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BackgroundRenal dysfunction is a known predictor of long-term functional dependency after anterior circulation large vessel occlusion (ACLVO) stroke. However, the impact of renal dysfunction on early infarct growth rate (IGR) has not been previously demonstrated. The objective of this study was to define the association of creatinine-based renal biomarkers with fast or slow progressor phenotypes and related clinical outcomes in ACLVO stroke.MethodsThis retrospective study examined patients with acute intracranial internal carotid artery or middle cerebral artery-M1 occlusions admitted between 2014 and 2019. Patients were included if they received baseline CT perfusion (CTP) or MRI on presentation within 24 h of estimated stroke onset. Infarct growth rate (IGR) was determined by ischemic core volume on CTP or MRI divided by time from stroke onset to imaging. IGR was used to stratify fast progressor (IGR ≥10 mL/h) and slow progressor (IGR

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Introduction The current FDA approved intracranial stent delivery system requires a multi‐step deployment involving the use of exchange length microwire (ELW), typically 0.014‐inch 300 cm wire, to navigate the balloon catheter, which is then exchanged, after performing the angioplasty, over the ELW to a 0.017’ microcatheter that is used to deploy the intracranial stent. Herein, we describe a single‐step approach to deploy Neuroform Atlas stent (Stryker Neurovascular, Fremont, CA) which is a hybrid laser‐cut, nitinol self‐expanding stent without the need for ELW or lesion re‐access using MINI TREK RX (Abbott Vascular, Inc., Santa Clara, CA, USA) semi compliant balloon adapted from cardiovascular literature which showed a pre‐dilation angioplasty capability in coronary stenotic lesions. Methods We performed a retrospective review of prospectively maintained mechanical thrombectomy (MT) databases of 2 comprehensive stroke centers between November 2020, and May 2023. The inclusion criteria were consecutive large vessel occlusion stroke patients in whom single step MINI TREK RX balloon angioplasty followed by Neuroform Atlas intracranial stent deployment was performed without using ELW (Figure‐1). There was no restriction on time from last known well (TLKW) to MT. During the standard mechanical thrombectomy procedure, intracranial atherosclerotic disease/ significant stenotic lesion was suspected by immediate re‐occlusion/ persistent occlusion following at least 1 thrombectomy pass. This is followed by pursuing intracranial angioplasty and stent placement as a rescue recanalization measure. The primary outcome was successful reperfusion defined as a Modified Treatment in Cerebral Ischemia (mTICI) score of 2b or greater at the end of the procedure. Secondary outcomes included NIH Stroke Scale (NIHSS) at 24 hours, NIHSS at discharge, median modified Rankin Scale (mRS) score at discharge and at 90‐day follow‐up. Safety measures included rates of symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results Among 9 patients who met our criteria, the median age was 63 (51‐69.5) years and 55.6% were females. Most patients had left middle cerebral artery‐ M1 occlusion (66.7%) and one third received thrombolytics (33.3%). All patients underwent the single‐step approach and achieved successful reperfusion (m TICI 2b‐3) with 2 median number of passes. The median NIHSS was reduced from 13.5 (8.5‐17.5) at baseline to 4 (1‐16.5) at discharge. In addition, median mRS was 1 (1‐3.5) at discharge and 3 (3‐4) at 90 days. None of the patients included in this series had sICH while only one patient with basilar artery occlusion underwent ventriculostomy during hospital stay and was sedated/intubated and died. Conclusion This preliminary experience showed technical feasibility and success of using single‐ step to deploy Neuroform Atlas stent after performing angioplasty using MINI TREK RX without the need for ELW or lesion re‐access. Prospective studies with larger sample size and long‐term clinical follow‐up are warranted to confirm these results.

Introduction Vertebro‐vertebral arteriovenous fistula (VV‐AVF) is a rare vascular malformation with abnormal high flow shunt between extracranial vertebral artery and an adjacent vertebral vein plexus without intervening capillaries.1 While seen in both adult and pediatric populations, the majority of the VV‐AVFs seen in childhood are largely congenital, seen in the setting of connective tissue diseases such as Ehler‐Danlos Syndrome, Neurofibromatosis type 1, and Marfan’s syndrome, with abnormal involution of the proatlantal system also thought to be implicated.2,3,4 Approximately 70% of the presenting population are symptomatic at presentation, with a pulsatile mass over the side of the neck or pulsatile tinnitus. Additionally, symptoms of vertebrobasilar insufficiency including gait abnormalities, limb weakness, vertigo, recurrent vomiting, diplopia, and in severe cases, cardiac decompensation can also be seen.5 Methods This is a case report of a 2‐year‐old boy presented to our pediatric neurovascular center of excellence with a progressively enlarging pulsatile left neck mass appreciated a year ago. Further evaluation with neck MRA followed by catheter cerebral angiogram revealed an upper cervical AVF with primary arterial feeders from V3 segment of the left vertebral artery, enlarged left occipital artery, and retrograde filling via the right vertebral artery into the left V4 with a direct shunt into a large venous pouch which drained into the vertebral venous plexus. Results Given the progressive enlargement of the mass, location of AVF, and concern for detrimental subsequent venous congestion, decision was made to pursue elective endovascular embolization of the VV‐AVF. The goal was set to obtain complete occlusion of the venous pouch to obliterate all arterial inflow contribution and prevent further recruitment. Occipital artery catheterization was attempted however given the redundant anatomical loops; optimum microcatheter navigation was not feasible. Given the non‐dominant configuration of the left VA, along with the presence of left AICA‐PICA system off the basilar trunk, coil embolization of the venous pouch followed by sacrifice of the V3 segment left VA was achieved satisfactorily leading to obliteration of the AVF along with all the arterial contributions from bilateral vertebral arteries and left occipital artery (Figure‐1). Given the potential vertebrobasilar inadvertent embolization, the procedure was performed under continuous neurophysiological monitoring and post‐periprocedural therapeutic anticoagulation. The patient tolerated the procedure well without any intraoperative issues. He was monitored in the pediatric ICU for 24 hours after the procedure, and subsequently discharged home. Conclusion We report a successful endovascular coil embolization of a VV‐AVF. To our knowledge, this is the youngest reported case where endovascular technique was successfully utilized to achieve cure of such high flow VV‐AVF in this 2‐year‐old patient. Systematic and methodical angiographic analyses with close post‐procedural monitoring are pivotal in ensuring successful outcomes.

Introduction There is growing evidence supporting endovascular treatment with middle meningeal artery embolization (MMAE) for the treatment of chronic subdural hematoma (cSDH). We aimed to compare Onyx vs. N‐Butyl cyanoacrylate (n‐BCA) as liquid embolic materials for MMAE. Methods We included all eligible patients undergoing MMAE for cSDH at University of Pittsburgh Medical Center from April 2019 to December 2022. The main outcomes included radiographic resolution of cSDH with at least 50% reduction of hematoma thickness as a surrogate for treatment success in addition to the need for rescue surgical intervention. Additional outcomes including complication rates and hematoma thickness at the last available follow up. Results A total of 195 patients underwent embolization of 234 hemispheres including 39 bilateral procedures and had available data for final analysis (168 (71.8%) in Onyx group vs. 66 (28.2%) in n‐BCA group). There were no significant differences in age, sex, co‐morbidities, prior SDH/evacuation, pre‐operative cSDH thickness, or use of antithrombotic therapy(P>0.05) while concurrent surgical intervention and midline shift showed a statistically significant difference (P

Introduction Delirium is an acute cognitive or perceptual disturbance that is associated with prolonged hospital and ICU length of stay, therefore, extending recovery time. According to a recent study, approximately one in five patients undergoing intracranial procedures are vulnerable to postoperative delirium within the first three days of surgery.1‐4 Retrospective cohort studies found a link between postoperative delirium and intraoperative hypotension, indicating reduced cerebral blood flow.5 ICSS‐ MRI study (International Carotid Stenting Study Magnetic Resonance Imaging Study), indicated that patients with periprocedural hemodynamic depression had decreased cerebral blood flow and increased the risk of new lesions in imaging.6 Ruptured intracerebral aneurysms are associated with higher morbidity and mortality than unruptured ones. This is secondary to delayed postoperative cerebral ischemia and infarction caused by vasospasm.7 Clinical indicators like delirium can play a role in evaluating for delayed cerebral ischemia and infarction leading to timely management of vasospasms.5,8,9 Our study aimed to assess the association between imaging findings of stroke and delirium in patients who underwent treatment for ruptured aneurysms. Methods We reviewed the medical records of 167 patients with ruptured intracranial aneurysms between 2015‐2019. We included all the patients who had a postoperative delirium assessment, neurological assessments, and MRI/CT scans for evaluation of cerebral ischemia. Patients were divided into 2 groups, one group with delirium and the other without delirium. Delirium was assessed by using the ICD9/10 codes and The Intensive Care Delirium Screening Checklist (ICDSC).10 Results A total of 167 patients presented with ruptured aneurysm and the incidence of delirium was 38.3% (64 patients). Patients with delirium had a median age of 57 (50.0‐65.8) compared to a median age of 55 (44.0‐64.0) in patients without delirium. Additional risk factors (delirium vs no delirium) included a history of stroke (17.5%/7.8%), smoking (30.1% vs 40.6%), female gender (63.1% vs 71.9%), preop‐benzodiazepines (26.2% vs 23.4%), intraoperative hypotension (78.6% vs 85.9%), and history of alcohol abuse (9.7% vs 9.4%). None of these factors reached statistical significance between patients with and without Delirium (p‐value >0.05). A new neurological deficit was noted in 17 (26.6%) patients with delirium compared to 12 (11.7%) patients without delirium (p‐value, 0.01). 24/29 (82.8%) patients with new neurological deficits had imaging finding suggesting acute ischemic changes (p‐value,

Introduction Current evidence supports endovascular therapy (EVT) for eligible patients with acute ischemic stroke in the anterior and posterior circulation. However, there is no consensus regarding the choice of anesthetic approach during EVT and early reported studies were observational with potential biases and confounding. Therefore, we sought to build concrete evidence from randomized clinical trials (RCTs) comparing the general anesthesia (GA) vs. non‐GA via a systematic review and meta‐analysis approach. Methods Data from inception to June 2023 were reviewed and only RCTs comparing the GA vs. non‐GA were included. We then pooled data for the main procedural, safety, and efficacy outcomes with odds ratios (ORs) and 95% CI for dichotomous data and mean difference (MD) with 95% CI for continuous data under random effect model. Results Eight RCTs were included in the final analysis (n=1203) with seven of them reporting data for the anterior circulation (n=1116) and one for the posterior circulation (n=87). Regarding efficacy outcomes, pooled results revealed non‐statistically significant difference between GA and non‐GA for functional independence at 90 days defined as modified Rankin Score scale of 0‐2 (OR = 1.17, 95% CI: 0.88–1.56, P= 0.28; I2 = 26%, Figure A) and the results of the anterior circulation subgroup showed non‐statistically significant difference (OR = 1.22, 95% CI: 0.90–1.67, P= 0.2; I2 = 31%) and the difference was not also evident for posterior circulation (48.8% vs 54.5%; RR, 0.89; 95% CI, 0.58‐1.38; adjusted OR, 0.91; 95% CI, 0.37‐2.22). Successful recanalization, defined as Thrombolysis in Cerebral Infarction score of 2b‐3, showed a statistically significant results favoring GA over non‐GA (OR = 1.94, 95% CI: 1.42–2.63, P=0.0001; I2 = 0%, Figure B) and this continued to show statistically significant in both anterior and posterior circulation subgroups. Onset to reperfusion time was not statistically significant between GA and non‐GA (MD, ‐2.59; 95% CI: ‐22.38 to 17.21, P= 0.8; I2=24%, Figure C). Regarding safety outcomes, there were no statistically significant differences in intracranial hemorrhage (OR = 0.95, 95% CI: 0.67–1.35, p = 0.79; I2 =0%, Figure D) or mortality (OR = 0.95, 95% CI: 0.71–1.29, p = 0.76; I2 =0%, Figure E). However, GA showed a higher risk of hypotension compared to non‐GA (OR = 6.05, 95% CI: 3.25–11.25, P=0.00001; I2 =69%, Figure F). Sensitivity analysis by leave one out removing Ren et al (5) showed homogenous results (OR = 8.43, 95% CI: 5.85–12.16, P=0.00001; I2 =0%) Conclusion In this study‐level meta‐analysis, GA resulted in higher rates of successful reperfusion as compared to non‐GA despite being associated with higher rates of hypotension. Since many of the included studies were small and single center, more studies are warranted to support these findings.

Introduction Cerebral venous sinus thrombosis (CVST) is a rare form of stroke that usually affects young females especially during pregnancy and the postpartum period. Several risk factors can contribute to the development of cerebral venous sinus thrombosis including hypercoagulable states, dehydration, infections, head or neck injuries, cancer, and some rheumatological diseases (1). The symptoms of cerebral venous sinus thrombosis can vary depending on the location and extent of the clot. Common signs and symptoms may include severe headaches, visual disturbances, seizures, focal neurological deficits, altered mental status, and in severe cases, coma. The initial treatment for CVST is systemic anticoagulation (2‐3). However, endovascular treatment (EVT) of CVST is typically reserved for cases associated with significant thrombus burden and lack of clinical improvement or worsening of symptoms despite systemic anticoagulation therapy without current conclusive evidence of its benefit. The aim of this study is to evaluate the evidence of EVT in patients with CVST. Methods A systemic literature search was conducted via PubMed to identify relevant studies. Only studies with sample sizes larger than 10 were included. We excluded small case series, meta‐analyses, systematic reviews, and studies that lack the main outcomes of interest. Our main outcomes included functional outcome defined as modified Rankin Scale score (mRS 0‐3), mortality, new or expanded ICH and recanalization rates. Results We finally included 10 studies (4‐13) in our qualitative synthesis. Only one study was a small, randomized clinical trial while the rest were observational studies. In our included studies, 267 patients underwent EVT for CVST. Among them, the median age was ranging from 12 to 75 and 162 (60 %) of patients were females. Patients were followed up for a mean ranging from 3 to 12 months. Recanalization was observed in 161 patients, out of which 111 were complete recanalization (68.9%) and 50 were partial recanalization (31.1%). Good functional outcome defined as mRS 0‐3 was achieved in a total of 181 patients. Additionally, 26 (9.7%) patients had a new onset or expanded ICH while 26 patients had died (9.7%). Conclusion EVT for CVST was associated with improved clinical outcomes with acceptable safety profile in severe cases. There is a lack of evidence from large randomized clinical trials so more prospective studies are needed to confirm these results.

Objective To measure the impact of the covid-19 pandemic on admissions to hospital and interventions for acute ischemic stroke and acute myocardial infarction.Design A retrospective analysis.Setting 746 qualifying hospitals in the USA from the Premier Healthcare Database.Participants Patients aged 18 years and older who were admitted to hospital with a primary diagnosis of acute ischemic stroke or acute myocardial infarction between 1 March 2019 and 28 February 2021.Main outcome measures Relative changes in volumes were assessed for acute ischemic stroke and acute myocardial infarction hospital admissions as well as intravenous thrombolysis, mechanical thrombectomy, and percutaneous coronary intervention (overall and for acute myocardial infarction only) across the first year of the pandemic versus the prior year. Mortality in hospital and length of stay in hospital were also compared across the first year of the pandemic versus the corresponding period the year prior. These metrics were explored across the different pandemic waves.Results Among 746 qualifying hospitals, admissions to hospital were significantly reduced after the covid-19 pandemic compared with before the pandemic for acute ischemic stroke (−13.59% (95% confidence interval−13.77% to −13.41%) and acute myocardial infarction (−17.20% (−17.39% to −17.01%)), as well as intravenous thrombolysis (−9.47% (−9.99% to −9.02%)), any percutaneous coronary intervention (−17.89% (−18.06% to −17.71%)), and percutaneous coronary intervention for acute myocardial infarction (−14.36% (−14.59% to −14.12%)). During the first year of the pandemic versus the previous year, the odds of mortality in hospital for acute ischemic stroke were 9.00% higher (3.51% v 3.16%; ratio of the means 1.09 (95% confidence interval (1.03 to 1.15); P=0.0013) and for acute myocardial infarction were 18.00% higher (4.81% v 4.29%; ratio of the means 1.18 (1.13 to 1.23); P

Background In patients undergoing mechanical thrombectomy for acute ischemic stroke, a few studies have compared transradial access (TRA) to transfemoral access (TFA) with inconsistent results. We conducted this systematic review and meta‐analysis to provide comprehensive evidence regarding the comparison of procedural and clinical outcomes of TRA versus TFA in patients with acute ischemic stroke undergoing mechanical thrombectomy. Methods We performed a comprehensive literature search of 4 electronic databases from inception until May 1, 2022. After title and full text screening, relevant data were extracted and then analyzed. For outcomes that constituted continuous data, the mean difference between the 2 groups and its SD were pooled. For outcomes that constituted dichotomous data, the frequency of events and the total number of patients in each group were pooled as odds ratio (OR) between the 2 groups. Results Nine observational studies were included in this meta‐analysis. The population of the studies was homogenous comprising a total of 2161 patients undergoing mechanical thrombectomy, including 446 patients via TRA and 1715 patients via TFA. There were no significant differences across the 2 groups in terms of successful recanalization (OR, 0.83 [95% CI, 0.55–1.25]; P=0.36), complete recanalization (OR 1.16 [95% CI, 0.50–2.68]; P=0.73), favorable functional outcomes (OR, 0.86 [95% CI, 0.53–1.41]; P=0.56), first‐pass reperfusion (OR, 0.88 [95% CI, 0.64–1.19]; P=0.41), number of passes (mean difference, 0.12 [95% CI, −0.18 to 0.42]; P=0.43), access‐to‐reperfusion time (mean difference, −3.92 minutes [95% CI, −9.49 to 1.65]; P=0.17), or symptomatic intracranial hemorrhage (OR, 0.86 [95% CI, 0.47–1.57]; P=0.62). However, access site complications were significantly less frequent in the TRA group as compared with the TFA group (OR, 0.18 [95% CI, 0.06–0.51; P=0.001). Conclusion In patients undergoing mechanical thrombectomy for acute ischemic stroke, the collective evidence suggests that TRA seems to result in lower rates of access site complications than TFA without significant compromise in other clinical or procedural metrics. Randomized or prospective studies are warranted to confirm these results.

Introduction In certain circumstances, mobile stroke units (MSU) with on‐site treatment teams and a computed tomography scanner may offer faster therapy with tissue plasminogen activator (tPA) for stroke patients who need immediate treatment. We conducted a systematic review and meta‐analysis to compare clinical outcomes in MSU patients to those in conventional care. Methods We searched key electronic databases from inception till September 2021. The primary outcomes were mortality at 7 days and 90 days. The secondary outcomes included modified Rankin scale (mRS) at 90 days, alarm to intravenous thrombolysis (IVT) or intra‐arterial recanalization, and time from symptom onset or last known well (LKW) to thrombolysis. Results We included nineteen controlled trials and cohort studies to conduct our final analysis. Our comparison revealed that 90‐day mortality rate significantly declined in MSU group as compared to conventional care group (OR = 0.81, 95%CI [0.69,0.95]), while there was no significant difference at 7 days (OR = 0.88, 95%CI [0.68,1.15]). As regard achieving functional independence at 90 days (mRS = 0–2), MSU showed better results (OR = 1.24, 95%CI [1.03,1.49]). MSU was associated with shorter time from symptoms onset or LKW to thrombolysis (MD = ‐36.79, 95%CI [‐47.48, ‐26.10]) and alarm to IV thrombolysis or intra‐arterial recanalization (MD = ‐29.69, 95%CI [‐34.46, ‐24.92]). Conclusions Stroke patients treated in MSU had a lower incidence of the 90‐day mortality. They also had better functional independence at 90 days and time from symptom onset or LKW to thrombolysis than those treated with conventional care.

Introduction Previous studies have compared the transradial access (TRA) with the transfemoral access (TFA) in patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We conducted this meta‐analysis to provide comprehensive evidence regarding the comparison of procedural and clinical outcomes of the TRA versus the TFA in AIS patients undergoing MT. Methods We performed a comprehensive literature search of four electronic databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL) from inception until 1 May 2022. All duplicates were removed, and all references of the included studies were screened manually for any eligible studies. The full‐text articles of eligible abstracts were retrieved and screened for continued eligibility. Relevant data were extracted and then analyzed. For outcomes that constitute continuous data, the mean difference (MD) between the two groups and its standard deviation (SD) were pooled. For outcomes that constitute dichotomous data, the frequency of events and the total number of patients in each group were pooled as odds ratio (OR) between the two groups. Results Nine studies were included in this meta‐analysis, all of which were observational studies. The population of the studies was homogenous comprising a total of 2,161 patients who underwent MT, including 446 in the TRA group and 1,715 in the TFA group. There were no significant differences across the two groups in terms of successful recanalization (Thrombolysis in cerebral Infarction [TICI] score of 2b‐3: OR 0.83, 95% CI [0.55 to 1.25], P = 0.36) (Figure 1, A), complete recanalization (TICI 3: OR 1.16, 95% CI [0.50 to 2.68], P = 0.73), favorable functional outcome (90‐day modified Rankin scale [mRS] score of 0–2 (OR 0.86, 95% CI [0.53 to 1.41], P = 0.56), first‐pass reperfusion (OR 0.88, 95% CI [0.64 to 1.19], P = 0.41), number of passes (MD 0.12, 95% CI [‐0.18 to 0.42], P = 0.43) (Figure 1, B), access‐to‐reperfusion time (MD ‐3.92 minutes, 95% CI [‐9.49 to 1.65], P = 0.17), the amount of contrast used (MD 5.03 mL, 95% CI [‐20.27 to 30.33], P = 0.70), or symptomatic intracranial hemorrhage (OR 0.86, 95% CI [0.47 to 1.57], P = 0.62). However, access‐site complications were significantly less frequent in the TRA group as compared to the TFA group (OR 0.18, 95% CI [0.06 to 0.51], P = 0.001) (Finger 1, C). Conclusions In patients undergoing MT for AIS, the collective evidence suggests that the TRA seems to result in lower rates of access‐site complications than the TFA without any significant compromise in other clinical or procedural metrics. Large prospective studies are warranted.

Introduction For more than three decades, robotic assisted surgery has been proposed, studied and put into action clinically. Likewise, it was cleared by the Food and Drug Administration for percutaneous coronary intervention in 2012 (K120834) and peripheral vascular intervention including carotid intervention in 2018 (K173288), but has not yet received clearance for intracranial neurovascular intervention in the USA. Recently, several pilot clinical studies assessed robotically performed neurointerventions. Methods We performed comprehensive electronic search till July 2022 on PubMed/Medline to retrieve all relevant studies and data were extracted for baseline characteristics, design, procedure type, safety and feasibility outcomes for qualitative synthesis. Results Our results yielded nine single center studies in UK, USA and China performed since 2015. The performed procedures included diagnostic cerebral angiography (36 patients), caroti aartery stenting (37 patients), unspecified robotic assisted intracranial intervention (18 patients) and stent‐assisted coil embolization of a basilar artery aneurysm (one case). The used robotic systems included Corpath GRX (5 studies), Magellan (2 studies), RobEnt (one study) and VIR‐2 (one study). The robotic assisted neurointervention was successful clinically without complications across all studies and for all procedures. The learning curve sounded promising but there were limitations in the design of systems for completing all steps robotically. Conclusions Robotics assisted procedures appear to be feasible and safe in neuro‐intevention field. Advantages include high accuracy, stability, safety, simplicity, versatility, monitoring, endothelial protection, and potential for remote access for procedures such as mechanical thrombectomy for acute ischemic stroke. However, there are many challenges including cost, manual steps, lack of manual resistance feeling, irrationality in the spatial arrangement of the robotic system and operating table. Additionally, most of the included studies were retrospective with small sample size and short term follow up and more well‐designed comparative prospective studies are needed to confirm these results.

Introduction The published clinical data assessing stem cell therapy for ischemic stroke (IS) are inconclusive. We conducted this comprehensive meta‐analysis to evaluate the efficacy and safety of stem cell therapy in the treatment of IS. Methods We searched electronic databases/search engines for studies comparing stem cell therapy to control in the treatment of IS from inception to June 2022. References were screened manually for eligibility. The relevant baseline data along with outcomes measured by modified Rankin scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI) and death were extracted and analyzed. Results We included 18 studies (12 randomized controlled trials (RCTs) and six non‐RCTs) comprising a total of 724 patients including 365 in the stem cells and 359 in the control group. Pooled results considering the last follow‐up point across 12 studies showed that stem cells significantly decreased mRS scores in relation to control (MD = ‐0.265, 95% CI [‐0.403 to ‐0.1269], P‐value = 0.00017). There was no publication bias (P = 0.4). The univariate meta‐regression demonstrated that route of administration, stem cell type, stroke type, and study design did not significantly contribute to the heterogeneity of the stem cells effect estimate (P >0.05). Additional analyses showed no significant differences in mRS scores between stem cells and control after seven days to three months (n = seven studies; MD = ‐0.039, 95% CI [‐0.22 to 0.15], P‐value = 0.681) and six to twelve months (n = ten studies; MD = ‐0.13, 95% CI [‐0.37 to 0.089], P‐value = 0.234). However, stem cells significantly decreased mRS scores in relation to control after two to four years (n = four studies; MD = ‐0.28, 95% CI [‐0.49 to ‐0.068], P‐value = 0.0096). Similarly, pooled results considering the last follow‐up point across nine studies showed that stem cells marginally decreased NIHSS scores in relation to control (MD = ‐1.185, 95% CI [‐2.37 to 0.00], P‐value = 0.05) with no publication bias (P = 0.5). Moreover, pooled results from 11 studies showed that stem cells significantly increased BI in relation to control (MD = 5.36, 95% CI [2.51 to 8.21], P‐value = 0.0002) with no publication bias (P = 0.675). Pooled results from 17 studies showed that stem cells treatment was significantly associated with lower risk of death in relation to control group (RR = 0.565, 95% CI [0.345 to 0.927], P‐value = 0.024). Conclusions Stem cell therapy for the treatment of IS seems to be associated with improved functional outcomes and reduced mortality. Notably, the demonstration of the functional outcome benefit appears to be more evident on longer follow‐up times (>2 years). Additional prospective studies are needed and should consider longer follow‐up periods.