Quantifying the burden of generalized tonic‐clonic seizures in patients with drug‐resistant epilepsy

Abstract

Objective: Compared to other seizure types, generalized tonic-clonic (GTC) seizures may be disproportionately related to increased morbidity, and reducing seizure frequency could translate into improvements across measures of morbidity in medically treated patients with drug-resistant epilepsy (DRE). The primary objective of this analysis was to quantify the burden of patients with DRE who experience GTC seizures (GTC+) compared to patients with DRE who do not experience GTC seizures (GTC−). Methods: Adult patients from the Cleveland Clinic Epilepsy Center-Neurological Institute from 2012-2016 with DRE with epilepsy for at least 1 year were eligible for inclusion and were divided into GTC ± groups based on whether the patient had experienced a GTC seizure in the year preceding the first visit. Epilepsy duration, comorbidities, antiepileptic drug use, patient-reported outcomes (PROs) and seizure type, frequency, and etiology were captured. Generalized linear models, negative binomial regression, logistic regression, and linear regression were used as appropriate for multivariate analyses. Results: A total of 379 patients met inclusion criteria and had data at 1-year followup after their baseline visit (192 GTC+ and 187 GTC−). Although DRE patients experiencing GTC seizures had fewer seizures per day over the preceding 6 months than those not experiencing GTC seizures, seizure severity and levels of depression and anxiety were greater. GTC+ patients who reported five or more seizures in the preceding 4 weeks had 82% lower odds (1−0.18 = 0.82) of working than patients with no seizures. Significance: Patients with DRE experience a significant burden and decreased quality of life. Multivariate analysis is necessary to understand the complex relationship between seizure type, frequency, and impact on health-related quality of life (HRQoL) and changes over time. Effective treatments to reduce the burden for DRE patients who experience GTC seizures continue to be needed.

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“…Sheikh et al observed that their cohort of patients with generalized tonic-clonic seizures had significantly higher levels of depression and anxiety and a lower quality of life compared with those who did not have generalized tonic-clonic seizures, even if the seizure frequency was less than those without generalized tonic-clonic seizures. 20 It would be of interest to know if these psychiatric comorbidities preceded the onset of generalized tonic-clonic seizures, as observed in our study.…”

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“… 40 , 133 , 134 The burden of epilepsy could also vary according to the type of seizure, given that generalized tonic-clonic seizures, even though less frequent, are associated with more severe seizure-related complications and are associated with increased risk of depression and anxiety. 135 For children and adolescents, a close relation exists between QOL and cognitive impairment, particularly attention deficit. 82 , 136 In adults, specific data are scarce but point to the same direction, 137 particularly the relation with cognitive impairment and treatment adverse events.…”