Assessment of possible small fiber Neuropathy in early-stage vitamin B12 deficiency using electrophysiological methods

Q: Why are routine nerve conduction studies insufficient for early small fiber neuropathy?

Small fiber neuropathy affects thinly myelinated and unmyelinated fibers, which often produce subtle signs that routine nerve conduction studies may not detect.

Q: Which electrophysiological methods were evaluated in the study?

The study assessed sympathetic skin response (SSR) and cutaneous silent period (CSP), including CSP recordings from the right median and sural nerves.

Q: What were the main diagnostic findings for patients with early-stage vitamin B12 deficiency?

Median and tibialis anterior–sural CSP durations were shorter, CSP latencies differed versus controls, and SSR latencies were prolonged, while SSR amplitudes did not differ significantly.

Sep 29, 2026

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Study evaluates noninvasive electrophysiological tools for early detection of possible subclinical small-fiber neuropathy (pSFN) in people with early-stage vitamin B12 deficiency. Twenty-eight patients with B12 deficiency, nonspecific complaints, DN4 <4, and normal nerve conduction studies were compared with 25 healthy controls. Sympathetic skin response (SSR) and cutaneous silent period (CSP) were recorded. CSP durations and SSR latencies differed, indicating combined somatic and autonomic involvement, supporting diagnostic utility of SSR plus CSP.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Rationale for early diagnosis

Article published online: 2025-09-19 Original Article 1 Assessment of possible small ﬁber Neuropathyin early-stage vitamin B12 deﬁciency using electrophysiological methods Elif Simin Issi 1,2 1 Eskişehir City Hospital, Neurology Department, Eskişehir, Turkey. 2 Afyonkarahisar Health Sciences University, Faculty of Medicine, Department of Neurology, Afyonkarahisar, Turkey. Arq. Neuro-Psiquiatr. 2025;83(9):s00451811722 . Address for correspondence Elif Simin Issi (email: [elifsiminissi@hotmail.com](elifsiminissi@hotmail.com)) Abstract Keywords ► Vitamin B 12 Deficiency ► Small Fiber Neuropathy ► Galvanic Skin Response ► Reflex, Abnormal ► Electrodiagnosis Background Small ﬁber neuropathy (SFN) affects thinly myelinated and unmyelinated ﬁbers, often presenting with subtle clinical signs that are undetectable in routine nerve conduction studies. Vitamin B12 deﬁciency is a known risk factor for SFN, yet early-stage cases frequently remain undiagnosed. Sympathetic skin response (SSR) and cutaneous silent period (CSP) are noninvasive electrophysiological techniques used to assess autonomic and somatic small ﬁber function. Objective The present study aimed to evaluate the diagnostic utility of SSR and CSP in detecting possible subclinical small-ﬁber neuropathy (pSFN) in individuals with earlystage vitamin B12 deﬁciency. Methods The present observational study included 28 patients with vitamin B12 deﬁciency who had nonspeciﬁc complaints, Douleur Neuropathique en 4 Questions (DN4) scores <4, and normal nerve conduction studies, along with 25 healthy controls. Electrophysiological testing involved SSR recordings from all extremities and CSP measurements from the right median and sural nerves. Results In the patient group, Median Nerve Cutaneous Silent Period (MN-CSP) and Tibialis Anterior -Sural Cutaneous Silent Period (TA-sural CSP) durations were signiﬁcantly shorter, while termination and onset latencies were prolonged compared with controls. MN-CSP and TA-sural CSP durations demonstrated high diagnostic accuracy. Sympathetic skin response latencies were signiﬁcantly prolonged in both hands and feet, indicating autonomic dysfunction. No signiﬁcant differences were observed in SSR amplitudes. Conclusion Sympathetic skin response and CSP are valuable tools for detecting possible subclinical SFN in vitamin B12 deﬁciency. Sympathetic skin response effectively identiﬁed autonomic dysfunction, while CSP provided additional diagnostic value for somatic small ﬁber impairment. Combining SSR and CSP may enhance early detection of pSFN in vitamin B12 deﬁciency and allow timely intervention. received April 21, 2025 received in its ﬁnal form June 18, 2025 accepted July 7, 2025 DOI [https://doi.org/](https://doi.org/)[ ](https://doi.org/)10.1055/s-0045-1811722 . ISSN 0004-282X. Editor-in-Chief: Hélio A. G. Teive. Associate Editor: Carlos Otto Heise. © 2025 . The Author(s) . This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)) Thieme Revinter Publicações Ltda. , Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil 2 Small fiber neuropathy and vitamin B-12 Issi INTRODUCTION Vitamin B12 deﬁciency is a prevalent condition with signiﬁ cant neurological consequences worldwide. It can lead to various disorders affecting both the central and peripheral nervous systems. The most well-known neurological manifestations include sensory-motor axonal polyneuropathy and subacute combined degeneration, which may present symptoms such as muscle weakness, numbness, paresthesia, balance impairment, and gait disturbances.1 Small ﬁber neuropathy (SFN), primarily affecting thinly myelinated A-delta and unmyelinated C

FAQs

Why are routine nerve conduction studies insufficient for early small fiber neuropathy?

Small fiber neuropathy affects thinly myelinated and unmyelinated fibers, which often produce subtle signs that routine nerve conduction studies may not detect.

Which electrophysiological methods were evaluated in the study?

The study assessed sympathetic skin response (SSR) and cutaneous silent period (CSP), including CSP recordings from the right median and sural nerves.

What were the main diagnostic findings for patients with early-stage vitamin B12 deficiency?

Median and tibialis anterior–sural CSP durations were shorter, CSP latencies differed versus controls, and SSR latencies were prolonged, while SSR amplitudes did not differ significantly.

Sep 29, 2026

Uploaded by Finn