Abstracts

Rationale: Idiopathic generalized epilepsies (IGE) are highly heritable syndromes. Previous work in juvenile myoclonic epilepsy (JME) identified a specific cognitive profile implicating high-level frontal lobe functions, which has been correlated with atypical neurodevelopment in imaging studies. Importantly, JME patients exhibited significant overlap of cognitive and imaging metrics with their unaffected siblings, indicating cognitive trait heritability and neurodevelopmental pathological mechanisms. Neuropsychological profiles in other subsyndromes, such as juvenile absence epilepsy (JAE), and their determinants remain poorly understood. Here, we aimed to firstly characterise the neuropsychological profile in JAE patients, comparing them to controls and secondly, explore cognitive trait heritability by studying unaffected JAE siblings. Methods: We studied 24 JAE patients, 17 JAE siblings (SIB), and 26 controls (CTR). All participants were assessed with a comprehensive neuropsychological test battery (Figure 1), as well as with the Hospital Anxiety and Depression Scale questionnaire. For patients, we obtained clinical information, i.e. disease duration, age at onset, seizure frequency, and medication usage. The neuropsychological data were processed using R (version 3.5.2), and general linear models were used to compare cognitive performance across the measured domains between the groups. Age, sex, and education level were also included as covariates in intergroup analyses. In JAE patients, clinical measures were correlated with cognitive performance, to identify possible effects of disease severity on cognitive function. Statistical significance was set at FDR corrected p < .05. Results: Groups were comparable for age (JAE m: 24.27 SD: 6.42; SIB m: 25.38 SD: 7.82; CTR m: 25.96 SD: 5.71; p = .656). Groups differed for sex (p < .012) and for education level (p < .002). Complete findings of the neuropsychological test battery are shown in Figure 1, where it can be seen that the patients performed worse than the controls in tests of verbal comprehension, working memory, fluency, psychomotor speed, and mental flexibility. Notably, both patients and siblings were impaired compared to controls for measures of phonological and semantic fluency. SIB reported lower levels of both depression and anxiety than their patient relatives, whereas CTR only reported lower levels of depression. In the JAE group, age at onset and medication usage did not correlate with any cognitive measures in the patient group. Results from the JAE MANCOVA however, indicated a significant negative relationship between disease duration, and performance on tests of verbal comprehension (WAIS-III similarities), as well as processing speed (Stroop baseline task). Seizure frequency was also related to decreased performance during tests of processing speed, as well as phonological and semantic fluency. Conclusions: JAE patients exhibit impairment in several functions reliant on frontal lobe processing, including expressive language, working memory, and executive functions. Siblings generally show intermediate performance in relation to JAE and CTR, and share impairment with patients in fluency tasks, indicative of a familial trait. In addition, disease severity contributes to poorer performance in visuo-spatial information processing, processing speed, and fluency. Funding: National Institute for Health Research, University College London Hospitals Biomedical Research CentreHenry Smith Charity (ref 20133416)Brain Research UKEpilepsy Society