Background and Purpose-Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods-All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (nϭ1104). After excluding basilar artery occlusions (nϭ119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results-One or more license contraindications to thrombolysis was present in 51% of our patients (nϭ499). The most common of these were age Ͼ80 years (nϭ159), mild stroke National Institutes of Health Stroke Scale score Ͻ5 (nϭ129), use of intravenous antihypertensives prior to treatment (nϭ112), symptom-to-needle time Ͼ3 hours (nϭ95), blood pressure Ͼ185/110 mm Hg (nϭ47), and oral anticoagulation (nϭ39). Age Ͼ80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions-Off-license thrombolysis was not associated with poorer clinical outcome, except for age Ͼ80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available. (Stroke.

Background and Purpose-Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury.We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis. Methods-Patients were randomized 1:1 to mild hypothermia (35°C) or to standard stroke unit care within 6 hours of symptom onset. Hypothermia was induced with a surface-cooling device and cold saline infusions. Active cooling was restrained gradually after 12 hours at <35.5°C. The primary outcome measure was the number of patients with <36°C body temperature for >80% of the 12-hour cooling period. Results-We included 36 patients with a median of National Institutes of Health Stroke Scale score of 9 one hour after thrombolysis. Fifteen of 18 (83%) patients achieved the primary end point. Sixteen (89%) patients reached <35.5°C in a median time of 10 hours (range, 7-16 hours) from symptom onset, spent 10.5 hours (1-17 hours) in hypothermia, and were back to normothermia in 23 hours (15-29 hours). Few serious adverse events were more common in the hypothermia group. At 3 months, 7 patients (39%) in both groups had good outcome (modified Ranking Scale, 0-2), whereas poor outcome (modified Ranking Scale, 4-6) was twice as common in the normothermia group (44% versus 22%). Conclusions-Mild hypothermia with a surface-cooling device in an acute stroke unit is safe and feasible in thrombolyzed, spontaneously breathing patients with stroke, despite the adverse events. Clinical Trial Registration-URL: http://www. clinicaltrials.gov. Unique identifier: NCT00987922.(Stroke. 2014;45:486-491.)

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Background: Treating hyperglycemia in acute ischemic stroke may be beneficial, but knowledge on its prognostic value and optimal target glucose levels is scarce. We investigated the dynamics of glucose levels and the association of hyperglycemia with outcomes on admission and within 48 h after thrombolysis. Methods: We included 851 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in the Helsinki University Central Hospital during 1998–2008. Outcome measures were unfavorable 3- month outcome (3–6 on the modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH) according to NINDS criteria. Hyperglycemia was defined as a blood glucose level of ≧8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia), (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent hyperglycemia (baseline plus 48-hour hyperglycemia). Results: 480 (56.4%) of our patients (median age 70 years; onset-to-needle time 199 min; National Institutes of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) = 2.33, 95% confidence interval (CI) = 1.41–3.86, and OR = 2.17, 95% CI = 1.30–3.38, respectively], death (OR = 6.63, 95% CI = 3.25–13.54, and OR = 3.13, 95% CI = 1.56–6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68–5.43, and OR = 1.89, 95% CI = 1.04–3.43, respectively), whereas baseline hyperglycemia did not. Conclusions: Hyperglycemia (≧8.0 mmol/l) during 48 h after intravenous thrombolysis of ischemic stroke is strongly associated with unfavorable outcome, sICH, and death.