Generalized periodic discharges: Pathophysiology and clinical considerations

•Generalized periodic discharges are commonly encountered in metabolic encephalopathies and cerebral hypoxia.•We propose that a common mechanism is dysfunction of inhibitory interneurons.•Whether treatment with antiepileptic drugs is beneficial is unclear.

Generalized periodic discharges (GPDs) are commonly encountered in metabolic encephalopathy and cerebral hypoxia/ischemia. The clinical significance of this EEG pattern is indistinct, and it is unclear whether treatment with antiepileptic drugs is beneficial. In this study, we discuss potential pathophysiological mechanisms. Based on the literature, supplemented with simulations in a minimal computational model, we conclude that selective synaptic failure or neuronal damage of inhibitory interneurons, leading to disinhibition of excitatory pyramidal cells, presumably plays a critical role. Reversibility probably depends on the potential for functional recovery of these interneurons. Whether antiepileptic drugs are helpful for regaining function is unclear.This article is part of a Special Issue entitled “Status Epilepticus”.