Published Online
on June 10, 2004

A more recent version of this article appeared on August 1, 2004

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Submitted on December 3, 2003
Revised on April 16, 2004
Accepted on April 21, 2004

Hyperhomocysteinemia, Low Folate and Vitamin B₁₂ Concentrations, and Methylene Tetrahydrofolate Reductase Mutation in Cerebral Venous Thrombosis

Carlos Cantu MD, MSc^*; Elisa Alonso MD; Aurelio Jara BSc; Leticia Martínez BSc; Camilo Ríos Ch, PhD; María de los Angeles Fernández BSc; Irma Garcia BSc; and Fernando Barinagarrementeria MD

From the Stroke Clinic (C.C., F.B.) and the Departments of Genetics (E.A., A.J., L.M.), Neurochemistry (C.R.), and Radioimmunoassay (M.d.l.A.F., I.G.), Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez," Mexico C.C. is now appointed at the Stroke Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City. F.B. has moved to Hospital Angeles, Querétaro, Mexico.

^* To whom correspondence should be addressed. E-mail: carloscantu_brito{at}hotmail.com.

Background--Elevated plasma levels of homocysteine are associated with an increased risk of deep-vein thrombosis. Through a case-control study, we examined the potential association among homocysteine, folate and vitamin B₁₂ levels, and the common C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene in patients with cerebral venous thrombosis (CVT).

Methods--Forty-five patients with CVT and 90 control subjects were studied. Plasma levels of homocysteine (fasting and after methionine load), folate, and vitamin B₁₂ were measured. Genotyping of the MTHFR gene was also performed. The estimated risk of CVT associated with hyperhomocysteinemia, low vitamin levels, and MTHFR mutation were expressed as odds ratio (OR) and its 95% CI (crude and after adjusting by other independent variables).

Results--The adjusted OR for CVT associated with high (>90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (<10th percentile) and presence of CVT was 3.5 (1.2 to 10.0) after adjustment for confounding factors. There was a higher frequency of MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant (P=0.098). Patients with MTHFR mutation and low folate levels presented the highest homocysteine levels.

Conclusions--High plasma concentrations of homocysteine and low plasma folate levels were associated with an increased risk of CVT in this population in which low socioeconomic conditions and deficient nutritional status may contribute to its relatively high incidence.

Key words: cerebral thrombosis • sinus thrombosis • risk factors • coagulation • homocysteine

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