Within a year of treatment, drug therapy completely eliminates seizures in one of two patients with new-onset epilepsy and greatly reduces the frequency of seizures in another one of six; in one of three, however, seizures cannot be controlled by antiepileptic drugs (AEDs).

It is not well known how often drug resistance, a major clinical problem, occurs early or late in the course of epilepsy and how often epilepsy follows a continuous, remitting, or relapsing–remitting pattern. To provide evidence if, in fact, different patterns of evolution of drug resistance and remission exist, a prospective, long-term population-based study of 144 patients followed for 40 years (median) since their first seizure before the age of 16 was performed (1). At the end of the follow-up, 67% patients were in terminal 5-year remission, on or off AEDs, the remainder will never enter remission (19%), and 14% will have only transient periods of 5-year remission. In 16% of those with terminal remission, first remission continued uninterrupted, whereas half of those with terminal remission became seizure free only after a delay of 9 years, suggesting improvement over time. However, outcome may worsen over time in 14%, who entered one or more periods of 5-year remission but did not maintain remission at the end of follow-up. This outcome suggests that patients seem to fall broadly into three groups: (1) In 50% of patients, the seizure prognosis is good to excellent. This group includes those with self-limiting epilepsies with few seizures, for whom AEDs may not even be necessary for seizure control, and the first single AED controls the epilepsy; once seizure control is achieved, AEDs may be successfully tapered in many patients. Whether the AEDs suppress or affect the course of epilepsy in this group is unclear. (2) In another 10–20%, seizure prognosis is still good, but there may be a struggle to find the right AED. Seizure control may take years to achieve, and the relapse rate is high whether AEDs are withdrawn or not. Many need drug treatment for life. Surgery may improve the seizure outcome in this group. (3) Up to 30% carry a bad seizure prognosis with a continuous tendency to have seizures. AEDs seem to be palliative rather than suppressant, but new AEDs may improve outcome in some patients. Predictors of good outcome include less than weekly seizures prior to treatment and nonsymptomatic etiology.

An often-quoted study based on patients evaluated and treated in Glasgow, Scotland suggests that seizure refractoriness can be determined based on the patient’s response to the first two or three AEDs. Kwan and Brodie (2) found that of 470 patients who had never before received an AED, 301 (64%) became seizure free for at least 12 months during treatment. Of these patients, 113 discontinued the first drug because of lack of efficacy, 69 because of intolerable side effects, 29 because of idiosyncratic reactions, and 37 for other reasons. Only 79 of these 248 patients (32%) subsequently became seizure free. The outcome among these patients was strongly associated with the reason for the failure of the first drug. Another 12 (11%) of the patients in whom treatment with the first drug was ineffective subsequently became seizure free. Only 4% adequately responded to a third drug. Similarly, only 3% of patients responded to two drugs.

  1. M. Sillanpää and D. Schmidt, Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study, Brain 129 (2006), pp. 617–24.
  2. P. Kwan and M.J. Brodie, Early identification of refractory epilepsy, N Engl J Med 342 (2000), pp. 314–39.

Adapted from Elger CE, Schmidt D. Modern management of epilepsy. Epilepsy Behav 2008;12:501-39.

Authored by: Steven C. Schachter MD on 5/2008
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