Abstracts

Rationale: Brain injury, genetic or acquired, micro- or macroscopic, would tend to limit cerebral development in pediatric epilepsy patients. In our patients with childhood absence epilepsy (CAE), we were surprised to find many with larger than average head circumferences (HC), including many with macrocephaly. We evaluated these patients to determine a) the incidence of macrocephaly in CAE, b) whether macrocephaly was a cause or consequence of epilepsy and c) whether CAE patients with macrocephaly differed clinically or genetically from those with normocephaly. Methods: This is a retrospective chart review of CAE patients followed in pediatric epilepsy clinics at Cedars-Sinai and Harbor-UCLA Medical Centers in Los Angeles. Only patients who met criteria for CAE established by the International League against Epilepsy were included. Exclusion criteria included seizure onset > 11 years, mental retardation, persistent unilateral frontal lobe onset and photo-convulsive seizures. Macrocephaly was defined as > 2 S.D. from the mean for age and gender. Height, weight and HC were obtained for all patients during clinic visits. Birth HC and HC of both parents were also obtained. Results: From a cohort of 40 patients with CAE (21F, 19M), we identified 14 children with macrocephaly (35%)(8F, 7M). Neuroimaging studies showed no intracranial pathology (n=9). All subjects had stable HC during their seizure periods. In the macrocephaly group, HC at birth or by one year of age was macrocephalic in 8/8 CAE patients, while all normocephalic subjects had normal HC in the first year of life. Parental incidence of macrocephaly was 90% in the macro group (9/10)and 28% in the normocephalic group (4/14), p<0.01. None of the macrocephalic parents had a seizure history, while 3 normocephalic parents and 6 family members (37.5%) in the normocephalic group had seizures. Absence seizures in both HC groups were well-controlled with standard medications. Age at seizure onset, 6.6 (macro, n=13) vs. 6.2 yrs.(normo, n=20), duration of seizure period, 3.8 (macro, n=5) vs. 3.5 yrs. (normo, n=9) and age at seizure resolution 12.9 (macro, n=5) vs. 11.9 yrs. (normo, n=9), were similar (p>0.3). The incidence of school problems (learning disability, ADHD or reading problems) was similar in both groups, 28.5% (macro, n=14) vs. 37.5% (normo, n=24). However, macro CAE patients were bigger than their cohorts, weight: 77.5%ile (macro, n=14) vs. 51.5%ile (normo, n=19) (p<0.05) and height: 63.0%ile (macro, n=10) vs. 50.3%ile (normo, n=16). Average HC in the normo group was 60.3%ile (n=26). Conclusions: One third of our CAE patients had macrocephaly. Clinically, they were similar to normocephalic CAE patients, though genetically distinct. Macrocephaly is a dominantly-inherited trait and was present before seizure onset. Macrocephaly may be an important biomarker or play a causative role in absence epilepsy.