Abstracts

Patients with mitochondrial (MT) electron transport chain (ETC) dysfunction and seizures often express progressive cognitive decline. When both processes are present, the contributions of the ETC dysfunction and/or antiseizure medication (AEDs) on cognitive decline are unclear. Simplfying the seizure medication regimen in this population may improve cognitive status and reveal a nonprogressive state.
Two females, aged 8 years (patient 1) and 17 years (patient 2), presented with status epilepticus. Both were treated with seizure medications and underwent testing for possible MT ETC dysfunction. Muscle biopsies were assayed for both common MT DNA mutations and enzymatically for ETC activity. Once seizure control (clinical seizure freedom) was obtained, both underwent neuropsychological testing (NPT). NPT was repeated after simplifying AEDs, 18 months later (patient 1) and 8 months later (patient 2).
Both patients obtained A and B grades in school prior to seizure onset. Both presented in status epilepticus; patient 1 with atypical absence and patient 2 with epilepsia partialis continua. Both demonstrated a pronounced decrease in school performance after seizure control, and families noticed cognitive decline. Both were initially tested on polytherapy, including topiramate, and retested on lamotrigine monotherapy. Patient 1 had ETC dysfunction in complex III ([lt] 15% of control activity) without MT DNA mutation. Initial seizure control was achieved on therapeutic levels of toprimate and valproic acid, later switched to lamotrigine monotherapy. Full Scale IQ increased from 94 to 102, Verbal IQ from 107 to 118, and Performance IQ from 81 to 84. An overall memory score increased from 93 to 116, with the greatest improvement in story recall. Patient 2 had ETC complex III dysfunction ([lt]20% of control activity) as well as 5 kb deletions in the MT DNA. She was initially on therapeutic levels of topiramate and phenytoin, and later changed to lamotrigine. Full Scale IQ increased from 69 to 81, Verbal IQ from 75 to 85, and Performance IQ from 68 to 80. All verbal and nonverbal subtest scores increased slightly with the best improvement in Matrix Reasoning (4 points). NPT showed the best improvement on Trails B (reduction from 148 to 81 seconds).
Two patients with ETC dysfunction demonstrated cognitive decline by decrease in school performance and by family assessment. Both showed NPT and functional improvement after AED simplification. Although seizures remained controlled, alteration of AEDs suggested that some of the cognitive decline was due to AED side effect as opposed to ETC dysfunction. Efforts to maintain seizure control on minimal AEDs should be pursued in this patient population.