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Stefan Evers, MD; Hans-Georg Koch, MD; Karl-Heinz Grotemeyer, MD; Bernd Lange, MD; Thomas Deufel, MD; Erich-Bernd Ringelstein, MD

Arch Neurol. 1997;54(10):1276-1282.

Abstract
Background
Hyperhomocysteinemia has been shown to be a mild independent risk factor for premature atherosclerosis, and there is evidence of an increased rate of peripheral vascular occlusive disease, myocardial infarction, and stroke.

Objective
To evaluate clinical, biochemical, and neurophysiological findings in patients with ischemic stroke with and without hyperhomocysteinemia.

Subjects
One hundred twenty-five consecutive patients with a history of stroke and 60 healthy control subjects.

Methods
Patients were divided into those with and those without hyperhomocysteinemia, which was defined as blood levels beyond the mean total plasma homocysteine level plus 2 SDs of the healthy control group. History, symptoms, cause, patterns of infarction, biochemical data, continuous and transcranial Doppler sonography, and event-related potentials were recorded in all patients.

Results
Twenty-seven patients had hyperhomocysteinemia. Compared with the 98 patients without hyperhomocysteinemia, they had an increased rate of hypertension (odds ratio, 3.5; 95% confidence interval, 1.0-12.6), an increased level of uric acid (P<.007), an increased hematocrit (P<.02), a higher rate of microangiopathy (odds ratio, 2.8; 95% confidence interval, 1.1-7.2), and a trend to a higher rate of multiple infarction. Furthermore, the P3 latency of the event-related potential was significantly increased in hyperhomocysteinemia (P<.004).

Conclusions
Hyperhomocysteinemia is probably an independent risk factor for stroke, with a prevalence of about 20% in all patients with a history of stroke; however, additional factors (eg, hypertension, hyperuricemia) may have an enhancing effect. There are significant differences in stroke patterns between patients with and without hyperhomocysteinemia, with a higher rate of lesions typical of cerebral microangiopathy and a trend to multiple infarctions in the former. Impairment of cognitive processing as measured by visual event-related potential is more pronounced in hyperhomocysteinemia.

Author Affiliations
From the Departments of Neurology (Drs Evers, Grotemeyer, and Ringelstein) and Pediatrics (Drs Koch, Lange, and Deufel), University of Münster, Münster, Germany.

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