BMJ Neurology Open最新文献

{"title":"Effectiveness of escalation versus early high-efficacy therapies on progression independent of relapse activity in multiple sclerosis: a Danish nationwide study.","authors":"Eliza Varju, Luigi Pontieri, Mie Reith Mahler, Melinda Magyari","doi":"10.1136/bmjno-2026-001690","DOIUrl":"https://doi.org/10.1136/bmjno-2026-001690","url":null,"abstract":"<p><strong>Background: </strong>The effect of early high-efficacy therapy initiation versus escalation from moderate-efficacy therapy on progression independent of relapse activity (PIRA) in multiple sclerosis remains unclear. This study aimed to compare the treatment strategies on effectiveness against PIRA.</p><p><strong>Methods: </strong>From the Danish MS Registry, treatment-naïve adult patients with multiple sclerosis started on high-efficacy therapies or moderate-efficacy therapies between 2012 and 2022 were included in this nationwide cohort study. Stabilised inverse probability of treatment weights, derived from propensity scores, were applied to balance confounders and to perform weighted Cox and negative binomial regression models. Patients were followed under an intention-to-treat framework until the latest clinical visit before the data extraction date (2 June 2025). The primary outcome was time to first PIRA; the secondary outcome was annualised relapse rate (ARR).</p><p><strong>Results: </strong>Among 3316 patients (594 high-efficacy, 2722 moderate-efficacy) with a median follow-up time of 7.4 years (min-max: 1.5-13.4), we found no statistical difference in time to first progression independent of relapse activity with a HR of 0.89, 95% CI 0.59 to 1.36, p=0.60. Early high-efficacy therapy initiation was associated with a 40% reduction in ARR (incidence rate ratio of 0.60, 95% CI 0.46 to 0.77, p<0.001).</p><p><strong>Conclusions: </strong>In this nationwide cohort study, we found a reduction in relapse activity associated with early initiation of high-efficacy therapies but no statistically significant difference when investigating time to first PIRA. Our findings indicate a therapeutic gap in the current treatment landscape with respect to mitigating PIRA.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001690"},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term functional outcomes and caregiver burden in survivors after decompressive hemicraniectomy for malignant hemispheric infarction: a real-world experience from South India.","authors":"Harikrishna SaiPramodh Veliveli, Angel T Miraclin, Deepti Bal, Selvakumar Selvaganesan, Santhi Thinahar, Kevin Robbie John, George Abraham Ninan, Shalini Nair, Swaminathan G, Krishna Prabhu, Ranjith K Moorthy, Gandham Edmond Jonathan, Aditya Nair, Shaikh Atif Ahmed, Appaswamy Thirumal Prabhakar, Ajith Sivadasan, Vivek Mathew, Mathew Joseph, Sanjith Aaron","doi":"10.1136/bmjno-2026-001665","DOIUrl":"https://doi.org/10.1136/bmjno-2026-001665","url":null,"abstract":"<p><strong>Background: </strong>Malignant hemispheric infarction (MHI) is associated with high early mortality when managed conservatively. Decompressive hemicraniectomy (DHC) improves survival, but long-term functional outcomes and caregiver burden in low-resource settings remain poorly characterised, particularly in India. This study aimed to evaluate long-term outcomes and caregiver burden among MHI survivors undergoing DHC at a tertiary care centre in South India.</p><p><strong>Methods: </strong>We conducted an ambispective study of adult patients who underwent DHC for MHI between 2018 and 2023 and had at least 6 months of follow-up. Functional outcome was assessed using the modified Rankin Scale (mRS) and caregiver burden was evaluated using the Zarit Burden Interview. Subgroup analyses were performed based on infarct lateralisation and timing of surgery. Logistic regression was used to identify predictors of a favourable functional outcome.</p><p><strong>Results: </strong>66 patients (mean age 44±12.8 years; 80% male) were included, with a median follow-up of 2 years (IQR: 1-4). Overall mortality was 24.2% (n=16). Among the 50 survivors, 26 (52.0%) achieved a good functional outcome (mRS ≤3) and 13 (26.0%) achieved an excellent outcome (mRS ≤2). Infarct lateralisation did not significantly influence mortality or functional recovery. Although early surgery and higher admission Glasgow Coma Scale scores were associated with better outcomes in univariate analysis, these factors were not significant in multivariate models. Caregivers of patients with mRS >2 reported significantly higher burden, particularly in emotional, physical and social domains.</p><p><strong>Conclusions: </strong>DHC for MHI results in meaningful long-term survival and functional recovery in selected patients, regardless of hemisphere involvement. However, residual disability imposes a substantial caregiver burden. Stroke care pathways in resource-limited settings should incorporate comprehensive rehabilitation and long-term caregiver support.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001665"},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of double-blind and open-label decline rates in lecanemab and donanemab trials in Alzheimer's disease.","authors":"Alok K Dwivedi, Bruno P Imbimbo, Jesus Abanto, Alberto J Espay","doi":"10.1136/bmjno-2026-001649","DOIUrl":"https://doi.org/10.1136/bmjno-2026-001649","url":null,"abstract":"<p><strong>Background: </strong>Phase 3 trials of the anti-amyloid monoclonal antibodies lecanemab and donanemab in Alzheimer's disease demonstrated modest slowing of cognitive decline over 18 months. Subsequent open-label extensions (OLE) suggested greater long-term benefit based on comparisons with historical untreated cohorts, which are vulnerable to selection and attrition bias.</p><p><strong>Methods: </strong>We simulated longitudinal Clinical Dementia Rating-Sum of Boxes trajectories using mixed-effects models calibrated to reproduce published means, variances and attrition patterns from the Clarity-AD and TRAILBLAZER-ALZ 2 trials, separately for early- and delayed-start cohorts and in combined analyses. Observed annualised slopes were also directly compared between double-blind (DB) and OLE phases. Placebo effects were estimated by comparing DB placebo arms with matched untreated historical cohorts derived from published natural history data.</p><p><strong>Results: </strong>Simulations closely reproduced reported trajectories. In both trials, the early-start cohorts showed significantly faster annualised decline during OLE than during DB treatment (lecanemab ∆=0.53; 95% CI 0.40 to 0.66; donanemab ∆=0.66; 95% CI 0.41 to 0.91), whereas delayed-start cohorts showed no meaningful phase-related differences. OLE decline rates approximated those observed in DB placebo groups. In the lecanemab trial, DB placebo participants declined more slowly than matched untreated controls; decline in the donanemab trial varied by baseline severity.</p><p><strong>Conclusions: </strong>Despite selective retention favouring slower progressors, both lecanemab and donanemab accelerated cognitive decline during OLE phases and paralleled placebo-level declines.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001649"},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap between guidelines and practice: neurologists' readiness for the updated McDonald criteria in Egypt.","authors":"Nesma Am Ghonimi, Jida Al-Mulki, Mohamed E Mahdy","doi":"10.1136/bmjno-2026-001687","DOIUrl":"https://doi.org/10.1136/bmjno-2026-001687","url":null,"abstract":"<p><strong>Background: </strong>The McDonald criteria (MC) are fundamental in diagnosing multiple sclerosis (MS). Despite advancements in diagnosis, misdiagnosis remains a persistent challenge. The 2024 MC revisions incorporate new radiological features (central vein sign (CVS), paramagnetic rim lesions (PRLs)) and biomarkers (kappa free light chain (KFLC)) to enhance diagnostic specificity, even in asymptomatic individuals.</p><p><strong>Objective: </strong>To explore Egyptian neurologists' understanding of and readiness to implement the updated 2024 MC for multiple sclerosis diagnosis.</p><p><strong>Methods: </strong>An exploratory cross-sectional, open online survey was conducted among 143 neurologists in Egypt. A 16-item questionnaire assessed their professional background, MS exposure, attitudes towards the updated MC and access to relevant diagnostic and imaging resources. Domain scores for clinical confidence and knowledge/familiarity were computed, and associations with demographic factors were analysed.</p><p><strong>Results: </strong>Most neurologists (98%) actively managed MS cases, and 83% reported familiarity with the updated MC. Clinical confidence scores were moderate overall, whereas knowledge/familiarity scores were generally higher; the two measures were positively correlated (Spearman ρ = 0.24, p=0.02). Knowledge gaps remained: nearly 62% were unfamiliar with PRLs, and 38% were unaware of the CVS. Resource limitations were notable, with 83% lacking access to KFLC testing and 75% limited to 1.5 T MRI machines.</p><p><strong>Conclusion: </strong>Egyptian neurologists demonstrate strong engagement with the updated MC; however, limited awareness of novel markers and restricted access to essential diagnostic resources (3 T MRI, KFLC) present barriers to their optimal application.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001687"},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicians' decisions about antibiotic treatment in advanced dementia: an international survey.","authors":"João Pedro Lima, Lawrence Mbuagbaw, Manya Prasad, Amit Kumar, Guy Sadeu Wafeu, Romain Bonnet, Thomas Agoritsas, Sheyu Li, Zhanming Liu, Pablo Alonso-Coello, Fábio Akio Nishijuka, Reza Mirza, Caroline Matos Silva, Rajaa Alshanketi, Imtinan Khalid Alsahafi, Alanood Alnuaimi, Anja Fog Heen, Peter J Mattingly, Sheri A Keitz, Agustin Bengolea, Ariel Izcovich, Surbhi Gupta, Priyanka Aggarwal, Jessyca Matos Silva, Lisa Schwartz, Derek K Chu, Gordon Guyatt","doi":"10.1136/bmjno-2026-001692","DOIUrl":"10.1136/bmjno-2026-001692","url":null,"abstract":"<p><strong>Objectives: </strong>In patients living with advanced dementia, the intensity of care during life-threatening infections remains controversial and marked by wide variation in practice. This international survey investigated physicians' and physicians-in-training's management choices for individuals with advanced dementia and the factors associated with those choices.</p><p><strong>Design: </strong>Vignette-based survey.</p><p><strong>Setting: </strong>Twelve countries across five continents.</p><p><strong>Methods: </strong>We administered our vignette-based survey to medical students, residents and physicians. The survey elicited participants' views on whether antibiotics should be administered to an elderly patient with advanced dementia and very poor quality of life, presenting with bacterial pneumonia. We explored factors associated with treatment choices using univariable analysis and multiple logistic regression models.</p><p><strong>Results: </strong>Of the 785 participants (age, mean (SD): 31.1 (11.5) years), one-third (31.2%) resided in the Region of the Americas, 21.9% in Europe, 16.2% in the Eastern Mediterranean region and 17.1% in China. In the univariable analysis, choice to treat was associated with younger age, country/WHO region (African region highest overall, European region lowest overall), stage of medical training (medical student most inclined to treat) and absence of medical assistance in dying (MAiD) legislation. Multivariable analyses provided evidence that country was the variable most strongly associated with the choice to treat with antibiotics (Cameroon, China, Saudi Arabia highest; Norway, Switzerland, Spain lowest), with the presence of MAiD legislation also strongly associated (OR 0.35, 95% CI 0.23 to 0.51). Age (OR 0.82, 95% CI 0.66 to 1.00) and religiosity level (OR 0.93, 95% CI 0.87 to 0.99) showed weaker associations with treatment decisions.</p><p><strong>Conclusion: </strong>Inclination to treat individuals with advanced dementia who develop pneumonia varies greatly between and within jurisdictions. Social factors (in particular country but also presence of MAiD legislation) proved the most prominent associations, with individual characteristics much less influential. These findings underscore the importance of contextual and cultural factors in value-sensitive clinical decisions.</p><p><strong>Registration: </strong>We registered the protocol at Open Science Framework (osf.io/6kfbt).</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001692"},"PeriodicalIF":2.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological complications induced by checkpoint inhibitors: characterising the clinical spectra.","authors":"Anne Merel van Wylick, Martin van den Bent, Bart C Jacobs, Maarten Titulaer, Jeroen Kerstens, Esther Brusse, Ron H J Mathijssen, Daphne W Dumoulin, Astrid A M van der Veldt, Marjolein Geurts","doi":"10.1136/bmjno-2026-001591","DOIUrl":"10.1136/bmjno-2026-001591","url":null,"abstract":"<p><strong>Background: </strong>Timely recognition of immune checkpoint immune-related neurological adverse events (irNAEs) is critical given their potential severity, yet remains challenging due to limited clinical experience. This study investigates clinical presentation and management of irNAEs from a neurological perspective.</p><p><strong>Methods: </strong>We retrospectively identified all patients treated with immune checkpoint inhibitors (ICIs) at Erasmus MC Cancer Institute, Rotterdam, The Netherlands between 2017 and 2024. Patient records were analysed by a neurologist for clinical and treatment of irNAE post-ICI initiation.</p><p><strong>Results: </strong>Of 3176 ICI-treated patients, irNAE was diagnosed in 76 cases (2.4%). Peripheral syndromes occurred in 55 (70%), central in 21 (30%) patients. Classification into distinct disease entities was challenging due to remarkable overlap in affected neurological structures. Median onset of irNAE was 8 weeks after ICI initiation (range 1-104 weeks); 70% developed within 18 weeks. IrNAE-related mortality was 13%, observed only in the first 18 weeks. Fewer non-small cell lung cancer patients developed irNAE (OR, 0.36; 95% CI 0.16 to 0.8; p=0.012) compared with other tumour types. Males (OR, 1.78; 95% CI 1.1 to 2.90; p=0.019) and PD1/CTLA4 combination therapy (OR 2.1, 95% CI 1.28 to 3.46, p=0.004) were associated with increased irNAE incidence. Glucocorticoids were given in 64% of patients; 14% received immunosuppressive therapy beyond steroids. Treatment response varied widely, both clinically and temporally.</p><p><strong>Conclusion: </strong>This retrospective single-centre study confirms irNAEs are infrequent complications of ICI. The distinct symptom profile, with substantial overlap within affected neurological structures, underscores the need for neurological expertise in irNAE care. While most develop within 18 weeks of treatment, late-onset cases occur. Mortality occurred only in early-onset cases.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001591"},"PeriodicalIF":2.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the clinical phenotype associated with an ASXL1 pathogenic variant causing a novel neuromuscular disorder with neurodevelopmental features.","authors":"Dominic Spicer, Kathryn Friend, Bing Wu, Nicholas Chia, Roula Ghaoui","doi":"10.1136/bmjno-2025-001540","DOIUrl":"10.1136/bmjno-2025-001540","url":null,"abstract":"<p><strong>Background: </strong>Germline pathogenic variants in the Additional Sex Combs-Like 1 (<i>ASXL1</i>) gene are associated with the neurodevelopmental Bohring-Opitz syndrome and cancers like Wilms' tumours. Bohring-Opitz syndrome is a phenotypically heterogeneous condition characterised by feeding difficulties, syndromic facial abnormalities, abnormal posturing and developmental delays, and it has only been reported in infant/adolescent patients. There are no reported neuromuscular phenotypes associated with <i>ASXL1</i>.</p><p><strong>Case presentation: </strong>A 71-year-old male proband exhibited congenital facial, extraocular, proximal upper limb and generalised/distal lower limb muscle weakness/wasting. This was associated with dysphagia, childhood motor developmental delay, bilateral upper limb tremor and bilateral pes cavus. He demonstrated some features of Bohring-Opitz syndrome including feeding difficulties, microcephaly, micrognathia and anteverted nares but lacked the characteristic posturing. Muscle imaging demonstrated symmetrical lower limb atrophy. His adult age diagnosis is unique among <i>ASXL1</i>-associated conditions. A genetic diagnosis of the <i>ASXL1</i> variant (c.1210C>T; p.Arg404Ter) was achieved through phenotype-driven genetic neurodevelopmental panel testing given some overlap with neurodevelopmental patients following unsuccessful initial genetic sequencing.</p><p><strong>Conclusions: </strong>This expands the phenotype of <i>ASXL1</i> pathogenic variants with a novel and distinct neuromuscular presentation. This case demonstrates the importance of thorough and accurate phenotype for unusual presentations, as this diagnosis was missed through routine genetic testing.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001540"},"PeriodicalIF":2.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rising burden of Alzheimer's disease and other dementias in Sierra Leone, 1990-2023: analysis of Global Burden of Disease 2023 estimates.","authors":"Mohamed B Jalloh, Gibrilla Fadlu Deen, Omar Bah, Ishmaela Bah, Abdul Aziz Suma, Onome T Abiri, Melvina C Thompson, Edries Tejan, Fatima Jalloh, Foray Mohamed Foray, Monalisa M J Faulkner, Bamba Gaye","doi":"10.1136/bmjno-2025-001507","DOIUrl":"10.1136/bmjno-2025-001507","url":null,"abstract":"<p><strong>Background: </strong>Dementia is an increasing cause of disability and mortality worldwide. Primary dementia surveillance data remain limited in many low-income settings, including Sierra Leone.</p><p><strong>Objective: </strong>To describe trends in Burden of Disease (GBD) 2023 modelled estimates for Alzheimer's disease and other dementias in Sierra Leone from 1990 to 2023, and to decompose the change in estimated deaths into demographic and age-specific mortality components.</p><p><strong>Methods: </strong>We conducted a secondary analysis of GBD 2023 estimates for the cause category 'Alzheimer's disease and other dementias' in Sierra Leone. We analysed estimated counts and age-standardised rates for prevalence, deaths, years of life lost, years lived with disability and disability-adjusted life years (DALYs) stratified by age and sex. Temporal trends were described with log-linear regression to estimate annual per cent change, and a three-component decomposition attributed changes in deaths to population growth, ageing and age-specific mortality.</p><p><strong>Results: </strong>GCD 2023 estimated that dementia deaths in Sierra Leone increased from 188 in 1990 to 474 in 2023, an absolute increase of 286 estimated deaths (152% relative increase). Estimated DALYs increased from 3703 to 7440. The modelled age-standardised death rate rose 26.8% (16.3 to 20.7 per 100 000) and the age-standardised DALY rate 13.4% (293.7 to 333.2 per 100 000). Estimated prevalent cases increased from 5647 to 8887, while the modelled age-standardised prevalence rate declined from 430.7 to 404.0 per 100 000 population. The log-linear annual percentage change was +1.02% for age-standardised death rates, +0.60% for DALY rates and -0.18% for prevalence rates. Decomposition attributed 62% of the increase in estimated deaths to changes in age-specific mortality, 30% to population growth and 8% to population ageing.</p><p><strong>Conclusions: </strong>GBD 2023 estimates show a rising absolute burden of dementia in Sierra Leone, against a background of limited local surveillance and mortality ascertainment.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001507"},"PeriodicalIF":2.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case of Aicardi-Goutières syndrome diagnosed in adulthood on whole-genome sequencing.","authors":"Lewis Cobb, Jayant Kumar, Amit Roy, Sarah Walsh, Una-Marie Sheerin","doi":"10.1136/bmjno-2025-001407","DOIUrl":"10.1136/bmjno-2025-001407","url":null,"abstract":"<p><p><b>Background</b>: Aicardi-Goutières syndrome (AGS) is a neurogenetic leukoencephalopathy that typically manifests within the first 6 months of life. Classically, AGS presents with an early encephalopathic episode characterised by feeding difficulties, irritability and psychomotor regression or delay. Cutaneous lesions affecting the extremities and epilepsy are common, with symptoms usually evolving over weeks to months before stabilising. Milder phenotypes have been described, often demonstrating relative preservation of language and cognitive function. <b>Case presentation</b>: Here, we report a case of a 31-year-old woman with compound heterozygous variants in the <i>ADAR</i> gene: (GRCh38) NM_001111.4:c.577C>G p.(Pro193Ala) and (GRCh38) NM_001111.4:c.1111_1112del p.(Ser371Cysfs*3), consistent with AGS. The developmental history revealed normal early motor milestones. At age 3, she developed progressive ataxia and hypotonia. Over time, she exhibited spasticity, dystonia and learning difficulties, along with significant cardiac valvular calcification. <b>Conclusions</b>: The patient was recently referred for consideration of treatment with baricitinib, a selective JAK1/JAK2 inhibitor. This case underscores the importance of considering AGS in individuals with non-classical presentations, particularly when extracerebral calcification is a notable feature.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001407"},"PeriodicalIF":2.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in cerebrovascular reserve function assessment for moyamoya disease.","authors":"Siyu Chen, Tianrui Yu, Yuanyuan Xiang, Liang Chen, Hao Liu, Xuezhi Chen, Xianming Cao, Yanghang Chen, Manqing Zhang, Xiaoping Yin, Zhiying Chen","doi":"10.1136/bmjno-2025-001526","DOIUrl":"10.1136/bmjno-2025-001526","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a rare cerebrovascular disease characterised by gradual progressive stenosis and occlusion of the terminal internal carotid arteries, anterior cerebral arteries and proximal middle cerebral arteries bilaterally. This pathology leads to the formation of a compensatory and fragile collateral vascular network at the brain's base. With disease progression, MMD may result in ischaemic or haemorrhagic stroke. However, the lack of reliable and effective methods to assess disease progression leaves many patients at high risk of stroke without timely clinical intervention. Therefore, determining the disease course and assessing stroke risk are critical. Cerebrovascular reserve (CVR) reflects the ability of brain tissue to increase blood flow under stress. CVR evaluation assists clinicians in understanding MMD severity, guiding therapeutic decisions and determining prognosis. This narrative review analyses recent literature, highlights the advantages and disadvantages of various CVR assessment techniques, and discusses the interplay between CVR and MMD. In addition, it examines the role of CVR in evaluating disease progression and associated treatments.</p>","PeriodicalId":52754,"journal":{"name":"BMJ Neurology Open","volume":"8 2","pages":"e001526"},"PeriodicalIF":2.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}