Browsing by Author "Moss, Robert"

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    A Bayesian switching linear dynamical system for estimating seizure chronotypes
    (National Academy of Sciences, 2022) Wang, Emily T.; Vannucci, Marina; Haneef, Zulfi; Moss, Robert; Rao, Vikram R.; Chiang, Sharon
    Epilepsy is a disorder characterized by paroxysmal transitions between multistable states. Dynamical systems have been useful for modeling the paroxysmal nature of seizures. At the same time, intracranial electroencephalography (EEG) recordings have recently discovered that an electrographic measure of epileptogenicity, interictal epileptiform activity, exhibits cycling patterns ranging from ultradian to multidien rhythmicity, with seizures phase-locked to specific phases of these latent cycles. However, many mechanistic questions about seizure cycles remain unanswered. Here, we provide a principled approach to recast the modeling of seizure chronotypes within a statistical dynamical systems framework by developing a Bayesian switching linear dynamical system (SLDS) with variable selection to estimate latent seizure cycles. We propose a Markov chain Monte Carlo algorithm that employs particle Gibbs with ancestral sampling to estimate latent cycles in epilepsy and apply unsupervised learning on spectral features of latent cycles to uncover clusters in cycling tendency. We analyze the largest database of patient-reported seizures in the world to comprehensively characterize multidien cycling patterns among 1,012 people with epilepsy, spanning from infancy to older adulthood. Our work advances knowledge of cycling in epilepsy by investigating how multidien seizure cycles vary in people with epilepsy, while demonstrating an application of an SLDS to frame seizure cycling within a nonlinear dynamical systems framework. It also lays the groundwork for future studies to pursue data-driven hypothesis generation regarding the mechanistic drivers of seizure cycles.
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    Bayesian non-homogeneous hidden Markov model with variable selection for investigating drivers of seizure risk cycling
    (Project Euclid, 2023) Wang, Emily T.; Chiang, Sharon; Haneef, Zulfi; Rao, Vikram R.; Moss, Robert; Vannucci, Marina
    A major issue in the clinical management of epilepsy is the unpredictability of seizures. Yet, traditional approaches to seizure forecasting and risk assessment in epilepsy rely heavily on raw seizure frequencies which are a stochastic measurement of seizure risk. We consider a Bayesian nonhomogeneous hidden Markov model for unsupervised clustering of zero-inflated seizure count data. The proposed model allows for a probabilistic estimate of the sequence of seizure risk states at the individual level. It also offers significant improvement over prior approaches by incorporating a variable selection prior for the identification of clinical covariates that drive seizure risk changes and accommodating highly granular data. For inference, we implement an efficient sampler that employs stochastic search and data augmentation techniques. We evaluate model performance on simulated seizure count data. We then demonstrate the clinical utility of the proposed model by analyzing daily seizure count data from 133 patients with Dravet syndrome collected through the Seizure TrackerTMTM system, a patient-reported electronic seizure diary. We report on the dynamics of seizure risk cycling, including validation of several known pharmacologic relationships. We also uncover novel findings characterizing the presence and volatility of risk states in Dravet syndrome which may directly inform counseling to reduce the unpredictability of seizures for patients with this devastating cause of epilepsy.
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    Epilepsy as a dynamic disease: A Bayesian model for differentiating seizure risk from natural variability
    (Wiley, 2018) Chiang, Sharon; Vannucci, Marina; Goldenholz, Daniel M.; Moss, Robert; Stern, John M.
    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 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.