Object: The purpose of this report was to provide overall arteriovenous malformation (AVM) hemorrhage rates and, with enhanced statistical power, to elucidate significant risk factors for hemorrhage. Methods: The authors performed a meta-analysis via the PubMed database through January 2012 using the terms “AVM,” “arteriovenous malformation,” “natural history,” “bleed,” and “hemorrhage.” Additional studies were identified through reference searches in each reviewed article. English language studies providing annual hemorrhage rates for AVMs were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hazard ratios for hemorrhage risk factors. The analysis was performed using a random effects model. Results: Nine natural history studies with 3923 patients and 18,423 patient-years of follow-up were identified for analysis. The overall annual hemorrhage rate was 3.0% (95% CI 2.7%–3.4%). The rate of hemorrhage was 2.2% (95% CI 1.7%–2.7%) for unruptured AVMs and 4.5% (95% CI 3.7%–5.5%) for ruptured AVMs. Prior hemorrhage (HR 3.2, 95% CI 2.1–4.3), deep AVM location (HR 2.4, 95% CI 1.4–3.4), exclusively deep venous drainage (HR 2.4, 95% CI 1.1–3.8), and associated aneurysms (HR 1.8, 95% CI 1.6–2.0) were statistically significant risk factors for hemorrhage. Any deep venous drainage (HR 1.3, 95% CI 0.9–1.75) and female sex (HR 1.4, 95% CI 0.6–2.1) demonstrated a trend toward an increased risk of hemorrhage that was not statistically significant. Small AVM size and older patient age were not significant risk factors for hemorrhage. Conclusions: Arteriovenous malformations with prior hemorrhage, deep location, exclusively deep venous drainage, and associated aneurysms have greater annual hemorrhage rates than their counterparts, influencing surgical decision making and the selection of radiosurgery for these lesions.

To understand the kinetics of protein folding, we introduce the concept of a “transition coordinate” which is defined to be the coordinate along which the system progresses most slowly. As a practical implementation of this concept, we define the transmission coefficient for any conformation to be the probability for a chain with the given conformation to fold before it unfolds. Since the transmission coefficient can serve as the best possible measure of kinetic distance for a system, we present two methods by which we can determine how closely any parameter of the system approximates the transmission coefficient. As we determine that the transmission coefficient for a short-chain heteropolymer system is dominated by entropic factors, we have chosen to illustrate the methods mentioned by applying them to geometrical properties of the system such as the number of native contacts and the looplength distribution. We find that these coordinates are not good approximations of the transmission coefficient and therefore, cannot adequately describe the kinetics of protein folding.

Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature’s spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically "expensive" organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective.

Literature reports on the natural history of cerebral cavernous malformations (CMs) are numerous, with considerable variability in lesion epidemiology, hemorrhage rates, and risk factors for hemorrhage. In this review, the authors performed a meta-analysis of 11 natural history studies. The overall male-to-female ratio was 1:1, and the mean age at presentation was 30.6 years. Overall, 37% of patients presented with seizures, 36% with hemorrhage, 23% with headaches, 22% with focal neurological deficits, and 10% were asymptomatic. Some patients had more than one symptom. Seizure presentation was most prevalent among supratentorial CMs, while focal neurological deficits were common in patients with infratentorial CMs. By location, CMs were in the cerebral hemispheres (66%), brainstem (18%), basal ganglia or thalamus (8%), cerebellum (6%), and other (2.5% [combined supra- and infratentorial, callosal or insular]). Overall, 19% of patients harbored multiple intracranial CMs, and 9% had radiographically apparent associated developmental venous anomalies. An overall annual hemorrhage rate of 2.4% per patient-year (range 1.6%–3.1%) was identified across 3 studies. Prior hemorrhage and female sex were risk factors for bleeding, while CM size and multiplicity did not affect hemorrhage rates. Although not impacting the hemorrhage rate itself, deep location was a risk factor for increased clinical aggressiveness.

BACKGROUND:. Hemorrhage from cerebral dural arteriovenous fistulae (dAVF) is a considerable source of neurological morbidity and even mortality.OBJECTIV