K. McKie

The use of transcranial ultrasonography to predict stroke in sickle cell disease

BACKGROUND Stroke, especially cerebral infarction, is a major cause of morbidity and mortality in children with sickle cell disease. Primary prevention of stroke by transfusion therapy may be feasible if there is a way to identify the patients at greatest risk. Transcranial Doppler ultrasonography can measure flow velocity in the large intracranial arteries. The narrowing of these arteries, which leads to cerebral infarction, is characterized by an increased velocity of flow. METHODS Using transcranial Doppler ultrasonography, we prospectively measured the velocity of cerebral blood flow in children and young adults being followed because of sickle cell disease. The results were classified as either normal or abnormal on the basis of the highest velocity of flow in the middle cerebral artery. Abnormal velocity was defined as a flow greater than or equal to 170 cm per second, a definition determined by post hoc analysis to maximize the predictive success of the test. The end point was a clinically apparent first cerebral infarction. RESULTS Two hundred eighty-three transcranial ultrasound examinations were performed in 190 patients with sickle cell disease (age at entry, 3 to 18 years). After an average follow-up of 29 months, cerebral infarction was diagnosed in seven patients. In 23 patients the results of the ultrasound examinations were abnormal, and in 167 patients they were normal. The clinical and hematologic characteristics of the two groups were similar, but six of the seven strokes occurred among the 23 patients with abnormal ultrasound results (P less than 0.00001 by Fishers exact test). In this group, the relative risk of stroke was 44 (95 percent confidence interval, 5.5 to 346). CONCLUSIONS Transcranial ultrasonography can identify the children with sickle cell disease who are at highest risk for cerebral infarction. Periodic ultrasound examinations and the selective use of transfusion therapy could make the primary prevention of stroke an achievable goal.

Cerebral infarction in sickle cell anemia Mechanism based on CT and MRI

We studied 25 patients with sickle cell anemia and cerebral infarction. We classified lesions as to probable mechanism (large versus small vessel disease) based on the CT/MRI appearance of established infarction. Most patients had CT/ MRI patterns of major cerebral vessel occlusion (41%) or borderzone (distal insufficiency) infarcts (31%) best explained by large cerebral vessel vasculopathy. Seven of 25 (28%) had either isolated subcortical (12%) or small cortical branch occlusion (16%) consistent with other mechanisms such as small vessel occlusion or embolism. These results suggest that most clinically recognized cerebral infarctions in sickle cell anemia are caused by large vessel disease, but this mechanism may not account for symptoms of cerebral ischemia in all cases.

Cerebral vessel stenosis in sickle cell disease: Criteria for detection by transcranial doppler

Ischemic stroke is a common and disabling complication of sickle cell disease (Hb SS). Most infarctions occur in the presence of intracranial stenotic lesions of the large vessels of the circle of Willis. Transcranial Doppler (TCD), by measuring flow velocity in these arterial segments, can detect focal stenosis on the basis of elevated flow velocity. We report the preliminary results of a prospective study to develop criteria for detection of stenotic lesions based on TCD and identification of patients with Hb SS at risk for stroke. Comparing the TCD findings from six patients with lesions demonstrated by angiography to those from 115 Hb SS children without stroke, we conclude: (a) middle cerebral (MCA), anterior cerebral (ACA), or internal carotid (ICA) artery mean velocities greater than 190 cm/s strongly suggest focal stenosis; (b) MCA or ACA mean velocities of 150 to 190 cm/s suggest abnormality but at present cannot be considered diagnostic of stenosis; (c) mean velocities up to 150 cm/s are possibly due to the effects of low hematocrit and/or young age, and cannot as yet be distinguished from velocity elevations due to vessel stenosis.