BACKGROUND:Cardiac pathologies can occur after acute ischemic stroke (AIS) even in patients without prior heart disease, reflecting bidirectional brain-heart interactions. We investigated sex-specific differences in newly diagnosed cardiac pathologies within 1 year after noncardioembolic AIS. METHODS:We screened 7113 patients with a first cerebrovascular event (December 2013 to March 2021) at a tertiary stroke center and included 673 patients (39% women, aged 61.2 years) with noncardioembolic AIS and no evidence of previous cardiac disease. After AIS, all patients received standard cardiologic evaluation (24-hour in-hospital telemetry, 24-hour blood pressure monitoring, echocardiography, and 48-hour Holter ECG). Electronic health records were reviewed for cardiology consultations and testing within 1 year after the index event (eg, ECG, echocardiography, coronary computed tomographic angiography, cardiac magnetic resonance imaging, myocardial perfusion single-photon emission computed tomography). Multivariable binary logistic regression models were adjusted for age, antihypertensive and lipid-lowering therapy, hypertension, diabetes, hyperlipidemia, and smoking. RESULTS:Compared with women, men more frequently exhibited nonsustained ventricular tachycardia (odds ratio, 3.97 [95% CI, 1.14-13.86]; P=0.031), first-degree atrioventricular block (odds ratio, 5.71 [95% CI, 1.48-22.01]; P=0.013), bradycardia (odds ratio, 3.40 [95% CI, 1.50-7.67]; P=0.003), and polymorphic ventricular extrasystoles (odds ratio, 2.61 [95% CI, 1.43-4.74]; P=0.002) within 1 year after AIS. Findings were consistent after multivariable adjustment. CONCLUSIONS:In this single-center cohort of patients without known heart disease and noncardioembolic AIS, poststroke cardiac findings were more common in men, particularly nonsustained ventricular tachycardia and polymorphic ventricular extrasystoles. These hypothesis-generating observations support further investigation into sex-informed poststroke cardiac evaluation.

BACKGROUND:Intracranial hypertension (IH) from brain edema is a life-threatening complication of large vessel occlusion (LVO) stroke, yet clinical monitoring is often unreliable. Non-invasive methods for early IH prediction are needed. This study assessed whether sonographic measurement of the optic nerve sheath diameter (ONSD) could improve the prediction of IH after stroke. PATIENTS AND METHODS:We prospectively measured the internal optic nerve sheath diameter (ONSDint) via transorbital ultrasound in 65 stroke patients and 30 controls. ONSD was also measured on the initial CT or MRI. The primary endpoint of IH was a composite of clinical and radiological signs of brain swelling. A predictive ONSD cut-off was determined from a multivariable logistic regression model, adjusted for age and infarct volume. Predictive performance was assessed using leave-one-out cross-validation. RESULTS:Seven of 65 stroke patients (11%) developed IH. The initial sonographic ONSDint was significantly increased in patients who developed IH. The multivariable model identified an optimal predictive cut-off of ⩾5.51 mm, which predicted IH with a sensitivity of 85.7% and a specificity of 94.8%. In comparison, ONSD derived from initial neuroimaging was also a strong predictor, with an optimal cut-off of 6.80 mm yielding a sensitivity of 100% and a specificity of 91.1%, and showed superior predictive accuracy in the cross-validation (AUC 0.905 vs 0.687). DISCUSSION:Our sonographic ONSDint cut-off of ≥5.51 mm aligns well with recent stroke literature that used similar standardized measurement techniques. Our findings also highlight the distinct roles of different imaging modalities. While the initial CT/MRI provides a static measurement with high predictive power, the unique advantage of sonography is its bedside applicability, allowing for the crucial, non-invasive serial monitoring of ONSD as a dynamic marker of intracranial pressure changes. CONCLUSION:Early ONSD assessment is a valuable predictor of IH after severe stroke. A sonographic ONSDint of ⩾5.51 mm identifies patients at high risk with excellent accuracy. While initial neuroimaging may offer superior predictive power, bedside sonography remains a crucial, repeatable tool for monitoring these critically ill patients.

BACKGROUND:Atrial cardiopathy is an important cause of embolic stroke and a potential cause of cognitive impairment. Increased left atrial volume indexed to body surface area (LAVi) has been widely used as a marker for atrial cardiopathy. However, because physiological remodeling, for example, due to exercise, may also increase LAVi, it lacks specificity. Left atrial to ventricular volume (LA:LV) ratio has been suggested as an improved marker of atrial cardiopathy, allowing detection of imbalanced, pathological atrial remodeling. We investigated if LA:LV ratio is associated with different sequelae of atrial cardiopathy. METHODS:We analyzed data from 2 cohorts, the population-based UK Biobank cohort (n=38 848) and a cohort of patients with ischemic stroke from the University Hospital Zürich (n=1273). In the UK Biobank cohort, we compared the association of LAVi and LA:LV ratio with risk of incident ischemic stroke or transient ischemic attack ascertained from linked health records, using competing risks survival analysis. We also investigated the association with cognitive function using linear regression models. In the ischemic stroke patient cohort, we compared LAVi and LA:LV ratio for identifying atrial fibrillation/flutter as a cause of stroke. RESULTS:While LAVi was not significantly associated with risk of ischemic stroke/transient ischemic attack (adjusted hazard ratio, 1.11 [95% CI, 0.97-1.26]; P=0.14), a larger LA:LV ratio was (adjusted hazard ratio, 1.15 [95% CI, 1.01-1.30]; P=0.04). Besides, LA:LV ratio was more strongly associated with worse cognitive function. In a stroke patient cohort, LA:LV ratio significantly outperformed LAVi at identifying atrial fibrillation/flutter as underlying cause of ischemic stroke compared with LAVi (area under the receiver operating characteristic curve, 0.856 [95% CI, 0.803-0.908] versus 0.808 [95% CI, 0.750-0.866]; P=0.03). CONCLUSIONS:We provide evidence that LA:LV ratio is a strong, novel marker of atrial cardiopathy. Hence, LA:LV ratio has the potential to improve the diagnosis of atrial cardiopathy, facilitating the prophylaxis of ischemic stroke and maintaining brain health.

IntroductionIschemic cerebrovascular disease (ICD) poses a major global burden. Non-adherence to medical secondary prevention leads to recurrent events and disability. Real-world data on adherence to preventive medications is scarce. The objective here is to determine adherence to secondary prevention of ICD and its effect on clinical outcomes.MethodsThis retrospective observational study was based on claims data from a large Swiss health insurance. We studied patients aged 18 years or older, who were hospitalized for ICD between 2017 and 2021. Patients’ one-year medication adherence was determined by the medication possession ratio (MPR, high adherence defined as MRP ≥ 0.80). Outcome variables were all-cause death, recurrent stroke, admission to nursing home, and major adverse cardiovascular events.ResultsA total of 9,911 patients with ischemic stroke or TIA were included in the analysis. Lipid-lowering drugs (LLD) had the largest proportion of high adherence users (63.2%), followed by antihypertensives (55.4%) and antiplatelets (50.0%). Female patients were 37% less likely to adhere to LLD therapy than men, highlighting a significant gender gap. Users with high adherence to LLD had a significantly reduced risk for all-cause death (HR 0.86, 95% CI 0.79, 0.94); Direct oral anticoagulants (HR 0.88, 95% CI 0.78, 1.00) and antihypertensives (HR 0.93, 95% CI 0.85, 1.01) showed a trend towards a protective effect.DiscussionA remarkable proportion of patients were non-users or had low adherence to medical secondary prevention. Since insufficient secondary prevention may lead to an increased all-cause death rate, efforts are needed to raise awareness among healthcare professionals and improve patient compliance.

Lipoprotein(a) (Lp(a)) is a causal risk-factor for atherosclerotic cardiovascular disease including acute ischemic stroke (AIS). The underlying pathomechanisms mediating this risk are less well understood, especially in AIS caused by large artery atherosclerosis (LAA). In this observational cohort study, we evaluated the association of Lp(a) with markers of LAA, namely carotid intima media thickness (cIMT) and the presence of extra- or intracranial vessel narrowing plaques. Among participants of the BIOSIGNAL cohort study we determined Lp(a) levels within 24 h after symptom onset in 1161 AIS patients from the single center of Zurich. cIMT was determined using a semi-automated computerized edge tracking software, internal carotid artery (ICA) stenosis was graded according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, intracranial ultrasound was performed by transcranial color-coded duplex (TCCD). Higher Lp(a) levels were not associated with an increased cIMT in univariable or multivariable regression models containing known cardiovascular risk factors. Higher Lp(a) levels were not associated with the presence of neither extracranial high-grade ICA-stenosis nor significant intracranial stenosis assessed by neurovascular ultrasound. In AIS patients higher Lp(a) levels were not associated with clinical markers of atherosclerotic burden despite its association with LAA-stroke etiology and an increased risk for stroke recurrence. Date of registration: 17–10-2014. Registration-URL: http://www.clinicaltrials.gov; Unique identifier: NCT-02274727.

BACKGROUND:Despite the proven effectiveness of intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) presenting within 4.5 h of symptom onset, less than 40% receive the treatment. We aimed to understand current reasons for withholding IVT to increase its administration. METHODS:We conducted a retrospective single-center analysis of AIS patients arriving within the treatment time window of 4.5 h at the hospital not undergoing IVT. 493 patients of the Swiss Stroke Registry (SSR) met the inclusion criteria between 2020 and 2022. We revisited medical records to identify the reasons for not administering IVT. RESULTS:958 patients with suspicion of AIS arrived within 4.5 h at the University Hospital Zurich (USZ), 493 (51.5%) did not undergo IVT. The primary reasons for not administering IVT were mild symptoms (41.8%, n = 167), prior use of Direct-Oral-Anticoagulants (DOACs) (27%, n = 108), or a demarcated subacute infarction on neuroimaging (8.3%, n = 41). Among patients with DOAC intake, specific anti-factor-Xa-(aFXa)-activity was not tested in 50% (n = 54). The posthoc-imaging analysis classified 41.2% (n = 14) of patients among the initially described demarcated infarction on NCCT as early signs of brain ischemia (EIS). CONCLUSION:Mild symptoms and prior DOAC intake were the main reasons for withholding IVT in stroke patients arriving within the treatment time window. Furthermore, EIS on neuroimaging classified as a subacute demarcated infarction by the neuroradiologist in charge constituted another important factor to reconsider IVT among other coexisting reasons. Identification of EIS and more data about the safety of IVT despite DOAC therapy have the potential to change clinical routine and enhance the number of patients suitable for IVT.

INTRODUCTION:Post-stroke depression (PSD) frequently occurs after acute stroke and negatively affects rehabilitation. Dopamine has beneficial effects on motivation and emotional stability. In stroke patients, low dopamine levels are linked to PSD. This study investigated whether levodopa treatment during in-hospital rehabilitation impacts PSD compared to placebo. PATIENTS AND METHODS:ESTREL-Depression was a pre-planned analysis of the multicenter, randomized, double-blind, placebo-controlled ESTREL trial. Participants with an acute ischemic or hemorrhagic stroke were randomly assigned to receive either levodopa/carbidopa (100/25 mg) or placebo three times daily for 39 days. All ESTREL participants with (1) information about the presence or absence of depression at three months and (2) who took at least 80% of the study medication were eligible for the study. Participants with a history of depression were excluded. For the primary outcome, the presence of PSD was defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a 3 months after randomization. Binary logistic regression was performed to assess the effect of levodopa on PSD. RESULTS:The study included 407 ESTREL participants (median age 72, 60% male), 209 receiving levodopa, and 198 receiving placebo. At 3 months, the frequency and odds of PSD did not differ between the levodopa group (26%) and the placebo group (28%) (OR = 0.93, 95% CI, 0.60-1.43). CONCLUSION:In the ESTREL-Depression study, treatment with levodopa had no impact on the occurrence of PSD. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov: NCT03735901 (https://clinicaltrials.gov/study/NCT03735901).

INTRODUCTION:Levodopa did not enhance early motor recovery at 3 months after stroke in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial. However, whether levodopa modifies the time course of recovery, leading to a delayed benefit remains unclear. Here, we examined levodopa's effects on the trajectories of motor recovery up to 6 months after stroke. PATIENTS AND METHODS:The ESTREL trial, a double-blind, randomised controlled clinical trial, compared a 39-day regimen of levodopa/carbidopa (100 mg/25 mg, 3×/day) to placebo alongside standardised task-oriented training. We longitudinally analysed Fugl-Meyer Motor Assessment (FMA) total scores (primary outcome), mRS and NIHSS (secondary outcomes) at baseline (0-7 days post stroke), 5 weeks, 3 and 6 months using linear mixed-effects models including timepoint, treatment allocation and their interaction. RESULTS:In total, 576 of 610 (94%) participants (median age 73 years; 40% female) were analysed. FMA scores improved over time in both groups (P < .001), with no overall levodopa effect across visits (estimate 0.65 points, 95% CI, -3.3 to 4.6; P = .75). There was no indication that levodopa modified the recovery trajectory (χ2 = 0.52, df = 3, P = .91), and estimated levodopa-placebo differences in FMA changes across visit intervals were small, ranging from -0.7 to +0.8 points, with confidence intervals crossing zero. Secondary outcomes showed similar longitudinal improvement, without evidence of a treatment effect. CONCLUSION:In this post hoc analysis of ESTREL participants with repeated FMA assessments, motor impairment improved from the first days after stroke up to 6 months. Levodopa added to task-oriented inpatient rehabilitation did not improve motor recovery or alter its trajectory over this period. CLINICAL TRIAL REGISTRATION:NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.

Endovascular stroke treatment has become the standard of care for acute large vessel occlusion and has significantly improved clinical outcomes. However, the procedure is still associated with possible complications, including vessel injury and reocclusion. This monocentric retrospective observational cohort study aims to evaluate the outcomes of the STent retriever Assisted endoluminal Reconstruction (STARecon) technique. In this case series we propose temporary deployment of a stent retriever as a potential bailout strategy in situations of spontaneous vessel reocclusion or uncertain vessel narrowing not associated with intracranial atherosclerotic disease (ICAD), including suspected iatrogenic dissection. Eight cases of temporary stenting using STARecon technique with stent retriever to treat spontaneous vessel reocclusion after thrombectomy were analysed. All patients underwent pre- and postinterventional non-invasive angiographic imaging (CTA or MRA) and clinical evaluation. The endovascular technique involved temporary deployment of a stent retriever under glycoprotein IIb/IIIa inhibitor infusion, followed by antithrombotic medication after atraumatic resheathing and removal of the stent retriever. Successful vessel recanalization was achieved in all cases with the duration of temporary stenting using stent retriever between 15 and 50 min (average 30 min 37 s). Postinterventional follow-up imaging demonstrated resolution of the spontaneous reocclusion without significant residual stenosis in all the cases at the treated site with STARecon technique. Our findings suggest that temporary stent retriever deployment using the STARecon technique may represent a valuable alternative to stent reconstruction in endovascular management of spontaneous vessel reocclusion after thrombectomy, including suspected iatrogenic dissection, especially in patients deemed at high risk of intracranial hemorrhage.

The Action Research Arm Test (ARAT) is a widely-used upper limb outcome measure in neurorehabilitation, but its ordinal scoring is subjective and suffers from limited sensitivity and specificity. We evaluated whether artificial-intelligence (AI)-based markerless motion capture (MMC), embedded into ARAT assessments during clinical routine, accurately reconstructs upper limb movement and yields valid, objective kinematic metrics carrying clinically meaningful information beyond the ordinal score. Across 47 sessions from 20 mixed-neurological patients (1,174 ARAT tasks), biomechanical reconstruction was accurate and robust across impairment levels, and kinematic metrics showed the discrimination pattern expected of a construct-valid measure. In longitudinal case studies, the metrics added the specificity and sensitivity the ordinal score lacks: a domain decomposition exposed patient-specific recovery profiles underlying equal ARAT gains (specificity), and kinematic improvement continued to be detected after the ARAT had saturated (sensitivity). MMC in clinical routine can thus provide valid, objective, sensitive, and specific kinematic measurement complementing ordinal scoring.

INTRODUCTION:Post-stroke fatigue (PSF) is common and impacts stroke rehabilitation. Dopaminergic treatment may have beneficial effects on PSF. This study investigated whether levodopa, compared with placebo, was associated with a lower frequency or severity of PSF during in-hospital rehabilitation. PATIENTS AND METHODS:Enhancement of Stroke Rehabilitation with Levodopa (ESTREL)-Fatigue was an exploratory analysis of secondary outcome data obtained in the multicentre, randomised, placebo-controlled ESTREL trial. Participants with acute stroke received levodopa 100 mg/carbidopa 25 mg or placebo 3 times daily for 39 days to enhance motor recovery. Participants who (i) reported fatigue at 5 weeks and who (ii) took at least 80% of the study medication were included in ESTREL-Fatigue. No adjustments for confounding were made. The primary endpoint was the presence of PSF at 5 weeks, defined as a T-score of ≥ 55 on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short-form-4a. As secondary endpoints, T-score cutoffs of ≥ 60 (moderate fatigue) and ≥ 70 (severe fatigue) were used. Binary logistic regression was used to compare PSF at 5 weeks between treatment groups. Results are presented as odds ratios (ORs) with 95% CI. RESULTS:A total of 456 of 505 (90.3%) participants were included (levodopa/placebo 235/221, median age 73 years, 41% female). Post-stroke fatigue at 5 weeks was present in 63/235 (26.8%) levodopa-treated participants and in 65/221 (29.4%) placebo-treated participants (OR: 0.88; 95% CI, 0.58-1.32; risk ratio 0.91; risk difference - 2.6%). For cutoffs of ≥ 60 and ≥ 70, ORs were 0.78 (95% CI, 0.43-1.41) and 0.8 (95% CI, 0.25-2.44), respectively. A sensitivity analysis as per intention-to-treat with all 610 randomised ESTREL participants also showed no significant difference in fatigue presence between levodopa and placebo groups (OR: 0.95; 95% CI, 0.65-1.39) and a sensitivity analysis using a mixed-effects logistic regression showed no evidence of centre-related clustering. CONCLUSION:In ESTREL-Fatigue, levodopa, compared to placebo, was not associated with less PSF during in-hospital rehabilitation.

Early after stroke, a period of heightened plasticity in the peri-infarct cortex is thought to provide the physiological substrate for functional motor recovery through increased expression of long-term potentiation (LTP). Previous slice electrophysiology studies on the capacity for LTP after stroke reported conflicting results. Slice preparation could have influenced the results by disrupting neuromodulatory processes known to be altered after stroke. Therefore, whether LTP can be induced in the peri-infarct cortex remains to be elucidated. In this study, we assessed synaptic transmission, short-term plasticity and LTP, operationalized as increased evoked field potentials, in 15 rats under urethane anaesthesia (11 with focal stroke to the primary motor cortex, and four sham-operated controls). Rats were tested one or two weeks after stroke using a minimally perturbed in vivo LTP induction protocol validated in naïve rats. Motor function was evaluated using the cylinder test at baseline and at one or two weeks post-stroke. The results showed a strong reduction of the capacity for LTP in the M1 peri-infarct cortex in comparison with the sham rats. In addition, synaptic transmission was reduced for higher stimulation intensities, and short-term plasticity shifted from facilitation to depression, indicating impaired synaptic function at one and two weeks post-stroke. Behaviourally, the lesioned rats exhibited motor deficits at one week but showed full recovery two weeks post-stroke. The results suggest that both LTP and synaptic transmission are profoundly impaired in the peri-infarct cortex during motor recovery after a stroke in M1. KEY POINTS: Increased expression of LTP in the peri-infarct cortex is thought to support motor recovery after stroke. However, to what extent LTP can be induced in the peri-infarct cortex remains unclear. We investigated whether, and to what extent, LTP can be induced in the peri-infarct cortex after an ischaemic stroke in urethane-anaesthetized rats using a novel stimulation protocol developed in naïve rats. The results show that LTP can be induced in the primary motor cortex (M1) in naïve and sham-operated rats by simultaneously stimulating the ventral tegmental area and M1. One and two weeks after a focal ischaemic stroke, the capacity for LTP induced using this method was strongly reduced in the peri-infarct cortex in recovering rats. Our results suggest that spontaneous recovery is independent of the capacity for LTP in the peri-infarct M1.

Introduction: Cervical artery dissection is a major cause of stroke in the young. The optimal choice and duration of antithrombotic treatment for stroke prevention are debated, particularly beyond 3 months after symptom onset. Patients and methods: TREAT-CAD (TREATment of Cervical Artery Dissection) was a randomized controlled trial with blinded outcome assessment comparing non-inferiority of aspirin to anticoagulation (Vitamin-K-antagonists) in participants with symptomatic, Magnetic-Resonance-(MR)-imaging-verified cervical artery dissection. TREAT-CAD could not establish non-inferiority of aspirin to anticoagulation at 3 months. Thereafter participants could continue antithrombotic medication and obtained a standardized assessment of clinical and MR-Imaging outcomes between 3 and 6 months. As crossover to the other treatment arm was possible, we performed an as-treated analysis as main analysis. The main outcomes were new clinical (ischemic stroke, intracranial/major extracranial bleeding, or death) and new MR-Imaging outcomes (ischemic or hemorrhagic brain lesions). Results: Among the 122 participants in the as-treated analysis, 3/93 (3.2%) aspirin-treated participants had new clinical ( n = 1) and MRI-outcomes ( n = 2) between 3 and 6 months while 1/29 (3.4%) anticoagulated participants had an MRI-outcome ( n = 1). All outcome events were hemorrhagic while ischemic events were absent. No deaths occurred. This yields an absolute difference of 0.2% (95% CI −8.0% to 7.5%, p = 1.0). Discussion and conclusion: During the extended follow-up period of a controlled randomized trial comparing aspirin to anticoagulation in cervical artery dissection, outcomes between 3 and 6 months after randomization occurred rarely, similarly often in both groups and were exclusively hemorrhagic events. Thus, studies balancing benefits versus harms of antithrombotic treatment beyond 3 months are warranted. Registration: ClinicalTrials.gov: NCT02046460. https://clinicaltrials.gov/ct2/show/NCT02046460 .

Real-time biofeedback, particularly visual, is gaining attention in neurorehabilitation, especially for gait training. However, its impact on cognitive load remains poorly understood, despite its role in influencing gait performance. We present here the protocol for a study where 40 healthy participants will be recruited and asked to complete a series of gait tasks with and without visual real-time biofeedback. This work aims to investigate the cognitive load associated with different visual real-time biofeedback paradigms during gait training. Cognitive load will be evaluated using electroencephalography of the frontal and parietal lobes, power spectral density analysis of the corresponding channels, and a questionnaire. The findings will enhance our understanding of how visual biofeedback affects cognitive load, informing future designs to optimize both cognitive load and gait performance in rehabilitation settings.

Stroke and Parkinson’s disease (PD) are prevalent neurological conditions causing significant disability in the elderly. Gait impairments are common targets for rehabilitation, yet responses to interventions vary widely. Within the scope of the StimuLOOP project, this monocentric, proof-of-concept clinical trial, is conducted to explore the efficacy of personalized real-time biofeedback for enhancing gait quality. Participants aged ≥18 years with stroke (≥30 days post-event, Functional Ambulation Category ≥3) or PD (UPDRS III gait/postural instability scores 1–3) undergo 15 days of personalized real-time biofeedback gait training. The dominant gait deficit of the participant is objectively evaluated in order to tailor the biofeedback by selecting a target parameter that the participant should actively modulate during training. Preliminary findings suggest participants are able to use personalized real-time biofeedback to adjust their dominant gait deficit, and subsequently maintain their gait adaptations in the absence of visual biofeedback. Ongoing analyses aim to validate these observations and expand our understanding of how motor learning evolves within and across these training sessions.

Importance:Levodopa enhances dopaminergic signaling and may stimulate neuroplasticity, which could potentially enhance motor recovery after stroke. Levodopa is used in stroke rehabilitation despite mixed evidence for its effectiveness. Objective:To determine whether levodopa compared with placebo, administered in addition to standardized rehabilitation based on active task-oriented training, is associated with enhanced motor recovery in patients with acute stroke. Design, Setting, and Participants:A double-blind, placebo-controlled randomized clinical trial at 13 stroke units and centers and 11 collaborating rehabilitation centers in Switzerland. Between June 14, 2019 (first patient, first visit), and August 27, 2024 (last patient, last visit), 610 patients with acute ischemic or hemorrhagic stroke with clinically meaningful hemiparesis (ie, a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo. Statistical analyses were conducted from November 2024 to August 2025. Intervention:Patients received levodopa/carbidopa (100 mg/25 mg; n = 307) or placebo (n = 303) 3 times daily for 39 days, alongside standardized rehabilitation therapy based on active task-oriented training. Main Outcomes and Measures:The primary outcome was the adjusted mean between-group difference in the Fugl-Meyer Assessment (FMA) total score (range, 0-100 points; fewer points indicate worse motor function; 6-point difference considered patient-relevant) at 3 months. Results:Among the 610 participants (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]), 28 participants died by 3 months, leaving 582 (95.4%) participants eligible for the primary analysis. At 3 months, the median (IQR) FMA total score was 68 (42-85) points in the levodopa group and 64 (44-83) points in the placebo group. The mean difference in the FMA total score between the levodopa and placebo groups was -0.90 points (95% CI, -3.78 to 1.98; P = .54). There were 126 serious adverse events in the levodopa group and 129 in the placebo group; the most common was infection (levodopa, n = 55; placebo, n = 44). Conclusions and Relevance:In this randomized clinical trial, among patients receiving inpatient rehabilitation for acute stroke, levodopa added to standardized rehabilitation did not significantly improve motor function at 3 months compared with placebo plus standardized rehabilitation. These results do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke. Trial Registration:ClinicalTrials.gov Identifier: NCT03735901.

BACKGROUND AND PURPOSE:The endovascular treatment for tandem occlusion (TO) in anterior circulation acute ischemic stroke represents a major challenge. Tandem occlusion involves an intracranial large vessel occlusion combined with a simultaneous occlusion or high-grade stenosis of the ipsilateral extracranial internal carotid artery. Atherosclerotic carotid artery disease (ACAD) and carotid artery dissection (CAD) are the primary causes. This study aims to assess the effect of etiology on clinical and radiological features, patient outcomes, and complications after revascularization procedures. MATERIALS AND METHODS:A retrospective analysis was performed analyzing TO patients who underwent mechanical thrombectomy and percutaneous transluminal angioplasty and stenting at our comprehensive stroke center from January 2019 to July 2023. The study was conducted using chart review and angiogram analysis. Successful reperfusion, peri‑procedural complications, and functional independence at 90 days were collected as outcome measures. RESULTS:Among the 89 patients, 22 were CAD patients, and 67 were associated with ACAD. CAD patients were significantly younger with a mean age of 55 years compared to 74 years for patients with ACAD (p < 0.001). Additionally, CAD patients exhibited fewer cardiovascular risk factors. Complete revascularization was achieved at a significantly higher rate in CAD patients (72.7 % vs. 40.3 %, p = 0.003). At 90 days post-procedure, CAD patients demonstrated a higher incidence of favorable outcomes (68.2 % vs. 43.2 %, p = 0.038). Multivariate logistic regression analysis identified age as a significant predictor of outcomes (OR = 0.905, 95 % CI: 0.851-0.962, p = 0.001), whereas etiology did not show a statistically significant effect. Furthermore, ACAD patients exhibited a lower incidence of stent occlusion at hospital discharge (3.4 % vs. 25.0 %, p = 0.004). CONCLUSION:This study on tandem occlusions found that patients with carotid dissection experienced better clinical outcomes than those with atherosclerotic carotid disease, despite a higher rate of stent reocclusion. However, multivariate analysis indicated that the underlying etiology was not an independent predictor of outcome; instead, patient age and initial stroke severity were more influential factors. Given the increased risk of reocclusion, patients with carotid dissection may benefit from a more individualized antithrombotic strategy to maintain stent patency.

Stroke and Parkinson's disease often result in significant gait impairments reducing mobility, independence and overall quality of life. While biofeedback has proven effective in restoring healthy gait, it is typically designed without considering the patient perspective. Therefore, this study aimed to implement a co-design process for personalized real-time biofeedback, to determine its impact on patient motivation and gait outcomes. Five participants (4 stroke, 1 stroke and Parkinson's disease) participated in multiple personalized real-time biofeedback-based gait training sessions using a Computer Assisted Rehabilitation Environment, actively shaping the features (e.g. visual biofeedback presentation, background settings, sound preferences, etc.). Continuous adjustments to the biofeedback and its difficulty effectively maintained patient motivation and engagement. Combined with eliciting changes in gait outcomes, personalized real-time biofeedback represents a promising approach to improve current gait training approaches, with potential implications in the rehabilitation process.

Construct validity and responsiveness of upper limb outcome measures are essential to interpret motor recovery poststroke. Evaluating the associations between clinical upper limb measures and sensor-based arm use (AU) fosters a coherent understanding of motor recovery. Defining sensor-based AU metrics for intentional upper limb movements could be crucial in mitigating bias from walking-related activities. Here, we investigate the measurement properties of a comprehensive set of clinical measures and sensor-based AU metrics when gait and non-functional upper limb movements are excluded. In this prospective, longitudinal cohort study, individuals with motor impairment were measured at days 3 ± 2 (D3), 10 ± 2 (D10), 28 ± 4 (D28), 90 ± 7 (D90), and 365 ± 14 (D365) after their first stroke. Using clinical measures, upper limb motor function (Fugl-Meyer Assessment), capacity (Action Research Arm Test, Box Block Test), and perceived performance (14-item Motor Activity Log) were assessed. Additionally, individuals wore five movement sensors (trunk, wrists, and ankles) for three days. Thirteen AU metrics were computed based on functional movements during non-walking periods. Construct validity across clinical measures and AU metrics was determined by Spearman’s rank correlations for each time point. Criterion responsiveness was examined by correlating patient-reported Global Rating of Perceived Change (GRPC) scores and observed change in upper limb measures and AU metrics. Optimal cut-off values for minimal important change (MIC) were estimated by ROC curve analysis. Ninety-three individuals participated. At D3 and D10, correlations between clinical measures and AU metrics showed variability (range rs: 0.44–0.90). All following time points showed moderate-to-high positive correlations between clinical measures and affected AU metrics (range rs: 0.57–0.88). Unilateral nonaffected AU duration was negatively correlated with clinical measures (range rs: -0.48 to -0.77). Responsiveness across outcomes was highest between D10-D28 within moderate to strong relations between GRPC and clinical measures (rs: range 0.60–0.73), whereas relations were weaker for AU metrics (range rs: 0.28–0.43) Eight MIC values were estimated for clinical measures and nine for AU metrics, showing moderate to good accuracy (66–87