most common source point for electricity is the hand, and the second most common is the head. The most common ground point is the foot. A current that travels from arm to arm or from arm to leg may go through the heart and is much more dangerous than a current that travels between a leg and the ground .A current that travels through the head may affect the brain.[28]
[iv]-The duration of exposure to the current and the duration Of Contact to the electrical source.
This also influences the outcome of electrical injuries Alternating current is much more dangerous than direct current, partly because of its ability to produce tetanic muscular contractions which prevent the victim from being able to release contact with the circuit. This is usually accompanied by sweating which lowers skin resistance, allowing current of still greater intensity to pass into the body until fatal cardiac arrhythmia results. While the effects of electricity on the body is incompletely comprehended, many pathophysiological features of severe electrical injury have been described. In general when sudden death occurs following low-voltage shock, it is due to the direct effect of relatively small amounts of current upon the myocardium resulting in ventricular fibrillation. With high-tension injury (greater than one thousand Volts) cardiac asystole and respiratory arrest occur probably as a result of injury to the medullary centers of the brain. In general, the longer, the person is exposed to the current, the worse the injury.
Therefore the duration of the contact with electrical current is an important determinant of electrical injuries. Thus, an electric shock caused by AC will produce greater injury than a shock caused by DC of the same amperage because the DC causes a single muscle contraction that “throws” the victim away from the power source, thus minimizing the injury. (Cooper 1995. Emergent care of lightning and electrical injuries) [3]
These differences have practical significance only at low voltages, whereas in high voltages, both currents have a similar effect.
The pathway of the current through the body (from the entry to the exit point) determines the number of organs that are affected and, as a result, the type and severity of injury .The determination of the electrical pathway is important both for acute management and for overall prognosis .A vertical pathway parallel to the axis of the body is the most dangerous because it involves virtually all the vital organs ( central nervous system, heart ,respiratory muscles ,and in pregnant women, the uterus and the fetus ) A horizontal pathway from hand to hand will spare the brain but can still be fatal due to involvement of the heart, respiratory muscles, or spinal cord. A pathway through the lower part of the body may cause severe local damage but will probably not be lethal. These aspects were elaborated upon by Jain and Bandi in their scholarships on Electrical and lightning injuries of 1999. [29]
Whereas electric shock from a low-voltage line is delivered on contact of the victim with the source, in high-voltage injury, the current is carried from the source of the person through an arc before any physical contact is made. The arc may form over or into the body of the person .Arcs can generate extremely high temperatures (up to 5000 degrees centigrade) that are usually responsible for the severe thermal injuries from high voltage. (Bernstein 1994. Electrical injury: Electrical engineers perspective and an historical review.) [1]
For an excellent review see the book chapters of Price and Cooper on .Electrical and Lightening injuries. Edited by Marx, Hockberger, Walls and Rosens in the, 2002 edition of their book on Emergency Medicine. [30]
PATHOLOGY
In patients who die immediately from electrocution, autopsy findings are limited to burns and generalized petechial hemorrhages. If patients survive for a period of days or longer, post mortem examination reveals focal necrosis of bone, large blood vessels, muscle, peripheral nerves, spinal cord, or brain. Renal tubular necrosis may also be seen when acute renal failure follows extensive tissue destruction.
The Histopathologic Features of Electrical Burns Injuries:
Demonstrable in the photomicrograph of a biopsy of the cutaneous burns area are elongated pyknotic keratinocyte nuclei with vertical streaming and homogenization of the dermal collagen
ELECTRIC BURNS.
The Physico-Chemical Aspects of Cutaneous Injuries And Burns.
In addition, contact with high intensity current may cause three types of thermal injuries. Current coursing externally to the body from the contact point to the ground may generate temperatures as high as ten thousand degrees centigrades and cause extensive carbonification of the skin and juxtaposed underlying tissues termed arc or flash burns. Such burns often ignite surrounding clothing or nearby objects giving rise to flame burns .Finally, there is injury due to the direct thermal injury of tissues by electric current.
As it traverses the skin, energy from an electrical current is converted into heat which produces coaliquative coagulation necrosis at the points where it enters and exits from the skin as well as in the striated skeletal and cardiac muscles and blood vessels through which it navigates. The associated vascular injury results in thromboses, often at sites distant from the body surface, and accounts for the observation that a greater amount of tissue destruction characteristically occurs in an electrical injury than is apparent on first inspection.
The Intricacies in the Pathophysiology of the Morbidity and Mortality Related to Cutaneous Burns.
Exposure to currents generated by low-voltage sources (including household electric sources) may cause a variety of cutaneous injuries from the transformation of electrical to thermal energy. The injuries could range from local erythema to full-thickness burns.The severity of the burn depends on the intensity of the current, the surface area, and the duration of exposure. First degree electrical burns require an exposure of at least twenty seconds to a current of more than twenty milliamperes per millimeters squared, whereas a second or third degree burn requires exposure to at least seventy five milliamperes per millimeters squared, which is well within the range capable of causing ventricular fibrillation .In order words, a patient may die before there is time to cause significant surface burns. Erudite histriographic data was proffered in 1965 by Robinson &Others in a review and analysis of 33 cases of electrical burns.[31] In addition, chronologically, several scholarships on these thematic aspects exist, in 1980.Hunt, Sato and Baxter reviewed and discussed Acute electric burns; current diagnostic and therapeutic approaches to management.
[32] And thereafter, corroborative data were provided by Fish in 1993 from his work on Electric Shock: Part 1.Physics and Pathophysiology [25]
In addition to Bernstein in 1994.following his scholarships on electrical injury: Electrical engineers perspective and an historical review. [1]
In addition, because the resistance of the skin may be significantly and markedly altered by moisture, electric current may be transmitted by deeper tissues before it causes significant damage to the skin. Electric current may be adsorbed and sustained by resistant bony structures, and the heat generated may be circumscribed and localized causing massive coagulation and necrosis of deep muscles and other tissues, almost completely sparing the skin. Thus in contrast with burns caused by fires, the severity of skin burns cannot be used to assess the degree of internal injury in an electrical accident with low voltage.
Chronologically, these subtle and covert intricacies and complexities with potential deleterious implications of the impact of electric current and lightning injuries was highlighted and discussed in 1977 by Burke, Quinby and Bondoc in their seminally disseminated scholarships on the patterns of high tension electrical injury in children and adolescents and their management. [33]
As did the 1980; reviews of Hunt, Sato and Baxter on the acute electric burns; current diagnostic and therapeutic approaches to management [32] In addition to the combined electrical and lightnine injuries reviews of Cooper of 1984, [34]
and [29] Jain and Bandi of 1984 and 1999 respectively. More serious burns are usually caused by exposure to arcs that are created in accidents with high-voltage currents (more than 1000 volts)
In such cases, the severity of the burn depends not only on the temperature but also on the energy within the arc. Exposure to an arc may rapidly break down the epidermis of the skin (as fast as one millisecond), thus decreasing the body’s resistance to that of the internal organs (five hundred to one thousand ohms) The combination of high temperature and high current in an arc causes a variety of burns including:”flash burns”, which are thermal burns due to the heat generated by the arc;” electrothermal burns,” due to the passage of the electric current through the body ; and “flame burns” ,usually from ignition of the clothing .Burns due to lightning are common ( up to eighty five to ninety five in several credible series) ,but despite the massive energy and heat that lightening generates, its short duration and flash-over effect proffers a protective and injury ameliorating buffering advantage. As a result deep burns occur only in five percent of the victims. For an excellent review of this theme see the literature on the Prognostic signs for death in Lightning injuries by Cooper of 1980. [35]
When they occur ,burns may be of different morphological forms, including partial-thickness linear burns ,mostly in areas of amplified sudiferous glands localizations such as the armpits with much sweaty skin), it may be punctate burns which are groups of small, deep, circular burns, thermal burns following the ignition of clothing or contact with effective metallic conductors ), and feathering burns.The latter also called Lichtenburg figures, ferns or keraunographic markings) are cutaneous marks that are considered pathognomonic of lightning, but it is unclear whether they are actual burns.
In 1996, Elegant Forensic Medical Pathological updates and other reviews on Lichtenberg figures was provided by Resnik and Welti [36]
Special mention should be made of oral electrical burns in children and burns caused by lightning .The most common mode of electrical shock in young children is from chewing or biting on electrical cords. In such cases, arcing of the current through the lips causes the burn. The burn may be full thickness, involving the mucosa, submucosa, muscle, nerves, and blood vessels. Significant edema and eschar formation follow within hours after the injury. The eschar usually falls off after two to three weeks, being replaced by granulation tissue and scarring that may cause considerable deformity. Injury to the labial artery may cause significant bleeding .However, because the eschar is usually covering the artery, bleeding may not present until the eschar falls off days after the initial injury. For the paediatric domiciliary aspects of electrical injuries the 1989 erudite scholarships of Baker and Chiavello on the .Household electrical injuries in children. Epidemiology and identification of avoidable hazards should be reviewed. [37] Supplemented by the classic data of Cooper on the Emergent care of lightning and electrical injuries of 1995. [3]
Pathophysiological pathway of current of injury.
Depending on the voltage, current pathway, duration of contact, and type of circuit, electrical burns can cause a variety of injuries through several different mechanisms
Direct Current:
A direct current passing directly through the body will heat the tissue causing electrothermal burns, both to the surface of the skin as well as deeper tissues, depending on their résistance. It will typically cause damage at the source contact point and the ground contact point. Contact burns are shown in the image below.
CONTACT ELECTRICAL BURNS:
A 120-V alternating current nominal could cause primary thermal burns in the energized side and secondary contact electrical burns on the grounded side.
The contact electrical burns are otherwise morphologically indistinguishable from the thermal burns.
It is important to note that entrance and exit points are not viable concepts in alternating currents.
ELECTRICAL ARCS.
Current sparks are formed between objects of different electrical potentials that are not in direct contact with each other, most often a highly charged source and a ground. The temperature of an electrical arc can reach 2500-5000 degrees centigrade, resulting in deep thermal burns where it contacts the skin.
These are high-voltage injuries that may cause both thermal and flame burns in addition to injury from direct current along the arc pathway,
Flame:
Ignition of clothing causes direct burns from flames. Both electrochemical and arcing currents can ignite clothing.
Flash
When heat from a nearby electrical arc causes thermal burns but current does not actually enter the body, the result is a flash burn. Flash burns may cover a large surface area of the body but are usually only partial thickness.
MECHANISMS OF LIGHTNING INJURIES.
Lightning current strikes the victim in an altogether different way than low or high voltage. At least four primary modes of lightening current injury have been described.
[I]-Direct strike
In this the major pathway of lightning current is through the victim;
[II]-Side flash.
In which a direct strike to an object (or a person) is followed by a secondary discharge from the object to a near by victim.
[III]-STRIDE POTENTIAL
In which the lightning hits the ground and then enters the victims’ body from one foot and exits from the other foot. In addition to the:
[IV]-Flash-over Phenomenon:
This occurs when the energy flows outside the body, often causing vaporization of surface water with a blast effect to clothing and shoes. The salient aspects of the mechanisms of lightening injuries was detailed and summed up by Fahmy, Brinsden and Smith, in their medical scientific updates on Lightning ;the multisystem group injuries of 1999.[24] As did the established mature data of Bernstein (1994) [1] And Cooper (1995)[3]
ELECTRICAL INJURY TO SPECIFIC TISSUES AND ORGANS.
Electrical injury should be viewed and managed as a multisystem injury, and there is virtually no organ that is exempt from its complications. Although multisystem can be very extensive, it is damage to the vital organs that may require intensive care and accounts for the fatalities. The most important potential injuries are as follows.
CARDIOVASCULAR SYSTEM:
PATHOPHYSIOLOGY OF CARDIOVASCULAR IMPACTED ELECTRICAL INJURIES.
Electrical injury may affect the cardiovascular system by causing direct necrosis of the myocardium and by causing cardiac dysarrythmias.To some extent, the degree of the myocardial injury depends on the voltage and the type of current ,being more extensive with higher voltage and for any given voltage ,it is more severe with AC than with DC.The injury may be focal or diffuse and usually consists of wide spread ,discrete ,patchy contraction band necrosis involving the myocardium ,nodal tissue ,conduction pathways, and the coronary arteries.
Following observational studies on this associational pathological entity, Carlton in 1995 compiled and discussed cardiac problems associated with electrical injury. [38] And other review on this theme exists. Myocardial damage associated with electrical injury was dissected by Ku, Lin and Hsu et al. in 1989. [39]The significance of the early elevation of CPK-MB isoenzymes in myocardial damage [40] Previous efforts of Housinger, Green and Shahangian et al of 1985 was directed towards a prospective study of myocardial damage in electrical injuries.[41]
Rhythm disturbances may be produced with exposure to relatively low currents.
A current of more than 50-100 m-A ( which is less than half the maximal current can be generated after exposure to regular household current) with hand to hand or hand to foot transmission could cause ventricular fibrillation. Exposure to high-voltage current (AC or DC) will most likely cause ventricular asystole.Lightning acts as a massive cosmic counter-shock that causes cardiac standstill. interestingly, because of the inherent automaticity of the heart, sinus rhythm may return. The astonishing intrigue in this recovery following an apparently grave irreversible standstill was epitomized by Taussig in his histriographic scholarship on Death “from lightning and the possibility of living again .of 1968. [2]
A miscellaneous variety of other (usually transient) cardiac dysarrythmias have been reported in survivors of electrical injuries, and their pathogenesis is rather unclear and most likely multifactorial .Possible mechanisms include arrythmogenic foci due to myocardial necrosis, alterations in the Sodium-Potassium –adenosine triphosphate concentration ,and changes in the permeability of myocyte membranes. Finally. Cardiac injury and rhythm disturbances can be caused by anoxic injuries in cases in which respiratory arrest precedes the injury to the heart. Although delayed dysarrythmias are possible, they tend to occur only in patients who had some other form of dysarrythmias on presentation .Late dysarrythmias are probably due to arrythmogenic foci secondary to patchy myocardial necrosis and especially due to injury to the SA node. Arrhythmias related to electrical and lightning injuries was referred to and discussed by Chandra, Siu and Munster in their scholarship investigations on the clinical predictors of myocardial damage after high voltage electrical injury of 1990. [42] And other reviews on the arrythmogenic impact of electrical and lightening injuries are available.Housinger, Green and Shahangian et al. (1985) [41] Taussig (1968) [2] Hammond and Ward (1986). [40]
Ku, Lin and Hsu et al (1989) [39] In addition to (Carlton (1995). [38]
Electrical injury may cause direct and indirect effects on the vascular bed, which due to its high water content, is an excellent conductor .The effects of the electric current vary amongst the different size of blood vessels. Large arteries are not acutely affected because their rapid flow allows them to dissipate the heat produced by the electric current. However, they are susceptible to medial necrosis, with aneurysm formation and rupture. These makes it imperative for an utmost prevention of even minutiae amounts of electrical injury to the elderly with predisposing CVS pathologies such as HBP metabolic syndrome ,leutic disease smoking etc,but also immediate or interval aneurismal dilatation of the arteries may be a concern with the paediatric population with risk or predispositions of connectivopathiies such as Marians syndrome , Élans- Danlos syndromes,Osteogenesis Imperfecta and the other subsets with syndromic and non syndromic arrythmogenic or haemodynamically relevant cardiovascular syndromes. Concerted scholarships of Hunt, McManus and Haney, et al. on vascular lesions in acute electrical injuries of 1974 intimates that. [43]
Smaller vessels are acutely affected due to coagulation necrosis and tend to be affected primarily as a result of high-voltage injury (but only rarely with lightning) .Vascular injury in the extremities is very likely to cause compartment syndrome that further compromises the circulation and could cause or complicate vital end organs ischaemic dysfunctions and insufficiencies. Therafter, two decades later these data were reechoed and corroborated by the eminent reviews of Cooper of 1995. [3]
CLINICAL MANIFESTATIONS:
Cardiac standstill and ventricular fibrillation are obviously the most obvious and acutely serious of the cardiac complications of electric injury and are invariably fatal unless immediate resuscitative efforts are undertaken. However, there are also several other dysarrythmias that have a much better prognosis .Amongst the most common are sinus tachycardia and non-specific ST and T wave changes .Conduction defects ,such as various degrees of heart blocks, bundle-branch blocks, and prolongation of the QT interval, are also common.Finally,supraventricular tachycardias and atrial fibrillations have been reported. In the majority of cases, these dysarrythmias do not cause significant haemodynamic compromise. On echocardiogram, there may be some depression of the right and left ejection fractions. The ECG data of electrical and lightning injuries was discussed by Carlton (1995). [38] And previous publications on this theme exists.Ku, Lin and Hsu et al. (1989). [39]
Hammond and Ward (1986) [40] Housinger, Green and Shahangian (1985). [41]In addition to Taussig (1968) [2]
NERVOUS system INJURY.
Periodic paralysis, stroke, myotonia congenita, myasthenia gravis or epileptic and non-epileptic paroxysmal events could predispose to or make electrical injuries worse etc.
The Clinicopathological Features and The Pathophysiology and Neuropathology of Electrical and Lightening injuries.
Although nervous system injury (involving the central and the peripheral nervous system) is a common manifestation of electrical injury, there is no specific histologic or clinical finding that is considered pathognomonic.Furthermore, in many instances; nervous system injury is not due to the direct effect of the electrical current itself, but due to trauma or dysfunction of other organ systems (usually Cardiorespiratory).Amongst the acute direct effects of passage of electrical current through the brain, the most serious is injury to the respiratory control centre that results in respiratory arrest. Acute cranial nerve deficits and seizures may also occur after electric injury to the brain. Direct injury to the spinal cord with transection at the C4-C8 level may occur with a hand-to-hand flow.
Even relatively low-intensity current (30milliamperes) at the frequency of household current (60Hz) may induce an indefinite refractory state at the neuromuscular junction, causing continous tetanic contractions of the involved muscles. These tetanic contractions are responsible for the “locking-on” phenomenon that prevents the victims hand from separating from the electrical source and for suffocation that is caused by contraction of the respiratory muscles .Amongst the most common indirect injuries causing significant central nervous system injury are brain ischemia or anoxia secondary to antecedent cardio-respiratory arrest and traumatic brain or spinal cord injury secondary to a fall. Peripheral nerves may incur secondary damage due to local burns or entrapment from scar formation, vascular injury, or edema. Upper-motor neuro-deficits are relatively common; affecting primarily the lower limbs. The neuropatholgical aspects of electrical and lightning catastrophic events attracted a lot of academic investigative scholarship interests.
Ten Duis and Klasen in 1985. Itemized, depicted and discussed Keraunoparalysis, as a specific form of lightning injury related neuropathology.
[44]
In 1986.Varghese, Mani and Redford approached and dissected Paraplegic and paraparetic spinal cord injuries following electrical accidents. [45]
As a seminal and topical concept, the central nervous system complications of lightning and electrical injuries was tackled by Cherington in 1995. [46],
Whereas Kleinschmidt-DeMasters .approached the neuropathology of lightning strike injuries in 1995. [47]
Eminent Scholarships by Wilbourn intimates that Peripheral nerves are not exempt in electrical and lightning injuries. [48] Related data by (Cooper 1995.)
[3] And Jain and Bandi.of 1999 on Electrical and lightning injuries made references to this neuropatholgical electrical and lightning injuries related associational entity
Loss of consciousness, confusion, and impaired recall tend to be very common amongst victims of electrical injury. If there is no other associated injury, they tend to recover well. Dysfunction of peripheral motor and sensory nerves acutely causes a variety of motor and sensory deficits. Seizures, visual disturbances and deafness may be present. In most severe cases involving brain hemorrhage or other traumatic or ischaemic/anoxic injury, the patient may become comatose.Hemiplegia or quadriplegic are common with significant spinal cord injury .Transient paralysis (keraunoparalysis) and autonomic instability causing hypertension and peripheral vasospasm have been described primarily in the context of electrical injury due to lightning, and they are believed to result from massive release of catecholamines.Several reviews on this theme exists.[3],
[29], [46], [48], [45], [31], [45], [31], [47], [32], [47], [44]
RESPIRATORY SYSTEM:
Pathophysiology respiratory involvements in electrical injuries:
Although respiratory arrest is one of the common causes of acute death in serious electrical injuries, there are no specific injuries to the lungs or the airways directly attributable to electric current. Respiratory arrest is usually the result either of direct injury to the respiratory control centre, causing cessation of respiration, or to suffocation secondary to tetanic contractions of the respiratory muscles, which occurs when the thorax is an involved pathway for the electric current.It is speculated that in a number of fatalities, it is actually the anoxic injury rather than the electric current that causes irreversible injury to the brain and the heart. Thermal burns of the airways or inhalation of toxic fumes and hot debris may occur especially in cases of industrial accidents. Blunt trauma to the chest with pulmonary contusion and associated respiratory dysfunction is also possible, especially with exposure to high-voltage current that knocks the victim to the ground.
CLINICAL MANIFESTATIONS of respiratory pathology on electrical injuries:
In addition to apnea in cases of respiratory arrest, patients may exhibit a variety of non-specific respiratory patterns that reflect perturbations of other organ systems (such as hyperpnoea or hypopnea due to central nervous system dysfunction, fluid shifts, cardiac dysfunction, and pain.) rather than from specific injury to the respiratory system. Of course, as is the case with almost every other critical illness, survivors of electrical injury may develop respiratory complication as a result of their injury or therapeutic intervention (such as (acute respiratory dysfunction syndrome secondary to, or aggressive fluid resuscitation, in addition to ventilator associated pneumonitis.
OTHER SYSTEMIC INVOLVEMENT IN ELECTRICAL AND LIGHTNING INJURIES.
The Renal system.
Amongst other organ systems that may incur significant damage due to electrical injury, the kidneys are of particular importance .Although direct injury from electric current is unusual, the kidneys are very susceptible to anoxic/ischaemic injury that accompanies severe electrical injuries.In addition, vascular compromise and muscle necrosis may cause renal tubular damage, leading to renal failure from release of myoglobin and creatinine phosphokinase.
The Musculo-skeletal System.
The skeletal system may have fractures either from severe muscle contractions or from injury due to falls from significant heights .Fractures are more common in upper limb bones and in vertebrae .The latter may cause spinal cord injuries, further complicating the problem. Extensive skeletal muscle damage (Rhabdomyolisis) from high voltage electrical current injuries may lead to myoglobunuria, which could be precipitated in the kidneys causing ARF or it could also release potassium from damaged muscle cells and cause hyperkalaemia thereby compounding the hyperkalaemia related cardio-toxicity of ARF.
THE EYES:
The eyes could be an entry point for a lightning strike presenting a number of problems .Transient autonomic disturbances may cause fixed pupils after a lightning injury that in association with an often unconscious patient may be perceived as severe brain injury or even death. Cataracts are a very common complication of lightning injury but are rarely, acutely present, especially after lightning injury. [3], [29]
THE EARS.
Up to one half of patients may experience rupture of the tympanic membranes and temporary sensorineural hearing loss.
CLINICAL MANIFESTATIONS of Electrical Injuries
Clinical manifestations of burns will depend on their extent and severity. When extensive flash and flame burns are present the patient is expected to develop severe haemodynamic, autonomic, cardiopulmonary, renal, metabolic, and neuroendocrine responses that accompany more common thermal burns and that are described in details elsewhere. Burns caused by lightening may require special care.
TYPES OF ELECTRICAL BURNS:
Depending on the voltage, current, pathway, duration of contact, and type of circuit, electrical burns can cause a variety of injuries through several different mechanisms.
Immediately after a severe electrical shock, patients are usually comatose, apneic, and in circulatory collapse from ventricular fibrillation or cardiac standstill. If they survive this stage, they often are disorientated, combative and frequently may have seizures. Often they will be found to have fractures caused of bone caused either by convulsive muscular contractions accompanying the shock or from falls at the time of the accident.Hypovolemic shock often appears soon after high-tension electrical injury and is due to the rapid loss of tissue into areas of tissue damage, and from body surface burns.Hypotension,direct injury to the kidneys by the electric current ,and renal tubular damage from myoglobin and haemoglobin pigments liberated during massive muscle necrosis and haemolysis may lead to acute renal failure. Besides the extensive destruction of tissue occurring instantly in electrical burns, additional injury from ischaemia produced by swelling of damaged tissues may appear later and is often accompanied by severe metabolic acidosis. Other serious complications which may be seen are gastrointestinal hemorrhage from pre-existing or acute ulcers and both anaerobic and aerobic infections originating in inadequately debrided necrotic muscle masses.
Late effects include various neurological disabilities, visual disturbances, and the residual damage by burns .Nervous system injuries are frequent and include peripheral neuropathies, incomplete transection of the spinal cord, and reflex sympathetic dystrophies, as well as late convulsive disorders and intractable headaches. The development of cataracts of one or both eyes has been reported to occur up to three years following electrical injury. Histriographically, these interval cataracts complicating electrical injuries was highlighted and discussed by Solem et al in their earlier reviews on the natural history of longitudinally and prospectively tracked cases following electrical injuries in 1977.[49]
Symptomatology of electrical injuries:
Very frequently the most common symptom of an electrical injury is a skin burn, albeit not all electrical injuries cause external damages. High-voltage injuries cause massive internal burns. If muscle damage is extensive a limb may swell so much that its arteries becomes compressed.( acute compartment syndrome) ,cutting off blood supply to the limb .If a current travels close to the eyes, it may lead to cataracts, Cataracts following electrical injuries could develop within days thereafter or several years later.
Electrical injuries could occasionally be accompanied by extensive muscle damage (rhabdomyolisis) with resultant myoglobinaemia and myoglobunuria, which if precipitated in the kidneys could lead to renal failure (acute tubular necrosis) and acute cortical nephrosis.
Young children who bite or suck on extension cords could burn their mouth or lips.These burns may cause facial deformities and growth problems of the teeth, jaw, and face. An added danger is that severe bleeding from an artery in the lip may occur when the scab falls off, usually between a week and a half.
A Mild or minor shock may cause muscle pain and may trigger a mild muscle contractions or startle people, causing a fall. Severe shocks can trigger powerful muscle contractions sufficient to throw people to the ground or cause joint dislocations, bone fractures, and other blunt injuries.
The nerves and the brain can be injured in various ways, causing seizures, bleeding (haemorrhage) in the brain, poor short-term memory, personality changes, irritability, difficulty sleeping .Damage to the nerves in the body or spinal cord may cause weakness,paralysis,numbness,tingling ,chronic pain, erectile dysfunction( impotence)
The peculiarities of lightening injuries.
A lightening injury occurs after brief exposure to the very intense current of the strike.
[i]-About one in ten of the people who are struck by lightning die because the heart stops beating and breathing stops.
[ii]-In some people who survive severe lightening injury, an electrocardiogram is done to monitor the heart beat and blood and imaging tests are warranted.
[iii]-Once the person is resuscitated, burns and other injuries are treated.
Lightning delivers a massive electrical pulse over a fraction of a millisecond.
The brief duration of the exposure frequently limits the damage to the outer layer of skin. In addition, lightening is much less likely to cause internal burns than generated electricity.
However; it can kill a person by instantaneously short – circuiting the heart or the brain .Lightening is the second most frequent cause of storm –related deaths in the United States, resulting in about thirty to fifty deaths each year and nearly 10 times that many injuries, some of which result in permanent disability.
Lightening tends to strike tall or isolated objects, including trees, towers, shelters, flagpoles, bleachers, and fences.
A person may be the tallest object in an open field. Metal objects and water do not attract lightening but easily transmit electricity once they are hit.
Electricity from lightening can travel from outdoor power or telephone lines to electrical equipment or telephone lines inside a house.
Lightning can injure a person in several ways. Lightning can strike a person directly. In addition, electricity can reach a person who is touching or near an object that has been struck. Current can also reach a person through the ground. The shock can also throw a person, producing blunt injuries.
Symptomatologies of Lightening.
After a person has been struck by lightening, the heart may stop beating (cardiac arrest) or may beat erratically, and breathing often stops. The heart may beat again on its own, but if breathing has not restarted, the body is deprived of oxygen. The lack of oxygen and possibly. neurologic damage can cause the heart to stop beating again.
In Electric Shock, consciousness is rapidly lost. If the current continues, death from asphyxia due to ventricular fibrillation or respiratory arrest occurs within a few minutes. Interrupt the power source or knock wire away from the skin with a dry piece of wood or other non-conducting material and institute external cardiac massage or mouth-to-mouth respiration, depending on whether asphyxia is cardiac or respiratory. Supply oxygen if available and institute appropriate treatment for shock.
Brain Injury usually causes loss of consciousness .If brain damage is severe, coma may develop. Typically, the person awakens but does not remember what happened before the injury (amnesia) the person may be confused, think slowly, and have difficulty concentrating and remembering recent events. Personality changes may occur.
The ear drums are often perforated .Many eye injuries can develop including cataracts. Often both legs become temporarily paralysed, blue, and numb (kerataunoparalysis) the skin may show no marks at all, or may have minor burns that have a feathering, branching pattern, consist of clusters of tiny pinpoint spots like a cigarette burn, or consist of streaks where sweat has been turned into steam.Numbness, tingling, and weakness may develop because the nerves branching out from the spinal cord have been damaged (peripheral neuropathy)
A comparative overview of the major characteristics, effects and clinical manifestations of lightning versus high voltage or low voltage direct or alternating currents.
The voltage (V) of a lightning is usually above thirty million volts, whereas high voltage appliances have a voltage above one thousand volts and the low voltage appliances have a voltage range of less than six hundred volts in some circuits or less than two forty volts in the other. The current from lightening is usually more than two hundred thousand amperes, where as the current from high voltage sources are usually less than one thousand and those from low voltages are usually less than two hundred and forty amperes. The typology of lightenings is usually direct currents, those of high voltages could be direct or alternating currents and those of low voltages are commonly alternating currents.
The cause of cardiac arrest in lightning is usually due to asystole, whereas those of high voltages and low voltages are usually due to ventricular fibrillation respectively. The duration of Lightenings are usually instantaneous, where as those of high voltages are usually less than one thousand amperes, and those of low voltages are usually less than two hundred and forty amperes.
The myogenic contractility in lightning injuries is usually single, in lightning and high voltage events from direct current, whereas in high voltages of alternating current flow and the low voltages with always AC flow the myogenic contractilies are usually tetanic.
The pulmonary arrest in lightning is usually due to a direct central nervous system injury, whereas for the high voltage events, it is usually due to indirect trauma or tetanic contractions of the respiratory muscles, and that of the low voltages is usually due to tetanic contractions.
Burns are rare and uncommon in lightning injuries, but when they occur are usually superficial, however burns are common in high voltage injuries and are usually deep, whereas they usually occur in low voltage injuries where they are usually superficial.
THE PRENATAL AND PERINATAL ASPECTS OF ELECTRICAL INJURY .
Electrical or lightning injury in a pregnant woman carries additional risk of complications to the pregnancy or the fetus. Due to the small number of cases reported, the actual risks are unknown .Reports of fetal mortality vary widely, ranging from as high as three of four cases to as low as one of six to seven cases after electrical injury and about one half after lightening strike injuries.
It is not clear whether fetal mortality is due to primary electrical injury to the fetus or secondary to injury to the mother.
Diagnostic Considerations for electrical injuries:
Doctors check people for burns, fractures, dislocations, and spinal cord or other injuries. Most people who have no symptoms do not require testing or monitoring.
An Electrocardiogram (ECG) Is Done To Monitor The Heartbeat In Some People.
In some instances, blood and urine tests may be needed .If people are unconscious, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) may be needed.
LABORATORY FINDINGS for Electrical Injuries:
Immediately following major electrical injury the haematocrit is elevated and the plasma volume is reduced, reflecting sequestration of fluid in the wound. Unless extensive flame burns are also present, serial determinations of either of these parameters provide a good means of monitoring the adequacy of fluid replacement therapy.Myoglobinuria is seen frequently in association with severe shocks, and when it persists following establishment of urine flow, usually indicates massive muscle injury .In many patients arterial blood p-H determinations will indicate the presence of metabolic acidosis.
Lumbar puncture may show elevated pressure associated with cerebral oedema or bloody spinal fluid as a result of intracerebral hemorrhage.
The electrocardiogram not infrequently shows tachycardia and minor ST-segment alterations which can persist for several weeks following injury.
Unexplained acute hypokalaemia leading to respiratory arrest and cardiac arrhythmias has developed in some patients between the second and fourth weeks following injury.
Diagnosis
Lightening injuries are often witnessed, but they may also be suspected when a person is found unconscious or with amnesia outside during or shortly after a thunderstorm.In the hospital, electrocardiography (ECG) may be done if injury is severe (for example if a person collapsed and may have had a temporary cardiac arrest) The ECG, when done, determines whether the heart is beating normally .Sometimes blood tests or imaging tests, such as computed tomography (CT) scan or magnetic resonance imaging (MRI), are needed.
MANAGEMENT OF ELECTRICAL INJURIES.
The management of severe electrical injuries requires a combination of cardiopulmonary resuscitation and acute multiple trauma care. Treatment generally follows the same principles of pediatric and adult resuscitation as any other traumatic injury .The type of care that the victim of an electrical injury requires varies according to the type and severity of the initial injury .However, certain conditions need to be evaluated, monitored, and treated in almost all cases. Specifically for patients admitted to the ICU, The following issues should be considered.
Thorough evaluation for hidden injury (especially spinal cord injury) and for blunt thoracic abdominal trauma.
Serial evaluation of liver, pancreatic and renal function for traumatic, anoxic or ischemic injury (in case of cardiorespiratory arrest), supplemented by appropriate imaging studies (such as computed tomography or abdominal sonogram as necessary)
Cranio-facial CT scan is indicated in all severe cases of lightning injury, of injuries due to a fall, and if there are persistent abnormal findings in the neurologic examination.
Preventive treatment for stress ulcers.
Psychiatric assessment and support as soon as the patient is conscious and haemodynamically stable.
Patients with high-voltage injury also require the following:
Evaluation for rhabdomyolysis and myoglobunuria (uncommon in lightning injury).
Nutritional support due to increased energy expenditures and requirements.
Ophthalmic and otoscopic evaluation (common in cases of lightning injury)
SPECIAL CONSIDERATIONS:
In contrast with other traumatic injuries, electrical injuries present some rather unique problems that require special considerations.
ACCESS TO THE VICTIM:
In contrast with other types of trauma, electrical injury poses the same threat to the rescuer as it does to the victim because, if the victim is still in contact with the source of the current (as commonly happens with AC), he or she becomes a conductor that may electrocute the rescuer .Similarly in cases of injury with high voltage, the ground especially it is wet) may conduct current to the rescuers Thus no attempt to provide medical care should be made until either the source of the electrical current has been cut off or the victim has been extricated safely away from the current source with the use of properly insulated equipment .In contrast to popular belief, contact with a lightning victim does not pose any threat to the rescuer; therefore, treatment may be commenced immediately. For an achievable non-futuristic overview see the Management Concepts in major electrical injury of 1970.by Baxter. [50]
TRIAGE:
It is not unusual for electrical injuries (especially lightning injuries) to cause multiple casualties. In general, in cases of severely injured people, patients believed to be already dead are given the least priority, and efforts are focusing on those who have signs of life .Lightning victims are an exception to this rule because patients struck by lightning may become acutely apneic due to paralysis of the central respiratory control, may have dilated non-reactive pupils due to autonomic dysfunction, and may be pulseless due to the cardiac standstill caused by the mega-counter shock of the lightning strike. Because of its inherent automaticity it is possible for the heart to recover spontaneously .Considering that the majority of lightning victims tend to be relatively young and previously healthy individuals ,the possibility of successful resuscitation is high if proper care is instituted immediately .
Therefore administration of oxygen and ventilation with bag and mask should be started immediately on an apneic victim, and an artificial airway should be established as soon as possible to minimize the effect of anoxia, a major cause of mortality .The potential fur successful resuscitation has led people to believe that lightning causes a state of “suspended animation” from which the victim can recover virtually unharmed. Unfortunately, this claim is not substantiated .If the patient remains apneic, anoxia will lead to further brain and cardiac damage refractory to treatment.
EVALUATION OF THE PATIENT FOR THE SEVERITY OF THE INJURY.
Because the actual severity of the electrical injury depends on the pathway of the electric current .it is important to determine how the injury occurred, if the patient was exposed to DC, there may be visible burns at the entry and exit sites. In contrast, because of its cyclic movement.AC may not cause discernible entry and exit points. Another problem is that severe injury may occur when the skin is wet and its resistance is low, thus allowing current to travel freely and damage internal organs without leaving significant surface marks. Thus although the presence of burns on the chest should raise the possibility of internal injuries, their absence does not preclude them. Similarly, skeletal injuries (including vertebral injuries) may occur as a result of even a severe muscle contraction, which can dislocate or fracture bones without any sign of external traumatic injury. Therefore, any victim of a severe electrical accident should be assumed to have a spinal cord injury and should be managed with the proper head and neck immobilization that is required for all victims with suspected or known spinal injury.
Therapeutic Interventions for ELECTRICAL Shock injuries.
First, the person must be separated from the currents source.The safest way to do so is to shut off the current-for example, by throwing a circuit breaker or switch or by disconnecting the device from electrical outlet. No one should touch the person until the current has been shut off, particularly if high-voltage lines could be involved. High voltage and low-voltage lines are difficult to distinguish especially outdoors, Shutting off current to high-voltage lines is done by local power company, Many well meaning rescuers have been injured by electricity when trying to free a person. Once the person could be safely touched, the rescuer should check to see if the person is breathing and has a pulse, cardiopulmonary resuscitation (CPR) should be commenced immediately Emergency medical assistance should be called for any person who has more than a minor injury. Because the extent of an electrical burn may be deceptive, medical assistance should be sought if any doubt exists regarding its severity.
People with rhabdomyolisis may receive large amounts of fluids given intravenously .A tetanus shot is given if needed .Skin burns are treated with burn cream( such as silver sulfadiazine,Bacitracin,or sterile aloe vera) and sterile dressings. A person with only minor skin burns can usually be treated at home. If the injury is more severe, the person is admitted to the hospital, ideally to a burn centre.The person is kept in the hospital for 6 to 24 hours if any of the following exists.
[i]-The results of an ECG are abnormal.
[ii]-The person has lost consciousness.
[iii]-The Person has symptoms of a heart condition (such as chest pain, shortness of breath, awareness of heartbeats palpitations.
[iv]-The person has other severe injuries.
[v]-The person is pregnant (in many, but not necessarily all, cases)
[iv]-The person has a known heart problem (in many, but not necessarily all, cases)
Young children who bite or suck on extension cords should be referred to a children’s orthodontist in the care of these injuries.
THE THERAPEUTIC ASPECTS OF ELECTRICAL INJURIES.
Removal of victims from contact with the current should be accomplished immediately without touching them directly. Rescuers should use a rubber sheet, a leather belt applied as a sling, a wooden pole or other nonconductive material to detach them, and this should be preceded by cutting off the source of current when possible. If the victim is not breathing, mouth-to-mouth ventilation should be instituted at once. Although most cases who survive develop spontaneous respiration within half an hour, complete recovery after prolonged period occurs often enough so that respiratory support should be continued for at least four hours.If there is no evidence of heart beat, external cardiac massage should accompany ventilatory resuscitation.
Persons struck by lightening frequently have cardiac asystole which responds to a manual blow to the chest, while victims of low-voltage shocks will usually require defibrillation to restore heart action, during cardiopulmonary resuscitation and evacuation to the hospital, attention should be paid to possible broken bones and spinal cord injuries incurred at the time of the accident.
Subsequent hospital management of patients with electrothermal injuries requires considerable specialized care, when-ever feasible, they should be referred to an appropriate burn or trauma unit. In 1974, therapeutically achievable and useful classic data on the pathophysiology and treatment of lightning injury was provided by Apfelberg, et al [51]
Rapid institution of fluid and electrolyte therapy for hypovolemic shock and acidosis is essential, with guidelines being the patients urine output, haematocrit, osmolality, central venous pressure, and arterial blood gases. Standard burn formulas should not be used to estimate fluid therapy since these are based only upon extent of body surface area injury and do not take into account the extensive damage to muscle which is usually present.Instead,fluid replacement principles used in the treatment of crush injury, which electrical injury closely resemble ,should be followed. Large volumes of fluid, preferably lactated Ringers solution, should be administered in order to maintain urine output greater than fifty milliliters per hour. If myoglobunuria persists after adequate urine flow has been established, the use of furosemide or an osmotic diuretic such as mannitol along with alkalinisation of the urine is indicated. Management of the electrical wound should include adequate debridement of necrotic tissue and often will require fasciotomy to prevent further ischaemic injury. In 1979, elegant techniques and guidelines on the optimal surgical management of electrical injuries were produced by Sances et al [52]
Anticlostridial prophylaxis, including tetanus toxoid and high doses of penicillin, should be administered to all severely injured patients, while topical antimicrobial therapy with mafenide (sulfamylon) or silver sulfadiazine may be useful in preventing or delaying infections in extensive surface burns. Survivors of the acute episode often require extensive treatment for infection, cerebral oedema, visceral injury, and delayed haemorrhage as devitalized tissues slough. If acute renal failure occurs, it should be managed accordingly. Previously, seminal collative scholarships by Rouse, and Dimick et al on the treatment of electrical injury compared to burn injury and review of the pathophysiology and comparison of patient management protocols were provided in 1978. [53]
Therapeutic Interventions:
A person struck by lightning does not retain electricity, so there is no danger to the person providing first aid. People without a heartbeat and who are not breathing need cardiopulmonary resuscitation (CPR) immediately .If an automated external defibrillator (AED) is available, it should be used. Emergency medical assistance should be called. Many people struck by lightning are in good general health and are more likely to recover if given CPR.
Burns and other injuries are treated as needed. If resuscitative efforts are not successful within the first twenty minutes, they are unlikely to be, so resuscitation efforts are then discontinued.
FLUID MANAGEMENT.
The combination of extensive burns and significant internal visceral injury in cases of severe high-voltage electrical leads to increased fluid requirements due to fluid extravasations into third space compartments and to ongoing fluid losses. In addition, the massive muscle destruction that accompanies these injuries may cause significant myoglobunuria, which if significant, may lead to renal failure.
Thus, it is important to establish good intravenous access as soon as is achievable and provide adequate fluids to maintain a normal urine output.
If the patient presents with signs of hypovolemic shock, immediate fluid resuscitation is indicated .Otherwise, the overall fluid management should be judicious in consideration of other problems that may already be present or develop( such as syndrome of inappropriate ADH secretion in case of traumatic or anoxic brain injury or acute respiratory dysfunction syndrome) and warrant fluid restriction.
PATIENT MONITORING:
Patients, who experienced cardiopulmonary arrest, have abnormal neurologic findings suggesting central nervous system or spinal cord injury, or have severe burns and extensive visceral or vascular injury will obviously require admission to the ICU or to a specialized burn unit. The criteria for intensive in patient monitoring following electrical injuries was discussed by Bailey ,Forget and Gaudreault in their scholarship on the prevalence of potential risk factors in victims of electrocution of 2001.[54]
Although somewhat debatable and controversially discussed in the global medical literature, Cunningham in 1991 employing his them “the need for cardiac monitoring after electrical injury “ Strived to unify and harmonize the theme on what has been less well defined in the need for cardiac monitoring after electrical injury. In the opinion of Cunningham ,although late cardiac problems after electrical injuries have been reported, evidence from several studies suggests that the most severe cardiac complications present acutely, and it is very unlikely for a patient to develop a serious or life-threatening dysarrythmias hours or days later. Therefore patients who are asymptomatic and have a normal ECG at admission to the emergency department do not need mandatory cardiac monitoring as such. [55]
On the basis of the data from his research investigations on the theme, Electrical Injury: Part III: Cardiac monitoring indications, the pregnant patient, and lightning. Fish in the year 2000 proposed that for most patients, dispositions become clear after their initial evaluation in the emergency department. Victims of a low-voltage electrical injury or a lightning injury, who do not have cardiac arrest, have no loss of consciousness and no burns, and whose neurologic examination and electrocardiogram (ECG) are normal could safely be discharged home. [56]
These criteria for the selection of candidates for cardiac monitoring following electrical Injury and the peculiar situation of the electrically injured expecting mother was discussed in 2000 by Fish.[56]In a closely related activity, Bailey, Gaudreault and Thivierge, reported that none of the patients who were discharged from their hospital after electrical injury had late adverse effects, especially arrhythmias .But, they nevertheless recommended an ECG and a 24 hour cardiac monitoring for children with history of heart disease.[57]
It is not clear whether these recommendations should apply to patients with a history of heart disease before injury. In one retrospective study, of adults who died due to electrical injury, a history of coronary artery was not found to be a risk factor between those who died acutely from arrhythmia and those who died later from other causes .Until more data become available on the actual risk that pre-existing heart disease poses for the patient with electrical injury, it seems reasonable to monitor such patients for twenty four hours following electrical current injuries.
Considering that the numbers of potential victims who fit this category is very limited, such recommendations will not pose any unreasonable burden to ICUs or the overall costs of health care. On the basis of studies in adults and children, the criteria for cardiac monitoring after an electrical injury are, but not confined to the following: exposure to high voltages, loss of consciousness, abnormal ECG at admission to the emergency department, and past medical history of cardiac disease (especially a history of cardiac arrhythmia) The type of recommended cardiac monitoring was also controversially discussed . Bailey, Forget and Gaudreault in their 2001 Forensic Science International Literature indicated that traditionally, cardiac monitoring refers to continous telemetry, serial ECGs, and serial measurements of cardiac enzymes. [54]
(Myocardial muscle creatine kinase isoenzyme CK-MB) and the use of noninvasive and invasive imaging studies (echocardiography, thallium studies, and angiography) has been rather poor and inconsistent.The CK-MB fraction as an index of myocardial injury may be markedly elevated due to skeletal muscle and not myocardial injury. It has been reported that muscle injured by an electrical current can contain up to twenty five percent CK-MB fraction (as opposed to the normal two to three percent)
In answering the research question, Is serum creatinine kinase-MB in electrically injured patients predictive of myocardial injury? Mc Bride in 1986 lucidly dissected and discussed the therapeutically directing and useful positive predictive value of serum creatinine kinase-MB in electrically injured patients for myocardial injury. [58]
There may be some information regarding the changes in troponin levels after electrical injury. Momentary contact, particularly with a high voltage outlet, will lead to localized, sharply demarcated, painless gray areas without associated inflammation of the skin.
Also .in addition, the examiner should search for a second area of grayness where the current has exited and emerged from the body. Sloughing occurs after a couple of weeks.
With simple burns, the skin should be cleansed and a dry dressing applied. Deeper burns should be treated with silver sulphadiazine (Silvadene) under an occlusive dressing. Management is the same as for other types of burns.Infection occurs less often than with electric burns, but reconstructive surgery for scarring after healing may be required.
Toddlers and young children may sustain electric burns of the mouth by biting an electric cord. They are rarely electrocuted because the circuit is completed locally in the mouth. There is a local slough of tissue on the seventh to tenth days that may lead to brisk bleeding. The defect should be allowed to heal by scarring and the corner of the mouth revised later.
Multimodal Prevention Measures.
Weather Forecasting and Precautionary Broadcasts.
During the thunderstorm season, listening to weather reports, which is particularly important for the organizers of outdoor events, can assist in deciding whether to delay or postpone outdoor activities and in planning for any emergencies that may develop.
High winds, rain, and clouds may mean that a thunderstorm is imminent. By the time the thunderstorm is audible, the observers are already in danger and should be seeking safe shelter, such as a large habitable building or a fully enclosed metal vehicle ( for example , a car ,van ,or truck ) with the windows closed .Sheltering in small open structure such as gazebo is not safe. It is not safe to resume outdoor activties until about half an hour after the last sound of thunderstorm is heard or lightning is seen.
To prevent lightening injuries when indoors, people should avoid contact with plumbing or electrical wiring, talking on a hard wired telephone, working on a computer, using a video game console or using head sets attached by a cable to a sound system. Being away from windows and doors increases safety, as does turning off and unplugging electrical equipment before the thunderstorm arrives. Cellular telephones, personal digital assistants (PDAs), and MP3 Players Are Safe Because They Do Not Attract Lightning.
Prevention: of electrical injuries through proper installation of electrical appliances.
Proper installation of appliances, grounding of telephone lines and radio and television aerials, and the use of rubber gloves and dry shoes when working with electrical circuits should be a routine preventive health practice. Unused wall sockets should be kept closed and live extension cords not left unattended, particularly in households where there are young children. Of equal importance is the holistic approach to injury prevention as a whole by offering age appropriate supervisory activities to children. During a severe thunderstorm, refuge near hill tops, riverbanks, hedges, telephone poles, and trees should be eschewed.
The most secured shelter is the closed house, while a closed automobile, cave, ditch, or even lying on the ground curled up with hands close together is relatively secure. Therapeutic agents that could induce giddiness or an altered mental alertness should be employed with caution, preferably nocturnally as much as would be achievable, intoxications with alcoholic liquors should be eschewed and counseled against.
Several preventive deterrent options to preclude Lightning injuries were provided by McCrady-Kahn and Kahn in 1981. [59]
In hospitalized patients, the hazard of ventricular fibrillation precipitated by minute current leaks conducted directly to the myocardium from monitoring equipment via pacemakers or intravascular manometric catheters should be more widely appreciated. Hospital personnel should be aware that, in addition to medical instruments patient contact with two or more other power line-operated devices such as television sets, radio, electric razors, lamps, and especially electric beds can also result in electrocution if the heart lies within the current path through the patient. These hazards can be minimized by proper grounding of equipment before a patient is connected to the instrument, periodic measurement for leakage of current supplied by each device, and instruction in the principles of electrical safety for hospital personnel who use the complex and potentially hazardous equipment that is so much a part of modern medical practice are other potential deterrent options.
Prevention of Electrical Injuries Through Educational Enlightenment Programmes.
Education about the pros and cons of the utility of electricity and respect for electrical installations and appliances are crucial. Ensuring that all electrical devices are properly designed, installed, and maintained assists prevent electrical injuries at the domiciliary and occupational settings.
Electrical wiring should be installed and serviced by properly trained people Outlet guards reduce risk in homes with infants or young children. Any electrical device that touches or may be touched by the body should be properly grounded. Three-pronged outlets offers the utmost safety. Cutting off the lower (ground) prong of a power cord with three prongs (so that it will fit older two-pronged plugs) is potentially hazardous and increases the risks of occurrence of electrical injuries. Circuit breakers that interrupt (trip) circuits when currents as low as five milliamperes leaks should be made available in areas that get wet, such as kitchens, bathrooms and outdoors. To avoid Injury from current that jumps (arcing injury), poles and ladders should not be used near high-voltage power lines.
PROGNOSIS:
About one in ten of the individuals with lightning injuries die.The main cause of death are cardiac arrest and cessation of breathing at the time of the injury.
People whose heartbeat and breathing resume survive. If memory of recent events is impaired or thinking is slow, the person may have permanent brain injury.Keraunoparalysis usually resolves within several hours, though the person may occasionally be left with some weakness or clumsiness. People with nerve injury often have long-term problems, including chronic pain, sleep difficulties, erectile dysfunction (impotence)
For those without prolonged unconsciousness or cardiac arrest, the prognosis for recovery is excellent. Burns And Traumatic Injuries Continue To Cause The Majority Of the morbidity and mortality from electrical injuries. Morbidity and mortality are largely affected by the particular type of electrical contact involved in each exposure. Overall, mortality is estimated to be between three to fifteen percent by most series. [12] Flash burns have a better prognosis than arc or conductive burns. Persons who experience low-voltage injuries without immediate cardiac or respiratory arrest have low mortality, but there may be significant morbidity from oral trauma in children who bite electrical cords. Or adults who suffer burns to the hand.Persons who experience low-voltage injuries with cardiac or respiratory arrest may recover completely with immediate CPR on scene, however, prolonged CPR and transport time may result in permanent brain damage. High-voltage injuries often produce severe burns and blunt trauma.Patients are at high risk of myoglobunuria and renal failure .Burns are often ultimately much worse than they initially appear in the ED.
The long-term prognosis depends on the severity of the initial injury and the development and severity of subsequent complications. Due to the complexity of the problem, patients are at risk of developing multisystem organ failure that carries high mortality and even higher morbidity. Recent advances in ICU care in the areas of resuscitation, cardiopulmonary and nutritional support of the patients and new medical and surgical interventions such as immunologic therapy, early wound excision, and skin substitutes have significantly improved the outcome. Retrospectively, Waymack and Rutan histriographically relative data on the recent advances in burn care in 1994. [60] However, considering that electrical injuries are almost always preventable, it seems that the best way to manage electrical injuries can still be summarized by the old saying ,” One ounce of prevention is worth a pound of treatment .” Public education, regarding electrical safety, careful inspection, and safe use according to specifications of electric equipment at home and at work are the best means of eliminating mortality and minimizing the morbidity of electrical injuries.
The victims of electrical injuries and lightning’s will need to be followed up not only for the physical complications of the impact of electrical injuries, but also for its accompanying Post traumatic stress disorders.
The Forensic and Medical jurispedence aspects of electrical injuries:
Litigation concerning occupational injuries is to be expected, but law suits against practitioners in such cases are rare. Detailed documentation of the presence of electrical burns, including diagrams, can be extremely helpful. Obtain photographic records with proper consent if possible.
Conclusive Remarks.
The impact of subtle lightning related events during rains in causing perturbations of consciousness, multiple organ dysfunction syndromes, cataracts, tympanic membrane rupture needs to be examined rigorously. It would be worthwhile to examine the impact of seasonality in inducing perturbations of the cardiac rhythm (i.e are cardiac rhythm disorders, lenticular opacities and markers of end vital organ dysfunctions more common and frequent in the rainy season compared to the dry seasons .
The case for the position of the elderly and certain metabolic vital organ dysfunctions associated cardiopulmonary difficulties and neuropathies in this scale may warrant an enhanced anti-electric shock measures for this subsets as a group.
Categorically, patients with electric shock injuries will need longer term more diligent follow ups.These themes are prophylactically, diagnostically and therapeutically unexplored aspects.
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Suggested key words: high- and low-voltage electrical injury; lightening; multiple system organ failure.
