Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation

Abstract

Background: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory.

Results: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO₄, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit.

Conclusion: Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO₄ for select forms of GRIN disorders.

Keywords: /Terms epileptic encephalopathy; Cerebral palsy; Dystonia; GRIN Disorders; N-of-1 treatment trial; NMDA receptor; Neurodevelopmental Disorders; Precision Medicine.