Unraveling Cryptogenic Stroke

Abstract & Commentary

Source: Bang OY, et al. Frequency and mechanisms of stroke recurrence after cryptogenic stroke. Ann Neurol. 2003;54:227-234.

Stroke with no determined cause, or cryptogenic stroke [CS], accounts for nearly 40% of all ischemic strokes, a staggering percentage given the resources and technologies used as part of stroke evaluation. Traditionally, it has been held that CS carries a more benign prognosis than other stroke subtypes such as large artery disease [LAD] or cardioembolic disease [CE]. However, until this recent study, the long-term risk of recurrent stroke in this large segment of the stroke population had never been prospectively studied.

Bang and associates identified 204 patients after an index stroke and classified them among 5 stroke subtypes: small artery disease [SAD], LAD, CE, 2 or more causes, and no determined cause [NC]. Stroke recurrence was reported over the following 1-year period. Stroke recurrence rates were significantly higher in the NC group, 30% compared to 16% in the LAD group, 14% in the CE group, and 2% in the SAD group. Furthermore, in 6 of 11 NC recurrent stroke patients, an association with intracranial atherosclerosis [IA] was found. There was found to be moderate stenosis [30-50%] of a symptomatic vessel or significant [greater than 50%] stenosis of a nonrelevant artery. All the recurrent strokes in the NC group occurred in the territory of a stenosed intracranial artery or at the same site as the index stroke, lending some credence to their suggestion that IA might be the mechanism of stroke in these patients. They also noted that the NC group had recurrences throughout the year of the study, while the other subtypes showed recurrence often within the first month. Bang et al conclude that a subset of CS actually represents a mild form of large artery atherosclerosis. The implication is that early detection of such vascular lesions might be crucial in preventing recurrent stroke in these patients.

Commentary

The study is limited by a small number of patients and a lack of a transesophageal echocardiogram evaluation in some patients. Anomalies as a PFO, atrial thrombus, or vegetations are not adequately excluded. This report is important, however, as it emphasizes that CS is not a homogenous disease with a benign prognosis. Rather, CS accounts for a significant proportion of ischemic stroke and has a higher 1-year recurrence rate than previously reported. Secondary stroke prevention in this group is, therefore, crucial and requires that we better understand the pathophysiology of this disease. Bang et al make a step toward that goal, finding that intracranial atherosclerosis may be a mechanism of stroke in some patients with CS. Treatment implications of this certainly include aggressive risk-factor reduction (such as statin therapy), and anticoagluation with warfarin is possibly warranted. — Shyam Prabhakaran, MD, Chief Resident in Neurology at Cornell University Medical College, New York, NY, and Alan Z. Segal, MD, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital, Assistant Editor, Neurology Alert.