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.

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.

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.

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.

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.).

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.

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.

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.

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.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Prevalence, Trajectory, and Predictors of Poststroke Pain: Retrospective Analysis of Pooled Clinical Trial Data Set.

BACKGROUND: Poststroke pain remains underdiagnosed and inadequately managed. To inform the optimum time to initiate interventions, we examined prevalence, trajectory, and participant factors associated with poststroke pain. METHODS: Eligible studies from the VISTA (Virtual International Stroke Trials Archives) included an assessment of pain. Analyses of individual participant data examined demography, pain, mobility, independence, language, anxiety/depression, and vitality. Pain assessments were standardized to the European Quality of Life Scale (European Quality of Life 5 Dimensions 3 Level) pain domain, describing no, moderate, or extreme pain. We described pain prevalence, associations between participant characteristics, and pain using multivariable models. RESULTS: From 94 studies (n>48 000 individual participant data) in VISTA, 10 (n=10 002 individual participant data) included a pain assessment. Median age was 70.0 years (interquartile range [59.0-77.1]), 5560 (55.6%) were male, baseline stroke severity was National Institutes of Health Stroke Scale score 10 (interquartile range [7-15]). Reports of extreme pain ranged between 3% and 9.5% and were highest beyond 2 years poststroke (31/328 [9.5%]); pain trajectory varied by study. Poorer independence was significantly associated with presence of moderate or extreme pain (5 weeks-3 months odds ratio [OR], 1.5 [95% CI, 1.4-1.6]; 4-6 months OR, 1.7 [95% CI, 1.3-2.1]; >6 months OR, 1.5 [95% CI, 1.2-2.0]), and increased severity of pain (5 weeks-3 months: OR, 1.2 [95% CI, 1.1-1.2]; 4-6 months OR, 1.1 [95% CI, 1.1-1.2]; >6 months, OR, 1.2 [95% CI, 1.1-1.2]), after adjusting for covariates. Anxiety/depression and lower vitality were each associated with pain severity. CONCLUSIONS: Between 3% and 9.5% of participants reported extreme poststroke pain; the presence and severity of pain were independently associated with dependence at each time point. Future studies could determine whether and when interventions may reduce the prevalence and severity of poststroke pain.

Diagnostic accuracy of large and medium vessel occlusions in acute stroke imaging by neurology residents and stroke fellows: A comparison of CT angiography alone and CT angiography with CT perfusion.

INTRODUCTION: Neurology senior residents and stroke fellows are first to clinically assess and interpret imaging studies of patients presenting to the emergency department with acute stroke. The aim of this study was to compare the diagnostic accuracy of brain CT angiography (CTA) with and without CT perfusion (CTP) between neurology senior residents and stroke fellows. METHODS: In this neuroimaging study, nine practitioners (four senior neurology residents (SNRs) and five stroke fellows (SFs)) clinically assessed and interpreted the imaging data of 50 cases (15 normal images, 21 large vessel occlusions (LVOs) and 14 medium vessel occlusions (MeVOs) in two sessions, 1 week apart in comparison to final diagnosis of experienced neuroradiologist and experienced stroke neurologist consensus. Interrater agreement of CTA alone and CTA with CTP was quantified using kappa statistics, sensitivity, specificity and overall accuracy. RESULTS: Overall, arterial occlusions were correctly identified in 221/315 (70.1%) with CTA alone and in 266/315 (84.4%) with CTA and CTP (p < 0.001). The sensitivity of overall arterial occlusions detection with CTA alone was 94.2% (95% CI: 90.8%-96.6%) while with addition of CTP was 98% (95% CI: 95.6%-99.3%), The specificity of CTA alone was 74.7% (95% CI: 67.2%-81.3%) which increased with CTP to 84.4% (95% CI: 77.7%-89.8%). The likelihood of correct identification with CTA alone was 156/189 (82.54%) for LVOs and 65/126 (51.59%) for MeVOs. This increased to 169/189 (89.42%; p = 0.054) for LVOs and 97/126 (76.98%; p < 0.001) for MeVOs when the CTA images with CTP were viewed. There was good overall interrater agreement between readers when using CTA alone (k 0.71, 95% CI, 0.62-0.80) and almost perfect (k 0.85, 95% CI, 0.76-0.94) when CTP was added to the image for interpretation. CTA and CTP had a significantly lower median interquartile range (IQR) interpretation time than CTA alone (114 [IQR, 103-120] s vs 156 [IQR, 133-160] s, p < 0.001). DISCUSSION: In cerebral arterial occlusions, the rate of LVO and MeVOs detections increases when adding CTP to CTA. The accuracy and time for diagnosing arterial occlusion can be significantly improved if CTP is added to CTA. As MeVOs are commonly missed by front-line neurology senior residents or stroke fellows, cases with significant deficits and no apparent arterial occlusions need to be reviewed with neuroradiological expertise.

Appropriate use of antiplatelet medications following transient ischemic attacks and stroke: a 9-year study from the Middle East.

Background and purpose: Guidelines recommend that patients with high-risk TIAs and minor strokes presenting within 1-3 days from onset should be offered dual antiplatelet therapy (DAPT). There are little data on real-world adherence to these recommendations. We evaluated the appropriateness of DAPT use in TIA and stroke patients in a prospective database. Methods: The Qatar Stroke Database began the enrollment of patients with TIAs and acute stroke in 2014 and currently has ~16,000 patients. For this study, we evaluated the rates of guideline-adherent use of antiplatelet treatment at the time of discharge in patients with TIAs and stroke. TIAs were considered high-risk with an ABCD2 score of 4, and a minor stroke was defined as an NIHSS of 3. Patient demographics, clinical features, risk factors, previous medications, imaging and laboratory investigations, final diagnosis, discharge medications, and discharge and 90-day modified Rankin Scale (mRS) were analyzed. Results: After excluding patients with ICH, mimics, and rare secondary causes, 8,082 patients were available for final analysis (TIAs: 1,357 and stroke: 6,725). In high-risk TIAs, 282 of 666 (42.3%) patients were discharged on DAPT. In patients with minor strokes, 1,207 of 3,572 (33.8%) patients were discharged on DAPT. DAPT was inappropriately offered to 238 of 691 (34.4%) low-risk TIAs and 809 of 3,153 (25.7%) non-minor stroke patients. Conclusion: This large database of prospectively collected patients with TIAs and stroke shows that, unfortunately, despite several guidelines, a large majority of patients with TIAs and stroke are receiving inappropriate antiplatelet treatment at discharge from the hospital. This requires urgent attention and further investigation.

Assessment of remote ischemic conditioning delivery with optical sensor in acute ischemic stroke: Randomised clinical trial protocol.

BACKGROUND: Remote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible. METHODS: The study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days. DISCUSSION: RIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.

Women and stroke: disparities in clinical presentation, severity, and short- and long-term outcomes.

Objectives: There are limited data from the Middle East on sex-related differences in short- and long-term stroke outcomes. We present 8 years of experience based on the Qatar stroke database. Setting: The Qatar stroke database prospectively collects data on all stroke patients admitted to Hamad General Hospital. For this study, we compared female and male acute ischemic stroke patients on their characteristics at admission, short-term outcomes [modified Rankin Scale (mRS) score], and long-term outcomes [incidence of major adverse cardiovascular events (MACEs)]. Participants: A total of 7,300 patients [F: 1,406 (19.3%), M: 5,894 (80.7%); mean age 55.1 ± 13.3 (F: 61.6 ± 15.1, M: 53.5 ± 12.3; p < 0.001)] were admitted with acute ischemic stroke. Results: Significantly fewer women presented within 4.5 h of onset (F: 29% vs. M: 32.8%; p = 0.01). Although women were more likely to experience severe stroke (NIHSS >10; F: 19.9% vs. M: 14.5%; p < 0.001), fewer were treated with thrombolysis (F: 9.8% vs. M: 12.1%; p = 0.02). Women experienced more medical complications (F: 11.7% vs. M: 7.4%; p < 0.001) and tended to have a more prolonged length of stay in the hospital (F: 6.4 ± 7.6 days vs. M: 5.5 ± 6.8 days; p < 0.001). Primary and secondary outcome measures: Good outcomes at 90 days (mRS score of 0-2) were less frequent in women (F: 53.3% vs. M: 71.2%; p < 0.001). Fewer female patients were taking antiplatelets (F: 78% vs. M: 84.8%; p < 0.001) or statins (F: 81.2% vs. M: 85.7%; p < 0.001). Significantly more female patients experienced a MACE (F: 12.6% vs. M: 6.5%; p < 0.001). Conclusion: Older age at presentation contributes to poor outcomes following acute stroke in women. Other contributing factors include delays in admission to the hospital, lower rates of thrombolysis, and lower rates of provision of preventative treatments.

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.

Collateral Circulation in Ischemic Stroke: An Updated Review.

The collateral circulation plays a crucial role in maintaining perfusion to brain tissue in ischemic stroke, which prolongs the time window for effective therapies to be provided and ultimately avoids irreversible damage that may lead to worse clinical outcomes. The understanding of this complex vascular bypass system has advanced greatly in the past few years, yet effective treatments for its potentiation as a therapeutic target remain a challenge. The assessment of the collateral circulation is now part of the routine neuroimaging protocols for acute ischemic stroke, which provides a more complete pathophysiological picture in each patient that allows for a better selection for acute reperfusion therapies and a more accurate prognostication of outcomes, among other potential uses. In this review, we aim to provide a structured and updated approach to the collateral circulation while highlighting ongoing research areas with promising future clinical applications.