This year's American Academy of Neurology (AAN) meeting featured key drug trials for diseases ranging from epilepsy to Alzheimer's disease (AD) to multiple sclerosis (MS). About 1% of all children up to the age of 16 are affected by epilepsy. Despite broadened and improved pharmacologic options, about 25% of these are refractory to standard therapy. Oxcarbazepine (Trileptal, Novartis), a newer antiepileptic drug (AED), has been assessed and found to be safe and effective both as monotherapy and adjunctive therapy in children.

In a multicenter randomized study presented by J. Eric Pia-Garza, M.D., assistant professor of neurology, Vanderbilt University Medical Center, Nashville, oxcarbazepine was evaluated in 115 children (from one month to less than four years old). All had inadequately controlled partial seizures despite being given up to two AEDs. To be entered into the study, patients needed to show a minimum of two study-defined focal seizures of at least 20 seconds' duration. They were randomized to either a low- or high-dose oxcarbazepine regimen and evaluated at the end of nine days on their ultimate dose.

Investigators found that the high dose reduced seizures by 83% as compared with the low dose. Adverse events were increased at the higher dose. Tracy Stites, Ph.D., Novartis trial leader, suggested that the longer period on the drug for the higher-dose group owing to the titration period might have caused the higher adverse event rate. The safety profile was similar to that in older children and adults. The study confirmed that oxcarbazepine is a valuable treatment option in the management of partial seizures in infants and young children, Pia-Garza concluded.

A trial among patients with mild cognitive impairment (MCI) taking either donepezil (Aricept, Eisai/ Pfizer), vitamin E, or placebo revealed no benefit for vitamin E and benefits for donepezil that diminished over time. The three-year trial, which enrolled 769 patients meeting MCI criteria, evaluated progression to AD and decline in cognition and function. About 55% of subjects were positive for the Apo-E4 lipoprotein allele associated with higher risk of developing AD.

Leon J. Thal, M.D., chair of the neurosciences department at University of California, San Diego, reported that at the study conclusion, there were no significant differences in the probability of conversion to AD among treatment groups. Looking at conversions to AD over time, however, revealed significant benefits for donepezil.

David Knopman, M.D., Mayo Clinic, pointed to positive and negative aspects of treatment that need to be raised with MCI patients and families. Treatment is too expensive for too little benefit, and it does not alter the natural history of the disease and offers no public health benefit. On the other hand, he said, "a 58% one-year risk reduction may be clinically meaningful to some MCI patients, and the delay in decline may translate into enhanced quality of life for some with MCI."

A report on the longest trial of MS treatment, a 16-year follow-up on the pivotal study of interferon beta-1b (IFNB-1b, Betaseron, Berlex), turned up no safety issues and some indications of benefit for early treatment. Betaseron was the first immunomodulatory therapy approved for relapsing MS. In the original trial, patients received one of two IFNB-1b doses (50 mcg/250 mcg) or placebo for two years. Patients were then offered double-blind continuation for up to five years, after which all were offered the subsequently approved 250-mcg dose. The result was that the original group started therapy a median of 46 months earlier.

George Ebers, M.D., professor of clinical neurology at Oxford University, reported that investigators have succeeded in tracing 234 of the original 272 patients, representing more than 3,000 treatment years. Preliminary analysis showed individuals in the 250-mcg group were more likely to be able to walk unaided or using aids than those in the placebo group. Also, more in the 250-mcg group remain alive. The findings suggest that "early treatment initiation may have a long-lasting beneficial impact," he said.

Walter Alexander, Ph.D. is a clinical writer based in New York.