Pierson et al reported in 2014 the case of a child with a GRIN2A mutation that changed leucine to methionine at amino acid position 812. This change increased the potency of the NMDA agonists glutamate and glycine. Investigators found that, with this mutation, memantine can block the excessive gain of function response. With adjunctive memantine therapy, the child had a dramatic reduction in seizures, although not a dramatic improvement in development, Dr. Poduri said. The child had been receiving treatment with lacosamide, rufinamide, and valproic acid. After starting memantine, lacosamide and rufinamide were tapered off.
A precise genetic diagnosis also might influence the decision between epilepsy surgery and medical treatment. For example, if a patient with infantile spasms and a mutation in SCN1A has a focal lesion, a neurologist may consider surgery, but some studies suggest that outcomes are not always favorable for these patients, Dr. Poduri said.
Need for Awareness
Neurologists should pursue updated genetic testing for their patients to take advantage of the latest genetic discoveries, Dr. Poduri said. They should learn which genes are associated with epilepsy syndromes, and bear in mind that the list of identified genes is growing.
Dr. Poduri hopes clinical practices will engage with clinical researchers and gene discovery efforts, which can lead to clinically relevant models, preclinical trials, and eventually precision medicine. “This may seem like a bit of a dream, but I think it’s really where we’re moving, and we actually have traction now in all of these areas,” she said.
—Jake Remaly
