Instructor Boston Children's Hospital, Massachusetts
Rationale: SSADHD is a rare disorder of GABA degradation with use-dependent downregulation of postsynaptic GABAA/B receptors based on prior flumazenil-PET and TMS studies. We report TMS data from our natural history study to measure cortical excitability and GABAergic tone longitudinally. Methods: Resting motor threshold (rMT) was measured by single pulse TMS (sp-TMS) in 18 SSADHD subjects, nine age-matched healthy controls, and 44 age-matched patients with focal epilepsy. Separately, spTMS measures of the cortical silent period, and paired pulse TMS (pp-TMS) measures of long-interval intracortical inhibition were obtained in eight SSADHD subjects and seven controls. One-way ANOVA comparisons were done between subjects and controls and patients with focal epilepsy. Results: rMT was significantly higher in the SSADHD cohort compared to age-matched controls (p=0.005), but lower than rMT in either hemisphere of age-matched patients with focal epilepsy. The rate of rMT decline as a function of age did not differ between the SSADHD and control groups. While there was no statistically significant difference in LICI between the SSADHD and control groups overall, CSP was increased in SSADHD subjects compared to controls (p=0.047). Conclusions: Given that rMT declines throughout childhood in normal subjects, the elevated rMT in SSADHD patients compared to age-matched healthy controls suggests a dysmature corticospinal tract physiology. However, a retained capacity for maturation in SSADHD is indicated by the trajectory toward lower rMT with age. Contrary to findings from prior studies, no significant difference was found in LICI, and CSP was increased in our cohort, indicating a trend toward increased GABAergic tone, particularly in the very young patients. Funding: Please list any funding that was received in support of this abstract.: Funding provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Grant Number: 5R01HD091142 supported the work presented.