Epileptic discharges are classified as generalized paroxysmal fast activity with low expert agreement: findings from an international survey
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Objective
The current International League Against Epilepsy (ILAE) guidelines for Lennox-Gastaut syndrome (LGS) mandate the presence of generalized paroxysmal fast activity (GPFA) on EEG. However, GPFA is not necessarily restricted to LGS and has been described in, among others, idiopathic generalized epilepsies. A clear definition for GPFA is currently lacking, hampering research into its utility as a diagnostic or treatment biomarker. Here, we assessed expert agreement in the interpretation of GPFA to explore feasibility of a consensus-based definition.
Methods
We internationally distributed a two-part survey on GPFA to EEG experts. First, participants completed thirteen questions gauging their preferred clinical and EEG criteria for GPFA, including duration, frequency, amplitude and topography. Second, participants classified the presence versus absence of GPFA in eleven EEG clips, while blinded to clinical context, from patients with LGS, other epilepsies, and physiological variants.
Results
162 respondents, predominantly from North America and Europe, completed the survey. 87% considered GPFA to also occur in epilepsies other than LGS. Considerable heterogeneity was present on defining duration, spectral frequency, amplitude and topographic distribution of GPFA. Particularly poor agreement was seen for lower limits of duration and frequency, with no single response option receiving a majority consensus (36% and 30% agreement, respectively). Similarly, the degree of agreement on interpretations was highly variable across real-world EEG clips.
Significance
Marked discrepancies exist in the EEG identification and clinical interpretation of GPFA, undermining its utility as a potential biomarker in research and clinical trials of LGS and other epilepsies. The findings also highlight the need to establish a consensus-based and eventually evidence-informed definition to formally operationalize the clinical and EEG criteria for GPFA.
Key points
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Generalized paroxysmal fast activity (GPFA) is variably defined in the literature, limiting its utility as a diagnostic or treatment biomarker
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In this international survey (n = 162 respondents, 25 countries) we found limited agreement on GPFA’s defining features and on interpretation of fast activity on EEG clips
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87% of respondents considered GPFA to occur in epilepsies other than Lennox-Gastaut syndrome
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Pending further elucidation of the pathophysiology underlying GPFA or its computational characterization (i.e., to inform a biologically-or evidence-based definition), we underscore the need for an interim consensus-based definition
