Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.
In contrast patients with seizures related to GAD65-antibodies (an intracellular antigen) frequently develop epilepsy and have suboptimal response to treatment (including surgery).
Using both a tagging and functional single nucleotide polymorphism (SNP) approach, we genotyped the GAD1 and GAD2 genes and linked them with PTS data, regarding time to first seizure, obtained for 257 adult subjects with severe TBI.
Labeling for GAD65 mRNA and associated protein is substantially increased in the remaining GABA neurons at 2-4 months after the initial seizure episode.
Three of the seven patients with LE with different antibodies (NMDAR: n=1, Ma-2/Ta: n=1 and GAD65: n=1) achieved persistent seizure freedom along with no accelerated memory decline after surgery.