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
Editor's note: Stroke is one of the topics most requested by Neurology Alert readers. With this issue, we begin a new feature that gives you a concise review of the most recent literature on stroke.
Intravenous Thrombolysis Time-window Can Be Extended to 4.5 Hours
In a follow-up subgroup analysis to their landmark report (N Engl J Med 2008:359;1317-1329), the ECASS III investigators have given us more robust evidence to support extending the window for treatment of patients with acute ischemic stroke using intravenous alteplase (rTPA). After giving the standard dose (0.9 mg/kg bodyweight with a maximum of 90 mg, over one hour) of intravenous rTPA, the investigators showed a statistically significant improvement in the treated group v. placebo in functional endpoints at day 30 and day 90 (mRS 0-1, mRS 0-2, Barthel index > 85, and global outcome statistic), and treatment response (8-point improvement or 0-1 score on the NIH stroke scale).
Although not reaching statistical significance, additional end-points all showed a clear trend in favor of rTPA, including older patients (<65 years: OR=1.61 and >65 years; OR= 1.15), and the effectiveness was independent of the severity of strokeall groups showed benefit. The incidence of symptomatic intracranial hemorrhage, the most feared complication, seemed to be independent of previous antiplatelet drug use and time of onset of symptoms to treatment, but was higher in older age groups (<65 years: OR=0.74, >65 years: OR=5.79. It is notable that the upper limit of age for patient enrollment in this study was 80 years.
Based on the ECASS III reports, stroke teams in the U.S. should consider extending the time window of administration of intravenous rTPA to 4.5 hours, but should take special care in using informed consent, since this extension is not yet approved by the FDA.
Bluhmki E, et al. Stroke treatment with alteplase given 3.0 - 4.5 h after onset of acute ischemic stroke (ECASS III): Additional outcomes and subgroup analysis of a randomized controlled trial. Lancet Neurology 2009:8:1095-1102
Niacin Added to a Statin Increases HDL and Reduces Carotid Atherosclerosis
Neurologists who are caring for stroke patients are becoming more involved in secondary prevention efforts in addition to primary care physicians. This study, from Walter Reed Army Medical Center, provides guidance on the most effective drug combination to lower LDL cholesterol, raise HDL cholesterol, and in the end, hopefully reduce carotid atherosclerosis. The authors enrolled patients at high-risk for coronary artery disease who were receiving long-term statin therapy, with LDL cholesterol under 100 mg/dl and HDL cholesterol under 50 mg/dl for men and under 55 mg/dl for women, and randomized them to receive extended-dose niacin (target=2000 mg/day) or ezetimibe (10 mg /day). The primary end-point was change in mean common carotid intima-media thickness after 14 months.
Mean HDL level increased in the niacin group by 18.4% to 50 mg/dl and mean LDL decreased in the ezetimibe group by 19.2% to 66 mg/dl. Niacin therapy also reduced LDL and triglyceride levels, and ezetimibe reduced HDL and triglyceride. Compared to ezetimibe, niacin had greater efficacy in reducing both mean and maximum carotid intima-media thickness. Paradoxically, greater reductions in LDL in the ezetimibe group were associated with an increase in carotid intima-media thickness. The incidence of major cardiovascular events was lower in the niacin group (1% v. 5%, p=0.04).
Based on this study, we would recommend the addition of slow-release niacin to a statin, in patients who would benefit from a lower LDL, or a higher HDL.
Taylor AJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009:361: 2113-2122.
Chagas Disease Is a Risk Factor for Stroke
Chagas disease (CD), or american trypanosomiasis, is a common protozoan infection and public health problem in South America, and is a leading cause of cardiomyopathy. It is estimated that it may affect up to 18 million people in South America, and can be acquired as a child but not show any manifestations until late in life, presenting with heart failure and cardiac arrhythmias. Because of extensive immigration and international travel, the U.S. FDA recently approved the first screening test for CD among blood donors. Older autopsy studies have shown a high rate of cerebral infarctions in patients who have died from CD, and now a Brazilian group has done a case-control study to look at the prevalence of CD is Brazilian patients who presented with acute cerebral infarction. In comparing 101 consecutive stroke patients with 100 acute coronary syndrome patients who all had similar cardiovascular risk factors, these investigators found that CD-positive serology was an independent risk factor for stroke (OR=7.17;95%CI,1.50-34.19). The mechanism is uncertain, but may be due to cardiomyopathy, undiagnosed atrial fibrillation, or other inflammatory endothelial disorders. It is recommended that patients with acute stroke whose country of origin is in South America, have blood testing for CD.
Paixão LC, et al. Chagas disease: Independent risk factor for stroke. Stroke 2009;40:3691-3694.
"TIAs" May Be Caused by Focal Cortical Subarachnoid Hemorrhage
The authors, from Sunnybrook Health Sciences Center in Toronto, report 4 patients, all elderly (68-85 years), who presented with recurrent episodes of unilateral paresthesias beginning in the face or arm, and spreading over the contiguous body regions at a speed similar to migraine aura (about 20 minutes) and followed by unilateral headache. The time course of symptoms was consistent with the phenomenon of "speading cortical depression." Brain imaging with CT and MRI revealed a small focus of subarachnoid hemorrhage (SAH) in a cortical sulcus in the hemisphere contralateral to the sensory symptoms. The focus of SAH was clearly seen on gradient-echo MRI, and cerebral angiography did not show any vascular lesions to explain the SAH. The authors speculate that these patients probably have cerebral amyloid angiopathy (CAA) as a cause for the focal, spontaneous SAH. Focal, cortical SAH has been shown to induce "speading cortical depression" and other investigators have reported similar cases in patients with CAA. Pathologically, the meningeal vessels are heavily infiltrated with amyloid and the subarachnoid space is often the place where cerebral hemorrhage begins in these patients. Antiepileptic medications had a variable benefit in preventing the episodes, but in all cases, the spells stopped after several months.
Izenberg A, et.al. Crescendo transient aura attacks: A transient ischemic attack mimic caused by focal subarachnoid hemorrhage. Stroke 2009;40:3725-3729.
Phenytoin Use May Worsen Outcome after Intracerebral Hemorrhage
There is considerable debate over the use of prophylactic antiepileptic medications (AED) in patients with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). Recently, large survey series have indicated that overall functional outcome and mortality may be worse in patients with SAH who are prophylactically treated with phenytoin, and guidelines now recommend AED use for only a few days after the acute episode. In this prospective, observational study from Northwestern University in Chicago, 98 patients with ICH were followed, free-phenytoin levels were measured, and patients with depressed consciousness were monitored with continuous electroencephalography (EEG). Seven patients had a clinical seizurefive on the day of the ICH. Phenytoin use was associated with more fever, worse NIH stroke scale and modified Rankin at 14 days, and an increased risk of poor outcome at three months. Levetiracetam, a newer medication with limited use, could not be assessed in this study.
Naidech AM, et al. Anticonvulsant use and outcomes after intracerebral hemorrhage. Stroke 2009;40:3810-3815.
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