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.


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 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/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 micromol/ L; P = .02).


CONCLUSIONS
Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.
Flemming
K D
KD
Division of Cerebrovascular Diseases Mayo Clinic, Rochester, Minn. 55905, USA.
Nguyen
T T
TT
Abu-Lebdeh
H S
HS
Parisi
J E
JE
Wiebers
D O
DO
Sicks
J D
JD
O'Fallon
W M
WM
Petty
G W
GW
D000328:Adult; D017677:Age Distribution; D001706:Biopsy; D016022:Case-Control Studies; D002539:Cerebral Arterial Diseases / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D015161:Dementia, Multi-Infarct / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D015140:Dementia, Vascular / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D005215:Fasting; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008715:Methionine; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D017678:Sex Distribution
D006710:Homocysteine; D008715:Methionine