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.

Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms.

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

SIRT1 Activation Promotes Long-Term Functional Recovery After Subarachnoid Hemorrhage in Rats.

BACKGROUND: An increase in sirtuin 1 (SIRT1) reportedly attenuates early brain injury, delayed cerebral ischemia, and short-term neurologic deficits in rodent models of subarachnoid hemorrhage (SAH). This study investigates the effect of resveratrol, a SIRT1 activator, on long-term functional recovery in a clinically relevant rat model of SAH. METHODS: Thirty male Wistar rats were subjected to fresh arterial blood injection into the prechiasmatic space and randomized to receive 7 days of intraperitoneal resveratrol (20 mg/kg) or vehicle injections. Body weight and rotarod performance were measured on days 0, 3, 7, and 34 post SAH. The neurologic score was assessed 7 and 34 days post SAH. Morris water maze performance was evaluated 29-33 days post SAH. Brain SIRT1 activity and CA1 neuronal survival were also assessed. RESULTS: Blood pressure rapidly increased in all SAH rats, and no between-group differences in blood pressure, blood gases, or glucose were detected. SAH induced weight loss during the first 7 days, which gradually recovered in both groups. Neurologic score and rotarod performance were significantly improved after resveratrol treatment at 34 days post SAH (p = 0.01 and 0.04, respectively). Latency to find the Morris water maze hidden platform was shortened (p = 0.02). In the resveratrol group, more CA1 neurons survived following SAH (p = 0.1). An increase in brain SIRT1 activity was confirmed in the resveratrol group (p < 0.05). CONCLUSIONS: Treatment with resveratrol for 1 week significantly improved the neurologic score, rotarod performance, and latency to find the Morris water maze hidden platform 34 days post SAH. These findings indicate that SIRT1 activation warrants further investigation as a mechanistic target for SAH therapy.

Inhalational Versus Intravenous Anesthetic Conditioning for Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia.

BACKGROUND: Inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). Whether intravenous anesthetics provide similar level of protection is not known. METHODS: Anesthetic data were collected retrospectively for patients with SAH who received general anesthesia for aneurysm repair between January 1, 2014 and May 31, 2018, at 2 academic centers in the United States (one employing primarily inhalational and the other primarily intravenous anesthesia with propofol). We compared the outcomes of angiographic vasospasm, DCI, and neurological outcome (measured by disposition at hospital discharge), between the 2 sites, adjusting for potential confounders. RESULTS: We compared 179 patients with SAH receiving inhalational anesthetics at one institution to 206 patients with SAH receiving intravenous anesthetics at the second institution. The rates of angiographic vasospasm between inhalational versus intravenous anesthetic groups were 32% versus 52% (odds ratio, 0.49 [CI, 0.32-0.75]; P=0.001) and DCI were 21% versus 40% (odds ratio, 0.47 [CI, 0.29-0.74]; P=0.001), adjusting for imbalances between sites/groups, Hunt-Hess and Fisher grades, type of aneurysm treatment, and American Society of Anesthesiology status. No impact of anesthetics on neurological outcome at time of discharge was noted with rates of good discharge outcome between inhalational versus intravenous anesthetic groups at (78% versus 72%, P=0.23). CONCLUSIONS: Our data suggest that those who received inhalational versus intravenous anesthetic for ruptured aneurysm repair had significant protection against SAH-induced angiographic vasospasm and DCI. Although we cannot fully disentangle site-specific versus anesthetic effects in this comparative study, these results, when coupled with preclinical data demonstrating a similar protective effect of inhalational anesthetics on vasospasm and DCI, suggest that inhalational anesthetics may be preferable for patients with SAH undergoing aneurysm repair. Additional investigations examining the effect of inhalational anesthetics on other SAH outcomes such as early brain injury and long-term neurological outcomes are warranted.

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. RESULTS: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026). CONCLUSIONS: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm.

OBJECTIVE: For patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity during surgery. A neoadjuvant (preoperative) approach to radiation therapy avoids these limitations and offers improved patient convenience. This study assessed the efficacy of neoadjuvant SRS as a new treatment paradigm for patients with brain metastases. METHODS: A retrospective review was performed at a single institution to identify patients who had undergone neoadjuvant SRS (specifically, Gamma Knife radiosurgery) followed by resection of a brain metastasis. Kaplan-Meier survival and log-rank analyses were used to evaluate risks of progression and death. Assessments were made of local recurrence and leptomeningeal spread. Additionally, an analysis of the contemporary literature of postoperative and neoadjuvant SRS for metastatic disease was performed. RESULTS: Twenty-four patients who had undergone neoadjuvant SRS followed by resection of a brain metastasis were identified in the single-institution cohort. The median age was 64 years (range 32-84 years), and the median follow-up time was 16.5 months (range 1 month to 5.7 years). The median radiation dose was 17 Gy prescribed to the 50% isodose. Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months. In 4 patients who had local treatment failure, salvage therapy included repeat resection, laser interstitial thermal therapy, or repeat SRS. One hundred thirty patients (including the current cohort) were identified in the literature who had been treated with neoadjuvant SRS prior to resection. Overall rates of local control at 1 year after neoadjuvant SRS treatment ranged from 49% to 91%, and rates of leptomeningeal dissemination from 0% to 16%. In comparison, rates of local control 1 year after postoperative SRS ranged from 27% to 91%, with 7% to 28% developing leptomeningeal disease. CONCLUSIONS: Neoadjuvant SRS for the treatment of brain metastases is a novel approach that mitigates the shortcomings of postoperative SRS. While additional prospective studies are needed, the current study of 130 patients including the summary of 106 previously published cases supports the safety and potential efficacy of preoperative SRS with potential for improved outcomes compared with postoperative SRS.

Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH. METHODS: We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome. RESULTS: Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3-11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients. CONCLUSIONS: Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

Outcome Following Hemorrhage From Cranial Dural Arteriovenous Fistulae: Analysis of the Multicenter International CONDOR Registry.

Background and Purpose: Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula­related hemorrhage. Methods: A retrospective review of patients in CONDOR who presented with dural arteriovenous fistula­related hemorrhage was performed. Patient characteristics, clinical follow-up, and radiographic details were analyzed for associations with poor outcome (defined as modified Rankin Scale score ≥3). Results: The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%­21.7%) at follow-up, including a 3.6% (95% CI, 1.3%­6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly. Conclusions: Within the CONDOR registry, dural arteriovenous fistula­related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.

Role of Anesthetics and Their Adjuvants in Neurovascular Protection in Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or endovascular repair of their aneurysm. Given the potential impact certain anesthetics have on secondary brain injury after SAH, appropriate selection of anesthetics may prove impactful on overall outcome of these patients. This narrative review focuses on the available evidence of anesthetics and their adjuvants in neurovascular protection in aneurysmal subarachnoid hemorrhage and discusses current impact on clinical care and future investigative directions.

Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage.

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. EX-527, a selective SIRT1 inhibitor, 10 mg/kg was injected intraperitoneally immediately after SAH in the EX-527 group. SIRT1 mRNA expression and activity levels were measured. Vasospasm, microvessel thrombosis, and neurological outcome were assessed. SIRT1 mRNA expression was downregulated, and no difference in SIRT1 activity was noted after isoflurane exposure. Isoflurane conditioning with and without EX-527 attenuated vasospasm, microvessel thrombosis and improved neurological outcomes. Our data validate our previous findings that isoflurane conditioning provides strong protection against both the macro and micro vascular deficits induced by SAH, but this protection is likely not mediated through the SIRT1 pathway.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery.

PURPOSE: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

T2-Weighted-Fluid-Attenuated Inversion Recovery Hyperintensity on Magnetic Resonance Imaging Is Associated With Aggressive Symptoms in Patients With Dural Arteriovenous Fistulas.

Background and Purpose- Several angiographic factors of dural arteriovenous fistulas (dAVFs) are associated with aggressive presentation and poor natural history. We examined the association of magnetic resonance imaging T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) hyperintensity with aggressive presentation. Methods- A cohort of dAVF patients from 2 centers was retrospectively examined. T2/FLAIR hyperintensity was determined by blinded, de-identified review and compared with angiographic grade and presenting symptoms. Results- T2/FLAIR hyperintensity was only identified in dAVF patients with cortical venous drainage (CVD). Among patients with CVD, those with T2/FLAIR hyperintensity were more likely to present with aggressive symptoms (20/23, 87.0%) than those without (6/21, 28.5%), P<0.001. All cured dAVFs with symptom resolution and available post-treatment imaging had resolution of T2/FLAIR hyperintensity. Conclusions- T2/FLAIR hyperintensity strongly correlates with aggressive presentation and CVD in dAVF patients, and may identify a subset that would benefit from early treatment.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

Common Data Elements for Unruptured Intracranial Aneurysms and Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Working Group on Hospital Course and Acute Therapies-Proposal of a Multidisciplinary Research Group.

INTRODUCTION: The Common Data Elements (CDEs) initiative is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) effort to standardize naming, definitions, data coding, and data collection for observational studies and clinical trials in major neurological disorders. A working group of experts was established to provide recommendations for Unruptured Aneurysms and Aneurysmal Subarachnoid Hemorrhage (SAH) CDEs. METHODS: This paper summarizes the recommendations of the Hospital Course and Acute Therapies after SAH working group. Consensus recommendations were developed by assessment of previously published CDEs for traumatic brain injury, stroke, and epilepsy. Unruptured aneurysm- and SAH-specific CDEs were also developed. CDEs were categorized into "core", "supplemental-highly recommended", "supplemental" and "exploratory". RESULTS: We identified and developed CDEs for Hospital Course and Acute Therapies after SAH, which included: surgical and procedure interventions; rescue therapy for delayed cerebral ischemia (DCI); neurological complications (i.e. DCI; hydrocephalus; rebleeding; seizures); intensive care unit therapies; prior and concomitant medications; electroencephalography; invasive brain monitoring; medical complications (cardiac dysfunction; pulmonary edema); palliative comfort care and end of life issues; discharge status. The CDEs can be found at the NINDS Web site that provides standardized naming, and definitions for each element, and also case report form templates, based on the CDEs. CONCLUSION: Most of the recommended Hospital Course and Acute Therapies CDEs have been newly developed. Adherence to these recommendations should facilitate data collection and data sharing in SAH research, which could improve the comparison of results across observational studies, clinical trials, and meta-analyses of individual patient data.

Completion of Gamma Knife radiosurgery for AVM treatment after unplanned interruption-technical note.

BACKGROUND AND IMPORTANCE: Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. CLINICAL PRESENTATION: In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. CONCLUSION: Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Seizures occur in 10-20% of patients with subarachnoid hemorrhage (SAH), predominantly in the acute phase. However, anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis. The objective of this study was to compare brief versus extended seizure prophylaxis after aneurysmal SAH. METHODS: We performed a prospective, single-center, randomized, open-label trial of a brief (3-day) course of levetiracetam (LEV) versus extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome. RESULTS: Eighty-four SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in three (9%) of 35 in the brief LEV group versus one (2%) of 49 in the extended group (p = 0.2). Ten (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on computed tomography (CT) scans (adjusted OR 12.5, 95% CI 1.2-122, p = 0.03). Good functional outcome (mRS 0-2) was more likely in the brief LEV group (83 vs. 61%, p = 0.04). CONCLUSIONS: This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment.

Management of Brain Arteriovenous Malformations: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this statement is to review the current data and to make suggestions for the diagnosis and management of both ruptured and unruptured brain arteriovenous malformations. METHODS: The writing group met in person and by teleconference to establish search terms and to discuss narrative text and suggestions. Authors performed their own literature searches of PubMed, Medline, or Embase, specific to their allocated section, through the end of January 2015. Prerelease review of the draft statement was performed by expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. RESULTS: The focus of the scientific statement was subdivided into epidemiology; diagnosis; natural history; treatment, including the roles of surgery, stereotactic radiosurgery, and embolization; and management of ruptured and unruptured brain arteriovenous malformations. Areas requiring more evidence were identified. CONCLUSIONS: Brain arteriovenous malformations are a relatively uncommon but important cause of hemorrhagic stroke, especially in young adults. This statement describes the current knowledge of the natural history and treatment of patients with ruptured and unruptured brain arteriovenous malformations, suggestions for management, and implications for future research.

Baseline Hemodynamic Impairment and Future Stroke Risk in Adult Idiopathic Moyamoya Phenomenon: Results of a Prospective Natural History Study.

BACKGROUND AND PURPOSE: The purpose was to test the hypothesis that increased oxygen extraction fraction (OEF), a marker of severe hemodynamic impairment measured by positron emission tomography, is an independent risk factor for subsequent ischemic stroke in this population. METHODS: Adults with idiopathic moyamoya phenomena were recruited between 2005 and 2012 for a prospective, multicenter, blindly adjudicated, longitudinal cohort study. Measurements of OEF were obtained on enrollment. Subjects were followed up for the occurrence of ipsilateral ischemic stroke at 6-month intervals. Patients were censored at the time of surgical revascularization or at last follow-up. The primary analysis was time to ischemic stroke in the territory of the occlusive vasculopathy. RESULTS: Forty-nine subjects were followed up during a median of 3.7 years. One of 16 patients with increased OEF on enrollment had an ischemic stroke and another had an intraparenchymal hemorrhage. Three of 33 patients with normal OEF had an ischemic stroke. On a per-hemisphere basis, 21 of 79 hemispheres with moyamoya vasculopathy had increased OEF at baseline. No ischemic strokes and one hemorrhage occurred in a hemisphere with increased OEF (n=21). Sixteen patients (20 hemispheres), including 5 with increased OEF at enrollment, were censored at a mean of 5.3 months after enrollment for revascularization surgery. CONCLUSIONS: The risk of new or recurrent stroke was lower than expected. The low event rate, low prevalence of increased OEF, and potential selection bias introduced by revascularization surgery limit strong conclusions about the association of increased OEF and future stroke risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00629915.

Passive immunotherapy targeting amyloid-ß reduces cerebral amyloid angiopathy and improves vascular reactivity.

Prominent cerebral amyloid angiopathy is often observed in the brains of elderly individuals and is almost universally found in patients with Alzheimer's disease. Cerebral amyloid angiopathy is characterized by accumulation of the shorter amyloid-ß isoform(s) (predominantly amyloid-ß40) in the walls of leptomeningeal and cortical arterioles and is likely a contributory factor to vascular dysfunction leading to stroke and dementia in the elderly. We used transgenic mice with prominent cerebral amyloid angiopathy to investigate the ability of ponezumab, an anti-amyloid-ß40 selective antibody, to attenuate amyloid-ß accrual in cerebral vessels and to acutely restore vascular reactivity. Chronic administration of ponezumab to transgenic mice led to a significant reduction in amyloid and amyloid-ß accumulation both in leptomeningeal and brain vessels when measured by intravital multiphoton imaging and immunohistochemistry. By enriching for cerebral vascular elements, we also measured a significant reduction in the levels of soluble amyloid-ß biochemically. We hypothesized that the reduction in vascular amyloid-ß40 after ponezumab administration may reflect the ability of ponezumab to mobilize an interstitial fluid pool of amyloid-ß40 in brain. Acutely, ponezumab triggered a significant and transient increase in interstitial fluid amyloid-ß40 levels in old plaque-bearing transgenic mice but not in young animals. We also measured a beneficial effect on vascular reactivity following acute administration of ponezumab, even in vessels where there was a severe cerebral amyloid angiopathy burden. Taken together, the beneficial effects ponezumab administration has on reducing the rate of cerebral amyloid angiopathy deposition and restoring cerebral vascular health favours a mechanism that involves rapid removal and/or neutralization of amyloid-ß species that may otherwise be detrimental to normal vessel function.