Topiramate in migraine prevention: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase. RESULTS: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Morphometric effects of use and disuse on peripheral nerve.

Rat peripheral nerve was evaluated morphometrically following hemicordotomy, tenectomy, or both to assess the effects of disuse and hyperactivity on the peripheral nervous system. Hemicordotomy resulted in an increase in diameter of nerve fibers supplying both "fast" and "slow" skeletal muscles in hypoactive and hyperactive limbs. Nerve fiber atrophy occurred only in nerve to "fast" muscle following disuse induced by hemicordotomy and tenectomy. The possible role of "motor nerve growth factor" or altered axoplasmic flow in bringing about these morphologic changes in peripheral nerve is discussed.

Nitrous oxide neurotoxicity studies in man and rat.

To assess the effects of chronic exposure to low levels of nitrous oxide on neural function of man, the authors evaluated the neurologic condition, motor and sensory nerve conduction, and computerized tests of sensation of approximately half of the dentists in Rochester, Minnesota. Results of scored tests of neural function were not significantly different for dentists who used nitrous oxide extensively in their practices and dentists who did not. To assess the effects of chronic exposure to high levels of nitrous oxide on neural function and structure of experimental animals, groups of rats were exposed to 70 per cent N2O in 30 per cent oxygen for four hours, five days a week, for six months. Rats exposed to N2O and control rats showed no difference in well-being, in caudal nerve conduction, in axonal content and transport of acetylcholinesterase and dopamine-beta-hydroxylase, or in number and size distribution and pathologic abnormality of teased myelinated fibers. Although these results indicate a lack of peripheral nerve neurotoxicity of N2O in the rat, one cannot assume a similar lack of neurotoxicity in man with heavy exposures.

The analysis of collagen in glutaraldehyde-fixed, osmicated peripheral nerve.

Glutaraldehyde fixation and osmication of rat sciatic nerve and human sural nerve did not appreciably alter the apparent weight of collagen in nerve fasciculi as determined by hydroxyproline analysis of hydrolysed samples. The collagen content of autopsied peripheral nerve is unaltered at least up to 24 h after death. The mean endoneurial weight of collagen per fascicle in rat sciatic nerve was 123 mug (all results expressed for 1 cm length). In human sural nerve the mean weight was 57 mug and the mean fascicular volume 1.75 mm3. Human endoneurial collagen fibrils gave a unimodal distribution of diameters with a peak at 40 nm.