Future of Endovascular and Surgical Treatments of Atherosclerotic Intracranial Stenosis.

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies.

A contemporary analysis of surgical ligation versus endovascular embolization in patients with intracranial dural arteriovenous fistulas: a propensity score-matched and mixed-effects model study.

OBJECTIVE: Intracranial dural arteriovenous fistulas (dAVFs) are rare vascular lesions that can be asymptomatic or can lead to devastating hemorrhage based on the dAVF's aggressiveness. Several approaches can be taken to treat dAVFs, such as endovascular embolization and surgical ligation. However, very few studies have evaluated the influence of surgery compared to endovascular approaches on patient outcomes. This study was performed to analyze the clinical characteristics and outcomes of patients who underwent treatment for intracranial dAVF in which either endovascular embolization or microsurgical ligation was used. METHODS: The Nationwide Readmissions Database was reviewed for all patients who underwent treatment for dAVFs (n = 18,152) between 2016 and 2019. Patients who received only surgical ligation or endovascular embolization (i.e., not both) were included. Variables regarding demographics, clinical outcomes, and healthcare utilization were queried. Primary outcome measures were nonroutine discharge, 1-year readmission, top quartile length of stay (LOS), and top quartile of inpatient all-payer cost. Propensity score matching was performed to evaluate the influence of either surgery or embolization on patient outcomes. Receiver operating characteristic (ROC) curves were created for each outcome measure. The area under the curve (AUC) of each ROC was used to estimate mixed-effects model performance. RESULTS: Following propensity score matching, 127 and 113 patients made up the surgical ligation and endovascular embolization cohort, respectively. There were no differences found in age (p = 0.16), sex (p = 0.57), or average Elixhauser Comorbidity Index (p = 0.32). Patients receiving surgical ligation had lower odds of readmission (OR 0.37, p = 0.028) and greater odds of nonroutine discharge (OR 2.21, p = 0.03) compared to patients who underwent endovascular embolization. The authors found no differences in the top quartile of LOS (p = 0.84), top quartile of cost (p = 0.38), or mortality (p > 0.99) between cohorts. ROC curves revealed that the mixed-effects models inclusive of approach outperformed models agnostic to approach with respect to nonroutine discharge (AUC with approach, 0.871; AUC without approach, 0.850; p = 0.018) and readmission (AUC with approach, 0.686; AUC without approach, 0.651; p = 0.019), but no differences were observed regarding top quartile of LOS (p = 0.17) and top quartile of cost (p = 0.40). CONCLUSIONS: Surgical approach may influence perioperative outcomes in patients treated for intracranial dAVF-most significantly discharge disposition and 1-year readmission. Future longitudinal prospective studies with more clinical detail will be required to fully capture the predictive utility of surgical approach in patients treated for intracranial dAVF, particularly for various dAVF subtypes.

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.

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

BACKGROUND: Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. METHODS: Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. RESULTS: A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028). CONCLUSIONS: Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

Antiangiogenesis and medical therapy failure in intracranial atherosclerosis.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.

Whole-brain vessel wall MRI: A parameter tune-up solution to improve the scan efficiency of three-dimensional variable flip-angle turbo spin-echo.

PURPOSE: To propose and evaluate a parameter tune-up solution to expedite a three-dimensional (3D) variable-flip-angle turbo spin-echo (TSE) sequence for whole-brain intracranial vessel wall (IVW) imaging. MATERIALS AND METHODS: Elliptical k-space sampling and prolonged echo train length (ETL), were used to expedite a 3D variable-flip-angle TSE-based sequence. To compensate for the potential loss in vessel wall signal, optimal combination of prescribed T2 and ETL was experimentally investigated on 22 healthy volunteers at 3 Tesla. The optimized protocol (7-8 min) was then compared with a previous protocol (reference protocol, 11-12 min) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and wall delineation quality on a 4-point scale (0:poor; 3:excellent) in 10 healthy volunteers. A pilot study of five patients was performed and lesion delineation score was used to demonstrate the diagnostic quality. RESULTS: A protocol with ETL = 52 and prescribed T2 = 170 ms was deemed an optimized one, which, compared with the reference protocol, provided significantly improved wall SNR (12.0 ± 1.3 versus 10.0 ± 1.1; P = 0.002), wall-lumen CNR (9.7 ± 1.2 versus 8.0 ± 0.9; P = 0.002), wall-CSF CNR (2.8 ± 1.0 versus 1.7 ± 1.0; P = 0.026), similar vessel wall sharpness at both inner (1.59 ± 0.18 versus 1.58 ± 0.14, P = 0.87) and outer (1.71 ± 0.25 versus 1.83 ± 0.30; P = 0.18) boundaries, and comparable vessel wall delineation score for individual segments (1.95-3; P > 0.06). In all patients, atherosclerotic plaques (10) or wall dissection (5) were identified with a delineation score of 3 or 2. CONCLUSION: A parameter tune-up solution can accelerate 3D variable-flip-angle TSE acquisitions, particularly allowed for expedited whole-brain IVW imaging with preserved wall delineation quality. LEVEL OF EVIDENCE: 2. Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:751-757.

Remote Ischemic Conditioning Alters Methylation and Expression of Cell Cycle Genes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC. METHODS: Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein-protein interactions. RESULTS: We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10(-4)) and inflammatory responses (P<1.4×10(-4)). The cell cycle pathway genes form a significant protein-protein interaction network of tightly coexpressed genes (P<0.00001). CONCLUSIONS: Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.

An integrated, ontology-driven approach to constructing observational databases for research.

The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm.

Characterization of the relationship between intracranial pressure and electroencephalographic monitoring in burst-suppressed patients.

BACKGROUND: The objective of this study is to characterize the relationship between ICP and EEG METHODS: Simultaneous ICP and EEG data were obtained from burst-suppressed patients and segmented by EEG bursts. Segments were categorized as increasing/decreasing and peak/valley to investigate relationship between ICP changes and EEG burst duration. A generalized ICP response was obtained by averaging all segments time-aligned at burst onsets. A vasodilatation index (VDI) was derived from the ICP pulse waveform and calculated on a sliding interval to investigate cerebrovascular changes post-burst. RESULTS: Data from two patients contained 309 bursts. 246 ICP segments initially increased, of which 154 peaked. 63 ICP segments decreased, and zero reached a valley. The change in ICP (0.54 ± 0.85 mmHg) was significantly correlated with the burst duration (p < 0.001). Characterization of the ICP segments showed a peak at 8.1 s and a return to baseline at 14.7 s. The VDI for increasing segments was significantly elevated (median 0.56, IQR 0.31, p < 0.001) and correlated with burst duration (p < 0.001). CONCLUSIONS: Changes in the ICP and pulse waveform shape after EEG burst suggest that these signals can be related within the context of neurovascular coupling. SIGNIFICANCE: Existence of a physiological relationship between ICP and EEG may allow the study of neurovascular coupling in acute brain injury patients.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Natural history of asymptomatic unruptured cerebral aneurysms evaluated at CT angiography: growth and rupture incidence and correlation with epidemiologic risk factors.

PURPOSE: To characterize the relationship between aneurysm size and epidemiologic risk factors with growth and rupture by using computed tomographic (CT) angiography. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board approved study, patients with known asymptomatic unruptured intracerebral aneurysms were followed up longitudinally with CT angiographic examinations. Growth was defined as an increase in one or more dimensions above the measurement error, and at least 5% volume by using the ABC/2 method. Associations of epidemiologic factors with aneurysm growth and rupture were analyzed by using logistic regression analysis. Intra- and interobserver agreement coefficients for dimension, volume, and growth were evaluated by using the Pearson correlation coefficient and difference of means with 95% confidence intervals, the agreement statistic, and the McNemar χ(2). RESULTS: Patients (n = 165) with aneurysms (n = 258) had a mean follow-up time of 2.24 years from time of diagnosis. Forty-six of 258 (18%) aneurysms in 38 patients grew larger. Spontaneous rupture occurred in four of 228 (1.8%) intradural aneurysms of average size (6.2 mm). Risk of aneurysm rupture per patient-year was 2.4% (95% CI: 0.5%, 7.12%) with growth and 0.2% (95% CI: 0.006%, 1.22%) without growth (P = .034). There was a 12-fold higher risk of rupture for growing aneurysms (P < .002), with high intra- and interobserver correlation coefficients for size, volume, and growth. Tobacco smoking (3.806, one degree of freedom; P < .015,) and initial size (5.895, two degrees of freedom; P < .051) were independent covariates, predicting 78.4% of growing aneurysms. CONCLUSION: These results support imaging follow-up of all patients with aneurysms, including those whose aneurysms are smaller than the current 7-mm treatment threshold. Aneurysm growth, size, and smoking were associated with increased rupture risk.

Management of arterial vasospasm following aneurysmal subarachnoid hemorrhage.

Despite recent advances, cerebral vasospasm and delayed cerebral ischemia (DCI) still represent a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Although a significant portion of the morbidity and mortality associated with aSAH is related to the initial hemorrhagic ictus, cerebral vasospasm and DCI are still the leading cause of poor outcomes and death in the acute posthemorrhage period, causing long-term disability or death in more than one in five of all patients who have suffered aSAH and initially survived.Management of patients following aSAH includes four major considerations: (1) prediction of patients at highest risk for development of DCI, (2) prophylactic measures to reduce its occurrence, (3) monitoring to detect early signs of cerebral ischemia, and (4) treatments to correct vasospasm and cerebral ischemia once it occurs. The authors review the pertinent literature related to each, including both the current management guidelines supported by the literature as well as novel management strategies that are currently being investigated.

Intracranial arterial stenoses: current viewpoints, novel approaches, and surgical perspectives.

Ten percent of all strokes occurring in the USA are caused by intracranial arterial stenosis (IAS). Symptomatic IAS carries one of the highest rates of recurrent stroke despite intensive medical therapy (25 % in high-risk groups). Clinical results for endovascular angioplasty and stenting have been disappointing. The objectives of this study were to review the contemporary understanding of symptomatic IAS and present potential alternative treatments to resolve factors not addressed by current therapies. We performed a literature review on IAS pathophysiology, natural history, and current treatment. We present an evaluation of the currently deficient aspects in its treatment and explore the role of alternative surgical approaches. There is a well-documented interrelation between hemodynamic and embolic factors in cerebral ischemia caused by IAS. Despite the effectiveness of medical therapy, hemodynamic factors are not addressed satisfactorily by medications alone. Collateral circulation and severity of stenosis are the strongest predictors of risk for stroke and death. Indirect revascularization techniques, such as encephaloduroarteriosynangiosis, offer an alternative treatment to enhance collateral circulation while minimizing risk of hemorrhage associated with hyperemia and endovascular manipulation, with promising results in preliminary studies on chronic cerebrovascular occlusive disease. Despite improvements in medical management for IAS, relevant aspects of its pathophysiology are not resolved by medical treatment alone, such as poor collateral circulation. Surgical indirect revascularization can improve collateral circulation and play a role in the treatment of this condition. Further formal evaluation of indirect revascularization for IAS is a logical and worthy step in the development of intracranial atherosclerosis treatment strategies.

Cerebral hemodynamic and metabolic effects of remote ischemic preconditioning in patients with subarachnoid hemorrhage.

BACKGROUND: Remote ischemic preconditioning (RIPC) is a form of endogenous neuroprotection induced by transient, subcritical ischemia in a distant tissue. RIPC effects on cerebral hemodynamics and metabolism have not been explored in humans. This study evaluates hemodynamic and metabolic changes induced by RIPC in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: Patients underwent three or four RIPC sessions 2-12 days following SAH. Continuous vitals, intracranial pressure (ICP), and transcranial Doppler (TCD) data were collected. Brain microdialysis metabolic changes were monitored. ICP and TCD morphological clustering and analysis of intracranial pulse (MOCAIP) metrics were compared to positive and negative control groups for cerebral vasodilation. RESULTS: Seven ICP and six TCD recordings from four patients demonstrated an increase in mean ICP (8-14.57 mmHg, p < 0.05). There was a reduction in middle cerebral artery (MCA) mean velocities (111-87 cm/s, p = 0.039). ICP and TCD MOCAIP metrics demonstrated variances consistent with vasodilation that returned to baseline following the RIPC. Over the duration of the RIPC, microdialysis showed reduction in the lactate/pyruvate (L/P) ratio (42.37-33.77, p = 0.005) and glycerol (174.04-126 µg/l, p < 0.005), which persisted for 25-54 h after the last RIPC. CONCLUSIONS: This study demonstrated cerebrovascular effects induced by RIPC consistent with transient vasodilation. Cerebral metabolic effects suggest protection from ischemia and cell membrane preservation lasting up to 2 days following RIPC.

Supracerebellar infratentorial resection of a torcular lesion causing fulminant intracranial hypertension: illustrative case.

BACKGROUND: Venous sinus stenosis has been implicated in intracranial hypertension and can lead to papilledema and blindness. The authors report the unique case of a cerebellar transtentorial lesion resulting in venous sinus stenosis in the torcula and bilateral transverse sinuses that underwent resection. OBSERVATIONS: A 5-year-old male presented with subacute vision loss and bilateral papilledema. Imaging demonstrated a lesion causing mass effect on the torcula/transverse sinuses and findings of increased intracranial pressure (ICP). A lumbar puncture confirmed elevated pressure, and the patient underwent bilateral optic nerve sheath fenestration. Cerebral angiography and venous manometry showed elevated venous sinus pressures suggestive of venous hypertension. The patient underwent a craniotomy and supracerebellar/infratentorial approach. A stalk emanating from the cerebellum through the tentorium was identified and divided. Postoperative magnetic resonance imaging showed decreased lesion size and improved sinus patency. Papilledema resolved and other findings of elevated ICP improved. Pathology was consistent with atrophic cerebellar cortex. Serial imaging over 6 months demonstrated progressive decrease in the lesion with concurrent improvements in sinus patency. LESSONS: Although uncommon, symptoms of intracranial hypertension in patients with venous sinus lesions should prompt additional workup ranging from dedicated venous imaging to assessments of ICP and venous manometry.

Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy. METHODS: We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome. RESULTS: Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale≤2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001). CONCLUSIONS: Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.

Cost-Effectiveness Analysis of Encephaloduroarteriosynangiosis Surgery for Symptomatic Intracranial Atherosclerotic Disease.

Encephaloduroarteriosynangiosis (EDAS) is a promising treatment for cerebral arterial steno-occlusive disorders, with proven efficacy in moyamoya disease and a growing interest in potential application for patients with symptomatic intracranial atherosclerotic disease, given the early results of intermediate development trials showing reduced rates of recurrence stroke and improved clinical outcomes compared with those patients treated with intense medical management (IMM) alone. Although clinical outcomes are the fundamental goal when considering patient care paradigms, a cost-effective analysis is key to obtaining a comprehensive understanding of the impact EDAS may provide to patients with atherosclerotic disease on a larger scale. Here, we evaluate the EDAS + IMM cost-effectiveness over time in the treatment of intracranial atherosclerotic disease compared with IMM alone.

Aneurysmal subarachnoid haemorrhage-cerebral vasospasm and prophylactic ibuprofen: a randomised controlled pilot trial protocol.

INTRODUCTION: Cerebral vasospasm (CVS) is the leading cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (aSAH). One of the recently implicated underlying mechanisms of CVS is inflammatory cascades. Specific feasibility objectives include determining the ability to recruit 30 participants over 24 months while at least 75% of them comply with at least 75% of the study protocol and being able to follow 85% of them for 3 months after discharge. METHODS AND ANALYSIS: This is a feasibility study for a randomised controlled trial. Eligible participants are adult patients who are 18 years of age and older with an aSAH confirmed by a brain CT scan, and CT angiography, or magnetic resonance angiography, or digital subtraction angiography who admitted to the emergency department within 12 hours of the ictus. Eligible subjects will be randomised 1:1 for the administration of either ibuprofen or a placebo, while both groups will concomitantly be treated by the standard of care for 2 weeks. Care givers, patients, outcome assessors and data analysts will be blinded. This will be the first study to investigate the preventive effects of a short-acting non-steroidal anti-inflammatory drug on CVS and the key expected outcome of this pilot study is the feasibility and safety assessment of the administration of ibuprofen in patients with aSAH. The objectives of the definitive trial would be to assess the effect of ibuprofen relative to placebo on mortality, CVS, delayed cerebral ischaemia, and level of disability at 3-month follow-up. ETHICS AND DISSEMINATION: This study is approved by Mashhad University of Medical Sciences ethical committee (IR.MUMS.MEDICAL.REC.1398.225). Results from the study will be submitted for publication regardless of whether or not there are significant findings. TRIAL REGISTRATION NUMBER: ISRCTN14611625.

Encephaloduroarteriosynangiosis Operative Technique and Intraoperative Anesthesia Management: Treatment From Both Sides of the Curtain.

BACKGROUND: Encephaloduroarteriosynangiosis (EDAS) is a form of indirect revascularization for cerebral arterial steno-occlusive disorders. EDAS has gained growing interest as a technique applicable to pediatric and adult populations for several types of ischemic cerebral steno-occlusive conditions. OBJECTIVE: To present a team-oriented, multidisciplinary update of the EDAS technique for application in challenging adult cases of cerebrovascular stenosis/occlusion, successfully implemented in more than 200 cases. METHODS: We describe and demonstrate step-by-step a multidisciplinary-modified EDAS technique, adapted to maintain uninterrupted intensive medical management of patients' stroke risk factors and anesthesia protocols to maintain strict hemodynamic control. RESULTS: A total of 216 EDAS surgeries were performed in 164 adult patients, including 65 surgeries for patients with intracranial atherosclerotic disease and 151 operations in 99 patients with moyamoya disease. Five patients with intracranial atherosclerotic disease had recurrent strokes (3%), and there was one perioperative death. The mean clinical follow-up was 32.9 mo with a standard deviation of 31.1. There was one deviation from the surgical protocol. There were deviations from the anesthesia protocol in 3 patients (0.01%), which were promptly corrected and did not have any clinical impact on the patients' condition. CONCLUSION: The EDAS protocol described here implements a team-oriented, multidisciplinary adaptation of the EDAS technique. This adaptation resides mainly in 3 points: (1) uninterrupted administration of intensive medical management, (2) strict hemodynamic control during anesthesia, and (3) meticulous standardized surgical technique.

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.