{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:10:00Z","timestamp":1779927000747,"version":"3.53.1"},"reference-count":32,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["519779"],"award-info":[{"award-number":["519779"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G060194"],"award-info":[{"award-number":["G060194"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre","award":["BRC51\/NS\/MR"],"award-info":[{"award-number":["BRC51\/NS\/MR"]}]},{"name":"National Institutes of Neurological Diseases and Stroke and office of Rare Diseases","award":["U54NS065712"],"award-info":[{"award-number":["U54NS065712"]}]},{"name":"Swiss National Foundation SNF","award":["Project 31003A_153390\/1"],"award-info":[{"award-number":["Project 31003A_153390\/1"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202747\/Z\/16\/Z"],"award-info":[{"award-number":["202747\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Assessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies, quantitative sensory testing, intraepidermal nerve fibre density (thigh), computerised myometry (lower limbs), plasma 1-deoxysphingolipid levels, calf-level intramuscular fat accumulation by MRI and patient-based questionnaires (Neuropathic Pain Symptom Inventory and 36-Short Form Health Survey version 2 [SF-36v2]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>35 patients with HSN1 were recruited. There was marked heterogeneity in the phenotype mainly due to differences between the sexes: males generally more severely affected. The outcome measures that significantly changed over 1\u2009year and correlated with CMTNSv2, SF-36v2-physical component and disease duration were MRI determined calf intramuscular fat accumulation (mean change in overall calf fat fraction 2.36%, 95%\u2009CI 1.16 to 3.55, p=0.0004), pressure pain threshold on the hand (mean change 40\u2009kPa, 95%\u2009CI 0.7 to 80, p=0.046) and myometric measurements of ankle plantar flexion (median change \u22120.5\u2009Nm, IQR \u22129.5 to 0, p=0.0007), ankle inversion (mean change \u22120.89\u2009Nm, 95%\u2009CI \u22121.66 to \u22120.12, p=0.03) and eversion (mean change \u22121.61\u2009Nm, 95%\u2009CI \u22122.72 to \u22120.51, p=0.006). Intramuscular calf fat fraction was the most responsive outcome measure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MRI determined calf muscle fat fraction shows validity and high responsiveness over 12 months and will be useful in HSN1 clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2018-320198","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T21:35:14Z","timestamp":1555536914000},"page":"895-906","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1"],"prefix":"10.1136","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8932-5009","authenticated-orcid":false,"given":"Umaiyal","family":"Kugathasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R B","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper M","family":"Morrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D J","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek A","family":"Yousry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Hornemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya","family":"Suriyanarayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadijah","family":"Owusu-Ansah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lauria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Polke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L H","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian C","family":"Blake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Laura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-2896","authenticated-orcid":false,"given":"Mary M","family":"Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"2020050722344763000_90.8.895.1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh712"},{"key":"2020050722344763000_90.8.895.2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.3.329"},{"key":"2020050722344763000_90.8.895.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-6397-y"},{"key":"2020050722344763000_90.8.895.4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.092973"},{"key":"2020050722344763000_90.8.895.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2536-09.2009"},{"key":"2020050722344763000_90.8.895.6","doi-asserted-by":"crossref","unstructured":"Garofalo K , Penno A , Schmidt BP , et al . 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