Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Respiratory function in Becker muscular dystrophy: a comprehensive longitudinal study.","authors":"Pietro Riguzzi, Emma Grover, Marianela Schiava, Meredith K James, Jordi Diaz-Manera, Giorgio Tasca, John Bourke, Holly Borland, Dionne Moat, Maha Elseed, Jassi Michell-Sodhi, Carla Bolaño-Díaz, Karen Wong, Ariele Barreto Haagsma, Emma Robinson, Tara Reeves, Peter Waldock, Elizabeth Harris, Michelle McCallum, Giulio Gadaleta, Elena Pegoraro, Luca Bello, Ben Messer, Robert Muni-Lofra, Volker Straub, Chiara Marini Bettolo, Michela Guglieri","doi":"10.1136/jnnp-2025-337953","DOIUrl":"10.1136/jnnp-2025-337953","url":null,"abstract":"<p><strong>Background: </strong>Becker muscular dystrophy (BMD) is a rare X-linked neuromuscular disorder predominantly affecting males. While respiratory function has been characterised in small cohorts over limited time frames, comprehensive long-term longitudinal data remain lacking, as do established care guidelines to inform respiratory surveillance in BMD.</p><p><strong>Methods: </strong>In this retrospective analysis, we present a large longitudinal analysis of respiratory function in patients with BMD, based on 1360 spirometry measurements from a single-centre cohort of 152 patients. Analysed assessments spanned paediatric to adult ages (3.4-86.3 years), with a mean follow-up duration of 11 years per patient.Linear mixed-effects models were used to study longitudinal changes in respiratory function.</p><p><strong>Results: </strong>Respiratory decline in BMD appears gradual and variable, typically not affecting children (<18 years of age).Respiratory support was infrequent (11.2%), always non-invasive and limited to nocturnal use.Loss of ambulation emerged as a strong predictor of faster decline in forced vital capacity percentage of predicted (FVC%) (estimate -0.58%/year, p=0.002), with the requirement for assistive walking devices marking a critical transitional stage.Upper limb function, assessed via the PUL 2.0 entry item, correlated significantly with FVC%, particularly among non-ambulant patients (rho=0.60, p=0.02). Cardiac involvement showed a limited effect on respiratory function, likely driven by patients with more advanced cardiomyopathy.No consistent genotype-phenotype correlations were observed.</p><p><strong>Conclusion: </strong>These findings provide important evidence to inform clinical management, supporting the recommendation of individualised respiratory monitoring strategies and contributing to the design and interpretation of clinical trials in BMD.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"456-463"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317049","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}

{"title":"Appropriate use recommendations in search of reimbursement: lecanemab and the UK dilemma.","authors":"Antonio Ancidoni","doi":"10.1136/jnnp-2025-337659","DOIUrl":"10.1136/jnnp-2025-337659","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"371"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751871","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":"Epigenetic ageing and the risk of Parkinson's disease.","authors":"Xiaojing Peng, Mario H Flores-Torres, Marianna Cortese, Cheng Peng, Albert Y Hung, Michael Schwarzschild, Alberto Ascherio, Kjetil Bjornevik","doi":"10.1136/jnnp-2025-336802","DOIUrl":"10.1136/jnnp-2025-336802","url":null,"abstract":"<p><strong>Background: </strong>Estimators of biological age, such as epigenetic clocks, are promising biomarkers for neurological disorders where the risk significantly increases with age, such as Parkinson's disease (PD). The purpose of this study was to prospectively investigate whether epigenetic age acceleration can predict PD risk, age at PD onset and time to phenoconversion.</p><p><strong>Methods: </strong>We conducted a prospective, nested case-control study within the Nurses' Health Study, including participants who provided two blood samples before being diagnosed with PD. DNA methylation profiles were obtained from 75 individuals who developed PD, 79 individuals who developed prodromal features suggestive of PD and 154 age-matched controls. We estimated epigenetic age acceleration using six different epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE and the cortical epigenetic clock) and assessed their associations with PD risk, age at PD onset and time to PD onset.</p><p><strong>Results: </strong>Epigenetic age acceleration was not consistently associated with a higher PD risk, using estimates of biological ageing neither in the first sample (collected a median of 19 years before PD onset) nor in the second sample (collected a median of 8 years before PD onset). These results remained similar in multivariable models adjusted for smoking status, physical activity, body mass index, caffeine intake, alcohol intake and Mediterranean diet score. Furthermore, epigenetic age acceleration was not associated with earlier age at PD onset or time to PD phenoconversion.</p><p><strong>Conclusions: </strong>In our study, epigenetic clock-based biomarkers do not reliably predict PD risk, age at PD onset or time to PD phenoconversion.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"385-392"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863183","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}

{"title":"Genetic subtypes associated with multiple sclerosis severity and response to treatment.","authors":"Karim L Kreft, Nienke J Mekkes, Emeka Uzochukwu, Sam Loveless, Ray Wynford-Thomas, Katharine Elizabeth Harding, Mark Wardle, Peter Holmans, J William L Brown, Michael Lawton, Emma Clare Tallantyre, Inge R Holtman, Neil P Robertson","doi":"10.1136/jnnp-2025-337337","DOIUrl":"10.1136/jnnp-2025-337337","url":null,"abstract":"<p><strong>Background: </strong>Predicting response to treatment and long-term disability in multiple sclerosis (MS) remains challenging. In other complex diseases, combining genetic risk variants has enabled the detection of relevant clinical endophenotypes associated with important outcomes, but this strategy has never been applied to MS.</p><p><strong>Methods: </strong>We applied unsupervised hierarchical clustering to genomic risk scores in a prospective Welsh MS cohort (n=1455) and replicated the findings in the postmortem Netherlands Brain Bank (NBB) MS (NBB-MS) cohort (n=272). Disease progression was assessed using survival analysis to determine the time to Expanded Disability Status Scale (EDSS) milestones.</p><p><strong>Results: </strong>Three genomic clusters were identified, each with similar genetic profiles. Baseline demographics did not differ between clusters. Welsh patients in cluster 1 attained EDSS 6 and EDSS 8 significantly later than clusters 2 and 3 (by 6 years, p=3×10^-3 and 13 years, p=0.02, respectively). These findings were replicated in the NBB-MS cohort (6-year delay to EDSS 6 for cluster 1 vs 2, p=0.04). Genomic clustering independently predicted disease progression (HRs 1.3-2.0, all p<0.05), beyond established risk factors. Clusters 2 and 3 showed a greater annual increase in T2 lesion load on serial MR imaging (p=0.04). In cluster 2, patients receiving disease-modifying treatments had delayed progression to EDSS 6 (p=3×10^-³), while no such benefit was observed in clusters 1 or 3. Cluster 2 patients also had earlier onset of symptoms, including dysphagia (p=0.02) and spasticity (p=8×10^-⁴) in the NBB-MS cohort.</p><p><strong>Conclusions: </strong>Genetic clustering reveals clinically meaningful MS subtypes with distinct prognoses and treatment responses, highlighting its potential role in precision medicine for MS management.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"413-421"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989620","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":"Physical activity decreases the likelihood of peripheral neuropathy in persons with diabetes.","authors":"Evan L Reynolds, David Russman, Georgios Baskozos, Stephanie Eid, Eva L Feldman, David L H Bennett, Brian C Callaghan","doi":"10.1136/jnnp-2025-337592","DOIUrl":"10.1136/jnnp-2025-337592","url":null,"abstract":"<p><strong>Background: </strong>Clinical guidelines recommend physical activity (PA) to prevent diabetic peripheral neuropathy (DPN). However, these recommendations lack specificity in terms of optimal PA intensity and duration. We aimed to determine associations between PA, DPN and painful DPN (pDPN).</p><p><strong>Methods: </strong>In a cross-sectional study of persons with diabetes, PA was assessed with a wrist-worn accelerometer, recording time spent at different milli-gravity (mG) intensity levels with categories set as light (45-100 mG), moderate (100-400 mG), or vigorous (>400 mG). DPN was defined by Michigan Neuropathy Screening Instrument questionnaire and pDPN by presence of bilateral foot pain.</p><p><strong>Results: </strong>In 2878 participants (mean (SD) age: 58.6 (7.1) years, 39.1% female), time spent above 75 mG decreased DPN odds (OR, 95% CI) (0.97, 0.95 to 0.997). Further, more time spent performing moderate (0.95, 0.91 to 0.99) or vigorous (0.40, 0.22 to 0.70) PA decreased DPN odds. Overall, PA did not affect pDPN; however, among females, more time spent above 50 mG (0.92, 0.87 to 0.98) decreased pDPN odds.</p><p><strong>Conclusions: </strong>Increased PA decreased DPN likelihood, and in females, pDPN likelihood. Whether lack of PA occurs secondary to the presence of DPN or contributes to DPN remains to be determined.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"464-468"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355489","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":"Multicentre validation of a patient-reported outcome measure for functional movement disorders.","authors":"Rosa Michaelis, Leonie Hagedorn, Anne Weissbach, Christoph van Riesen, Kirsten E Zeuner, Tamara Schmidt, Christina Bolte, Felix Bernsdorff, Maximilian J Löw, Carl A Gless, Annemarie Reincke, Desiree Sykora, Kathrin LaFaver, Alexander C Lehn, Christoph Kleinschnitz, Corinna Seliger, Stoyan Popkirov","doi":"10.1136/jnnp-2025-337168","DOIUrl":"10.1136/jnnp-2025-337168","url":null,"abstract":"<p><strong>Background: </strong>No disorder-specific patient-reported outcome measure (PROM) has yet been validated for functional movement disorders (FMDs), leaving a critical gap in clinical care and research.</p><p><strong>Objective: </strong>To validate the FMD questionnaire (FMDQ) in a prospectively recruited sample through a multicentre study.</p><p><strong>Methods: </strong>Confirmatory factorial analysis (CFA) tested the assumed structure of the questionnaire with factors reflecting severity of motor symptoms, impairment of everyday activities, impact of non-motor symptoms and impairment of social functioning. Internal consistency and floor/ceiling effects were examined. The 36-item short form health survey (SF-36), patient health questionnaire-15 (PHQ-15), the fatigue assessment scale (FAS) and a clinician-rated scale corresponding to motor symptom items of the FMDQ (FMDQ-CR) were used to test criterion and construct validity. The minimally clinically important difference (MCID) was assessed through distribution-based and anchor-based methods in a convenience sample of patients with follow-up assessments.</p><p><strong>Results: </strong>Complete datasets from 157 patients were analysed; follow-up assessments were available from 30 patients. CFA confirmed that a four-factor model provides a better fit to the data compared with a more restrictive one-factor model. Internal consistency was appropriate for all factors/subscales. No floor or ceiling effects were detected. Criterion and content validity were supported by significant correlations with respective SF-36 subscores, PHQ-15, FAS and FMDQ-CR. Anchor-based MCID was estimated at 8 to 20 points, with the central value aligning with the distribution-based MCID of 12 points (8% of the total score range).</p><p><strong>Conclusions: </strong>The FMDQ is a psychometrically robust PROM, making it a useful tool for clinical practice and treatment trials.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"431-437"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113139","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}

{"title":"Incidence of cerebral cavernous malformations among adults in Scotland: a prospective, population-based study.","authors":"Abel Clemens Adriaan Sandmann, Jonathan M Coutinho, Dagmar Verbaan, William Peter Vandertop, Philip Michael White, Rustam Al-Shahi Salman","doi":"10.1136/jnnp-2025-338343","DOIUrl":"https://doi.org/10.1136/jnnp-2025-338343","url":null,"abstract":"<p><strong>Background: </strong>Information about the incidence of cerebral cavernous malformations (CCM) is sparse and the effect of increasing MRI availability is uncertain. Our objective was to assess the incidence of symptomatic and incidental CCM over time.</p><p><strong>Methods: </strong>This prospective, population-based study used multiple overlapping sources of case ascertainment to identify all adults aged ≥16 years who were newly diagnosed with CCM using brain MRI or pathology in Scotland between 1 January 1999 and 31 December 2003 or 1 January 2006 and 31 December 2010 inclusive. Crude, age-stratified, sex-stratified and symptomatic versus incidental CCM incidence rates were calculated using Scottish mid-year population estimates.</p><p><strong>Results: </strong>The crude incidence for 300 newly diagnosed CCM cases (median age 44 years, 141 (47%) men) was 0.72 (95% CI 0.64 to 0.80) per 100 000 adults per year, with similar rates for men and women. The incidence of symptomatic CCM was higher than that of incidentally detected CCM (0.40 (0.34 to 0.47) versus 0.31 (0.26 to 0.37), p=0.028). Between 1999-2003 and 2006-2010, there were statistically non-significant increases in symptomatic and incidental incidence of CCM (0.36 (0.28 to 0.45) to 0.44 (0.36 to 0.54), p=0.18; 0.30 (0.23 to 0.38) to 0.33 (0.26 to 0.41), p=0.59). The estimated probability of becoming symptomatic for people with asymptomatic CCM was 0.25% (0.22%-0.29%) per year. Overall incidence increased with age, adjusted for year of diagnosis and sex (adjusted incidence rate ratio 1.09 (1.01 to 1.17) per decade increase, p=0.019).</p><p><strong>Conclusions: </strong>The incidence of symptomatic CCM exceeded that of incidentally discovered CCM; however, no significant change was observed over time. Approximately 1 in 400 people with asymptomatic CCM become symptomatic annually. These findings can help plan healthcare service delivery and research study recruitment.</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":"147690596","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":"Diffusivity anisotropy signature of slowly expanding lesions predicts progression independent of relapse activity in multiple sclerosis.","authors":"Alberto Calvi, Francesc Vivó Pascual, Elisabeth Solana, Elisabet Lopez-Soley, Baris Kanber, Salut Alba-Arbalat, Maria Sepulveda, Eugenia Martínez-Hernández, José Maria Cabrera-Maqueda, Elianet Fonseca, Santiago Medrano-Martorell, Albert Saiz, Yolanda Blanco, Pablo Villoslada, Ferran Prados Carrasco, Eloy Martinez-Heras, Sara Llufriu","doi":"10.1136/jnnp-2025-335884","DOIUrl":"10.1136/jnnp-2025-335884","url":null,"abstract":"<p><strong>Background: </strong>Slowly expanding lesions (SELs) in multiple sclerosis (MS) are markers of chronic active lesions and seem to trigger disability. This study aimed to analyse spatial features of SELs through diffusion MRI and their clinical impact on progression independent of relapse activity (PIRA).</p><p><strong>Methods: </strong>An observational study of MS subjects prospectively followed since 2011; inclusion required at least three longitudinal T1/T2-weighted and diffusion-weighted MRIs. Subjects followed clinical assessments, using Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale. At MRI, lesions were categorised using non-linear deformation as definite or possible SELs, and non-SELs. Fractional anisotropy (FA) was extracted from each lesion core and perilesional area. Differences in FA values across core and perilesional areas by SEL category were assessed using the Mann-Whitney test. Associations with PIRA and clinical outcomes were evaluated using mixed-effects, logistic and Cox regression models.</p><p><strong>Results: </strong>130 subjects underwent MRI (median 25 months) and clinical assessments (median follow-up 9.2 years), of which 29 (22%) developed PIRA. Of 4811 lesions, 8% were definite SELs. Definite SELs exhibited FA decline over time in core and perilesional areas compared with other lesions. Longitudinal core FA reductions within definite SELs were associated with worse MSFC z-score evolution (β=0.03, 95% CI 0.01 to 0.05, p=0.003), higher odds for PIRA (OR=0.01, 95% CI 0.01 to 0.12, p=0.001) and predicted faster time to reach first PIRA event (HR=0.03, 95% CI 0 to 0.49, p=0.015).</p><p><strong>Conclusions: </strong>Definite SELs show distinct greater microstructural damage and are associated with PIRA, making their FA signature a potential predictor of MS progression.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"405-412"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957674","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}

{"title":"Biologic therapy and brain atrophy in neuromyelitis optica: a Japanese-German longitudinal MRI study.","authors":"Hiroki Masuda, Lina Anderhalten, Masahiro Mori, Tadashi Shiohama, Norihide Maikusa, Shigeki Hirano, Akiyuki Uzawa, Mayumi Muto, Ryohei Ohtani, Tomohiko Uchida, Reiji Aoki, Hitomi Kitagawa, Yoshiyuki Hirano, Friedemann Paul, Satoshi Kuwabara","doi":"10.1136/jnnp-2025-338166","DOIUrl":"https://doi.org/10.1136/jnnp-2025-338166","url":null,"abstract":"<p><strong>Background: </strong>Differences in brain atrophy rates between patients with aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder (AQP4Ab+NMOSD) and healthy controls (HCs), as well as the impact of biologic agents (BIO) on brain atrophy, have not been fully examined.</p><p><strong>Methods: </strong>In total, 72 patients with AQP4Ab+NMOSD identified at Chiba University Hospital or in the Berlin Registry of Neuroimmunological Entities (Chiba, 63; Berlin, 9) and 52 age-matched and sex-matched HCs (Chiba, 47; Berlin, 5) were included. Only patients without relapses between the baseline and follow-up MRI scans were included. Regional brain volumes were normalised to the intracranial volume. Patients who continuously used BIOs or non-BIO preventive treatments between the two MRI scans were assigned to the BIO or non-BIO subgroups, respectively. We applied a longitudinal combined association test to correct for MRI scanner differences.</p><p><strong>Results: </strong>Patient age and the interval between MRI scans did not differ between the groups. The NMOSD group exhibited a lower whole-brain volume than the HC group at follow-up (p<0.001) and a significantly higher whole-brain atrophy rate (p=0.009). Patients with smaller subcortical grey matter (SGM) volumes at follow-up MRI exhibited greater clinical disability (ρ = -0.27, p=0.022). In the BIO subgroup, early initiation of treatment (p=0.013) and a higher relative duration of BIO exposure (p=0.028) were associated with lower annualised SGM atrophy rates.</p><p><strong>Conclusions: </strong>This study suggested progressive silent brain atrophy in patients with AQP4Ab+NMOSD and that early BIO initiation might prevent the progression of brain atrophy.</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":"147690581","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":"Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis.","authors":"Marcus Koch, Jop Mostert, Eva M Strijbis, Miguel D'Haeseleer, Øivind Torkildsen, Jacynthe Comtois, Pavle Repovic, Bernard M J Uitdehaag, Joep Killestein, Tarrant Mcpherson, Gary Cutter","doi":"10.1136/jnnp-2025-337940","DOIUrl":"10.1136/jnnp-2025-337940","url":null,"abstract":"<p><strong>Background: </strong>Phase 2 clinical trials in primary progressive multiple sclerosis (PPMS) often use MRI brain volume measures as their primary endpoint. Here, we investigate the longitudinal association between change in MRI outcomes and change in disability over 2 years of follow-up in a large and well-characterised PPMS trial dataset.</p><p><strong>Methods: </strong>Using the dataset from PROMISE (n=943, mean age of 58.0 years, mean Expanded Disability Status Scale (EDSS) 5.0, and mean disease duration of 10.5 years at baseline), a phase 3 trial of glatiramer acetate in PPMS, we described the change in MRI and disability measures during follow-up and used multivariable logistic regression models to investigate whether change in four MRI outcomes (grey matter volume, white matter volume, brain fraction and total burden of disease) was associated with seven measures of clinical disability worsening (including the EDSS, Timed 25 Foot Walk, Nine-Hole Peg Test and Paced Auditory Serial Addition Test).</p><p><strong>Results: </strong>We found only weak and inconsistent associations between change in MRI and physical and cognitive outcome measures over 2 years of follow-up. Change in MRI measures in year 1 of the trial did not predict change in physical nor cognitive disability in year 2.</p><p><strong>Discussion: </strong>The association of the investigated volumetric MRI measures and clinical disability outcomes was noticeably weak and inconsistent. Our findings question the suitability of brain volume loss and lesion burden accumulation as functionally relevant trial endpoints in PPMS and inform the design and interpretation of clinical trials in PPMS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":"97 5","pages":"422-430"},"PeriodicalIF":7.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690616","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}