Outcomes demonstrated response and adherence rates similar to research populations. These data indicate that TMS is an effective treatment for those unable to benefit from initial antidepressant medication.

Background and Purpose Patients with intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) have a reported mortality of 50–80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events and for its effect on the rate of intraventricular clot lysis. Methods 48 Patients were enrolled at 14 centers and randomized to treatment with 3mg recombinant tissue plasminogen activator (rt-PA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the two groups. Results Severity factors, including admission GCS, ICH volume, IVH volume and blood pressure, were evenly distributed, as were adverse events except for an increased frequency of respiratory system events in the placebo-treated group. Neither ICP nor Cerebral Perfusion pressure (CPP) differed substantially between treatment groups on presentation, with EVD closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the pre-specified threshold: mortality (18%, rt-PA; 23%, placebo); ventriculitis (8%, rt-PA; 9%, placebo); symptomatic bleeding (23%, rt-PA; 5% placebo, which approached statistical significance (p=0.1)). The median duration of dosing was 7.5 days for rt-PA and 12 days for placebo. There was a significant beneficial effect of rt-PA on rate of clot resolution Conclusions Low-dose rt-PA for the treatment of ICH with IVH has an acceptable safety profile compared to placebo and prior historical controls. Data from a well-designed Phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration Information Participant enrollment began prior to July 1, 2005.

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.