AUTHOR=Nataraj Jaya , MacLean Jennifer A. , Davies Jordan , Kurtz Joshua , Salisbury Amanda , Liker Mark A. , Sanger Terence D. , Olaya Joffre 

TITLE=Application of deep brain stimulation for the treatment of childhood-onset dystonia in patients with MEPAN syndrome

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1307595

DOI=10.3389/fneur.2023.1307595

ISSN=1664-2295

ABSTRACT=Introduction: Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome is a rare inherited metabolic condition caused by MECR gene mutations. This gene encodes a protein essential for fatty acid synthesis, and defects cause progressively worsening childhood-onset dystonia, optic atrophy, and basal ganglia abnormalities. Deep brain stimulation (DBS) has shown mixed improvement in other childhood-onset dystonia conditions. To the authors' knowledge, DBS has not been investigated as a treatment for dystonia in patients with MEPAN syndrome. Methods: Two children with MEPAN were identified as possible DBS candidates due to severe generalized dystonia unresponsive to pharmacotherapy. Temporary depth electrodes were placed in six locations bilaterally and tested during a 6-day hospitalization to determine best locations for permanent electrode placement. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) were used for pre-and post-operative testing to quantitatively assess dystonia severity changes. Patient 1 had permanent electrodes placed at the globus pallidus internus (GPi) and pedunculopontine nucleus (PPN). Patient 2 had permanent electrodes placed at GPi and ventralis intermedius nucleus of the thalamus (VIM). Results: Both patients successfully underwent DBS placement with no perioperative complications and significant improvement in their BFMDRS score. Patient 2 also demonstrated improvement in the BADS. Discussion: We demonstrated a novel application of DBS in MEPAN syndrome patients with childhood-onset dystonia. These patients showed clinically significant improvements in dystonia following DBS, indicating that DBS can be considered for dystonia in patients with rare metabolic disorders that currently have no other proven treatment options.