搜索结果：European journal of neurology

Mobile health (mHealth) apps are useful tools for research and disease management. However, implementation of mHealth apps is lacking in many areas. While mHealth apps offer various advantages to researchers and patients, their effectiveness depends on their actual use. Barriers to using mHealth apps are often due to human factors such as usability or technology acceptance. Although prior studies have examined the acceptance of mHealth apps in patient treatment, the key factors driving or hindering the use of mHealth apps in research remain unclear. This study explores user perceptions of 2 mHealth apps in the setting of an observational technology evaluation study using the unified theory of acceptance and use of technology. We aim to evaluate the technology acceptance of these specific apps and to investigate challenges in choosing suitable mHealth apps in research. The apps were intended for data collection; no effect on health was expected. Patients with chronic diseases as well as healthy participants used a symptom tracking app and a cognitive test app over the course of 4 weeks within the feasibility study of the project "Identifying Digital Endpoints to Assess Fatigue, Sleep and Activities of Daily Living in Neurodegenerative Disorders and Immune-Mediated Inflammatory Diseases." Thereafter, 61 qualitative interviews were conducted, recorded, and transcribed. A qualitative content analysis using the unified theory of acceptance and use of technology was performed. An important aspect of motivation for participants was feedback on their health data and performance in the cognitive tests. Effort played a significant role in app use. Patients rated the apps as easy to use and quick. Using the app multiple times per day at fixed times was perceived as disruptive. Participants preferred using their own phone. Social influence as well as facilitating conditions played a lesser role in intention to use the apps. Data security was no concern for most participants. They stressed the importance of good relations with the study team. In choosing suitable apps, one size will certainly not fit all. For medical research, pretesting of all materials with the potential users is of utmost importance. If the positive effects of the app on users' health are not immediately apparent, other factors may motivate use, for example, feedback, gamification, adjustable functions, applicability on all smartphone operating systems, and good relations to the study team.

Stroke often causes spasticity, impacting mobility and quality of life. Botulinum Toxin type A (BTX-A) and Dry Needling (DN) are treatments that reduce spasticity, although Botulinum Toxin type A injections can cause adverse effects. No studies have directly compared their effects at spinal, muscular, functional, quality-of-life, and cost-effectiveness levels. This study aims to determine the spinal mechanisms of BTX-A and DN on post-stroke lower limb spasticity, while also assessing feasibility, safety, and exploratory effects at muscular, functional, quality-of-life, and cost-effectiveness levels. This is a protocol of a proof-of-concept, feasibility randomized clinical trial including 90 participants from Canada, Belgium, and Spain who experienced a first stroke in the previous 12 months and present plantar flexor spasticity. Time since stroke (0-12 months) will be recorded and explored as a potential modifier of treatment response. Participants will be randomly assigned to receive either one session of BTX-A or 12 weekly sessions of DN. Blinded evaluators will assess outcomes before, during, and after treatment, with a 4-week follow-up. The primary outcome will be spinal mechanisms of spasticity, measured using the Tonic Stretch Reflex Threshold and its velocity sensitivity. Secondary outcomes will assess: a) muscular architecture and echotexture (measured with ultrasound); b) muscle tone/resistance using the Modified Ashworth Scale; c) gait and mobility (instrumented analysis, Timed Up and Go, 10-Meter Walk Test); d) muscle strength with dynamometry; e) quality of life with the EuroQoL questionnaire; and f) cost-effectiveness (analytic model). The findings will provide preliminary data to inform a future definitive trial. This research project has secured funding from the NEURON ERA-NET 2022 call, supported by the European Union's Horizon 2020 program (GA 964215) and co-funded by the European Union-Next Generation, and has undergone peer review. Ethical approval has been obtained from Spain, Canada, and Belgium. The study is registered in ClinicalTrials.gov (NCT06296082) and the Clinical Trials Information System (CTIS) under the number 2024-510866-18-00. The study protocol is registered on Zenodo (https://doi.org/10.5281/zenodo.20034064). Clinical Trials NCT06296082; https://clinicaltrials.gov/study/NCT06296082.

This study investigates differing aspects of wishes to hasten death (WTHD) distinguished by the extent to which WTHD were linked to patients' agency: desire for hastened death (DHD), defined as general wishes for death to come sooner, and hastening death intentions (HDI), defined as thoughts about ending one's life. In particular, this study aims to examine the differences between DHD and HDI in patients with amyotrophic lateral sclerosis (pALS) and identify predictive factors for both. A cross-sectional nested study was conducted within a multi-center longitudinal study involving pALS from 5 European countries. Data collected included DHD (Schedule of Attitudes toward Hastened Death), HDI ("could you currently imagine ending your life?"), sociodemographic and clinical characteristics, psychological distress, quality of life, and social and spiritual-existential aspects. In our sample of 121 pALS, 12.4% (15/121) expressed DHD, and 28.1% (34/121) expressed HDI. Of the 38 patients reporting any WTHD, only 11 experienced both DHD and HDI simultaneously. 23 patients reported HDI without DHD, while 4 patients expressed DHD without HDI. Multivariable logistic regression identified loneliness (OR&#xa0;=&#xa0;1.33, 95% CI 1.03-1.71, p&#xa0;=&#xa0;0.028) and reduced meaning in life (OR&#xa0;=&#xa0;0.89, 95% CI 0.84-0.95, p&#xa0;<&#xa0;0.001) as independent predictors of DHD. For HDI, independent predictors were female gender (OR&#xa0;=&#xa0;3.31, 95% CI 1.37-7.98, p&#xa0;=&#xa0;0.008) and lower spirituality (OR&#xa0;=&#xa0;0.92, 95% CI 0.88-0.95, p&#xa0;<&#xa0;0.001). One in 3 pALS expressed WTHD. Our separate analysis of DHD and HDI supports the existence of distinct manifestations of WTHD and varying underlying factors. While DHD and HDI were associated with different predictors, our results point to the crucial role of spiritual-existential factors in the experience of WTHD, identifying these aspects as target points for intervention. This study highlights the importance of a nuanced understanding and communication regarding WTHD.

Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by pathogenic variants in the TSC1 or TSC2 genes. Apart from multisystem physical manifestations, most individuals with TSC experience TSC-associated neuropsychiatric disorders (TAND). Little is known about how TAND severity changes over time and what factors may predict these changes. Preliminary data suggest the presence of differential TAND severity trajectories. Caregiver well-being may act as a mediator of TAND severity, and a well-being intervention designed for caregivers of children with developmental disabilities may improve caregiver well-being. The study aims are to (1) examine longitudinal trajectories of TAND severity in a large sample of individuals with TSC and to examine potential predictors of differential trajectories, (2) evaluate the association between caregiver well-being characteristics, TAND severity, and severity trajectories, and (3) adapt and evaluate the feasibility, acceptability, and potential efficacy of a brief, online group-based well-being intervention for family caregivers. For the first 2 aims, 500 individuals with TSC or their caregivers will be recruited in an accelerated longitudinal design to document TAND severity at 5 time points over 12 months via a web-based app. At each time point, participants will complete demographic, TSC characteristics, intervention, and well-being questionnaires. Data will be analyzed using latent class mixed and multinomial regression modeling (aim 1) and structural equation and mediation modeling (aim 2). Participatory methods will be used to adapt an existing caregiver well-being intervention for the TSC community (aim 3). Thirty caregivers will be invited to participate in the adapted group-based online well-being intervention. This study was funded from July 2024 (HT94252410790 and HT94252410791), and ethics approvals were obtained from the University of Cape Town (July 2024), Vrije Universiteit Brussel (November 2024), and the Department of Defense Office of Human Research Oversight (December 2024). The TAND Toolkit app was adapted for longitudinal data collection (aims 1 and 2). Recruitment started in December 2025 and will continue until 500 participants are enrolled (anticipated December 2026). Primary outputs are expected by July 2028. For aim 3, experiential and adaptation workshops were completed in June 2025, the pilot intervention was delivered in November 2025, and data collection will continue till May 2026. Outputs are expected by December 2026. Identification of differential longitudinal TAND trajectories and their correlates will stimulate research in TSC and generate evidence for the self-report quantified TAND checklist as a clinical outcome measure. Understanding the association between caregiver well-being and TAND severity will provide support for targeted well-being interventions. A successful pilot trial will provide preliminary data for larger-scale clinical trials, with the potential to support caregivers and improve TAND outcomes. Together, the findings from the study will help close the gap in interventions for TAND. ClinicalTrials.gov NCT06879665; https://clinicaltrials.gov/study/NCT06879665. DERR1-10.2196/91726.

In the European Union (EU), donanemab is indicated in adults with early symptomatic Alzheimer's disease who are apolipoprotein E &#x3b5;4 non-carriers or heterozygotes. Among these, patients without superficial siderosis at baseline, uncontrolled hypertension, or anticoagulant use are eligible. To assess efficacy and safety of donanemab in the EU-eligible population. A post-hoc conservative hybrid imputation method was implemented for clinical efficacy analyses during the TRAILBLAZER-ALZ 2 placebo-controlled period. In the 78-week long-term extension (LTE) participants in the early-start (randomised to donanemab) and delayed-start (randomised to placebo with donanemab initiation during the LTE) groups were compared to a propensity-weighted external control. Participants were switched to placebo after meeting amyloid-based treatment course completion criteria. By 76 weeks, donanemab-treated participants in the EU-eligible population had a mean Clinical Dementia Rating Scale (CDR)-Sum of Boxes change from baseline difference from placebo of -0.7 points (95% confidence interval, -1.0, -0.4) and a 40.3% lower risk of disease progression to the next stage (per CDR-Global score). Treatment benefit increased over 154 weeks for non-carriers and heterozygotes, including those meeting treatment course completion criteria by 52 or 76 weeks. In the placebo-controlled period, 119 (19.5%) and 49 (8.0%) donanemab-treated eligible participants experienced amyloid-related imaging abnormalities-edema/effusion and infusion-related reactions, respectively. Safety findings were similar among donanemab-treated participants in the placebo-controlled period and LTE delayed-start group. Consistent with previous TRAILBLAZER-ALZ 2 and LTE findings, donanemab significantly slowed disease progression compared to controls with a manageable safety profile in non-carriers and heterozygotes.

Narcolepsy types 1 and 2 (NT1/NT2) and idiopathic hypersomnia (IH) are central disorders of hypersomnolence (CDHs) that significantly impact patients' quality of life (QoL). We investigated the recent medication use, comorbidities, and clinical burden among participants with CDHs from six European countries. In this cross-sectional observational study, self-reported data were collected from adults with CDHs using a three-part survey. Assessed endpoints included the Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale for Clinical Trials (NSS-CT), IH Severity Scale (IHSS), and EuroQoL-5 dimension-5 level (EQ-5D-5L). EQ-5D health state utilities were evaluated by ESS category to measure the impact of symptom severity. Of 2797 surveys, 1818 (65%) were completed (NT1, 51.1%; NT2, 11.2%; IH, 19.9%; undefined CDH, 17.8%). Most participants reported receiving narcolepsy/IH medication in the past 30 days (NT1, 91.3%/NT2, 84.5%/IH, 79.4%). The most common comorbidities were back pain (NT1, 27.4%/NT2, 25.5%/IH, 30.4%), headache/migraine (22.4%/27.2%/34.7%), and depression (22.5%/24.5%/29.5%). For NT1/NT2/IH, mean (interquartile range) ESS total scores were 15.5 (12-19)/14.4 (11-18)/13.6 (10-17), NSS-CT scores (excluding cataplexy items) were 17.4 (11-23)/14.6 (9-20)/12.1 (7-17), IHSS scores were 27.0 (20-34)/27.5 (22-35)/32.4 (27-38), and EQ-5D VAS scores were 62.4 (50-78)/63.6 (50-79)/61.0 (48-79). Mean (SD) health state utilities decreased from 0.914 (0.152) in the lowest ESS category to 0.726 (0.259) in the highest (severe) ESS total score category. These findings underscore the ongoing clinical burden in individuals with CDHs, including those receiving treatment. Symptom persistence and QoL impacts highlight the limitations of current treatments and the need for more comprehensive management strategies for CDHs.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a relevant differential diagnosis for progressive polyneuropathy, with effective treatment options available. In case of an ambiguous diagnosis, supportive tests like nerve imaging are recommended. However, MRI is considered of limited use by the current guidelines. This meta-analysis provides an analysis of current data on morphological MRI features in CIDP. We searched databases in PubMed, Scopus, Web of Science, and Google Scholar and reported findings following PRISMA guidelines. We included prospective and retrospective case-control and cohort studies on qualitative or quantitative assessment of cervical and lumbar nerve roots in CIDP. The size and morphological appearance of nerve roots were compared between affected vs. non-affected subjects. We included 11 studies with qualitative and 15 with quantitative outcome measures. Odds ratios indicated hypertrophy, hyperintensity, and gadolinium enhancement in CIDP patients. Quantitative analysis confirmed larger nerve root diameters averaging at 5&#x2009;mm in the cervical and 7&#x2009;mm in the lumbosacral area. Few studies investigated the cross-sectional area and volume of nerve roots, confirming larger values in CIDP patients. Plexus imaging provides valuable adjunctive support in the diagnosis of CIDP and our analysis revealed greater diagnostic significance for lumbar nerve roots. Yet its utility must be interpreted with nuance because of data heterogeneity and potential imaging mimics simulating CIDP features on MRI. Future advancements should focus on refining imaging techniques and developing quantitative metrics to enhance diagnostic specificity. The integration of imaging modalities with clinical and electrophysiological findings remains essential in diagnosis of CIDP.

BackgroundClinicians encounter difficulties in differentiating between headache/facial pain of true sinogenic origin, and clinically similar pain related to primary headache disorders, such as migraine. The International Classification of Headache Disorders and International Classification of Orofacial Pain, together with clinical definitions of acute and chronic rhinosinusitis as refined by the European Position Paper on Rhinosinusitis and Nasal Polyps, have produced a unique opportunity to improve the current diagnostic criteria of headache/facial pain attributed to rhinosinusitis.MethodsAn international multidisciplinary panel reviewed clinical evidence regarding the overlap of primary headaches and rhinosinusitis in order to harmonize and clarify diagnostic frameworks.ResultsThe proposal integrates validated rhinologic definitions into headache and facial pain classifications. Key suggestions include the removal or adjustment of non-specific criteria (e.g., headache exacerbated by pressure applied over the paranasal sinuses) which also frequently occur in primary headache disorders. To enhance specificity, evidence-based negative predictors - such as the absence of nausea, osmophobia or photophobia and phonophobia - are introduced. Only for chronic rhinosinusitis, it has been proposed to include endoscopic or radiological evidence of inflammation, as necessary to confirm the diagnosis.ConclusionAligning ICHD-4 with contemporary rhinologic guidelines through the use of positive and negative predictors may help improve diagnostic accuracy, ensure appropriate therapy and increase the reliability of trial design.

Essential tremor (ET) is a common movement disorder characterized by heterogeneous features, though the rate and pattern of worsening are variable. Longitudinal data combining clinical and objective motor measures remain limited, resulting in uncertainty regarding trajectories and predictors of progression in ET. Twenty-two patients from a previously established ET/ET-plus cohort underwent a third clinical and kinematic evaluation almost seven years after baseline. Kinematic analysis assessed postural, kinetic, rest tremor, and finger-tapping performance. Longitudinal changes were evaluated using non-parametric statistics and linear mixed-effects models adjusting for clinical covariates. Over time, tremor worsened overall. Kinematic measures indicated a selective increase in kinetic tremor severity, while rest and postural tremor amplitude remained stable. Clinically, tremor spread to a greater number of body regions. Soft neurological signs increased over time and were associated with greater tremor spread. Cognitive performance showed only a mild decline, partly related to age and affective symptoms. Higher baseline tremor severity was associated with greater worsening of kinetic tremor, and lower baseline cognitive scores with changes in postural tremor. ET progression is heterogeneous and often non-linear. Kinematic measures were particularly sensitive in capturing worsening of kinetic tremor, the most disabling clinical feature. The accumulation of soft neurological signs and their association with tremor spread support the notion of ET-plus as a more advanced disease stage with broader cerebral involvement. Independent of disease progression, there were strong aging-related effects. Future multimodal longitudinal studies may clarify how aging interacts with disease trajectories in essential tremor.

Reproducibility of computational algorithms is a challenging but crucial requirement for medical research and an important component of trustworthy training and application of AI algorithms. Federated Learning (FL) is commonly used to enable privacy-preserving AI in medical research. One prerequisite of reproducibility is traceability. A majority of publications on traceable FL platforms leverage blockchain technology to achieve traceable FL. In healthcare settings, resource-efficient alternatives to blockchains are possible; however, their traceability features require separate design considerations. To meet the growing demand for reproducible AI, as outlined in guidelines published by governing bodies such as the European Commission, we propose a novel concept TrainTracks. TrainTracks extends the established Personal Health Train (PHT) Platform for Analytics and Distributed Machine Learning for Enterprises (PADME) to support reproducible and traceable federated learning in medical research. PADME already partially supports tracing the FL and changes to the analysis algorithms used in the FL projects. We extend PADME by adding privacy-preserving change tracing of the data, metadata, and computational experiment execution through integrating it with the tools specialized in distributed data management (DataLad and MetaLad). Finally, we evaluate the proposed concept against the detailed list of requirements to analyze the advantages of the TrainTracks and the need for further design improvements. Evaluation of the TrainTracks concepts' compliance with a checklist for reproducible AI showed that TrainTracks improves the original PADME platform in 15 points out of 47 points applicable to FL. The greatest improvement was in data reproducibility, improving 10 of 12 points from no support to full support for automatic information extraction. No improvements were made to method reproducibility, aside from introducing a dedicated reproducibility repository. Experiment reproducibility saw upgrades in 5 of 30 applicable points, mainly through workflow and code traceability. Our concept of combining FL technology with a data versioning tool provides a structured, automated workflow that traces the FL algorithm itself, delivered algorithms, and the used data. TrainTracks demonstrated high compliance with recommendations for reproducible AI experiments, methods, and data. Our work emphasizes the importance of complete FL process traceability, as all considered aspects individually contribute to the reproducibility of the medical research. Tracking dataset versions in FL is crucial for dynamic application areas, such as medical research, where new data, e.g. electronic health records, are continuously recorded and added.

Large vessel occlusion (LVO) recanalization before endovascular thrombectomy (EVT) is known as spontaneous recanalization (SR) or early recanalization (ER) after treatment with intravenous thrombolysis. In this study, we aim to investigate predictors for SR/ER and evaluate its association on functional outcomes. Patients with an anterior circulation LVO who received groin puncture for intended EVT between 2014 and 2019 were included from the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. SR/ER was defined as a presence of a LVO CTA but recanalized on first run of digital subtraction angiography. Multivariable logistic regression was used to evaluate the association between predictor variables and SR/ER. Additionally, we evaluated the association of SR/ER with functional outcomes (modified Rankin Scale [mRS] at 90 days, mortality, and National Institutes of Health Stroke Scale [NIHSS] scores at 24 hours), and performed multivariable ordinal, binary, and linear regression, where appropriate. SR/ER occurred in 251/4448 (5.6%) of patients. Multivariable logistic regression identified male sex (aOR 1.41, 95%CI 1.07-1.84), treatment with intravenous thrombolysis (aOR 3.19, 95%CI 2.03-5), and M2 occlusions (aOR 1.96, 95%CI 1.45-2.66), as independent predictors for higher odds of SR/ER. Higher NIHSS (aOR 0.94, 95%CI 0.92-0.96), use of direct oral anticoagulation (aOR 0.12, 95%CI 0.02-0.91), presence of hyperdense artery sign (aOR 0.62, 95%CI 0.47-0.83), and ICA-T occlusion (aOR 0.18, 95%CI 0.08-0.41), were significant independent predictors for a lower odds of SR/ER. SR/ER resulted in a lower NIHSS at 24 hours (a&#x3b2; -1.95, 95%CI -3.08- -0.83), a shift towards a lower mRS (acOR 0.67, 95%CI 0.53-0.86), and less mortality (aOR 0.53, 95%CI 0.34-0.82). When compared to patients who achieved successful recanalization through EVT these associations lost significance. SR/ER is associated with male sex, treatment with intravenous thrombolysis, baseline NIHSS, direct oral anticoagulation medication use, hyperdense artery sign, and ICA-T and M2 occlusions. Patients with SR/ER achieved significant better functional outcomes compared to all patients achieving successful recanalization through EVT.

Cognitive impairment associated with schizophrenia (CIAS) is a prevalent, meaningful feature of schizophrenia with limited real-world data on its recognition and care setting impact. The LUCIA initiative is an international multi-stakeholder study that explored awareness, assessment practices, and the burden of CIAS to inform future care pathways. A three phase, Delphi-informed design was applied, comprising expert interviews to frame the enquiry, qualitative interviews with health and social care professionals (HCPs; n = 74) and caregiver advocates (n = 11), two waves of a Delphi survey among HCPs (n=449 and 343, respectively) and one round among 61 patients and 112 caregivers across 15 countries (n = 964). The results showed poor awareness of CIAS across stakeholders. Structured cognitive assessment was infrequent, and clinicians largely relied on the dementia oriented Mini-Mental State Examination (MMSE) rather than schizophrenia specific tools, citing time, training, and unclear actionability as key barriers. CIAS imposed broad humanistic, clinical, societal, and economic burden - poorer quality of life, social isolation, higher comorbidities, increased hospital days and health care costs, and heavy informal care. Consensus actions prioritized the development of brief, validated screening instruments, improved psychoeducation, and accelerated research into effective pharmacological and non pharmacological interventions. These results provide additional evidence for the under-recognition of CIAS worldwide, despite its substantial multidimensional societal burden. The use of dementia-oriented cognitive tests carries significant risks of misclassification and inappropriate management. Therefore, improving awareness, implementing assessment guidelines, and accelerating therapeutic innovation is critical to improve the quality of life of CIAS patients and the wider community.

Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer's disease (AD), complicating diagnosis in patients with cognitive impairment. The CSF biomarker profile of CAA remains poorly understood, particularly with AD co-pathology. We aimed to characterize CSF biomarkers in CAA, assess diagnostic accuracy, and examine associations with neuroimaging markers. We included 261 participants from a hospital-based cohort, recruited from memory clinic outpatients and neurology inpatients. Groups comprised healthy controls (HC, n&#x2009;=&#x2009;35), CAA without AD co-pathology (CAA-nonAD, n&#x2009;=&#x2009;27), CAA with AD co-pathology (CAA-AD, n&#x2009;=&#x2009;30), and AD (n&#x2009;=&#x2009;169). CSF A&#x3b2;40, A&#x3b2;42, p-tau181, and t-tau were quantified using automated immunoassays. Group differences were tested using ANCOVA adjusted for age and sex. ROC analyses with 10-fold cross-validation and bootstrapping assessed diagnostic performance. Associations between CSF biomarkers and CAA-related MRI markers were examined using ANCOVA. A&#x3b2;40 concentrations were lower in CAA-nonAD and CAA-AD compared to AD and HC (p-valuebf&#x2009;<&#x2009;0.05). A&#x3b2;42 was reduced in CAA-AD and AD versus HC, with no difference between CAA-nonAD and AD. p-tau181 and t-tau were elevated in AD and CAA-AD compared with CAA-nonAD and HC (p-valuebf&#x2009;<&#x2009;0.05). A&#x3b2;40 showed the highest diagnostic accuracy for CAA (AUC&#x2009;=&#x2009;0.73; 95% CI: 0.66-0.80), followed by A&#x3b2;42 (AUC&#x2009;=&#x2009;0.71; 95% CI: 0.64-0.78). In AD patients, A&#x3b2;42 best discriminated coexisting CAA (AUC&#x2009;=&#x2009;0.77). Higher CAA-SVD burden scores were associated with lower A&#x3b2;40 (p-valuebf&#x2009;<&#x2009;0.05). CSF A&#x3b2;40 and A&#x3b2;42 provide complementary diagnostic value for identifying CAA, both in isolation and with AD co-pathology. Reduced A&#x3b2;40 is associated with greater CAA-related vascular burden, supporting its role as a marker of vascular amyloid pathology.

The cause of facial pain often remains unknown after ruling out dental disorders and arterial compression of the trigeminal nerve. New pathologic models and treatment options are needed. Review of 30 patients with unexplained facial pain who were diagnosed with internal jugular vein (IJV) entrapment. Mean age 48.8&#x2009;&#xb1;&#x2009;12.8&#x2009;years, duration of symptoms 68.4&#x2009;&#xb1;&#x2009;100.4&#x2009;months, women (28/30, 93%). Symptom laterality: left only (11/30, 37%), right only (8/30, 27%), bilateral equally (7/30, 23%), left worse than right (3/30, 10%), right worse than left (1/30, 3%). Facial pain lateralized to the side of underlying venous compression in 19/30 (63%) patients or was unilateral with underlying bilateral compressions in 9/30 (30%). The IJV obstructed at the atlas (lateral process of the atlas, styloid process, posterior belly digastric muscle), between muscles in the mid-neck (sternocleidomastoid, omohyoid, and anterior scalene), and at the thoracic outlet. This led to dilation of the superior petrosal sinus that abuts the trigeminal nerve and shunting through vertebral veins that congested the lower brainstem and cervical spinal cord where the spinal trigeminal nucleus originates and descends. Targeting the IJV obstruction with physical therapy, neurotoxin injections in the neck, and surgical decompression significantly improved facial pain in most patients (20/30, 67%) but was too advanced in some to achieve meaningful relief. Increasing awareness of venous outflow obstruction as a contributor to facial pain could explain complex regional neurological symptoms, provide an option beyond oral medications, and lead to earlier diagnosis when the pathology is amenable to treatment.

Clinical utility and dynamics of plasma biomarkers in early-onset dementia remain underexplored. To investigate plasma biomarker trajectories and their associations with clinical outcomes in early-onset Alzheimer disease (EOAD) and frontotemporal dementia (FTD). This multicenter, prospective cohort study analyzed participants in phase 1 of the Longitudinal Study of Early-onset Dementia and Family Members (LEAF), which was conducted from April 2021 through December 2023 in 34 centers across South Korea. Patients with &#x3b2;-amyloid-positive EOAD and FTD were included and underwent annual blood sampling and clinical assessment, within a follow-up period of approximately 2 years. Data were analyzed between June 2025 and March 2026. Levels of plasma phosphorylated tau 217 (p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) biomarkers were analyzed using assays. (1) Associations of baseline biomarkers with clinical outcomes (assessed with the Mini-Mental State Examination [MMSE] and the Clinical Dementia Rating-Sum of Boxes [CDR-SB] for the EOAD group, or the frontotemporal lobar degeneration [FTLD]-modified CDR-SB for the FTD group), (2) biomarker trajectories, and (3) association of biomarker level changes and clinical outcomes. A total of 322 participants with p-tau217, GFAP, and NfL analyses were stratified into the EOAD or FTD group based on their diagnosis. The EOAD group (n&#x2009;=&#x2009;245) had a mean (SD) age of 61.8 (5.4) years and included 163 females (66.5%), while the FTD group (n&#x2009;=&#x2009;77) had a mean (SD) age of 65.1 (7.3) years and included 45 females (62.3%). In the EOAD group, higher log2-transformed baseline p-tau217, GFAP, and NfL were each associated with faster decline in the MMSE score (association estimate [SE], -0.390 [0.127], P&#x2009;=&#x2009;.002; -0.775 [0.164], P&#x2009;<&#x2009;.001; and -0.679 [0.182], P&#x2009;<&#x2009;.001, respectively) and the CDR-SB score (estimate [SE], 0.401 [0.099], P&#x2009;<&#x2009;.001; 0.535 [0.126], P&#x2009;<&#x2009;.001; and 0.693 [0.122], P&#x2009;<&#x2009;.001, respectively). In the FTD group, GFAP and NfL were associated with MMSE decline (estimate [SE], -2.118 [0.566], P&#x2009;<&#x2009;.001 and -2.360 [0.428], P&#x2009;<&#x2009;.001, respectively), whereas p-tau217 was not (estimate [SE], 0.071 [0.418], P&#x2009;=&#x2009;.87). No biomarker was associated with FTLD-modified CDR-SB score change. Longitudinally, all mean (SD) biomarker levels increased in the EOAD group (p-tau217: 0.253 [0.077] pg/mL, P&#x2009;=&#x2009;.001; GFAP: 0.173 [0.040] pg/mL, P&#x2009;<&#x2009;.001; NfL: 0.149 [0.045] pg/mL, P&#x2009;=&#x2009;.001), whereas in the FTD group, only NfL level showed an upward pattern (0.251 [0.127] pg/mL, P&#x2009;=&#x2009;.05). Annualized biomarker changes were associated with worsening clinical outcomes in the EOAD group, but not in the FTD group. GFAP and NfL level increases were associated with MMSE score decline (estimate [SE], -0.005 [0.002], P&#x2009;=&#x2009;.007 and -0.010 [0.003], P&#x2009;=&#x2009;.001, respectively), while p-tau217 level increases were associated with CDR-SB score worsening (estimate [SE], 0.072 [0.024], P&#x2009;=&#x2009;.003) in the EOAD group. In this cohort study of patients with EOAD and FTD, baseline p-tau217, GFAP, and NfL were consistently associated with clinical outcomes in the EOAD group, whereas GFAP and NfL were associated with cognition only in the FTD group. These findings demonstrate distinct characteristics of plasma biomarkers in EOAD and FTD, supporting their potential utility for risk stratification.

To investigate the association of intracranial atherosclerotic disease (ICAD), alone and comorbid with cerebral small vessel disease (SVD), with ischemic or hemorrhagic events in patients receiving antithrombotic therapy. In this prospective, multicenter, observational study, baseline brain MRI was performed to assess SVD (white matter hyperintensities, cerebral microbleeds, lacunes, enlarged perivascular spaces [PVS]), nonlacunar infarcts, and ICAD. SVD burden was defined as SVD score >&#x2009;2. ICAD was classified as normal-to-mild, moderate, and severe stenosis-to-occlusion. The outcomes were any ischemic event, ischemic stroke, major bleeding, intracranial hemorrhage, and all-cause mortality. We assessed associations of ICAD with outcomes via Cox regression and mediation analyses, adjusting for SVD burden. Among 5250 patients (mean age: 71&#x2009;&#xb1;&#x2009;11&#x2009;years, 33% women), 3947 (75%) received antiplatelets and 1304 (25%) anticoagulants at baseline. ICAD was normal-to-mild in 3781 (72%), moderate in 571 (11%), and severe-to-occluded in 894 (17%). SVD burden was observed in 1400 (27%). ICAD was associated with a higher frequency of non-lacunar infarcts and a lower frequency of PVS. There was no graded association between ICAD severity and SVD burden. During a median follow-up of 2&#x2009;years, 278 ischemic events, 197 ischemic strokes, 97 major bleedings, 55 intracranial hemorrhages, and 217 deaths occurred. Severe-to-occluded ICAD independently increased the risk of any ischemic event (adjusted hazard ratio: 1.39 [1.03-1.86]) and mortality (2.01 [1.48-2.74]); coexisting SVD burden further increased the risk of all outcomes. ICAD directly affected ischemic events, while mortality was mainly driven by its additive interaction with SVD. ICAD increases the risk of any ischemic events and, with comorbid SVD, contributes to hemorrhagic events and excess mortality.

Patients with generalized myasthenia gravis (gMG) frequently have variable and fluctuating symptoms. Treatments providing long-term, sustained disease control are essential for improving function and health-related quality of life. In the phase 3 Vivacity-MG3&#xa0;study, nipocalimab improved clinical outcomes in adults with gMG when added to standard-of-care (SOC) therapy. These post hoc analyses further assessed the ability of nipocalimab to produce sustained responses over 24&#x2009;weeks, using the following response categories for total score improvements in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG), respectively: Meaningful Clinical Improvement (MCI; &#x2265;&#x2009;2- and &#x2265;&#x2009;3-point), Substantial Improvement (SI; &#x2265;&#x2009;3- and &#x2265;&#x2009;4-point), Considerable Improvement (CIP; &#x2265;&#x2009;4- and &#x2265;&#x2009;5), Composite Response (CR; MG-ADL improvement &#x2265;&#x2009;2-points plus QMG improvement &#x2265;&#x2009;3-points), and Minimal Symptom Expression (MSE; MG-ADL 0 or 1). Significantly higher percentages of nipocalimab-treated than placebo-treated participants achieved MG-ADL MCI, SI, and CIP, sustained for &#x2265;&#x2009;12 consecutive weeks; achievement of these outcomes occurred as early as week 1 among nipocalimab-treated participants. Similar results were observed for QMG MCI, SI, and CIP. Significantly higher percentages of nipocalimab-treated participants achieved CR, sustained for &#x2265;&#x2009;8 consecutive weeks versus placebo; the likelihood of achieving sustained CR for &#x2265;&#x2009;8&#x2009;weeks was higher with nipocalimab (odds ratio&#x2009;=&#x2009;6.3). Nipocalimab-treated participants were 4-fold more likely to achieve MSE, sustained for &#x2265;&#x2009;8 consecutive weeks versus placebo (p&#x2009;=&#x2009;0.022). MSE and CR were achieved earlier among nipocalimab-treated participants. Nipocalimab treatment improves gMG symptoms earlier than placebo and provides meaningful and long-term sustained disease control over 24&#x2009;weeks among participants with gMG.

Central disorders of hypersomnolence (CDH) are, except for Narcolepsy Type 1 (NT1), difficult to diagnose and manage because of overlapping features and the lack of reliable biomarkers. Machine learning (ML) has the potential to improve diagnosis by detecting subtle physiological patterns and distinguishing between CDH subtypes. This review systematically explores current ML applications in CDH, assesses their limitations, and suggests future directions. Following PRISMA guidelines, MEDLINE, Embase, PsycINFO, IEEE Xplore, CINAHL, Web of Science, and Google Scholar (up to June 2025) were searched for studies using ML to classify or characterize CDH in adults. ML methods, data types, and diagnostic outcomes were extracted and analyzed. Out of 3274 studies, 41 met the inclusion criteria (37 peer-reviewed articles and 4 preprints). Data sources included neuroimaging (fMRI, PET), sleep assessments (MSLT, polysomnography), demographics, and standardized questionnaires. Supervised ML reliably identified known features, including early REM onset, hypocretin deficiency, and spectral EEG changes, showing strong performance for NT1 but limited generalizability across other CDH subtypes. Although many studies reported high accuracy, clinical relevance was often limited by rigid diagnostic labels that may not reflect the true complexity of CDH. Unsupervised learning uncovered heterogeneous phenotypes and exposed limitations in existing diagnostic labels. ML has the potential to improve CDH diagnosis. Deep learning models are promising for feature extraction; however, their black-box nature and high data requirements hinder clinical application. Future advancements depend on large, diverse datasets, multimodal and longitudinal data, and close collaboration between clinicians and data scientists.

The acute imbalance syndrome (AIS) refers to acute-onset and persistent vertigo, dizziness and/or imbalance without nystagmus, reflecting a subset of the acute vestibular syndrome (AVS) with or without nystagmus. While AVS with nystagmus is well characterized and the approach to these patients is validated, much less is known about patients presenting with AIS. This systematic review synthesizes current epidemiologic and clinical evidence on AIS. MEDLINE and Embase (2000-2024) were searched for English-language original articles addressing acute imbalance, vertigo/dizziness and reporting on nystagmus and/or AVS/AIS. Two reviewers independently screened articles and extracted predefined parameters. The review was registered with PROSPERO (CRD42024623068). Forty studies (n&#x2009;=&#x2009;11,731 patients) were included, with 2730 patients being classified as AVS. Prevalence of AVS (with/without nystagmus) amongst all acutely dizzy patients was 16.4% and 50.5%, respectively, in two studies. 49.4% of central AVS cases were classified as AIS. Whereas AIS presentation was rare in AICA strokes (9%), fractions reached 40% (PICA), 57% (SCA), and 62% (PCA) for other vascular territories. Data on underlying causes in noncentral AIS was limited, with dysautonomia, drug intoxication, and heart disease being most frequently identified. With almost 50% of central AVS cases presenting as AIS, this emphasizes the importance of selecting bedside testing appropriately, focusing on algorithms such as STANDING or graded truncal instability. Patients presenting with AIS have a distinct differential diagnosis than those with AVS with nystagmus, mostly due to the distribution of noncentral causes. Promoting awareness of AIS and its diagnostic approach should be prioritized in emergency and acute neurological settings.