Contemporary cohort of cerebral cavernous malformations: natural history and utility of follow-up MRI.

OBJECTIVE: This study reports the natural history of cerebral cavernous malformations (CCMs) in a contemporary cohort with prospectively collected data from multiple sources, access to follow-up imaging, integrated electronic medical records, and detailed imaging review by study investigators. The authors aimed to define the first prospective symptomatic hemorrhage (SH) and severe SH rates, determine the risk of a second prospective SH, and identify risk factors for SH. METHODS: From a prospectively maintained database of adult patients with radiologically defined CCM, those with radiation-induced CCM, those who underwent surgery within 3 months postdiagnosis, and those with < 1 year of follow-up were excluded. The patients' medical history and radiological features of the CCM were recorded at the time of diagnosis. Follow-up annual written surveys were completed for 5 years after the initial diagnosis and then semiannually thereafter in addition to medical record and follow-up imaging review. Outcomes of interest included SH and severe SH. RESULTS: Of 315 patients, 58.7% were female and 19.7% had familial CCMs. At diagnosis, 37.1% of patients had ruptured CCMs and 28.9% of the CCMs were located in the brainstem. The 5-year cumulative rates of prospective SH and severe SH in those with ruptured CCMs at diagnosis were 41.2% and 12.8%, respectively, compared with 6.1% and 2.5% in patients with unruptured CCMs at diagnosis (p < 0.0001). Risk factors for prospective SH included a ruptured CCM at diagnosis and persistent or new hyperintensity on T1-weighted MRI performed > 3 months after baseline MRI. For those with a ruptured CCM at diagnosis, the risk of developing a second prospective SH was similar to that of developing a first SH. CONCLUSIONS: In a contemporary cohort of adult patients with CCM, the authors report 5-year SH and severe SH rates, rates of second prospective hemorrhage, and predictors of SH. Persistent or new hyperintensity on T1-weighted MRI may be a useful marker of disease activity.

A review of histopathologic and radiologic features of non-atherosclerotic pathologies of the extracranial carotid arteries.

Diseases of the carotid arteries can be classified into different categories based on their origin. Atherosclerotic carotid disease remains the most encountered arterial wall pathology. However, other less-common non-atherosclerotic diseases can have detrimental clinical consequences if not appropriately recognized. The underlying histological features of each disease process may result in imaging findings that possess features that are obvious of the disease. However, some carotid disease processes may have histological characteristics that manifest as non-specific radiologic findings. The purpose of this manuscript is to review various non-atherosclerotic causes of carotid artery disease as well as their histologic-radiologic characteristics to aid in the appropriate recognition of these less-commonly encountered pathologies.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

OBJECTIVE: Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS: The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS: Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS: Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration.

BACKGROUND: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes. METHODS: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC. RESULTS: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8. CONCLUSION: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

Quantitative image signature and machine learning-based prediction of outcomes in cerebral cavernous malformations.

PURPOSE: There is increasing interest in novel prognostic tools and predictive biomarkers to help identify, with more certainty, cerebral cavernous malformations (CCM) susceptible of bleeding if left untreated. We developed explainable quantitative-based machine learning models from magnetic resonance imaging (MRI) in a large CCM cohort to demonstrate the value of artificial intelligence and radiomics in complementing natural history studies for hemorrhage and functional outcome prediction. MATERIALS AND METHODS: One-hundred-eighty-one patients from a prospectively registered cohort of 366 adults with CCM were included. Fluid attenuated inversion recovery (FLAIR) T2-weighted brain images were preprocessed, and CCM and surrounding edema were segmented before radiomic feature computation. Minority class oversampling, dimensionality reduction and feature selection methods were applied. With prospective hemorrhage as primary outcome, machine learning models were built, cross-validated, and compared using clinico-radiologic, radiomic, and combined features. SHapley Additive exPlanations (SHAP) was used for interpretation to determine the radiomic features with most contribution to hemorrhage prediction. RESULTS: The highest performances in hemorrhage predictions on the test set were combining radiomic and clinico-radiological features with an area under the curve (AUC) of 83% using linear regression and selected features, and an F1 score of 61% and 85% sensitivity using K-nearest neighbors with principal component analysis (PCA). Multilayer perceptron had the best performance predicting modified Rankin Scale ≥ 2 with an AUC of 74% using PCA derived features. For interpretation of the selected radiomic signature XGBoost model, Shapley additive explanations highlighted 6 radiomic features contributing the most to hemorrhage prediction. CONCLUSION: Quantitative image-based modeling using machine learning has the potential to highlight novel imaging biomarkers that predict hemorrhagic and functional outcomes, ensuring more precise and personalized care for CCM patients.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.

Prevalence of Developmental Venous Anomalies in Association with Sporadic Cavernous Malformations on 7T MRI.

BACKGROUND AND PURPOSE: The etiology of sporadic cavernous malformations is not well-understood. However, recent evidence suggests that they may arise from a developmental venous anomaly. The goal of this study was to evaluate the prevalence of developmental venous anomalies associated with sporadic cavernous malformations using 7T MR imaging. MATERIALS AND METHODS: We retrospectively identified patients with a sporadic cavernous malformation imaged with 7T MR imaging between August 2019 and July 2022. Two raters determined whether a developmental venous anomaly was associated with each malformation. RESULTS: The study included 59 patients with a total of 61 cavernous malformations. Of the sixty-one, 44 (72%) had an associated developmental venous anomaly. An associated anomaly was most common for cavernous malformations in the brainstem (88%) compared with the cerebral hemispheres or cerebellum (60%-67%). CONCLUSIONS: By means of high-quality 7T imaging, most patients with a sporadic cavernous malformation were found to have an associated developmental venous anomaly. These findings support the hypothesis that cavernous malformations may arise secondary to hemodynamic abnormalities.

Are there differences in clinical presentation, radiologic findings, and outcomes in female patients with cavernous malformation?

BACKGROUND: Little data exist regarding sex differences in cavernous malformations (CM) patients. METHODS: From an ongoing, prospective registry of consenting adults with CM, we assessed the differences between male and female patients in regard to age at presentation, type of presentation, radiologic characteristics and prospective, symptomatic hemorrhage and or focal neurologic deficit (FND) risk and functional outcome. Cox proportional-hazard ratios and 95% confidence intervals with P values < 0.05 were considered significant in the outcome analysis. Familial form CM female patients were compared to sporadic form. RESULTS: As of 1/1/2023, our cohort comprised 386 people (58.0% female) after excluding radiation-induced CM. There were no demographic or clinical presentation differences between male and female patients. Radiological features did not differ between sexes, except that female, sporadic patients were more likely to have an associated developmental venous anomaly (DVA) (43.2% male vs. 56.2% female; p = 0.03). Overall, there was no difference in prospective symptomatic hemorrhage or functional outcome between sexes. Female sex was a predictor of symptomatic hemorrhage or FND in sporadic patients with ruptured CM (39.6% males versus 65.7% females; p = 0.02). The latter was not due to presence or absence of DVA. Familial CM females were more likely to have a spinal cord CM (15.2% familial female vs. 3.9% sporadic female; p = 0.001) and had a longer time to recurrent hemorrhage than sporadic female (2.2 years sporadic vs. 8.2 years familial; p = 0.0006). CONCLUSION: Minimal differences in clinical, radiologic, and outcomes were found in male versus female patients and familial versus sporadic females in the overall CM patient group. The finding that sporadic form female patients with history of prior hemorrhage had increased rates of prospective hemorrhage or FND compared to male patients raise the question whether to "lump" or "split" ruptured versus unruptured CM patients when analyzing risk factors for prospective hemorrhage in natural history studies.

Patients with Carotid Intraplaque Hemorrhage Have Higher Incidence of Cerebral Microbleeds.

AIMS: Carotid intraplaque hemorrhage (IPH) is considered a marker of plaque vulnerability. Cerebral microbleeds (CMBs) are recognized on magnetic resonance imaging (MRI) in patients with cerebrovascular disease. Any connection between carotid IPH and CMBs remains scantly investigated. This study aimed to determine whether the histologic evidence of carotid IPH is related to CMBs. METHODS: We retrospectively enrolled 101 consecutive patients undergoing carotid endarterectomy with symptomatic (ischemic stroke, TIA, and amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. The presence and the extent (%) of IPH were identified on carotid plaques stained with Movat Pentachrome. CMBs were localized on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging sequence on brain MRI before surgery. The degree of carotid stenosis was measured by neck CTA. RESULTS: IPH was identified in 57 (56.4%) patients, and CMBs were found in 24 (23.7%) patients. CMBs were more commonly observed in patients with carotid IPH compared to those without [19 (33.3%) vs 5 (11.4%); P=0.010]. The carotid IPH extent was significantly higher in patients with CMBs than in those without [9.0 % (2.8-27.1%) vs 0.9% (0.0-13.9%); P=0.004] and was associated with the number of CMBs (P=0.004). Logistic regression analysis demonstrated an independent association between carotid IPH extent and the presence of CMBs [OR 1.051 (95% CI 1.012-1.090); P=0.009]. Additionally, patients with CMBs had a lower degree of ipsilateral carotid stenosis compared to those without [40% (35-65%) vs 70% (50-80%); P=0.049]. CONCLUSIONS: CMBs may be potential markers of the ongoing process of carotid IPH, especially in those with nonobstructive plaques.

Developmental venous anomaly associated with dural arteriovenous fistula: Etiopathogenesis and hemorrhagic risk.

Introduction: Developmental venous anomalies (DVAs) have traditionally been defined as non-pathological congenital lesions. Compared to isolated DVAs, the association of DVAs with arteriovenous shunts seems to have a more adverse clinical connotation. In this review, we describe the association between DVA and dAVF and discuss the hemorrhagic risk. We also advance a hypothesis about the potential de novo formation of a DVA and challenge the dogma about their "developmental" or "congenital" nature. Methods: A systematic review of the literature on the association of DVA and dAVF was performed in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Results: A number of 678 papers was initially identified, but only 9 studies were included in the final qualitative analysis. Most of the patients presented with bleeding (56%), with a median GCS of 14 (range 10-15). In 56% of the cases the DVA had a supratentorial location. Supratentorial DVAs mostly drained in the superior sagittal sinus (80%), while all of infratentorial/combined DVAs drained in deep ependymal veins of the 4th ventricle. All the supratentorial dAVFs drained into the superior sagittal sinus, while the infratentorial/combined dAVFs mostly drained in the jugular bulb, Vein of Rosenthal, or transverse-sigmoid sinuses (75%). Most of the dAVFs were classified as Cognard type IIa + b (67%), while in a smaller number of cases type I (22%) and type V (11%). The dAVF was the target of treatment in each case and most patients underwent endovascular treatment (78%). The dAVF was completely occluded in 78% of cases and no periprocedural complications were reported. Conclusion: The clinical presentation, radiological findings, and treatment outcomes of DVAs and associated dAVFs have been discussed. Despite the general opinion that DVAs are benign congenital lesions, increasing epidemiological and radiological evidence supports a potential acquired origin, and the venous system seem to play a pivotal role in their post-natal genesis and development.

Clinical presentation, hemorrhage risk, and outcome in patients with familial cavernous malformations: a pragmatic prospective analysis of 75 patients.

OBJECTIVE: Newly diagnosed patients with a familial cavernous malformation (FCM) and their families are concerned about their future outlook, which is scarcely discussed in the literature. The authors studied a prospective contemporary cohort of patients with FCMs to assess demographics, mode of presentation, prospective risk of hemorrhage and seizures, need for surgery, and functional outcome over an extended interval. METHODS: A prospectively maintained database beginning January 1, 2015, of patients diagnosed with a cavernous malformation (CM) was queried. Data on demographics, radiological imaging, and symptoms at first diagnosis were collected in adult patients who gave their consent to prospective contact. Follow-up was done using questionnaires, in-person visits, and medical record review to assess for prospective symptomatic hemorrhage (i.e., the first hemorrhage after enrollment in the database), seizure, functional outcome measured by the modified Rankin Scale (mRS), and treatment. The prospective hemorrhage rate was calculated by the number of prospective hemorrhages divided by patient-years of follow-up censored at last follow-up, first prospective hemorrhage, or death. A Kaplan-Meier curve of survival free of hemorrhage was obtained comparing patients with versus without hemorrhage at the time of presentation and compared with a log-rank test for p < 0.05. RESULTS: A total of 75 patients with FCM were included, of whom 60% were female. The mean age at diagnosis was 41 ± 16 years. Most symptomatic or large lesions were located supratentorially. At first diagnosis, 27 patients had no symptoms, and the remaining were symptomatic. Over an average of 9.9 years, the rate of prospective hemorrhage was 4.0% per patient-year, and the rate of new seizure was 1.2% per patient-year, with 64% and 32% of patients experiencing at least one symptomatic hemorrhage and at least one seizure, respectively. Thirty-eight percent of the patients underwent at least 1 surgery and 5.3% underwent stereotactic radiosurgery. At the last follow-up, 83.0% of patients remained independent with an mRS score ≤ 2. CONCLUSIONS: The authors' findings provide clinically useful information on hemorrhage rate, seizure rate, the likelihood of surgery, and functional outcome. These findings can be helpful to practicing physicians when counseling patients with FCM and their families, who are often apprehensive about their future and well-being.

Female Hormone Therapy and Risk of Intracranial Hemorrhage From Cerebral Cavernous Malformations: A Multicenter Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Female hormone therapy (oral contraception in female patients of reproductive age and menopausal hormone therapy in postmenopausal patients) is not withheld from patients with cerebral cavernous malformations (CCMs), although the effects of these drugs on the risk of intracranial hemorrhage are unknown. We investigated the association between female hormone therapy and intracranial hemorrhage in female patients with CCM in 2 large prospective, multicenter, observational cohort studies. METHODS: We included consecutive patients with a CCM. We compared the association between use of female hormone therapy and the occurrence of intracranial hemorrhage due to the CCM during up to 5 years of prospective follow-up in multivariable Cox proportional hazards regression. We performed an additional systematic review through Ovid MEDLINE and Embase from inception to November 2, 2021, to identify comparative studies and assess their intracranial hemorrhage incidence rate ratio according to female hormone therapy use. RESULTS: Of 722 female patients, aged 10 years or older at time of CCM diagnosis, 137 used female hormone therapy at any point during follow-up. Female hormone therapy use (adjusted for age, mode of presentation, and CCM location) was associated with an increased risk of subsequent intracranial hemorrhage (46/137 [33.6%] vs 91/585 [15.6%] and adjusted hazard ratio 1.56, 95% CI 1.09-2.24; p = 0.015). Use of oral contraceptives in female patients aged 10-44 years adjusted for the same factors was associated with a higher risk of subsequent intracranial hemorrhage (adjusted hazard ratio 2.00, 95% CI 1.26-3.17; p = 0.003). Our systematic literature search showed no studies reporting on the effect of female hormone therapy on the risk of intracranial hemorrhage during follow-up. DISCUSSION: Female hormone therapy use is associated with a higher risk of intracranial hemorrhage from CCMs. These findings raise questions about the safety of female hormone therapy in clinical practice in patients with CCM. Further studies evaluating clinical factors raising risk of thrombosis may be useful to determine which patients may be most susceptible to intracranial hemorrhage. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that female hormone therapy use is associated with a higher risk of intracranial hemorrhage in patients with CCM.

Zilver stent versus Carotid Wallstent for endovascular treatment of idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenting (VSS) is a promising treatment option for medically refractory idiopathic intracranial hypertension (IIH). There are no published studies comparing the performance of different types of stents employed in VSS procedures. In this study we aimed to compare the safety and efficacy outcomes of the Zilver 518 (Cook Medical, Bloomington, Indiana, USA) and the Carotid Wallstent (Boston Scientific, Marlborough, Massachusetts, USA) devices. METHODS: Records of patients with IIH who underwent VSS between January 2015 and February 2022 at a single referral center were retrospectively reviewed. Patients treated with the Zilver stent or Carotid Wallstent were included in the study. Stent model and size data, pre- and post-treatment pressure gradients, technical and safety outcomes, and pre- and post- stenting papilledema, headache, and tinnitus severity were collected. The χ2 and Fisher-Freeman-Halton tests were used for categorical data and the Student's t-test and Mann-Whitney U test were employed to examine the differences in non-categorical variables. RESULTS: A total of 81 procedures (28 (34.5%) with the Zilver stent and 53 (65.5%) with the Carotid Wallstent) were performed in 76 patients. The mean procedure time was significantly shorter with the Zilver stent (22.56±10.2 vs 33.9±15 min, p=0.001). The papilledema improvement and resolution rates did not significantly differ between groups (94.7% vs 94.5%, p>0.99 for improvement; 78.9% vs 67.5%, p=0.37 for resolution). The tinnitus improvement and resolution rates in the Zilver stent group were significantly higher than those of the Carotid Wallstent group (100% vs 78.9%, p=0.041; 90% vs 63.1%, p=0.03, respectively). Additionally, the Zilver stent provided a significantly higher rate of headache resolution and improvement than the Carotid Wallstent (84.6% vs 27.6%, p=0.001 for resolution; 92.3% vs 72.3%, p=0.043 for improvement). One patient from the Carotid Wallstent group underwent re-stenting due to in-stent stenosis and refractory papilledema. No significant in-stent stenosis was observed in the Zilver stent group. CONCLUSION: Stent choice may affect VSS outcomes. The Zilver stent provided better clinical outcomes than the Carotid Wallstent, with significantly shorter procedure times. Larger studies are needed to determine the efficacy of available venous stents for IIH.

Cortical Thinning in High-Grade Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. METHODS: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. RESULTS: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). CONCLUSIONS: Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Treatment of large and giant posterior communicating artery aneurysms with the Surpass streamline flow diverter: results from the SCENT trial.

BACKGROUND: The Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the communicating artery segment. METHODS: The Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms (SCENT) trial is an international, multicenter, prospective, non-randomized trial comparing the outcomes of Surpass flow diverter treatment with historic control designed to evaluate the effectiveness and safety of Surpass for the treatment of wide neck (≥4 mm) large or giant intracranial aneurysms ≥10 mm. The primary effectiveness endpoint is the percentage of subjects with 100% aneurysm occlusion without significant stenosis of the parent artery and without retreatment of the target aneurysm at 12 months. The primary safety endpoint is the percentage of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. We report the effectiveness and safety of flow diversion in the subgroup of posterior communicating artery (PComA) aneurysms. RESULTS: Of the 180 patients treated, 38 harbored a PComA aneurysm. Mean aneurysm size was 12.2 mm and mean neck width was 4.8 mm. The mean number of Surpass devices used was 1.1 per procedure, with 94.7% of aneurysms treated with one flow diverter. The 12 month primary effectiveness rate was 73.7% (28/38). At 36 months, 68.4% (26/38) of aneurysms remained completely occluded. The 12 month major ipsilateral stroke or neurological death rate was 10.5%. No patients with PComA occlusion after flow diverter placement (54.5%) had clinical sequelae. CONCLUSIONS: SCENT demonstrated acceptable 12 month effectiveness of flow diversion in PComA aneurysms. Despite associated PComA occlusions in many cases, arterial occlusions were clinically silent. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01716117.

Natural history, angiographic presentation and outcomes of anterior cranial fossa dural arteriovenous fistulas.

BACKGROUND: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs. METHODS: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed. RESULTS: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs. CONCLUSION: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

Cervical Artery Dissections: Etiopathogenesis and Management.

Cervical Artery Dissection (CeAD) is a frequent stroke etiology for patients younger than 50 years old. The most common immediate complications related to CeAD are headache and neck pain (65-95%), TIA/ischemic stroke (>50%), and partial Horner's syndrome (25%). The prevailing hypothesis regarding the pathogenesis of sCeAD is that the underlying constitutional vessel wall weakness of patients with sCeAD is genetically determined and that environmental factors could act as triggers. The stroke prevention treatment of CeAD remains controversial, involving anticoagulation or antiplatelet therapy and potentially emergent stenting and/or thrombectomy or angioplasty for selected cases of carotid artery dissection with occlusion. The treatment of headache associated with CeAD depends on the headache phenotype and comorbidities. Radiographically, more than 75% of CeAD cases present with occlusion or non-occlusive stenosis. Many patients demonstrate partial and complete healing, more commonly in the carotid arteries. One-fifth of the patients develop dissecting pseudoaneurysm, but this is a benign clinical entity with an extremely low rupture and stroke recurrence risk. Good recovery is achieved in many CeAD cases, and mortality remains low. Family history of CeAD, connective tissue disorders like Ehlers-Danlos syndrome type IV, and fibromuscular dysplasia are risk factors for recurrent CeAD, which can occur in 3-9% of the cases. This review serves as a comprehensive, updated overview of CeAD, emphasizing etiopathogenesis and management.