Review The effect of antiepileptic drugs on epileptiform discharges in genetic generalized epilepsy: A systematic review Claire Gunawan a,b , Udaya Seneviratne b,c, ⁎, Wendyl D'Souza a,b a St Vincent's Clinical School, The University of Melbourne, Melbourne, Australia b Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia c Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia abstract article info Article history: Received 22 December 2018 Revised 2 February 2019 Accepted 14 April 2019 Available online xxxx Objective: The objective of this study was to evaluate the current evidence regarding the effect of antiepileptic drugs (AEDs) on epileptiform discharge (ED) burden in genetic generalized epilepsy (GGE). Methods: We conducted a comprehensive literature search of PubMed, Embase, PsycINFO, and the Web of Sci- ence Core Collection databases using the keywords ‘genetic generalized epilepsy’, ‘antiepileptic drugs’ and ‘epi- leptiform discharge’. Primary human studies published in English that reported the effect of AEDs on EDs captured on electroencephalogram (EEG) recordings of at least 24 h in duration in patients with GGE were in- cluded. Results: Six studies published between 1984 and 2017, which reported the effect of AEDs on EDs, involving a total of 116 patients with GGE, were analyzed. Our systematic review found a tendency for AEDs to reduce ED density, frequency, cumulative duration, and burst duration in GGE. Furthermore, we found evidence that the AED-medi- ated reduction in ED burden was associated with improved seizure control and cognitive outcomes. Conclusions: Antiepileptic drugs tend to reduce ED burden in GGE, but the significance of this association remains uncertain. © 2019 Elsevier Inc. All rights reserved. Keywords: Antiepileptic drugs EEG Generalized epilepsy Treatment response Seizure control Cognition 1. Introduction Conventionally, patient- or third party-reported seizure frequency is used to measure response to antiepileptic drugs (AEDs) [1]. However, patients are often unaware of seizures and epileptiform discharges (EDs) when they occur [2,3]. Therefore, ED burden in the electroen- cephalogram (EEG) rather than reported seizure frequency may be a more reliable measure of disease burden [4–9]. Additionally, ED burden may be a better estimate of prognosis including cognitive deficits [7,10– 12]. For those reasons, long-term EEG recordings measuring ED burden may potentially offer a more objective biomarker of prognosis and clin- ical response after AED initiation [13,14]. However, little is known about the quantitative effect of AEDs on EDs in both focal and generalized ep- ilepsies. Because of pathophysiologic differences in the generation of EDs, the value of it as a biomarker in focal and generalized epilepsies has to be studied separately. We pooled the studies based on EEGs recorded for at least 24 h to re- port the effect of AEDs on EDs in genetic generalized epilepsy (GGE) in order to answer the question ‘Do AEDs reduce the ED burden in GGE?’. Current evidence regarding AED-mediated changes in ED density, frequency, cumulative duration, and ED burst duration in GGE was eval- uated. We aimed to identify gaps and limitations in the current litera- ture that can guide future research regarding AED-mediated changes in EDs in GGE. Our review also addresses the use of EEG features as bio- markers of seizure control and prognosis including cognitive outcomes. Finally, it focuses on the use of 24-hour ambulatory EEGs in the mea- surement of treatment response. We hope that results of this systematic review will help design future research in this field. 2. Methods We conducted a comprehensive literature search of PubMed, Embase, PsycINFO, and the Web of Science Core Collection databases from their inception to February 2018 using the search strategy de- scribed in Table 1. In brief, key search words included variations and synonyms of the terms ‘idiopathic generalised epilepsy’, ‘antiepileptic drugs’, and ‘epileptiform discharges’. Boolean operators were used to combine the search terms. We formulated this systematic review based on the Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [15,16]. Primary human studies published in English that reported the effect of AEDs on EDs, captured on EEG recordings of at least 24 h in duration in patients with GGE, were included. The EEG recordings of at least 24 h were chosen to account for the circadian variations in EDs in GGE [17– Epilepsy & Behavior 96 (2019) 175–182 ⁎ Corresponding author at: Department of Medicine, St Vincent's Hospital Melbourne, PO Box 2900, Fitzroy 3065, Victoria, Australia. E-mail address: udaya.seneviratne@monash.edu (U. Seneviratne). https://doi.org/10.1016/j.yebeh.2019.04.030 1525-5050/© 2019 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh