Abstracts

Rationale: The incidence of epilepsy is highest in the first year of life. However the prognosis remains poor for neurodevelopmental and seizure outcome, affecting quality of life. The assumption has been made that cognitive impairment is at least in part related to epileptic activity (i.e. epileptic encephalopathy) and that accordingly optimal seizure control will improve neurodevelopmental outcome. However, there is also growing evidence that underlying cause is independently contributing to cognitive impairment. We report on a prospective population based study documenting clinical course and etiology in children with infantile epilepsy, aimed at identifying early predictors of neurodevelopment and informing best clinical practice. Methods: All children presenting with epilepsy in the first year of life in the South East of England are being recruited over a 12 month period. Families are visited by a pediatric neurologist and a neuropsychologist shortly after diagnosis for clinical and neurodevelopmental (Bayley Scales of Infant & Toddler Development - III) assessment. A second evaluation takes place at age 12 months. EEG and MRI results and clinical updates on seizure evolution and medication are regularly obtained. Genetic and metabolic testing is performed based on clinical suspicion. Unsolved cases are offered whole exome sequencing on research basis. Results: Fifty patients have been seen for initial assessment (21 female). Mean age at presentation is 4.84 months (0-10, SD=2.53). Presenting seizure type were focal seizures (FS) in 18 (36%), generalized tonic-clonic seizures (GTCS) in 11 (22%), IS in 20 (40%) and myoclonic jerks (MJ) in 1(2%) patients. Most frequent seizure type were FS in 18 (36%), GTCS in 11 (22%), IS in 20 (40%) and MJ in 1(2%) patients. Initial EEG was normal in 22 (44%), hypsarrythmic in 18 (36%) and showing other epileptiform features in 10 (20%). MRI results were available in 43 patients, with normal appearances in 30 (60%). The underlying cause of the epilepsy is structural in 5 (10%), genetic in 17 (34%), whilst diagnostics are still ongoing in 28 (56%) patients. On their current treatment 29 (58%) children were seizure free. Mean age at first assessment was 8.2 months (2.6-13, SD=2.63). Parents reported developmental regression with seizure onset in 10 (20%) children, all presenting with infantile spasms (IS). Mean Bayley developmental scores were 84 (55-115, SD=17.67) for cognition, 79.4 (46-124, SD=22.4) for gross motor skills and 83 (47-115, SD=17.1) for language. Neurodevelopment was within the normal range in 28 (56%), whilst 11(22%) had moderate and 11 (22%) severe impairment. Predominant seizure type was correlated with developmental scores reaching significance for language (p=0.005) and motor skills (p=0.002) between IS and GTCS. Normal EEG background also predicted better language and motor skills compared to hypsarrythmia (p=0.004, p=0.001) and other EEG abnormality (p=0.01, p=0.033). Age at onset and seizure freedom after medication did not predict better development. Conclusions: Interictal EEG findings and seizure type strongly correlated with language and motor skills in our cohort of children with infantile epilepsy. Interestingly response to medication did not result in better developmental scores weakening the correlation between seizure burden and developmental outcome. Nevertheless this assessment was performed very early in the course of the epilepsy and follow-up assessments are important to further explore this association. Funding: Charles Wolfson Foundation, True Colours Trust, SPARKS, Child Brain Research, Epilepsy Research UK and Willie and Mabel Morris Charitable Trust