{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:23:46Z","timestamp":1792787026498,"version":"4.5.0"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,24]],"date-time":"2016-01-24T00:00:00Z","timestamp":1453593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008088","name":"IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute, Ricerca Corrente, Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008088","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione Italiana di ricerca per la SLA - Sclerosi Laterale Amiotrofica"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"\n Background and purpose<\/jats:title>\n \n Our aim was to address the correlation between small fiber loss and amyotrophic lateral sclerosis (\n ALS<\/jats:styled-content>\n ) for disease onset, phenotype, genotype, duration, severity and sensory findings.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Consecutive patients referred for suspected\n ALS<\/jats:styled-content>\n were screened. Exclusion criteria were possible\n ALS<\/jats:styled-content>\n and previous diagnosis or known risk factors for small fiber neuropathies. A sural nerve conduction study (\n NCS<\/jats:styled-content>\n ) was bilaterally recorded. The\n ALS<\/jats:styled-content>\n functional rating scale revised was administered and loss of functions were calculated using the Milano\u2212Torino staging (MITOS) system. Sensory symptoms and signs were recorded. Genetic analysis was performed by the next\u2010generation sequencing approach. Skin biopsy was performed at the distal leg and intraepidermal nerve fiber (\n IENF<\/jats:styled-content>\n ) density was quantified in three non\u2010consecutive sections following published guidelines. Findings were referred to age\u2010 and sex\u2010adjusted normative values.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Fifty\u2010seven patients including six with facial onset sensory and motor neuronopathy (\n FOSMN<\/jats:styled-content>\n ) were enrolled. Eight (15.7%) pure\n ALS<\/jats:styled-content>\n patients and five (83%)\n FOSMN<\/jats:styled-content>\n patients complained of sensory disturbances with different distributions. Sural\n NCS<\/jats:styled-content>\n was normal in all except two patients.\n IENF<\/jats:styled-content>\n density was reduced in 75.4% of pure\n ALS<\/jats:styled-content>\n and 50% of\n FOSMN<\/jats:styled-content>\n patients, without correlation with any disease features.\n IENF<\/jats:styled-content>\n density was similarly reduced in bulbar (78.5%), flail limb (87.5%), pyramidal (100%), and spinal (68.2%) onset, as well as in genetic (83.3%) and sporadic (82%)\n ALS<\/jats:styled-content>\n . There was no correlation with genotype, disease duration and severity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Intraepidermal nerve fiber loss is a feature of most\n ALS<\/jats:styled-content>\n patients. It does not correlate with onset, phenotype, course and severity of the disease, and cannot be considered a clinical or prognostic biomarker.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ene.12936","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:18:50Z","timestamp":1453681130000},"page":"416-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Amyotrophic lateral sclerosis causes small fiber pathology"],"prefix":"10.1111","volume":"23","author":[{"given":"E.","family":"Dalla Bella","sequence":"first","affiliation":[{"name":"Motor Neuron Diseases Centre IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"},{"name":"Third Neurology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Third Neurology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Porretta\u2010Serapiglia","sequence":"additional","affiliation":[{"name":"Third Neurology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ciano","sequence":"additional","affiliation":[{"name":"Motor Neuron Diseases Centre IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"},{"name":"Clinical Neurophysiology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gellera","sequence":"additional","affiliation":[{"name":"Motor Neuron Diseases Centre IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"},{"name":"Genetics of Neurodegenerative and Metabolic Diseases Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Pensato","sequence":"additional","affiliation":[{"name":"Motor Neuron Diseases Centre IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"},{"name":"Genetics of Neurodegenerative and Metabolic Diseases Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Third Neurology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lauria","sequence":"additional","affiliation":[{"name":"Motor Neuron Diseases Centre IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"},{"name":"Third Neurology Unit IRCCS Foundation \u2018Carlo Besta\u2019 Neurological Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.25.8.781"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.098533"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821e553a"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7672-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835804c5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-310176"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00269.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00271.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31825dce13"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-307416"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl258"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-307756"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn102"}],"container-title":["European 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