Abstracts

Rationale: Zonisamide (ZNS) is an antiepileptic drug that may have unfavorable effects on cognition. In spite of that, it is difficult to find electrophysiologic data describing the functional changes of the brain exerted by ZNS. The purpose of this study is to investigate the changes of brain current source density (CSD) of the high frequency band (22-30 Hz) of electroencephalography (EEG) background activity induced by ZNS monotherapy in patients with newly diagnosed epilepsy, and correlate the results with the neuropsychological outcome of the patients.Methods: We conducted a 24-week, open-labeled, prospective study of ZNS monotherapy in 19 patients with newly diagnosed epilepsy. Neuropsychological test (NP) and scalp EEG were done twice, at baseline and 24 weeks after starting medication. In NP, we evaluated List Learning, Immediate and Delayed Word Recall, Visual Reproduction, Forward and Backward Digital Span, Trail-Making Test Part A and B, and Verbal Fluency. Six patients were excluded due to the difficulty to select artifact free EEG segments. Thirteen patients with newly diagnosed epilepsy, who completed follow-up EEG and NP, were included in this study. The patients included 8 females and 5 males, with a mean age of 24.2 7.6 years (mean SD). The EEGs were recorded using 19 electrodes placed on the scalp according to the International 10-20 System. The sampling rate was 200 Hz. We applied a distributed source model using LORETA (low resolution brain electromagnetic tomography) to determine the changes of CSD of EEG background activity. We did a cross-spectral analysis and statistical nonparametric maps of high frequency beta band (22-30 Hz) between the pretreatment EEGs and post-treatment EEGs were obtained. We observed the results of NP and EEG current source analysis and tried to understand their relationship. Results: Among the items of NP, only the score of Verbal Fluency was significantly decreased after 24-week ZNS trial. The initial score was 17.2 3.0 (mean SD) and the score after 24-week ZNS trial was 13.4 4.6 (p = 0.004). The CSD in the 22-30 Hz band of EEG background activity decreased in the superior-middle-inferior frontal and anteiror cingulate gyrus, and insula of the right cerebral hemisphere, and in the superior frontal and anterior cingulate gyrus of the left hemisphere. Conclusions: The CSD changes suggest that ZNS may diminish the activity of the neuronal networks in the frontal and anterior cingulate gyrus in both cerebral hemispheres, and the insula of the right hemisphere. The decrement of Verbal Fluency observed after the ZNS monotherapy trial in the patients with newly diagnosed epilepsy may be associated with the functional decline in the anterior cingulate gyrus of the left cerebral hemisphere.