Using Semiology to Classify Epileptic Seizures vs Psychogenic Nonepileptic Seizures: A Meta-analysis

A misdiagnosis of psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) is common. In the absence of the diagnostic gold standard (video EEG), clinicians rely on semiology and clinical assessment. However, questions regarding the diagnostic accuracy of different signs remain. This meta-analysis aimed to evaluate the diagnostic accuracy of semiology in PNES and ES.

We systematically searched PubMed, PsycInfo, and Medline for original research publications published before 8 February 2021 with no restriction on search dates to identify studies that compared semiology in ES and PNES in epilepsy monitoring units. Non-English publications, review articles, studies reporting on only PNES or ES, and studies limited to patients with developmental delay were excluded. Study characteristics and proportions of event groups and patient groups demonstrating signs were extracted from each article. A bivariate analysis was conducted, and data were pooled in a random effects model for meta-analysis. The I ² statistic was calculated to assess statistical heterogeneity. The revised Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the risk of bias in included studies. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were calculated. A PLR >10 or an NLR <0.1 largely affected the posttest probability of a diagnosis (ES or PNES), whereas a PLR between 5 and 10 or an NLR between 0.1 and 0.2 moderately affected the posttest probability of a diagnosis (ES or PNES).

The meta-analysis included 14 studies comprising 800 patients with ES and 452 patients with PNES. For PNES, ictal eye closure (PLR 40.5 95% confidence interval [CI] 16.2-101.3; I ² = 0, from 3 studies) and asynchronous limb movements (PLR 10.2; 95% CI 2.8-37.7; I ² = 0, from 3 studies) reached a PLR threshold >5. No single sign reached a PLR threshold >5 for ES.

While all signs require an interpretation in the overall clinical context, the presence of ictal eye closure and asynchronous limb movements are reliable discriminative signs for PNES.