{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T07:15:25Z","timestamp":1758438925999,"version":"3.44.0"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","issue":"09","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq Neuropsiquiatr"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p><jats:p>The present study aimed to evaluate the diagnostic utility of SSR and CSP in detecting possible subclinical small-fiber neuropathy (pSFN) in individuals with early-stage vitamin B12 deficiency.<\/jats:p><jats:p>The present observational study included 28 patients with vitamin B12 deficiency who had nonspecific complaints, Douleur Neuropathique en 4 Questions (DN4) scores\u2009&lt;\u20094, 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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1055\/s-0045-1811722","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:17:36Z","timestamp":1758323856000},"page":"001-007","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of possible small fiber Neuropathy in early-stage vitamin B12 deficiency using electrophysiological methods"],"prefix":"10.1055","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-9141","authenticated-orcid":false,"given":"Elif Simin","family":"Issi","sequence":"additional","affiliation":[{"name":"Eski\u015fehir City Hospital, Neurology Department, Eski\u015fehir, Turkey."},{"name":"Afyonkarahisar Health Sciences University, Faculty of Medicine, Department of Neurology, Afyonkarahisar, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1176\/appi.neuropsych.11020052","article-title":"The neuropsychiatry of vitamin B12 deficiency in elderly patients","volume":"24","author":"C Lachner","year":"2012","journal-title":"J Neuropsychiatry Clin Neurosci"},{"issue":"03","key":"ref2","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s13760-017-0847-y","article-title":"The histopathological evaluation of small fiber neuropathy in patients with vitamin B12 deficiency","volume":"118","author":"H N G\u00fcne\u015f","year":"2018","journal-title":"Acta Neurol Belg"},{"issue":"02","key":"ref3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.5455\/medarh.2014.68.98-101","article-title":"Cutaneous silent period in the evaluation of small nerve fibres","volume":"68","author":"M Tiric-Campara","year":"2014","journal-title":"Med Arch"},{"issue":"04","key":"ref4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/mus.10447","article-title":"Cutaneous silent periods","volume":"28","author":"M K Floeter","year":"2003","journal-title":"Muscle Nerve"},{"issue":"04","key":"ref5","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.clinph.2019.01.003","article-title":"Cutaneous silent periods - Part 2: Update on pathophysiology and clinical utility","volume":"130","author":"M Kofler","year":"2019","journal-title":"Clin Neurophysiol"},{"issue":"02","key":"ref6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3233\/JND-200490","article-title":"Current View of Diagnosing Small Fiber Neuropathy","volume":"8","author":"L RM Raasing","year":"2021","journal-title":"J Neuromuscul Dis"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.pain.2004.12.010","article-title":"Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)","volume":"114","author":"D Bouhassira","year":"2005","journal-title":"Pain"},{"issue":"03","key":"ref8","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1152\/jn.1984.52.3.435","article-title":"Monosynaptic and oligosynaptic contributions to human ankle jerk and H-reflex","volume":"52","author":"D Burke","year":"1984","journal-title":"J Neurophysiol"},{"key":"ref9","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780199738687.001.0001","volume-title":"Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice","author":"J Kimura","year":"2013","edition":"4th ed."},{"key":"ref10","first-page":"183","volume-title":"Laboratory evaluation of autonomic failure","author":"P A Low","year":"1993"},{"issue":"04","key":"ref11","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1179\/1476830513Y.0000000073","article-title":"Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up","volume":"17","author":"J Kalita","year":"2014","journal-title":"Nutr Neurosci"},{"issue":"12","key":"ref12","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.3748\/wjg.v24.i12.1343","article-title":"Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis","volume":"24","author":"G T Yang","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"06","key":"ref13","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1111\/ene.14786","article-title":"Association between neuropathy and B-vitamins: A systematic review and meta-analysis","volume":"28","author":"J Stein","year":"2021","journal-title":"Eur J Neurol"},{"issue":"02","key":"ref14","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.mayocpiqo.2019.03.002","article-title":"The Many Faces of Cobalamin (Vitamin B12) Deficiency","volume":"3","author":"B HR Wolffenbuttel","year":"2019","journal-title":"Mayo Clin Proc Innov Qual Outcomes"},{"issue":"01","key":"ref15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/jns.12298","article-title":"Small-fiber neuropathy: Expanding the clinical pain universe","volume":"24","author":"M Sopacua","year":"2019","journal-title":"J Peripher Nerv Syst"},{"issue":"01","key":"ref16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0165-1838(98)00058-7","article-title":"Autonomic dysfunction in vitamin B12 deficiency: a heart rate variability study","volume":"71","author":"A B S\u00f6zen","year":"1998","journal-title":"J Auton Nerv Syst"},{"issue":"06","key":"ref17","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1111\/j.1540-8159.2000.tb00883.x","article-title":"Assessment of autonomic nervous system functions in patients with vitamin B12 deficiency by power spectral analysis of heart rate variability","volume":"23","author":"K Aytemir","year":"2000","journal-title":"Pacing Clin Electrophysiol"},{"issue":"01","key":"ref18","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/s1566-0702(01)00393-9","article-title":"Autonomic dysfunction and hemodynamics in vitamin B12 deficiency","volume":"97","author":"M Beitzke","year":"2002","journal-title":"Auton Neurosci"},{"issue":"04","key":"ref19","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.amjmed.2018.09.027","article-title":"Autonomic Disorders","volume":"132","author":"P Novak","year":"2019","journal-title":"Am J Med"},{"issue":"06","key":"ref20","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1136\/jnnp.66.6.804a","article-title":"Autonomic dysfunction and orthostatic hypotention caused by vitamin B12 deficiency","volume":"66","author":"S Toru","year":"1999","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.autneu.2011.12.002","article-title":"Vitamin B12 supplementation improves heart rate variability in healthy elderly Indian subjects","volume":"168","author":"S Sucharita","year":"2012","journal-title":"Auton Neurosci"},{"issue":"01","key":"ref22","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/s0022-510x(98)00005-7","article-title":"Polyneuropathy due to cobalamin deficiency in the rat","volume":"156","author":"G Tredici","year":"1998","journal-title":"J Neurol Sci"},{"issue":"01","key":"ref23","first-page":"57","article-title":"Vitamin B12 deficiency neurological syndromes: a clinical, MRI and electrodiagnostic study","volume":"43","author":"U K Misra","year":"2003","journal-title":"Electromyogr Clin Neurophysiol"},{"issue":"03","key":"ref24","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s00415-008-0660-x","article-title":"Vitamin B12 deficiency neurological syndromes: correlation of clinical, MRI and cognitive evoked potential","volume":"255","author":"J Kalita","year":"2008","journal-title":"J Neurol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.cnp.2019.05.002","article-title":"Reversible cutaneous silent period abnormalities in vitamin B12 deficiency: A case report","volume":"4","author":"E Fava","year":"2019","journal-title":"Clin Neurophysiol Pract"},{"issue":"03","key":"ref26","doi-asserted-by":"publisher","first-page":"182","DOI":"10.4103\/nsn.nsn_92_24","article-title":"The electrophysiological evaluation of small fiber neuropathy in symptomatic patients with Vitamin B12 deficiency before and after treatment","volume":"41","author":"D Agircan","year":"2024","journal-title":"Neurol Sci Neurophysiol."},{"issue":"04","key":"ref27","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/mus.26639","article-title":"Utility of the H-reflex in diagnosing polyneuropathy","volume":"60","author":"O H Teigland","year":"2019","journal-title":"Muscle Nerve"}],"container-title":["Arquivos de Neuro-Psiquiatria"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0045-1811722.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:17:43Z","timestamp":1758323863000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0045-1811722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":27,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2025,6,21]]},"published-print":{"date-parts":[[2025,9]]}},"alternative-id":["s00451811722"],"URL":"https:\/\/doi.org\/10.1055\/s-0045-1811722","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0004-282X","1678-4227"],"issn-type":[{"type":"print","value":"0004-282X"},{"type":"electronic","value":"1678-4227"}],"subject":[],"published":{"date-parts":[[2025,9]]}}}