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From the Departments of Clinical Genetics (Drs. Lesnik Oberstein and Breuning), Radiology (Drs. van den Boom and van Buchem), Medical Statistics (Dr. van Houwelingen), Human Genetics (Dr. Bakker and E. Vollebregt), and Neurology (Drs. Ferrari and Haan), Leiden University Medical Center, and Department of Neurology (Dr. Haan), Rijnland Hospital, Leiden, the Netherlands.
Address correspondence and reprint requests to Dr. S.A.J. Lesnik Oberstein, Department of Clinical Genetics, K5-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands; e-mail: lesnik{at}lumc.nl
Background:— Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL.
Objective:— To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding.
Methods:— T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype.
Results:— Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds.
Conclusion:— Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.
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