{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:34:47Z","timestamp":1786746887973,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyneuropathy is a common condition that limits the quality of life among patients with primary Sj\u00f6gren disease (pSjD). Somatic sensory fiber neuropathy involving small myelinated (A-\u03b4) and unmyelinated C fibers may precede the development of sicca syndrome. The cutaneous silent period (CSP) is an inhibitory spinal reflex that can be used as a tool for evaluating the dysfunction of A-\u03b4 fibers. This study sought to examine CSP parameters, and their correlates, in patients with pSjD vs. healthy controls. We recruited 134 consecutive patients with a diagnosis of pSjD, of whom 109 subjects were included in the analysis. Electrodiagnostic tests comprised a nerve conduction study (NCS) and CSP analysis, alongside laboratory tests and questionnaires (the ESSPRI and SF-36). The examination of the healthy control (HC) group consisted of 113 NCSs and CSP studies. NCS tests of the median nerve in both groups were within the normal range. Statistical analysis revealed a significant difference in CSP duration (p &lt; 0.001), S1 latency (p &lt; 0.001) and S2 latency (p &lt; 0.001) between the pSjD and HC groups. We observed prolonged CSP duration in approximately 38% of patients with pSjD and prolonged S2 latency in 18.35%. Small A-delta fiber neuropathy was diagnosed in 38% (41 subjects) patients. A regression analysis of CSP parameters indicated an association between the age of patients and PM Scl-75 antibodies (ab) levels in the pSjD cohort. As a new, noninvasive method of assessing A-\u03b4 nerve fibers, CSP was found to have a relation to the age and PM Scl-75 antibodies in patients with pSjD. The utility and sensitivity of CSP as a test for screening A-\u03b4 fiber function require further investigation in large cohorts of the pSjD population.<\/jats:p>","DOI":"10.3390\/ijms262412013","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prevalence of Small A-Delta Fiber Neuropathy in Sj\u00f6gren\u2019s Disease: Findings from a Cohort Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-3430","authenticated-orcid":false,"given":"Magdalena","family":"Chyli\u0144ska","sequence":"first","affiliation":[{"name":"Department of Adult Neurology, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-0671","authenticated-orcid":false,"given":"Iga","family":"Ko\u015bci\u0144ska-Shukla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Connective Tissue Diseases and Geriatrics, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwia","family":"Grudzie\u0144","sequence":"additional","affiliation":[{"name":"Department of Adult Neurology, University Clinical Center, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Jask\u00f3lska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Connective Tissue Diseases and Geriatrics, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-1439","authenticated-orcid":false,"given":"Adam","family":"Wyszomirski","sequence":"additional","affiliation":[{"name":"Department of Adult Neurology, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-6227","authenticated-orcid":false,"given":"Natalia","family":"Du\u0142ak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Connective Tissue Diseases and Geriatrics, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Rytlewska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Connective Tissue Diseases and Geriatrics, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-0016","authenticated-orcid":false,"given":"Bartosz","family":"Karaszewski","sequence":"additional","affiliation":[{"name":"Department of Adult Neurology, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00296-024-05753-8","article-title":"Diversity of central nervous system manifestations in Sjogren\u2019s Disease: A case-based review","volume":"45","author":"Rytlewska","year":"2025","journal-title":"Rheumatol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMcp1702514","article-title":"Primary Sj\u00f6gren\u2019s Syndrome","volume":"378","author":"Mariette","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Paroli, M., and Sirinian, M.I. (2025). Pathogenic Crosstalk Between the Peripheral and Central Nervous System in Rheumatic Diseases: Emerging Evidence and Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136036"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1097\/WCO.0b013e32833de6ab","article-title":"Neurological manifestations of primary Sjogren\u2019s syndrome","volume":"23","author":"Chai","year":"2010","journal-title":"Curr. Opin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejim.2020.05.004","article-title":"Differences in clinical features between small fiber and sensitive large fiber neuropathies in Sj\u00f6gren\u2019s syndrome","volume":"79","author":"Lacout","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/mus.26824","article-title":"Small fiber neuropathy in Sj\u00f6gren syndrome: Comparison with other small fiber neuropathies","volume":"61","author":"Descamps","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Furia, A., Liguori, R., and Donadio, V. (2025). Small-Fiber Neuropathy: An Etiology-Oriented Review. Brain Sci., 15.","DOI":"10.3390\/brainsci15020158"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/WCO.0000000000000472","article-title":"Small fibre neuropathy","volume":"30","author":"Cazzato","year":"2017","journal-title":"Curr. Opin. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/acr.23762","article-title":"Biopsy-Proven Small-Fiber Neuropathy in Primary Sj\u00f6gren\u2019s Syndrome: Neuropathic Pain Characteristics, Autoantibody Findings, and Histopathologic Features","volume":"71","author":"Birnbaum","year":"2019","journal-title":"Arthritis Care Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117421","DOI":"10.1016\/j.jns.2021.117421","article-title":"Peripheral nervous system manifestations of rheumatological diseases","volume":"424","author":"Gwathmey","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1080\/14397595.2020.1830484","article-title":"Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sj\u00f6gren\u2019s syndrome","volume":"31","author":"Yoshida","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1468-1331.2010.03023.x","article-title":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society","volume":"17","author":"Lauria","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3728","DOI":"10.1093\/brain\/awz333","article-title":"Diagnostic criteria for small fibre neuropathy in clinical practice and research","volume":"142","author":"Devigili","year":"2019","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1093\/brain\/awn093","article-title":"The diagnostic criteria for small fibre neuropathy: From symptoms to neuropathology","volume":"131","author":"Devigili","year":"2008","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Matsumoto, Y., Ibrahim, O.M.A., Kojima, T., Dogru, M., Shimazaki, J., and Tsubota, K. (2020). Corneal In Vivo Laser-Scanning Confocal Microscopy Findings in Dry Eye Patients with Sj\u00f6gren\u2019s Syndrome. Diagnostics, 10.","DOI":"10.3390\/diagnostics10070497"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jtos.2022.07.003","article-title":"In vivo confocal microscopic study of corneal innervation in Sj\u00f6gren\u2019s Syndrome with or without small fiber neuropathy","volume":"25","author":"Luzu","year":"2022","journal-title":"Ocul. Surf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/pathophysiology29010001","article-title":"Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?","volume":"29","author":"Lukashenko","year":"2021","journal-title":"Pathophysiology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cambieri, C., Libonati, L., Moret, F., Tartaglia, G., Garibaldi, M., Chimenti, C., Inghilleri, M., and Ceccanti, M. (2022). The Silent Period for Small Fiber Sensory Neuropathy Assessment in a Mixed Cohort of Transthyretin-Mediated Amyloidosis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092073"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/0168-5597(91)90023-Q","article-title":"Silent period induced by cutaneous stimulation","volume":"81","author":"Uncini","year":"1991","journal-title":"Electroencephalogr. Clin. Neurophysiol. Potentials Sect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/mus.880181218","article-title":"Spinal motor neuron excitability during the cutaneous silent period","volume":"18","author":"Leis","year":"1995","journal-title":"Muscle Nerve"},{"key":"ref_21","first-page":"300","article-title":"Electrophysiology of small peripheral nerve fibers in man. A study using the cutaneous silent period","volume":"42","author":"Svilpauskaite","year":"2006","journal-title":"Medicina"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1136\/jnnp.36.6.960","article-title":"Cutaneous reflexes in small muscles of the hand","volume":"36","author":"Caccia","year":"1973","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.clinph.2014.11.013","article-title":"Cutaneous silent period recordings in demyelinating and axonal polyneuropathies","volume":"126","author":"Lopergolo","year":"2015","journal-title":"Clin. Neurophysiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/mus.21877","article-title":"Assessment of symptomatic diabetic patients with normal nerve conduction studies: Utility of cutaneous silent periods and autonomic tests","volume":"43","author":"Koytak","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"326","DOI":"10.5455\/medarh.2019.73.326-330","article-title":"Diabetes Mellitus Type Has Impact on Cutaneous Silent Period","volume":"73","author":"Drnda","year":"2019","journal-title":"Med. Arch."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/1097-4598(200008)23:8<1179::AID-MUS4>3.0.CO;2-7","article-title":"Cutaneous silent periods in patients with Fabry disease","volume":"23","author":"Syed","year":"2000","journal-title":"Muscle Nerve"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1085-9489.2004.09400.x","article-title":"Cutaneous silent period in human immunodeficiency virus-related peripheral neuropathy","volume":"9","author":"Osio","year":"2004","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1007\/s00415-022-11431-1","article-title":"Clinical and paraclinical features of small fiber neuropathy in Sj\u00f6gren\u2019s syndrome","volume":"270","author":"Seeliger","year":"2023","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/WCO.0000000000001418","article-title":"Small fiber neuropathy: Expanding diagnosis with unsettled etiology","volume":"38","author":"Devigili","year":"2025","journal-title":"Curr. Opin. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1212\/WNL.39.3.390","article-title":"Peripheral neuropathy in primary Sj\u00f6gren\u2019s syndrome","volume":"39","author":"Mellgren","year":"1989","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1093\/brain\/awh605","article-title":"The wide spectrum of clinical manifestations in Sj\u00f6gren\u2019s syndrome-associated neuropathy","volume":"128","author":"Mori","year":"2005","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1016\/S1388-2457(01)00675-7","article-title":"Cutaneous afferents mediating the cutaneous silent period in the upper limbs: Evidences for a role of low-threshold sensory fibres","volume":"112","author":"Serrao","year":"2001","journal-title":"Clin. Neurophysiol."},{"key":"ref_33","first-page":"31","article-title":"Electromyographic mixed nerve and cutaneous silent period in evaluating the A-delta fibres in a patient with hereditary sensory-autonomic neuropathy","volume":"17","author":"Corsi","year":"2002","journal-title":"Funct. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/ene.15555","article-title":"Primary Sj\u00f6gren syndrome-related peripheral neuropathy: A systematic review and meta-analysis","volume":"30","author":"Liampas","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"718","DOI":"10.4103\/aian.aian_165_25","article-title":"Assessment of Small Nerve Fibers Using the Cutaneous Silent Period: Effect of Age and Gender","volume":"28","author":"Kaddah","year":"2025","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1136\/jnnp.57.8.983","article-title":"Peripheral neuropathy associated with primary Sjogren\u2019s syndrome","volume":"57","author":"Gemignani","year":"1994","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1097\/MD.0000000000000005","article-title":"Sj\u00f6gren Syndrome-Associated Small Fiber Neuropathy: Characterization From a Prospective Series of 40 Cases","volume":"92","author":"Cacoub","year":"2013","journal-title":"Medicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1007\/s00415-023-11613-5","article-title":"Sj\u00f6gren\u2019s syndrome with and without neurological involvement","volume":"270","author":"Seeliger","year":"2023","journal-title":"J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s10067-010-1458-7","article-title":"Clinical manifestations of neurological involvement in primary Sj\u00f6gren\u2019s syndrome","volume":"30","author":"Gono","year":"2011","journal-title":"Clin. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/BOR.0b013e3282f01a8c","article-title":"Autoantibodies in idiopathic inflammatory myopathy: An update on clinical and pathophysiological significance","volume":"19","author":"Mimori","year":"2007","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_41","first-page":"47","article-title":"Identification of an \u03b1-helical epitope region on the PM\/Scl-100 autoantigen with structural homology to a region on the heterochromatin p25\u03b2 autoantigen using immobilized overlapping synthetic peptides","volume":"78","author":"Mahler","year":"2000","journal-title":"J. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/ar147","article-title":"The human exosome: An autoantigenic complex of exoribonucleases in myositis and scleroderma","volume":"3","author":"Brouwer","year":"2001","journal-title":"Arthritis Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.4049\/jimmunol.137.12.3802","article-title":"Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis\/scleroderma overlap syndromes","volume":"137","author":"Reimer","year":"1986","journal-title":"J. Immunol."},{"key":"ref_44","first-page":"1552","article-title":"Pure sensory neuropathy in primary Sj\u00f6gren\u2019s syndrome. Longterm prospective followup and review of the literature","volume":"30","author":"Font","year":"2003","journal-title":"J. Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1001\/archneur.63.11.1612","article-title":"Peripheral Neuropathy in Primary Sj\u00f6gren Syndrome: A Population-Based Study","volume":"63","author":"Herigstad","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_46","first-page":"1333","article-title":"Sjogren\u2019s syndrome-associated neuropathy","volume":"65","author":"Koike","year":"2013","journal-title":"Brain Nerve Shinkei Kenkyu No Shinpo"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ejim.2013.10.005","article-title":"Immunological profiles determine neurological involvement in Sj\u00f6gren\u2019s syndrome","volume":"25","author":"Jamilloux","year":"2014","journal-title":"Eur. J. Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/art.39859","article-title":"2016 American College of Rheumatology\/European League Against Rheumatism Classification Criteria for Primary Sj\u00f6gren\u2019s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts","volume":"69","author":"Shiboski","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1007\/s00296-024-05640-2","article-title":"Elevated concentration of beta2-microglobulin among patients with carpal tunnel syndrome in the course of primary Sj\u00f6gren syndrome\u2014A prospective observational study on 50 patients","volume":"44","author":"Chmielewski","year":"2024","journal-title":"Rheumatol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00296-020-04543-2","article-title":"Peripheral neuropathy and health-related quality of life in patients with primary Sj\u00f6gren\u2019s syndrome: A preliminary report","volume":"40","author":"Masiak","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/mus.25204","article-title":"Yuen Establishing high-quality reference values for nerve conduction studies: A report from the normative data task force of the American Association Of Neuromuscular & Electrodiagnostic Medicine","volume":"54","author":"Dillingham","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1136\/ard.2010.143743","article-title":"EULAR Sj\u00f6gren\u2019s Syndrome Patient Reported Index (ESSPRI): Development of a Consensus Patient Index for Primary Sj\u00f6gren\u2019s Syndrome","volume":"70","author":"Seror","year":"2011","journal-title":"Ann. Rheum. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12013\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:57:55Z","timestamp":1765879075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":52,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412013"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412013","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]}}}