Abstracts

Rationale: Down syndrome (DS) is the most common genetic cause of mental retardation. The prevalence of epilepsy in children with DS is higher than the general population, but lower than in other causes of mental retardation. Seizure onset is reported to occur within a year of birth in 40% of epileptic DS. A majority of these patients will suffer from Infantile Spasms (IS). Often IS with DS can be attributed to secondary lesions however many lack any identifiable risk factors. Most neuroimaging studies have demonstrated global brain volume reduction and disproportionate reduction in the cerebellum, brainstem, frontal lobe and hippocampus. Interestingly, among mental retardation syndromes, only DS exhibits hippocampal dysfuntion. Additionally, studies of DS children, demonstrate that these low hippocampal volumes are not attributed to neurodegenerative changes, but likely are due to early developmental differences. However no definitive study of hippocampal structures of DS with IS patients has been conducted to date. We hypothesized that DS with IS patients would have abnormal hippocampal volumes and morphology compared to IS patients without DS. Methods: An IRB approved retrospective cohort study was conducted to evaluate hippocampal rotation and volumes in patient with DS with IS, and symptomatic and cryptogenic IS without DS. Controls were matched for age and gender. Axis of rotation and volume was assessed on coronal thin section STIR, with secondary confirmation using sagittal T1 and coronal FLAIR by a board certified pediatric neuroradiologist blinded to the diagnosis. Volume loss and axis of rotation were scored in using a 4 point Likert scale (0 normal, 1 mild, 2 moderate, 3 severe). Intrasubject asymmetry in shape, volume and signal intensity was also evaluated. Continuous variables were compared with a 2-tailed t-test. Discrete variables were compared using a Fisher's exact test. Results: Twelve subjects were included in this study. Six patients had diagnosis of DS with IS ( age 1.07 years +/- 0.65) and six patients had a diagnosis of IS without DS (age 1.05 years +/- 1.00). Four IS without DS patients were classified as cryptogenic and two as symptomatic. Each group contained 3 males and 3 females. Hippocampal volumes were significantly lower in the DS with IS group (p = 0.0046). And hippocampal malrotation was more likely to be present in DS with IS group (p=0.0361). Conclusions: This study reviewed the hippocampal structures of 12 subjects diagnosed with Infantile Spasms. We were able to demonstrate in this retrospective cohort study, that children with Down Syndrome and Infantile Spasms have morphologicially different hippocampi compared to children with Infantile Spasms without Down Syndrome. These findings may be a demonstration of reported immunohistological evidence of pathologic changes in the GABAergic interneurons in all hippocampal subregions in Down Syndrome patients who suffer from Infantile Spasms.