Brian L. Hoh

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods— A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Councils Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Results— Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. Conclusions— aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.

Stenting versus aggressive medical therapy for intracranial arterial stenosis

BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. METHODS We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. RESULTS Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. CONCLUSIONS In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).

2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. When there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized, clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, for the endovascular procedure, and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. Where there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee (MOC). Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, the endovascular procedure and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs. SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team. A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients. The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines. Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury. Recommendations were developed using the GRADE system. Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice. Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data.

Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): The final results of a randomised trial

BACKGROUND Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial. METHODS We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70-99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693. FINDINGS During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (-0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009). INTERPRETATION The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis. FUNDING National Institute of Neurological Disorders and Stroke (NINDS) and others.

Exacerbation of Cerebral Injury in Mice That Express the P-Selectin Gene Identification of P-Selectin Blockade as a New Target for the Treatment of Stroke

There is currently a stark therapeutic void in the treatment of evolving stroke. Although P-selectin is rapidly expressed by hypoxic endothelial cells in vitro, the functional significance of P-selectin expression in stroke remains unexplored. In order to identify the pathophysiological consequences of P-selectin expression and to identify P-selectin blockade as a potential new approach for the treatment of stroke, experiments were performed using a murine model of focal cerebral ischemia and reperfusion. Early P-selectin expression in the postischemic cerebral cortex was demonstrated by the specific accumulation of radiolabeled anti-murine P-selectin IgG, with the increased P-selectin expression localized to the ipsilateral cerebral microvascular endothelial cells by immunohistochemistry. In experiments designed to test the functional significance of increased P-selectin expression in stroke, neutrophil accumulation in the ischemic cortex of mice expressing the P-selectin gene (PS +/+) was demonstrated to be significantly greater than that in homozygous P-selectin-null mice (PS -/-). Reduced neutrophil influx was accompanied by greater postischemic cerebral reflow (measured by laser Doppler) in the PS -/- mice. In addition, PS -/- mice demonstrated smaller infarct volumes (5-fold reduction, P<.05) and improved survival compared with PS +/+ mice (88% versus 44%, P<.05). Functional blockade of P-selectin in PS +/+ mice using a monoclonal antibody directed against murine P-selectin also improved early reflow and stroke outcome compared with control mice, with reduced cerebral infarction volumes noted even when the blocking antibody was administered after occlusion of the middle cerebral artery. These data are the first to demonstrate a pathophysiological role for P-selectin in stroke and suggest that P-selectin blockade may represent a new therapeutic target in the treatment of stroke.

Results of a prospective protocol of computed tomographic angiography in place of catheter angiography as the only diagnostic and pretreatment planning study for cerebral aneurysms by a combined neurovascular team.

OBJECTIVE:At many centers, patients undergo both computed tomographic angiography (CTA) and digital subtraction angiography (DSA). This practice negates most of the advantages of CTA, and it renders the risks and disadvantages of the two techniques additive. Previous reports in the literature have assessed the sensitivity and specificity of CTA compared with DSA; however, these investigations have not analyzed the clinical implications of a protocol that replaces DSA with CTA as the only diagnostic and pretreatment planning study for patients with cerebral aneurysms. METHODS:Since late 2001/early 2002, the combined neurovascular unit of the Massachusetts General Hospital has adopted a prospective protocol of CTA in place of DSA as the only diagnostic and pretreatment planning study for patients with cerebral aneurysms (ruptured and unruptured). We report the results obtained during the 12-month period from January 2002 to January 2003. RESULTS:During the study period, 223 patients with cerebral aneurysms underwent initial diagnostic evaluation for cerebral aneurysm by the combined neurovascular team of Massachusetts General Hospital. Of the 223 patients, 109 patients had confirmed subarachnoid hemorrhage (Group A) and 114 patients did not have SAH (Group B). All of these patients were included in the prospective CTA protocol. Cerebral aneurysm treatment was initiated on the basis of CTA alone in 93 Group A patients (86%), in 89 Group B patients (78%), and in 182 patients (82%) overall. Treatment consisted of surgical clipping in 152 patients (68%), endovascular coiling in 56 patients (25%), endovascular parent artery balloon occlusion in 4 patients (2%), and external carotid artery to internal carotid artery bypass and carotid artery surgical occlusion in 2 patients (1%). Nine patients (4%) did not undergo treatment. The cerebral aneurysm detection rate by CTA was 100% for the presenting aneurysm (ruptured aneurysm in Group A or symptomatic/presenting aneurysm in Group B) in both groups. The detection rate by CTA for total cerebral aneurysms, including incidental multiple aneurysms, was 95.3% in Group A, 98.3% in Group B, and 97% overall. The overall morbidity associated with DSA (pretreatment or as intraoperative or postoperative clip evaluation) was one patient (1.3%) with a minor nonneurological complication, one patient (1.3%) with a minor neurological complication, and no patients (0%) with a major neurological complication. CONCLUSION:We have demonstrated promising results with a prospective protocol of CTA in place of DSA as the only diagnostic and pretreatment planning study for patients with ruptured and unruptured cerebral aneurysms. It seems safe and effective to make decisions regarding treatment on the basis of CTA, without performing DSA, in the majority of patients with ruptured and unruptured cerebral aneurysms.

Use of a Spectrophotometric Hemoglobin Assay to Objectively Quantify Intracerebral Hemorrhage in Mice

BACKGROUND AND PURPOSE There is great interest in developing novel anticoagulant or thrombolytic strategies to treat ischemic stroke. However, at present there are limited means to accurately assess the hemorrhagic potential of these agents. The present studies were designed to develop and validate a method to accurately quantify the degree of intracerebral hemorrhage (ICH) in murine models. METHODS In a murine model, ICH was induced by stereotaxic intraparenchymal infusion of collagenase B alone (6 x 10(-6) U; n = 5) or collagenase B followed by intravenous recombinant tissue plasminogen activator (rt-PA) (0.1 mg/kg; n = 6). Controls consisted of either sham surgery with stereotaxic infusion of saline (n = 5) or untreated animals (n = 5). ICH was (1) graded by a scale based on maximal hemorrhage diameter on coronal sections and (2) quantified by a spectrophotometric assay measuring cyanomethemoglobin in chemically reduced extracts of homogenized murine brain. This spectrophotometric assay was validated with the use of known quantities of hemoglobin or autologous blood added to a separate cohort of homogenized brains. With this assay, the degree of hemorrhage after focal middle cerebral artery occlusion/reperfusion was quantified in mice treated with postocclusion high-dose intravenous rt-PA (10 mg/kg; n = 11) and control mice subjected to stroke but treated with physiological saline solution (n = 9). RESULTS Known quantities of hemoglobin or autologous blood added to fresh whole brain tissue homogenates showed a linear relationship between the amount added and optical density (OD) at the absorbance peak of cyanomethemoglobin (r = 1.00 and .98, respectively). When in vivo studies were performed to quantify experimentally induced ICH, animals receiving intracerebral infusion of collagenase B had significantly higher ODs than saline-infused controls (2.1-fold, increase; P = .05). In a middle cerebral artery occlusion and reperfusion model of stroke, administration of rt-PA after reperfusion increased the OD by 1.8-fold compared with animals that received physiological saline solution (P < .001). When the two methods of measuring ICH (visual score and OD) were compared, there was a linear correlation (r = .88). Additional experiments demonstrated that triphenyltetrazolium staining, which is commonly used to stain viable brain tissue, does not interfere with the spectrophotometric quantification of ICH. CONCLUSIONS These data demonstrate that the spectrophotometric assay accurately and reliably quantifies murine ICH. This new method should aid objective assessment of the hemorrhagic risks of novel anticoagulant or thrombolytic strategies to treat stroke and can facilitate quantification of other forms of ICH.

Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team

OBJECTIVE Advances in surgical and endovascular techniques have improved treatment for paraclinoid aneurysms. A combined surgical and endovascular team can formulate individualized treatment strategies for patients with paraclinoid aneurysms. Patients who are considered to be at high surgical risk can be treated endovascularly to minimize morbidity. We reviewed the clinical and radiographic outcomes of 238 paraclinoid aneurysms treated by our combined surgical and endovascular unit. METHODS From 1991 to 1999, the neurovascular team treated 238 paraclinoid aneurysms in 216 patients at the Massachusetts General Hospital. The modality of treatment for each aneurysm was chosen based on anatomic and clinical risk factors, with endovascular treatment offered to patients considered to have higher surgical risks. One hundred eighty aneurysms were treated by direct surgery, 57 were treated by endovascular occlusion, and one was treated by surgical extracranial-intracranial bypass and endovascular internal carotid artery balloon occlusion. Locations were transitional, 12 (5%); carotid cave, 11 (5%); ophthalmic, 131 (55%); posterior carotid wall, 38 (16%); and superior hypophyseal 46 (19%). Lesions contained completely within the cavernous sinus were excluded from this analysis. RESULTS Using the Glasgow Outcome Scale (GOS), overall clinical outcomes were excellent or good (GOS 5 or 4), 86%; fair (GOS 3), 7%; poor (GOS 2), 4%; and death (GOS 1), 3%. Among the surgically treated patients, 90% experienced excellent or good outcomes (GOS 5 or 4), 6% had fair outcomes (GOS 3), 2% had poor outcomes (GOS 2), and 3% died (GOS 1). Among the endovascularly treated patients, 74% had excellent or good outcomes (GOS 5 or 4), 12% had fair outcomes (GOS 3), 10% had poor outcomes (GOS 2), and 4% died (GOS 1). The overall major and minor complication rate from surgery was 29%, with a 6% surgery-related permanent morbidity rate and a mortality rate of 0%. The overall major and minor complication rate from endovascular treatment was 21%, with a 3% endovascular-related permanent morbidity rate and a 2% mortality rate. Visual outcomes for patients who presented with visual symptoms were as follows: improved, 69%; no change, 25%; worsened, 6%; and new visual deficits, 3%. In general, angiographic efficacy was lower in the endovascular treatment group. CONCLUSION A combined team approach of direct surgery and endovascular coiling can lead to good outcomes in the treatment for paraclinoid aneurysms, including high-risk lesions that might not have been treated in previous surgical series.