Nonepileptic seizures: an updated review

Abstract

Psychogenic nonepileptic seizures (PNES) are a functional neurological disorder/conversion disorder subtype, which are neurobehavioral conditions at the interface of neurology and psychiatry. Significant advancements over the past decade have been made in the diagnosis, management, and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions, and outcome studies. Epidemiology and healthcare utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid in the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES; these should be assessed in diagnostic evaluations and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot, multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy-informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control, and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders.

Keywords: cognitive behavioral therapy; conversion disorder; fMRI; functional neurological disorder; neuroimaging; psychogenic nonepileptic seizures; sertraline.

Figures

Figure 1. Display of volumetric and resting-state functional connectivity (FC) findings in Psychogenic Nonepileptic Seizures (PNES) neuroimaging studies

Left panel displays peak coordinates of cortical thickness and voxel-based morphometry findings in PNES vs. healthy controls,. Right panel shows peak coordinates of abnormal resting-state FC in individuals with PNES vs. healthy controls,,,. Blue circles indicate decrease and red circles indicate increase. Evidence from neuroimaging studies, while requiring replication and further investigations, suggests that PNES may potentially develop in the context of alterations within and across brain networks implicated in sensori-motor (e.g. pre- and post-central gyrus, premotor regions), emotion processing/regulation (e.g. anterior cingulate cortex (ACC), middle cingulate cortex (MCC), orbitofrontal cortex, insula), cognitive control (e.g. lateral prefrontal cortex, dorsal ACC, MCC), and multimodal integration functions (e.g. cingulate gyrus, posterior parietal cortex, precuneus). Only main findings are displayed using Caret 5. Cerebellar and basal ganglia foci, and seed region coordinates are not shown.