Abstracts

Rationale: Tuberous sclerosis complex (TSC) is a common cause of infantile spasms but only a subset of patients develop infantile spasms (IS). IS is a catastrophic childhood epilepsy characterized by clusters of epileptic spasms with usual onset before 1 year of age. Despite conventional treatment, the outcomes are poor prompting the need to identify new treatment approaches. We investigated whether gene expression abnormalities obtained from surgically resected brain tissue of TSC patients with and without IS can provide clues into the underlying molecular pathology .Methods: Gene expression data were obtained from 6 surgical brain tissue samples of TSC. Four samples were obtained from TSC patient with IS and two from TSC patients without IS. Agilent SurePrint G3 Unrestricted GE 8x60K gene expression microarray was used for obtaining gene expression data. Genes expressed at low levels (log2 value < 5) and those with differential expression less than 4 fold were excluded from analysis. Top differentially expressed genes were subsequently identified.Results: Among the top 100 differentially expressed genes, several genes involved in inflammation showed robust and large differences in the 4 subjects with IS compared to the 2 without IS. These involve several inflammation-associated genes such as TLR2, ALOX5, TIMD4, CLC,C1QA, LILRB4. Many of these genes are specifically enriched in CD14 monocyte/macrophages lineage, suggesting that the pathologic process involves activated microglia (the primary resident macrophages of brain). Conclusions: Brain tissue from TSC patients with IS shows the gene expression signature of activated microglia. The identification of these expression abnormalities opens up the possibilities of new anti-inflammatory therapies in IS.