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Response to first drug trial predicts outcome in childhood temporal lobe epilepsy

From the Pediatric Regional Epilepsy Program (Dr. Dlugos), Division of Neurology, Children’s Hospital of Philadelphia; and Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology (Drs. Dlugos, Sammel, Strom, and Farrar), University of Pennsylvania School of Medicine, Philadelphia, PA.

Address correspondence and reprint requests to Dr. D.J. Dlugos, Pediatric Regional Epilepsy Program, Division of Neurology, Children’s Hospital of Philadelphia, 34th St. and Civic Center Blvd., Wood Bldg. 6th fl., Philadelphia, PA 19014; e-mail: dlugos{at}email.chop.edu

Objective: To construct a clinical prediction model for the early identification of children destined to develop refractory temporal lobe epilepsy (TLE) 2 years after epilepsy onset.

Methods: Patients with TLE between 1 and 18 years old seen in the Division of Neurology at Children’s Hospital of Philadelphia during 1999 were identified through billing records and chart review. Data were abstracted independently on 5 candidate predictor variables for refractory TLE and on seizure frequency outcome at 2 years after epilepsy onset.

Results: One hundred twenty patients met inclusion criteria and had at least 2 years of follow-up. Forty-five of 120 patients (37.5%) had refractory TLE at 2 years after onset, and 75 of 120 (62.5%) were seizure free. Three significant predictors of refractory TLE were found on bivariate analysis: an early risk factor for epilepsy (risk ratio = 3.5 [95% CI 2.2, 5.6]), temporal lobe abnormality on MRI scan (2.9 [95% CI 1.9, 4.6]), and failure of the first antiepileptic drug (AED) trial (16.5 [95% CI 6.3, 43.9]). Logistic regression indicated that the best model to predict refractory TLE contained only the variable "failure of first AED trial," with a positive predictive value of 0.89 (95% CI 0.76, 0.96) and negative predictive value of 0.95 (95% CI 0.87, 0.99) to predict "refractory TLE" at 2 years.

Conclusions: Failure of first AED trial accurately predicts refractory TLE at 2 years after onset, based on retrospective cohort data in children. If verified prospectively and with longer follow-up, this finding should support earlier consideration of surgical options.

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