Stroke Alert: A Review of Current Clinical Stroke Literature

By Matthew E. Fink, MD, Interim Chair and Neurologist-in-Chief, Director, Division of Stroke & Critical Care Neurology, Weill Cornell Medical College and New York Presbyterian Hospital

Extracranial-Intracranial Bypass Surgery is No Better Than Medical Therapy for Stroke Prevention

Source: Powers WJ, et al, for the COSS Investigators. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia. The Carotid Occlusion Surgery Study randomized trial. JAMA 2011;306:1983-1992.

Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada participated in a randomized, blinded-adjudication clinical treatment trial of 195 patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) who also had hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Anastomosis of a superficial temporal artery branch to a middle cerebral artery cortical branch was performed in the surgical group and all patients were treated with antithrombotic therapy and risk factor interventions as appropriate. Primary outcome measures were (1) all stroke and death from surgery (or randomization) through 30 days, and (2) ipsilateral ischemic stroke within 2 years of randomization.

The trial was terminated early for futility. Two-year rates for stroke were 21.0% (95% confidence interval [CI], 12.8% to 29.2%) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%) for the medical group (P = 0.78). Thirty-day stroke rate for the surgical group was 14.4% and 2.2% in the medical group. In this trial, bypass surgery did not reduce the risk of recurrent stroke at 2 years. These results are similar to the trial reported in 1985 (N Engl J Med 1985;313:1191).

Overweight May Be Associated with a Reduced Risk of Aneurysmal Subarachnoid Hemorrhage

Source: Sandvei MS, et al. Risk factors for aneurysmal subarachnoid hemorrhage — BMI and serum lipids: 11-year follow-up of the HUNT and the Tromso Study in Norway. Acta Neurol Scand DOI: 10.1111/j.1600-0404.2011.01578.x.

Lifestyle factors, including smoking, hypertension, and excessive alcohol intake, have been associated with increased risk for aneurysmal subarachnoid hemorrhage (aSAH). In this study, investigators analyzed the impact of body mass index (BMI) and serum lipids on the risk of aSAH in a prospective cohort of 102,408 participants in two large population health studies from Norway. Measurements included body weight and height, serum lipids, and self-administered questionnaires. Participants who subsequently experienced aSAH were identified and hazard ratios were calculated.

During 11 years of follow-up, aSAH was identified in 122 cases, and overweight (BMI 25-29.9 kg/m2) was negatively associated with the risk of aSAH (hazard ratio 0.7: 95% CI, 0.4 to 1.0). There was no association with total serum cholesterol, HDL, or triglycerides with the risk of aSAH, but in persons < 50 years of age, HDL was inversely associated with risk of aSAH. This study also confirmed previously noted risk factors, including female gender, hypertension, smoking, and excessive alcohol consumption.

Intra-Arterial Therapy for Acute Ischemic Stroke Does Not Increase the Risk of Symptomatic Intracranial Hemorrhage

Source: De Marchis GM, et al. Intracranial hemorrhage, outcome, and mortality after intra-arterial therapy for acute ischemic stroke in patients under oral anticoagulants. Stroke 2011;42:3061-3066.

Symptomatic intracranial hemorrhage (sich) is the most feared complication of thrombolysis for acute ischemic stroke (AIS), and has been documented to occur in 5% to 7% of patients who are treated in intravenous tPA. Current guidelines recommend the use of IV tPA in patients who have an INR < 1.7, and many patients being treated with oral anticoagulants (OAC) are referred for intra-arterial therapies (IAT), which include locally applied thrombolysis or mechanical clot extraction. A recent study (Arch Neurol 2010;67:559) noted that the risk of sICH was increased by 10-fold in all patients being treated with OAC who then received IV tPA, even if their INR was less than 1.7. This study examined the risk of hemorrhagic complications after intra-arterial therapies for AIS in patients who were receiving OAC.

In this study, 714 consecutive patients were treated with IAT at a single center in Bern, Switzerland, from 1992 to 2010. Twenty-eight patients (3.9%) were taking OAC at the time of AIS symptom onset. Median INR in the OAC group was 1.79 and 1.01 in the group without OAC. Patients treated with OAC on admission were more often treated with mechanical-only clot extraction (46.4% vs 12.8%). Comparing patients with or without previous use of OAC, there was no statistically significant difference in the rate of sICH (7.1% vs 6.0%), unfavorable outcome as measured by the modified Rankin Scale (67.9% vs 50.9%), or mortality (17.9% vs 21.6%).

Intraventricular tPA Can Be Safely Administered Via Ventricular Catheter to Patients with Intracerebral and Intraventricular Hemorrhage

Source: Naff N, et al. Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage. The intraventricular hemorrhage thrombolysis trial. Stroke 2011;42:3009-3016.

Intracerebral hemorrhage (ich) carries a high mor- tality (50%) and intraventricular extension (IVH) makes the prognosis worse. The investigators used a clot lysis protocol by administering tPA via ventricular catheter to enhance resolution of the hematoma. Forty-eight patients at 14 centers were randomized to treatment with 3 mg of tPA given every 12 hours, and compared to a group with ventricular drainage alone. Clinical features were evenly distributed, including Glasgow Coma Scale, ICH volume, IVH volume, and blood pressure. There were no differences between the groups in intracranial pressure or cerebral perfusion pressure.

In both groups, the frequency of death (18% rtPA; 23% placebo) and ventriculitis (8% vs 9%) was lower than expected and symptomatic bleeding was higher in the tPA group (23% vs 5%). Median duration of dosing was 7.5 days for tPA and 12 days for placebo, indicating a beneficial effect of tPA on clot resolution. This study was not designed to assess functional outcomes and a larger Phase 3 trial will be needed to fully evaluate the potential benefit of this therapy.