Abstracts

Rationale: We previously reported epilepsy surgery as an effective acute treatment option in pediatric status epilepticus (SE) (Neurol 2005;64:567-70) and electrical status epilepticus in sleep (ESES) (Neurosurg 2009;64:328-37). Multiple studies reveal altered neurotransmitter receptor expression in tissue resected from selected pediatric and adult epilepsy syndromes. To date, there is little information regarding expression in tissue from pediatric acute status and electrical status in sleep. We hypothesized that the tissue from patients resected in acute SE or those with ESES would exhibit more pronounced receptor alterations than tissue of patients undergoing elective surgery for chronic refractory epilepsy. Methods: Using western blotting, glutamate and GABA receptor subunit expression (GluR1, GluR2, NR2A, NR2B, GABAR-α1, GABAR-α2) was ascertained in children with refractory epilepsy (EPI=6), acute SE (3), ESES (3), and non-epileptic postmortem controls (CON=4): all values normalized to actin. EPI, SE, and ESES groups were diagnosed by video-EEG recordings prior to epilepsy surgery and matched by pathology (malformation of cortical development (MCD) =7, Stroke =5). Results: For AMPARs, GluR1 was higher in ESES (ESES 1306±386%, p<0.01) as compared to CON. GluR2 was not significantly elevated in any epilepsy group compared to CON. The GluR1/GluR2 ratio was elevated in ESES (465%± 119) and EPI (329%±125) groups compared to CON (p<0.01), but not significantly changed in SE. For NMDARs, NR2B expression was increased in SE (2543%+ 1363; p<0.05) but not significantly changed in the EPI or ESES compared to CON. No changes in NR2A expression were seen in any of the epilepsy groups. However, the NR2B/NR2A ratio was elevated in ESES (3682%±1000) and SE (3520%± 751) compared to CON (p<0.05). For GABARs, α1 and α2 subunit expression were not significantly changed in any epilepsy group compared to CON, but the α2/α1 ratio showed a significant increase in both the EPI (321%±138p<0.05) and SE (346%±74;p<0.05), but not in the ESES group as compared to CON. Independent of EEG pattern, cases with underlying MCD showed a significant increase in GluR1/GluR2 ratio (382%±149; p<0.01), an increase in NR2B/NR2A ratio (3321%±1581; p<0.05) and elevated α2/α1 ratios (303%±86; p<0.01) compared to CON. The presence of stroke pathology in the tissue was not associated with significant changes in any of these receptor subunits.