{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T17:12:32Z","timestamp":1794503552552,"version":"4.9.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870929"],"award-info":[{"award-number":["81870929"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Funds for the Innovation of Science and Technology of Fujian Province","award":["2017Y9094"],"award-info":[{"award-number":["2017Y9094"]}]},{"name":"Joint Funds for the Innovation of Science and Technology of Fujian Province","award":["2018Y9082"],"award-info":[{"award-number":["2018Y9082"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2019J02010"],"award-info":[{"award-number":["2019J02010"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Clinical Specialty Discipline Construction Program of Fujian"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|&gt;\u20090.5) to estimate sample sizes for disease progression (disease duration\u2009&gt;\u200914\u00a0years vs.\u2009\u2264\u200914\u00a0years).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13\u201349\u00a0years; median disease duration, 14\u00a0years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12\u201327%; thoracic levels 41\u201360%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n\u2009=\u200922) much less that what would be required if using clinical disability assessment (n\u2009=\u2009124).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04006418?term=NCT04006418&amp;draw=2&amp;rank=1\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04006418?term=NCT04006418&amp;draw=2&amp;rank=1<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-02014-w","type":"journal-article","created":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T15:02:17Z","timestamp":1632063737000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potential markers for sample size estimations in hereditary spastic paraplegia type 5"],"prefix":"10.1186","volume":"16","author":[{"given":"Qianqian","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dairong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-3945","authenticated-orcid":false,"given":"Ying","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,19]]},"reference":[{"key":"2014_CR1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/S1474-4422(08)70258-8","volume":"7","author":"S Salinas","year":"2008","unstructured":"Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 2008;7:1127\u201338.","journal-title":"Lancet Neurol"},{"key":"2014_CR2","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/S1474-4422(19)30235-2","volume":"18","author":"S Shribman","year":"2019","unstructured":"Shribman S, Reid E, Crosby AH, Houlden H, Warner TT. Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches. Lancet Neurol. 2019;18:1136\u201346.","journal-title":"Lancet Neurol"},{"key":"2014_CR3","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1093\/brain\/awx273","volume":"140","author":"L Schols","year":"2017","unstructured":"Schols L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, et al. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain. 2017;140:3112\u201327.","journal-title":"Brain"},{"key":"2014_CR4","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1093\/brain\/awx297","volume":"141","author":"C Marelli","year":"2018","unstructured":"Marelli C, Lamari F, Rainteau D, Lafourcade A, Banneau G, Humbert L, et al. Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5. Brain. 2018;141:72\u201384.","journal-title":"Brain"},{"key":"2014_CR5","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.nicl.2018.05.031","volume":"19","author":"I Faber","year":"2018","unstructured":"Faber I, Martinez ARM, de Rezende TJR, Martins CR Jr, Martins MP, Louren\u00e7o CM, et al. SPG11 mutations cause widespread white matter and basal ganglia abnormalities, but restricted cortical damage. Neuroimage Clin. 2018;19:848\u201357.","journal-title":"Neuroimage Clin"},{"key":"2014_CR6","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1093\/brain\/aww068","volume":"139","author":"A Castellano","year":"2016","unstructured":"Castellano A, Papinutto N, Cadioli M, Brugnara G, Iadanza A, Scigliuolo G, et al. Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: in vivo assessment of structural changes. Brain. 2016;139:1735\u201346.","journal-title":"Brain"},{"key":"2014_CR7","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1093\/brain\/awy352","volume":"142","author":"D Eden","year":"2019","unstructured":"Eden D, Gros C, Badji A, Dupont SM, De Leener B, Maranzano J, et al. Spatial distribution of multiple sclerosis lesions in the cervical spinal cord. Brain. 2019;142:633\u201346.","journal-title":"Brain"},{"key":"2014_CR8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","volume":"14","author":"M Khalil","year":"2018","unstructured":"Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577\u201389.","journal-title":"Nat Rev Neurol"},{"key":"2014_CR9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13024-018-0269-1","volume":"13","author":"EL Dong","year":"2018","unstructured":"Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, et al. Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China. Mol Neurodegener. 2018;13:36.","journal-title":"Mol Neurodegener"},{"key":"2014_CR10","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1212\/01.wnl.0000228242.53336.90","volume":"67","author":"R Sch\u00fcle","year":"2006","unstructured":"Sch\u00fcle R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V, et al. The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. Neurology. 2006;67:430\u20134.","journal-title":"Neurology"},{"key":"2014_CR11","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/acn3.51019","volume":"7","author":"CT Chou","year":"2020","unstructured":"Chou CT, Soong BW, Lin KP, Tsai YS, Jih KY, Liao YC, et al. Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5. Ann Clin Transl Neurol. 2020;7:486\u201396.","journal-title":"Ann Clin Transl Neurol"},{"issue":"10","key":"2014_CR12","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1007\/s00234-005-1415-3","volume":"47","author":"P Hedera","year":"2005","unstructured":"Hedera P, Eldevik OP, Maly P, Rainier S, Fink JK. Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia. Neuroradiology. 2005;47(10):730\u20134.","journal-title":"Neuroradiology"},{"issue":"3","key":"2014_CR13","doi-asserted-by":"publisher","first-page":"610","DOI":"10.3174\/ajnr.A7017","volume":"42","author":"KR Servelhere","year":"2021","unstructured":"Servelhere KR, Casseb RF, de Lima FD, Rezende TJR, Ramalho LP, Fran\u00e7a MC Jr. Spinal Cord Gray and White Matter Damage in Different Hereditary Spastic Paraplegia Subtypes. AJNR Am J Neuroradiol. 2021;42(3):610\u20135.","journal-title":"AJNR Am J Neuroradiol"},{"key":"2014_CR14","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.3389\/fneur.2018.01117","volume":"9","author":"FF da Graca","year":"2018","unstructured":"da Graca FF, de Rezende TJR, Vasconcellos LFR, Pedroso JL, Barsottini OGP, Fran\u00e7a MC Jr. Neuroimaging in hereditary spastic paraplegias: current use and future perspectives. Front Neurol. 2018;9:1117.","journal-title":"Front Neurol"},{"key":"2014_CR15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.nmd.2008.10.009","volume":"19","author":"R Biancheri","year":"2009","unstructured":"Biancheri R, Ciccolella M, Rossi A, Tessa A, Cassandrini D, Minetti C, et al. White matter lesions in spastic paraplegia with mutations in SPG5\/CYP7B1. Neuromuscul Disord. 2009;19:62\u20135.","journal-title":"Neuromuscul Disord"},{"key":"2014_CR16","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1093\/brain\/awp073","volume":"132","author":"C Goizet","year":"2009","unstructured":"Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, et al. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain. 2009;132:1589\u2013600.","journal-title":"Brain"},{"key":"2014_CR17","doi-asserted-by":"publisher","first-page":"e1007","DOI":"10.1212\/WNL.0000000000007032","volume":"92","author":"J Kuhle","year":"2019","unstructured":"Kuhle J, Kropshofer H, Haering DA, Kundu U, Meinert R, Barro C, et al. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019;92:e1007\u201315.","journal-title":"Neurology"},{"key":"2014_CR18","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1056\/NEJMoa1917246","volume":"383","author":"SL Hauser","year":"2020","unstructured":"Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, et al. Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med. 2020;383:546\u201357.","journal-title":"N Engl J Med"},{"key":"2014_CR19","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1093\/brain\/awy154","volume":"141","author":"C Barro","year":"2018","unstructured":"Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, et al. Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain. 2018;141:2382\u201391.","journal-title":"Brain"},{"issue":"1","key":"2014_CR20","doi-asserted-by":"publisher","first-page":"e122","DOI":"10.1212\/NXG.0000000000000122","volume":"3","author":"N Chrestian","year":"2016","unstructured":"Chrestian N, Dupr\u00e9 N, Gan-Or Z, Szuto A, Chen S, Venkitachalam A, et al. Clinical and genetic study of hereditary spastic paraplegia in Canada. Neurol Genet. 2016;3(1):e122.","journal-title":"Neurol Genet"},{"key":"2014_CR21","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/S0140-6736(83)92879-9","volume":"1","author":"AE Harding","year":"1983","unstructured":"Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet. 1983;1:1151\u20135.","journal-title":"Lancet"},{"key":"2014_CR22","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1093\/brain\/aww005","volume":"139","author":"L Harper","year":"2016","unstructured":"Harper L, Fumagalli GG, Barkhof F, Scheltens P, O\u2019Brien JT, Bouwman F, et al. MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases. Brain. 2016;139:1211\u201325.","journal-title":"Brain"},{"key":"2014_CR23","volume-title":"Statistical power analysis for the behavioral sciences","author":"J Cohen","year":"1988","unstructured":"Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Erlbaum; 1988.","edition":"2"}],"updated-by":[{"DOI":"10.1186\/s13023-021-02078-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000}}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02014-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-02014-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02014-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T06:07:17Z","timestamp":1635401237000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-02014-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,19]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2014"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-02014-w","relation":{"correction":[{"id-type":"doi","id":"10.1186\/s13023-021-02078-8","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,19]]},"assertion":[{"value":"26 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13023-021-02078-8","URL":"https:\/\/doi.org\/10.1186\/s13023-021-02078-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol and informed consent procedures were approved by the institutional review board at First Affiliated Hospital of Fujian Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"391"}}