Abstracts

Rationale: Psychogenic non-epileptic seizures (PNES) has been associated with a history of sexual abuse, mild traumatic brain injury, and other significant historical events, but there is a long delay to diagnosis of PNES during which patients are treated as if they have epileptic seizures. Therefore, novel, low-cost and objective tools based on these factors may assist in early identification of patients at risk for PNES. Methods: Based on data from 1,375 patients with video-electroencephalography (vEEG) confirmed diagnoses, we used logistic regression to compare the frequency of specific patient-reported historical events, demographic information, age of onset and delay from first seizure until vEEG in five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of this information to differentiate PNES only from ES only, we used multivariate piecewise-linear logistic regression trained using retrospective data from chart review and validated based on data from 246 prospective standardized interviews. Results: The prospective area under the curve of our weighted multivariate piecewise-linear by-sex score was 73%, with the threshold that maximized overall retrospective accuracy resulting in a prospective sensitivity of 74% (95% CI 70-79%) and prospective specificity of 71% (95% CI 64-82%). The linear model and piecewise linear without an interaction term for sex had very similar performance statistics. In the multivariate piecewise-linear sex-split predictive model, the significant factors positively associated with ES were a history of febrile seizures, current employment or active student status, history of traumatic brain injury, and longer delay from first seizure until VEEG. The significant factors associated with PNES were female sex, older age of onset, concussion, significant stressful events with sexual abuse, in particular, increasing the likelihood of PNES. Delays longer than 20 years, age of onset higher than 31 years for men, and age of onset higher than 40 years for women had no additional effect on the likelihood of PNES. Conclusions: Our promising results suggest that our objective score has the potential to serve as an early outpatient screening tool to identify patients with PNES when considered in combination with other factors. In addition, our analysis suggests that sexual abuse, more than other psychological stressors including physical abuse, is more associated with PNES. There was a trend of increasing frequency of PNES was seen for women during childbearing years and plateauing outside those years that was not observed in men, suggesting a possible role for cumulative female sex hormone exposure in the onset of PNES. Funding: This work was supported by the UCLA-California Institute of Technology Medical Scientist Training Program (NIH T32 GM08042), the Neuroimaging Training Program (NIH T90 DA022768, R90 DA022768 & R90 DA023422 to MSC), the William M. Keck Foundation, research grants to JE (NS03310 & NS080181), and the UCLA Departments of Psychiatry & Biobehavioral Sciences and Biomathematics.