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
OBJECTIVE
To investigate changes in quality of life (QoL) dimensions and their relationship with seizure outcome, depression, and suicidality after the addition or substitution of an anti-seizure medication (ASM) in adults with drug-resistant focal epilepsy.
METHODS
A total of 665 consecutively enrolled patients were followed prospectively and assessed with Quality of Life in Epilepsy Inventory 31 (QOLIE-31) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). QoL changes over time for the overall population and seizure outcome categories were analyzed with analysis of variance (ANOVA), whereas factors affecting QoL changes were assessed by using a linear regression model.
RESULTS
Seizure freedom was associated with a marked improvement across all QoL domains, ranging from 11 points for Seizure worry to 4 points for Emotional well-being. The presence of depression before starting medication and its persistence during the observation period was associated with a global worsening of QoL across all domains, ranging from 10 points worse for Social functioning, almost 8 points for Energy and fatigue, 6 points for Cognitive functioning, and to nearly 5 points for Seizure worry. The new development of depression during treatment was associated with worsening in specific QoL domains such as Cognitive functioning, Social functioning, and Overall QoL subscales. Persistent positive suicidality screening was associated with progressive worsening in the domain Emotional well-being.
SIGNIFICANCE
Seizure freedom can improve all domains of QoL, but mainly Seizure worry, although this can be negatively affected by depressed mood. Improvement in the domain of Social functioning requires a period of sustained seizure freedom longer than 6 months to improve, and it is negatively influenced by persistent depressed mood. In contrast, changes in Emotional well-being are negatively influenced by suicidality. Clinical and demographic variables, including duration of epilepsy and number of comorbidities or concomitant medical problems, showed no correlation with changes in QoL.
Marco Mula, S. Borghs, Bruno Ferrò et al.· Epilepsia· 0 citations