Abstracts

Rationale: Epilepsy with myoclonic-atonic seizures (MAE), or Doose Syndrome, is an electroclinical syndrome in which development, neurological examination, and imaging is normal prior to the onset of seizures of generalized onset between 7 months and 6 years of age. The EEG shows theta activity in the parietal regions with interictal generalized or multifocal polyspike/spike and slow wave discharges. Valproic acid, zonisamide, levetiracetam, felbamate and ketogenic diet are considered effective treatments for MAE whereas carbamazepine (CBZ), oxcarbazepine (OXC), phenytoin (PHT), and lamotrigine (LTG) are often thought to exacerbate seizures . We hypothesized that early exposure to CBZ, OXC, PHT, or LTG might have a negative impact on the ability of later appropriate therapies to control seizures and preserve development. Methods: Patients with MAE were identified by a keyword search for MAE in the database of all video-EEG recordings performed at our center from 2002-2012. The diagnosis of MAE was confirmed by a review of all clinical information. Bad outcome was defined as either or both persistent seizures or poor cognition despite multiple appropriate trials of AEDs or ketogenic diet. Good outcome was defined as complete control of seizures and normal developmental course or mild delays only. Results: Retrospective chart review identified 73 patients with confirmed MAE (43 boys and 30 girls). The ages of onset of epilepsy ranged from 3 months to 5 years. 20 patients (14 boys; 6 girls) had a "bad" and 53 had "good" outcomes. "Bad" outcomes occurred in 16/29 (55%) of children previously treated with one or more of CBZ, OXC, PHT or LTG and in 4/44 (9 %) of those who had never been treated with any of those four drugs (p<0.0001). In the "bad" outcome group, 3 of the children continued to have only persistent seizures, 1 had significant cognitive impairment alone and 16 had both persistent seizures and poor developmental course. The children in this " bad" outcome group with persistent seizures had either multiple seizures per week or multiple daily seizures, ranging from 50 absence seizures per day to six convulsions per night. Conclusions: Our retrospective review suggests that worse clinical outcome in MAE is associated with early exposure to CBZ, OXC, PHT, and LTG. These findings raise the possibility that these drugs may actually worsen the prognosis in MAE and underscore the importance of early and accurate diagnosis of childhood electroclinical syndromes and of selecting appropriate and effective treatments early in the course in order to improve long-term outcomes.