Abstracts

Rationale: Prior studies found an association between disruptions of cognitive task performance and the presence of focal interictal epileptiform discharges (IEDs). There is evidence suggesting that levetiracetam (LEV) reduces IED activity. It is unknown, however, if treatment of IEDs improves cognition. This study tests the hypotheses that LEV will decrease the frequency of focal IEDs and that treatment of the discharges will improve cognitive task performance. Methods: This pilot study is a non-randomized, open label trial. Subjects include adults newly diagnosed with focal-onset epilepsy who are treatment-naïve (Table 1). Participants are placed on LEV monotherapy for 11 weeks, titrated to 1500mg bid. Subjects undergo EEG recording with concurrent cognitive testing pre-and post-treatment. IEDs are quantified by the number and duration of spikes and sharps, averaged per unit time of the recording period. Subjects have either infrequent (<1 IED/min) or frequent (≥1 IED/min) discharges. The neuropsychological (NP) test battery includes measures of memory, executive function, attention and psychomotor speed. Questionnaires regarding quality of life, mood and side effects are also administered at each testing session (Table 2). Healthy adults, untreated with anticonvulsants, complete the same EEG/NP testing procedures to control for practice effects. Results: In this preliminary analysis, a Wilcoxon signed-ranks test indicated no change in IED frequency, IED duration or NP task performance in those with epilepsy and infrequent IEDs tested pre- and post-treatment. Nor were there any significant changes in measures of mood, adverse events or quality of life. The control subjects did not demonstrate any IEDs on EEG and had no notable changes in NP task performance. Results to date suggest baseline deficits in those with frequent IEDs. The subject with the most frequent IEDs demonstrated the lowest baseline NP test scores on several measures involving executive function, attention, verbal fluency and word recognition. Conclusions: The present results demonstrate the feasibility of subject recruitment. All subjects with epilepsy were placed on LEV monotherapy without breakthrough CPS or GTC seizures during the study period. One subject had continued simple partial seizures of slightly decreased frequency. Rapidity of titration was a common factor guiding medication choice. In subjects without frequent IEDs, there were no significant differences in NP test performance when comparing pre- and post-treatment scores. The subject with the most frequent IEDs demonstrated the lowest baseline NP test scores across many tasks, supporting the notion that focal IEDs may impair cognition more broadly. Recruitment and data collection are ongoing. This study is supported by a grant from the UCB Young Investigators Research Program.