We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., "penumbral") tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm x min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p < 0.04 to p < 0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials.

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] # 4 points from baseline or NIHSS 5 0) and major neurologic improvement (NIHSS # 8 points from baseline or NIHSS 5 0) at 7 days and favorable (modified Rankin Scale [mRS] # 2) and excellent functional outcome (mRS # 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS $ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS $ 4 points from baseline or death within 36 hours, and 3-month death. Statins are recommended for primary and secondary stroke prevention in patients at risk of cerebrovascular events. Results1 In addition to reducing the risk of first and recurrent ischemic stroke, statin treatment may also improve outcome through pleiotropic non-cholesterol-dependent effects. 2An association between statin use before stroke and favorable outcome has been previously reported.3-5 Moreover, a prospective clinical trial showed that statin withdrawal during the first 3 days after a stroke event was associated with increased risk of death or dependency at 3 months. 6 To date, very few studies have investigated the effect of statin use in the acute phase on ischemic stroke outcome.7-9 The Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial showed a trend toward less severity for outcome 90 days after stroke with atorvastatin administration (80 mg), compared with placebo, in patients having a stroke during the trial. 10So far, few studies have assessed the efficacy and safety of statin treatment in ischemic stroke patients treated with IV thrombolysis. Two recent meta-analyses showed that prior statin use may increase the risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours after IV recombinant tissue plasminogen activator (rtPA), though without influencing 3-month functional outcome. 11,12 Two large observational studies reported that previous treatment with statin was not an independent predictor of functional outcome or of ICH. 13,14 The aim of the THRombolysis and STatins (THRaST) study was to assess the impact of statin use in the acute phase of ischemic stroke on clinical outcome in patients treated with IV thrombolysis.Authors' affiliations are listed at the end of the article. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.