TORONTO—More than 90% of patients with newly diagnosed epilepsy who will eventually go into remission do so within three years, according to Martin J. Brodie, MD, FRCP. Dr. Brodie, Professor of Medicine and Clinical Pharmacology at the University of Glasgow, and his research fellow, Rajiv Mohanraj, MD, evaluated the natural history of 780 patients with newly diagnosed epilepsy (52% male; median age, 29) followed for a median of 79 months (range, two to 21 years). Seizure freedom was achieved in 504 patients (65%), while in 276 (35%), seizures were never controlled. Of the 504 who became seizure-free, 105 relapsed, but 63 ultimately regained control, yielding 462 (59%) with prolonged remission and 318 (41%) uncontrolled. “Two hundred and forty-five patients (31.4%) never had another seizure after taking the first dose of their first antiepileptic drug, and 92% who ultimately achieved seizure control did so within the first three years,” Dr. Brodie observed.

REMISSION IMPOSSIBLE?

“A number of factors weigh against remission,” said Dr. Brodie (see Table, page 67). “If you have a family history of epilepsy, then the chances of remission were only 44% compared to 61%. If there was psychiatric comorbidity either before developing the epilepsy or at the time of epilepsy diagnosis, the chances of remission were less (43% versus 62%) because psychiatric morbidity is further evidence of brain dysfunction. Febrile convulsions also predicted against remission; only 34% of patients with febrile convulsions achieved remission, compared to 60% without.

“In addition, the more seizures you have in the three months before starting treatment, the more likely you are to have refractory seizures,” Dr. Brodie noted. “If you have more than 20 seizures, the likelihood of remission is only 36%. Age was also a factor; the elderly had a remission rate of 85%; adolescents, 65%; and adults, 53%. Patients with poststroke epilepsies do particularly well, which is why the elderly do so much better. The group that does the worst is posttraumatic epilepsy, with a 35% remission rate. Interestingly, gender, perinatal injury, mental retardation, neurologic deficit, and seizure clustering were not predictive of remission,” he added.

BEYOND SEIZURES

“Refractory epilepsy isn’t just about uncontrolled seizures,” Dr. Brodie explained in his presentation of the study findings at the Seventh Annual Neurology Outcomes Research Meeting at the 129th Annual Meeting of the American Neurological Association. “Because the seizures are not controlled, these patients get excessive drug burden with sedation and long-term side effects, which can be a worse problem than the actual seizures. They have cognitive deterioration, psychosocial dysfunction, restricted lifestyle, and are two to three times more likely to die than the general population. Sudden unexplained death in epilepsy is the commonest cause of seizure-related death. Other causes include drowning, burns, aspiration pneumonia, status epilepticus, and suicide.”

Dr. Brodie added, “Regarding seizure control, there is only one number that matters to the patient, and that’s zero—no seizures.” In the past 15 years, he said, there has been a dramatic increase in the number of new medications for epilepsy. However, their impact on patient outcomes has not yet been quantified.

“Most patients respond to monotherapy (59.2%), and generally at modest doses—for example, carbamazepine at 800 mg/day or less, sodium valproate at 1,500 mg/day or less, lamotrigine at 300 mg/day or less. Only 37 patients were controlled on duotherapy, and one each on triple or quadruple therapy. If a patient fails the first drug because of adverse effects, the prognosis for remission is 48%. However, if a patient fails the first drug because of lack of efficacy, the prognosis for remission is only 21%.”

PRACTICAL VALUE

Jacqueline French, MD, Professor of Neurology at the University of Pennsylvania in Philadelphia, commented, “Dr. Brodie’s results are very important for the practitioner. For one thing, it allows them to give a realistic prognosis to the individual who is presenting with the first diagnosis of epilepsy. It also gives them a time frame after which they should begin a consideration of more aggressive therapy, which could include evaluation for surgery or the vagus nerve stimulator.”

Dr. French added, “Dr. Brodie presents a relatively gloomy picture for patients who have not gained control of seizures within three years. Since many of Dr. Brodie’s patients were diagnosed and treated before the advent of new antiepileptic drugs, it remains to be seen whether the newer drugs can improve the statistics.”

Dr. Brodie concluded, “The prognosis for the majority of people with newly diagnosed epilepsy, whether good or bad, becomes apparent within a few years of starting treatment. A patient who does not attain seizure control with the first two to three antiepileptic drug regimens is unlikely ever to have a useful period of remission and can be given a diagnosis of refractory epilepsy. These are the patients who should go to a specialist epilepsy program at least once. Sometimes patients may be surgical candidates or are on narrow-spectrum drugs when they should be on broad-spectrum drugs. Surgery is much better for the right patients than continuing medications.”

NR

—Andrew Wilner, MD

Suggested Reading
Kwan P, Brodie MJ. Drug treatment of epilepsy: when does it fail and how to optimize its use? CNS Spectr. 2004;9:110-119.

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