Clinical Briefs

By Louis Kuritzky, MD

Migraine and Subclinical Brain Lesions

The data on the relationship between migraine and other vascular events such as stroke have been conflicting, although in some populations (such as young women smokers who suffer migraine with aura) the adverse association is more clear-cut. Because such a high proportion of women, and a not-insubstantial population of men suffer migraine, any important association with other major morbidities becomes epidemiologically compelling.

Using MRI scans in a population of migraine sufferers without history of prior stroke or TIA, infarcts and white matter lesions were defined, all by the same neuroradiologist who was blinded to the clinical data about the patients (n = 435, inclusive of 140 controls). Most patients (71%) were female, the mean age was 48 years, and patients were equally divided between migraine with and without aura.

Although the absolute number of infarcts demonstrated only a trend towards being more frequent in migraneurs, it was the posterior circulation infarcts which were markedly more common (7-fold increase in migraine population vs controls), an effect which was even more exaggerated in the migraine with aura category (odds ratio = 13.7). In the total unselected population, no difference in white matter lesions between migraine sufferers and controls was discerned; however women migraneurs had an increased odds ratio (OR = 2.1) for white matter lesions compared to controls.

None of these patients had any prior evidence of cerebral ischemic events. The relationship between migraine and increased risk of cerebral ischemia prompts consideration of whether more vigorous prevention of migraine might reduce risk of subsequent tissue damage.

Kruit MC, et al. JAMA. 2004;291: 427-434.

Memantine Treatment in Alzheimer Disease

Memantine (MEM) is the first clinically available NMDA receptor antagonist with demonstrated clinical efficacy and an acceptable adverse event profile for persons with Alzheimer disease (ALZ). Cholinesterase inhibitors like donepezil (DON) might work in a complementary fashion, hence this MEM + DON trial.

Subjects with ALZ (n = 404) who had been on a stable dose of DON for at least 6 months, and were free of known secondary etiologies for dementia, were randomized in a double-blind fashion to MEM titrated from 5 mg/d up to 20 mg/d (administered as 10 mg b.i.d.) for 6 months, vs placebo. DON was continued in both the placebo and the MEM treatment arm.

Changes in cognitive function, functional capacity, and global outcome were measured throughout the trial, the primary outcome being based upon scores on the Severe Impairment Battery and Activities of Daily Living Inventory.

There was a statistically significant positive effect of MEM when added to DON, complemented with a very favorable adverse effect profile: more patients in the placebo group withdrew due to adverse events than in the MEM group. Only headache and confusion were more common in the MEM group, both of which occurred in less than 10% of recipients. In addition to being useful as ALZ monotherapy, there may be additional clinical benefits from combining MEM with DON in ALZ therapy.

Tariot PN, et al. JAMA. 2004;291: 317-324.

PPG in Type 2 DM

Tight control of type 2 diabetes (DM2) has been proven to reduce microvascular complications. Use of the hemoglobin A1c to assess long-term control is standard, but for modulation of treatment, timed specimens (eg, fasting, 1-2 hours postprandial) obtained by patient self-monitoring of blood glucose are often the information clinicians use to make choices about therapy modification.

Unless instructed otherwise, most DM2 patients are 1-4 hours postprandial at the time of an office visit. El-Kebbi, et al, investigated whether casual glucose levels obtained at the office visit might function as an adequate barometer of glucose control to help modify treatment.

Established DM2 patients (n = 1827) at the Grady Diabetes Clinic (Atlanta) underwent simultaneous A1c and casual glucose measurement during their regular visit. The correlation between casual glucose measurement and A1c was strong (correlation coefficient = 0.63). The presence of a casual glucose > 150 predicted an A1c > 7.0 with a sensitivity of 78% (positive predictive value = 80%).

El-Kebbi and colleagues suggest that a casual plasma glucose greater than 150 mg/dL may serve as a surrogate for A1c; results above this level should prompt an intensification of therapy. 

El-Kebbi IM, et al. Diabetes Care. 2004;27:335-339.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.