Frontiers in Neurology

Variable recovery in vestibular rehabilitation underscores the need for objective biomarkers to identify patients at risk of poor clinical outcomes. This study aimed to establish proof of concept for a multidimensional prognostic framework using structural cervical vestibular evoked myogenic potential (cVEMP) and functional modified Clinical Test of Sensory Interaction on Balance (mCTSIB) markers to predict therapeutic success. This prospective cohort study was conducted at a tertiary rehabilitation center between June 2023 and May 2025. Participants were adults with peripheral vestibular disorders, including unilateral vestibular dysfunction, Meniere disease, or superior semicircular canal dehiscence. All participants underwent a customized five-session vestibular rehabilitation protocol. Primary outcomes were subjective clinical success, defined as an 18-point reduction in Dizziness Handicap Inventory (DHI) score, and functional success, defined as a 3-point increase in Dynamic Gait Index score. Among 30 participants (mean age 60.8 years; 77% female), the rehabilitation protocol was associated with significant improvements in mean DHI (53.7 to 37.8; P = .003) and Dynamic Gait Index (19.5 to 22.1; P = .003) scores. While 83% of participants showed raw DHI improvement, only 37% achieved the 18-point minimal clinically important difference. Notably, no participants in the bilateral cVEMP absence group achieved subjective success, compared with 52.6% in the bilateral present group (P trend = .08). Multivariable logistic regression identified baseline DHI severity as an independent predictor of success (odds ratio, 1.05; 95% CI, 1.00-1.10; P = .04). Functional gait success was significantly correlated with baseline vestibular and visual preference ratios. These findings suggest that baseline otolithic structural integrity is a primary determinant of subjective recovery. Bilateral structural loss may represent a "structural floor" where meaningful relief is physiologically limited despite functional gains. These results support a precision-based model using structural and sensory biomarkers to tailor rehabilitation

Background Functional neurological disorder (FND) is a common neurological condition characterised by symptoms which vary characteristically with attention. In the sensory realm, these symptoms frequently take the form of 'phantom' perception in the absence of sensation. While the condition is generally regarded not to cause auditory symptoms, tinnitus is a phantom perception which varies with symptom-focused attention, and is suggested to have similar underlying mechanisms to those proposed for FND. Based on this, we hypothesized that tinnitus might reflect the same underlying process as FND, and that it would therefore be more common in people with FND (pwFND). Methods Using an international database, we compared the proportions of pwFND who reported tinnitus with a control group. To ensure that observed differences were not attributable to agreement bias in symptom reporting, we also conducted an experiment where pwFND and controls were asked to report which symptoms they had experienced in the past month, 14 of which were symptoms of FND, and 7 of which were unrelated. Results Rates of tinnitus were significantly higher in the FND group (54% HDI 50 - 57%, n=732) than the control group (17% HDI 8.5 - 25%, n=59). In the symptom reporting experiment, pwFND (n=38) reported more FND-related symptoms than controls (n=38), but there was no between-group difference in reporting of non-FND related symptoms. Discussion Based on the markedly higher prevalence of tinnitus in pwFND than controls, and the substantial overlap in mechanisms and phenomenology, we believe tinnitus should be considered a possible symptom of FND, where both conditions reflect a failure of symptom resolution after incitement by a peripheral stimulus.

Withdrawal StatementThe authors have withdrawn this manuscript because the authors have decided to conduct a comprehensive and substantial revision of the manuscript. This revision will involve significant adjustments to the study design, data analysis, and key conclusions, which will fundamentally change the content and focus of the original manuscript. Therefore, we believe it is inappropriate to keep the current version as a preprint, as it does not reflect the final direction and quality of our research. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

Introduction: High-intensity locomotor training (HIT) is recommended for improving walking capacity, but treatment responses are variable. Understanding the brain changes underlying responsiveness to training could provide insight into this variability. Emerging evidence suggests upregulation of the contralesional cortico-reticulospinal tract (CRST) may contribute to walking function after stroke. However, it is unclear whether CRST upregulation is supportive or maladaptive, and no studies have examined CRST changes after HIT. This study investigated how CRST and corticospinal tract (CST) strength and laterality reorganize, and their relationship with walking capacity after locomotor HIT. Methods: Ten participants with chronic stroke completed a 4-week no-intervention control phase then 4-weeks of HIT. Diffusion MRI and 6-minute walk distance were obtained at weeks 0, 4, and 8. Analysis tested changes in ipsilesional and contralesional CRST and CST strength and laterality. Associations between changes in tract laterality and walking capacity were examined. Results: During the treatment phase (vs. the control phase), there were significantly greater increases in contralesional CRST strength (1.02 SD [95% CI: 0.25, 1.79]), contralesional CRST laterality (4.44 [2.15, 6.72]), and 6-minute walk distance (33 meters [17, 50]). Walking capacity improvements were associated with changes in CRST laterality (r = 0.77, p = 0.01), but not CST laterality (r = -0.01, p = 0.98). Discussion: Following HIT, increases in contralesional CRST strength and laterality were observed. CRST laterality changes were strongly associated with walking improvements, suggesting a possible supportive role of contralesional CRST in mediating training-related improvements in walking function after stroke.

BackgroundAcute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. ObjectivesThis trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and designThe CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. OutcomesThe primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. ConclusionsResults of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry numberChiCTR2300074147 (www.chictr.org.cn).

Objectives: Among individuals attending stroke rehabilitation, we aimed to determine the proportion who participated in cardiorespiratory exercise, identify patient characteristics predicting participation, and describe exercise characteristics. Design, setting, and participants: This was an observational cohort study involving all patients admitted to four stroke rehabilitation centres in Ontario, Canada, during March or October 2019, or over 12 months starting in 2021. Main measures: Patient characteristics extracted during chart review included age, sex, marital status, employment status, date of stroke, time post-stroke at admission, length of stay for rehabilitation, past medical history that could affect exercise participation, Functional Independence Measure, Functional Ambulation Category, mobility aid use, Chedoke-McMaster Stroke Assessment, Montreal Cognitive Assessment, National Institutes of Health Stroke Scale, and details describing cardiorespiratory exercise completed. Results: 40.1% of stroke patients participated in cardiorespiratory exercise, with 26.4% having it included in their treatment plan. Diagnosed cardiac disease (OR=0.74), poor left ventricular function (OR=0.09), history of mental health conditions (OR=0.69), lower functional ambulation ability (OR=0.74), and wheelchair use at rehabilitation admission (OR=0.46) were associated with lower odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Use of a walker or rollator at rehabilitation admission (OR=3.22), having a cardiorespiratory exercise goal (OR=2.13), and longer lengths of stay (OR=1.01) were associated with higher odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Only 1.5% of patients (N=9/601) who participated in cardiorespiratory exercise completed it with recommended intensity and duration. Conclusion: Improving participation in cardiorespiratory exercise during stroke rehabilitation may require addressing cardiovascular, mental health, and mobility-related barriers.

Background: Previous studies have shown the benefit of dual antiplatelet therapy (DAPT) for acute minor ischemic stroke. Argatroban, is a thrombin inhibitor and is primarily used in patients with acute ischemic stroke experiencing early neurological deterioration. There is no study about the benefit of antiplatelet plus anticoagulant in this population. We aim to study the difference between the combination of argatroban and clopidogrel and DAPT in the outcomes of patients with acute minor ischemic stroke (AMIS, NIHSS <5) presenting within 72 hours after onset. Methods: Argatroban combined with clopidogrel versus aspirin combined with clopidogrel in Stroke (ACAP study) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded endpoint evaluation conducted at four centers in China. This trial will randomize 464 eligible patients with minor ischemic stroke of NIHSS 5 (232 in each arm) within 72 hours of the last known well to receive intravenous argatroban with clopidogrel (treatment group) or aspirin plus clopidogrel (control group). The primary outcome is the proportion of patients achieving excellent outcome, defined as a score of 0-1 on the modified Rankin scale, at 90 days. Conclusions: The ACAP trial will provide important data on the role of intravenous argatroban in patients with acute minor ischemic stroke presenting within 72 hours of last known well.

Background: High-dose high-intensity upper limb neurorehabilitation can lead to meaningful clinical gains even in chronic stroke, yet substantial variability in recovery remains unexplained. Identifying neurophysiological markers linked to neuroplasticity and recovery could provide mechanistic insights and guide personalised rehabilitation. Objective: To characterise stroke-related alterations in {beta}-activity during movement and neural activity at rest and explore associations between brain activity and changes in upper limb clinical outcomes in chronic stroke survivors undergoing three-week high-dose rehabilitation. Methods: Electroencephalography (EEG) was recorded during the three-week rehabilitation programme in 40 chronic stroke survivors participating in the Queen Square Upper Limb (QSUL) Programme, as well as in 26 healthy controls. Recordings were taken during passive movement of the affected and unaffected index fingers (~70 movements per hand) and at rest (~7 min). Clinical assessments included the Fugl-Meyer Upper Limb Assessment (FM-UE), reflecting impairment-level deficits, and the Chedoke Arm and Hand Activity Inventory (CAHAI-13), capturing real-world upper limb activity, to examine their differential relationships with movement-related {beta}-activity. Results: Stroke survivors showed significant improvements in FM-UE and CAHAI scores following the rehabilitation programme (Mean {Delta}: FM-UE = 7.5, CAHAI = 7.4), exceeding minimum clinically important differences. Compared to controls, stroke survivors exhibited less strong {beta}-event-related desynchronization/synchronization ({beta}-ERD/ERS) during passive movement of the affected and unaffected index finger, with effects lateralised to the lesioned hemisphere. No significant differences at rest were observed between stroke participants and healthy controls. Only improvements in CAHAI, but not FM-UE, were associated with stronger {beta}-ERD (more negative) and stronger {beta}-ERS (more positive) responses during passive movement. Conclusions: Stronger movement-related {beta}-activity is associated with improvements in upper limb activity following high-dose high-intensity neurorehabilitation, suggesting {beta}-activity as a potential marker of neuroplasticity.

Background. Carotid webs (CaWs) are shelf-like protrusions in carotid bifurcation recognized as a potential cause of ischemic stroke. However, their impact on wall-based hemodynamic metrics (TAWSS, OSI, RRT) in distinguishing from normal bifurcations remains unclear. Methods. Carotid geometries were reconstructed from CT angiography in patients with CaWs, classified as symptomatic (with ischemic stroke) or asymptomatic (incidentally detected), and controls with normal bifurcations. Influence of three blood viscosity models (Newtonian, Carreau-Yasuda, Casson) was evaluated. Metrics were quantified using a Gaussian-weighted spatial averaging method and compared between groups. Results. CFD simulations were performed in 22 CaW cases (16 symptomatic, 6 asymptomatic) and 6 normal bifurcations. Simulations predicted recirculation corresponding to delayed contrast clearance on DSA. Viscosity models had minimal influence on flow patterns (<2% differences). CaWs showed greater inter-patient variability than normal bifurcations, but overlap remained (e.g., TAWSS 3.39 (2.72-8.96) vs 4.18 (3.09-4.56) Pa, p = 0.858). Symptomatic CaWs showed lower TAWSS and higher OSI and RRT than asymptomatic CaWs (TAWSS 3.39 vs 6.63 Pa), although did not reach statistical significance (p > 0.25). Conclusion. Symptomatic CaWs show lower shear stress and stronger oscillations than asymptomatic CaWs. However, wall-based hemodynamic metrics alone may not distinguish CaWs from normal carotid geometries.

Background:Stroke continues to be one of the major causes of death and long-term disability worldwide, with a greater impact in low-and middle-income countries. In India, there is limited evidence examining stroke burden and its changes over time and across regions. Therefore, we aimed to assess the burden of stroke in India from 1990 to 2023 using the latest data from the Global Burden of Disease (GBD) Study, along with projections up to 2035. Methods:We used estimates from the GBD 2023 study to examine stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in India from 1990 to 2023. Age-standardized rates were analyzed to understand how these measures have changed over time. We also conducted state-level analyses to explore regional differences in stroke burden. The contributions of all major modifiable risk factors were assessed using population-attributable fractions. In addition, we projected future trends in stroke burden up to 2035. Results:From 1990-2023, the percentage change in overall stroke burden in India showed minimal variation across key indicators. Incidence remained largely stable (0.00%[-0.04 to 0.05]), while prevalence showed a slight increase(0.06%[0.03 to 0.10]). Mortality (-0.11%[-0.36 to 0.20]) and DALYs (-0.17%[-0.38 to 0.12]) demonstrated modest declines over the study period. Notable regional disparities were evident, with states such as Chhattisgarh, Assam, and Jharkhand bearing the highest burden. High systolic blood pressure remained the leading risk factor in 2023, contributing the largest share of stroke-related deaths, followed by dietary risks, air pollution, tobacco use, and high body mass index. Future projections indicate that by 2035, stroke prevalence is likely to increase, while incidence, mortality, and DALYs are expected to show only modest changes. Conclusions: Stroke remains a major and growing public health challenge in India with a continuing increase in burden despite slight improvements in age-standardized rates over time. Addressing this challenge will require stronger prevention efforts, better control of key risk factors, and focused strategies to reduce regional disparities in stroke burden nationwide.

Background. Up to 70% of stroke survivors develop cognitive impairment, yet clinicians lack non-invasive vascular biomarkers that could meaningfully inform risk stratification. Carotid-femoral pulse wave velocity (cfPWV), the gold-standard measurement of central arterial stiffness, is a novel biomarker of vascular aging linked to cognitive impairment. This study evaluated the association between cfPWV and post-stroke cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), in individuals [&ge;]6 months post-stroke. Methods. This is a secondary cross-sectional analysis of baseline data from a randomized control trial. Logistic regression analyses examined the association between cfPWV (m/s) and MoCA score at the primary cut point of [&le;]26/30, with secondary cut points of [&le;]24/30 and [&le;]22/30. Models were adjusted for age, sex, systolic blood pressure, type-2 diabetes, National Institutes of Health Stroke Scale (NIHSS) score, and smoking status. Results. Of 82 participants enrolled in the main trial, 68 participants (n = 45 males, age 64.6 {+/-} 9.6 years, 1.8 {+/-} 1.2 years post-stroke) with mild-to-moderate stroke severity (NIHSS median [IQR] = 1 [2]) were included. In the fully adjusted model using the MoCA [&le;]26/30 cut point, each 1 m/s increase in cfPWV was associated with a 35% increase in the odds of post-stroke cognitive impairment (adjusted OR [aOR] = 1.35; 95% CI 1.06, 1.81; p = 0.027; Area Under the Curve [AUC] = 0.77). Consistent associations were observed at the MoCA [&le;]24/30 (aOR = 1.41; 95% CI 1.04, 2.01; p = 0.037; AUC = 0.88) and MoCA [&le;]22/30 (aOR = 1.33; 95% CI 1.03, 1.79; p = 0.039; AUC = 0.82) cut points. Conclusions. Higher cfPWV was independently associated with post-stroke cognitive impairment across clinically referenced MoCA cut points. cfPWV may be a complementary vascular biomarker to support cognitive risk stratification and identify stroke survivors who could benefit from closer monitoring or vascular-targeted intervention.

Background: Stroke is a time-sensitive neurological emergency in which early EMS activation and presentation to definitive care are cornerstones of effective therapy. Large language models (LLMs) are increasingly consulted by the public for medical advice, but the veracity of the guidance provided by commercially available models responding to potential stroke symptoms is not well understood. Methods: We performed a cross-model benchmarking study comparing the triage choices of three frontier LLMs (Claude Sonnet 4.6, GPT-4o, and Llama 3.3-70b-versatile) on first-person vignettes describing a unilateral arm symptom on waking, across 10 symptom descriptors, and two clinical phases (before and after a partially reassuring self-examination), with or without a clinical distractor (n=50 per condition). Results: Claude sought emergency care most often, Llama least, and GPT-4o in between, diverging most sharply in the post-examination phase where Claude called 911 in 100% of runs, Llama called for non-emergency help in 100%, and GPT-4o was symptom-dependent. A distractor shifted behavior away from emergency care in almost all conditions: calling 911 fell from 37.9% to 14.6% and waiting rose from 0% to 45.9% in the post-examination vignette. Responses were also sensitive to symptom word: weak, limp, heavy, and clumsy generated higher alarm, whereas numb, tingly, odd, strange, and weird generated less urgent responses. Conclusions: The increasing use of LLMs for medical advice has significant public health implications. Commercially available LLMs show significant model-to-model variability and framing sensitivity when confronted with potential stroke symptoms, including under-recognition of canonical CDC warning descriptors, underscoring the need for systematic benchmarking as these tools become de facto first points of contact for patients experiencing neurological emergencies.

Background: Clinical evidence on the contemporary management and functional outcomes of patients with Wernicke encephalopathy remains limited. This study aimed to clarify the nationwide patterns of thiamine administration and functional outcomes at discharge. Methods: Using the Japanese nationwide inpatient Diagnosis Procedure Combination database, we identified patients hospitalized with Wernicke encephalopathy between July 2010 and March 2024. Initial intravenous thiamine doses were categorized as low ([&le;]300 mg/day), medium (301-900 mg/day), or high (>900 mg/day). Outcomes included in-hospital mortality and functional status (Barthel Index) at discharge. Results: We identified 7856 patients with Wernicke encephalopathy. Over the 13-year study period, the proportion of patients receiving initial high-dose thiamine increased markedly from 5.4% to 49.0%, while the frequency of low-dose therapy decreased from 83.0% to 37.9%. Despite prompt intervention [median time to initial administration: 0 days (interquartile range, 0 to 0 days)], 56.1% of patients were discharged with impaired activities of daily living (Barthel Index <90), and the in-hospital mortality rate was 3.8%. Conclusions: High-dose thiamine treatment is increasingly implemented for Wernicke encephalopathy in Japan. Although in-hospital mortality was relatively low, the high prevalence of functional impairment at discharge, despite early treatment initiation, indicates substantial burden of Wernicke encephalopathy. Given the limited clinical evidence, further research investigating the optimal thiamine dose and develop effective primary prevention strategies for Wernicke encephalopathy is needed.

Background: Huntington ' s disease (HD) causes progressive postural control deficits, but how sensory reweighting mechanisms degrade across disease stages remains poorly understood. Objective: To determine whether objective markers of postural sway track disease severity and altered sensory reweighting across the HD spectrum. Methods: Ninety-seven adults (46 {+/-} 14 yrs) were categorized into four groups: 29 with HD, 27 pre-manifest (PM), 28 not at risk (AR-), and 13 age-matched healthy controls (HC). Participants performed three trials of quiet standing with eyes open and eyes closed on a force plate. Results: Manifest HD individuals exhibited greater AP, ML, and total COP sway displacement compared with the PM, AR-, and HC groups. HD and PM groups demonstrated greater instability with eyes closed. COP wavelet power was concentrated below 1 Hz across all groups. The eyes-open to eyes-closed change in 0-1 Hz power predicted total COP sway in HC (68%), AR- (45%), and PM (46%), but this relation was substantially weaker in HD. Conclusions: Progressive weakening of oscillatory-sway coupling distinguishes manifest HD from premanifest stages. PM individuals demonstrate early sensory reweighting deficits that manifest only when vision is removed, while HD individuals show decoupled oscillatory activity that fails to support stable postural regulation. This progressive decoupling may serve as a candidate marker of disease conversion prior to overt motor diagnosis.

ObjectiveTo describe the design, feasibility, and baseline characteristics of the Migraine Impact on Neurocognitive Dynamics (MIND) study, a 30-day smartphone-based cohort for high-frequency assessment of cognition and symptoms in adults with migraine. BackgroundCognitive symptoms are an important component of migraine burden, but they are difficult to measure using single-visit testing or retrospective questionnaires. Repeated smartphone-based assessment may better capture real-world variability in cognition and symptoms. MethodsAdults meeting International Classification of Headache Disorders, 3rd edition, criteria for migraine were enrolled remotely and completed 30 days of once-daily ecological momentary assessments and mobile cognitive tasks delivered through the Mobile Monitoring of Cognitive Change platform. Baseline measures assessed demographics, migraine characteristics, disability, mood, stress, and treatment patterns. Feasibility was evaluated using enrollment, completion, and retention metrics. ResultsA total of 177 participants enrolled (mean age 38.8 {+/-} 11.9 years; 79.7% female), including 80/177 (45.2%) with chronic migraine. Across the 30-day protocol, 3688 daily assessments were completed, representing 70.8% of all possible study days, and 70.6% of participants completed at least 20 days of monitoring. Completion remained above 60% across study days. At baseline, chronic migraine was associated with greater burden than low-frequency and high-frequency episodic migraine, including higher MIDAS scores (98.6 vs. 38.7 and 70.3), more days with concentration difficulty (16.0 vs. 7.9 and 11.5), and more days with functional interference (18.5 vs. 7.6 and 13.0). ConclusionsThe MIND study demonstrates the feasibility of high-frequency smartphone-based assessment of cognition and symptoms in migraine and provides a methodological foundation for future analyses of within-person cognitive and symptom dynamics across the migraine cycle.

Bakground and Purpose Antiplatelet resistance is a recognized risk factor for recurrent ischemic stroke, yet evidence supporting platelet function test?guided antiplatelet therapy modification in stroke prevention remains limited. We investigated whether VerifyNow-guided antiplatelet therapy modification reduces recurrent ischemic stroke in patients with atherothrombotic or lacunar infarction. Methods This retrospective observational study enrolled consecutive patients with atherothrombotic or lacunar infarction at a single center (April 2023-March 2025). Of 302 patients, 243 were analyzed: 122 in the modified group, whose antiplatelet agent was selected based on VerifyNow Aspirin Reaction Units and P2Y12 Reaction Units, and 121 in the unmodified group, whose agent was empirically selected. The mean follow-up period was 1.62 {+/-} 0.61 years. In the modified group, when both aspirin and clopidogrel showed inadequate inhibition, prasugrel or cilostazol was selected. The primary endpoint was recurrent ischemic stroke; the secondary endpoint was intracranial hemorrhage. Cox proportional hazards models with inverse probability weighting were used to adjust for confounders. Results Recurrent ischemic stroke occurred in 1 patient (0.8%) in the modified group versus 8 (6.6%) in the unmodified group (log-rank P=0.018). After adjustment, the modified group had a significantly lower risk of recurrent stroke (HR, 0.10; 95% CI, 0.012-0.84; P=0.033). Intracranial hemorrhage occurred in 0 (0%) and 1 (0.8%) patients, respectively. Conclusions In Japanese patients with atherothrombotic or lacunar infarction, VerifyNow-guided antiplatelet therapy modification was associated with a significantly lower incidence of recurrent ischemic stroke without increased hemorrhagic risk. Given the single-center retrospective design and small sample size, validation in a multicenter randomized controlled trial is warranted.

Background: The past decade has witnessed rapid growth of clinical-trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the U.S. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing geographic origin, funding source, and clinical impact of practice-changing RCTs. Methods: From the 2018 and 2026 American Heart Association/American Stroke Association (AHA/ASA) Acute Ischemic Stroke (AIS) Guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/USA/Other), funding source (government/academic/non-profit vs. industry (private/mixed); NIH vs. non-NIH), and research topic (endovascular therapy (EVT), thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the chi-square/Fisher?s exact tests, with Rao-Scott adjusted chi-square tests accounting for weighting. Results: We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the U.S. (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the U.S. declined to the smallest share (14.6%), across all weighted analyses (p<0.01). NIH-funded trials declined significantly from 21.3% (unweighted), 27.4% (reference-density-weighted), and 27.3% (clinical-impact-weighted) in 2018 to 4.5%, 4.8%, and 3.4%, respectively in 2026 (p<0.01 across all weighted strategies). Conclusion: In this analysis, we identify a shift away from U.S.-based clinical trials and increasing contributions from China. U.S.-based RCTs fell from the second most cited to the least cited sources of practice-changing recommendations. NIH-funded research fell from nearly one-quarter in 2018 to <5% in 2026, highlighting increasing dependence on non-U.S. studies for U.S.-based care. These findings raise questions about the effectiveness of current AIS research paradigms in the U.S. Keywords: Acute Ischemic Stroke, Endovascular Thrombectomy, Thrombolytic Therapy, NIH Funding

Measuring neuromotor control after stroke is crucial for identifying the mechanisms underlying asymmetrical walking and guiding rehabilitation. The lower extremity portion of the Fugl-Meyer (FM-LE) and the number of muscle synergies are commonly used measures, but have important limitations. The dynamic motor control index has emerged as a complementary metric, yet its relationship to established clinical measures (i.e., FM-LE), muscle synergy number, and gait biomechanics remains unclear. This study evaluated the ability of the dynamic motor control index to quantify post-stroke neuromotor impairment relative to FM-LE and muscle synergy number and examined its relationship with propulsion asymmetry. Electromyography data from 22 individuals post-stroke and 31 neurotypical controls were analyzed using non-negative matrix factorization. The dynamic motor control index and not the muscle synergy number differentiated paretic, non-paretic, and neurotypical limbs ({chi}2(2) = 27.57, p < .001). It also differed significantly between less and more impaired individuals classified by FM-LE (p = .05) and demonstrated good discriminative performance between these groups (AUC: 0.777, p = .017). The index also moderated the relationship between FM-LE and propulsion asymmetry ({Delta}R2 = 0.223, p = .007). These findings support the dynamic motor control index as a clinically relevant msarker of post-stroke neuromotor impairment and recovery.

Saccadic eye movements are established biomarkers in neuroscience and clinical neurology, where video-oculography (VOG) remains the gold standard. However, VOGs high cost, bulky equipment, and poor portability restrict its clinical utility. Electrooculography (EOG) offers a promising alternative by detecting cornea-retinal potential changes during eye movements. To enable quantitative saccadic analysis using EOG as a VOG alternative, this study develops and validates a mathematical transformation model converting EOG data into VOG-equivalent values. A prospective observational study was conducted on 4 healthy adults without neurological or sleep disorders. Horizontal saccades were recorded simultaneously using EOG and VOG during controlled gaze shifts. EOG peak saccadic velocity was derived from voltage change rate, whereas VOG was calculated from angular displacement over time. A derivation dataset of fixed horizontal saccades ({+/-}20{degrees}) formulated the transformation model, achieving a strong correlation coefficient (r = 0.95 rightward, r = 0.93 leftward, p < 0.0001). Multiple filter settings were evaluated, and 0.3 Hz high-pass and 35 Hz low-pass filtering were identified as optimal. The fixed horizontal saccades derived model was applied to a validation dataset of random horizontal saccades, confirming robustness across saccades without significant differences from VOG measurements. These findings establish EOGs feasibility for quantitative analysis of horizontal saccades and provide a validated transformation model. By systematically optimizing filtering parameters, this approach enables EOG as a cost-effective VOG alternative while maintaining high-precision measurement accuracy.