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Open Access Publications from the University of California

Epilepsy as a dynamic disease: A Bayesian model for differentiating seizure risk from natural variability.

  • Author(s): Chiang, Sharon
  • Vannucci, Marina
  • Goldenholz, Daniel M
  • Moss, Robert
  • Stern, John M
  • et al.

Objective:A fundamental challenge in treating epilepsy is that changes in observed seizure frequencies do not necessarily reflect changes in underlying seizure risk. Rather, changes in seizure frequency may occur due to probabilistic variation around an underlying seizure risk state caused by normal fluctuations from natural history, leading to seizure unpredictability and potentially suboptimal medication adjustments in epilepsy management. However, no rigorous statistical approach exists to systematically distinguish expected changes in seizure frequency due to natural variability from changes in underlying seizure risk. Methods:Using data from, a patient-reported seizure diary tool containing over 1.2 million recorded seizures across 8 years, a novel epilepsy seizure risk assessment tool (EpiSAT) employing a Bayesian mixed-effects hidden Markov model for zero-inflated count data was developed to estimate changes in underlying seizure risk using patient-reported seizure diary and clinical measurement data. Accuracy for correctly assessing underlying seizure risk was evaluated through a simulation comparison. Implications for the natural history of tuberous sclerosis complex (TSC) were assessed using data from Results:EpiSAT led to significant improvement in seizure risk assessment compared to traditional approaches relying solely on observed seizure frequencies. Applied to TSC, four underlying seizure risk states were identified. The expected duration of each state was <12 months, providing a data-driven estimate of the amount of time a person with TSC would be expected to remain at the same seizure risk level according to the natural course of epilepsy. Significance:We propose a novel Bayesian statistical approach for evaluating seizure risk on an individual patient level using patient-reported seizure diaries, which allows for the incorporation of external clinical variables to assess impact on seizure risk. This tool may improve the ability to distinguish true changes in seizure risk from natural variations in seizure frequency in clinical practice. Incorporation of systematic statistical approaches into antiepileptic drug (AED) management may help improve understanding of seizure unpredictability as well as timing of treatment interventions for people with epilepsy.

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