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.

Thrombolysis has become established as an acute treatment for human stroke. But despite multiple clinical trials, neuroprotective strategies have yet to be proved effective in humans. Here we discuss intrinsic tissue mechanisms of ischaemic brain injury, and present a perspective that broadening of therapeutic targeting beyond excitotoxicity and neuronal calcium overload will be desirable for developing the most effective neuroprotective therapies.

Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward.

The brain is particularly vulnerable to ischemia. Complete interruption of blood flow to the brain for only 5 minutes triggers the death of vulnerable neurons in several brain regions, whereas 20-40 minutes of ischemia is required to kill cardiac myocytes or kidney cells. In part, the prominent vulnerability of brain tissue to ischemic damage reflects its high metabolic rate. Although the human brain represents only about 2.5% of body weight, it accounts for 25% of basal metabolism, a metabolic rate 3.5 times higher even than that of the brains of other primate species. In addition, central neurons have a nearexclusive dependence on glucose as an energy substrate, and brain stores of glucose or glycogen are limited. However, over the last 15 years, evidence has emerged indicating that energetics considerations and energy substrate limitations are not solely responsible for the brain's heightened vulnerability to ischemia. Rather, it appears that the brain's intrinsic cell-cell and intracellular signaling mechanisms, normally responsible for information processing, become harmful under ischemic conditions, hastening energy failure and enhancing the final pathways underlying ischemic cell death in all tissues, including free radical production, activation of catabolic enzymes, membrane failure, apoptosis, and inflammation. Since these common pathways are explored in other accompanying JCI Perspectives, we will emphasize the role of injury-enhancing signaling mechanisms specific to the central nervous system (CNS) and discuss potential therapeutic approaches to interrupting these mechanisms. Mechanisms of injury after ischemiaCerebral ischemia may be either transient and followed by reperfusion, or essentially permanent. A region of the brain may be affected, as occurs during an arterial or venous stroke, or the entire brain may become globally ischemic, as occurs during a cardiac arrest. In addition to such settings where ischemia is the primary insult, ischemia may also contribute secondarily to brain damage in the setting of mass lesions, hemorrhage, or trauma.Within seconds of cerebral ischemia, local cortical activity as detected by electroencephalography ceases; if the ischemia is global, unconsciousness rapidly ensues (witness the Stokes-Adams attack). This massive shutdown of neural activity is induced by K + efflux from neurons, mediated initially by the opening of voltage-dependent K + channels and later by ATPdependent K + channels, leading to transient plasma membrane hyperpolarization. A few minutes later, despite this energy sparing response, an abrupt and dramatic redistribution of ions occurs across the plasma membrane, associated with membrane depolarization (efflux of K + and influx of Na + , Cl -, and Ca 2+ ). This "anoxic depolarization" results in the excessive release of neurotransmitters, in particular, glutamate, promoting further spatial spread of cellular depolarization, depletion of energy stores, and advancement of injury cascades (see below). Neurotransmitter-induced toxicityGlutamate-i...

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.