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.

Middle meningeal artery embolization reduces recurrence following surgery for septated chronic subdural hematomas.

BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. METHODS: Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. RESULTS: Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. CONCLUSION: In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Rescue intracranial stenting for failed posterior circulation thrombectomy: analysis from the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study.

BACKGROUNDS: Recent trials have shown improved outcomes after mechanical thrombectomy (MT) for vertebrobasilar occlusion (VBO) stroke. However, there is a paucity of data regarding safety and outcomes of rescue intracranial stenting (RS) after failed MT (FRRS+) for posterior circulation stroke. We sought to compare RS to failed reperfusion without RS (FRRS-). METHODS: This is a retrospective analysis of the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study, a multicenter collaboration involving prospectively collected databases. Patients were included if they had posterior circulation stroke and failed MT. The cohort was divided into two groups: FRRS+ and FRRS- (defined as modified Thrombolysis In Cerebral Infarction (mTICI) score 0-2a). The primary outcome was a shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0-2 and mRS 0-3 at 90 days. Safety measures included rates of symptomatic intracranial hemorrhage (sICH), procedural complications, and 90-day mortality. Sensitivity and subgroup analyses were performed to identify outcomes in a matched cohort and in those with VBO, respectively. RESULTS: A total of 152 failed thrombectomies were included in the analysis. FRRS+ (n=84) was associated with increased likelihood of lower disability (acOR 2.24, 95% CI 1.04 to 4.95, P=0.04), higher rates of mRS 0-2 (26.8% vs 12.5%, aOR 4.43, 95% CI 1.22 to 16.05, P=0.02) and mRS 0-3 (35.4% vs 18.8%, aOR 3.13, 95% CI 1.08 to 9.10, P=0.036), and lower mortality (42.7% vs 59.4%, aOR 0.40, 95% CI 0.17 to 0.97, P=0.04) at 90 days compared with FRRS- (n=68). The rates of sICH and procedural complications were comparable between the groups. Sensitivity and subgroup analyses showed similar results. CONCLUSION: In patients with posterior circulation stroke who had failed MT, RS resulted in better functional outcomes with comparable safety profile to procedure termination.

Middle meningeal artery embolization of septated chronic subdural hematomas.

INTRODUCTION: Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence-septated cSDH-remains undetermined. METHODS: From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation. RESULTS: Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59-77) with 20% females. Twenty-eight cSDHs (35%) had septations identified on imaging. Surgical evacuation with burr holes was performed in 45% and craniotomy in 18.8%. Baseline characteristics between no-septations (no-SEP) and septations (SEP) groups were similar except for median age (SEP vs no-SEP, 72.5 vs. 65.5, p = 0.016). The recurrence rate was lower in the SEP group (SEP vs. no-SEP, 3 vs. 16.7%, p = 0.017) with higher odds of response from MMAE for septated lesions even when controlling for evacuation strategy and antithrombotic use (OR = 0.06, CI [0.006-0.536], p = 0.012). MMAE resulted in higher mean absolute thickness reduction (SEP vs. no-SEP, -8.2 vs. -4.8 mm, p = 0.016) with a similar midline shift change. The rate of reoperation did not differ (6.2 vs. 3.1%, p = 0.65). CONCLUSION: MMAE appears to be equal to potentially more effective in preventing the recurrence of cSDH in septated lesions. These findings may aid in patient selection.

General anesthesia vs procedural sedation for failed NeuroThrombectomy undergoing rescue stenting: intention to treat analysis.

BACKGROUND: There is little data available to guide optimal anesthesia management during rescue intracranial angioplasty and stenting (ICAS) for failed mechanical thrombectomy (MT). We sought to compare the procedural safety and functional outcomes of patients undergoing rescue ICAS for failed MT under general anesthesia (GA) vs non-general anesthesia (non-GA). METHODS: We searched the data from the Stenting and Angioplasty In Neuro Thrombectomy (SAINT) study. In our review we included patients if they had anterior circulation large vessel occlusion strokes due to intracranial internal carotid artery (ICA) or middle cerebral artery (MCA-M1/M2) segments, failed MT, and underwent rescue ICAS. The cohort was divided into two groups: GA and non-GA. We used propensity score matching to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included functional independence (90-day mRS0-2) and successful reperfusion defined as mTICI2B-3. Safety measures included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among 253 patients who underwent rescue ICAS, 156 qualified for the matching analysis at a 1:1 ratio. Baseline demographic and clinical characteristics were balanced between both groups. Non-GA patients had comparable outcomes to GA patients both in terms of the overall degree of disability (mRS ordinal shift; adjusted common odds ratio 1.29, 95% CI [0.69 to 2.43], P=0.43) and rates of functional independence (33.3% vs 28.6%, adjusted odds ratio 1.32, 95% CI [0.51 to 3.41], P=0.56) at 90 days. Likewise, there were no significant differences in rates of successful reperfusion, sICH, procedural complications or 90-day mortality among both groups. CONCLUSIONS: Non-GA seems to be a safe and effective anesthesia strategy for patients undergoing rescue ICAS after failed MT. Larger prospective studies are warranted for more concrete evidence.

Asymptomatic carotid artery stenosis: a summary of current state of evidence for revascularization and emerging high-risk features.

Carotid artery stenosis is a leading cause of ischemic stroke. While management of symptomatic carotid stenosis is well established, the optimal approach in asymptomatic carotid artery stenosis (aCAS) remains controversial. The rapid evolution of medical therapies within the time frame of existing landmark aCAS surgical revascularization trials has rendered their findings outdated. In this review, we sought to summarize the controversies in the management of aCAS by providing the most up-to-date medical and surgical evidence. Subsequently, we compile the evidence surrounding high-risk clinical and imaging features that might identify higher-risk lesions. With this, we aim to provide a practical framework for a precision medicine approach to the management of aCAS.

Middle Meningeal Artery Embolization for Chronic Subdural Hematomas With Concurrent Antithrombotics.

BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment. OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma. METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in CSDH thickness, and midline shift. RESULTS: Fifty-seven patients met inclusion criteria. The median age was 66 years (IQR 58-76) with 21.1% females. Sixty-six embolizations were performed. The median length to follow-up was 20 days (IQR 14-44). Nineteen patients (33.3%) had rapid reinitiation of antithrombotics (5 antiplatelet, 11 anticoagulation, and 3 both). Baseline characteristics between the no antithrombotic (no-AT) and the AT groups were similar. The recurrence rate was higher in the AT group (no-AT vs AT, 9.3 vs 30.4%, P = .03). Mean absolute reduction in CSDH thickness and midline shift was similar between groups. Rate of reoperation did not differ (4.7 vs 8.7%, P = .61). CONCLUSION: Rapid reinitiation of AT after MMA embolization for CSDH leads to higher rates of recurrence with similar rates of reoperation. Care must be taken when initiating antithrombotics after treatment of CSDH with MMA embolization.

Stenting and Angioplasty in Neurothrombectomy: Matched Analysis of Rescue Intracranial Stenting Versus Failed Thrombectomy.

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P<0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P<0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P=0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P=0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P<0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P<0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P=0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P=0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Outcomes of interfacility helicopter transportation in acute stroke care.

OBJECTIVE: To evaluate the long-term functional outcome of interhospital transfer of patients with stroke with suspected large vessel occlusion (LVO) using Helicopter Emergency Medical Services (HEMS). METHODS: Records of consecutive patients evaluated through 2 telestroke networks and transferred to thrombectomy-capable stroke centers between March 2017 and March 2018 were reviewed. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to address confounding factors. Multivariate logistic regression analysis with IPTW was used to determine whether HEMS were associated with good long-term functional outcome (modified Rankin scale score ≤ 2). RESULTS: A total of 199 patients were included; median age was 67 years (interquartile range [IQR] 55-79 years), 90 (45.2%) were female, 120 (60.3%) were white, and 100 (50.3%) were transferred by HEMS. No significant differences between the 2 groups were found in mean age, sex, race, IV tissue plasminogen activator (tPA) receipt, and thrombectomy receipt. The median baseline NIH Stroke Scale score was 14 (IQR 9-18) in the helicopter group vs 11 (IQR 6-18) for patients transferred by ground (p = 0.039). The median transportation time was 60 minutes (IQR 49-70 minutes) by HEMS and 84 minutes (IQR 25-102 minutes) by ground (p < 0.001). After weighting baseline characteristics, the use of HEMS was associated with higher odds of good long-term outcome (OR 4.738, 95% CI 2.15-10.444, p < 0.001) controlling for transportation time, door-in-door-out time, and thrombectomy and tPA receipt. The magnitude of the HEMS effect was larger in thrombectomy patients who had successful recanalization (OR 1.758, 95% CI 1.178-2.512, p = 0.027). CONCLUSIONS: HEMS use was associated with better long-term functional outcome in patients with suspected LVO, independently of transportation time.

A Retrospective Cohort Analysis of Hemorrhagic Arteriovenous Malformations Treated with Combined Endovascular Embolization and Gamma Knife Stereotactic Radiosurgery.

BACKGROUND: The management of brain arteriovenous malformations (AVMs) remains a controversial topic. Given the relatively low incidence, high heterogeneity, and high morbidity and mortality of these lesions, consensus on treatment strategies is an issue of concern to organized neurosurgery. The present retrospective analysis examined and quantified the outcomes of patients with an initial presentation of intracranial hemorrhage from a Spetzler-Martin grade III or IV AVM, later ruled out as surgical candidates. METHODS: A total of 16 patients (5 females; 11 males) had presented with symptomatic hemorrhage confirmed by non-contrast-enhanced computed tomography and were deemed to not be surgical candidates owing to AVM location and/or architecture. The patients underwent combined endovascular embolization and gamma knife stereotactic radiosurgery (SRS). The modified Rankin scale was used to measure the clinical outcomes, comparing the scores at presentation, gamma knife treatment, and the last known follow-up examination. A radiographic evaluation was used to determine the level of AVM nidus involution after the procedure. RESULTS: The present study identified 16 patients with ruptured high-grade AVMs of high surgical risk. All the patients had undergone immediate embolization with delayed SRS for treatment of the hemorrhage and nidus of the AVM. A statistically significant proportion of patients showed marked improvement in the modified Rankin scale scores. No subsequent repeat hemorrhage or any associated complications after embolization occurred in any patient. CONCLUSION: These findings warrant consideration of endovascular embolization with adjuvant SRS as a powerful treatment option for cases with high surgical morbidity due to AVM characteristics.

Stem Cell Therapy in Cerebrovascular Disease.

PURPOSE OF REVIEW: The purpose of this article is to provide a review of state-of-the-art cellular therapy in cerebrovascular diseases by discussing published and ongoing clinical trials. RECENT FINDINGS: In spite of the challenge in translating the success of cellular therapy in acute strokes from preclinical models to clinical trials, early phase clinical trial have recently shown promise in overcoming these challenges. Various stem cell types and doses are being studied, different routes of administration are under investigation, as well as defining the optimal time window to intervene. In addition, experimental methods to enhance cellular therapy, such as ischemic preconditioning, are evolving. After the failure of neuroprotectants in cerebrovascular diseases, researchers have been keen to provide a way of replacement of damaged brain tissue and to promote recovery in order to achieve better outcomes. The field has progressed from intravenous delivery in the 24- to 36-h time window to later intracerebral administration in chronic stroke in clinical trials. New optimism in acute stroke care fostered by the success of mechanical thrombectomy will hopefully extend into cell therapy to promote recovery.