Clinical, imaging, and management features of symptomatic carotid web: Insight from CAROWEB registry.

BACKGROUND: Although carotid web (CaW) is increasingly diagnosed as a cause of cryptogenic stroke, data are still limited to monocentric small sample cohort. To broaden knowledge on symptomatic CaW, CAROWEB registry has been recently implemented. AIMS: In a large cohort of symptomatic CaW patients, we described epidemiologic characteristics, admission clinical and imaging features, and the current management including the secondary preventive strategy choice made in comprehensive French Stroke Units. METHODS: CAROWEB is an ongoing French observational multicenter registry enrolling consecutive CaW patients diagnosed after an ipsilateral ischemic stroke (IS) or transient ischemic attack (TIA). Submitted cases were validated by two experienced neurologist and neuroradiologist. Clinical, imaging, and management features were collected for this study. RESULTS: Between June 2019 and December 2021, 244 cases were submitted by 14 centers, 42 rejected, and 202 included (IS, 91.6%; TIA, 7.9%; retinal infarction, 0.5%; mean age, 50.8 ± 12.2 years; female, 62.9%; Caucasian, 47.5%; Afro-Caribbean, 20.3%). IS patients showed median (interquartile range (IQR)) admission National Institutes of Health Stroke Scale (NIHSS) score, 8 (2-15); intracranial artery occlusion, 71.8%; ipsilateral chronic cerebral infarction (CCI), 16.3%; and reperfusion treatment, 57.3%. CaW was not identified during the mechanical thrombectomy procedure in 30 of 85 (35.3%) patients. Secondary prevention was invasive in 55.6% (stenting, n = 80; surgery, n = 30). In multivariable analysis, the invasive therapeutic option was associated with ipsilateral CCI (odds ratio (OR): 4.24 (1.27-14.2), p = 0.019) and inversely associated with risk factors (OR: 0.47 (0.24-0.91), p = 0.025) and admission NIHSS score (OR: 0.93 (0.89-0.97), p = 0.001). CONCLUSION: CaW must be considered in all ethnic groups including Caucasians. Secondary prevention is heterogeneous in large French Stroke Centers. The absence of risk factors, milder severity strokes, and ipsilateral CCI were predictive variables of secondary invasive treatment. The high rate of invasive treatment suggests that medical treatment alone is deemed ineffective to avoid recurrence and emphasize the need of randomized trials.

Ticagrelor versus clopidogrel dual antiplatelet therapy for unruptured intracranial aneurysms treated with flowdiverter.

BACKGROUND AND PURPOSE: Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter. METHODS: We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813). CONCLUSION: First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Etiologic and prognostic value of external carotid artery thrombus detection during endovascular therapy for anterior circulation proximal occlusions.

BACKGROUND AND PURPOSE: An early understanding of stroke mechanism may improve treatment and outcome in patients presenting with large vessel occlusion stroke (LVOS) treated with mechanical thrombectomy (MT). We aimed to investigate whether spontaneous external carotid artery (ECA) embolism detection during MT is associated with stroke etiology and clinical outcome. METHODS: We retrospectively reviewed our prospectively maintained institutional database including consecutive patients with anterior circulation LVOS treated with MT between January 2015 and August 2020. RESULTS: An ECA embolus was detected in 68 of 1298 patients (5.2%). The kappa coefficient for interobserver agreement was 0.89 (95% confidence interval [CI] 0.82-0.95). ECA embolism was significantly associated with intracranial internal carotid artery (ICA) occlusion (p < 0.001), cardioembolic etiology (p < 0.001) and a lower clot burden score (p < 0.001). Day-1 variation of National Institutes of Health Stroke Scale score (adjusted odds ratio [OR] -2.7, 95% CI -4.9 to 0.3; p = 0.021) and delta Alberta Stroke Program Early Computed Tomography Score (adjusted OR 0.9, 95% CI 0.2 to 1.5; p = 0.004) were worse among patients with ECA emboli. There was no significant difference in 90-day functional outcome between groups (adjusted OR 0.8, 95% CI 0.42 to 1.52; p = 0.50). CONCLUSION: In patients with anterior circulation LVOS treated with MT, ECA embolism was significantly associated with cardioembolic etiology, high thrombus burden and proximal intracranial ICA occlusions. This underexplored angiographic pattern might provide a valuable etiologic clue to the underlying cause of anterior circulation LVOS and may also help determine the appropriate revascularization strategy.

Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey.

BACKGROUND: Neurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France. METHODS: In April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active trainee-led research collaborative network (the JENI-RC). RESULTS: All 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications. CONCLUSION: This nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field.

Embolization as adjunctive treatment to achieve complete cure of ruptured arachnoid cyst associated with chronic subdural hematoma.

INTRODUCTION: Chronic Subdural Hematoma (CSDH) is a rare but classical evolutive complication of arachnoid cysts (AC). Its management has rarely been evaluated to date. Several approaches have been proposed including conservative and surgical treatments. Endovascular treatment in such CSDH subtype remains poorly reported. CASE PRESENTATION: We present here an original case of a 16 years-old-boy suffering from ruptured AC responsible for CSDH successfully treated with embolization. CONCLUSION: Endovascular approach may be considered in the treatment of CSDH related to arachnoid cyst rupture.

Bifurcation geometry remodelling of vessels in de novo and growing intracranial aneurysms: a multicenter study.

BACKGROUND: Geometrical parameters, including arterial bifurcation angle, tortuosity, and arterial diameters, have been associated with the pathophysiology of intracranial aneurysm (IA) formation. The aim of this study was to investigate whether these parameters were present before or if they resulted from IA formation and growth. METHODS: Patients from nine academic centers were retrospectively identified if they presented with a de novo IA or a significant IA growth on subsequent imaging. For each patient, geometrical parameters were extracted using a semi-automated algorithm and compared between bifurcations with IA formation or growth (aneurysmal group), and their contralateral side without IA (control group). These parameters were compared at two different times using univariable models, multivariable models, and a sensitivity analysis with paired comparison. RESULTS: 46 patients were included with 21 de novo IAs (46%) and 25 significant IA growths (54%). The initial angle was not different between the aneurysmal and control groups (129.7±42.1 vs 119.8±34.3; p=0.264) but was significantly wider at the final stage (140.4±40.9 vs 121.5±34.1; p=0.032), with a more important widening of the aneurysmal angle (10.8±15.8 vs 1.78±7.38; p=0.001). Variations in other parameters were not significant. These results were confirmed by paired comparisons. CONCLUSION: Our study suggests that wider bifurcation angles that have long been deemed causal factors for IA formation or growth may be secondary to IA formation at pathologic bifurcation sites. This finding has implications for our understanding of IA formation pathophysiology.

Validation of an automatic tool for the rapid measurement of brain atrophy and white matter hyperintensity: QyScore®.

OBJECTIVES: QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. METHODS: Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland-Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. RESULTS: The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. CONCLUSIONS: QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. KEY POINTS: • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

Pediatric brain arteriovenous malformation recurrence: a cohort study, systematic review and meta-analysis.

BACKGROUND: Recurrence following obliteration of brain arteriovenous malformations (AVMs) is common in children surgically treated, but recurrences following endovascular (EVT) and radiosurgical approaches are scantily reported. OBJECTIVE: To analyze the rates and risk factors for AVM recurrence after obliteration in a single-center cohort of children with ruptured AVMs treated with multimodal approaches, and to carry out a comprehensive review and meta-analysis of current data. METHODS: Children with ruptured AVMs between 2000 and 2019 enrolled in a prospective registry were retrospectively screened and included after angiographically determined obliteration to differentiate children with/without recurrence. A complementary systematic review and meta-analysis of studies investigating AVM recurrence in children between 2000 and 2020 was aggregated to explore the overall recurrence rates across treatment modalities by analyzing surgery versus other treatments. RESULTS: Seventy children with obliterated AVMs were included. AVM recurrences (n=10) were more commonly treated with EVT as final treatment (60% in the recurrence vs 13.3% in the no-recurrence group, p=0.018). Infratentorial locations were associated with earlier and more frequent recurrences (adjusted relative risk=4.62, 95% CI 1.08 to 19.04; p=0.04).In the aggregate analysis, the pooled rate of AVM recurrence was 10.9% (95% CI 8.7% to 13.5%). Younger age at presentation was associated with more frequent recurrences (RR per year increase, 0.97, 95% CI 0.93 to 0.99; p=0.046). CONCLUSION: Location of infratentorial AVMs and younger age at presentation may be associated with earlier and more frequent recurrences. The higher rates of recurrence in patients with AVMs obliterated with EVT questions its role in an intent-to-cure approach and reinforces its position as an adjunct to surgery and/or radiosurgery.

Influence of prior intravenous thrombolysis on outcome after failed mechanical thrombectomy: ETIS registry analysis.

BACKGROUND: Despite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization. METHODS: We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0-2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates. RESULTS: Among 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54). CONCLUSIONS: Among patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.

Doughnut vertebroplasty for circumferential aggressive vertebral hemangiomas.

BACKGROUND: To assess the feasibility, safety and efficacy of a percutaneous doughnut vertebroplasty of circumferential aggressive vertebral hemangiomas (VHs). METHODS: We retrospectively reviewed our prospectively collected database of patients with VHs treated with vertebroplasty between January 2009 and January 2018. Patient demographics, clinical presentations and procedural details were recorded. All patients underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI). All vertebroplasties were performed under conscious sedation in the prone position, predominantly using biplane fluoroscopic guidance. A clinical and imaging evaluation (early CT scan and MRI) as well as a final follow-up clinical assessment was performed. RESULTS: Twenty-two patients with aggressive VHs who underwent circumferential vertebroplasty with cementation of the entire vertebral body and at least one posterior hemi-arch were included (six males, mean age 53 years). At 3 months follow-up, nine patients (41%) had complete, 11 (50%) had partial and two (9%) had no resolution of pain. Nine of 14 patients had a decrease in venous swelling on MRI. No complications were observed. Five patients (23%) underwent adjunctive surgery within 1 year for persistence or worsening of neurological symptoms. Clinical and radiographic improvements were maintained to final follow-up. CONCLUSIONS: Doughnut vertebroplasty offers a mini-invasive, safe and effective treatment of aggressive circumferential VHs. This technique improves pain in over 90% of patients as well as a reduction in radicular and neurological symptoms associated with a tendency to regression of the compressive epidural venous component of these lesions.

Carotid artery direct access for mechanical thrombectomy: the Carotid Artery Puncture Evaluation (CARE) study.

BACKGROUND: In acute ischemic stroke due to anterior large vessel occlusion (AIS-LVO), accessing the target occluded vessel for mechanical thrombectomy (MT) is sometimes impossible through the femoral approach. We aimed to evaluate the safety and efficacy of direct carotid artery puncture (DCP) for MT in patients with failed alternative vascular access. METHODS: We retrospectively analyzed data from 45 stroke centers in France, Switzerland and Germany through two research networks from January 2015 to July 2019. We collected physician-centered data on DCP practices and baseline characteristics, procedural variables and clinical outcome after DCP. Uni- and multivariable models were conducted to assess risk factors for complications. RESULTS: From January 2015 to July 2019, 28 149 MT were performed, of which 108 (0.39%) resulted in DCP due to unsuccessful vascular access. After DCP, 77 patients (71.3%) had successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b) and 28 (25.9%) were independent (modified Rankin Scale (mRS) score 0-2) at 3 months. 20 complications (18.5%) attributed to DCP occurred, all of them during or within 1 hour of the procedure. Complications led to extension of the intubation time in the intensive care unit in 7 patients (6.4%) and resulted in death in 3 (2.8%). The absence of use of a hemostatic closure device was associated with a higher complication risk (OR 3.04, 95% CI 1.03 to 8.97; p=0043). CONCLUSION: In this large multicentric study, DCP was scantly performed for vascular access to perform MT (0.39%) in patients with AIS-LVO and had a high rate of complications (18.5%). Our results provide arguments for not closing the cervical access by manual compression after MT.

Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

BACKGROUND AND PURPOSE: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. METHODS: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. RESULTS: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. CONCLUSIONS: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.

Thrombolysis Improves Reperfusion and the Clinical Outcome in Tandem Occlusion Stroke Related to Cervical Dissection: TITAN and ETIS Pooled Analysis.

BACKGROUND AND PURPOSE: Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT. METHODS: We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0-1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80). CONCLUSIONS: Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome.

Relevance of Brain Regions' Eloquence Assessment in Patients With a Large Ischemic Core Treated With Mechanical Thrombectomy.

OBJECTIVE: Individualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT. METHODS: We performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0-3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models. RESULTS: A total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0-3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0-3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant (p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant. CONCLUSIONS: Considering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months.

Antiplatelet therapy increases symptomatic ICH risk after thrombolysis and thrombectomy.

BACKGROUND AND PURPOSE: The influence of chronic treatment by antiplatelet drug (APD) at stroke onset on the outcomes of patients with acute ischemic stroke (AIS) treated with combined intravenous thrombolysis (IVT) and endovascular therapy (EVT) is unclear. We investigated whether prior APD use influences the risk of symptomatic intracranial hemorrhage (sICH) and functional outcome in AIS patients treated with combined reperfusion therapy. METHODS: A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent IVT and EVT between January 2015 and May 2017. The main outcomes were the incidence of sICH using the Heidelberg Bleeding Classification and patients' functional status at 90 days, as defined by the modified Rankin scale (mRS). Outcomes were evaluated according to daily exposure to APD, and associations were assessed using multivariate logistic regression analysis. RESULTS: This study included 204 patients: 71 (34.8%) were taking APD before AIS. Patients with chronic treatment by APD at stroke onset had a higher rate of sICH (26.7% vs. 3.7%; p< .001) and worse functional outcome (mRS >2) at 90 days (69% vs. 36.8%; p < .001). Prior APD use was associated with an increased likelihood of sICH (OR 9.8; 95%CI [3.6-31.3], p < .05) and of functional dependence at 90 days (OR 5.72; 95%CI [2.09-1.72], p < .001), independent of confounders on multivariate analysis. CONCLUSIONS: Chronic treatment by APD at stroke onset in AIS patients with proximal intracranial occlusion treated using IVT and EVT increases the risk of sICH and worsens the functional prognosis. Further investigation to refine acute revascularization strategies in this population might be required.

Mortality and functional outcome after pediatric intracerebral hemorrhage: cohort study and meta-analysis.

OBJECTIVE: The clinical outcome of pediatric intracerebral hemorrhage (pICH) is rarely reported in a comprehensive way. In this cohort study, systematic review, and meta-analysis of patients with pICH, the authors aimed to describe the basic clinical outcomes of pICH. METHODS: Children who received treatment for pICH at the authors' institution were prospectively enrolled in the cohort in 2008; data since 2000 were retrospectively included, and data through October 2019 were analyzed. The authors then searched PubMed and conducted a systematic review of relevant articles published since 1990. Data from the identified populations and patients from the cohort study were pooled into a multicategory meta-analysis and analyzed with regard to clinical outcomes. RESULTS: Among 243 children screened for inclusion, 231 patients were included. The median (IQR) age at ictus was 9.6 (4.6-12.5) years, and 128 patients (53%) were male. After a median (IQR) follow-up of 33 (13-63) months, 132 patients (57.4%) had a favorable clinical outcome, of whom 58 (44%) had no residual symptoms. Nineteen studies were included in the meta-analysis. Overall, the proportion of children with complete recovery was 27% (95% CI 19%-36%; Q = 49.6; I2 = 76%); of those with residual deficits, the complete recovery rate was 48.1% (95% CI 40%-57%; Q = 75.3; I2 = 81%). When pooled with the cohort study, the aggregate case-fatality rate at the last follow-up was 17.3% (95% CI 12%-24%; Q = 101.6; I2 = 81%). CONCLUSIONS: Here, the authors showed that 1 in 6 children died after pICH, and the majority of children had residual neurological deficits at the latest follow-up. Results from the cohort study also indicate that children with vascular lesions as the etiology of pICH had significantly better clinical functional outcomes.

Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children. METHODS: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King's Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5. RESULTS: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P=0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04-217]; P=0.048). sHE was independently associated with poor outcome (King's Outcome Scale for Childhood Head Injury <5A, odds ratio, 5.77 [95% CI, 1.01-38.95]; P=0.043). CONCLUSIONS: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.

Etiology of intracerebral hemorrhage in children: cohort study, systematic review, and meta-analysis.

OBJECTIVE: Understanding the etiological spectrum of nontraumatic pediatric intracerebral hemorrhage (pICH) is key to the diagnostic workup and care pathway. The authors aimed to evaluate the etiological spectrum of diseases underlying pICH. METHODS: Children treated at the authors' institution for a pICH were included in an inception cohort initiated in 2008 and retrospectively inclusive to 2000, which was analyzed in October 2019. They then conducted a systematic review of relevant articles in PubMed published between 1990 and 2019, identifying cohorts with pICH. Identified populations and patients from the authors' cohort were pooled in a multicategory meta-analysis. RESULTS: A total of 243 children with pICH were analyzed in the cohort study. The final primary diagnosis was an intracranial vascular lesion in 190 patients (78.2%), a complication of a cardiac disease in 17 (7.0%), and a coagulation disorder in 14 (5.8%). Hematological and cardiological etiologies were disproportionately more frequent in children younger than 2 years (p < 0.001). The systematic review identified 1309 children in 23 relevant records pooled in the meta-analysis. Overall, there was significant heterogeneity. The dominant etiology was vascular lesion, with an aggregate prevalence of 0.59 (95% CI 0.45-0.64; p < 0.001, Q = 302.8, I2 = 92%). In 18 studies reporting a detailed etiological spectrum, arteriovenous malformation was the dominant etiology (68.3% [95% CI 64.2%-70.9%] of all vascular causes), followed by cavernoma (15.7% [95% CI 13.0%-18.2%]). CONCLUSIONS: The most frequent etiology of pICH is brain arteriovenous malformation. The probability of an underlying vascular etiology increases with age, and, conversely, hematological and cardiac causes are dominant causes in children younger than 2 years.

Acute surgical management of children with ruptured brain arteriovenous malformation.

OBJECTIVE: Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM. METHODS: This study was a single-center retrospective analysis of children treated for ruptured AVM. The authors evaluated the occurrence of HE, its association with other acute surgical procedures (e.g., nidal excision, decompressive hemicraniectomy), and clinical outcome. Variables associated with each intervention were analyzed using univariable and multivariable models. Clinical outcome was assessed at 18 months using the ordinal King's Outcome Scale for Childhood Head Injury. RESULTS: A total of 104 patients were treated for 112 episodes of ruptured AVM between 2002 and 2018. In the 51 children (45.5% of cases) who underwent HE, 37 procedures were performed early (i.e., within 24 hours after initial cerebral imaging) and 14 late. Determinants of HE were a lower initial Glasgow Coma Scale score (adjusted odds ratio [aOR] 0.83, 95% CI 0.71-0.97 per point increase); higher ICH/brain volume ratio (aOR 18.6, 95% CI 13-26.5 per percent increase); superficial AVM location; and the presence of a brain herniation (aOR 3.7, 95% CI 1.3-10.4). Concurrent nidal surgery was acutely performed in 69% of Spetzler-Martin grade I-II ruptured AVMs and in 25% of Spetzler-Martin grade III lesions. Factors associated with nidal surgery were superficial AVMs, late HE, and absent alteration of consciousness at presentation. Only 8 cases required additional surgery due to intracranial hypertension. At 18 months, overall mortality was less than 4%, 58% of patients had a favorable outcome regardless of surgical intervention, and 87% were functioning independently. CONCLUSIONS: HE is a lifesaving procedure performed in approximately half of the children who suffer AVM rupture. The good overall outcome justifies intensive initial management.

First Line Onyx Embolization in Ruptured Pediatric Arteriovenous Malformations : Safety and Efficacy.

PURPOSE: Brain arteriovenous malformations (bAVM) are the main cause of pediatric intracerebral hemorrhage (pICH). Embolization with Onyx (ev3, Irvine, CA, USA) in children with ruptured bAVM has been infrequently reported. The aim of this study was to assess the safety and efficacy profile of Onyx embolization as first line endovascular treatment of ruptured pediatric bAVMs. METHODS: Children with non-traumatic pICH due to bAVM rupture at a pediatric quaternary care center were prospectively enrolled in a registry and retrospectively analyzed between 2013 and 2018. Clinical and demographic data, treatment modalities and clinical imaging follow-up were retrieved, and detailed procedural data were retrospectively assessed by two investigators. The safety (procedural morbidity and mortality) and efficacy (obliteration and interval rebleeding) were evaluated. RESULTS: In this study 29 children treated for a bAVM by Onyx embolization were included (14 girls, 48%; median age 11.1 years, interquartile range, IQR 8.1-12.7 years) with a total of 72 endovascular sessions (median of 2 sessions per patient IQR 1-3). The AVMs were deeply located in 23 patients (79%). No systemic complications occurred, and no child experienced embolization-related persistent neurological deficits. Non-clinically relevant complications were observed during five procedures, unrelated to Onyx. After a mean follow-up of 31 months from rupture complete obliteration rates were 100%, 89%, 29%, 14% in bAVM Spetzler Martin grades I, II, III and IV-V, respectively. CONCLUSION: It was found that Onyx embolization is safe and represents a good option for an initial treatment approach, in a sequential treatment strategy for pediatric ruptured brain AVMs. Younger age may not be an argument to deny Onyx embolization.