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.
© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).