Quantitative analysis of epidermal innervation in Fabry disease

Scott, L. J. C.; Griffin, John W.; Luciano, Carlos A.; Barton, Norman W.; Banerjee, Tapas Kumar; Crawford, Thomas O.; McArthur, Justin C.; Tournay, Anne; Schiffmann, Raphael

doi:10.1212/wnl.52.6.1249

Cited by 145 publications

(103 citation statements)

References 22 publications

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“…Eles encontraram que todos os pacientes com redução no antebraço tinham também redução na perna, o mesmo não acontecendo quando o achado estava só na perna, pelo que se pode concluir que, devido à natureza comprimento dependente das neuropatias, a realização de uma única biopsia na porção distal da perna é suficiente para a avaliação e diagnóstico de possíveis neuropatias sensitivas subclínicas ou de fibras finas. Este fato foi também confirmado por outro trabalho que concluiu que a região distal da perna (8 a 10 cm acima do maléolo lateral) seria o local mais indicado para realização das biopsias com objetivo de diagnóstico 12 .…”

Section: Discussionunclassified

Padronização normal das fibras nervosas intraepidérmicas em 30 voluntários saudáveis com PGP 9,5

Moura

Oliveira

Zanoteli

et al. 2004

Arq. Neuro-Psiquiatr.

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RESUMO -O recente método de avaliação das fibras nervosas intraepidérmicas com o PGP 9,5 vem se mostrando de grande utilidade no diagnóstico das neuropatias sensitivas de fibras finas, autonômicas e neuropatias periféricas subclínicas. Devido à variação da técnica relatada na literatura é de fundamental importância uma padronização normal. Estudamos 15 homens e 15 mulheres com média de idade de 34,5 anos. Em todos os voluntários foi realizada biopsia de pele na porção distal da perna.A média da densidade linear das fibras nervosas intraepidérmicas foi 5,3/mm com mediana de 6,0 e desvio padrão de 1,94. Essa técnica possui um grande número de vantagens em relação à biopsia de nervo convencional, é simples, pouco invasiva, reproduzível e pode ser repetida no mesmo paciente para avaliar progressão da neuropatia e possíveis respostas terapêuticas.PALAVRAS-CHAVE: biopsia de pele, fibras sensitivas finas, nervos intraepidérmicos, PGP 9,5. Normal pattern of intraepidermal nerve fibers in 30 healthy volunteers with PGP 9.5ABSTRACT -Skin biopsy has become an attractive technique to evaluate the terminal regions of small nerve fibers.There is extensive innervation of the skin by both sensory and autonomic fibers as demonstrated by staining for the pan-axonal marker PGP 9,5. The normal pattern is fundamental before any study, since three different techniques described in the literature with different results. Skin biopsy specimens of 3-mm in diameter were obtained from the distal leg of 30 healthy controls. Median intraepidermal nerve fiber density was 5.3/mm. Skin biopsy may be a useful tool for assessing the topographic extent and degree of nerve fiber damage in sensory neuropathies and may be particularly useful in experimental treatment trials for peripheral neuropathies since, in contrast to standard nerve biopsy, the test can be repeated.KEY WORDS: skin biopsy, small fibers, intraepidermal nerve fiber, PGP 9,5.A presença de fibras nervosas na epiderme humana tem sido debatida e especulada há mais de 120 anos. A primeira descrição essencialmente correta sobre fibras nervosas intraepidérmicas (FNIE) foi publicada em 1868 por Langerhans, enquanto ele ainda era estudante de Medicina 1 . Usando a coloração de Cohnneim para cloreto de ouro ele mostrou ramos penetrando na epiderme através da membrana basal. Posteriormente, vários pesquisadores confirmaram a presença de nervos na epiderme 2 . Na maioria dos exemplos, as descrições eram acompanhadas por desenhos e raramente por fotografias. Outros métodos foram tentados, posteriormente, com a intenção de detectar a presença de fibras nervosas intraepidérmicas, como a prata e o azul de metileno. Devido à dificuldade técnica que esses métodos apresentaram no objetivo de demonstrar a presença de terminações nervosas livres na epiderme, vários investigadores negaram durante muito tempo a presença de tais elementos na epiderme humana. Mais recentemente, com técnicas de imunohistoquímica para identificação de neurotransmissores como a substância P, produto gênico relacionado ao gene...

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Section: Discussionunclassified

Padronização normal das fibras nervosas intraepidérmicas em 30 voluntários saudáveis com PGP 9,5

Moura

Oliveira

Zanoteli

et al. 2004

Arq. Neuro-Psiquiatr.

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“…[2][3][4] The most common complication of Fabry disease is cardiac dysfunction, which may include cardiomyopathy, atrio-ventricular conduction defects, arrhythmia, valvular dysfunction, and non-atherosclerotic coronary vascular disease. 5,6 Increased stroke risk, 7 progressive renal failure, 8 and painful small-fiber neuropathy 9 occur commonly as well. 10 Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A and accumulation of the glycosphingolipid globotriaosylceramide (Gb 3 ) in most cells and organs, as well as an increase of Gb 3 in urine.…”

Section: Introductionmentioning

confidence: 99%

Low frequency of Fabry disease in patients with common heart disease

Schiffmann

Swift

McNeill

et al. 2018

Genetics in Medicine

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Purpose: To test the hypothesis that undiagnosed patients with Fabry disease exist among patients affected by common heart disease.Methods: Globotriaosylceramide in random whole urine using tandem mass spectroscopy, α-galactosidase A activity in dried blood spots, and next-generation sequencing of pooled or individual genomic DNA samples supplemented by Sanger sequencing.Results: We tested 2,256 consecutive patients: 852 women (median age 65 years (19-95)) and 1,404 men (median age 65 years (21-92)). The primary diagnoses were coronary artery disease (n = 994), arrhythmia (n = 607), cardiomyopathy (n = 138), and valvular disease (n = 568). Urinary globotriaosylceramide was elevated in 15% of patients and 15 males had low α-galactosidase A activity. GLA variants found included R118C (n = 2), D83N, and D313Y (n = 7);

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“…[12][13][14][15][16][17][18][19] Decreased ENFs/mm has also been shown to be characteristic of generalized sensorimotor neuropathies of various kinds. 7,13,15,[20][21][22][23][24][25][26][27] Consensus panels have accepted the assessment of ENFs as objective and valid indications of small sensory nerve fiber involvement in disease.…”

mentioning

confidence: 99%

Epidermal nerve fibers

et al. 2012

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Objectives: Our first objective was to explore the value of estimating 95% confidence intervals (CIs) of epidermal nerve fibers (ENFs)/mm for number of sections to be evaluated and for confidently judging normality or abnormality. Our second objective was to introduce a new continuous measure combining nerve conduction and ENFs/mm. Methods:The 95% CI studies were performed on 1, 1-2, 1-3 ---1-10 serial skip sections of 3-mm punch biopsies of leg and thigh of 67 healthy subjects and 23 patients with diabetes mellitus.Results: Variability of differences of ENFs/mm counts (and 95% CIs) from evaluation of 1, 1-2, 1-3 ---1-9 compared with 1-10 serial skip sections decreased progressively without a break point with increasing numbers of sections evaluated. Estimating 95% CIs as sections are evaluated can be used to judge how many sections are needed for adequate evaluation, i.e., only a few when counts and 95% CIs are well within the range of normality or abnormality and more when values are borderline. Also provided is a methodology to combine results of nerve conduction and ENFs/mm as continuous measures of normality or abnormality.Conclusion: Estimating 95% CIs of ENFs/mm is useful to judge how many sections should be evaluated to confidently declare counts to be normal or abnormal. Also introduced is a continuous measure of both large-fiber (nerve conduction) and small-fiber (ENFs/mm) normal structures/functions spanning the range of normality and abnormality for use in therapeutic trials. Neurology Enumeration of nerve endings in skin has been used to study differences among species, 1,2 development, maturation and aging, 3,4 and disease. 5,6 Light microscopic analysis of immune-stained intraepidermal nerve fibers (ENFs) and reference values were introduced to serve as objective and spatial indications of painful and small-fiber sensory polyneuropathy, "possibly useful for therapeutic trials." [7][8][9] The technique of biopsy was found to be acceptable to patients, and the estimation of ENFs/mm had high intraobserver and interobserver reproducibility.8 A somewhat different approach using punch skin biopsy, a blister technique with immunofluorescence and confocal microscopy, was also described (reviewed in Kennedy and Wendelschafer-Crabb 10 and Kennedy et al. 11). A series of reports showed the value of ENFs/mm in the diagnosis of painful small-fiber sensory polyneuropathy, especially in patients with few or no neurologic signs or test abnormalities.

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Quantitative analysis of epidermal innervation in Fabry disease

Cited by 145 publications

References 22 publications

Padronização normal das fibras nervosas intraepidérmicas em 30 voluntários saudáveis com PGP 9,5

Padronização normal das fibras nervosas intraepidérmicas em 30 voluntários saudáveis com PGP 9,5

Low frequency of Fabry disease in patients with common heart disease

Epidermal nerve fibers

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