Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).

Delayed traumatic intracranial aneurysms: literature review and case series.

Traumatic intracranial aneurysm (TICA) is a rare and aggressive pathology that requires prompt treatment. Nevertheless, early vascular imaging following head trauma may yield falsely negative results, underscoring the importance of subsequent imaging within the first week to detect delayed TICAs. This study aims to report our experience with delayed TICAs and highlight the clinical importance of repeated angiographic screening for delayed TICAs. In this retrospective analysis, we evaluated patients managed for a TICA at a tertiary care teaching institution over the last decade. Additionally, we conducted a systematic review of the literature, following the PRISMA guidelines, on previously reported TICAs, focusing on the time lag between the injury and diagnosis. Twelve delayed TICAs were diagnosed in 9 patients. The median time interval from injury to diagnosis was 2 days (IQR: 1-22 days), and from diagnosis to treatment was 2 days (IQR: 0-9 days). The average duration of radiological follow-up was 28 ± 38 months. At the final follow-up, four patients exhibited favorable neurological outcomes, while the remainder had adverse outcomes. The mortality rate was 22%. Literature reviews identified 112 patients with 114 TICAs, showcasing a median diagnostic delay post-injury of 15 days (IQR: 6-44 days), with 73% diagnosed beyond the first week post-injury. The median time until aneurysm rupture was 9 days (IQR: 3-24 days). Our findings demonstrate acceptable outcomes following TICA treatment and highlight the vital role of repeated vascular imaging after an initial negative computed tomography or digital subtraction angiography in excluding delayed TICAs.

Anterior interhemispheric approach for anterior fossa dural arteriovenous fistulas.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

Novel CCM2 missense variants abrogating the CCM1-CCM2 interaction cause cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three CCM genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few CCM2 missense variants have been shown to be deleterious by modifying the ternary CCM complex stability. OBJECTIVES: To investigate the causality of novel missense CCM2 variants detected in patients with CCM. METHODS: The three CCM genes were screened in 984 patients referred for CCM molecular screening. Interaction between CCM1 and CCM2 proteins was tested using co-immunoprecipitation experiments for the CCM2 missense variants located in the phosphotyrosine binding (PTB) domain. RESULTS: 11 distinct CCM2 rare missense variants were found. Six variants predicted to be damaging were located in the PTB domain, four of them were novel. When co-transfected with CCM1 in HEK293T cells, a loss of interaction between CCM1 and CCM2 was observed for all six variants. CONCLUSION: We showed, using co-immunoprecipitation experiments, that CCM2 missense variants located in the PTB domain were actually damaging by preventing the normal interaction between CCM1 and CCM2. These data are important for diagnosis and genetic counselling, which are challenging in patients harbouring such variants.

Is Anatomical Variations a Risk Factor for Cerebral Vasospasm in Anterior Communicating Complex Aneurysms Rupture?

Background and Purpose- One-third of ruptured aneurysms are located on the anterior communicating complex with high prevalence of anatomic variations of this arterial segment. In this study, we hypothesized that anatomic variations of the anterior communicating complex increase the risk of angiographic vasospasm. Methods- Retrospective study of prospectively collected data from a monocentric subarachnoid hemorrhage cohort of patients admitted to neurointensive care between 2002 and 2018. Univariate followed by multivariate logistic regression analysis was used to identify factors associated with angiographic vasospasm. Results- One thousand three hundred seventy-four patients with aneurismal subarachnoid hemorrhage were admitted to our institution; 29.8% (n=410) were related to an anterior communicating complex aneurysm rupture; 9.2% (n=38) of them showed an anterior communicating artery variation. Angiographic vasospasm was diagnosed in 55.6% of this subgroup (vs 28.1%, P=0.003). In the multivariate analysis, external ventricular drain (2.2 [1.32-3.65], P=0.003) and anterior communicating artery variation (2.40 [1.2-4.9], P=0.04) were independently and significantly associated with angiographic vasospasm, while age above 60 years (0.3 [0.2-0.7]; P=0.002) was a protective factor. However, anterior communicating artery variation was not statistically associated with ischemic vasospasm or poor neurological outcome after anterior communicating artery aneurysm rupture. Conclusions- Anatomic variation of anterior communicating artery could be a new biomarker to identify patients at risk to develop angiographic vasospasm post-subarachnoid hemorrhage. External validation cohorts are necessary to confirm these results.

Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen-Activated Protein Kinase Pathway Alterations.

BACKGROUND: Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined. MATERIALS AND METHODS: We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM. RESULTS: Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma. CONCLUSION: We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway. IMPLICATIONS FOR PRACTICE: Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.

Early Rebleeding after Brain Arteriovenous Malformation Rupture, Clinical Impact and Predictive Factors: A Monocentric Retrospective Cohort Study.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are a leading cause of intracranial hemorrhage in young adults. This study aimed to identify individual predictive factors of early rebleeding after BAVM rupture and determine its impact on prognosis. METHODS: Early rebleeding was defined as a spontaneous intracranial hemorrhage within 30 days of BAVM rupture in patients with nonobliterated BAVMs. One hundred fifty one patients with 158 BAVM hemorrhagic events admitted to a tertiary care center during 14 years were included. Univariate followed by multivariate logistic regression was performed to assess the impact of early rebleeding on in-hospital mortality and modified Rankin Scale (mRS) score beyond 3 months and to identify independent predictors of early rebleeding. RESULTS: Eight early rebleeding events were observed, 6 of which occurred during the first 7 days. Early rebleeding was independently and significantly associated with poor outcome (mRS ≥3 beyond 3 months, p = 0.004) but not with in-hospital mortality (p = 0.9). Distal flow-related aneurysms (p = 0.009) and altered consciousness with a Glasgow coma scale score of 3 (p = 0.01) were independently associated with early rebleeding. CONCLUSIONS: Early rebleeding is a severe complication that can occur after BAVM-related hemorrhage. Distal flow-related aneurysms and initial altered consciousness are associated with early rebleeding.

Risk factors for angiographic recurrence after treatment of unruptured intracranial aneurysms: Outcomes from a series of 178 unruptured aneurysms treated by regular coiling or surgery.

BACKGROUND: Long-term stability after intracranial aneurysm exclusion by coiling is still a matter of debate; after surgical clipping little is known. OBJECTIVE: To study outcome after endovascular and surgical treatments for unruptured intracranial aneurysms in terms of short- and long-term angiographic exclusion and risk factors for recanalization. METHODS: From 2004 and 2009, patients treated for unruptured berry intracranial aneurysms by coiling or clipping were reviewed. Aneurysmal exclusion was evaluated using the Roy-Raymond grading scale; immediate clinical outcome was also assessed. Clinical outcome, recanalization, risk factors for recurrence and bleeding during the follow-up period were analyzed by groups; "surgery" and "embolization". RESULTS: From 2004 to 2009, 178 consecutive unruptured aneurysms were treated. The post-procedure angiographic results for "surgery" were: total exclusion 75.6%; residual neck 13.5%; residual aneurysm 10.8%. For "embolization", the results were, respectively: 72%; 20.7%; and 7.2%. Morbidity was 3% for "surgery" and 1.6% for "embolization" (P=0.74); mortality was nil. Mean clinical and angiographic follow-up was 5years. Recurrence rate was of 11.5% for "surgery" vs. 44% for "embolization" with a mean follow-up of 4 and 5.75years, respectively (P=1.10-5). The retreatment rate was 8.4%. Two significant risk factors for recanalization were identified: maximum diameter of the aneurysm sac (P=0.0038) and pericallosal location (P=0.0388). No bleeding event occurred. CONCLUSION: Both techniques are safe. The rate of aneurismal recurrence was significantly higher for embolization, especially for large diameter aneurysms and pericallosal locations. No bleeding event occurred after recanalization.

Evaluation of intra-aortic CT angiography performances for the visualisation of spinal vascular malformations' angioarchitecture.

PURPOSE: To evaluate the performances of the CT-angiography by direct intra-aortic contrast media injection (IA-CTA) for spinal vascular malformations (SVMs)' imaging. MATERIALS AND METHODS: Thirteen patients (8 males, 5 females, mean age: 56 y) with suspected SVM underwent IA-CTAs by direct intra-aortic iodinated contrast media injection (5 cc/s; 100 cc) via an arterial femoral or humeral access. Two independent observers evaluated the angioarchitecture of the SVMs and the visualisation of both the Adamkiewicz artery and the anterior spinal artery. Then a consensus was obtained between the 2 reviewers; the results of the IA-CTA were finally compared with those of the full spinal DSA evaluated in consensus. RESULTS: The IA-CTA was feasible in all cases and depicted the SVM in all except one case (92 %). Interrater agreement was good for the location of the SVMs' level. Intermodality (IA-CTA/DSA) agreement was excellent for the level and side of the shunt point, as well as for the SVM subtype evaluation. In 77 % of the cases, the Adamkiewicz artery was satisfactorily seen at the same time on IA-CTA. CONCLUSION: IA-CTA is a new technique that seems helpful to reach a better understanding of SMVs and may help to tailor more precisely their treatment. KEY POINTS: • IA-CTA is an accurate technique for the SVMs' angioarchitecture analysis • IA-CTA can locate, at the same time, the Adamkiewicz artery (AKA) • IA-CTA may be helpful in elderly patients with troublesome vasculature.

Superficial middle cerebral vein connection to the cavernous sinus is not infrequent in brain arteriovenous malformations: an argument against their congenital origin?

INTRODUCTION: The aim of this study was to test the hypothesis that the superficial middle cerebral vein (SMCV) is frequently absent or fails to connect with the cavernous sinus (CS) in the presence of brain arteriovenous malformations (AVMs), a frequently reported argument for the congenital origin of brain AVMs. METHODS: The SMCV was retrospectively compared between patients with a brain AVM and a control group. The presence or absence of the SMCV, its direct or indirect connection to the CS and its termination in a laterocavernous sinus (LCS), paracavernous sinus (PCS), or directly in the CS was studied on digital subtraction angiography. RESULTS: One hundred twenty-five left or right side carotid angiograms from 70 patients with a brain AVM were compared to 125 angiograms from 74 controls. The SMCV was present in 88 (70.4 %) cases in the brain AVM group and 96 (76.8 %) cases in controls (p = 0.25). The SMCV was connected directly or indirectly to the CS in 65 (52 %) cases in the brain AVM group and 65 (52 %) cases in controls (p = 1). When comparing the subgroup of carotid angiograms ipsilateral to a supratentorial AVM, no statistically significant difference was found with controls. In three of six cases in which a SMCV drained an AVM, the vein terminated directly or indirectly in the CS. CONCLUSIONS: No difference of SMCV presence and direct or indirect connection to the CS was found between patients with AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVMs.

Patterns of relapse and growth kinetics of surgery- and radiation-refractory meningiomas.

Patients with surgery- and radiation-refractory meningiomas have a poor outcome. Due to our lack of knowledge concerning multi-recurrent meningioma natural history, their clinical course is poorly defined. This retrospective study aims at defining patterns of relapse in order to help in the definition of response criteria in future clinical trials. We performed a retrospective review of surgery- and radiotherapy-refractory meningioma cases with interpretable radiological follow-up treated in our department. Tumor volumes were measured on 3D T1 Gadolinium volumetric sequences using a semi-automated algorithm for tumor segmentation. Twenty nine patients with multi-treated meningioma (11 WHO Grade II, 5 de novo WHO Grade III and 13 transformed WHO Grade III), were evaluated. Median PFS was 16 months for patients with Grade II meningiomas. In patients with Grade III meningiomas, the de novo subgroup had a median PFS of 4 months compared with 7 months in patients with malignant transformation. Volumetric analysis of tumor growth concerned 95 tumor nodules in 50 relapses. The mean growth rate of tumor nodules was 10.4 cm(3)/year (95% CI 7.3-14.8 cm(3)/year). Three patterns of tumor growth were described: "classical" for 9 (31%) patients, "local multi-nodular" for 6 (21%) patients and "multi-nodular metastatic" for the last 14 (48%) patients. Considering all tumor nodules, median time to tumor progression (TTP) was 3.7 months. Progressing tumors represent the most frequent histological subgroup of surgery and radiation-refractory meningiomas while tumors with multi-nodular metastatic dissemination are the prominent radiological pattern of progression.

Recovery from oculomotor nerve palsy due to posterior communicating artery aneurysms: results after clipping versus coiling in a single-center series.

BACKGROUND: Oculomotor nerve palsy (ONP) is a common clinical manifestation of ruptured or unruptured posterior communicating artery (PcomA) aneurysms. Although microsurgical clip ligation has been proven a safe and durable treatment, endovascular management is emerging as an increasingly popular alternative. The aim of our study is to compare the recovery rate from ONP and assess the safety and long-term durability of both techniques. METHODS: We have reviewed the retrospective data concerning twenty-two patients treated at our institution between 2004 and 2012 for PcomA aneurysms with ONP. Seven patients were operated on via a standard pterional approach, and fourteen were treated by endovascular occlusion with coils. One patient was managed conservatively. Pre-treatment and post-treatment severity of ONP was recorded, as well as the duration of symptoms before admission and treatment-related complications. RESULTS: All seven patients who underwent surgery improved, with six total recoveries and one partial recovery. Among the fourteen patients treated by embolization, thirteen initially recovered, but long-term follow-up revealed three cases of exacerbation of ONP after refilling of the aneurysms. Two of them were clipped, and one embolized. Also, one partially resolved patient underwent a second embolization. No severe complications occurred in either group. CONCLUSIONS: Despite the small number of patients, our study suggests that both surgical clipping and embolization are safe and effective methods in regards to functional recovery (complete ONP recovery in about 85 % of the cases). However, coiling may lead to delayed recurrence of third cranial nerve (CN) palsy at long-term follow-up, requiring additional treatment.

Angiographic Evolution of Brain Arteriovenous Malformation Angioarchitecture After Partial Endovascular Treatment.

BACKGROUND AND OBJECTIVES: Endovascular embolization of brain arteriovenous malformations (AVMs) is sometimes intentionally partial, in the case of staged treatment for instance. Residual AVMs may be prone to angioarchitectural modification during follow-up. The objective of this work is to evaluate the nature and extent of these modifications. METHODS: We performed a retrospective monocentric study on a cohort of adult patients treated by incomplete endovascular embolization for ruptured and unruptured AVMs with an available angiographic follow-up, without any intervening confounding event between the 2 angiographic examinations. AVM angioarchitectural modifications (arterial, nidal, and venous) were analyzed. Clinical and radiological data were tested in univariate analyses for association with the occurrence of AVM regression or progression. RESULTS: Eighty-two partial embolization sessions in 57 patients were included in the study. A 40% (33/82) rate of modification was found on follow-up, with 23/82 (28%) controls showing at least one angioarchitectural regression feature and 15/82 (18.3%) showing at least one angioarchitectural progression item. Nidal growth was the most frequent modification occurring after 12/82 (14.6%) embolizations. The only factor associated with nidal volume growth was a longer time interval between embolization and follow-up (median [IQR]: 190 [250] days vs 89.5[133] days in the subgroup without nidal growth; P = .02). Specific modifications of arterial supply, nidal anatomy, and venous drainage were identified and documented. CONCLUSION: Angioarchitectural modifications (both progression and regression) of brain AVMs are frequent findings after partial embolization. Nidal volume growth is associated with longer time intervals between embolization and follow-up.

Ultra-early neurological deterioration following a brain arteriovenous malformation rupture.

Purpose: This study aims to explore the impact of ultra-early neurological deterioration (U-END) on the outcome (mortality and poor neurological status) following a brain arteriovenous malformation (BAVM) rupture and identify determinants of U-END. Methods: Patients with BAVM ruptures admitted to a single tertiary care center were retrospectively reviewed. U-END was defined as a worsening by two or more points on the Glasgow Coma Scale (GCS). U-END was tested as a potential predictor of in-hospital mortality and poor outcomes. Univariate and multivariate analyses were performed to identify determinants of U-END. Patients with U-END were also matched and compared with BAVM rupture controls presenting with a GCS close or equal to either their initial or their lowest GCS. Results: A total of 248 patients with BAVM ruptures met the inclusion criteria, with 39 (15.7%) patients presenting with U-END. U-END was not associated with and was not an independent predictor of in-hospital mortality (12.8 vs. 10.5% in the rest of the study population; p = 0.67) or poor outcomes (39.5 vs. 36.9%; p = 0.77). The only independent determinants of U-END were hydrocephalus (OR 2.6 [95%CI, 1.1-6.4]; p = 0.03) and intraventricular hemorrhage (IVH; OR 3.5 [95%CI, 1.1-11.7]; p = 0.04). When compared to the initial GCS control group, U-END patients more often presented with IVH (89.5 vs. 64.1%; p = 0.009) and hydrocephalus (73 vs. 38.5%; p = 0.003). When compared to the lowest GCS control group, U-END patients had lower early S100B serum levels (0.35 ± 0.37 vs. 0.83 ± 1; p = 0.009) and a lower rate of poor outcome (39.5 vs. 64.9%; p = 0.03). Conclusion: Ultra-early neurological deterioration in ruptured BAVMs did not result in increased mortality or poor outcomes and was most often related to IVH and hydrocephalus.

Endovascular treatment as first-line therapy in Spetzler-Martin grade III brain arteriovenous malformations: a multicenter retrospective study.

OBJECTIVE: The management of Spetzler-Martin grade (SMG) III brain arteriovenous malformations (bAVMs) may be challenging, whatever the exclusion treatment modality chosen. The purpose of this study was to evaluate the safety and effectiveness of endovascular treatment (EVT) as a first-line treatment of SMG III bAVMs. METHODS: The authors performed a retrospective, two-center, observational cohort study. Cases recorded in institutional databases between January 1998 and June 2021 were reviewed. Patients who were ≥ 18 years of age, had ruptured or unruptured SMG III bAVMs, and received EVT as first-line therapy were included. Baseline characteristics of patients and bAVMs, procedure-related complications, clinical outcome according to the modified Rankin Scale, and angiographic follow-up were assessed. The independent risk factors of procedure-related complications and poor clinical outcome were assessed using binary logistic regression. RESULTS: One hundred sixteen patients with 116 SMG III bAVMs were included. The mean age of the patients was 41.9 ± 14.0 years. The most common presentation was hemorrhage (66.4%). Forty-nine (42.2%) bAVMs were found to be completely obliterated by EVT alone at follow-up. Complications occurred in 39 patients (33.6%), including 5 (4.3%) major procedure-related complications. There was no independent predictor of procedure-related complication. Age > 40 years and poor preoperative modified Rankin Scale score were the independent predictors of poor clinical outcome. CONCLUSIONS: EVT of SMG III bAVMs provides encouraging results but needs further improvement. When the embolization procedure performed with intent to cure appears difficult and/or risky, a combined technique (with microsurgery or radiosurgery) may be a safer and more effective strategy. In terms of safety and effectiveness, the benefit of EVT (alone or included in a multimodal management strategy) for SMG III bAVMs needs to be confirmed by randomized controlled trials.

An admission bioclinical score to predict 1-year outcomes in patients undergoing aneurysm coiling.

BACKGROUND AND PURPOSE: A number of scores were developed to predict outcomes after clipping for subarachnoid hemorrhages, yet there is no score for patients undergoing endovascular treatment. Our goal was to develop, compare, and validate a predictive score for 1-year outcomes in patients with coiled subarachnoid hemorrhage. METHODS: We studied 526 patients for 1 year after intensive care unit discharge. We developed an admission bioclinical score (ABC score), which integrated biomarkers such as troponin I and S100ß, with the Glasgow Coma Scale. Using the receiver operating characteristic curve (95% CI), the ABC score was compared with the Glasgow Coma Scale, World Federation of Neurosurgical Societies score, and Fisher score in the derivation cohort and further validated in an independent cohort. RESULTS: In the derivation cohort (from 2003-2007, n=368), multivariate logistic regression analysis showed that only Glasgow Coma Scale (P<0.001), high S100ß (P<0.001), and high troponin (P<0.02) were independently associated with 1-year mortality. Troponin, S100ß, and Glasgow Coma Scale were thus integrated to derive the ABC score. In the derivation cohort, the ABC score reached an receiver operating characteristic curve of 0.82 (0.77-0.88, P<0.001) and was significantly greater than the receiver operating characteristic curves of the Glasgow Coma Scale, World Federation of Neurosurgical Societies, and Fisher scores for predicting 1-year mortality. In the validation cohort (from 2008-2009, n=158), the ABC score's receiver operating characteristic curve of 0.76 (0.67-0.86, P<0.001) remained superior to the 3 other scores for predicting 1-year mortality. CONCLUSIONS: The ABC score improves 1-year outcome prediction at admission for patients with coiled subarachnoid hemorrhage. Our study provides large cohort-based evidence supporting integration of individual biomarkers and clinical characteristics to predict outcomes. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01357057.

Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study.

OBJECTIVE: Statins, which improve the bioavailability of endogenous nitric oxide and upregulate endothelial nitric oxide synthase, have been used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The objective of this study was to determine whether statin therapy diminished vasospasm-induced ischemia as assessed using daily measurements of serum S100B, a biomarker for cerebral ischemia, and computed tomography measurement of ischemic lesion volume. DESIGN: Single-center study of cases and historical controls. SETTING: Neurointensive care unit in a university hospital. PATIENTS: Consecutive patients with aneurysmal subarachnoid hemorrhage treated with clipping or coiling within 96 hrs of symptom onset (n = 278) were included from April 2004 to October 2007. INTERVENTION: Oral atorvastatin, 40 mg/day for 21 days, was used routinely starting on December 1, 2005, in 142 patients, who were compared with the 136 patients managed earlier. MEASUREMENTS AND MAIN RESULTS: Ischemic lesion size was measured using computed tomography on the last available scan and serum S100B was assayed daily for 15 days after admission. Angiographic narrowing was semiquantitatively assessed in patients with vasospasm. In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes. CONCLUSIONS: Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.

Elderly age as a prognostic marker of 1-year poor outcome for subarachnoid hemorrhage patients through its interaction with admission hydrocephalus.

BACKGROUND: An increasing number of elderly patients are treated for aneurysmal subarachnoid hemorrhage. Given that elderly age is associated with both poor outcome and an increased risk of hydrocephalus, we sought to investigate the interaction between age and hydrocephalus in outcome prediction. METHODS: We enrolled 933 consecutive patients treated for subarachnoid hemorrhage between 2002 and 2010 and followed them for 1 yr after intensive care unit discharge. We first performed stepwise analyses to determine the relationship among neurologic events, elderly age (60 or more yr old), and 1-yr poor outcome (defined as Rankin 4-6). Within the most parsimonious model, we then tested for interaction between admission hydrocephalus and elderly age. Finally, we tested the association between age as a stratified variable and 1-yr poor outcome for each subgroup of patients with neurologic events. RESULTS: 24.1% (n=225) of subarachnoid hemorrhage patients were 60 yr old or more and 19.3% (n=180) had 1-yr poor outcomes. In the most parsimonious model (area under the receiver operating characteristic curve, 0.84; 95% CI: 0.82 to 0.88; P<0.001), elderly age and admission hydrocephalus were two independent predictors for 1-yr outcome (P<0.001 and P=0.004, respectively). Including the significant interaction between age and hydrocephalus (P=0.04) improved the model's outcome prediction (P=0.03), but elderly age was no longer a significant predictor. Finally, stratified age was associated with 1-yr poor outcome for hydrocephalus patients (P=0.007), but not for patients without hydrocephalus (P=0.87). CONCLUSION: In this observational study, elderly age and admission hydrocephalus predicted poor outcome, but elderly age without hydrocephalus did not. An external validation, however, will be needed to generalize this finding.

Incidence and risk factors of epilepsy following brain arteriovenous malformation rupture in adult patients.

BACKGROUND: Little is known about incidence, time of onset, clinical presentation, and risk factors of epileptic seizure following brain arteriovenous malformation (bAVM) rupture. METHODS: We performed a monocentric retrospective cohort study from January 2003 to March 2021. The main objective of this study was to determine the incidence of seizures after spontaneous bAVM rupture in nonepileptic adult patients and describe the corresponding clinical features. The secondary objective was to identify clinical, radiological, or biological predictors for the occurrence of de novo seizures after bAVM rupture. RESULTS: Of the 296 cases of bAVM rupture registered during the study period, 247 nonepileptic patients (male 53%, median age 40) were included in the study. Fifty-nine patients (23.9%) had at least one seizure after bAVM rupture. The use of preventive antiepileptic drugs (10.3 [1.5-74.1]; P = 0.02) and decompressive craniectomy (15.4 [2.0-125]; P < 0.009) were independently associated with the occurrence of epilepsy after the bAVM rupture. The factors independently associated with the absence of any seizure after the rupture were isolated intraventricular hemorrhage (0.3 [0.1-0.99]; P = 0.04) and infratentorial location of the bAVM (0.2 [0.1-0.5]; P = 0.09). The first seizure occurred within the first year or within 5 years in, respectively, 83.1% and 98.3% of the patients. CONCLUSIONS: Epilepsy affects nearly a quarter of patients after bAVM rupture. Decompressive craniectomy represents an independent risk factor significantly associated with the occurrence of epilepsy after bAVM rupture. The introduction of preventive AEDs after rupture could be considered in these most severe patients who have a decompressive craniectomy.