Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Predictors of B-cell repopulation in people with multiple sclerosis treated with ocrelizumab: insights from two large cohorts.","authors":"Laura Hogenboom, Antonia McLean, Lisa Schoof, Lisa Taylor, Eva M Strijbis, Joep Killestein, Zoé L E van Kempen, Tomas Kalincik, Izanne Roos","doi":"10.1136/jnnp-2026-338533","DOIUrl":"https://doi.org/10.1136/jnnp-2026-338533","url":null,"abstract":"<p><strong>Background: </strong>Evidence indicates that B-cell dynamics during ocrelizumab treatment vary among individuals with multiple sclerosis. However, our understanding of B-cell dynamics is incomplete. We aim to characterise temporal profiles of CD19+ B-cell repopulation and identify demographic and clinical predictors of B-cell dynamics.</p><p><strong>Methods: </strong>This was a retrospective multicentre cohort study including people with multiple sclerosis treated with ocrelizumab for ≥180 days from two academic centres. Variables of interest were visualised to explore their associations with CD19+ B-cell count. Generalised linear mixed effect models and logistic mixed effect models were used to identify predictors of CD19+ B-cell counts and early B-cell repopulation (>0.01×10⁹ cells/L, 150-210 days post infusion). We have explored the patterns of early B-cell repopulation and relapse incidence within these groups.</p><p><strong>Results: </strong>567 participants, contributing 4592 CD19+ B-cell counts, were included. Younger age (β=-0.01, 95% CI -0.02 to -0.003), heavier weight (β=0.02, 95% CI 0.008 to 0.02), fewer ocrelizumab infusions (β=-0.07, 95% CI -0.08 to -0.06) and higher pre-ocrelizumab CD19+ B-cell counts (β=1.42, 95% CI 0.82 to 2.03) were associated with higher CD19+ B-cells during treatment. Pre-ocrelizumab CD19+ B-cells were higher in patients previously treated with natalizumab (mean B-cell count 0.57×10⁹ cells/L (IQR=0.34-0.85)) and lower in patients previously receiving sphingosine-1-phosphate receptor modulators (mean B-cell count 0.03×10⁹ cells/L (IQR=0.02-0.13)). Early B-cell repopulation was more likely in patients with prior early repopulation (OR=3.00, 95% CI 1.61 to 5.61). Relapse incidence did not differ between the four patterns of B-cell repopulation dynamics.</p><p><strong>Conclusions: </strong>Age, weight, cumulative ocrelizumab exposure, pre-ocrelizumab CD19+ B-cell count and prior disease modifying therapy influence CD19+ B-cell repopulation during ocrelizumab treatment. With further elucidation of the association between B-cell dynamics and treatment effectiveness, these findings will help guide dosing of anti-CD20 therapies in the future.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856510","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":"Aetiological factors in functional seizures and functional motor symptoms: shared and distinct features.","authors":"L S Merritt Millman, Snigdha Bhuma, Yasmine Basamh, Jemima Uloyok-Job, Jessica Davies, Lauren Blunstone, Akshaana Manoharan, Jan A Coebergh, Anthony S David, Mark J Edwards, Laura H Goldstein, John Hodsoll, Mitul A Mehta, Timothy R Nicholson, Biba Stanton, Joel S Winston, Trudie Chalder, Matthew Hotopf, Susannah Pick","doi":"10.1136/jnnp-2025-337694","DOIUrl":"https://doi.org/10.1136/jnnp-2025-337694","url":null,"abstract":"<p><strong>Background: </strong>Functional seizures (FS) and functional motor symptoms (FMS), subtypes of functional neurological disorder, may involve shared and distinct predisposing, precipitating, perpetuating and triggering (PPPT) factors. This study investigated potential self-reported PPPT factors in FS and FMS separately.</p><p><strong>Methods: </strong>200 participants (FS=50, FMS=50, individuals with anxiety and/or depression (clinical controls [CC]=50, healthy controls [HC]=50) completed an in-depth medical history interview and online questionnaires to assess potential aetiological factors including traumatic/adverse life events, alexithymia, autistic traits, psychological and physical symptoms, illness perceptions, cognitive-behavioural responses and outcome measures of general functioning and health-related quality of life (HRQoL).</p><p><strong>Results: </strong>Participants with FS more frequently reported traumatic/adverse events and psychopathology (eg, dissociation, posttraumatic stress disorder) as possible illness causes/precipitating factors and sensory symptom triggers, relative to FMS and/or CCs. In contrast, participants with FMS endorsed physical illness causes/precipitating factors and physical activity and emotion-related symptom triggers more frequently than FS and/or CCs. Physical and dissociative symptoms were elevated, alongside reductions in HRQoL and general functioning in FS/FMS compared with CCs/HCs. Greater current, threatening illness-related beliefs/cognitions were disclosed in FS/FMS compared with CCs. Negative associations between HRQoL, cognitive-behavioural responses and traumatic/adverse events were also seen in FS/FMS.</p><p><strong>Conclusions: </strong>Traumatic events and psychopathology may be more prominently involved in the development/maintenance of FS and physical illness/injury, physical functioning and alexithymia may be more central to FMS. Unhelpful illness-related beliefs and impacts on HRQoL and general functioning are shared between these subtypes. The results of this study provide insight into potential unique and overlapping characteristics of FS/FMS, with implications for treatment.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839100","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":"Recovery of daily life upper limb use during stroke rehabilitation: neuroanatomical correlates and associated variables.","authors":"Janne Marieke Veerbeek, Brigitte Charlotte Kaufmann, Beatrice Ottiger, Meva Himmetoglu, Ender Konukoglu, Thomas Nyffeler","doi":"10.1136/jnnp-2025-337392","DOIUrl":"https://doi.org/10.1136/jnnp-2025-337392","url":null,"abstract":"<p><strong>Background: </strong>Early after stroke, the upper limb is impaired in ~50% of patients who had a stroke, posing a significant and restrictive challenge to their daily lives. It is unknown how many subacute stroke patients regain good upper limb use in everyday life (ie, performance) during inpatient neurorehabilitation and which clinical and stroke-related neuroanatomical factors are associated with recovery. This study explores these questions using real-world clinical data.</p><p><strong>Methods: </strong>Analysis of data prospectively collected on a weekly basis in the clinical routine of patients who had a subacute stroke admitted to a Swiss inpatient neurorehabilitation centre (January 2016-October 2023). Multivariable logistic regression was applied to determine predictors for return of good upper limb performance. Voxel-based lesion symptom mapping (VLSM) was used to determine neuroanatomical correlates for successful return.</p><p><strong>Results: </strong>794 out of 1169 patients who had a stroke (67.9%) did not have a good upper limb performance at a median of 8 days poststroke. Of these, 394 (49.6%) regained good upper limb performance during the subsequent 36 (quartile 1=27, quartile 3=52.75) days. Multivariable logistic regression showed that a younger age, fewer neglect symptoms and better dexterity, stereognosis and general cognition were associated with regaining good upper limb performance. VLSM revealed that less stroke-related injury in the corticospinal tract, right hemispheric attention networks, superior longitudinal fasciculus II and III, insula and putamen was associated with return of good outcome.</p><p><strong>Conclusions: </strong>These findings underline that in addition to sensorimotor functioning and intact motor tracts, cognitive functioning and spared attentional networks are essential for recovery of everyday use of the affected upper limb after stroke.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839055","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":"Autologous haematopoietic stem cell transplantation in multiple sclerosis: outcomes and predictors from German real-world data.","authors":"Felix Fischbach, Johanna Richter, Miriam Korporal-Kuhnke, Lena K Pfeffer, Paula Starke, Vivien Häußler, Bente Braun, Amanda Keller, Yekta Abbasi, Margarethe Daumen, Katja Lange, Stefanie Reinhardt, Jessica Stockmann, Juliane Brandt, Sandra Sauer, Ina Rudolph, Boris Fehse, Sina Cathérine C Rosenkranz, Tim Friede, Manuel Alexander Friese, Nicolaus Kröger, Norbert Blank, Francis Ayuk, Brigitte Wildemann, Christoph Heesen","doi":"10.1136/jnnp-2025-338129","DOIUrl":"https://doi.org/10.1136/jnnp-2025-338129","url":null,"abstract":"<p><strong>Background: </strong>Autologous haematopoietic stem cell transplantation (aHSCT) represents a treatment option for highly aggressive multiple sclerosis (MS). Here, we report outcome analyses from the two largest German centres performing aHSCT in MS.</p><p><strong>Methods: </strong>In this retrospective analysis, people with (pw) MS who underwent aHSCT between 2007 and 2025 were included. Outcomes comprise no evidence of disease activity (NEDA-3), 3-month confirmed disability changes on the Expanded Disability Status Scale and transplantation-related mortality (TRM). Predictors of treatment response were evaluated according to the European Committee for Treatment and Research in Multiple Sclerosis and the European Society of Blood and Marrow Transplantation consensus criteria.</p><p><strong>Results: </strong>A total of 109 pwMS were included: 55 (50.5%) with relapsing-remitting MS (RRMS), 23 (21.1%) with secondary progressive MS (SPMS) and 31 (28.4%) with primary progressive MS (PPMS). Median follow-up after aHSCT was 20.1 months. Overall, 82.8% (SE 4.9%) of pwMS maintained NEDA-3. PwRRMS had significantly higher NEDA-3 rates (Kaplan-Meier (KM) estimate 91%, SE 5%) than those with SPMS (KM 80.1%, SE 10.5%, p=0.018) or PPMS (KM 70.6%, SE 11.4%, p=0.035). Patients meeting core consensus criteria achieved NEDA-3 more often (KM 94.4%, SE 5.4%) than those meeting the extended criteria (KM 84.4%, SE 8.5%, p=0.199) or those outside the criteria (KM 73.7%, SE 8.8%, p=0.004). In progressive MS, a disease duration of <5 years indicated a potential prediction of NEDA-3 stability. TRM was 0.9% (n=1/109).</p><p><strong>Conclusions: </strong>In this heterogeneous cohort, comprising a substantial proportion of people with progressive MS, aHSCT provided sustained NEDA-3 stability and a marked reduction in inflammatory disease activity, particularly in RRMS, with a potential benefit in progressive MS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839139","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":"Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis.","authors":"Emilio Portaccio, Maria Grazia Aprea, Ermelinda De Meo, Matteo Betti, Ilaria Addazio, Luisa Pasto', Chiara Ballerini, Benedetta Nacmias, Maria Pia Amato","doi":"10.1136/jnnp-2025-338392","DOIUrl":"https://doi.org/10.1136/jnnp-2025-338392","url":null,"abstract":"<p><strong>Background: </strong>In multiple sclerosis (MS), disability accrual can arise from relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). While genetic variants associated with increased MS severity have been identified, little is known on apolipoprotein E (ApoE) gene. This study aims to investigate the impact of the ApoE ε4 allele (ApoE4) on disability accrual in relapsing MS patients.</p><p><strong>Methods: </strong>Patients with relapsing MS, aged <u>></u>18 years, consecutively referred to the MS centre at the University of Florence, Italy, were recruited (n=160). Patients were classified as ApoE4 carriers and non-carriers. The first confirmed disability accrual (CDA) was defined as ≥24-week confirmed disability increase from roving baseline. PIRA was defined as a CDA with absence of relapses <90 days before and <30 days after the onset of disability accrual and confirmation event. The association between APOE4 and type of first CDA was assessed using multivariable Cox proportional hazard regressions.</p><p><strong>Results: </strong>After a follow-up of 12.3±6.3 years, a first CDA occurred in 97 patients (60.6%). PIRA accounted for 58 (59.8%) CDA events in the whole sample and for 7 out of 18 (38.9%) CDA events in APOE4 non-carriers (p=0.045). Indeed, RAW was associated with ApoE4 in the whole sample (HR=3.33, 95% CI 1.53 to 7.27, p=0.002) and in patients with relapses during follow-up (HR=3.60, 95% CI 1.62 to 8.02, p=0.002).</p><p><strong>Interpretation: </strong>Our study underscores the importance of genetic factors such as ApoE4 in MS pathogenesis. The identification of genetic markers associated with specific patterns of disability accrual could unveil mechanisms of damage accumulation and provide new therapeutic targets.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815478","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":"Incidence and prevalence of small fibre neuropathy in the Netherlands: a multiple system estimation study.","authors":"Dennis Kool, Janneke G J Hoeijmakers, Catharina G Faber, Ingemar S J Merkies","doi":"10.1136/jnnp-2025-338181","DOIUrl":"https://doi.org/10.1136/jnnp-2025-338181","url":null,"abstract":"<p><strong>Background: </strong>Small fibre neuropathy (SFN) affects small myelinated Aδ- and unmyelinated C-fibres and causes neuropathic pain and autonomic symptoms. Earlier Dutch estimates, over a decade old, reported a minimum prevalence of 52.95 and an incidence of 11.75 per 100 000 adults. As recognition of SFN has likely increased, this study aimed to estimate the total SFN population in the Netherlands and to provide updated incidence and prevalence rates using a multiple system estimation (MSE) approach.</p><p><strong>Methods: </strong>MSE was used to estimate the total adult SFN population by matching patients from three national databases: the SFN expertise centre, the national SFN registry and the Dutch Neuromuscular Disorders Association. Prevalence was calculated by using total population numbers from Statistics Netherlands, adjusting for mortality with age- and sex-specific survival rates. Annual incidence and prevalence by sex and region were calculated using stratified MSE. Missing diagnosis years in the patient association data were imputed using multiple imputations.</p><p><strong>Results: </strong>The prevalence of SFN in 2024 was estimated at 69.69 and the incidence at 3.55 per 100 000 adults in the general Dutch population, with higher rates in females. Incidence increased over time, particularly among females.</p><p><strong>Conclusions: </strong>This study reveals a higher prevalence than previously reported. The lower incidence compared with previous estimates likely reflects differences in geographic coverage, while the rising trend suggests increasing awareness and recognition of SFN. These findings suggest that SFN represents a larger problem than previously recognised and the burden of SFN emphasises the urgent need for novel therapeutic strategies.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774144","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":"Comparing amyloid immunotherapy with cholinesterase inhibitors for Alzheimer's disease.","authors":"Christopher R S Belder, Nick C Fox","doi":"10.1136/jnnp-2026-338722","DOIUrl":"https://doi.org/10.1136/jnnp-2026-338722","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717083","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":"Tysabri Observational Program (TOP): long-term safety and effectiveness of natalizumab treatment in relapsing-remitting multiple sclerosis over 15 years.","authors":"Helmut Butzkueven, Ludwig Kappos, Heinz Wiendl, Maria Trojano, Tim Spelman, Andres Greco, Zhaonan Sun, Tyler Lasky","doi":"10.1136/jnnp-2025-337367","DOIUrl":"https://doi.org/10.1136/jnnp-2025-337367","url":null,"abstract":"<p><strong>Objective: </strong>This Tysabri Observational Program (TOP) final analysis evaluated the 15-year safety and effectiveness of natalizumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS).</p><p><strong>Methods: </strong>This multinational, real-world observational study assessed natalizumab-associated serious adverse events, annualised relapse rates (ARRs) and disability progression/improvement in patients with RRMS. These outcomes were evaluated in subpopulations receiving short- (1-2 years) versus long-term (≥10 years) natalizumab and in patients who switched from intravenous to subcutaneous (SC) natalizumab formulation. The probability of conversion to non-active secondary progressive multiple sclerosis (SPMS) was assessed in patients who remained on versus discontinued natalizumab after ≥1 year.</p><p><strong>Results: </strong>As of November 2023, TOP enrolled 6319 patients. Median time on natalizumab was 4.13 years. There were no new safety signals after up to 15 years of treatment. Marked, sustained reductions in pretreatment ARR occurred with natalizumab independent of baseline disease indicators (eg, Expanded Disability Status Scale score). On natalizumab, the ARR decreased by 91.5% after 15 years, relative to the year before baseline. At 15.5 years, cumulative probabilities of 24-week confirmed disability progression and improvement were 48.5% and 38.8%, respectively. Long-term natalizumab treatment significantly decreased ARR compared with short-term treatment. Switching from intravenous to SC formulation did not affect ARR after 1 year post-switch. The cumulative probability of converting to non-active SPMS was significantly lower in patients remaining on natalizumab compared with those who discontinued (0.22 vs 0.29, respectively).</p><p><strong>Conclusions: </strong>Follow-up of over 15 years did not reveal new safety concerns and confirmed sustained real-world effectiveness of natalizumab in patients with RRMS (NCT00493298).</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698784","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":"DNA methylation profiling in central nervous system tumours.","authors":"Yosef Ellenbogen, Muhammed Amir Essibayi, Leeor S Yefet, Alexander P Landry, Andrew Ajisebutu, Chloe Gui, Phooja Persaud, Farshad Nassiri, Kenneth Aldape, Gelareh Zadeh","doi":"10.1136/jnnp-2025-337691","DOIUrl":"https://doi.org/10.1136/jnnp-2025-337691","url":null,"abstract":"<p><p>The classification and management of central nervous system (CNS) tumours have undergone substantial transformation over the past two decades, with the recognition of an expanding set of molecularly defined disease entities. Genome-wide DNA methylation profiling has emerged as an important complement to histopathology and targeted molecular testing, providing an epigenetic framework that captures tumour lineage, biological state and large-scale genomic alterations within a single assay. Accumulating evidence demonstrates that methylation-based approaches improve diagnostic precision, resolve biologically heterogeneous entities and support clinically meaningful risk stratification across a broad spectrum of CNS tumours. Methylation profiling has also increasingly been applied to outcome prediction, liquid biopsy-based analyses and the resolution of diagnostically challenging or misclassified cases. In addition, advances in multi-omic integration, computational inference from routinely acquired clinical data and evolving implementation frameworks are extending the clinical applicability of epigenetic profiling. This review synthesises the current state of DNA methylation profiling within the diagnostic and clinical framework of CNS tumours and considers how emerging technologies and practice models are shaping its ongoing integration into neuro-oncological care.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690564","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":"Loss of ambulation in SMA III at the time of disease-modifying treatments: an international study.","authors":"Giorgia Coratti, Francesca Bovis, Valentina Franchino, Jacqueline Montes, Valeria Ada Sansone, Sally Dunaway Young, Chiara Cutrì, Amy Pasternak, Maria Carmela Pera, Marika Pane, Allan Glanzman, Elena Pegoraro, Tina Duong, Elena Sogus, Maria Sframeli, Sonia Messina, Elzo Cavalcante, Maria Cristina Scoto, Adele D'Amico, Rafael Rodriguez-Torres, Tiziana Mongini, Lorenzo Maggi, Michela Coccia, Massimiliano Filosto, Riccardo Zuccarino, Riccardo Masson, Giulia Ricci, Claudio Bruno, Lucia Ruggiero, Veria Vacchiano, Eustachio D'errico, Lorenzo Verriello, Vincenzo Nigro, Gaia Scarpini, Matteo Garibaldi, Mara Turri, Chiara Ticci, Angela Berardinelli, Caterina Agosto, Federica Ricci, Zarazuela Zolkipli-Cunningham, Basil T Darras, John Day, Michio Hirano, Francesco Muntoni, Richard S Finkel, Eugenio Mercuri","doi":"10.1136/jnnp-2025-337505","DOIUrl":"10.1136/jnnp-2025-337505","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by survival motor neuron (SMN1) deletion. While loss of ambulation in SMA type III typically occurs at a median age of 13.4 years, outcomes in the treatment era remain unclear. This study aims to address that gap by investigating ambulation outcomes in individuals with type III receiving disease-modifying therapies.</p><p><strong>Methods: </strong>This retrospective study analysed prospectively collected international data. Time-dependent Cox models assessed the association between treatment initiation and age at loss of ambulation, adjusting for age at onset, sex, SMN2 copies, birth year and country. Treatment was modelled as a time-dependent covariate to avoid immortal time bias. Descriptive analyses used Mann-Whitney U and χ² tests.</p><p><strong>Results: </strong>Among 555 individuals with type III, treatment halved the risk of ambulation loss (HR=0.50), with median loss at 44 vs 32 years in treated and untreated groups. Later onset, ≥4 SMN2 copies and female sex were also protective. The treatment effect was significant in type IIIA (HR=0.34) but not IIIB, with no significant interactions by sex, country or SMN2, though effects remained directionally protective.</p><p><strong>Conclusions: </strong>Treatment in type III reduced the risk of ambulation loss by 50%, extending median ambulation by 12 years, with the greatest benefit in type IIIA. Later onset, female sex and higher SMN2 copy number were also protective but did not modify treatment effect. These findings underscore the value of early treatment and support its broad use to preserve ambulation across clinical subgroups.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"449-455"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}