MRI of TIA faces barrier of therapeutic limitations

A growing body of research indicates that MR diffusion-weighted imaging (DWI) can help predict risk of recurrent stroke in patients presenting with transient ischemic attack. But a lack of proven therapeutic options-underscored by recent setbacks in trials of neuroprotective agents-will limit opportunities for imaging to play a preventive role in this frustrating patient population.

Recent evidence of MRI's predictive value in patients who have had a TIA came from researchers at the University of Pennsylvania, who found that patients with acute (within 48 hours) infarction on DWI were significantly more likely than patients with negative DWI findings to experience stroke, death, or other high-risk outcome within 90 days.1

In 61 patients who underwent MRI, 15 had 90-day outcomes categorized as high risk, which also included greater than 50% arterial stenosis related to symptoms or a cardioembolic source that warranted anticoagulation. In contrast, a scoring system based on age, blood pressure, clinical features, and duration of symptoms was not predictive of risk.

"It's kind of humbling, actually," said Brett L. Cucchiara, MD, an assistant professor of neurology at Penn and corresponding author of the study. "Patients with vague symptoms end up having diffusion abnormalities. Patients in whom I would have bet money that there was no diffusion abnormality ended up having an infarct."

The Penn findings, published in July 2006, were consistent with those of researchers from the University of Calgary in Alberta, Canada, published a year earlier.2 In 69 patients with TIA and 51 patients with minor stroke, the Calgary researchers found that the adjusted 90-day risk of new stroke was 32.6% in patients with an acute (within 24 hours of symptom onset) DWI lesion and vessel occlusion, 10.8% in those with a DWI lesion but no vessel occlusion, and 4.3% in those with negative DWIs. DWI findings also were predictive of functional dependence at 90 days.

As tempting as it may be to envision MRI becoming the type of screening tool for TIA that cardiac enzyme tests are for patients with chest pain, experts say that type of scenario is nowhere close to becoming reality.

"We may be able to identify patients who are vulnerable, but we don't necessarily have treatments that are proven," said Andrew M. Demchuk, MD, an associate professor of neurology and director of the Calgary stroke program.

Researchers and clinicians had hoped that neuroprotective agents might be just the type of therapy that could be used preventively in such a population. But optimism about neuroprotective agents, which surged after a successful trial of NXY-059 was published in February 2006,3 has waned since the second clinical trial of the same drug was discontinued in October because of lack of efficacy.

Whereas previous trials of NXY-059 and other potential neuroprotective agents have delivered the drugs in the hours following stroke onset, it's still possible that neuroprotective drugs might be more effective if administered preventively in the TIA population, according to Demchuk.

"In animals, some of the greatest benefit is that you can pretreat," he said. "But that's just a hypothesis. We've been so burned by neuroprotective approaches that the question is how much enthusiasm will there be to pursue this line of therapy."

References

• Cucchiara BL, Messe SR, Taylor RA, et al. Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack? Stroke 2006;37:1710-1714.

• Coutts SB, Simon JE, Eliasziw M, et al. Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging. Ann Neurol 2005;57:848-854.

• Lees KR, Zivin JA, Ashwood T, et al. NXY-059 for acute ischemic stroke. NEJM 2006;354:588-600.