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=14 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 best of our 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 the best locations for permanent electrode placement. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) were used for preoperative and postoperative 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 the 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.