Neurology

BackgroundLarge middle cerebral artery (MCA) infarctions can result in life-threatening cerebral edema. Quantitative brain atrophy may improve risk stratification for severe edema. We examined whether quantitative brain atrophy is associated with severe midline shift after large ischemic stroke and whether incorporating atrophy improves prediction beyond established clinical and radiographic predictors. MethodsThis was a retrospective observational cohort study of patients with [≥][1/2] MCA ...

ObjectiveTo compare early cerebrospinal fluid (CSF) cytokine profiles in intracerebral hemorrhage (ICH) versus subarachnoid hemorrhage (SAH), with a focus on angiography-negative SAH (anSAH). MethodsWe conducted a retrospective observational cohort study of adults with spontaneous hemorrhagic stroke (ICH or SAH). For cytokine analyses, we included patients with external ventricular drains (EVDs) and analyzed the first CSF sample obtained within 72 hours of symptom onset. Cytokines were measured...

Background: Platform trials are an efficient trial design which enable testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professiona...

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterised by progressive neurological disability and heterogeneous symptom trajectories. Current clinical monitoring methods, including magnetic resonance imaging (MRI) and episodic neurological assessments, provide limited insight into subtle disease progression and functional changes. Digital health technologies integrating multimodal biosignals and behavioural assessments may enable continuous monitoring and personalised rehab...

INTRODUCTIONAlzheimers disease (AD) diagnostic guidelines emphasize subjective cognitive decline (SCD) preceding mild cognitive impairment (MCI), implicitly assuming awareness of cognitive decline (ACD) is preserved in preclinical AD. This study aimed to evaluate associations of decreased ACD with multimodal core AD biomarkers in cognitively unimpaired (CU) individuals. METHODSWe analyzed data from CU individuals with baseline CSF biomarkers and 3-year longitudinal neuropsychological assessment...

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we include...

Background Whole-genome sequencing (WGS) has improved the diagnosis of rare genetic disorders, yet interpretation of non-coding variants that affect splicing remains challenging. In silico predictions alone are insufficient, and short-read RNA sequencing may fail to capture complex or low-abundance splicing events. Targeted amplicon-based long-read RNA sequencing (Amp-LRS) offers a cost-effective approach for functional validation of candidate splice-altering variants. Methods We applied Amp-LRS...

Protocadherin-12 (PCDH12), a cell-adhesion protein belonging to the non-clustered protocadherin family, plays a crucial role in the establishment and regulation of neuronal connections and communication. Bi-allelic loss-of-function (LoF) variants in the PCDH12 gene have been associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic junction dysplasia (DMJD) syndrome, cerebral palsy, and cerebellar ataxia, often accompanied by ocular abnormalities. However, ge...

Oscillatory coupling between respiration, heart rate, and cortical function is fundamental to physiological regulation yet remains poorly characterized in humans. Diminished respiratory heart rate variability (RespHRV)--the rhythmic heart rate modulation accompanying respiration--has emerged as a transdiagnostic biomarker of mental and physical health, reduced in anxiety, depression, cardiovascular disease, and aging (Beauchaine & Thayer, 2015; Menuet & Gourine et al., 2025). However, the cortic...

Importance: Dementia is common in Parkinson's disease (PD), causing greater disability than other symptoms, but varies in timing. Although visual deficits are linked with PD dementia, how these interact with genetic factors to predict PD dementia has not been characterised. Objective: To investigate whether visual deficits and genetic factors predict PD dementia. Design: Large prospective longitudinal case-control study, mean follow-up 32.7 (SD=12.3) months. Setting: Cases were recruited between...

Alzheimers disease and related dementias (ADRD)1 and Parkinsons disease and related disorders (PDRD)2 have substantial genetic contributions, yet the role of rare damaging coding variants remains incompletely characterized at population scale3-6. We performed gene-based burden testing of rare loss-of-function and deleterious missense variants using whole-genome sequencing data from large population biobanks combined with disease-specific sequencing cohorts, leveraging proxy phenotypes to maximiz...

IntroductionThe eligibility of anti-amyloid disease-modifying therapies (DMTs) and their integration into clinical practice in some institutions requires a specific range of Mini-Mental State Examination (MMSE) scores. Reliance on this pencil-and-paper psychometric instrument imposes operational burdens and risks perpetuating health disparities due to the tests known educational and cultural biases. This study evaluates the efficacy of the Digital Clock and Recall (DCR) - a rapid, FDA-listed dig...

We describe the design of the first non-pharmacological prevention trials of Parkinsons Disease worldwide: the randomised controlled Slow-SPEED trials. The three trials examine the feasibility and preliminary efficacy of a gamified, remotely administered exercise intervention vs. active control program over 18-36 months in the Netherlands (n=110), United Kingdom (n=110) and United States (n=600). Each trial focuses on a complementary prodromal subgroup: isolated/idiopathic REM sleep behavioural...

OBJECTIVEUsing two cohorts and synthetic datasets, we estimated effects of prospectively reported alcohol use on memory outcomes across middle age. METHODSData were from National Longitudinal Study of Youth 1979 (NLSY79, n=7540, alcohol reports from ages 18-26), Health and Retirement Study (HRS age 50-56 at enrollment, n=13,090), and a synthetic cohort matching early life exposure information from 3,259 NLSY79 participants to later life memory information from 5,451 HRS participants. Covariate-...

Background and ObjectivesAssociations of common infections with Alzheimer disease (AD) risk have been reported. A hypothesized mechanism to explain these is cerebral amyloid-beta (A{beta}) aggregation as a defence in response to infection, with subsequent tau accumulation. However, few studies have assessed associations of infections with tau and A{beta} pathology. We investigated associations of serological measures of several common infections with plasma p-tau217 and A{beta} status measured b...

BackgroundAdapted dance is a promising rehabilitation intervention for physical and psychosocial impairments in people with chronic stroke. However, in-person attendance is hindered by limited community ambulation, transportation, and schedule conflicts. At-home participation with a live-streamed dance program could address these issues, but psychosocial benefits may be diminished because of reduced social interactions. The primary objective of this study was to assess the feasibility and safety...

Resting-state electroencephalography (EEG) has been proposed as a scalable source of biomarkers for chronic pain, but its clinical potential remains uncertain. To systematically evaluate this potential, we benchmarked nine modeling strategies, spanning conventional machine learning with handcrafted features to state-of-the-art deep learning. Across 72 configurations of signal representations and model architectures, we trained models to predict self-reported pain intensity, using chronological a...

Purpose: Human anatomy remains foundational to clinical practice, yet reduced instructional hours raise concerns about graduate competence and preparedness for patient care. Although trainees often report confidence, supervisors may perceive deficiencies, creating a gap between self-assessment and external evaluation. This study examined stakeholder perspectives on anatomical competence within physical therapy education to identify areas of discordance in perceived capability. Methods: A cross-s...

BackgroundEvolocumab promotes coronary plaque regression in patients with coronary artery disease, but little is known regarding carotid plaques (CP). This study aimed to evaluate the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) compared to lipid-lowering therapy (LLT) alone. MethodsAsymptomatic patients with internal carotid stenosis[≥]50% and LDL-C[≥]100 mg/dL were randomized to ELLT or LLT and monito...

Background and Purpose: Magnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with...