Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Low natalizumab trough concentrations are associated with reduced seroconversion of the John Cunningham virus in natalizumab-treated patients with multiple sclerosis.","authors":"Liza M Y Gelissen, Alyssa A Toorop, Pien M Schipper, Elske Hoitsma, Esther M P E Zeinstra, Luuk C van Rooij, Caspar E P van Munster, Anke Vennegoor, Jop Mostert, Beatrijs Wokke, Nynke F Kalkers, Erwin L J Hoogervorst, Jeroen van Eijk, Christiaan M Roosendaal, Jolijn J Kragt, Marijke Eurelings, Jessie van Genugten, Jessica Nielsen, L G F Sinnige, Mark E Kloosterziel, Edo P J Arnoldus, Willem H Bouvy, Eva M Strijbis, Bob van Oosten, Brigit A De Jong, Bernard M J Uitdehaag, Birgit I Lissenberg-Witte, Floris C Loeff, Theo Rispens, Joep Killestein, Zoé L E van Kempen","doi":"10.1136/jnnp-2024-335761","DOIUrl":"10.1136/jnnp-2024-335761","url":null,"abstract":"<p><strong>Background: </strong>Natalizumab is a highly effective drug for patients with relapsing-remitting multiple sclerosis (MS). A disadvantage of this treatment is the risk of progressive multifocal leukoencephalopathy in patients who are seropositive for the John Cunningham virus (JCV). JCV seroconversion rates increase under natalizumab treatment compared with non-natalizumab using controls. The aim of this study was to assess whether lower natalizumab trough concentrations are associated with reduced JCV seroconversion compared with higher natalizumab trough concentrations.</p><p><strong>Methods: </strong>Two overlapping cohorts of patients treated with intravenous natalizumab in the Netherlands were combined for this study. JCV seroconversion was assessed during periods of high (≥15 µg/mL) and low (<15 µg/mL) natalizumab trough concentrations. Low trough concentrations were mainly the result of trough concentration guided personalised extended interval dosing (EID). The seroconversion rates during high and low trough concentrations were compared using a generalised linear mixed model with a Poisson link function.</p><p><strong>Results: </strong>A total of 357 patients from 21 hospitals in the Netherlands were included. The annual seroconversion rate of 8.4% observed in patients during periods of high trough concentrations (n=226) was 2.32 times higher than the seroconversion rate of 4.8% in patients during periods of low trough concentrations (n=252) (95% CI=1.32 to 4.08, p=0.0035).</p><p><strong>Conclusions: </strong>The seroconversion rate observed in patients with MS with low trough concentrations was substantially lower compared with those with high trough concentrations during natalizumab treatment. This emphasises the importance of personalised EID, where intervals between infusions are prolonged to achieve lower natalizumab trough concentrations, to increase drug safety.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1038-1045"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament light chain improves clinical prognostic models for Guillain-Barré syndrome.","authors":"Robin C M Thomma, Linda W G Luijten, Sander J van Tilburg, Eveline J A Wiegers, Charlotte E Teunissen, Lisa Vermunt, Pieter A van Doorn, Ruth Huizinga, Bart C Jacobs","doi":"10.1136/jnnp-2025-336046","DOIUrl":"10.1136/jnnp-2025-336046","url":null,"abstract":"<p><strong>Background: </strong>Several prognostic models predict clinical outcomes in Guillain-Barré syndrome (GBS). Recently, neurofilament light chain (NfL) has emerged as a prognostic biomarker. We investigated the added prognostic value of NfL in serum (sNfL) and cerebrospinal fluid (cNfL) to models based on clinical factors predicting respiratory failure and inability to walk in GBS.</p><p><strong>Methods: </strong>We included patients from a randomised placebo-controlled trial (second intravenous immunoglobulin dose in GBS). Serum was acquired at entry and week 1, 2, 4 and 12 and cerebrospinal fluid at entry. NfL levels were determined on a single molecule array. The additional prognostic value of NfL to the (modified) Erasmus GBS Outcome Score ((m)EGOS) and (modified) Erasmus GBS Respiratory Insufficiency Score was evaluated using logistic regression analyses.</p><p><strong>Results: </strong>In total, 293 patients were included (74 (25%) mechanically ventilated, 38/275 (13%) unable to walk at 26 weeks). Higher sNfL at entry, week 1 and week 2 and cNfL at entry were associated with inability to walk at 4 and 26 weeks. Neither sNfL nor cNfL levels at entry were associated with respiratory failure. The EGOS and mEGOS improved after adding NfL (∆C-statistic range: 0.01-0.11), especially the models predicting outcome at 26 weeks. A new model predicting inability to walk at 26 weeks consisting of sNfL at entry, GBS disability score at entry and Medical Research Council sum score at week 2 performed best (C-statistic: 0.88 (95% CI 0.83 to 0.94)).</p><p><strong>Conclusions: </strong>Addition of NfL may improve clinical prognostic models for the prediction of inability to walk, but not of respiratory failure.</p><p><strong>Trial registration number: </strong>NTR2224/NL2107.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1099-1108"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple sclerosis from onset to secondary progression: a 30-year Italian register study.","authors":"Aurora Zanghì, Massimiliano Copetti, Carlo Avolio, Damiano Paolicelli, Marzia Anita Lucia Romeo, Francesco Patti, Giovanna De Luca, Maria Pia Amato, Simonetta Galgani, Patrizia Sola, Giuseppe Salemi, Paolo Gallo, Franco Granella, Silvia Romano, Mauro Zaffaroni, Roberto Bergamaschi, Carlo Pozzilli, Giacomo Lus, Marika Vianello, Maria Trojano, Emanuele D'Amico","doi":"10.1136/jnnp-2025-335958","DOIUrl":"10.1136/jnnp-2025-335958","url":null,"abstract":"<p><strong>Background: </strong>Three decades have passed since the initial approval of disease-modifying therapies (DMTs). Ongoing discussion is focused on fundamental aspects of the disease, highlighting a growing division between successes in managing relapsing multiple sclerosis (MS) and the persistent challenges posed by disease progression.</p><p><strong>Methods: </strong>A cohort study on prospectively acquired data from the Italian MS register. The primary outcome was to describe the MS disease course from onset to secondary progression (SP) defined according to a data-driven algorithm over 30 years follow-up and according to five different eras of disease onset.</p><p><strong>Results: </strong>A total cohort of 9958 patients was analysed; 1364 converted to SP after a mean of 8.5 (SD 5.5) years. A higher rate of patients converting to SP had never been exposed to DMTs (135, 9.9% vs 424, 5.2%) than non-converting ones. The treatment coverage was also lower in patients converting to SP than non-converting ones 58.4 (SD 31.5) vs 73.6 (SD 27.6).The SP incidence rate was 1.26 (95% CI 1.19 to 1.32) overall. The rates showed a downward trend among the different eras: from 1st era 1.98 (95% CI 1.73 to 2.27) to 5th era 1.15 (95% CI 0.97 to 1.35).In the multivariable Cox model, 10% increase of treatment coverage was associated to 19% lower risk to convert to SP (10%, HR 0.89, 95% CI 0.87 to 0.90).</p><p><strong>Conclusions: </strong>This 30-year analysis suggests that SP conversion rates have decreased over time, partially explained by improvements in therapeutic coverage. Future research should adopt a multifaceted approach to develop more comprehensive models of disease progression.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1061-1069"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.","authors":"Ahmed Abdelhak, Franziska Bachhuber, Kiarra Ning, Pascal Benkert, W John Boscardin, Aleksandra Maleska Maceski, Sabine Schaedelin, Lutz Achtnichts, Sebastian Finkener, Patrice H Lalive, Marjolaine Uginet, Caroline Pot, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Claudio Gobbi, Chiara Zecca, Stefanie Müller, Patrick Roth, Cristina Granziera, Tanuja Chitnis, Evan Madill, Howard L Weiner, Ari J Green, Stephen L Hauser, Bruce Ac Cree, Tania Kümpfel, Joachim Havla, Thomas Skripuletz, Stefan Gingele, Makbule Senel, Ioannis Vardakas, Daniela Taranu, Ulf Ziemann, Markus C Kowarik, Ingo Kleiter, Muna-Miriam Hoshi, Uwe K Zettl, Axel Haarmann, Simon Thebault, Mark S Freedman, Hailey P Bergman, Ellen Iacobaeus, Mohsen Khademi, Diana Ferraro, Martina Cardi, Sara Mariotto, Manuel Comabella, Xavier Montalban, Andreu Vilaseca-Jolonch, Eva M Strijbis, Mark Hj Wessels, Joep Killestein, Bernhard Hemmer, Friederike Held, Finn Sellebjerg, Helene Højsgaard Chow, Roberto Alvarez-Lafuente, Maria Inmaculada Domínguez-Mozo, Harald Hegen, Klaus Berek, Florian Deisenhammer, Eric Thouvenot, Hanane Agherbi, Konrad Rejdak, Magda Gąsior, Dimitrios Tzanetakos, John S Tzartos, Maria Pia Sormani, Irena Dujmovic Basuroski, Georgina Arrambide, Michael Khalil, Fredrik Piehl, Charlotte E Teunissen, Jens Kuhle, Hayrettin Tumani","doi":"10.1136/jnnp-2025-335831","DOIUrl":"10.1136/jnnp-2025-335831","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).</p><p><strong>Methods: </strong>Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.</p><p><strong>Results: </strong>1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).</p><p><strong>Conclusions: </strong>GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1046-1052"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidities, safety and persistence in phase III clinical trials in multiple sclerosis.","authors":"Amber Salter, Samantha Lancia, Kaarina Kowalec, Kathryn Fitzgerald, Ruth Ann Marrie","doi":"10.1136/jnnp-2024-335710","DOIUrl":"10.1136/jnnp-2024-335710","url":null,"abstract":"<p><strong>Background: </strong>Associations between comorbidity and reduced persistence to disease-modifying therapies (DMTs) in multiple sclerosis (MS) have been identified. Limited information is available regarding the association of comorbidity with safety outcomes. The study objective was to evaluate the association of comorbidities with safety outcomes and persistence.</p><p><strong>Methods: </strong>We conducted a two-stage meta-analysis of individual participant data from phase III clinical trials of MS DMTs. Individual comorbidities and comorbidity burden, defined as the sum of all comorbidities (n=15), were examined. Safety outcomes, defined using adverse event (AE) data, were reviewed to identify specific AEs of interest, including infection; treatment-emergent autoimmune disease; cancer; elevated transaminases and lymphopenia. We also examined any early trial discontinuation.</p><p><strong>Results: </strong>We included 17 clinical trials representing 16 794 MS participants. Over a 2-year follow-up, the pooled proportion of AEs was 64% (95% CI 59.4% to 68.9%) and the majority were infection AEs. Increasing comorbidity burden was associated with an increased rate of AEs (rate ratio (95% CI) 1: 1.13 (1.09 to 1.17); 2: 1.19 (1.14 to 1.23); ≥3: 1.25 (1.18 to 1.33)) compared with those with no comorbidity. When pooled across trials, early discontinuation affected 17% of participants (95% CI 13.8% to 20.9%). A higher risk of trial discontinuation was associated with higher comorbidity burden (2: 1.23 (1.07 to 1.42); ≥3: 1.19 (1.01 to 1.40)) compared with those with no comorbidity. Psychiatric disorders were associated with trial discontinuation.</p><p><strong>Conclusions: </strong>Higher comorbidity burden is associated with increased risk of experiencing safety outcomes and early DMT discontinuation among individuals with MS enrolled in clinical trials of MS-DMTs, highlighting the important role of comorbidities in the safety and persistence of DMTs.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1070-1076"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological manifestations of immunoglobulin G₄ related disease: a systematic review of 393 cases.","authors":"Yau Zane Justin Ng, Scarlett Bowen, Jenna Phillips, Mugil Rajasekaran, Shi Sheng Lu, Bruce V Taylor","doi":"10.1136/jnnp-2025-336230","DOIUrl":"10.1136/jnnp-2025-336230","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin G₄ (IgG₄) related disease (RD) is a multisystem, immunologically mediated disease discovered within the last two decades. Within the nervous system, a broad range of both central and peripheral nervous system involvement has been reported. We aimed to systematically review the neurological manifestations of IgG₄-RD.</p><p><strong>Aim: </strong>To identify the clinical presentation, radiological findings, diagnostic methods, treatment and outcomes for neurological manifestations of IgG₄-RD.</p><p><strong>Methods: </strong>We systematically reviewed the literature to identify all reports of neurological manifestations of IgG₄-RD. Data on neurological manifestations, non-neurological manifestations, clinical presentation, radiological findings, diagnostic methods, treatment modalities and outcomes were extracted.</p><p><strong>Results: </strong>We identified 393 cases from 297 publications meeting the inclusion criteria. Hypertrophic pachymeningitis, IgG₄-related orbital disease and hypophysitis are the most common neurological manifestations of IgG₄-RD. Diagnostic evaluation involves testing for concomitant non-neurological manifestations, an MRI with gadolinium contrast, measurement of serum IgG₄ levels and a biopsy with specific staining for IgG₄ positive plasma cells. Treatment with corticosteroids leads to favourable outcomes.</p><p><strong>Conclusions: </strong>IgG₄-RD is an emerging neurological disease that can manifest in multiple ways within the nervous system. It is important to recognise as treatment is often successful.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1109-1116"},"PeriodicalIF":7.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting 'hot cross bun' sign: a multicentre MRI study of 97 patients with autopsy-confirmed multiple system atrophy.","authors":"Atsuhiko Sugiyama, Yuichi Riku, Shunsuke Koga, Hajime Yokota, Hiroki Mukai, Masaki Takao, Kentaro Hayashi, Takahiro Takeda, Shigeki Hirano, Mari Yoshida, Yasushi Iwasaki, Keizo Yasui, Takashi Ando, Yasuhiro Ito, Takuya Tamura, Hiroaki Sekiya, Dennis W Dickson, Erik H Middlebrooks, Yuji Takahashi, Noriko Sato, Masashi Mizutani, Terunori Sano, Ban Mihara, Takashi Komori, Satoshi Kuwabara","doi":"10.1136/jnnp-2025-336869","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336869","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to clarify the usefulness of the 'hot cross bun' sign (HCBS) as a diagnostic imaging marker in a large cohort of patients with multiple system atrophy (MSA) and spinocerebellar ataxia (SCA).</p><p><strong>Methods: </strong>This multicentre study included 97 patients with neuropathologically confirmed MSA, and 105 patients with genetically confirmed SCA. Neuroimaging features, including HCBS and middle cerebellar peduncle (MCP) hyperintensities, were assessed. HCBS was graded from 0 to 2: 0, none; 1, only a vertical hyperintense line; and 2, a cruciform hyperintense line. The neuropathological correlates of HCBS were evaluated in 15 patients with MSA with ≤3 months between MRI and autopsy.</p><p><strong>Results: </strong>In patients with a disease duration <3 years, grade 1 or 2 HCBS was detected in 100% patients with MSA with predominant cerebellar ataxia (MSA-C) and 39.0% with SCA; whereas grade 2 HCBS was observed in 50% with MSA-C and 2.4% with SCA. Moreover, the coexistence of grade 2 HCBS and MCP hyperintensities exhibited a specificity of 100%. A neuropathological assessment revealed myelin loss, alpha-synuclein aggregates and astrocytic reaction in the MCP, transverse fibres, central zone between longitudinal fasciculi and raphe nucleus, with relative preservation in the longitudinal fasciculi and medial lemniscus in patients with MSA and grade 2 HCBS.</p><p><strong>Conclusions: </strong>Grade 1 or 2 HCBS is a highly sensitive finding in patients with MSA-C, and the observation of grade 2 HCBS within 3 years of motor symptom onset has excellent specificity for discriminating MSA-C from SCA, especially when accompanied by MCP hyperintensities.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the modified Rankin Scale: the unseen burden of stroke in young adults.","authors":"Jukka Putaala, Karoliina Aarnio","doi":"10.1136/jnnp-2025-337290","DOIUrl":"https://doi.org/10.1136/jnnp-2025-337290","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended window of relapse recovery in RRMS: an analysis of the DECIDE dataset.","authors":"Jop Mostert, Eva M Strijbis, Miguel D'Haeseleer, Ester Moral, Luis Brieva, Jacynthe Comtois, Pavle Repovic, James D Bowen, Gary Cutter, Marcus Koch","doi":"10.1136/jnnp-2025-336660","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336660","url":null,"abstract":"<p><strong>Background: </strong>The main goal of treatment in relapsing-remitting multiple sclerosis (RRMS) is to reduce the occurrence of relapses. However, little is known about the natural history of relapse recovery.</p><p><strong>Methods: </strong>We accessed data from DECIDE (n=1841), a phase 3 trial. We investigated factors associated with time to relapse recovery (defined as a return of the Expanded Disability Status Scale (EDSS) score to the pre-relapse level or lower), relapse severity (0.5, 1.0, or >1.0 EDSS score change) and the new concept of 'acute clinical events with stable MRI' (ACES). Variables used were age, sex, disease duration, treatment arm, pre-relapse EDSS, corticosteroid use, number of relapses prior to study enrolment, MRI activity, relapse severity and affected functional system (FS).</p><p><strong>Results: </strong>We included 430 first relapses, of which 405 (94.2%) recovered during follow-up, 400 (93%) by 1 year (median time to recovery of 71 days, 95% CI 66 to 75 days). More severe relapses and relapses involving the bowel and bladder FS took a longer time to recover. Corticosteroids hastened the recovery of relapses but did not influence eventual relapse recovery. ACES occurred in 38% of relapses and was more frequent in older people and participants treated with daclizumab.</p><p><strong>Conclusions: </strong>Most relapses (94.2%) recover, but the process of recovery can take up to 1 year and depends mostly on relapse severity. Our findings challenge the concept of 3-month and 6-month confirmed disability progression as reliable markers of permanent disability in RRMS trials. ACES occurs frequently and is associated with age.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported outcomes after stroke in young adults: University College London (UCL) Young Stroke Systematic Evaluation Study (ULYSSES).","authors":"Raafiah Mussa, Gareth Ambler, Hatice Ozkan, John Mitchell, Gargi Banerjee, Alexander P Leff, Siobhan McLernon, Richard J Perry, Robert Simister, Arvind Chandratheva, David J Werring","doi":"10.1136/jnnp-2025-336411","DOIUrl":"https://doi.org/10.1136/jnnp-2025-336411","url":null,"abstract":"<p><strong>Background: </strong>Few studies have investigated patient-reported non-motor outcomes after stroke in young adults. We aimed to assess their prevalence and patterns in this population to identify unmet needs.</p><p><strong>Methods: </strong>This prospective cohort study included consecutive patients (aged <55) admitted to University College London (UCL) Hospitals Hyperacute Stroke Unit with ischaemic stroke or intracerebral haemorrhage (ICH) between 2017 and 2020. At 6 months, we collected data on eight non-motor domains (anxiety, depression, fatigue, sleep disturbance, pain interference, reduced social participation, bowel and bladder dysfunction). We assessed outcome co-occurrence, compared prevalence by modified Rankin Scale (mRS) score (favourable: 0-1 versus unfavourable: 2-5), and performed multivariable logistic regression to identify predictors of each adverse outcome and high non-motor outcome burden (≥3 adverse outcomes).</p><p><strong>Results: </strong>We included 493/527 (94%) eligible patients (median age 48, IQR 41-52; 33% female; 82% ischaemic stroke). Fatigue (55%) reduced social participation (47%) and sleep disturbance (46%) were most common. Prevalence rates did not differ significantly by mRS score. 91% reported ≥1 adverse outcome; 27% reported ≥4. Anxiety was predicted by ICH (OR 1.92; 95% CI 1.11 to 3.33; p=0.019) and higher education levels (per decile increase in education deprivation, OR 1.12; 95% CI 1.03 to 1.22; p=0.012). Pain interference was predicted by admission stroke severity (per National Institutes of Health Stroke Scale 10-point increase, OR 1.54; 95% CI 1.05 to 2.25; p=0.025).</p><p><strong>Conclusions: </strong>Adverse non-motor outcomes are common in young adults 6 months post-stroke, even in those with an mRS score of 0-1 (indicating a favourable functional recovery). Furthermore, non-motor outcomes rarely occur in isolation, highlighting the need for early and comprehensive screening, recognition and management.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}