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

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dc.citation.firstpage236en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitleEpilepsia Openen_US
dc.citation.lastpage246en_US
dc.citation.volumeNumber3en_US
dc.contributor.authorChiang, Sharonen_US
dc.contributor.authorVannucci, Marinaen_US
dc.contributor.authorGoldenholz, Daniel M.en_US
dc.contributor.authorMoss, Roberten_US
dc.contributor.authorStern, John M.en_US
dc.date.accessioned2019-12-06T15:32:20Zen_US
dc.date.available2019-12-06T15:32:20Zen_US
dc.date.issued2018en_US
dc.description.abstractObjective: 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 SeizureTracker.com, 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 SeizureTracker.com. 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.en_US
dc.identifier.citationChiang, Sharon, Vannucci, Marina, Goldenholz, Daniel M., et al.. "Epilepsy as a dynamic disease: A Bayesian model for differentiating seizure risk from natural variability." <i>Epilepsia Open,</i> 3, no. 2 (2018) Wiley: 236-246. https://doi.org/10.1002/epi4.12112.en_US
dc.identifier.digitalChiang_et_al-2018-Epilepsia_Openen_US
dc.identifier.doihttps://doi.org/10.1002/epi4.12112en_US
dc.identifier.urihttps://hdl.handle.net/1911/107785en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subject.keywordSeizure risken_US
dc.subject.keywordBayesian inferenceen_US
dc.subject.keywordEpilepsyen_US
dc.subject.keywordHidden Markov modelen_US
dc.subject.keywordMixed effectsen_US
dc.subject.keywordNatural historyen_US
dc.subject.keywordSeizure diary dataen_US
dc.subject.keywordTuberous sclerosis complexen_US
dc.subject.keywordZero‐inflated Poissonen_US
dc.titleEpilepsy as a dynamic disease: A Bayesian model for differentiating seizure risk from natural variabilityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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