Background and Purpose-Some studies report that women are less likely to receive IV rt-PA treatment for stroke than men. We undertook a meta-analysis to determine whether a sex disparity existed. Methods-We identified studies that reported sex-specific IV rt-PA treatment rates for acute stroke. Eligible studies included acute stroke admissions from single or multiple hospitals, registries, or administrative databases. Random effects odds ratios (OR) and 95% confidence intervals (CI) were generated to quantify sex differences (females versus males) among all ischemic stroke admissions and among the eligible subgroup who arrived within 3 hours without contraindications. Study design and geographic location were explored as sources of heterogeneity. Results-Eighteen studies were included. Study designs included single hospitals (nϭ5), multiple hospitals (nϭ6), registries (nϭ4), and administrative databases (nϭ3). The summary OR was 0.70 (95% CIϭ0.55 to 0.88) indicating that women had a 30% lower odds of receiving rt-PA treatment than men. However, substantial between-study variability existed. Among 13 hospital-based studies, the summary OR was 0.78 (95% CIϭ0.71 to 0.86) with no significant heterogeneity. Among the 3 administrative studies, the OR was 0.55 (95% CIϭ0.34 to 0.90) but with significant heterogeneity. Among 4 studies that included data on the eligible subgroup, women had a nonsignificant lower odds of treatment (ORϭ0.81, 95% CIϭ0.58 to 1.13). Conclusions-Despite the presence of significant between-study variation, women with acute stroke were consistently less likely to receive thrombolysis treatment compared with men. Further studies to explore the origins of this sex disparity are warranted.

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Our results support previous models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective for the spokes if spokes paid for more than half of implementation costs.

Background and Purpose An urgent need exists to develop therapies for stroke which have high efficacy, long therapeutic time windows and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically-relevant therapeutic time windows of 6 h and 9 h in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained at 14 d post-stroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust anti-excitotoxic, antioxidant, and mitochondria protecting activity. Conclusion In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure. Neurology ® 2012;79 (Suppl 1):S167-S173

Background and Purpose. Paroxysmal Atrial fibrillation/Flutter (PAF) detection rates in cryptogenic strokes have been variable. We sought to determine the percentage of patients with cryptogenic stroke who had PAF on prolonged non-invasive cardiac monitoring. Methods and Results. Sixty-two consecutive patients with stroke and TIA in a single center with a mean age of 61 (+/− 14) years were analyzed. PAF was detected in 15 (24%) patients. Only one patient reported symptoms of shortness of breath during the episode of PAF while on monitoring, and 71 (97%) of these 73 episodes were asymptomatic. A regression analysis revealed that the presence of PVCs (ventricular premature beats) lasting more than 2 minutes (OR 6.3, 95% CI, 1.11–18.92; P = .042) and strokes (high signal on Diffusion Weighted Imaging) (OR 4.3, 95% CI, 5–36.3; P = .041) predicted PAF. Patients with multiple DWI signals were more likely than solitary signals to have PAF (OR 11.1, 95% CI, 2.5–48.5, P < .01). Conclusion. Occult PAF is common in cryptogenic strokes, and is often asymptomatic. Our data suggests that up to one in five patients with suspected cryptogenic strokes and TIAs have PAF, especially if they have PVCs and multiple high DWI signals on MRI.

Background and Purpose Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). Methods Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. Results Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. Conclusions This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Levetiracetam is an effective AED with potential benefits in other neurologic and psychiatric disorders. The benefit-risk ratio in an individual patient with a specific condition should be used to determine its optimal use. Levetiracetam's use in nonepileptic conditions is not recommended until more data become available from larger trials.