OBJECTIVE
The polygenic risk score (PRS) for individuals with genetic generalized epilepsy (GGE) quantifies the common risk variants in genes identified in genome-wide association studies. We hypothesized that the phenotype of GGE patients differs based on their GGE PRS.
METHODS
We identified participants with highest (n = 59) versus lowest (n = 48) PRS from the GGE patients (n = 2256) recruited through the Epi25 Collaborative for comparison. Detailed clinical data were acquired retrospectively for the 59 high PRS and 48 low PRS individuals with GGE from the Epi25 database and from the contributing centers. For validation, we accessed a larger cohort (n = 1175) of patients with GGE included in the Epi25 Collaborative.
RESULTS
This study found no difference in phenotypic features of patients between the high-PRS GGE and low-PRS GGE subgroups, including age at onset, family history, and specific GGE syndrome. However, more patients from the lowest compared to the highest PRS subgroup were pharmacoresistant (31.7% vs. 8.9%, p = .01). On validation in a larger cohort, the PRS did not differ in the group of pharmacoresistant compared to nonpharmacoresistant patients.
SIGNIFICANCE
No meaningful association between PRS and age at onset, history of febrile seizures, pre-/perinatal complications, epilepsy syndromes, seizure types, co-occurrence of functional/dissociative (nonepileptic) seizures, psychiatric comorbidities, electroencephalographic/magnetic resonance imaging findings, or drug response could be demonstrated in this study of people with GGE.
Sophie von Brauchitsch, Nils Hartung, R. Karge et al.· Epilepsia· 0 citations
Background Status epilepticus (SE) is associated with substantial mortality and morbidity that increase with seizure duration. Prompt diagnosis is essential, but access to electroencephalography (EEG) is often limited outside regular working hours. We examined whether EEG delay due to prolonged waiting times for EEG is associated with worse outcomes. Methods This retrospective cohort study comprised adults (≥18 years; n=163) with first-time, non-anoxic, EEG-verified non-convulsive SE treated at Odense University Hospital, Denmark (2008–2017). EEG delay was defined as the time from last antiseizure treatment or clinical suspicion of SE to EEG confirmation. Outcomes were new neurological deficit at discharge and 2-year all-cause mortality. External validation used two retrospective German cohorts (n=906) differing in weekend EEG availability. Results Median EEG delay was 11.7 hours (IQR 3.5–22.6) and correlated with SE duration (r=0.2, p<0.01). Longer delay was associated with new neurological deficits at discharge (p<0.001 across delay groups; ρ=0.152, p=0.03) and higher long-term mortality (log-rank p=0.007), driven mainly by delays>22.6 hours. Multivariable analyses for 1 year mortality adjusting for factors including aetiology and age supported an independent association between delay and higher mortality. Delays were longer for Friday/Saturday admissions when next-day EEG was unavailable, with lower survival. In validation, lack of weekend EEG access showed etiology-dependent weekend-weekday mortality differences (eg, +18.8% in remote symptomatic SE; p=0.01) not seen in centres with weekend EEG availability. Conclusion In this cohort, prolonged waiting times for EEG for the diagnosis of SE were associated with worse neurological outcomes at discharge and higher mortality. Improving timely EEG access, including weekends, may be a modifiable system-level target to improve SE outcomes.
Vinna Tran, Bernadette Thuy Uyen Nguyen, T. Krøigård et al.· Journal of Neurology Neurosu...· 1 citation
