{"id":"https://openalex.org/W7214284697","doi":"https://doi.org/10.64898/2026.09.23.26363839","title":"Chronic lesion expansion persists in secondary progressive multiple sclerosis and is associated with neurodegeneration","display_name":"Chronic lesion expansion persists in secondary progressive multiple sclerosis and is associated with neurodegeneration","publication_year":2026,"publication_date":"2026-09-25","ids":{"openalex":"https://openalex.org/W7214284697","doi":"https://doi.org/10.64898/2026.09.23.26363839"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.23.26363839","doi":"https://doi.org/10.64898/2026.09.23.26363839","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.26363839","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/25/2026.09.23.26363839.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/25/2026.09.23.26363839.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5025471517","display_name":"Samuel Klistorner","orcid":"https://orcid.org/0000-0001-5761-5178","observed_orcids":["https://orcid.org/0000-0001-5761-5178"]},"institutions":[{"id":"https://openalex.org/I129604602","display_name":"The University of Sydney","ror":"https://ror.org/0384j8v12","country_code":"AU","type":"education","lineage":["https://openalex.org/I129604602"]}],"countries":["AU"],"is_corresponding":true,"raw_author_name":"Samuel Klistorner","raw_affiliation_strings":["Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia"],"raw_orcid":"https://orcid.org/0000-0001-5761-5178","affiliations":[{"raw_affiliation_string":"Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia","institution_ids":["https://openalex.org/I129604602"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083946982","display_name":"Michael Harry Barnett","orcid":"https://orcid.org/0000-0002-2156-8864","observed_orcids":["https://orcid.org/0000-0002-2156-8864"]},"institutions":[{"id":"https://openalex.org/I129604602","display_name":"The University of Sydney","ror":"https://ror.org/0384j8v12","country_code":"AU","type":"education","lineage":["https://openalex.org/I129604602"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Michael H Barnett","raw_affiliation_strings":["Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia","Sydney Neuroimaging Analysis Centre, Camperdown, New South Wales, Australia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia","institution_ids":["https://openalex.org/I129604602"]},{"raw_affiliation_string":"Sydney Neuroimaging Analysis Centre, Camperdown, New South Wales, Australia","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5089004523","display_name":"Alexander I. Klistorner","orcid":"https://orcid.org/0000-0003-0361-6399","observed_orcids":["https://orcid.org/0000-0003-0361-6399"]},"institutions":[{"id":"https://openalex.org/I129604602","display_name":"The University of Sydney","ror":"https://ror.org/0384j8v12","country_code":"AU","type":"education","lineage":["https://openalex.org/I129604602"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Alexander Klistorner","raw_affiliation_strings":["Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia","institution_ids":["https://openalex.org/I129604602"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5025471517"],"corresponding_institution_ids":["https://openalex.org/I129604602"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10137","display_name":"Multiple Sclerosis Research Studies","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10137","display_name":"Multiple Sclerosis Research Studies","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11827","display_name":"Polyomavirus and related diseases","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/secondary-progressive-multiple-sclerosis","display_name":"secondary progressive multiple sclerosis","score":1.0},{"id":"https://openalex.org/keywords/neurodegeneration","display_name":"neurodegeneration","score":0.7860000133514404},{"id":"https://openalex.org/keywords/white-matter-lesions","display_name":"white matter lesions","score":0.7850000262260437},{"id":"https://openalex.org/keywords/mean-diffusivity","display_name":"mean diffusivity","score":0.871999979019165},{"id":"https://openalex.org/keywords/brain-atrophy","display_name":"brain atrophy","score":0.9769999980926514},{"id":"https://openalex.org/keywords/ventricular-dilation","display_name":"ventriculomegaly","score":0.9890000224113464},{"id":"https://openalex.org/keywords/tissue-damage","display_name":"tissue damage","score":0.7229999899864197},{"id":"https://openalex.org/keywords/longitudinal-mri","display_name":"longitudinal MRI","score":0.5619999766349792}],"concepts":[{"id":"https://openalex.org/C2781156865","wikidata":"https://www.wikidata.org/wiki/Q827023","display_name":"Lesion","level":2,"score":0.8514000177383423},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7720000147819519},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.6704000234603882},{"id":"https://openalex.org/C2780640218","wikidata":"https://www.wikidata.org/wiki/Q8277","display_name":"Multiple sclerosis","level":2,"score":0.6528000235557556},{"id":"https://openalex.org/C2781172350","wikidata":"https://www.wikidata.org/wiki/Q194520","display_name":"Atrophy","level":2,"score":0.5932999849319458},{"id":"https://openalex.org/C2781192897","wikidata":"https://www.wikidata.org/wiki/Q822050","display_name":"White matter","level":3,"score":0.4684999883174896},{"id":"https://openalex.org/C2776925932","wikidata":"https://www.wikidata.org/wiki/Q1755122","display_name":"Neurodegeneration","level":3,"score":0.4607999920845032},{"id":"https://openalex.org/C166252455","wikidata":"https://www.wikidata.org/wiki/Q6736610","display_name":"Trinucleotide repeat expansion","level":4,"score":0.4214000105857849},{"id":"https://openalex.org/C2779354088","wikidata":"https://www.wikidata.org/wiki/Q15467261","display_name":"Degeneration (medical)","level":2,"score":0.41760000586509705},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.4140999913215637},{"id":"https://openalex.org/C2777645973","wikidata":"https://www.wikidata.org/wiki/Q3062074","display_name":"Tissue expansion","level":2,"score":0.40400001406669617},{"id":"https://openalex.org/C149550507","wikidata":"https://www.wikidata.org/wiki/Q899360","display_name":"Diffusion MRI","level":3,"score":0.3727000057697296},{"id":"https://openalex.org/C101070640","wikidata":"https://www.wikidata.org/wiki/Q3737215","display_name":"Fluid-attenuated inversion recovery","level":3,"score":0.35569998621940613},{"id":"https://openalex.org/C146638467","wikidata":"https://www.wikidata.org/wiki/Q10529587","display_name":"Hyperintensity","level":3,"score":0.334199994802475},{"id":"https://openalex.org/C2779281540","wikidata":"https://www.wikidata.org/wiki/Q5062122","display_name":"Central nervous system disease","level":2,"score":0.31630000472068787},{"id":"https://openalex.org/C2776728740","wikidata":"https://www.wikidata.org/wiki/Q2279175","display_name":"Progressive muscular atrophy","level":4,"score":0.30959999561309814},{"id":"https://openalex.org/C2777682930","wikidata":"https://www.wikidata.org/wiki/Q1531490","display_name":"Gliosis","level":2,"score":0.259799987077713},{"id":"https://openalex.org/C2777799939","wikidata":"https://www.wikidata.org/wiki/Q1711381","display_name":"Perivascular space","level":2,"score":0.25200000405311584}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.23.26363839","doi":"https://doi.org/10.64898/2026.09.23.26363839","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.26363839","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/25/2026.09.23.26363839.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.23.26363839","doi":"https://doi.org/10.64898/2026.09.23.26363839","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.23.26363839","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/25/2026.09.23.26363839.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/observational-study","display_name":"Observational Study"}],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7214284697.pdf","grobid_xml":"https://content.openalex.org/works/W7214284697.grobid-xml"},"referenced_works_count":18,"referenced_works":["https://openalex.org/W1971334524","https://openalex.org/W2063001897","https://openalex.org/W2071881327","https://openalex.org/W2136145485","https://openalex.org/W2542350582","https://openalex.org/W2772291758","https://openalex.org/W2905522261","https://openalex.org/W2922528121","https://openalex.org/W2928702083","https://openalex.org/W2967956895","https://openalex.org/W2970233240","https://openalex.org/W2970898057","https://openalex.org/W3099080023","https://openalex.org/W3137295710","https://openalex.org/W4220747781","https://openalex.org/W4285744151","https://openalex.org/W4309374247","https://openalex.org/W4401826939"],"related_works":["https://openalex.org/W3099080023","https://openalex.org/W4220892375","https://openalex.org/W4396967506","https://openalex.org/W2463861876","https://openalex.org/W4220688869","https://openalex.org/W4389376348","https://openalex.org/W4391566952","https://openalex.org/W4210366840","https://openalex.org/W4415897542","https://openalex.org/W4220747781"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Secondary":[2],"progressive":[3],"multiple":[4,136],"sclerosis":[5],"(SPMS)":[6],"is":[7],"traditionally":[8],"viewed":[9],"as":[10,83],"predominantly":[11],"neurodegenerative,":[12],"with":[13,58,110,156,166,192],"limited":[14],"inflammatory":[15],"activity.":[16],"However,":[17],"chronic":[18,39,47,76],"active":[19],"lesions":[20,71,128,150],"characterised":[21],"by":[22],"persistent":[23],"rim":[24],"inflammation":[25],"and":[26,44,54,66,75,95,103,129,153,183,195],"gradual":[27],"expansion":[28,49,79,114,161,179],"may":[29],"continue":[30],"to":[31,33,51,134],"contribute":[32],"tissue":[34,52,78,189],"injury.":[35],"Objectives":[36],"To":[37],"characterise":[38],"lesion":[40,48,77,89,157,160,178],"dynamics":[41],"in":[42,181],"SPMS":[43,59,182],"determine":[45],"whether":[46],"contributes":[50],"damage":[53],"neurodegeneration.":[55],"Thirty-one":[56],"patients":[57],"underwent":[60],"longitudinal":[61],"MRI":[62],"including":[63],"T1-weighted,":[64],"FLAIR":[65],"diffusion":[67],"imaging.":[68],"White":[69],"matter":[70],"were":[72,98],"manually":[73],"segmented":[74],"(CLTE)":[80],"was":[81,154,162],"quantified":[82],"annualised":[84],"percentage":[85],"change.":[86],"Associations":[87],"between":[88],"expansion,":[90],"mean":[91,112],"diffusivity":[92],"(MD)":[93],"changes":[94],"brain":[96,196],"atrophy":[97],"assessed":[99],"using":[100],"correlation,":[101],"regression":[102],"mixed-effects":[104],"modelling.":[105],"Results":[106],"CLTE":[107,138],"remained":[108],"prominent,":[109],"a":[111,185],"annual":[113],"rate":[115],"of":[116,125,188],"7.1":[117],"\u00b1":[118],"4.1%.":[119],"Expansion":[120],"substantially":[121],"exceeded":[122],"the":[123],"contribution":[124],"newly":[126],"formed":[127],"occurred":[130],"at":[131],"rates":[132],"comparable":[133],"relapsing":[135],"sclerosis.":[137],"demonstrated":[139],"moderate":[140],"intra-patient":[141],"clustering":[142],"(ICC":[143],"=":[144,171],"0.23).":[145],"MD":[146],"increased":[147],"significantly":[148],"within":[149],"during":[151],"follow-up":[152],"associated":[155,165,191],"expansion.":[158],"Chronic":[159,177],"also":[163],"strongly":[164],"ventricular":[167],"enlargement":[168],"(partial":[169],"r":[170],"0.72,":[172],"p":[173],"<":[174],"0.001).":[175],"Conclusions":[176],"persists":[180],"represents":[184],"major":[186],"source":[187],"injury":[190],"microstructural":[193],"degeneration":[194],"atrophy.":[197]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-09-26T00:00:00"}
