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

IntroductionVestibular migraine is a major cause of recurrent vertigo, yet its mechanisms and diagnostic markers remain limited. Abnormal vestibular-cervical integration and convergence insufficiency, reflected by impaired near point convergence (NPC),suggest multisensory dysfunction. This study tested whether cervical proprioceptive perturbation provokes vertigo and nystagmus in vestibular migraine and evaluated NPC as a predictor of these responses. MethodsFifty-one vestibular migraine patients and 12 controls underwent interictal vestibular testing. Peripheral function was assessed with vHIT. Participants received randomized 100-Hz cervical (proprioceptive) and mastoid (vestibular) vibration without visual fixation, with eye movements recorded via video Frenzel goggles and NPC measured using standard methods. Analyses included McNemars, Wilcoxon signed-rank, Mann-Whitney U, correlations, and multivariable logistic regression. ResultsNeck vibration provoked vertigo in all vestibular migraine patients and none of the controls, producing nystagmus in 76.5%. Horizontal, ipsiversive nystagmus predominated, while less frequent vertical responses showed higher velocities. Mastoid vibration elicited no nystagmus. NPC was the only independent predictor of nystagmus and correlated with slow-phase velocity and bilateral responses. Age correlated with drift velocity, whereas vestibulo-ocular reflex gain showed no association. DiscussionNeck vibration elicits vertigo and nystagmus in vestibular migraine, providing the first objective physiological marker. NPC predicts and correlates with nystagmus severity, highlighting its value as a surrogate of multisensory dysfunction. Together, these findings implicate abnormal cervical-vestibular integration and position NPC and neck-vibration testing as practical tools for diagnosis and phenotyping. Key pointsO_LIVestibular migraine affects [~]3% of population yet remains highly controversial. C_LIO_LIObjective measures reveal reproducible vertigo and nystagmus in vestibular migraine. C_LIO_LIImpaired convergence strongly predicts vibration-induced nystagmus in VM patients. C_LIO_LIFindings support sensory mismatch model linking cervical proprioception to vertigo. C_LI

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.

Abstract Background: Acute 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. Objectives: This 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 design: The 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. Outcomes: The 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. Conclusions: Results 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 number: ChiCTR2300074147 (www.chictr.org.cn).

BackgroundRespiration is a key central nervous system rhythm that modulates sensorimotor function in healthy individuals, but the neurophysiological mechanisms of volitional breathing-mediated sensorimotor modulation and its preservation in stroke patients remain unclear. This study aimed to characterize the effects of volitional fast inspiration on sensorimotor pathway excitability in healthy and stroke populations, and provide a mechanistic basis for respiratory-integrated post-stroke rehabilitation. MethodsA multimodal case-control neurophysiology study was conducted in 52 healthy volunteers (26 {+/-} 3 years, 30 males) and 44 first-ever subacute stroke patients (66 {+/-} 10 years, 30 males). Three complementary experiments assessed transcranial magnetic stimulation-induced motor-evoked potentials (MEPs), peripheral nerve stimulation-induced somatosensory-evoked potentials (SEPs), and functional electrical stimulation -evoked muscle force under three breathing conditions: volitional fast inspiration (IN), fast expiration (EX), and spontaneous breathing (CON). Two-way and one-way repeated measures ANOVA with Bonferroni post hoc tests were used for statistical analysis. ResultsVolitional fast inspiration significantly enhanced sensorimotor pathway excitability and muscle force generation in both groups. Volitional fast inspiration increased MEP amplitudes relative to spontaneous breathing and fast expiration (p {inverted exclamation} 0.05), with further amplification during active muscle contraction (p {inverted exclamation} 0.05). It also elevated SEP amplitudes in healthy parietal/frontal cortical regions and the stroke parietal cortex (p {inverted exclamation} 0.05). Synchronizing volitional fast inspiration with voluntary finger contraction increased muscle force evoked by functional electrical stimulation by 16-18% relative to spontaneous breathing (p {inverted exclamation} 0.05), with non-significant force gains at rest. ConclusionsVolitional fast inspiration bidirectionally enhances corticospinal transmission, somatosensory integration, and functional force generation in both healthy individuals and stroke patients, with preserved respiratory modulation in stroke-damaged neuropathways. By demonstrating preserved respiratory modulation in stroke-damaged neuropathways, our results provide mechanistic support for integrating controlled breathing into low-cost, non-invasive post-stroke rehabilitation paradigms.

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.

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.

ObjectiveA comparative analysis was conducted on the rehabilitation effects of limb functions in patients with post-stroke yawning-induced parakinesia brachialis oscitansysis (PBO), patients without PBO, and patients whose PBO naturally disappeared after the onset of the disease. MethodsThe study included ischemic stroke patients diagnosed and treated in our hospital from March 2024 to June 2024. Patients were divided into two groups: the PBO group and the non-PBO group, based on whether PBO was administered. Propensity score matching was employed to account for all covariates and perform a 1:2 matching to balance the baseline characteristics of the two groups. The matched data were used for subsequent analysis to observe the Lovett scores and FMA scores of the two groups 3 months after the onset. For 33 patients with PBO, they were divided into two groups: the persistent group and the disappearing group, based on whether the PBO lasted for more than 1 month. The Lovett scores and FMA scores of the two groups were observed 3 months after the onset. ResultsAfter propensity score matching, there were 26 patients in the PBO group and 52 patients in the non-PBO group. The baseline characteristics of the two groups were basically balanced, and the difference was not statistically significant (P>0.05). Compared with the non-PBO group, the Lovett scores and FMA scores of the PBO group 3 months after the onset were higher, and the difference was statistically significant (P < 0.05). Compared with the PBO persistent group, the FMA score of the PBO disappearing group 3 months after the onset was higher than that of the persistent group, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in Lovett muscle strength between the two groups (P > 0.05). ConclusionThe functional recovery of patients with PBO was better than that of patients without PBO manifestation 3 months after the initial diagnosis. Moreover, patients whose PBO appeared first and then disappeared had better functional recovery than those whose PBO persisted.

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: 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.

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.

BackgroundChitinases, including chitotriosidase (CHIT1) and chitinase-3-like protein 1 (CHI3L1), are markers of neuroinflammation, a key process in amyotrophic lateral sclerosis (ALS). Tear fluid (TF) can be collected non-invasively and may represent a promising alternative to CSF or blood to study chitinases. MethodsTF was collected from 50 ALS patients and 50 control subjects using Schirmer strips. CHIT1 and CHI3L1 levels in TF, serum, and CSF were quantified using ELISA. Serum NfL was measured using SIMOA. The frequency of a 24 bp-duplication polymorphism in the CHIT1 gene influencing CHIT1 expression was assessed by PCR. ResultsNo group differences in the distribution of the CHIT1 polymorphism were detected. Carriers of the polymorphism in both ALS and controls showed lower CHIT1 levels in serum and TF. CHI3L1 levels in TF were higher in ALS patients compared to controls (p = 0.007), consistent with changes in CSF but not serum. In ALS, males showed higher TF CHIT1-values compared to females (p = 0.009). Combining TF chitinase values with serum NfL values improved discrimination between ALS and controls. ConclusionsChitinases are detectable in TF, and CHI3L1 levels recapitulate changes observed in CSF, highlighting its potential for non-invasive longitudinal assessment. Furthermore, chitinase values in TF, together with serum NfL, may act complementary by capturing distinct aspects of the disease, neuroinflammation and axonal damage. These results suggest TF chitinases and serum NfL could complementarily contribute to the diagnosis and monitoring of the disease, and call for further evaluation of TF as a biomarker source in ALS.

BackgroundPost-stroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and significantly impairs functional recovery. Brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase-{beta} (Trk{beta}) signalling is crucial for synaptic plasticity and cognitive function. While altered expression of truncated TRK{beta}-T1 isoforms has been linked to stroke, the contribution of the TRK{beta}-SHC isoform to PSCI in humans remains poorly understood. ObjectivesThis study aimed to (i) assess isoform-specific expression changes of NTRK2 associated with PSCI, (ii) evaluate the role of an isoform-specific genetic variant in disease susceptibility, and (iii) identify DNA methylation changes regulating NTRK2 expression (if any). MethodsGene expression levels of three major NTRK2 isoforms and MEK2 were analyzed in peripheral blood mononuclear cells from 19 PSCI patients, 21 post-stroke cognitively normal (PSCN) individuals, and 11 healthy controls. Expression data were correlated with raw memory scores and MEK2 expression. DNA methylation profiles of NTRK2 and its transcriptional regulators were assessed using whole-genome bisulfite sequencing. ResultsTRK{beta}-FL expression was significantly reduced in stroke patients compared with controls. In contrast, TRK{beta}-SHC expression was elevated in PSCN individuals relative to PSCI cases and showed a positive correlation with MEK2 expression and memory performance. No significant association was observed between rs65339833 and cognitive subdomains. Gene body hypermethylation, but not promoter methylation, was detected in NTRK2 and its regulatory genes. ConclusionsElevated TRK{beta}-SHC expression may contribute to preserved cognitive function following stroke. DNA methylation status of NTRK2 may regulate alternative splicing and thus represent a novel therapeutic avenue for preventing or mitigating PSCI.

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

Spinal cord injury (SCI) is associated with cardiovascular deficits that affect cerebral blood flow, cerebral perfusion, and cerebrovascular control. While several studies use neuroimaging techniques such as functional magnetic resonance imaging (fMRI) to understand neuroplasticity following SCI, more work needs to be done to evaluate the cerebrovascular changes following SCI. Understanding these effects using neuroimaging is essential as these deficits also affect neurovascular coupling and how we interpret neuroplasticity measured based on neuroimaging. Hence, we conducted a pilot study in twelve healthy males and thirteen males with thoracolumbar SCI using functional near-infrared spectroscopy (fNIRS) to understand the effects of breath-holding induced hypercapnia on the hemodynamics of the sensorimotor cortex and prefrontal cortex (PFC) after SCI. Participants performed 30 seconds of regular breathing alternated by 15 seconds of breath-holding for 5 minutes. Compared to controls, the SCI group presented with a greater initial decrease in oxy-hemoglobin concentration change and a delayed subsequent increase in oxy-hemoglobin concentration change in response to hypercapnia at p<. Additionally, the net increase in oxy-hemoglobin concentration change following BH in the PFC was negatively correlated with the level of injury at p=0.005, where higher levels of injury were associated with a smaller increase in oxy-hemoglobin concentration following hypercapnia. These findings confirm that a) SCI, including lower levels of injury (below T6) are associated with cerebrovascular changes that are quantifiable using fNIRS, and b) fNIRS could be a robust tool to understand the neuroplastic and cerebrovascular changes in people with SCI.

BackgroundChronic autoimmune diseases such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN), and Thyroid Eye Disease (TED) impose a considerable burden on affected individuals. Patient-reported outcome measures (PROMs)--both disease-specific and generic--are widely used to assess functioning, quality of life, and treatment effects in these populations. However, most PROMs currently lack reference values derived from the general population, limiting the interpretability of patient scores. ObjectiveThe GENESIS (GENEral population normS--An International Survey) study aims to establish general population norms for a range of PROMs used in CIDP, MMN, and TED across six countries: Germany, Italy, Japan, Spain, the United Kingdom, and the United States. These norms will improve patient score interpretation and help quantify unmet needs in patients with these rare autoimmune diseases. MethodsGENESIS is an observational, cross-sectional, online survey of the adult general population (N=21,000). Participants will be recruited to be representative by age, gender, region, and education. The survey includes validated instruments such as the EQ-5D-5L, I-RODS, MMN-RODS, CAP-PRI, GO-QoL, BPI-SF, RT-FSS, FACIT-Fatigue, HADS, and WPAI, along with items on demographics, caregiver need, and healthcare utilization. To reduce respondent burden, participants will be randomized into two groups, each completing a subset of the full questionnaire. A subset of respondents (n=2,333) will be re-surveyed after two months to support psychometric validation. Data will be analyzed descriptively to generate normative values for each PROM by country and in aggregate. Results and DisseminationData collection is scheduled to begin in August 2025, with results expected by Q4 2025. Findings will be disseminated via peer-reviewed publications and conference presentations. ConclusionGENESIS will provide foundational normative data across six countries for PROMs commonly used in rare autoimmune diseases. These data will support more meaningful interpretation of PROM scores in both clinical practice and research settings.

Background: Stroke guidelines recommend intravenous thrombolysis (IVT) within 4.5 hours of symptom onset for patients with minor acute ischemic stroke (AIS) but disabling symptoms. However, such patients are often overlooked for treatment, increasing their risk of stroke-related disability. Tenecteplase is endorsed as an alternative to alteplase for IVT in patients with AIS. More evidence is required regarding its efficacy and safety in the minor stroke population. Methods: This post hoc analysis of the ORIGINAL randomized clinical trial aimed to evaluate the efficacy and safety of tenecteplase versus alteplase in the patient subgroup with minor (National Institutes of Health Stroke Scale [NIHSS] 5) disabling stroke. Primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 at Day 90. Results: Data were analyzed for 299 patients treated with tenecteplase 0.25 mg/kg and 297 patients treated with alteplase 0.9 mg/kg. At Day 90, 86.3% of tenecteplase recipients and 82.8% of alteplase recipients achieved a mRS score of 0 or 1 (risk ratio=1.04 [95% confidence interval 0.971?1.114]; non-significant). No heterogeneity of treatment effect was observed across predefined subgroups according to baseline NIHSS score, time to drug administration, sex, age, presence (yes/no) of atrial fibrillation and diabetes and thrombectomy performed. No statistically significant differences were observed between tenecteplase and alteplase across secondary efficacy and safety outcomes. Conclusions: The comparable efficacy and safety of tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg in the minor stroke population of the ORIGINAL randomized clinical trial suggests that tenecteplase is a suitable alternative to alteplase in this setting. Trial registration: ClinicalTrials.gov NCT04915729 (ORIGINAL randomized clinical trial; https://clinicaltrials.gov/study/NCT04915729). Submitted 4 June 2021. Key words: acute ischemic stroke, alteplase, intravenous thrombolysis, minor stroke, tenecteplase