Although effects on cognitive function have been reported during cenobamate (CNB) treatment, far less is known about how it may affect neuropsychological domains such as apathy, emotion dysregulation, and impulsivity. This prospective longitudinal study aims to assess psychopathological and cognitive changes after CNB introduction in adults with drug-resistant focal epilepsy, accounting for seizure outcome and burden of concomitant anti-seizure medication (ASM). We consecutively recruited adults with drug-resistant focal epilepsy who had undergone a comprehensive neuropsychological evaluation at baseline, before starting CNB, and at follow-up, 12 months after treatment introduction. The psychopathological battery included Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory, Difficulties in Emotion Regulation Scale (DERS-36), Barratt Impulsiveness Scale (BIS-11), Apathy Evaluation Scale (AES), and Quality of Life in Epilepsy Inventory (QoLIE-31). The cognitive assessment comprised Rey Auditory Verbal Learning Test (RAVLT), Digit-Span, Rey–Osterrieth Complex Figure Test, WEIGL, FAS, Stroop Color and Word Test, and Symbol Digit Modalities Test (SDMT). We applied linear mixed-effects models adjusted for responder status and total concomitant ASM defined daily dose (DDD) ratio. Our cohort included 27 individuals (16 female; mean age 42.4 ± 16.7 years) showing a 74
The real-world characteristics of patients with advanced Parkinson’s disease (PD) who receive foslevodopa/foscarbidopa (LDp/CDp) continuous subcutaneous infusion therapy (CSCI) remain poorly understood. This study aimed to describe the characteristics and hospitalization details of patients with advanced PD hospitalized for LDp/CDp CSCI in Japan. This study was a retrospective descriptive analysis conducted using a hospital-based database provided by Medical Data Vision, Co. Ltd. Patients with advanced PD who underwent LDp/CDp CSCI during hospitalization between July 2023 and June 2024 were enrolled. The index date was defined as the date of the first LDp/CDp prescription. Baseline patient characteristics, levodopa-equivalent dose (LED), number of pills/transdermal patches, medication classes for concomitant PD medications, and non-motor symptom medications assessed within 4 weeks prior to and including the index date, along with hospitalization details, were collected. We enrolled 96 patients with a mean age of 65.6 years [standard deviation (SD), 10.2], of whom 58 (60.4
Timely identification of Parkinson’s disease (PD) is often delayed because of clinical heterogeneity and limited awareness of early symptoms. Digital biomarkers obtained via smartphones offer scalable screening potential. However, unimodal assessments may lack sufficient sensitivity or specificity given the multidimensional nature of PD. The aim of this study was to develop and validate a smartphone-based, multimodal digital biomarker framework for PD screening and diagnostic support. The study progressed through two phases: an initial version [n = 368; 233 PD, 135 healthy controls (HC)] was used for data-driven task refinement, and a final version (n = 296; 204 PD, 92 HC) containing optimized motor (Touch, Swipe, Balloon, Spiral, Wave), visual, and speech tasks and a refined questionnaire task was evaluated. Feature selection and speech subtask selection were performed exclusively within the training set using stratified cross-validation. Random Forest and XGBoost classifiers were trained using (1) single-task features, (2) all-task multimodal features, and (3) selected task subsets. The primary outcome was area under the receiver operating characteristic curve (AUROC) on the independent test set. In the final version, single-task models demonstrated heterogeneous performance (Random Forest AUROC range 0.5689–0.8397), with the questionnaire (0.8397) and Touch task (0.7789) performing best individually. The all-task multimodal model achieved AUROC 0.8620. A reduced multimodal subset combining Touch, Spiral, and questionnaire features yielded the highest discriminative performance (AUROC 0.9053). Additional feature- and task-level analyses showed significant multivariate group differences (Hotelling’s T2 p < 0.001) and stronger inter-feature association in PD compared with HC, providing interpretability. A smartphone-only multimodal digital biomarker framework achieved high discrimination between PD and controls. Multimodal integration outperformed unimodal approaches, supporting the potential utility of scalable, smartphone-based tools for PD screening and diagnostic support. External validation in broader populations is warranted. Parkinson’s disease is often difficult to identify early because symptoms vary widely between individuals and access to clinical evaluation can be limited. Smartphones may provide a practical and accessible way to support screening through the use of digital biomarkers, which are measurable patterns collected through digital devices that reflect health conditions. In this study, we developed and tested a smartphone-based system for Parkinson’s disease screening and diagnostic support. The system combined several types of information, including hand movement tasks, drawing tasks, speech recordings, visual tasks, and symptom questionnaires. We analyzed data from 664 participants, including people with Parkinson’s disease and healthy controls. Artificial intelligence methods were used to determine how accurately the smartphone tasks could distinguish people with Parkinson’s disease from healthy individuals. Some single tasks performed reasonably well, particularly the questionnaire and touch-based finger movement task. However, combining multiple tasks produced better results than using any single task alone. The best-performing model combined a touch task, a spiral drawing task, and questionnaire responses, showing high accuracy in identifying Parkinson’s disease. These findings suggest that smartphone-based multimodal digital biomarkers may provide a scalable and accessible tool for Parkinson’s disease screening and diagnostic support. Further validation in broader populations is still needed.
Neuromuscular diseases (NMDs) encompass over 800 distinct entities affecting approximately one in 1000 individuals worldwide, with progressive muscle weakness, atrophy, and motor impairment as primary clinical manifestations. The rarity of most NMDs creates fundamental challenges for artificial intelligence (AI) and machine learning (ML) applications that typically require large-scale datasets. In this narrative review we synthesize the literature published between 2018 and 2025 on AI applications across the NMD spectrum, organized by clinical application domain. We examine how AI has advanced diagnostic capabilities through genetic variant interpretation, muscle magnetic resonance imaging analysis, electromyography-based classification, and computational pathology. In disease monitoring and prognosis, wearable-derived digital biomarkers have achieved regulatory qualification (US Food and Drug Administration [FDA] and European Medicines Agency [EMA]) as clinical trial endpoints for Duchenne muscular dystrophy, while AI-driven survival models for amyotrophic lateral sclerosis (ALS) have been validated across 14 European centers. Proteomic and multi-omics analyses using ML have identified diagnostic panels for ALS. However, most reported models were developed and internally validated on single-center datasets, and few have undergone external or prospective validation or clinical implementation. Despite these achievements, research intensity varies dramatically across NMD subtypes, with ALS and Duchenne muscular dystrophy dominating while myotonic dystrophy, congenital myopathies, and metabolic myopathies remain virtually unexplored. Critical gaps persist in computational pathology, multi-center validation, and clinical translation. In this review, we discuss how federated learning, international collaborative networks (TREAT-NMD, Solve-RD, EURO-NMD), and foundation models can address these challenges, and propose directions for future AI-enhanced clinical studies in this data-scarce field.
Focal seizures are the most common form of epilepsy. This narrative review analyzes the efficacy, safety, and tolerability of five newer third-generation antiseizure medications (ASMs) approved for treatment of focal seizures: lacosamide, perampanel, eslicarbazepine acetate, brivaracetam, and cenobamate. A search of PubMed and ClinicalTrials.gov identified phase 2/3 randomized controlled trials and long-term open-label extension (OLE) studies for the five most recently approved ASMs for focal seizures. Efficacy data were summarized, including median percent reduction in seizure frequency, ≥ 50
Inebilizumab is used in Japan for relapse prevention in aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Nationwide post-marketing surveillance (PMS) is underway to evaluate the real-world safety and effectiveness of inebilizumab in Japanese patients with NMOSD. This PMS interim analysis assessed safety and effectiveness of inebilizumab in Japanese patients with NMOSD initiating treatment between June 2021 and November 2023, using data through June 2025. The safety analysis set included 228 patients, and the effectiveness analysis set included 224 patients after excluding three patients from N-MOmentum (NCT02200770) and one without confirmed anti-AQP4 antibody positivity. Twenty-one (safety analysis set) and 20 (effectiveness analysis set) patients discontinued treatment. In the safety analysis set, 194 patients (85.1
Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism that frequently involves the central nervous system and may be associated with secondary sleep disturbances. Excessive daytime sleepiness (EDS) in WD is typically attributed to metabolic or structural brain injury rather than primary sleep–wake dysregulation. Narcolepsy type 1 (NT1), caused by autoimmune loss of hypothalamic hypocretin neurons, is a distinct primary sleep disorder. The coexistence of WD and NT1 has not previously been reported. We describe a 23-year-old woman with a 15-year history of WD who developed long-standing EDS accompanied by emotionally triggered cataplexy, sleep paralysis, and hypnagogic hallucinations. Genetic analysis identified pathogenic ATP7B variants (p.R778L and p.R919G). Brain MRI revealed symmetric signal abnormalities involving the basal ganglia, midbrain nuclei, cerebellar dentate nuclei, and hypothalamus, suggesting chronic neurotoxicity. Comprehensive sleep evaluation supported a diagnosis clinically consistent with NT1, further corroborated by HLA-DQB1*06:02 positivity. Importantly, hepatic encephalopathy and other secondary causes of hypersomnolence were excluded. This case suggests the possibility that NT1 can coexist with WD as an independent primary sleep disorder rather than a secondary manifestation of metabolic or structural brain disease. The findings support a multifactorial neurobiological mechanism in which copper-related neurotoxicity and genetic susceptibility converge on hypothalamic injury. Clinicians should maintain a high index of suspicion for primary sleep–wake disorders when patients with WD present with cataplexy or other REM-related symptoms, as accurate differentiation has important implications for diagnosis, management, and prognosis. Infographic available for this article.
Intracerebral haemorrhage (ICH) remains a devastating stroke subtype with limited therapeutic options, creating an urgent need for complementary strategies that target secondary brain injury and recovery. Traditional Chinese herbal medicines (TCHMs) have attracted interest because of their potential multitarget actions on neuroinflammation, oxidative stress, apoptosis, ferroptosis, blood–brain barrier dysfunction, haematoma resolution, gut microbiota dysbiosis and neurovascular repair. Relevant preclinical, clinical and translational studies were identified through a structured search of international and Chinese bibliographic databases. Preclinical studies suggest that selected TCHM-derived bioactive compounds and multicomponent formulae may modulate key pathological processes after ICH, although compound-level mechanisms should not be directly extrapolated to formula-level effects without further validation. Clinically, several small-scale randomized trials, observational studies and meta-analyses have reported potential benefits of selected TCHM preparations, including improved neurological scores, haematoma absorption, oedema reduction and functional recovery when used as adjuncts to conventional care. However, the clinical evidence remains heterogeneous. Larger and more rigorously designed multicentre trials, including CHAIN and CRRICH, have either failed to confirm clear functional benefit or raised safety concerns under specific conditions, particularly regarding ultra-early use of potent blood-activating formulations. Translation into mainstream ICH management is further hindered by variable study quality, insufficient risk-of-bias control, uncertainty regarding active material basis, potential synergistic or antagonistic interactions within multicomponent formulae and limited standardisation of herbal preparations. Future research should focus on formulation-specific, stage-specific and patient-stratified evaluation using rigorous randomized controlled trials, transparent pharmacological characterization, standardised quality control and careful safety monitoring. This review synthesises current evidence from bench to bedside and highlights a cautious pathway toward evidence-based integration of selected TCHMs into ICH management.
Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterised by inflammation, demyelination and neurodegeneration. The aetiology of MS is complex, arising from interactions among genetic susceptibility, environmental exposures and stochastic immune processes. Over the past 2 decades, large-scale genomic studies have fundamentally shaped our understanding of MS pathogenesis, establishing disease risk as highly polygenic and predominantly driven by immune regulatory mechanisms. Genome-wide association studies (GWAS) have identified 233 common susceptibility variants, including 201 outside the major histocompatibility complex (MHC), with the strongest effects localised to the MHC, particularly HLA-DRB1*15:01. These genetic associations implicate pathways involved in antigen presentation, T- and B-cell activation, cytokine signalling and innate immune responses. Family-based studies have identified putative rare susceptibility variants, but no single gene has been confirmed to cause MS. However, genetic risk alone is insufficient to cause disease, and gene-environment interactions, most notably with Epstein-Barr virus infection, vitamin D insufficiency, obesity, smoking and sex-specific hormonal factors, are critical determinants of disease manifestation. Here, we synthesise current evidence on the genetic architecture of MS, the biological mechanisms linking genetic risk to disease susceptibility and the ways in which genetic factors intersect with environmental exposures to shape clinical outcomes. We further review emerging data on the influence of genetic variation on disease course, prognosis and treatment response. Finally, we discuss unmet needs and future directions, including the role that family studies can play in further informing our understanding of MS pathology, the need for ancestry-diverse studies, multi-omics integration and the translation of genetic insights into clinical care.
Caregivers have first-hand experience of facing the daily challenges of Rett syndrome (RTT). The aim of this study was to understand caregivers’ experiences of RTT, including challenging symptoms that caregivers hope novel therapies will address. This non-interventional, qualitative and quantitative market research study engaged caregivers of individuals with RTT in the USA, the UK, Canada, and Israel, through an online survey comprising both closed- and open-ended items. Survey domains included age of symptom onset, symptom severity and impact on quality of life, the most challenging symptoms, and caregiver perspectives on meaningful improvement. A total of 323 caregivers completed the survey. Symptoms with the most severe and lasting impact on patients’ quality of life typically presented by 6 years of age. These symptoms included loss of speech, loss of purposeful use of hands, and gait disturbances. Caregivers reported a dynamic and lifelong burden associated with impairments in activities of daily living and expressed a desire for improvement across these functional domains following gene therapy treatment. Despite RTT’s clinical heterogeneity, similarities emerged in caregivers’ daily experiences and their hopes regarding gene therapy treatment. Caregivers believe meaningful improvements for people with RTT would be improved function and enhanced autonomy related to fine and gross motor abilities, and improved ability to communicate needs.
Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are both recommended for acute ischemic stroke (AIS) in China. Compared with rt-PA, UK is less expensive and more widely available in clinical practice. The Treatment of Acute Ischemic Stroke with Intravenous Urokinase (TASK-UK) study aims to investigate clinical outcomes among patients with AIS who receive UK thrombolysis, and to compare efficacy and cost-effectiveness between UK and rt-PA. TASK-UK is a multicenter, real-world observational study, with a planned sample size of 1000 patients in the UK group and 800 in the rt-PA group. This study enrolls patients with AIS who are eligible for intravenous thrombolysis from 20 participating centers and conducts follow-up until 90 days after thrombolysis. The primary efficacy outcome is functional independence at 90 days, defined as a modified Rankin scale (mRS) score of 0–2. The primary safety outcome is symptomatic intracranial hemorrhage (sICH) occurring within 22–36 h after thrombolysis. The exploratory outcome is defined as an intergroup comparison of direct medical costs during hospitalization. The TASK-UK study will provide high-quality real-world evidence on the effectiveness and cost-effectiveness of UK thrombolysis for AIS. NCT06194968 (ClinicalTrials.gov).
The interplay between glymphatic function and sleep quality is crucial for brain health and cognitive longevity in late adulthood. Beyond chronological age, whether brain age has specific effects on the associations between glymphatic function, sleep quality, and cognition are understudied in cognitive unimpaired adults. Structural and diffusion magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 582, age range 18–87 years) were used to calculate brain age metrics and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. Brain age metrics comprised estimated brain age and the brain predicted age difference (brain-PAD). Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Cognitive assessments included accuracy, reaction time, intraindividual variability of reaction time, and fluid intelligence. Leftward asymmetry of the DTI-ALPS index was consistently observed across brain age-specific groups. The brain-PAD score was significantly correlated with a lower left DTI-ALPS index. Adults with a positive brain-PAD score exhibited a robust correlation between DTI-ALPS indices and sleep quality features, whereas those with a negative brain-PAD score showed a reliable correlation between DTI-ALPS indices and cognition. Mediation analyses further revealed that the relationship between left DTI-ALPS index and sleep efficiency was mediated by brain age. This study provides the first demonstration that lateral differences in the DTI-ALPS index vary according to brain ageing statuses. The two distinct profiles of the sleep–glymphatic function–cognition connections observed in relation to brain-PAD scores suggest that a preserved brain age may serve as a protective factor against age-related decline in glymphatic function. These findings may underscore the translational potential of brain age models as both clinical biomarkers and modifiable targets for interventions aimed at promoting healthy longevity and brain resilience.
This study aimed to determine whether venous sinus opacification time on final digital subtraction angiography (DSA), a proposed marker of microcirculatory perfusion, predicts futile recanalization after successful endovascular thrombectomy (EVT) in patients who experienced anterior circulation large vessel occlusion (LVO) stroke. We retrospectively enrolled consecutive patients with anterior circulation LVO who underwent EVT and achieved successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3). Venous sinus opacification time was defined as the interval from first contrast opacification of the internal carotid artery to first venous sinus opacification on the final angiographic run. Futile recanalization was defined as poor functional outcome at 3 months (modified Rankin Scale [mRS] > 3). Multivariable logistic regression, restricted cubic spline, receiver operating characteristic (ROC), and subgroup interaction analyses were performed. Incremental prognostic value was assessed by comparing models with and without venous sinus opacification time. A total of 205 patients were included, and 102 (49.8
Acute ischemic stroke (AIS) remains a major cause of disability and death despite effective reperfusion therapies, intravenous thrombolysis (IVT) and mechanical thrombectomy (MT). Systemic inflammation critically shapes ischemic injury and recovery, but the prognostic value of inflammatory biomarkers in reperfused patients is unclear, and previous reviews have not consistently addressed pre-treatment inflammatory markers in patients treated with IVT or MT. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Cochrane Library, Web of Science, and Scopus were searched through November 30, 2024, for studies assessing associations between circulating inflammatory biomarkers measured before IVT or MT and 3-month functional outcome (modified Rankin Scale, mRS). Data were pooled using random-effects models, with odds ratios (OR) and 95
Migraine is a common neurological disorder that can severely diminish quality of life. Quantifying migraine-related changes in a real-world population over time can increase understanding of the natural history of migraine and improve clinical care of individuals with migraine. The Observational survey of the Epidemiology, treatment, and Care Of MigrainE (OVERCOME) is a web-based study that longitudinally assessed migraine-related outcomes in a demographically representative adult population with migraine in the United States. Migraine disease status was classified as “overall improved,” “overall worsened,” or “no net change” based on changes in monthly headache days (MHDs), the Migraine Disability Assessment Scale (MIDAS) score, and the Migraine-Specific Quality-of-Life Questionnaire–Role Function-Restrictive (MSQ-RFR) domain score over 1 year. Migraine-related characteristics and patient-reported outcomes were evaluated for each group. Among 11,634 individuals with migraine who completed the baseline and 1-year follow-up surveys, 40.4
Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuro-autoimmune disease. Monoclonal antibodies targeting B cell antigens CD19 and CD20, the interleukin-6 receptor, or the complement cascade are used as preventive therapies to reduce relapse rates. We conducted a network meta-analysis (NMA) to compare the effect of rituximab on time to first relapse with ravulizumab, eculizumab, inebilizumab, and satralizumab in patients with NMOSD who are aquaporin-4 (AQP4)-IgG-positive. A systematic search was conducted in PubMed, Scopus, CINAHL, EMBASE, Web of Science, the Cochrane Library, and gray literature sources up to October 31, 2024, and updated on November 1, 2025, following PRISMA guidelines. A network meta-analysis of randomized and open-label trials was conducted to compare time to first relapse between rituximab and other monoclonal antibody therapies. From 6337 records, 3825 duplicates were removed; 2512 were screened, 2327 excluded, leaving eight trials. The prior treatment, relapse history, and definitions and adjudication of relapse varied across studies. Rituximab showed higher hazard ratio (HR) point estimates for time to first relapse compared with ravulizumab with or without immunosuppressive therapies (IST) (HR 5.00, 95
Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder caused by pathogenic variants in the transthyretin (TTR) gene resulting in progressive sensorimotor neuropathy, autonomic dysfunction, and effects on other organs, particularly the heart. Historically, treatment options have been limited to liver transplantation and symptomatic management, and the disease was associated with poor prognosis and progressive disability. However, over the past decade, the therapeutic landscape has been transformed by the development of disease-modifying therapies that target the underlying pathophysiology of TTR amyloid formation. These therapies include TTR stabilizers, such as tafamidis, diflunisal, and acoramidis, as well as RNA-silencing agents, such as patisiran, vutrisiran, inotersen, and eplontersen, which reduce hepatic production of TTR and slow disease progression. Clinical trials of RNA interference therapies have demonstrated significant improvements in neuropathy impairment scores, quality of life, and functional outcomes, with acceptable safety profiles and sustained long-term benefits. Emerging gene-editing approaches, including CRISPR-based therapies like NTLA-2001, may provide a one-time treatment and long-term disease control, representing a promising future direction for managing ATTRv-PN. Despite these advances, important challenges remain. These include high treatment costs, limited global accessibility, uncertainty regarding optimal treatment selection and sequencing, and the need for long-term real-world, patient-centered outcome data. This review summarizes current disease-modifying therapies for ATTRv-PN, compares their mechanisms and clinical evidence, and discusses unmet needs and future research directions, with the aim of providing a practical and comprehensive overview for clinicians treating patients with ATTRv-PN.
To compare the efficacy of treatment with two different levels of intermittent negative pressure (INP), applied to the lower limb, on self-reported spasticity and pain in patients with multiple sclerosis (MS). A randomized, two-arm multicenter trial enrolled patients with spasticity in the leg ≥ 4 on the numeric rating scale (NRS). Patients were randomized to treatment with −10 mmHg INP (low-dose group [LDG]) or −40 mmHg INP (high-dose group [HDG]) on the most affected leg, using the FlowOx 2.0 device (Otivio AS, Oslo, Norway). The device applies alternating cycles of 10 s of negative pressure and 7 s of ambient pressure via a sealed pressure chamber around the lower leg, for 1 h daily for 4 weeks. There was no difference in the change in NRS spasticity and pain score between the two groups after 4 weeks (estimated treatment effect 0.72; 95
INTRODUCTION:Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness (ocular, bulbar, limb, and respiratory). Efgartigimod (VYVGART), a first-in-class neonatal Fc receptor antagonist, was approved for treatment of generalized MG (gMG). This study aimed to explore real-world sentiments, wherein in sentiments refer to real-world perceptions expressed by patients, caregivers, and healthcare professionals (HCPs) on VYVGART and VYVGART Hytrulo, through structured social media analysis. METHODS:This social media listening study was designed to collect posts mentioning VYVGART and VYVGART Hytrulo for gMG using predefined keywords from social media platforms across the globe. Organic English-language posts from several platforms, such as Reddit, X (formerly Twitter), Facebook, Forums, Review, and Tumblr etc., were analyzed for the timeframe August 1, 2021 to September 30, 2024. Posts were categorized into themes, namely "brand awareness," "treatment access," "treatment experience," and "treatment support." RESULTS:A total of 1046 posts (USA 9%, Europe 6%, Unknown 85%) contained relevant information; 1015 posts were related to VYVGART and 55 posts were related to VYVGART Hytrulo. Most posts focused on treatment experience (593 posts) and brand awareness (402 posts). Overall sentiments towards VYVGART and VYVGART Hytrulo were positive in 49%, 30%, and 20% of patient, caregiver, and HCP posts, respectively. Patient posts expressed optimism about initiating treatment. There were fewer caregiver and HCP discussions and these were predominantly neutral. CONCLUSION:These findings suggest positive real-world perceptions of VYVGART and VYVGART Hytrulo among patients in improving symptoms and health-related quality of life.
