Background and Purpose-Moderate hypothermia decreases ischemic damage in experimental stroke models. This multicenter study was performed to evaluate (1) the safety and feasibility of moderate hypothermia and (2) its potential to reduce intracranial hypertension in acute stroke patients. Methods-Fifty prospective patients with cerebral infarction involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated. Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22Ϯ9 hours after stroke onset and maintained for 24 to 72 hours; subsequently, patients passively rewarmed over a mean duration of 17 hours. Outcome was assessed at 4 weeks and at 3 months. Results-Time required for cooling to Ͻ33°C varied from 3.5 to 11 hours. The most frequent complications of hypothermic therapy were thrombocytopenia (70%), bradycardia (62%), and pneumonia (48%). Four patients (8%) died during hypothermia as a result of severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. An additional 15 patients (30%) died during or after rewarming because of rebound increase in intracranial pressure (ICP) and fatal herniation. A shorter (Ͻ16 hours) rewarming period was associated with a more pronounced rise of ICP.Elevated ICP values were significantly reduced under hypothermia. Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29, and Rankin Scale score 3 months after stroke was 2.9. Conclusions-Moderate hypothermia is feasible in patients with acute stroke, although it is associated with several side effects. Most deaths occur during rewarming as a result of excessive ICP rise. Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies.

Background and Purpose-Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. Methods-Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; nϭ19) or placebo (nϭ20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis.

Background and Purpose HeADDFIRST was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction (LSCHI). Methods All stroke patients were screened for eligibility [age 18–75, NIHSS ≥ 18 with Item 1a < 2 (responsive to minor stimulation), and CT demonstrating unilateral, complete MCA territory infarction by specific imaging criteria]. All enrolled patients were treated using a standardized medical treatment protocol. Those with both ≥ 4 mm of pineal shift and deterioration in level of arousal or ≥ 7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued Medical Treatment Only (MTO) or Medical Treatment plus Surgery (MTS). Death at 21 days was the primary outcome measure. Results Among 4,909 screened patients, only 66 (1.3%) were eligible for HeADDFIRST. Forty patients were enrolled, and 26 developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the MTO and 21% (3/14) and 36% (5/14) in the MTS arms, respectively. Conclusions HeADDFIRST randomization criteria effectively distinguished low from high risk of death from LSCHI. Lower mortality in the MTO group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials regarding patient selection and medical management.