Changes in inpatient brain arteriovenous malformation management in the United States following the ARUBA trial: analysis of an interrupted time series design.

The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates METHODS: This study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009-2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. RESULTS: Elective and asymptomatic patient admissions declined 2009-2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. CONCLUSIONS: The publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA's conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA's findings in managing unruptured brain AVMs.

Management of moyamoya disease: a review of current and future therapeutic strategies.

Moyamoya disease (MMD) is characterized by idiopathic, progressive stenosis of the circle of Willis and the terminal portion of the internal carotid arteries with the development of prominent small collateral vessels and a characteristic moyamoya or puff-of-smoke radiographic appearance. The incidence and prevalence of MMD varies by region, age, and sex, with higher rates in Asian and East Asian populations compared to North American or European populations. There is a bimodal distribution of patients diagnosed with MMD. Pediatric patients are more commonly diagnosed within the 1st decade of life, whereas adult patients present in the 5th or 6th decade of life. Overall, there is a nearly 2:1 female-to-male ratio. Ischemic symptoms are the most common presentation in pediatric and adult populations, but adult patients are nearly twice as likely to present with intracranial hemorrhage compared to their pediatric counterparts. Surgical revascularization is indicated in symptomatic cases, and antiplatelet therapy may be a useful adjunct to prevent recurrent symptoms. Direct and combined bypass procedures seem to be more effective in adults, whereas children respond well to indirect bypass. The identification of key genetic, molecular, and environmental factors including RNF213 and GUCY1A3 loss-of-function mutations, angiogenic growth factors, autoantibodies, CNS infections, and radiation exposure suggest multiple pathways for the development of moyamoya arteriopathy. Further research is needed to better understand the heterogeneity of pathogenetic mechanisms that lead to moyamoya and to identify novel therapeutic targets to prevent, stabilize, and treat MMD.

Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era.

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Disc Degeneration and Cervical Spine Intervertebral Motion: A Cross-Sectional Study in Patients with Neck Pain and Matched Healthy Controls.

While neck pain can be defined in clinical terms, in most cases the underlying pathophysiology is largely unknown. Regional cervical spine range of motion is often found to be reduced in patients with neck pain compared to persons without pain although it is not clear if the decreased range is cause or effect. Less is known about the role of intervertebral kinematics and how that might be related to the presence of disc degeneration. In this study, the prevalence of intervertebral disc degeneration and continuous cervical intervertebral motion were both measured utilizing quantitative fluoroscopy (QF) in patients with subacute or chronic neck pain (n = 29) and gender-matched healthy controls (n = 30). A composite disc degeneration (CDD) score was calculated for each participant from the first, neutral, lateral fluoroscopic image. Intervertebral motion sharing parameters of motion-sharing inequality (MSI) and motion-sharing variability (MSV) were derived from the active cervical motion sequences obtained while patients were seated. The objective was to determine if average age, CDD, MSI, and MSV values were correlated and if there were differences in these variables between the neck pain group and the healthy control group. Correlation analysis was conducted for age, CDD, MSI, and MSV in each group. Age was moderately correlated with MSV in cervical spine extension in patients only (r = 0.63, p < 0.001). There were no significant differences in the prevalence of disc degeneration (CDD) between patients, who had on average mild pain and related disability, and healthy controls (median CDD 2 both groups, p = 0.94). There were also no significant differences in either flexion or extension intervertebral motion-sharing inequality or variability (MSI or MSV) between groups as measured during active cervical motion.

Randomized Clinical Trials in Cerebrovascular Neurosurgery From 2018 to 2022.

There has been an exponential increase in randomized controlled trials (RCTs) on cerebrovascular disease within neurosurgery. The goal of this study was to review, outline the scope, and summarize all phase 2b and phase 3 RCTs impacting cerebrovascular neurosurgery practice since 2018. We searched PubMed, MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for relevant RCTs published between January 1, 2018, and July 1, 2022. We searched for studies related to eight major cerebrovascular disorders relevant to neurosurgery, including acute ischemic stroke, cerebral aneurysms and subarachnoid hemorrhage, intracerebral hemorrhage, subdural hematomas, cerebral venous thrombosis, arteriovenous malformations, Moyamoya disease and extracranial-intracranial bypass, and carotid and intracranial atherosclerosis. We limited our search to phase 2b or 3 RCTs related to cerebrovascular disorders published during the study period. The titles and abstracts of all relevant studies meeting our search criteria were included. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded.  From an initial total of 2,797 records retrieved from the database searches, 1,641 records were screened after duplicates and studies outside of our time period were removed. After screening, 511 available reports within our time period of interest were assessed for eligibility. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded. We found 80 unique phase 2b or 3 RCTs that fit our criteria, with 165 topic-relevant articles published within the study period.  Numerous RCTs in cerebrovascular neurosurgery have been published since 2018. Ischemic stroke, including mechanical thrombectomy and thrombolysis, accounted for a majority of publications, but there were large trials in intracerebral hemorrhage, subdural hemorrhage, aneurysms, subarachnoid hemorrhage, and cerebral venous thrombosis, among others. This review helps define the scope of the large RCTs published in the last four years to guide future research and clinical care.

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.

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

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

The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke.

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1-knockout (KO) mice and MT1-KO cultured neurons. For the first time, we report that the MT1 receptor is significantly depleted in the brain of MCAO mice, and ramelteon treatment significantly recovers the brain MT1 losses in MCAO mice, which is further explained by the Connectivity Map L1000 bioinformatic analysis that shows gene-expression signatures of MCAO mice are negatively connected to melatonin receptor agonist like Ramelteon. We demonstrate that ramelteon improves the cerebral blood flow signals in ischemic stroke that is potentially mediated, at least, partly by mechanisms of activating endothelial nitric oxide synthase. Our results also show that the neuroprotection of ramelteon counteracts reactive oxygen species-induced oxidative stress and activates the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Ramelteon inhibits the mitochondrial and autophagic death pathways in MCAO mice and cultured neurons, consistent with gene set enrichment analysis from a bioinformatics perspective angle. Our data suggest that Ramelteon is a potential neuroprotective drug candidate, and MT1 is the neuroprotective target for ischemic stroke, which provides new insights into stroke therapy. MT1-KO mice and cultured neurons may provide animal and cellular models of accelerated ischemic damage and neuronal cell death.

Cavernous venous malformations in and around the central nervous system. Part 1: Dural and extradural.

Cavernous-type malformations are venous lesions that occur in multiple locations throughout the body, and when present in the CNS, they have canonically been referred to as cavernomas, cavernous angiomas, and cerebral cavernous malformations. Herein all these lesions are referred to as "cavernous venous malformations" (CavVMs), which is congruent with the current International Society for the Study of Vascular Anomalies classification system. Even though histologically similar, depending on their location relative to the dura mater, these malformations can have different features. In Part 1 of this review, the authors discuss and review pertinent clinical knowledge with regard to CavVMs as influenced by anatomical location, starting with the dural and extradural malformations. They particularly emphasize dural CavVMs (including those in the cavernous sinus), orbital CavVMs, and spinal CavVMs. The genetic and histopathological features of CavVMs in these locations are reviewed, and commonalities in their presumed mechanisms of pathogenesis support the authors' conceptualization of a spectrum of a single disease entity. Illustrative cases for each subtype are presented, and the pathophysiological and genetic features linking dural and extradural to intradural CavVMs are examined. A new classification is proposed to segregate CavVMs based on the location from which they arise, which guides their natural history and treatment.

Cavernous venous malformations in and around the central nervous system. Part 2: Intradural.

Cavernous venous malformations (CavVMs) account for a spectrum of lesions with a shared pathogenesis. Their anatomical location dictates their clinical features and surgical treatment. Extradural and dura-based CavVMs were discussed in Part 1 of this review. In this part, intradural CavVMs are discussed, encompassing malformations growing within the intradural space without direct dural involvement. In addition to classic intra-axial CavVMs, cranial nerve CavVMs, intraventricular CavVMs, and intradural extramedullary spinal CavVMs are discussed in this group, given the similar natural history and specific management challenges. Herein the authors focus on critical clinical aspects of and surgical management of these malformations based on their location and discuss optimal surgical approaches at each of these anatomical locations with illustrative cases. The commonalities of the natural history and surgical management that are dictated by anatomical considerations lend to a new location-based taxonomy for classification of CavVMs.

Rupture risk and outcomes of giant aneurysms in pediatric patients: a multi-institutional case series and systematic review.

OBJECTIVE: Giant aneurysms in pediatric patients are vascular lesions that can cause significant neurological morbidity and mortality. Their rarity has precluded large cohort studies to inform their management. The objective of this study was to understand the clinical course and outcomes of giant aneurysms in pediatric patients. METHODS: The authors performed a multi-institutional cohort study of cases from Boston Children's Hospital and Barrow Neurological Institute, as well as a systematic review and pooled cohort analysis of previously reported cases using descriptive statistics and multivariate regression modeling. RESULTS: Fifteen patients were included in the multi-institutional cohort, and an additional 88 patients were included from 14 series, yielding 103 patients within the pooled cohort. Among the pooled cohort, the most common aneurysm locations were in the middle cerebral artery (36%), internal carotid artery (27%), vertebral artery (11%), and vertebrobasilar junction (8%). Within 69 cases containing radiographic data in the analysis, 38% of aneurysms were saccular. Twenty-eight cases presented with aneurysm rupture (28%), including 0% of cavernous carotid aneurysms, 26% of other anterior circulation aneurysms, and 44% of posterior circulation aneurysms (p = 0.003). In multivariate analysis, posterior circulation location (OR 2.66, 95% CI 1.03-6.86) and younger age (OR 0.90 per year, 95% CI 0.81-1.00) were associated with aneurysm rupture presentation. Most cases were treated (97%) rather than observed (3%). The mortality rate was 3% for unruptured aneurysms and 18% for ruptured aneurysms. A favorable neurological outcome occurred in 80% of unruptured aneurysm cases and 54% of ruptured cases. In multivariate analysis, unruptured aneurysm presentation (OR 3.74, 95% CI 1.24-11.29) and endovascular treatment modality (OR 5.05, 95% CI 1.56-16.29) were associated with a favorable outcome. CONCLUSIONS: Giant aneurysms are rare entities in pediatric patients that are unlikely to be discovered incidentally and usually merit treatment. Most patients survive with good neurological outcome, even in ruptured aneurysm cases. These data reveal that posterior circulation location and younger age are risk factors that correlate with an increased risk of aneurysm rupture.

Relationships between trunk muscle activation and thoraco-lumbar kinematics in non-specific chronic low back pain subgroups during a forward bending task.

BACKGROUND: Trunk muscle activity and thoraco-lumbar kinematics can discriminate between non-specific chronic low back pain (NSCLBP) subgroups and healthy controls. However, research commonly focuses on lumbar kinematics, with limited understanding of relationships between kinematics and muscle activity across clinical subgroups. Similarly, the thoracic spine, whilst intuitively associated with NSCLBP, has received less attention and potential relationships between spinal regions and muscle activity requires exploration. RESEARCH QUESTION: Is there a relationship between trunk muscle activation and regional thoracic and lumbar kinematics in NSCLBP subgroups during a forward bending task? METHODS: Observational, case-control study. Fifty subgrouped NSCLBP motor control impairment participants (27 Flexion Pattern (FP-MCI), 23 Active Extension Pattern (AEP-MCI)) and 28 pain-free controls were evaluated using 3D motion analysis (Vicon™) and surface electromyography during a forward bending and return to upright task. Mean sagittal angles for the upper-thoracic (UTx), lower-thoracic (LTx), upper-lumbar (ULx) and lower-lumbar (LLx) regions were compared with normalised (% sub-maximal voluntary contraction) mean amplitude electromyography of bilateral transversus abdominis/internal oblique, external oblique, superficial lumbar multifidus and erector spinae (longissimus thoracis) muscles between groups. Pearson correlations were computed to assess relationships (significance p < 0.01). RESULTS: AEP-MCI individuals demonstrated statistically significant relationships between superficial lumbar multifidus and ULx and LLx kinematics (-.812 to.659). FP-MCI individuals exhibited statistically significant relationships between erector spinae and superficial lumbar multifidus and LLx and LTx kinematics (-.686 to.664) in both task phases, and between external oblique and LTx during forward bending) (-.459 to.572). Correlations were moderate to strong for all significant relationships (-.812 to .664). SIGNIFICANCE: Relationships between muscle activity and regional spinal kinematics varied between NSCLBP subgroups, suggesting that those with flexion- or extension-related LBP adopt different motor control strategies when performing a bending task. As effectively mechanical biomarkers, these findings may inform treatment by improving understanding of varied motor strategies in subgroups.

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

Recurrent Intraventricular Haemorrhage in Cerebral Proliferative Angiopathy - A Case Report and Review of the Literature.

Cerebral proliferative angiopathy (CPA) is an entity distinct from that of classical arteriovenous malformations. As such, few reports have considered the long-term follow-up of patients with hemorrhage in CPA. Accordingly, herein the authors present a case of recurrent hemorrhage in CPA with 32 years of follow-up and in so doing summarize the literature of hemorrhagic cases in CPA. A 19-year-old presented with focal awareness seizures and diagnostic work-up revealed a left hemispheric vascular lesion. The patient presented again with intracranial hemorrhage at ages 28, 43 and 51. Angioarchitectural workup revealed intermingled brain parenchyma between vascular spaces, absence of dominant feeders and a clear nidus consistent with CPA. The size and diffuse nature of the lesion deemed it inoperable. Given our case and review of the literature it is apparent that CPA has a high risk of re-hemorrhage in the rare event that hemorrhage does occur.

Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.

A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

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.