Complement-dependent neuroinflammation in spinal cord injury: from pathology to therapeutic implications.

Spinal cord injury remains a major cause of disability in young adults, and beyond acute decompression and rehabilitation, there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population. Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation, a similar role for complement in spinal neuroinflammation is a focus of ongoing research. In this work, we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins, triggers of complement activation, and role of effector functions in the pathology. We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris, and or activation via antibody binding to damage-associated molecular patterns. Several effector functions of complement have been implicated in spinal cord injury, and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury. Following this pathophysiological review, we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects. This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury, to evaluate the phases of involvement of opsonins and anaphylatoxins, and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

FreeClimb 88 catheter with Tenzing 8 delivery for contact aspiration mechanical thrombectomy of anterior circulation large vessel occlusions.

PURPOSE: Contact aspiration mechanical thrombectomy (CAMT) with 0.088-inch catheters may improve first-pass success rates, but delivery of such catheters can be challenging and limit effectiveness. This study examines the initial multicenter experience using the FreeClimb 88 catheter paired with the Tenzing 8 delivery catheter. MATERIALS AND METHODS: Retrospective analysis was performed of consecutive patients with large vessel occlusion (LVO) of the internal carotid artery (ICA) or M1 segment of the middle cerebral artery treated with off-label CAMT using the FreeClimb 88 and Tenzing 8 at eight sites participating in the early limited release for these devices. Demographic and procedural variables were collected and analyzed with descriptive statistics and multivariable analysis. RESULTS: Fifty-three consecutive patients were treated. Large vessel occlusion was located in the ICA in 19/53 (35.8%) patients; 34/53 (64.2%) were in the M1 segment. FreeClimb 88 was successfully delivered to the site of occlusion in 50/53 (94.3%) of patients. First-pass TICI 2c or 3 was achieved with FreeClimb 88 delivered by Tenzing 8 in 36 (67.9%) cases. Among cases with successful FreeClimb 88 delivery 9/50 (18.0%) required additional smaller devices to perform thrombectomy of distal occlusions after recanalization of the initial LVO. No complications or symptomatic hemorrhages occurred following thrombectomy. CONCLUSION: Contact aspiration mechanical thrombectomy performed for ICA or M1 LVOs using FreeClimb 88 delivered with Tenzing 8 was safe, effective, and efficient in this early experience, with first-pass TICI 2c or 3 was achieved in 68% of patients without procedural complications occurring in any cases.

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in Early and Late Time Windows.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset. METHODS: A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal. RESULTS: Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04). CONCLUSION: Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset.

Reliability assessment of distal occlusion eTICI scoring.

BACKGROUND: The eThrombolysis in Cerebral Infarction (eTICI) score has been validated in proximal large artery occlusion (pLAOs). Despite the growing number of distal medium vessel occlusions (DMVOs) mechanical thrombectomies (MT) and the widespread utilization of the eTICI scoring system, its reliability and standardization for more distal occlusions have not been validated. We aim to evaluate the interrater reliability of eTICI scores in primary DMVOs. METHODS: This was a retrospective analysis of a prospectively maintained database for consecutive patients with pLAO and DMVO MT at a single comprehensive stroke center from 2015 to 2022. Two fellowship-trained neurointerventionalists blindly/independently assessed digital subtraction angiograms for final eTICI, followed by consensus reads for discrepancies. RESULTS: 59 DMVO of 2248 thrombectomies [M3:29(50%)/M4:1(2%)/A1:3(5%)/A2:12(22%)/A3: 5(9%)/P1:7(12%)/P2:1(2%)] and 124 pLAOs of 308 thrombectomies [i-ICA:13(11%)/MCA-M1: 111(90%)] were included. The distribution of final eTICI scores was comparable between pLAO vs DMVOs (p = 0.82). The pLAO final eTICI score assessment between two readers demonstrated moderate reliability with a kappa0.77 (95%CI: 0.67-0.88), while the DMVO eTICI score assessment exhibited almost-perfect agreement with kappa 0.94 (95%CI: 0.90-0.99). The agreement between the consensus read and the original report in DMVOs was 0.86 (95% CI: 0.71-1.00) while for pLAO it was 0.83(95% CI: 0.76-0.90). The performance of eTICI was comparable amongst different DMVO territories as well as for distal vs. very distal occlusions. CONCLUSION: eTICI score exhibited comparable performance for DMVO as compared to pLAO strokes. Further studies investigating DMVO eTICI grading and clinical outcomes are warranted.

Validation of a model for outcome prediction after endovascular treatment for ischemic stroke.

INTRODUCTION: The recently developed MR-PREDICTS@24 h model showed excellent performance in the MR-CLEAN Registry cohort in patients presenting within 12 h from onset. However, its applicability to an U.S. population and to patients presenting beyond 12 h from last known normal are still undetermined. We aim to externally validate the MR-PREDICTS@24 h model in a new geographic setting and in the late window. METHODS: In this retrospective analysis of a prospectively collected database from a comprehensive stroke center in the United States, we included patients with intracranial carotid artery or middle cerebral artery M1 or M2 segment occlusions who underwent endovascular therapy and applied the MR-PREDICTS@24 h formula to estimate the probabilities of functional outcome at day 90. The primary endpoint was the modified Rankin Scale (mRS) at 90 days. RESULTS: We included 1246 patients, 879 in the early (<12 h) and 367 in the late (≥12 h) cohort. For both cohorts, calibration and discrimination of the model were accurate throughout mRS levels, with absolute differences between estimated and predicted proportions ranging from 1% to 5%. Calibration metrics and curve inspections showed good performance for estimating the probabilities of mRS ≤ 1 to mRS ≤ 5 for the early cohort. For the late cohort, predictions were reliable for the probabilities of mRS ≤ 1 to mRS ≤ 4. CONCLUSION: The MR-PREDICTS@24 h was transferrable to a real-world U.S.-based cohort in the early window and showed consistently accurate predictions for patients presenting in the late window without need for updating.

Symptomatic carotid webs and patent foramen ovale: RoPE score in competing stroke etiologies.

BACKGROUND: Patent foramen ovale (PFO)-associated stroke is diagnosed more frequently in young patients with infrequent vascular risk factors and embolic appearing infarcts. The risk of paradoxical embolism (RoPE) score is used to identify PFO-associated stroke. Patients with symptomatic carotid artery web (CaW) share a very similar risk profile and these lesions are frequently overlooked. In this study, we evaluate the RoPE score profile in patients with suspected symptomatic CaW. METHODS: Retrospective analysis of prospectively collected data of patients with symptomatic CaW as the presumed cause of stroke presenting to 2 comprehensive stroke centers from 2014 to 2021. CaW was diagnosed using computed tomography angiography (CTA) of the neck & head. Shunt study was done using a transthoracic, transesophageal, and/or transcranial-Doppler with bubbles. RoPE score ≥7 was considered high. RESULTS: Seventy-five patients had stroke from a symptomatic ipsilateral CaW. Mean age was 49.7±11.2 years and 74.7 % were females. Median RoPE score was 7 [5-8], and 52.0 % had a high RoPE score. PFO was detected in 13.3 % of the patients and 20.5 % within the high RoPE score group. Ten percent of the cases would have been misclassified as PFO-associated strokes based on RoPE score. CONCLUSION: High RoPE scores were observed in the majority of patients with CaW-attributed stroke, and it should not be used to differentiate CaW- versus PFO-associated stroke. Careful extracranial internal carotid artery evaluation for CaW is warranted in cryptogenic strokes, including in PFO positive patients before defining stroke etiology.

Multiplane reconstruction modifies the diagnostic performance of CT angiography in carotid webs.

INTRODUCTION: Carotid Web (CaW) represents an overlooked stroke etiology and has been associated with high recurrence rates and to be amenable to stenting. We evaluated the diagnostic performance of different computed tomography angiography (CTA) projections in CaW. METHODS: Consecutive patients <65 years-old with symptomatic CaW (n=31), carotid atherosclerosis (n=27), or normal carotids (n=49) diagnosed with a thin-cut CTA were included. Deidentified CTAs were independently reviewed by three readers, who recorded the diagnosis and level of certainty after evaluating the axial plane alone, after adding sagittal/coronal maximum intensity projection (MIP), then after oblique MPR reformats. RESULTS: There were 93 total CaW, 81 atherosclerosis, and 147 normal carotid reads. With CTA axial projection alone, less CaW cases (44.1 %) were appropriately diagnosed as compared to atherosclerosis (87.7 %; p<0.001) and normal carotid (83 %; p<0.001) cases. Sagittal/coronal MIPS increased the rate of accurate CaW diagnosis (44.1-76.3 %; p<0.001). Inter-rater agreement in CaW detection increased from k= 0.46 (0.35-0.57) using axial to k= 0.80 (0.69-0.91) with sagittal/coronal planes. The axial projection alone had lower sensitivity (44 % vs. 76 %) but similar specificity (95 % vs. 96 %) in CaW detection compared to axial+ sagittal/coronal MIPS. The accuracy in detecting atherosclerosis or normal carotids did not increase after adding sagittal/coronal MIPS and oblique MPRs. The certainty level for CaW diagnosis was lower when compared to atherosclerosis and normal carotids using axial alone (3.0 [3.0-4.0] vs. 4.0 [3.0-5.0]; p<0.001 and 4.0 [3.0-5.0]; p<0.001) as well as after adding sagittal/coronal MIPS (4.0 [3.0-5.0] vs. 5.0[4.0-5.0]; p=0.01 and 4.0 [4.0-5.0]; p<0.001). CONCLUSION: CTA axial plane alone was insufficient for CaW detection. CTA sagittal/coronal MIP reconstructions as well as oblique MPR reformats enhanced the accuracy and confidence related to CaW diagnosis.

Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off-label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High-performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two-compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <-.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine.

Anesthesia modality in endovascular treatment for distal medium vessel occlusion stroke: intention-to-treat propensity score-matched analysis.

BACKGROUND: The optimal anesthesia modality during endovascular treatment (EVT) for distal medium vessel occlusion (DMVO) stroke is uncertain. We aimed to evaluate the association of the anesthesia modality with procedural and clinical outcomes following EVT for DMVO stroke. METHODS: This is a multicenter retrospective analysis of a prospectively collected database. Patients were included if they had DMVO involving the middle cerebral artery-M3/4, anterior cerebral artery-A2/3, or posterior cerebral artery-P1/P2-3, and underwent EVT. The cohort was divided into two groups, general anesthesia (GA) and non-general anesthesia (non-GA), and compared based on the intention-to-treat principle as primary analysis. We used propensity scores to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the 90-day modified Rankin Scale (mRS). Secondary outcomes included successful reperfusion, as well as excellent (mRS 0-1) and good (mRS 0-2) clinical outcomes at 90 days. Safety measures included procedural complications, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Among 366 DMVO thrombectomies, 61 matched pairs were eligible for analysis. Median age and National Institutes of Health Stroke Scale score as well as other baseline demographic and clinical characteristics were balanced between both groups. The GA group had no difference in the overall degree of disability (common OR 1.19, 95% CI 0.52 to 2.86, P=0.67) compared with the non-GA arm. Likewise, the GA group had comparable rates of successful reperfusion (OR 2.38, 95% CI 0.80 to 7.07, P=0.12), good/excellent clinical outcomes (OR 1.14, 95% CI 0.44 to 2.96, P=0.79/(OR 0.65, 95% CI 0.24 to 1.81, P=0.41), procedural complications (OR 1.00, 95% CI 0.19 to 5.16, P>0.99), sICH (OR 3.24, 95% CI 0.83 to 12.68, P=0.09), and 90-day mortality (OR 1.43, 95% CI 0.48 to 4.27, P=0.52) compared with the non-GA group. CONCLUSIONS: In patients with DMVO, our study showed that GA and non-GA groups had similar procedural and clinical outcomes, as well as safety measures. Further larger controlled studies are warranted.

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD).

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

OBJECTIVE: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). METHODS: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). INTERPRETATION: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024;96:343-355.

Developmental Venous Anomalies.

Developmental venous anomalies (DVAs) are the most common vascular malformation detected on intracranial cross-sectional imaging. They are generally benign lesions thought to drain normal parenchyma. Spontaneous hemorrhages attributed to DVAs are rare and should be ascribed to associated cerebral cavernous malformations, flow-related shunts, or venous outflow obstruction. Contrast-enhanced MRI, susceptibility-weighted imaging, and high-field MRI are ideal tools for visualizing vessel connectivity and associated lesions. DVAs are not generally considered targets for treatment. Preservation of DVAs is an established practice in the microsurgical or radiosurgical treatment of associated lesions.

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in Early and Late Time Windows.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset. METHODS: A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal. RESULTS: Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04). CONCLUSION: Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Impact of Procedure Time on First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Early technique switch following failed passes during mechanical thrombectomy for ischemic stroke: should the approach change and when?

BACKGROUND: Fast and complete reperfusion in endovascular therapy (EVT) for ischemic stroke leads to superior clinical outcomes. The effect of changing the technical approach following initially unsuccessful passes remains undetermined. OBJECTIVE: To evaluate the association between early changes to the EVT approach and reperfusion. METHODS: Multicenter retrospective analysis of prospectively collected data for patients who underwent EVT for intracranial internal carotid artery, middle cerebral artery (M1/M2), or basilar artery occlusions. Changes in EVT technique after one or two failed passes with stent retriever (SR), contact aspiration (CA), or a combined technique (CT) were compared with repeating the previous strategy. The primary outcome was complete/near-complete reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) of 2c-3, following the second and third passes. RESULTS: Among 2968 included patients, median age was 66 years and 52% were men. Changing from SR to CA on the second or third pass was not observed to influence the rates of eTICI 2c-3, whereas changing from SR to CT after two failed passes was associated with higher chances of eTICI 2c-3 (OR=5.3, 95% CI 1.9 to 14.6). Changing from CA to CT was associated with higher eTICI 2c-3 chances after one (OR=2.9, 95% CI 1.6 to 5.5) or two (OR=2.7, 95% CI 1.0 to 7.4) failed CA passes, while switching to SR was not significantly associated with reperfusion. Following one or two failed CT passes, switching to SR was not associated with different reperfusion rates, but changing to CA after two failed CT passes was associated with lower chances of eTICI 2c-3 (OR=0.3, 95% CI 0.1 to 0.9). Rates of functional independence were similar. CONCLUSIONS: Early changes in EVT strategies were associated with higher reperfusion and should be contemplated following failed attempts with stand-alone CA or SR.