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Objective: To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in skin nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB., Methods: We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein., Results: No p-syn was detected in any skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of skin was more severe in patients with autonomic dysfunctions., Conclusions: (1) In autonomic skin nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms., Classification of Evidence: This study provides Class III evidence that p-syn in skin nerve fibers on skin biopsy accurately distinguishes DLB from other forms of dementia., (© 2017 American Academy of Neurology.)

Objective: To assess the right-to-left and short-term variability of intraepidermal nerve fiber density (IENFD) at the distal site of the leg., Methods: Patients with possible or probable small fiber neuropathy (SFN) and healthy volunteers (HVs) underwent skin biopsies at the right and left distal leg. A subgroup of participants underwent follow-up biopsies 20 days later. Biopsies were immunostained by polyclonal anti-protein gene product 9.5 antibodies, and IENFD was quantified in nonconsecutive sections following published guidelines by operators blinded to the participants' condition (diagnosis, side, and time of biopsy). Findings were referred to sex- and age-adjusted normative values., Results: Forty patients and 17 HVs underwent bilateral skin biopsies; 15 patients and 8 HVs underwent follow-up skin biopsies. Sural nerve and dorsal sural nerve conduction studies were normal in all participants. Interside IENFD did not differ both in patients (median 2.45 IENF/mm ± 1.45 SD right; 2.2 IENF/mm ± 1.32 SD left) and HVs (median 6.3 IENF/mm ± 2.81 right; 6.2 IENF/mm ± 2.3 SD left). The right-to-left correlation coefficients were excellent (Pearson 0.95 in SFN and 0.97 in HVs). The analysis of IENFD at 20-day follow-up biopsy showed no difference between sides in both groups and yielded excellent correlation coefficients., Conclusions: The diagnosis of SFN can be reliably ascertained by unilateral skin biopsy at the distal site of the leg, and IENFD is not expected to vary within 3 weeks., (© 2015 American Academy of Neurology.)

Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)