Effects of antiepileptic drugs on interictal epileptiform discharges in focal epilepsies: an update on current evidence

Abstract

Interictal epileptiform discharges (IEDs), occurring in the electroencephalograms (EEG) of patients with focal epilepsy, are crucial for diagnosis, while their relationship with seizure severity and recurrence is controversial. The effects of antiepileptic drugs (AEDs) on IEDs are even more debated. In general, it is currently believed by experts in the field that most of the classical AEDs do not significantly affect IEDs occurrence in these patients, and that monitoring their EEG effects during treatment is useless. In this review, we update the existing literature on the effects of classical and newer AEDs on focal IEDs, emphasizing the scarcity of data concerning the latter. We also discuss potential limits of available clinical and experimental data and future perspectives.

Keywords:

• antiepileptic drugs
• electroencephalogram
• focal epilepsy
• hippocampal slices
• interictal epileptiform discharges
• temporal lobe epilepsy

Financial & competing interests disclosure

A Iudice has received research grants and consulting fees from Janssen, UCB, Eisai, Novartis, Biogen, Merck-Serono, Teva, Cyberonics and AIFA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Interictal epileptiform discharges (IEDs) occurring in the electroencephalograms (EEG) of patients with focal epilepsy are neurophysiological hallmarks playing a fundamental role in diagnosis.

• The first studies on the effects of antiepileptic drugs (AEDs) on IEDs date back to more than 40 years ago and were performed with the aim of assessing the potential use of IEDs as markers of seizure control. Many neurologists still continue to regularly prescribe, with this aim, routine EEGs to their patients with focal epilepsy.

• Concerning studies on the chronic effects of AEDs on focal IEDs, lamotrigine and topiramate have been shown to reduce IEDs, both in adults and children. Valproic acid might show a similar trend, but with conflicting results among studies. In children, a similar effect was observed also for levetiracetam, oxcarbazepine and vigabatrin. In adults, not only relatively newer AEDs such as gabapentin and vigabatrin but also classical AEDs such as phenytoin and carbamazepine have not shown a clear-cut effect on IEDs chronically.

• For most of those AEDs for which both the acute and the chronic effects on EEG of IEDs have been assessed, the chronic effects are in line with the acute ones.

• There are a number of IEDs experimental models in vitro, but they seem insufficient as yet to clarify in detail the mechanisms underlying IEDs onset, mainly because probably each one of them reproduces only partially the mechanisms of some of the IEDs substrates. Furthermore, thus far, experimental data have been obtained mainly in models of temporal lobe epilepsy, while there are not enough data on models of other common causes of focal epilepsy (e.g., postischemic/hemorrhagic).

• In any case, from our updated review of existing literature in patients, we confirm the opinion of many expert epileptologists concerning the role of EEG in patients with focal epilepsy treated with classical and relatively new AEDs. In these patients, repeating EEG and analyzing whether IEDs occurrence changes during AED treatment does not add any significant information in terms of seizure control, that is, a reduction/disappearance of IEDs does not seem to correlate with a reduction/disappearance of seizures.

• We emphasize that, for the newer AEDs, there are no (or are only very limited) recent data in patients concerning their effects on focal IEDs.

• Only developing more detailed experimental models and setting-up large, multicenter, controlled studies in focal epilepsy patients, designed ad hoc to address simultaneously the effect of different AEDs on both EEG and seizures, might provide evidence for the prognostic utility of EEG IEDs monitoring in different subcategories of patients under specific AED treatment.