Summary Objective Low-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost. Methods Based on data from 1,365 adult patients with video-electroencephalography confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizure-like events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database. Results Our model differentiated PNES only from ES only with a prospective accuracy of 78% (95% CI 72–84%) and AUC of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain and migraines (p<0.01). Comorbidities associated with ES were diabetes mellitus and non-metastatic neoplasm (p<0.01). The population-level analysis suggested that patients with mixed PNES plus ES may be a distinct population from patients with either condition alone. Significance An accurate patient-reported past medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication and medical history in the context of the seizure description and history.

Our promising results suggest that an objective score has the potential to serve as an early outpatient screening tool to identify patients with greater likelihood of 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 for women during childbearing years and plateauing outside those years that was not observed in men.

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