Zonisamide Decreases Current-Source Density of High Beta Frequency of Electroencephalogram

Abstract

Background and Purpose:The purpose of this study was to investigate changes in brain current-source density (CSD) of the high frequency band (22–30 Hz) induced by zonisamide (ZNS) in patients with newly diagnosed epilepsy and to correlate with the cognitive performances.Methods:We conducted a 24-week, open-labeled, prospective study in 19 patients. Eelectroencephalography (EEG) and neuropsychological tests (NPs) were conducted at baseline and 24 weeks after starting the medication. Six patients were excluded due to artifacts in EEG. One patient did not attend follow-up studies. Twelve patients who completed follow-up EEG and NPs were included. We used low-resolution brain electromagnetic tomography to determine CSD, and we obtained statistical nonparametric maps for the high beta frequency band (22–30 Hz) between pretreatment EEGs and post-treatment EEGs.Results:The CSD in the 22–30 Hz band decreased in the superior frontal, middle frontal, anterior cingulate, precentral, postcentral, and inferior parietal gyri of the left hemisphere, and the middle frontal, inferior frontal and anterior cingulate gyri of the right hemisphere. Among the NPs items, the performance of verbal fluency was significantly impaired after the 24-week ZNS trial.Conclusions:The CSD changes suggest ZNS may diminish the activity of cerebral networks related to verbal fluency.

Imaging Biomarkers of Anti-Epileptic Drug Action: Insights from Magnetic Resonance Imaging

“…As described for TPM, zonisamide also exhibits a sulpha moiety and weak carbon anhydrase inhibition properties, estimated as 100-1000 times lower than acetazolamide (Leppik, 2004). A recent electroencephalography (EEG) study on individuals taking zonisamide for recent-onset epilepsy reported reduced current source density of beta frequencies for areas implicated in language and working memory, such as inferior and middle frontal cortices, anterior cingulate gyri and inferior parietal lobules (Kwon and Park, 2013). In a retrospective analysis of verbal fluency fMRI, comparing patients taking Topiramate (n=32), Zonisamide (51) and Levetiracetam (62) (Wandschneider et al, 2017), we observed a similar influence of zonisamide and TPM on fronto-parietal cognitive networks in patients with focal epilepsy, as measured by verbal fluency fMRI.…”

Effect of topiramate and zonisamide on fMRI cognitive networks

“…Only one study investigated potential pathomechanisms of cognitive impairment due to ZNS, describing decreased current-source density of high beta frequency in regions relevant to language and working memory during a verbal fluency task. 9 All of the above studies are hampered by small sample sizes.…”

Apathy in people with epilepsy and its clinical significance: A case-control study

“…Some AEDs resulted in dysfunction of these regions when cognitive tasks were given. Executive dysfunction with topiramate (TPM) or zonisamide (ZNS) was demonstrated by functional MRI (fMRI) and current-source density of electroencephalogram (EEG) [38,39]. Because TPM and ZNS have multiple modes of action including GABAergic activity, we suggest any AED affecting these regions can cause apathy as well as cognitive dysfunction.…”