Clinical Benefit of NMDA Receptor Antagonists in a Patient With ATP1A2 Gene Mutation

Mutations in the gene cause familial hemiplegic migraine type 2, alternating hemiplegia of childhood, and cerebellar function deficits, epilepsy, and mental retardation. These symptoms are likely related to glutamatergic hyperexcitability. Our patient is a 12-year-old boy with a history of complex partial seizures, attention-deficit/hyperactivity disorder, and fine motor difficulty. During early childhood, he had episodes of a self-resolving right-sided hemiparesis and focal epilepsy. His seizures did not respond to several antiepileptic medications but stopped after he received valproate. His intermittent episodes of hemiplegia persisted. Additionally, he had pronounced bilateral fine motor impairment and significant executive deficits that gradually worsened. The whole exome sequencing revealed a de novo missense mutation in the gene and a maternally inherited gene mutation of unknown clinical significance. We hypothesized that glutamatergic excitotoxicity due to the mutation contributed to the pathogenesis of our patient's condition. He was started on N-methyl-D-aspartate receptor antagonists (memantine and dextromethorphan), as well as coenzyme Q One year later, he showed significant improvement in sustained attention, learning efficiency, general cognitive efficiency, and fine motor dexterity. We postulate that N-methyl-D-aspartate receptor antagonists were effective for behavioral, cognitive, and cerebellar symptoms in our patient with gene mutation.