BACKGROUND:Childhood-onset epilepsy has been linked to poor school performance but limited evidence exists for long-term educational achievement. We examined educational achievement from adolescence into adulthood in individuals with childhood-onset epilepsy compared with the general population. METHODS:In this nationwide population-based cohort study using Danish registers, we included 1 195 138 individuals born between 1987 and 2005 and followed through 2023. Epilepsy before age 15 years was identified from hospital diagnoses and antiseizure medication prescriptions (n=11 758). Individuals with epilepsy were matched on sex and age to reference individuals without epilepsy, with additional propensity score matching on perinatal and parental factors. Outcomes included completion of primary school, ninth grade mean grades and attainment of higher educational levels. Adjusted ORs (aORs), mean grade differences and adjusted incidence rate ratios were estimated using multivariable regression models. Educational trajectories were assessed from age 15 to 35 years. RESULTS:Compared with reference individuals, those with epilepsy had higher odds of not completing primary school (aOR 3.0, 95% CI 2.8 to 3.1) and lower grades in mathematics (-0.9, 95% CI -0.9 to -0.8) and language (-0.6, 95% CI -0.6 to -0.5). Educational attainment rates were reduced by 50%-56% across all higher levels, and only 9.3% of individuals with epilepsy attained the highest educational level versus 19.5% of matched reference individuals by age 35 years. CONCLUSIONS:Childhood-onset epilepsy was associated with significantly lower primary school completion rates, grades and long-term educational attainment. Targeted assessment of academic capacity, interventions and support are needed to optimise outcomes for young people with epilepsy.
BACKGROUND:Published cases of iatrogenic cerebral amyloid angiopathy (iCAA) are increasing; however, their geographic distribution and age-related clinical spectrum have not been systematically characterised. We aimed to characterise the published evidence, including Japan's contribution and differences in presentation by age. METHODS:A scoping review of published iCAA cases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA). We searched MEDLINE, Scopus and Ichushi-Web-a major Japanese medical literature database-from database inception to 31 January 2026. Reports were screened using broad clinical and exposure compatibility criteria, and included cases were retrospectively classified according to the revised Queen Square framework. We summarised the global distribution and clinical profiles of published cases; comparisons of cases reported from Japan versus other countries and onset before versus at or after 55 years were exploratory. RESULTS:57 reports describing 94 cases were included. Japan contributed the largest number of published cases although case counts cannot estimate incidence. The median age at first presentation and first exposure was 42 and 4 years, respectively; the median latency was 36 years. Cranial surgery was the main exposure event, with cadaveric dura mater identified in 44 cases. Acute intracerebral haemorrhage (ICH) was the first presentation in 58 cases. Among cases with older onset (≥55 years), acute ICH was less frequent at presentation. CONCLUSIONS:Published iCAA cases were most frequently reported from Japan; however, ascertainment and publication biases preclude geographic incidence comparisons. iCAA may present after age 55 and without acute ICH, supporting systematic exposure-history ascertainment and internationally coordinated registry-based surveillance.
BACKGROUND:Ofatumumab and ocrelizumab are widely used high-efficacy anti-CD20 therapies for relapsing-remitting multiple sclerosis (RRMS), but direct comparative evidence remains limited. We aimed to compare their effectiveness in routine clinical practice. METHODS:We conducted an observational cohort study emulating a target trial using data from the MSBase and Observatoire Français de la Sclérose en Plaques registries (January 2021 to December 2024). Adults with RRMS initiating ofatumumab or ocrelizumab were included. Patients were matched 1:1 using propensity scores. Primary outcomes were annualised relapse rate (ARR) and time to first relapse. Secondary outcomes included time to confirmed disability progression (CDP), progression independent of relapse activity (PIRA), confirmed disability improvement (CDI), MRI activity and treatment discontinuation. Negative binomial and Cox regression models were applied. RESULTS:A total of 5288 patients were matched with a median follow-up of 1.2 years for ofatumumab and 1.4 years for ocrelizumab. ARR was 0.07 (95% CI 0.05 to 0.08) with ofatumumab and 0.04 (0.03 to 0.05) with ocrelizumab, corresponding to an ARR ratio of 1.75 (1.43 to 2.13). Ofatumumab was associated with a lower risk of CDP (HR 0.66; 0.49 to 0.87) and PIRA (0.53; 0.39 to 0.73), but a lower probability of CDI (0.76; 0.60 to 0.96). No significant differences were observed in MRI activity or treatment discontinuation. CONCLUSIONS:Both therapies were highly effective in a large cohort of patients with RRMS, with very low relapse or CDP rates. Ofatumumab was associated with slightly greater disability control, while ocrelizumab more effectively suppressed relapses. These differences were modest, and their clinical relevance requires further evidence and should be interpreted with caution.
BACKGROUND:The role of physical activity in the risk of amyotrophic lateral sclerosis (ALS) is debated. It is also unclear whether the association differs in people at high genetic risk of ALS. METHODS:The strength and shape of the association between self-reported and device-measured physical activity and incident diagnosis of ALS in the UK Biobank cohort was analysed using Cox regression, adjusting for potential confounders. Cubic splines were used to assess non-linearity. Analyses were performed in the entire cohort and restricted to those with increased genetic risk due to C9ORF72 expansion carriage or C-allele homozygosity at rs12608932 in UNC13A. RESULTS:Among 384 836 participants with valid questionnaire data, the median age at recruitment was 57.0 years (IQR 50.0-63.0) and median follow-up was for 14.0 years (IQR 13.3-14.6), with 541 incident diagnoses of ALS. Higher self-reported physical activity was associated with a lower risk of ALS (HRhigh vs low=0.77, 95% CI 0.61 to 0.96). The relationship was non-linear, with lowest risk in those in the mid-range self-reported activity. Higher overall device-measured activity was also associated with a lower risk of ALS (HRper 1SD = 0.75, 95% CI 0.58 to 0.97, n=96 570, 98 ALS events) but with a linear dose-response relationship. The association of physical activity with ALS was similar in individuals with C-allele homozygosity at rs12608932 in UNC13A and directionally consistent but not statistically significant in C9ORF72-HRE carriers (n=535, 56 ALS events). CONCLUSION:Higher self-reported and device-measured overall physical activity were associated with a lower risk of ALS overall, but with a potentially non-linear dose-response relationship.
BACKGROUND:Epstein-Barr virus (EBV) is strongly implicated in the development of multiple sclerosis (MS) but whether EBV-related immune responses are also relevant for disease progression after diagnosis remains unclear. We investigated whether Epstein-Barr nuclear antigen 1 (EBNA1) antibody levels are associated with disability progression in MS and whether this association is modified by human leucocyte antigen (HLA)-A*02:01 and HLA-DRB1*15:01. METHODS:We analysed 5706 patients with MS from two population-based Swedish studies with longitudinal follow-up in the Swedish MS registry. EBNA1 IgG levels were analysed as a continuous variable, expressed per one SD increase. The primary outcome was confirmed disability worsening (CDW). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Effect modification by HLA-A*02:01 and DRB1*15:01 was assessed using interaction terms and stratified analyses. Secondary and sensitivity analyses included dichotomisation of EBNA1 levels, alternative progression outcomes, delayed-entry models and treatment-related analyses. RESULTS:Higher EBNA1 antibody levels were associated with a reduced risk of CDW among individuals carrying both A*02:01 and DRB1*15:01 (HR 0.87, 95% CI 0.81 to 0.93), whereas associations were weaker or absent in other HLA strata. Findings were similar in secondary and sensitivity analyses. CONCLUSION:Our findings suggest that EBV-related antibody responses may have prognostic relevance for MS progression in specific genetic contexts, highlighting the importance of host-virus interactions beyond disease onset.
BACKGROUND:To investigate whether exposure to pet hamsters may act as a potential trigger for autoimmune cerebellar ataxia (ACA). METHODS:We conducted a hospital-based case-control study based on our institutional ACA cohort. 57 patients were enrolled in the ACA group and 67 age-matched and sex-matched patients with other autoimmune central nervous system disorders served as controls. Clinical and paraclinical data were collected. Exposure to hamsters and other animals was defined as daily or near-daily contact for at least 2 months. RESULTS:Hamster exposure was significantly more common in the ACA group than in controls (56.1% vs 4.5%, p<0.001; adjusted OR 38.46, 95% CI 10 to 142.86, p<0.001), whereas exposure to other animals did not differ between groups. Among patients with ACA with hamster exposure, the median interval from contact to ataxia onset was 12 months and 11 patients had a history of hamster bites. Compared with patients with ACA without hamster contact, those with hamster exposure more frequently presented with pyramidal signs, diplopia and peripheral neuropathy/radiculopathy, together with higher cerebrospinal fluid (CSF) white blood cell counts, protein concentrations and positivity rates for oligoclonal bands. CSF pathogen testing was negative in all subjects. Neuronal autoantibodies were detected in nine patients with ACA with hamster exposure. HLA-A*24:02 and HLA-B*15:01 showed nominal correlations with hamster exposure, but these did not remain significant after Benjamini-Hochberg false discovery rate correction. CONCLUSIONS:Pet hamster exposure may be a risk factor for ACA. Hamster-associated ACA showed distinctive clinical and CSF inflammatory features. These findings support pet hamster exposure as a novel potential environmental trigger for ACA.
This is a consensus guidance document developed by the British Association for the Study of Headache (BASH), of practical recommendations in the use of advanced migraine treatments based on the current literature, guidelines, real-world experience and opinion from an expert consensus group. The target audience for this statement includes all clinical and allied healthcare professionals interested in headache. The introduction of calcitonin gene-related peptide-targeted migraine treatments in addition to botulinum toxin has widened the choice of migraine treatment options. However, there is a lack of consistency in the use and treatment of accessibility across the UK. We have developed a multidisciplinary consensus clinical guidance that makes recommendations on how to use advanced preventative treatments for migraine. The BASH consensus group was composed of consultants, nurses and general practitioners with specialist's experience in headache. Key clinical questions were agreed by consensus. Each recommendation was based on a selective search of evidence, including meta-analyses, systematic reviews and considered relevant national standards of care. A modified Delphi process was used to obtain consensus on the recommendations via an anonymous voting process by the Consensus Group and BASH Council members. Those not reaching the minimum required consensus level (≥75%) were amended until agreement was reached or were designated as lacking consensus. Expert practical recommendations on advanced migraine treatments covering common dilemmas are presented. These recommendations aim to optimise patient access and experience of advanced migraine treatments. This document will need to be revised periodically as new evidence emerges.
BACKGROUND/OBJECTIVE:Perimesencephalic subarachnoid haemorrhage (pmSAH) has traditionally been considered benign and of venous origin. However, advanced imaging increasingly identifies basilar artery perforator aneurysms (BAPAs) as a subset of cases historically labelled as non-aneurysmal, atraumatic (NAA) pmSAH. The objective was to compare clinical characteristics and outcomes of patients with NAA, BAPA and ruptured posterior circulation aneurysms (r-pc-AN), assessing the impact of pmSAH aetiology on patient outcomes. METHODS:This retrospective, multicentre, observational cohort study included BAPA cases from the international PERForator Aneurysm registry (2013-2025, 60 centres, 19 countries). Comparison cohorts were from a single high-volume tertiary care centre (2004-2025). The study included 444 patients (n=167 NAA, n=157 BAPA, n=120 r-pc-AN). Excellent outcome was defined as a modified Rankin Scale score of 0-1 at 3-6 months. RESULTS:Excellent outcomes were achieved in 137/167 (82%) of NAA, 96/140 (69%) of BAPA and 56/102 (55%) of r-pc-AN cohorts (p<0.001). Mortality rates were 1% (NAA), 11% (BAPA) and 18% (r-pc-AN). cCompared with BAPA, NAA patients had significantly higher odds of excellent outcome (adjusted OR, aOR 2.0, 95% CI 1.2 to 3.4, p=0.01), while r-pc-AN were associated with significantly lower odds of excellent outcome (aOR 0.5, 95% CI 0.3 to 0.9, p=0.01). Hydrocephalus and external ventricular drain rates were highest in r-pc-AN (83% and 87%), followed by BAPA (48% and 44%) and NAA (28% and 16%) (p<0.001). CONCLUSIONS:While pmSAH has been considered benign, our findings challenge this assumption. Patients with BAPA-related pmSAH demonstrated significantly worse outcomes than NAA but better outcomes than r-pc-AN. Further research is needed to distinguish BAPA-pmSAH from NAA-related pmSAH and to establish diagnostic and therapeutic guidelines. TRIAL REGISTRATION NUMBER:NCT06189014.
BACKGROUND:Status epilepticus (SE) is associated with substantial mortality and morbidity that increase with seizure duration. Prompt diagnosis is essential, but access to electroencephalography (EEG) is often limited outside regular working hours. We examined whether EEG delay due to prolonged waiting times for EEG is associated with worse outcomes. METHODS:This retrospective cohort study comprised adults (≥18 years; n=163) with first-time, non-anoxic, EEG-verified non-convulsive SE treated at Odense University Hospital, Denmark (2008-2017). EEG delay was defined as the time from last antiseizure treatment or clinical suspicion of SE to EEG confirmation. Outcomes were new neurological deficit at discharge and 2-year all-cause mortality. External validation used two retrospective German cohorts (n=906) differing in weekend EEG availability. RESULTS:Median EEG delay was 11.7 hours (IQR 3.5-22.6) and correlated with SE duration (r=0.2, p<0.01). Longer delay was associated with new neurological deficits at discharge (p<0.001 across delay groups; ρ=0.152, p=0.03) and higher long-term mortality (log-rank p=0.007), driven mainly by delays>22.6 hours. Multivariable analyses for 1 year mortality adjusting for factors including aetiology and age supported an independent association between delay and higher mortality. Delays were longer for Friday/Saturday admissions when next-day EEG was unavailable, with lower survival. In validation, lack of weekend EEG access showed etiology-dependent weekend-weekday mortality differences (eg, +18.8% in remote symptomatic SE; p=0.01) not seen in centres with weekend EEG availability. CONCLUSION:In this cohort, prolonged waiting times for EEG for the diagnosis of SE were associated with worse neurological outcomes at discharge and higher mortality. Improving timely EEG access, including weekends, may be a modifiable system-level target to improve SE outcomes.
BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with the global epidemiological profile remaining incompletely understood. While previous systematic reviews existed, an updated comprehensive synthesis is needed to delineate the disease burden. METHODS:We searched PubMed, Embase, Scopus, Web of Science and Cochrane databases from inception to 18 February 2025, for studies reporting the incidence, prevalence or mortality of ALS in the general population. Pooled estimates with 95% CIs were calculated, and subgroup analyses were performed. RESULTS:Of 29 110 articles initially screened, 142 were included. Global pooled incidence was 1.65 per 100 000 person-years (95% CI 1.43 to 1.91), prevalence was 5.05 per 100 000 population (95% CI 4.26 to 5.99) and mortality was 1.26 per 100 000 person-years (95% CI 0.94 to 1.69). Both incidence rate ratio (IRR=0.74) and prevalence rate ratio (PRR=0.69) indicated significantly lower disease burden in females than in males. The burden of disease exhibited a marked age-dependent pattern, peaking at ages 70-79. Temporal trend analyses revealed a consistent increase in prevalence from 1963 to 1999 onwards, while incidence peaked in 2014-2017. Geographically, incidence and prevalence were highest in Europe, North America and Oceania and lowest in Asia and South America. The disease burden was significantly higher in high-income countries compared with both upper-middle-income and lower-middle-income countries. CONCLUSION:This systematic review provides updated global ALS burden estimates, showing variations by sex, age, time and geography and underscoring the complex interplay of genetic, environmental and socioeconomic factors, with implications for health planning, resource allocation and etiological research.
BACKGROUND:Anti-amyloid therapies for Alzheimer's disease (AD) require efficient patient selection. The Clinical Dementia Rating (CDR) scale is the reference standard for staging, but it is time-consuming to administer. Simple tools to distinguish early-stage cognitive impairment (CDR 0.5-1) from more advanced stages (CDR 2-3) would therefore be of substantial clinical value. METHODS:Participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts 1-3 with CDR ≥0.5 were analysed. Three logistic regression models using Mini-Mental State Examination (MMSE), Functional Assessment Questionnaire (FAQ) or the FAQ/MMSE ratio as predictors were developed. Two cut-offs per model were selected to ensure minimum sensitivity and specificity of 0.99, defining rule-out, rule-in and intermediate (uncertain) zones. Performance was assessed using discrimination, calibration and decision curve analysis. RESULTS:Among 1533 ADNI participants with CDR ≥0.5, two-thirds (n=1022) were assigned to the training set and one-third (n=511) to the test set. FAQ/MMSE and FAQ showed excellent discrimination (area under the curve, AUC 0.97-0.98), outperforming MMSE (AUC 0.94-0.95). FAQ/MMSE demonstrated the best overall performance, although differences compared with FAQ were small and not statistically significant. Dual cut-offs for FAQ/MMSE (0.67 and 1.44) and FAQ (12 and 27) enabled clinically meaningful stratification, with 80% and 70% of participants classified into high-confidence zones, respectively. Results were consistent across the training and test sets. CONCLUSIONS:The FAQ/MMSE ratio and FAQ score show high accuracy in distinguishing early-stage (CDR 0.5-1) from more advanced cognitive impairment (CDR 2-3). These simple measures may support the clinical preselection of patients for further evaluation in the context of anti-amyloid therapy.
BACKGROUND:Visuospatial working memory (VSWM) deficits are among the earliest cognitive impairments evident in Huntington's disease (HD). They often precede motor symptoms and likely reflect early disruption of cortico-striatal circuits. Both the cognitive components and brain correlates are, however, poorly delineated. OBJECTIVES:This study aims to characterise the progression of VSWM deficits across HD stages and identify their structural brain correlates. METHODS:In this prospective international study, 92 HD mutation carriers (HDmc) (21 premanifest and 71 manifest) and 39 healthy controls underwent cognitive and clinical assessments and structural MRI at baseline; 49 manifest HD and 36 controls completed a 1-year follow-up. VSWM was assessed using the object-location task (OLT), providing continuous measures of location error, object recognition and object-location binding. MRI analyses included caudate, putamen and hippocampal volumes and cortical thickness. RESULTS:We found increased location error and spatial imprecision under high memory load, without binding errors in premanifest HD with an area under the curve of 0.731. Across all HDmc, these location deficits correlated with striatal atrophy and cortical thinning in parietal and middle cingulate regions. Manifest HD individuals exhibited swap errors and hippocampal atrophy. Both location and swap errors worsened over time alongside progressive striatal and hippocampal volume loss. Principal component analysis confirmed a dissociation between spatial location-related deficits (striato-cortically mediated) and binding errors (hippocampally mediated), supporting a hierarchical model of VSWM decline. CONCLUSIONS:HD-related VSWM impairment follows a staged, anatomically dissociable trajectory. The OLT offers sensitive, mechanistic markers of cognitive decline with potential utility for early detection and clinical trial stratification.
BACKGROUND:Risk and outcome of cancer for patients with multiple sclerosis (pwMS) remain disputed. We aimed to investigate cancer incidence and cancer-specific mortality rates in pwMS compared with a matched population sample. METHODS:In this nationwide retrospective population-based study, pwMS in Finland were identified from the National MS-registry and the Care Register for Healthcare and matched to up to five population controls with data from 1974 until 2021. Standardised incidence rates, relative risks and HRs were calculated for all cancers and cancer subtypes utilising the Finnish Cancer Registry. A standardised mortality ratio (SMR) for cancer-specific causes was calculated, and survival analysis using a cumulative incidence function with a competing risk model of the probability of death was performed. RESULTS:We found 16 815 MS patients and selected 80 950 controls. Follow-up time was a median of 15.2 (8.2-22.9) years for pwMS and 17.5 (9.5-26.0) years for controls. Mean age at the diagnosis of first cancer was lower in pwMS (61.4y; SD 11.89) compared with controls (64.5y; 12.53; p<0.001). PwMS had a similar risk for all cancers (SIR 0.96; 95% CI 0.90 to 1.03) compared with controls. For males, the risk was lower (SIR 0.83; 95% CI 0.72 to 0.94). SMR showed that cancer-specific mortality for all cancers was similar to controls (1.02; 95% CI 0.93 to 1.11). CONCLUSIONS:Patients with MS have a similar risk for cancer and equal cancer-specific mortality compared with population controls. However, pwMS are diagnosed with cancer at a younger age compared with controls.
OBJECTIVES:To validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH) and to assess its value as a real-time monitoring biomarker. DESIGN:Pre-registered multicentre prospective observational cohort study. SETTING:Eight neurosurgical tertiary centres in Switzerland, Germany and Austria between August 2021 and June 2024. PARTICIPANTS:366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days). INTERVENTIONS:Daily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested. MAIN OUTCOME MEASURES:CSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI) and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus and 3 month functional outcome. RESULTS:CSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 µM, IQR 2.64 to 25.90) and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential for same-day SAH-SBI (area under the curve 0.59, 95% CI 0.56 to 0.63), with substantial between-centre heterogeneity. In a post-hoc exploratory analysis, higher CSF methaemoglobin showed a positive point-estimate of association with SAH-SBI (OR 1.18 per log(µM), 95% CI 1.02 to 1.36). Higher acute-phase EVD-derived CSF-Hb was associated with chronic hydrocephalus and a poor 3 month functional outcome. Catheter-related infection rates were low (2.2%). CONCLUSIONS:In this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. Higher CSF methaemoglobin was associated with SAH-SBI; this hypothesis-generating observation requires prospective confirmation and motivates continued investigation of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates. TRIAL REGISTRATION NUMBER:NCT04998370.
BACKGROUND:Electric scooter (e-scooter)-related traumatic brain injuries (TBIs) have become increasingly common with the adoption of shared e-scooters. Previous studies have focused on severe injuries. We aimed to describe the characteristics and outcomes of e-scooter-related TBIs. METHODS:This retrospective cohort study included all e-scooter-related TBIs presenting to all three adult emergency departments in Helsinki during 2021-2023. Data were obtained based on a keyword search from the hospital database. TBI cases were identified using the International Classification of Diseases 10th Revision diagnostic codes and manually verified. All brain imaging reports were reviewed, and imaging-positive scans were re-evaluated. RESULTS:A total of 184 patients with e-scooter-related TBIs were included. The mean age was 32 years, and 128 (70%) were male. The incidence of TBIs was 1.3 per 100 000 e-scooter trips, decreasing from 2.2 to 1.0 per 100 000 trips after implementation of usage restrictions. Most injuries occurred during night-time hours, with Saturdays and Sundays being the most common days. Alcohol intoxication was documented in 82% of patients, while helmet use was reported in 9%. Concussion was the most common diagnosis (84%). 29 patients (16%) had intracranial findings on brain imaging, most commonly cerebral contusions, traumatic subarachnoid haemorrhages, subdural haematomas and diffuse axonal injuries. Four patients required operative treatment, including three who underwent neurosurgical procedures. CONCLUSIONS:Alcohol intoxication is highly prevalent among patients with e-scooter-related TBIs and represents an important modifiable risk factor for these injuries. Stricter enforcement against riding under the influence of alcohol may help reduce e-scooter-related TBI incidence and severity.
BACKGROUND:Accelerated biological ageing has been proposed as a key mechanism influencing disease progression in multiple sclerosis. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, may reflect biological ageing in women and could be associated with disability progression. We aim to evaluate the prognostic implications of AMH levels measured at the first demyelinating event (FDE) suggestive of multiple sclerosis (MS). METHODS:This retrospective study analysed prospectively collected data from three Spanish neuroimmunology centres (since 1994). It included 365 females aged 20-45 years with serum AMH measured within 2 years of onset. According to AMH tertiles (n, median ng/mL (range)), participants were classified as follows: high (n=121; 4.6 (3.2-17.4)), medium (n=122; 2.1 (1.3-3.2)) and low (n=121; 0.6 (0.01-1.3)). A total of 145 healthy females served as controls. Age-adjusted multivariable linear regression models assessed associations between AMH and baseline clinical, radiological and serum biomarkers. Cox regression models evaluated the risk of Expanded Disability Status Scale 3.0, second relapse, progression independent of relapse activity and relapse-associated worsening. RESULTS:At FDE, median (range) age was 32.9 (22.2-44.9) years, follow-up 6.5 years (0.01-29.4) and AMH 2.2 (0.01-17.4); 68% received disease-modifying treatment. AMH levels did not differ between patients and controls and were inversely correlated with chronological age (β -1.21 (95% CI -1.42 to -1.00), p<0.001). After adjustment for chronological age, AMH showed no independent association with clinical, radiological or biomarker measures, or long-term outcomes. CONCLUSIONS:AMH levels at the time of an FDE suggestive of MS were not associated with baseline activity or long-term outcomes related to relapses or disability. Our findings suggest that the apparent associations between AMH and disease characteristics are largely driven by chronological age, supporting the concept that ovarian reserve primarily reflects biological ageing rather than an independent determinant of MS progression.
BACKGROUND:The high incidence of in-stent restenosis (ISR) associated with bare-metal stents (BMS) undermines the viability of endovascular treatment as a treatment option for patients with severe symptomatic intracranial atherosclerotic stenosis (ICAS). The study aimed to evaluate whether durable fluoropolymer drug-eluting stents (DES) reduce the incidence of ISR compared with BMS in the treatment of severe ICAS. METHODS:This prospective, multicentre, open-label, blinded outcome clinical trial was conducted at 16 centres in China, enrolling patients with ischaemic stroke or transient ischaemic attack (<90 days) attributed to 70%-99% stenosis of an intracranial major artery. Eligible patients were randomly assigned to receive durable fluoropolymer DES or BMS for stenosis treatment. The primary outcome was ISR at 1 year postprocedure, which was defined as a stenosis rate of ≥50% occurring within or immediately adjacent to (within 5 mm) the stent. Secondary outcomes included symptomatic ISR and stroke or death within 30 days or stroke in the target vessel territory between 31 days and 1 year. RESULTS:Between 20 February 2023 and 10 April 2024, 156 patients were enrolled and assigned to receive DES (n=78) or BMS (n=78). The median age was 61 years (IQR 54-67), and 129 (82.7%) of 156 patients were male. At 1 year, the primary outcome occurred in 2.9% in the DES group versus 27.9% in the BMS group (risk difference -0.25, 95% CI -0.37 to -0.13, p<0.001). No significant differences were observed between the DES and BMS groups in symptomatic ISR (0% vs 2.9%, p=0.20) or in stroke or death within 30 days or stroke in the target vessel territory between 31 days and 1 year (7.7% vs 12.3%, p=0.45). CONCLUSIONS:Among patients with severe ICAS, treatment with durable fluoropolymer DES resulted in a lower 1-year ISR compared with BMS. TRIAL REGISTRATION NUMBER:NCT05719883.
BACKGROUND:Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS:We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS:Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS:ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.
