Small fiber dysfunction in patients with Wilson's disease

Abstract

Objective: Patients with Wilson's disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodoparesponsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). Results: Two men and 2 women (33±3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy).Keywords: autonomic nervous system diseases, small fiber neuropathy, Wilson's disease. RESUMOObjetivo: Pacientes com doença de Wilson (DW) podem desenvolver uma ampla variedade de sintomas neuropsiquiátricos, mas existem poucos relatos de disfunção autonômica. Aqui, nós descrevemos evidência de disfunção de fibras finas/autonômica em 4 pacientes com DW e parkinsonismo responsivo à levodopa. Método: Nós revisamos os prontuários de 4 pacientes com DW que foram submetidos a avaliação neuromuscular e ao teste de quantificação do enrugamento cutâneo (TEC). Resultados: Dois homens e 2 mulheres (33±3,5 anos) com DW foram avaliados. Todos apresentaram parkinsonismo durante o curso de sua doença. Parkinsonismo no paciente 4 quase completamente desapareceu com tratamento da DW. Dois pacientes apresentaram queixas sensitivas e 2 apresentaram queixas autonômicas significativas incluindo episódios de síncope. Eletroneuromiografia foi normal em todos e TEC foi anormal em metade deles (score do TEC nos 4 dedos de 0,25 e 1). Discussão: Um subgrupo de pacientes com DW apresenta evidência de TEC anormal (neuropatia de fibras finas).Palavras-chave: doenças do sistema nervoso autônomo, neuropatia de pequenas fibras, doença de Wilson.

Small Fiber Neuropathy and Wilson Disease

“…1 We also recently reported small fiber neuropathy mostly correlating with somatic rather than autonomic small fibers in WD patients. 4 Our patients had normal nerve conduction studies, but half of them had abnormal skin wrinkling test that, similar to corneal confocal microscopy, also strongly correlated with abnormalities on intraepidermal nerve fiber density. 4 Interestingly, our patients with small fiber involvement and WD also had parkinsonism.…”

“…4 Our patients had normal nerve conduction studies, but half of them had abnormal skin wrinkling test that, similar to corneal confocal microscopy, also strongly correlated with abnormalities on intraepidermal nerve fiber density. 4 Interestingly, our patients with small fiber involvement and WD also had parkinsonism. In his series, Sturniolo et al 1 included 10 patients with significant central nervous system disease and 14 patients with predominant hepatic involvement.…”

Small fiber neuropathy: Getting bigger!

“…Other rare associations Parkinson disease Pompe disease Fragile X–associated tremor ataxia syndrome Benign fasciculation syndrome Critical illness Celiac disease Wilson disease Amyotrophic lateral aclerosis X‐linked adrenoleukodystrophy …”

Author Response: Small Fiber Neuropathy and Wilson Disease

“…In our population, we did not find any difference in corneal involvement, even when separately evaluating central nervous system versus pure hepatic involvement. We congratulate Gondim et al 6 for their prospective studies, and we hope they are able to include the evaluation of cornal subasal nerve plexus by corneal confocal microscopy in their prospective analysis. …”

“…3 Moreover, the original article was written by Herrmann et al 4 It is not new that corneal confocal microscopy is able to demostrate small fiber peripheral neuropathy in diabetes, and we were the first research group to introduce in the literature the term ''corneal diabetic neuropathy,'' in 2006. 5 We have reviewed the article by Gondim et al 6 about small fiber dysfunction in Wilson disease, but it has nothing to do with our investigation. Skin wrinkling test has never been compared with corneal confocal study of subbasal nerve plexus, and it may represent a topic for future studies.…”