Mahesh Kate

Introduction: Remote ischemic conditioning (RIC) is delivered by a transient (5 min) pressure increase in the arm BP cuff by a variable 30-50 mmHg above systolic BP to a maximum of 200 mmHg. This inconsistency in pressure application may affect the fidelity of intervention delivery. We tested the hypothesis that monitoring remote ischemic conditioning (RIC) with an adjunct forearm skin tissue reflectance sensor (STRS) device may be feasible in patients with acute ischemic stroke (AIS) and cerebral small vessel disease (cSVD). Methods: We screened patients with AIS within 7 days of symptom onset for moderate-to-severe cSVD. Eligible patients were randomized 2:1 to receive intervention RIC or sham RIC. The primary outcome measure was a composite feasibility of the forearm STRS (patient-level comfort and technical aspects measured by IOx1 and IOx2). The secondary outcome was changes in forearm STRS-derived tissue reflectance responses during the pressure-on phase (5 min) and the early pressure-off phase (1 min) of RIC. Multivariable linear regression analysis assessed the relationship between IOx1 and intervention allocation. We also used receiver operating characteristic curve analysis to propose candidate thresholds for classifying the magnitude of the tissue oxygenation response to RIC. Results: Fifty-one [34 intervention (68 RIC sessions), 17 sham (29 RIC sessions)] patients with mean ± SD age of 69±12.8 years, 24(47.1%) were females, were enrolled at a median (IQR) 42(26-78) hours after symptom onset, and median baseline National Institute of Health stroke Scale of 5(3-7). STRS-derived median relative IOx1(β = 0.33, p = 0.002) and median relative IOx2 (β = 0.23, p = 0.04) slopes during the pressure-on phase were different in the intervention arm compared to the sham arm. A percent IOx1 change of 4- 13.7% can be considered a threshold to differentiate between intervention and sham treatment. The median Likert scale score was similar: 3.5 (3-4) in the intervention group and 4 (4-5) in the sham group. Conclusion: RIC monitoring with forearm STRS is feasible in patients with AIS. Clinical trials evaluating the efficacy of RIC interventions can use STRS to assess fidelity. Clinical Trial Registration Number: ClinicalTrials.gov ID: NCT05408130 (https://clinicaltrials.gov/study/NCT05408130)

Background: Remote ischemic conditioning, a low-cost, non-invasive therapy involving brief cycles of limb ischemia and reperfusion, may be a neuroprotective adjuvant or alternative to reperfusion therapies in acute ischemic stroke and may also have therapeutic effects in hemorrhagic stroke. This systematic review and meta-analysis evaluated the efficacy of remote ischemic conditioning in acute ischemic stroke and hemorrhagic stroke. Methods: This review was conducted in accordance with Preferred Reporting for Systematic review and Meta-Analyses guidelines and was registered in PROSPERO (CRD42024549594). Literature searches were conducted on MEDLINE, Embase, and Web of Science from inception to 9 December 2025. Randomized controlled trials involving adults with acute ischemic stroke or hemorrhagic stroke were included in the study. We focused on functional outcomes; secondary measures included cerebral hemodynamics and neuroimaging. Outcomes were analyzed using the DerSimonian–Laird model, while study heterogeneity was evaluated using Cochran’s Q. Results: Overall, 35 studies (6304 patients) were included. Functional outcomes were significantly better in acute ischemic stroke patients who received remote ischemic conditioning versus those who did not, as indicated by lower Modified Rankin Scale scores (standardized mean difference = −0.18, 95% confidence interval: −0.35 to −0.01, n = 11 studies) and higher odds for favorable (odds ratio = 1.28, 95% confidence interval: 1.05 to 1.57, n = 17 studies) and excellent (odds ratio = 1.27, 95% confidence interval: 1.06 to 1.51, n = 12 studies) outcomes; furthermore, post-treatment stroke severity (indicated by National Institutes of Health Stroke Scale scores) was also lower in acute ischemic stroke patients receiving remote ischemic conditioning (standardized mean difference = −0.64, 95% confidence interval: −0.96 to −0.31, n = 16 studies). The Modified Rankin Scale scores and outcomes were better when remote ischemic conditioning was initiated beyond 24 h, and the protocol involved bilateral application and/or use beyond 7 days. Favorable Modified Rankin Scale outcomes were only better in patients receiving remote ischemic conditioning without reperfusion. Conclusion: Remote ischemic conditioning appears to improve functional and neurological outcomes in acute ischemic stroke patients. However, the quality of evidence is limited by regional generalizability (i.e. most studies came from China), small sample sizes, and methodological heterogeneity. We encourage future trials to include patients presenting beyond 4.5 h and to incorporate bilateral remote ischemic conditioning application and to extend remote ischemic conditioning use beyond 7 days. We also encourage studies to focus on patients who are not eligible for reperfusion therapy.

There are few high-quality data on thrombolysis outcomes in the oldest patients, especially for minor stroke. We examined safety and efficacy outcomes of thrombolysis in patients older than 80 years, compared with those ≤80 years, in the Tenecteplase Versus Standard of care for Minor Ischaemic Stroke With Proven Occlusion (TEMPO-2) trial. In this post hoc analysis of the TEMPO-2 randomized controlled trial, we compared outcomes and adverse events in patients with minor stroke and symptomatic intracranial occlusion or focal perfusion lesion within 12 hours of symptom onset, assigned to tenecteplase vs nonthrombolytic standard of care, in those >80 years and ≤80 years. The primary outcome was responder analysis of the 90-day modified Rankin Scale (responder was mRS = 0-1 if premorbid mRS = 0-1, 0-2 if premorbid mRS = 2). Secondary outcomes included neurologic recovery according to the NIH Stroke Scale (NIHSS) at 5 days/discharge, vessel recanalization, Lawton Instrumental Activities of Daily Living Scale, EuroQol-5 Dimension (EQ-5D), and adverse events. We used mixed-effects Poisson, ordinal logistic, and quantile regression as appropriate, adjusted for sex, baseline NIHSS, and treatment assignment as fixed-effects and enrolling site as random effects. Among 884 patients in the intention-to-treat analysis (208 [23.5%] >80 years, 365 [41.6%] female). Significant interactions between age and treatment were observed for mRS responder, mRS 0-1, return to baseline function, EQ-5D index, and vessel recanalization. Patients >80 years generally fared worse with tenecteplase for mRS outcomes (mRS 0-1 in 49 [46.2%] vs 61 [59.8%] with control, adjusted risk ratio [aRR] 0.83, 95% CI 0.72-0.97), while among patients ≤80 years, there was no significant difference (249 [76.4%] vs 260 [74.7%], aRR 1.01, 95% CI 0.98-1.03). However, in both age groups, patients were more likely to achieve recanalization of visible occlusions (aRR ≤80 years 2.06, 95% CI 1.60-2.65, >80 years 2.77, 95% CI 2.21-3.47) and NIHSS = 0 at 5 days/discharge when assigned to tenecteplase (aRR ≤80 years 1.14, 95% CI 1.04-1.26, >80 years 1.21, 95% CI 1.10-1.33). Serious adverse events (SAEs) were more frequent with tenecteplase among patients >80 years (risk ratio 2.29, 95% CI 1.27-4.13), particularly hemorrhages and stroke progression/recurrence (any extra/intracranial hemorrhage in 5 [4.7%] vs 0 with standard of care, p = 0.026). Older patients (>80 years) with minor stroke and visible occlusion or perfusion lesion assigned to tenecteplase were more likely to achieve recanalization of occlusions and short-term neurologic recovery, as were younger patients, but they experienced worse 90-day outcomes with more frequent hemorrhagic and stroke progression/recurrence-related SAEs. Overall, these results, while post hoc, do not support thrombolysis for minor strokes in older patients. ClinicalTrials.gov: NCT02398656. This study provides Class III evidence that in patients >80 years with minor stroke and visible occlusion or perfusion lesion, IV thrombolysis with tenecteplase is associated with worse functional outcomes at 90 days compared with nonthrombolytic standard of care therapies.

BACKGROUND: Geographic disparities in urban-rural stroke outcomes are in part due to limited and delayed access to reperfusion therapies such as endovascular thrombectomy. This study evaluated the impact of a prehospital telephone consultation on transportation patterns and efficiency for rural patients with suspected large vessel occlusion stroke. METHODS: This retrospective cohort study utilized administrative data from consecutive patients in Alberta, Canada, who underwent an emergency medical services–initiated rural field consultation for suspected acute stroke with a Los Angeles Motor Scale score of ≥4 between April 2017 and March 2023. The impact of field calls on transport efficiency was quantified using a novel metric: the Stroke Speedometer, calculated as the distance from the emergency medical services origin to the final destination (in kilometers) divided by the travel time (in hours). RESULTS: Of the 704 included rural field consultations, 476 patients (67.6%) were directly transported to a comprehensive stroke center, 192 (27.3%) to a primary stroke center, and 36 (5.1%) to a nonstroke center. Direct transport to a comprehensive stroke center was associated with a significantly faster Stroke Speedometer (53±18 versus 44±24 km/h; P P =0.005), and increased likelihood of endovascular thrombectomy (adjusted relative risk, 2.25 [95% CI, 1.44–3.50]) compared with initial transport to a noncomprehensive stroke center hospital. CONCLUSIONS: A prehospital telephone consultation (ie, rural field call) is feasible and helps identify and facilitate direct transport of rural patients with suspected large vessel occlusion to an endovascular thrombectomy–capable comprehensive stroke center. These findings highlight the value of integrating real-time, neurological consultation early into prehospital workflows to overcome the geographic and logistical barriers that contribute to rural-urban disparities in stroke care. The Stroke Speedometer metric represents a novel approach for assessing and enhancing prehospital stroke logistics.

Organized stroke systems of care have been proven to reduce rates of mortality and disability, reduce costs and lead to increased availability of resources including stroke units, specialized healthcare professionals, stroke prevention clinics and virtual stroke care. The 7 ^th edition of the Canadian Stroke Best Practice Recommendations (CSBPR) Stroke Systems of Care module synthesizes the current evidence for the development and implementation of integrated and innovative stroke systems of care. It includes the core elements of a stroke system, general principles for integrated care, transitions of care, virtual stroke care, education and support for the individual experiencing a stroke, their family and caregivers, stroke care in long-term care, advance care planning, and palliative and end-of-life care. It serves as the foundation for other CSBPR modules by focusing on common, cross-functional and higher-level principles and processes of stroke care planning and delivery across the continuum of care. Other modules apply these elements and further refine and adapt them within the context of specific topics such as acute care, rehabilitation and recovery. It is critical that stroke systems are established locally, regionally and provincially/territorially through collaboration with all partners involved in stroke care planning and delivery to ensure timely access to care, optimize outcomes and meet the needs of individuals with stroke, families and caregivers. Healthcare providers and system leaders must demonstrate exemplary collaboration with ongoing effective communication to ensure these integrated systems are functioning at their highest level, with appropriate funding and a purposeful data collection and performance measurement strategy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is thought to increase the risk of postthrombolytic intracranial bleeding, yet CAA neuroimaging markers and magnetic resonance imaging criteria have not been systematically evaluated in large acute stroke trials. We, therefore, examined the association of radiological Boston CAA criteria and their constituent markers with hemorrhagic risks and functional outcomes after intravenous thrombolysis in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: Blinded raters recorded lobar cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity multispot sign, and centrum semiovale enlarged perivascular spaces, and classified possible and probable CAA according to radiological Boston criteria iterations, versions 1.0, 1.5, and 2.0. Multivariable logistic or ordinal regressions, adjusted for age, sex, baseline stroke severity, diabetes, hypertension, onset-to-needle time, thrombolytic agent, and endovascular therapy, assessed associations of these features/criteria with safety end points: symptomatic intracerebral hemorrhage (ICH), any ICH, Heidelberg hemorrhage grade, 90-day mortality, and functional outcomes (modified Rankin Scale score of 0–1 and ordinal modified Rankin Scale score shift). RESULTS: Among 1600 patients in the trial, 482 had suitable magnetic resonance imaging (mean age, 71 years; 47.1% female). Cortical superficial siderosis burden emerged as the dominant harmful marker: each increment was associated with increased risk of symptomatic ICH (adjusted odds ratio [aOR] per additional affected sulcus, 3.88 [95% CI, 2.87–5.26]), any ICH (aOR, 1.91 [95% CI, 1.22–2.98]), hemorrhage severity, 90-day mortality (aOR, 1.42 [95% CI, 1.18–1.71]), worse modified Rankin Scale scores (adjusted common odds ratio, 1.74 [95% CI, 1.58–1.91]), and lower odds of excellent functional recovery (aOR, 0.70 [95% CI, 0.64–0.77]). Fulfilling probable radiological Boston criteria, versions 1.0 and 1.5, increased odds of any ICH (aOR, 2.57 and 2.39 [95% CI, 2.05–3.23]; aOR, 2.39 [95% CI, 1.71–3.34], respectively), whereas fulfilling possible Boston criteria, version 1.5, was associated with worse modified Rankin Scale scores (adjusted common odds ratio, 2.34 [95% CI, 1.30–4.22]). Boston criteria, version 2.0, were not significantly associated with any hemorrhagic outcomes. CONCLUSIONS: In thrombolyzed patients with acute ischemic stroke, cortical superficial siderosis burden is strongly and consistently associated with higher risk of severe hemorrhage, disability, and death, making it a particularly relevant CAA marker when weighing thrombolytic risk versus benefit. Meeting radiological Boston criteria, versions 1.0 or 1.5, increases hemorrhagic risk, but meeting the latest 2.0 criteria does not.

BACKGROUND: With the increasing use of tenecteplase for acute ischemic stroke, it is important to determine its safety in young adults. We aimed to characterize the clinical characteristics and imaging findings of young adults (≤45 years) in the AcT trial (Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada) and to compare their safety and efficacy outcomes. METHODS: This is a secondary analysis of the AcT trial, a phase 3 pragmatic multicenter registry-linked randomized controlled trial. We describe clinical and imaging characteristics of young adults with acute ischemic stroke. Logistic regression adjusted for sex and stroke severity was performed to assess safety and efficacy outcomes between the tenecteplase and alteplase arms. RESULTS: Of the 1577 enrolled patients, 68 (4.31%) were ≤45 years. Of 53 patients with available comorbidity data, 33 (62.26%) had no comorbidities. Hypertension was the most common comorbidity (n=8, 15%), whereas cardiac pathologies were observed in a smaller proportion (n=4, 7.5%). Intracranial atherosclerosis was identified in 7 patients (10%) and carotid or vertebral artery dissection in 6 patients (9%). Safety outcomes, including mortality, intracranial hemorrhage, and serious adverse events, were similar between the tenecteplase and alteplase arms. Excellent functional outcome (modified Rankin Scale score 0–1) at 90 days was better in the tenecteplase arm (84.72% versus 45%; adjusted odds ratio, 6.55 [95% CI, 1.89–22.71]). CONCLUSIONS: The majority of young adults presenting with acute ischemic stroke did not have any traditional risk factors for stroke at presentation. Safety outcomes were similar between the tenecteplase and alteplase arms. Although functional outcomes were observed to be better in the tenecteplase arm, these findings are exploratory and should be interpreted cautiously, given the study’s limited sample size and lack of adjustment for key confounders. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03889249.

BACKGROUND: Following an acute ischemic stroke, the risk of recurrent stroke is highest in the first 90 days. It is unclear whether this risk is altered by reperfusion therapy. In this meta-analysis, we aim to evaluate the risk of early recurrent stroke and other nonstroke thrombotic events postreperfusion therapy in acute ischemic stroke. METHODS: In this meta-analysis, randomized controlled trials (RCTs) were included in adults aged 18 years or older with acute ischemic stroke, comparing reperfusion treatment with best medical management (MED). We searched PUBMED, Embase, Cochrane Library, and Web of Science databases. The studies were grouped into endovascular thrombectomy (EVT) versus MED and intravenous thrombolysis versus MED. We performed a meta-analysis using a random-effects model (restricted maximum likelihood) to estimate the log risk ratio (RR) of early recurrent stroke and nonstroke thrombotic events (NSTE)—including myocardial infarction, acute coronary syndrome, deep vein thrombosis, pulmonary embolism, and peripheral embolism—after reperfusion therapy compared with MED at 90 days after symptom onset. This study is registered with PROSPERO (The International Prospective Register of Systematic Reviews). RESULTS: A total of 15 RCTs (n=4898) comparing EVT versus MED observed no difference in early recurrent stroke (5.5%, 143/2618 versus 4.5%, 102/2280; RR, 1.2 [95% CI, 0.9–1.6]). Nine RCTs (n=7193) comparing intravenous thrombolysis versus MED observed no difference in early recurrent stroke (2%, 73/3615 versus 1.8%, 66/3578; RR, 1.1 [95% CI, 0.8–1.5]). Fourteen RCTs (n=4033) comparing EVT versus MED reported NSTE. There was no difference in NSTE in the EVT arm (3.1%, 62/2024 versus 3.1%, 62/2009; RR, 1 [95% CI, 0.7–1.4]). Five RCTs (n=4961) comparing intravenous thrombolysis versus MED observed no difference in NSTE (2%, 51/2479 versus 2.2%, 54/2482; RR, 0.9 [95% CI, 0.6–1.4]). CONCLUSIONS: Reperfusion therapies (EVT±intravenous thrombolysis) in acute ischemic stroke within 24 hours of symptom onset were not associated with increased recurrent stroke or NSTE within 90 days compared with best medical therapy. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42024542020.

Background: Referrals to the Stroke prevention clinic with incomplete preliminary investigations decrease clinic capacity due to additional workload and the need for multiple follow-ups. We aimed to improve the efficacy of the initial visit by increasing the completion rate of vascular imaging in a quality improvement (QI) project. Methods: This is a quasi-experimental study with three phases: Phase 1: Surveillance; Phase 2: Stakeholder feedback-informed intervention development (physicians and clinic staff); and Phase 3: Intervention. Interventions included a new standardized specific physician triage form listing required investigations (brain imaging, vascular imaging, cardiac tracing), and a nurse-led pre-visit via telephone. The primary outcome measure was the completion of vascular imaging by the time of visit, assessed using multivariable logistic regression adjusted for age (in years), sex, and triage category. Results: The study’s inclusion criteria were met by 397 patients, with a mean age of 67.7 ± 13.2 years; 47.8% were female, and 62.9% (250) were diagnosed with vascular events. An increase in vascular imaging before the initial visit was observed in Phase 3 (148/199, 75.5%) compared to Phase 1 (121/198, 61.1%), with an adjusted Odds ratio of 1.77 (95% CI 1.2–2.8; p = 0.01). A trend toward fewer follow-up visits was observed in Phase 3 (23.1%) compared with Phase 1 (31.8%; p = 0.052). Conclusions: Implementing a standardized triage process and a nurse-led pre-visit may improve completion of vascular imaging before patients visit the stroke prevention clinic. Further QI studies are required to improve the completion rate of rhythm monitoring in this patient group to enable early detection and management of atrial fibrillation.

Insights into motor cortex remodeling may enable the development of more effective rehabilitation strategies during the acute phase. We aim to assess the affected and unaffected motor/premotor/somatosensory cortex resting state functional connectivity (RSFC) and reactivity with continuous wave functional near-infrared spectroscopy (cw-fNIRS) in patients with ICH compared to age, sex, and comorbidity-matched subjects. We enrolled patients with acute–subacute hemispheric ICH (n = 37; two were excluded due to artifacts) and grouped them according to the side (right and left) of the stroke. Matched participants or patients with recent transient ischemic attack were enrolled as control subjects for the study (n = 44; five were excluded due to artifacts). RSFC was assessed in both affected and unaffected hemispheres by group-level seed-based (primary motor cortex, priMC) correlation analysis. FT-associated relative oxyhemoglobin (ΔHbO) changes were analyzed in affected and unaffected hemispheres with generalized linear model regression. In left hemispheric ICH, the resting state coherence between the affected priMC and the affected premotor cortex (preMC) increased (β = 0.83, 95% CI = 0.19, 1.47, p = 0.01). In contrast, in right hemispheric ICH, the coherence between the unaffected priMC and the affected preMC decreased (β = −0.6, 95% CI = −1.12, −0.09, p = 0.02). In the left hemispheric ICH, the left-hand FT was associated with increased ΔHbO over the affected preMC (β = 0.01, 95% CI = 0.003, 0.02, p = 0.01). In contrast, in right hemispheric ICH, the left-hand FT was associated with increased ΔHbO over the unaffected preMC (β = 0.02, 95% CI = 0.006, 0.04, p = 0.01). Left hemispheric preMC may be involved in motor cortex reorganization in acute ICH in either hemisphere. Further studies may be required to assess longitudinal changes in motor cortex reorganization to inform acute motor rehabilitation.