Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Objective: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack. Patients and Methods: We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test. Results: CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 μ mol/L; P=.03) and after methionine challenge (51.0 vs 34.0 μmol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs 24.0 μmol/ L; P=.02). Conclusion: Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.