Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study.

Acute ischemic stroke is the most common cause of neurologic dysfunction caused by focal brain ischemia and tissue injury. Diabetes is a major risk factor of stroke, exacerbating disease management and prognosis. Therefore, discovering new diagnostic markers and therapeutic targets is critical for stroke prevention and treatment. Extracellular vesicles (EVs), with their distinctive properties, have emerged as promising candidates for biomarker discovery and therapeutic application. This case-control study utilized mass spectrometry-based proteomics to compare EVs from non-diabetic stroke (nDS = 14), diabetic stroke (DS = 13), and healthy control (HC = 12) subjects. Among 1288 identified proteins, 387 were statistically compared. Statistical comparisons using a general linear model (log2 foldchange ≥0.58 and FDR-p≤0.05) were performed for nDS vs HC, DS vs HC, and DS vs nDS. DS vs HC and DS vs nDS comparisons produced 123 and 149 differentially expressed proteins, respectively. Fibrinogen gamma chain (FIBG), Fibrinogen beta chain (FIBB), Tetratricopeptide repeat protein 16 (TTC16), Proline rich 14-like (PR14L), Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKE), Biorientation of chromosomes in cell division protein 1-like 1 (BD1L1), and protein PR14L exhibited significant differences in the DS group. The pathway analysis revealed that the complement system pathways were activated, and blood coagulation and neuroprotection were inhibited in the DS group (z-score ≥2; p ≤ 0.05). These findings underscore the potential of EVs proteomics in identifying biomarkers for stroke management and prevention, warranting further clinical investigation.

Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Remote Ischemic Conditioning to Reduce Perihematoma Edema in Patients with Intracerebral Hemorrhage (RICOCHET): A Randomized Control Trial.

Background: Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. Methods: ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Results: Sixty patients were randomized with a mean ± SD age of 57.5 ± 10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5-0.9) mL vs. SC group 0.91 (0.5-1.2) mL, p = 0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3-0.8) cm vs. SC group 0.51 (0.3-0.8) cm, p = 0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6-1.2) cm vs. SC group 1 (0.9-1.2) cm, p = 0.75). Conclusions: Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention.

Short-term functional outcomes of patients with acute intracerebral hemorrhage in the native and expatriate population.

Objectives: Functional outcomes in patients with intracerebral hemorrhage (ICH) have not been well characterized in the Middle East and North Africa Region. We report the 30 and 90-day clinical outcomes in the native and expatriate of Qatar with ICH. Methods: We evaluated the Glasgow Coma Scale (GCS), NIHSS, and imaging in the Qatar Stroke Registry (2013-22). The outcome measures were a modified Rankin Scale (mRS) at 90 days and mortality at 30 and 90 days. Unfavorable outcome was defined as mRS of 4-6. We performed non-parametric ROC analyses to measure the concordance index (C-index) to assess the goodness-of-fit of ICH score for predicting 30 day and 90-day mortality and functional outcome. Results: 1,660 patients (median age of 49 (41.5-58) years; male 83.1%, expatriates 77.5%) with ICH, including supratentorial deep in 65.2%, cortical in 16.2%, infratentorial 16% and primary intraventricular in 2.5% were studied. The median baseline ICH volume was 7.5 (3.2-15.8) ml. An unfavorable outcome was seen in 673 (40.5%) patients at 90 days. The unfavorable 90-day outcome (mRS 4-6) was 49.2% in the native population vs. 44.4% in Africans, 39.0% in South Asian, 35.3% in Far Eastern, and 7.7% in Caucasians, p < 0.001. Mortality at 30 days and 90 days was 10.4 and 15.1%. Increasing age [OR (95% CI), 1.02 (1.00-1.03)], lower GCS [0.77 (0.73-0.80)], prior use of antiplatelet medications [1.82 (1.19-2.08)], higher ICH volume [1.03 (1.02-1.04)], and presence of any intraventricular hemorrhage [1.57(1.19-2.08)], were associated with unfavorable outcome. Conclusion: In this relatively younger ICH cohort more than 75% were expatriates. The ICH volume, 90-day unfavorable outcome and mortality was lower in the expatriates compared to the local Arab population, likely related to the younger age and smaller size of the hemorrhages. Prognostic scoring systems may have to be modified in this population to avoid early withdrawal of care.

Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review.

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. Methods: This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. Results: During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. Conclusion: PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.

Predictors of the unfavorable outcomes in acute ischemic stroke patients treated with alteplase, a multi-center randomized trial.

Worldwide, stroke is a leading cause of long-term disability in adults. Alteplase is the only approved treatment for acute ischemic stroke (AIS) and results in an improvement in a third of treated patients. We evaluated the post-stroke unfavourable outcome predictors in alteplase-treated patients from Egypt and Saudi Arabia. We assessed the effect of different risk factors on AIS outcomes after alteplase in Egypt and Saudi Arabia. Our study included 592 AIS alteplase-treated patients. The relationship between risk factors, clinical presentation, and imaging features was evaluated to predict factors associated with poor outcomes. An mRS score of three or more was used to define poor outcomes. Poor outcome was seen in 136 patients (23%), and Patients with unfavourable effects had significantly higher admission hyperglycaemia, a higher percentage of diabetes mellitus, cardioembolic stroke, and a lower percentage of small vessel stroke. Patients with higher baseline NIHSS score (OR 1.39; 95% CI 1.12-1.71; P = 0.003), admission hyperglycaemia (OR 13.12; 95% CI 3.37-51.1; P < 0.001), and post-alteplase intracerebral haemorrhage (OR 7.41; 95% CI 1.69-32.43; P = 0.008) independently predicted unfavourable outcomes at three months. In AIS patients treated with alteplase, similar to reports from other regions, in patients from Egypt and Saudi Arabia also reveal that higher NIHSS, higher serum blood sugar, and post-alteplase intracerebral haemorrhage were the predictors of unfavourable outcomes three months after ischemic stroke.Trial registration: (clinicaltrials.gov NCT06058884), retrospectively registered on 28/09/2023.

Association between serum triglycerides and stroke type, severity, and prognosis. Analysis in 6558 patients.

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller in patients with HT. We explored the relationship between triglyceride levels and stroke risk factors, severity and outcome in a large prospective database. DESIGN: Prospective Cross-sectional study. SETTING: We retrospectively interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between triglyceride, diabetes, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with HT. PARTICIPANTS: Six thousand five hundred fifty-eight patients ≥20 years were included in this study RESULTS: Six thousand five hundred fifty-eight patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) were included. Triglyceride levels upon admission were low-normal (≤1.1 mmol/L) in 2019 patients, high-normal (1.2-1.7 mmol/L) in 2142 patients, borderline-high (1.8-2.2 mmol/L) in 1072 patients and high (≥2.3 mmol/L) in 1325 patients. Higher triglyceride levels were associated with stroke and increased likelihood of having diabetes, obesity, active smoking, and small vessel/lacunar stroke type. An inverse relationship was noted whereby higher triglyceride levels were associated with lower stroke severity and reduced likelihood of poorer outcome (mRS 3-6) at discharge and 90 days. Long-term MACE events were less frequent in patients with higher triglyceride levels. After adjusting age, gender, diabetes, prior stroke, CAD, and obesity, multivariate analysis showed that hypertension and triglyceride levels were higher in mild ischemic strokes patients. CONCLUSIONS: Increasing triglycerides are associated with higher risk of small vessel disease and requires further prospective cohort studies for confirmation.

Accreditation of stroke programs at the MENA + region; between aspiration and reality.

INTRODUCTION: Despite global progress in stroke care, challenges persist, especially in Low- and Middle-Income countries (LMIC). The Middle East and North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) Stroke Program Accreditation Initiative aims to improve stroke care regionally. MATERIAL & METHOD: A 2022 survey assessed stroke unit readiness in the Middle East and North Africa (MENA) + region, revealing significant regional disparities in stroke care between high-income and low-income countries. Additionally, it demonstrated interest in the accreditation procedure and suggested that regional stroke program accreditation will improve stroke care for the involved centers. CONCLUSION: An accreditation program that is specifically tailored to the regional needs in the MENA + countries might be the solution. In this brief review, we will discuss potential challenges faced by such a program and we will put forward a well-defined 5-step accreditation process, beginning with a letter of intent, through processing the request and appointment of reviewers, the actual audit, the certification decisions, and culminating in granting a MIENA-SINO tier-specific certificate with recertification every 5 years.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Association between HDL levels and stroke outcomes in the Arab population.

Low HDL levels are associated with an increased stroke incidence and worsened long-term outcomes. The aim of this study was to assess the relationship between HDL levels and long-term stroke outcomes in the Arab population. Patients admitted to the Qatar Stroke Database between 2014 and 2022 were included in the study and stratified into sex-specific HDL quartiles. Long-term outcomes included 90-Day modified Rankin Score (mRS), stroke recurrence, and post-stroke cardiovascular complications within 1 year of discharge. Multivariate binary logistic regression analyses were performed to identify the independent effect of HDL levels on short- and long-term outcomes. On multivariate binary logistic regression analyses, 1-year stroke recurrence was 2.24 times higher (p = 0.034) and MACE was 1.99 times higher (p = 0.009) in the low-HDL compared to the high-HDL group. Mortality at 1 year was 2.27-fold in the low-normal HDL group compared to the reference group (p = 0.049). Lower sex-specific HDL levels were independently associated with higher adjusted odds of 1-year post-stroke mortality, stroke recurrence, and MACE (p < 0.05). In patients who suffer a stroke, low HDL levels are associated with a higher risk of subsequent vascular complication.

Stroke and high-risk TIA outcomes with reduction of treatment duration when treatment initiated in emergency rooms (SHORTER-study).

BACKGROUND: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment. STUDY DESIGN: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932. OUTCOMES: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage. STUDY PERIOD: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025. DISCUSSION: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

Validation of general pain scores from multidomain assessment tools in stroke.

Purpose: We describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke. Materials and methods: Analyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain. Results: European Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0-10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0-10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0-10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = -0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0-10 NPRS. Discussion: The EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0-10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.

Intravenous tenecteplase compared with alteplase for minor ischaemic stroke: a secondary analysis of the AcT randomised clinical trial.

BACKGROUND: In ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial. METHODS: The AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0-1 at 90-120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH). RESULTS: Of the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0-1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)). CONCLUSION: In this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.

Endovascular thrombectomy for acute ischemic stroke in Saudi Arabia: A single-center experience.

PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.

Direct to Angiosuite in Acute Stroke with Mobile Stroke Unit.

BACKGROUND: Early reperfusion has the best likelihood for a favorable outcome in acute ischemic stroke (AIS) with large vessel occlusion (LVO). Our experience with mobile stroke unit (MSU) for direct to angiosuite (DTAS) transfer in AIS patients with suspected LVO is presented. METHODS: Retrospective review of prospectively collected data from November 2019 to August 2022, of patients evaluated and transferred by the University of Alberta Hospital MSU and moved to angiosuite for endovascular thrombectomy (EVT). RESULT: A total of 41 cases were included. Nine were chosen for DTAS and 32 were shifted to angiosuite after stopping for computed tomography (CT) angiography of the head and neck (no-DTAS). Stroke severity measured by NIHSS (median with interquartile range (IQR)) was higher in patients of DTAS, 22 (14-24) vs 14.5 (5-25) in no-DTAS (p = 0.001). The non-contrast CT head in MSU showed hyperdense vessels in 8 (88.88%) DTAS vs 11 (34.35%) no-DTAS patients (p = 0.003). The EVT timelines (median with IQR, 90th percentile) including "door to artery puncture time" were 31 (23-50, 49.2) vs 79 (39-264, 112.8) minutes, and "door to recanalization time" was 69 (49-110, 93.2) vs 105.5 (52-178, 159.5) minutes in DTAS vs no-DTAS group, respectively. The workflow times were significantly shorter in the DTAS group (p < 0.001). Eight (88.88%) out of 9 DTAS patients had LVO and underwent thrombectomy. CONCLUSIONS: MSU for DTAS in patients with high NIHSS scores, cortical signs, and CT showing hyperdense vessel is an effective strategy to reduce the EVT workflow time.

Is telestroke more effective than conventional treatment for acute ischemic stroke? A systematic review and meta-analysis of patient outcomes and thrombolysis rates.

BACKGROUND: Telestroke systems operate through remote communication, providing distant stroke evaluation through expert healthcare providers. The aim of this study was to assess whether the implementation of a telestroke system influenced stroke treatment outcomes in acute ischemic stroke (AIS) patients compared with conventional in-person treatment. AIMS: The study group evaluated multiple studies from electronic databases, comparing telemedicine (TM) and non-telemedicine (NTM) AIS patients between 1999 and 2022. We aimed to evaluate baseline characteristics, critical treatment times, and clinical outcomes. SUMMARY OF REVIEW: A total of 12,540 AIS patients were included in our study with 7936 (63.9%) thrombolyzed patients. Of the thrombolyzed patients, 4150 (51.7%) were treated with TM, while 3873 (48.3%) were not. The mean age of TM and NTM cohorts was 70.45 ± 4.68 and 70.42 ± 4.63, respectively (p > 0.05). Mean National Institute of Health Stroke Scale scores were comparable, with the TM group reporting a non-significantly higher mean (11.89 ± 3.29.6 vs. 11.13 ± 3.65, p > 0.05). No significant difference in outcomes was found for symptoms onset-to-intravenous tissue plasminogen activator (ivtPA) times (144.09 ± 18.87 vs. 147.18 ± 25.97, p = 0.632) and door-to-needle times (73.03 ± 20.04 vs. 65.91 ± 25.96, p = 0.321). Modified Rankin scale scores (0-2) were evaluated, and no significant difference was detected between cohorts (odds ratio (OR): 1.06, 95% confidence interval (CI): 0.89-1.29, p = 0.500). Outcomes did not indicate any significance between both cohorts for 90-day mortality (OR: 1.16, 95% CI: 0.94-1.43, p = 0.17) or symptomatic intracranial hemorrhage (OR: 0.99, 95% CI: 0.73-1.34, p = 0.93). Results between groups were also non-significant when analyzing the rate of thrombolysis with ivtPA (30.86%± 30.7 vs. 20.5%± 18.6, p = 0.372) and endovascular mechanical thrombectomy (11.8%± 11.7 vs. 18.7%± 18.9, p = 0.508). CONCLUSION: The use of telestroke in the treatment of AIS patients is safe with minimal non-significant differences in long-term outcomes and rates of thrombolysis compared with face-to-face treatment. Further studies comparing the different methods of TM are needed to assess the efficacy of TM in stroke treatment.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). METHODS: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). FINDINGS: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. INTERPRETATION: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. FUNDING: Bristol Myers Squibb and Janssen Research & Development.

Tensor-valued diffusion MRI of human acute stroke.

PURPOSE: Tensor-valued diffusion encoding can disentangle orientation dispersion and subvoxel anisotropy, potentially offering insight into microstructural changes after cerebral ischemia. The purpose was to evaluate tensor-valued diffusion MRI in human acute ischemic stroke, assess potential confounders from diffusion time dependencies, and compare to Monte Carlo diffusion simulations of axon beading. METHODS: Linear (LTE) and spherical (STE) b-tensor encoding with inherently different effective diffusion times were acquired in 21 acute ischemic stroke patients between 3 and 57 h post-onset at 3 T in 2.5 min. In an additional 10 patients, STE with 2 LTE yielding different effective diffusion times were acquired for comparison. Diffusional variance decomposition (DIVIDE) was used to estimate microscopic anisotropy (µFA), as well as anisotropic, isotropic, and total diffusional variance (MKA , MKI , MKT ). DIVIDE parameters, and diffusion tensor imaging (DTI)-derived mean diffusivity and fractional anisotropy (FA) were compared in lesion versus contralateral white matter. Monte Carlo diffusion simulations of various cylindrical geometries for all b-tensor protocols were used to interpret parameter measurements. RESULTS: MD was ˜40% lower in lesions for all LTE/STE protocols. The DIVIDE parameters varied with effective diffusion time: higher µFA and MKA in lesion versus contralateral white matter for STE with longer effective diffusion time LTE, whereas the shorter effective diffusion time LTE protocol yielded lower µFA and MKA in lesions. Both protocols, regardless of diffusion time, were consistent with simulations of greater beading amplitude and intracellular volume fraction. CONCLUSION: DIVIDE parameters depend on diffusion time in acute stroke but consistently indicate neurite beading and larger intracellular volume fraction.