{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:43:22Z","timestamp":1789393402351,"version":"build-2803163510"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100019735","name":"MedDay Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100\u00a0mg taken orally three times a day over a maximum of 52\u00a0weeks.<\/jats:p>\n                <jats:p>The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov Identifier: NCT02967679; date 2016\/12\/05.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-023-03440-y","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:13:51Z","timestamp":1698639231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study"],"prefix":"10.1186","volume":"23","author":[{"given":"Alain","family":"Cr\u00e9ange","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Hutin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Sedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludivine","family":"Le Vigouroux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pascal","family":"Lefaucheur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"issue":"3","key":"3440_CR1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1002\/ana.410300309","volume":"30","author":"PK Stys","year":"1991","unstructured":"Stys PK, Waxman SG, Ransom BR. Na(+)-Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter. Ann Neurol. 1991;30(3):375\u201380.","journal-title":"Ann Neurol"},{"issue":"4","key":"3440_CR2","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/ana.96","volume":"49","author":"KJ Smith","year":"2001","unstructured":"Smith KJ, Kapoor R, Hall SM, Davies M. Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol. 2001;49(4):470\u20136.","journal-title":"Ann Neurol"},{"key":"3440_CR3","doi-asserted-by":"crossref","unstructured":"Lefaucheur JP, Bo\u00ebrio D, Hogrel JY, Cr\u00e9ange A. Nerve excitability studies in the assessment of dysimmune neuropathies. Rev Neurol (Paris). 2006;162(Suppl. 1). Spec No 1:3S17\u20133S26.","DOI":"10.1016\/S0035-3787(06)75154-2"},{"issue":"1\u20132","key":"3440_CR4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jns.2010.02.002","volume":"292","author":"D Boerio","year":"2010","unstructured":"Boerio D, Creange A, Hogrel JY, Gueguen A, Bertrand D, Lefaucheur JP. Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy. J Neurol Sci. 2010;292(1\u20132):63\u201371.","journal-title":"J Neurol Sci"},{"key":"3440_CR5","doi-asserted-by":"crossref","unstructured":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--First Revision. J Peripher Nerv Syst 2010;15(1):1\u20139.","DOI":"10.1111\/j.1529-8027.2010.00245.x"},{"key":"3440_CR6","first-page":"CD002827","volume":"5","author":"MP Lunn","year":"2012","unstructured":"Lunn MP, Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst Rev. 2012;5:CD002827.","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"3440_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.msard.2015.01.005","volume":"4","author":"F Sedel","year":"2015","unstructured":"Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015;4(2):159\u201369.","journal-title":"Mult Scler Relat Disord"},{"issue":"Pt B","key":"3440_CR8","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.neuropharm.2015.08.028","volume":"110","author":"F Sedel","year":"2016","unstructured":"Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2016;110(Pt B):644\u201353.","journal-title":"Neuropharmacology"},{"key":"3440_CR9","doi-asserted-by":"crossref","unstructured":"Cree BAC, Cutter G, Wolinsky JS, Freedman MS, Comi G, Giovannoni G, et al. Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2020;19:988\u201397.","DOI":"10.1016\/S1474-4422(20)30347-1"},{"issue":"10","key":"3440_CR10","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/0753-3322(90)90171-5","volume":"44","author":"D Koutsikos","year":"1990","unstructured":"Koutsikos D, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic peripheral neuropathy. Biomed Pharmacother. 1990;44(10):511\u20134.","journal-title":"Biomed Pharmacother"},{"issue":"3","key":"3440_CR11","doi-asserted-by":"publisher","first-page":"250","DOI":"10.4103\/1735-5362.314823","volume":"16","author":"AR Abed","year":"2021","unstructured":"Abed AR, Abed A, Banafshe HR, Malekabad ES, Gorgani-Firuzjaee S, Dadashi AR. Effect of biotin supplementation on neuropathic pain induced by chronic constriction of the sciatic nerve in the rat. Res Pharm Sci. 2021;16(3):250\u20139.","journal-title":"Res Pharm Sci"},{"issue":"1","key":"3440_CR12","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s13311-020-00926-2","volume":"18","author":"S Mathais","year":"2021","unstructured":"Mathais S, Moisset X, Pereira B, Taithe F, Ciron J, Labauge P, et al. Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis. Neurotherapeutics. 2021;18(1):378\u201386.","journal-title":"Neurotherapeutics"},{"issue":"7","key":"3440_CR13","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1001\/archneurol.2011.137","volume":"68","author":"CS-Y Lin","year":"2011","unstructured":"Lin CS-Y, Krishnan AV, Park SB, Kiernan MC. Modulatory Effects on Axonal Function After Intravenous Immunoglobulin Therapy in Chronic Inflammatory Demyelinating Polyneuropathy. Arch Neurol. 2011;68(7):862\u20139.","journal-title":"Arch Neurol"},{"issue":"1","key":"3440_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1529-8027.2010.00245.x","volume":"15","author":"Joint Task Force of the EFNS and the PNS","year":"2010","unstructured":"Joint Task Force of the EFNS and the PNS. J Peripher Nerv Syst. 2010;15(1):1\u20139.","journal-title":"J Peripher Nerv Syst"},{"issue":"8","key":"3440_CR15","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1136\/jnnp.2005.081547","volume":"77","author":"RC Graham","year":"2006","unstructured":"Graham RC, Hughes RA. A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale. J Neurol Neurosurg Psychiatry. 2006;77(8):973\u20136.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"3440_CR16","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1212\/WNL.54.4.943","volume":"54","author":"IS Merkies","year":"2000","unstructured":"Merkies IS, Schmitz PI, Van der Meche FG, Van Doorn PA. Psychometric evaluation of a new sensory scale in immune-mediated polyneuropathies. Inflammatory Neuropathy Cause and Treatment (INCAT) Group. Neurology. 2000;54(4):943\u20139.","journal-title":"Neurology"},{"key":"3440_CR17","unstructured":"Medical research council. Aids to the investigation of peripheral nerve injuries. 2nd ed.; 1943."},{"issue":"3","key":"3440_CR18","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0013-4694(87)90071-X","volume":"66","author":"DA Ingram","year":"1987","unstructured":"Ingram DA, Davis GR, Swash M. The double collision technique: a new method for measurement of the motor nerve refractory period distribution in man. Electroencephalogr Clin Neurophysiol. 1987;66(3):225\u201334.","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"3440_CR19","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1093\/brain\/119.4.1099","volume":"119","author":"MC Kiernan","year":"1996","unstructured":"Kiernan MC, Mogyoros I, Burke D. Differences in the recovery of excitability in sensory and motor axons of human median nerve. Brain. 1996;119:1099\u2013105.","journal-title":"Brain"},{"key":"3440_CR20","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/brain\/117.5.913","volume":"117","author":"H Bostock","year":"1994","unstructured":"Bostock H, Bergmans J. Post-tetanic excitability changes and ectopic discharges in a human motor axon. Brain. 1994;117:913\u201328.","journal-title":"Brain"},{"issue":"4","key":"3440_CR21","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00221-007-0955-7","volume":"181","author":"M Plotnik","year":"2007","unstructured":"Plotnik M, Giladi N, Hausdorff JM. A new measure for quantifying the bilateral coordination of human gait: effects of aging and Parkinson\u2019s disease. Exp Brain Res. 2007;181(4):561\u201370.","journal-title":"Exp Brain Res"},{"issue":"1","key":"3440_CR22","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S0268-0033(96)00040-X","volume":"12","author":"WE McIlroy","year":"1997","unstructured":"McIlroy WE, Maki BE. Preferred placement of the feet during quiet stance: development of a standardized foot placement for balance testing. Clin Biomech (Bristol, Avon). 1997;12(1):66\u201370.","journal-title":"Clin Biomech (Bristol, Avon)"},{"key":"3440_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jelekin.2017.01.005","volume":"33","author":"IM Albertsen","year":"2017","unstructured":"Albertsen IM, Gh\u00e9dira M, Gracies JM, Hutin \u00c9. Postural stability in young healthy subjects - Impact of reduced base of support, visual deprivation, dual tasking. J Electromyogr Kinesiol. 2017;33:27\u201333.","journal-title":"J Electromyogr Kinesiol"},{"issue":"2","key":"3440_CR24","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/(SICI)1097-4598(199802)21:2<137::AID-MUS1>3.0.CO;2-C","volume":"21","author":"H Bostock","year":"1998","unstructured":"Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve. 1998;21(2):137\u201358.","journal-title":"Muscle Nerve"},{"issue":"3","key":"3440_CR25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/(SICI)1097-4598(200003)23:3<399::AID-MUS12>3.0.CO;2-G","volume":"23","author":"MC Kiernan","year":"2000","unstructured":"Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve. 2000;23(3):399\u2013409.","journal-title":"Muscle Nerve"},{"issue":"1","key":"3440_CR26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1529-8027.2008.00155.x","volume":"13","author":"AV Krishnan","year":"2008","unstructured":"Krishnan AV, Lin CS, Park SB, Kiernan MC. Assessment of nerve excitability in toxic and metabolic neuropathies. J Peripher Nerv Syst. 2008;13(1):7\u201326.","journal-title":"J Peripher Nerv Syst"},{"issue":"Pt 5","key":"3440_CR27","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1093\/brain\/awn052","volume":"131","author":"AV Krishnan","year":"2008","unstructured":"Krishnan AV, Lin CS, Kiernan MC. Activity-dependent excitability changes suggest Na+\/K+ pump dysfunction in diabetic neuropathy. Brain. 2008;131(Pt 5):1209\u201316.","journal-title":"Brain"},{"issue":"4","key":"3440_CR28","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.clinph.2004.11.018","volume":"116","author":"D Boerio","year":"2005","unstructured":"Boerio D, Hogrel JY, Creange A, Lefaucheur JP. A reappraisal of various methods for measuring motor nerve refractory period in humans. Clin Neurophysiol. 2005;116(4):969\u201376.","journal-title":"Clin Neurophysiol"},{"issue":"1","key":"3440_CR29","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1388-2457(99)00199-6","volume":"111","author":"I Mogyoros","year":"2000","unstructured":"Mogyoros I, Lin C, Dowla S, Grosskreutz J, Burke D. Reproducibility of indices of axonal excitability in human subjects. Clin Neurophysiol. 2000;111(1):23\u20138.","journal-title":"Clin Neurophysiol"},{"issue":"1","key":"3440_CR30","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.neucli.2007.09.007","volume":"38","author":"D Boerio","year":"2008","unstructured":"Boerio D, Hogrel JY, Lefaucheur JP, Wang FC, Verschueren A, Pouget J, et al. Stimulus-response curve of human motor nerves: multicenter assessment of various indexes. Neurophysiol Clin. 2008;38(1):31\u20138.","journal-title":"Neurophysiol Clin"},{"issue":"Pt 12","key":"3440_CR31","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1093\/brain\/124.12.2439","volume":"124","author":"C Cappelen-Smith","year":"2001","unstructured":"Cappelen-Smith C, Kuwabara S, Lin CS, Mogyoros I, Burke D. Membrane properties in chronic inflammatory demyelinating polyneuropathy. Brain. 2001;124(Pt 12):2439\u201347.","journal-title":"Brain"},{"issue":"Pt 1","key":"3440_CR32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1093\/brain\/awh020","volume":"127","author":"H Nodera","year":"2004","unstructured":"Nodera H, Bostock H, Kuwabara S, Sakamoto T, Asanuma K, Jia-Ying S, et al. Nerve excitability properties in Charcot-Marie-Tooth disease type 1A. Brain. 2004;127(Pt 1):203\u201311.","journal-title":"Brain"},{"issue":"10","key":"3440_CR33","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.clinph.2018.07.021","volume":"129","author":"N Garg","year":"2018","unstructured":"Garg N, Park SB, Howells J, Noto YI, Vucic S, Yiannikas C, et al. Anti-MAG neuropathy: Role of IgM antibodies, the paranodal junction and juxtaparanodal potassium channels. Clin Neurophysiol. 2018;129(10):2162\u20139.","journal-title":"Clin Neurophysiol"},{"issue":"Pt 2","key":"3440_CR34","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1093\/brain\/119.2.439","volume":"119","author":"I Mogyoros","year":"1996","unstructured":"Mogyoros I, Kiernan MC, Burke D. Strength-duration properties of human peripheral nerve. Brain. 1996;119(Pt 2):439\u201347.","journal-title":"Brain"},{"issue":"Pt 1","key":"3440_CR35","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1113\/jphysiol.1997.sp021857","volume":"498","author":"H Bostock","year":"1997","unstructured":"Bostock H, Rothwell JC. Latent addition in motor and sensory fibres of human peripheral nerve. J Physiol. 1997;498(Pt 1):277\u201394.","journal-title":"J Physiol"},{"issue":"3","key":"3440_CR36","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.pneurobio.2009.08.002","volume":"89","author":"AV Krishnan","year":"2009","unstructured":"Krishnan AV, Lin CS, Park SB, Kiernan MC. Axonal ion channels from bench to bedside: a translational neuroscience perspective. Prog Neurobiol. 2009;89(3):288\u2013313.","journal-title":"Prog Neurobiol"},{"issue":"9","key":"3440_CR37","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1016\/S1388-2457(01)00595-8","volume":"112","author":"D Burke","year":"2001","unstructured":"Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol. 2001;112(9):1575\u201385.","journal-title":"Clin Neurophysiol"},{"issue":"21","key":"3440_CR38","doi-asserted-by":"publisher","first-page":"8168","DOI":"10.1073\/pnas.0402765101","volume":"101","author":"MJ Craner","year":"2004","unstructured":"Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG. Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+\/Ca2+ exchanger. Proc Natl Acad Sci U S A. 2004;101(21):8168\u201373.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"3440_CR39","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jclinepi.2007.03.012","volume":"61","author":"D Revicki","year":"2008","unstructured":"Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008;61(2):102\u20139.","journal-title":"J Clin Epidemiol"},{"key":"3440_CR40","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.msard.2017.04.003","volume":"14","author":"H Algahtani","year":"2017","unstructured":"Algahtani H, Shirah B, Alassiri A. Tumefactive demyelinating lesions: A comprehensive review. Mult Scler Relat Disord. 2017;14:72\u20139.","journal-title":"Mult Scler Relat Disord"},{"issue":"2","key":"3440_CR41","first-page":"205521731985575","volume":"5","author":"SA Brod","year":"2019","unstructured":"Brod SA, Lindsey JW, Nelson F. Tumefactive demyelination: Clinical outcomes, lesion evolution and treatments. Mult Scler J Exp Transl Clin. 2019;5(2):2055217319855755.","journal-title":"Mult Scler J Exp Transl Clin"},{"issue":"4","key":"3440_CR42","doi-asserted-by":"publisher","first-page":"483","DOI":"10.2169\/internalmedicine.52.8531","volume":"52","author":"Y Ohe","year":"2013","unstructured":"Ohe Y, Hayashi T, Mishima K, Nishikawa R, Sasaki A, Matsuda H, et al. Central nervous system lymphoma initially diagnosed as tumefactive multiple sclerosis after brain biopsy. Intern Med. 2013;52(4):483\u20138.","journal-title":"Intern Med"},{"key":"3440_CR43","volume-title":"No change in phosphorous magnetic resonance spectroscopy and diffusion tensor imaging in patients with progressive multiple sclerosis treated with high-dose biotin","author":"P Kauv","year":"2018","unstructured":"Kauv P, Chalah M, Cr\u00e9ange A, Ayache S, Hodel J. No change in phosphorous magnetic resonance spectroscopy and diffusion tensor imaging in patients with progressive multiple sclerosis treated with high-dose biotin. Berlin: A one-year follow-up study. ECTRIMS; 2018."}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-023-03440-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-023-03440-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-023-03440-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:14:07Z","timestamp":1698639247000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-023-03440-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,30]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["3440"],"URL":"https:\/\/doi.org\/10.1186\/s12883-023-03440-y","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,30]]},"assertion":[{"value":"24 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol, amendments, and patient-related documents, were approved by the Independent Ethics Committee (IEC\/IRB) of Ile de France VI \u2013 Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re 47, boulevard de l\u2019h\u00f4pital 75013 Paris, France (n\u00b0 128\u201315, Eudra-CT: 2015\u2013001150-15).Written informed consent was obtained from all the participants.All experiments were performed in accordance with relevant guidelines and regulations.","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":"AC reports grants and nonfinancial support from Medday, during the conduct of the study; personal fees from Medday, personal fees from Merck, grants from Octapharma, grants and personal fees from Novartis, grants and personal fees from Roche, and grants and personal fees from Biogen, outside the submitted work.EH has nothing to disclose.FS was employee and shareholder of Medday; personal fees from medday pharmaceuticals, outside the submitted work; In addition, FS has a patent Pharmaceutical Compositions highly dosed with Biotin EP2555771\/ US 20130084334 with royalties paid to Medday, a patent Method of treating Amyotrophic Lateral Sclerosis and neuropathies with Biotin EP 3273957\/ US 20190314342 issued, and a patent Methods of Treating Multiple Sclerosis with Biotin EP2729143\/US 20140030331 with royalties paid to Medday.LLV is an employee of ATLANSTAT.JPL has nothing to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"389"}}