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. Dr. Fink reports no financial relationships relevant to this field of study.
Warfarin-treated patients who receive TPA have a much higher risk for symptomatic intracerebral hemorrhage (ICH).
Prabhakaran S, et al. Symptomatic intracerebral hemorrhage among eligible warfarin-treated patients receiving intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2010;67: (doi:10.1001/archneurol.2010.25).
The authors reviewed records of 107 patients who were treated with intravenous TPA according to a standard protocol that required an INR < 1.7. Baseline warfarin use was present in 12.1% of all patients but the median INR = 1.04 (range 0.82–1.61). The overall rate of symptomatic ICH was 6.5%, but it was nearly 10-fold higher among patients taking warfarin compared to those not taking warfarin at baseline (30.8% vs 3.2%, respectively; p = .004) after adjustments for age, atrial fibrillation, NIH Stroke Score, and INR. Therefore, any use of warfarin, even with an INR that is in the normal range, increases the risk of ICH. In these situations, IV TPA should be given with the greatest caution and close monitoring.
Fever with ischemic stroke good or bad?
Prasad K, et al. Fever is associated with doubling of odds of short-term mortality in ischemic stroke: an updated meta-analysis. Acta Neurol Scand DOI: 10.1111/j.1600-0404.2010.01326.x. Naess H, et al. Inverse relationship of baseline body temperature and outcome between ischemic stroke patients treated and not treated with thrombolysis: the Bergen stroke study. Acta Neurol Scand DOI:1111/j.1600-0404.2010.01331.x.
Two companion articles focus on the role of fever in patients with acute ischemic stroke. The study by Prasad and colleagues is a meta-analysis that reviewed all studies that examined the relationship between fever in acute ischemic stroke and mortality, from January 1990 to November 2008. Heterogeneity was assessed using I2 and chi-square statistics and odds ratios (OR) from logistic regression were combined. Six cohort studies involving 2986 patients were included. Meta-analysis revealed a combined OR of 2.20(95% CI 1.59-3.03, p < 0.00001) for mortality in the first month. The authors concluded that fever within the first 24 hours of hospitalization in patients with ischemic stroke is associated with doubling of the odds of death within one month of onset of stroke. However, it is not known if the development of fever is a marker for subsequent poor outcome, or may be a contributing cause.
In the Naess et al. study, the authors evaluated the hypothesis that elevated body temperature would enhance the thrombolytic effects of tissue plasminogen activator (TPA) in patients who received this treatment, and low body temperature would be neuroprotective for patients who did not receive TPA. They included 111 patients who received TPA and 139 patients who were not treated with TPA but presented within 6 hours of stroke onset. NIH Stroke Scale was obtained on admission and outcome was assessed using the modified Rankin score (mRS). Using logistic regression analysis, high body temperature was associated with a favorable outcome (mRS 0-2) in patients treated with TPA (OR = 3.7, p=0.009) and low body temperature was associated with favorable prognosis in patients not treated with TPA(OR=2.0, p=0.042), but this barely reached statistical significance.
These conflicting findings about high and low body temperature certainly create a clinical conundrumthrombolysis is the most effective means to accomplish revascularization in ischemic stroke, and because it is an enzymatic effect, elevated temperature would enhance the potency of TPA. However, many groups are pursuing therapeutic hypothermia as a neuroprotective strategy, along with thombolysis. These conflicting findings point to the importance of answering these questions with well-designed, randomized clinical trials.
What is leukoaraiosis? Ischemia, edema, or inflammation?
Auriel E, et al. Clinical, radiological and pathological correlates of leukoaraiosis. Acta Neurol Scand DOI: 10.1111/j.1600-0404.2010.01341.x.
The imaging picture of leukoaraiosis (la) was first defined by Hachinski (Arch Neurol 1987;44:21-23) based on low-density lesions on CT scans in the white matter of the centrum semiovale, in patients who had vascular risk factors for ischemic stroke. With the advent of MRI, hyperintensities in the white matter on T2 and FLAIR-weighted imaging became even more prominent, and were shown to predict subsequent stroke, but even more important, subsequent cognitive impairment and dementia. The most common risk factor for LA is age, but other vascular risk factors, such as hypertension, diabetes, obesity and metabolic syndrome, were all contributory. What is the pathology that correlates with LA? This is a difficult question because it is difficult to find pathologic material that can be paired temporally with CT or MR imaging.
Auriel and colleagues studied 93 deceased patients who had premortem MRI with T2-weighted images. Tissue specimens were taken from 19 brains that demonstrated severe LA premortem, and these were compared to five control brains. The clinical variables that were found to significantly correlate with LA were age and a history of Parkinson's disease. Other risk factors and markers for atherosclerosis were not significantly correlated with LA, and those included hypertension and diabetes. The histology of the LA lesions did not show staining for any abnormalities of myelin, astrocytes, microglia, smooth muscles cells, or elastin. The lesions were not infarcts and did not show any inflammation. However, there was one consistent findingthickening of the walls of small arteries and arterioles, sometimes to the point of total occlusion. The authors postulate that LA, as seen on imaging, represents the effects on white matter of chronic hypoxia/ischemia that is not enough to cause cell death or demyelination, but causes functional impairment in neural conduction with increasing age, and increases the risk for infarction.