Diagnosis switching and outcomes in a cohort of patients with potential epilepsy with myoclonic-atonic seizures

Abstract

Introduction: There is overlap in the electroclinical features of many childhood epilepsy syndromes, especially those presenting with multiple seizure types, such as epilepsy with myoclonic-atonic seizures (EMAS) and Lennox-Gastaut syndrome (LGS). This study aimed to determine the frequency of diagnosis switching and the factors influencing epilepsy syndrome diagnosis in a cohort of children with possible EMAS, as well as to explore the relationship between epilepsy syndrome diagnoses, key electroclinical features, and clinically relevant outcomes.

Methods: This is a cross-sectional retrospective chart review of children treated at the Children's Hospital of Colorado with a potential diagnosis of EMAS.

Results: There were 77 patients that met eligibility criteria, including 39% (n = 30) with an initial diagnosis of EMAS and 74% (n = 57) with a final diagnosis of EMAS. On average, for the 65% of patients who received more than one epilepsy diagnosis, the first, second, and third diagnoses were received within one year, three years, and ten years after epilepsy onset, respectively. Final diagnosis was significantly related to obtaining at least a six-month period of seizure freedom, p = 0.03. Classic LGS traits, including paroxysmal fast activity, slow spike-and-wave, and tonic seizures were present in 50% of the overall cohort, although a minority of these patients had a final diagnosis of LGS. However, the presence of more LGS traits was associated with a higher likelihood of ongoing seizures. Adjusted for age of epilepsy onset, seizure freedom was half as likely for every additional LGS trait observed (0.49[0.31, 0.77], p = 0.002).

Conclusion: Current epilepsy syndrome classification has reduced applicability due to overlapping features. This results in diagnosis switching and limited prognostic value for patients with an overlapping clinical phenotype. Future studies should attempt to stratify patients based not only on epilepsy syndrome diagnosis, but also on the presence of various electroclinical traits to more accurately predict outcome.

Keywords: Epilepsy with myoclonic atonic seizures (EMAS); Lennox-Gastaut syndrome (LGS); Paroxysmal fast activity; Slow spike-and-wave; Tonic seizures.

Figure 1:

Epilepsy diagnosis switching over time since epilepsy onset (a) Epilepsy diagnosis for each individual patient since epilepsy onset, including all epilepsy diagnoses. (b) Mean cumulative function (MCF) with 95% CI (confidence interval) for average number of diagnoses over time for patients who have more than one epilepsy diagnosis (n=50). This demonstrates that for patients who received more than one epilepsy diagnosis, the first diagnosis is received within the first year after onset, the second diagnosis within three years, and the third diagnosis within ten years. EMAS - epilepsy with myoclonic atonic seizures; LGS - Lennox-Gastaut syndrome; CAE - childhood absence epilepsy

Figure 2:

Individual epilepsy syndrome diagnosis by category of diagnosis (EMAS, LGS, other) for each patient by the patient’s age over time in years. There is superimposed notation of the presence of classic LGS electroclinical features, including the age at which these occur. This figure demonstrates on an individual level the evolution over time of specific LGS electroclinical features and relationship to epilepsy diagnosis. EMAS - epilepsy with myoclonic atonic seizures; LGS - Lennox-Gastaut syndrome; SSW - slow spike-and-wave; PFA - paroxysmal fast activity.

Figure 3:

Relationship between classic LGS electroclinical traits (SSW, PFA, and tonic seizures) with final diagnosis and outcomes. (a) The number of LGS traits, including specific electroclinical feature, by final diagnosis category of either EMAS, LGS, or other. The percentage of patients from each final diagnosis cohort is represented on the y-axis. (b) Kaplein Meier curves demonstrating time to last seizure by number of positive LGS electroclinical traits, regardless of specific trait present. There is a higher likelihood of ongoing seizures with each additional LGS trait present (log rank test p=0.018). EMAS - epilepsy with myoclonic atonic seizures; LGS - Lennox-Gastaut syndrome; PFA - paroxysmal fast activity; SSW - slow spike-and-wave; tonic – tonic seizures.