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.

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.

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.

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.

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.

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.

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.

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.

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.).

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.

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.

Thrombectomy in Stroke Patients With Low Alberta Stroke Program Early Computed Tomography Score: Is Modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 Superior to mTICI 2b?

BACKGROUND AND PURPOSE: Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2-5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT. METHODS: This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke. RESULTS: Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0-3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18-4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07-4.41; P=0.04). CONCLUSION: In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.

Competitive leptomeningeal flow impact on thrombectomy reperfusion grade rating.

BACKGROUND: Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating. METHODS: Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification. RESULTS: A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5-75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12-22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8-10). Median last known well time to puncture was 7 hours (IQR 4-13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c-3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf's alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience. CONCLUSION: CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Pediatric infectious aneurysms: individual patient pooled analysis on presentation, management and outcomes.

BACKGROUND: Infectious intracranial aneurysms (IIAs) are a rare sequel of systemic infection and occur most commonly in patients with infective endocarditis (IE). Despite the increasing use of non-invasive screening angiography in patients with IE, the incidence remains low, yielding limited data on the management of IIAs in pediatric populations. We performed a pooled analysis of all published series of pediatric patients with IIAs to study the disease landscape including presentation, management, and outcomes. METHODS: Data included in this study were pooled from published literature on IIAs between 1960 and 2023. Abstracts were selected for full review to include only manuscripts reporting at least one case of pediatric IIA (age 0-18 years). RESULTS: A total of 145 pediatric patients with 178 IIAs were included. Patients presented with rupture in 68% of cases, of which 36% had intraparenchymal hemorrhage and 39% had subarachnoid hemorrhage. Using multivariate logistic regression, independent predictors of rupture were posterior location (aOR 10, P=0.041) and history of IE (aOR 7.2, P=0.001). Primary medical management was successful in 82% of cases with unruptured aneurysms while, in those with ruptured IIAs, medical management was successful in 26% of cases. The 90-day mortality rate was 28%. Using multivariate logistic regression, ruptured IIAs (aOR 5.4, P<0.01) and failure of medical management (aOR 11.1, P<0.05) were independent predictors of 90-day mortality. CONCLUSION: Pediatric IIAs remain a rare complication of systemic or localized CNS infection in the pediatric population. Medical management of unruptured aneurysms is highly successful, while ruptured aneurysms have a remarkably high rate of failure of medical management and should be treated by early surgical or endovascular intervention when feasible.

Repeat thrombectomy after large vessel re-occlusion: a propensity score matched analysis of technical and clinical outcomes.

BACKGROUND: Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat thrombectomy (rEVT) in recurrent LVO remains unclear. This study uses a large real-world patient cohort to study technical and clinical outcomes after rEVT. METHODS: This is a retrospective cohort study including patients who underwent thrombectomy between January 2013 and December 2022. Data were included from 21 comprehensive stroke centers globally through the Stroke Thrombectomy and Aneurysm Registry (STAR). Patients undergoing single EVT or rEVT within 30 days of LVO stroke were included in the study. Propensity score matching was used to compare patients undergoing single EVT versus rEVT. RESULTS: Out of a total of 7387 patients who underwent thrombectomy for LVO stroke, 90 (1.2%) patients underwent rEVT for the same vascular territory within 30 days. The median (IQR) time to re-occlusion was 2 (1-7) days. Compared with a matched cohort of patients undergoing a single EVT procedure, patients undergoing rEVT had a comparable rate of good functional outcome and mortality rate, but a higher rate of symptomatic intracranial hemorrhage (sICH). There was a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) score of patients who underwent rEVT at discharge compared with baseline (-4.8±11.4; P=0.006). The rate of successful recanalization was similar in the single thrombectomy and rEVT groups (78% vs 80%, P=0.171) and between index and rEVT performed on the same patient (79% vs 80%; P=0.593). CONCLUSION: Short-interval rEVT is associated with an improvement in the NIHSS score following large vessel re-occlusion. Compared with single thrombectomy, there was a higher rate of sICH with rEVT, but without a significant impact on rates of functional independence or mortality.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.