Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials

Abstract

Purpose The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Methods Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Results Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=−0.9, p=0.38). Conclusion Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials.

Identifying psychogenic seizures through comorbidities and medication history

“…This suggests that when seizures were epileptic, providers and patients attempted to control seizures with ASMs longer prior to referral, even though current international league against epilepsy (ILAE) guidelines recommend referral after failure of 2 ASMs 32 . Accordingly, more ASM trials in PNES was associated with longer delay to diagnosis 2 . These data suggest that a substantial proportion of patients with medication refractory seizures of both epileptic and psychogenic types are not being referred in a timely fashion.…”

“…However, this score has limited specificity and should be interpreted in the appropriate clinical context. We emphasize the ILAE guideline that irrespective of hypothesized seizure etiology any patient who has failed appropriate doses of two appropriately chosen ASMs should be referred for evaluation at an epilepsy center 2; 32 .…”

“…A recent study of time from first seizure to diagnosis of PNES at our center revealed an average of 8.4 years 2 , but this delay is exponentially distributed, varies substantially across centers and has been reported to be as short at 18 months in some pediatric populations 3; 4 . During this diagnostic delay, the direct and indirect cost of psychogenic seizures is similar to medication resistant epileptic seizures: 21,000 euros/22,500 US dollars annually 5; 6 .…”

Diagnostic implications of review-of-systems questionnaires to differentiate epileptic seizures from psychogenic seizures

“…Accurately characterizing the subtype of seizures in each patient helps physicians choose a medication that is most likely to reduce or eliminate seizures, and avoid the unnecessary risks of medications that are not likely to be effective [2, 4–6]. Despite this, 50–90% of patients diagnosed ultimately with PNES were treated initially with anti-seizure medications (ASMs) [3, 7], potentially delaying time to definitive diagnosis [8] while exposing patients to iatrogenic adverse effects. The most effective treatment of PNES is cognitive-behavioral-informed therapy to address the underlying psychological stressors that contribute to their seizures [9, 10].…”

“…Diagnosing PNES earlier results in reduced cost and better short and long-term seizure control [2, 4, 5, 11, 12]. Unfortunately, the average delay from first seizure to diagnosis of PNES is over 8 years [8]. Given this clinical scenario, high quality, low cost and objective screening tools to identify patients at risk for PNES are needed.…”