Early Identification of Refractory Epilepsy

TLDR

More than 30 % of epilepsy patients have uncontrolled seizures, and the reasons and predictability of refractory epilepsy remain unclear, with epilepsy classified as idiopathic, symptomatic, or cryptogenic. The study aimed to identify factors predicting poor seizure control in newly diagnosed epilepsy patients by analyzing antiepileptic drug responses. A prospective cohort of 525 newly diagnosed patients (ages 9–93) was followed at a single center, with seizure freedom defined as no seizures for at least one year; 63 % remained seizure‑free during or after treatment. Patients with symptomatic or cryptogenic epilepsy, or with more than 20 seizures before treatment, had higher persistent seizure rates (40 % vs 26 % and 51 % vs 29 %, respectively), while seizure‑free rates were similar for established and new drugs; overall 47 % became seizure‑free on first drug, 14 % on second or third, and only 3 % required two drugs, indicating that a high seizure burden or poor initial response predicts refractory epilepsy.

Abstract

More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures.We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year.Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent).Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.