Diagnostic misclassification in suspected new-onset seizures: a prospective study of non-epileptic paroxysmal events and age-dependent patterns

This is the authors' abstract. We don't add key points for this paper.

Objective Paroxysmal events resembling epileptic seizures frequently lead to diagnostic error and unnecessary treatment exposure. While non-epileptic paroxysmal events (NEPE) are recognized as common seizure mimics, the age-dependent structure of the differential diagnosis and patterns of antiseizure medication (ASM) exposure remain incompletely characterized. Methods We conducted a prospective national referral cohort study of consecutive patients referred for evaluation of suspected new-onset seizures. All patients underwent standardized clinical assessment, video-electroencephalography, and longitudinal follow-up. NEPE were classified into five predefined diagnostic subgroups, and multinomial logistic regression was used to model age-related diagnostic probabilities. Results Of 1,877 patients referred over 4 years, 428 (22.8%) were diagnosed with NEPE, including 305 pediatric and 123 adult cases. Syncope was the most frequent diagnosis (30.8%), followed by functional seizures (21.7%). Distinct age-dependent distributions of non-epileptic diagnoses emerged: infantile mimics (including breath-holding spells and Sandifer syndrome) predominated in early childhood, behavioral-movement phenomena peaked in childhood, functional seizures increased during adolescence and young adulthood, and syncope became progressively more prevalent with advancing age. Developmental delay was strongly associated with behavioral-movement diagnoses (OR 10.60, 95% CI 3.45–32.61). Pre-referral ASM exposure occurred in 102 patients (23.8%), with patients with functional seizures three times more likely to be treated before diagnostic clarification than those with syncope (adjusted OR 3.08, 95% CI 1.47–6.46). Significance NEPE follow predictable age-related distributions that may guide early clinical assessment. The high rate of ASM exposure prior to diagnostic clarification, particularly in functional seizures, highlights the clinical consequences of early misdiagnosis. Incorporation of age-based clinical reasoning may improve diagnostic accuracy and reduce unnecessary treatment exposure in patients with paroxysmal events.