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

Jaya Nataraj; Jennifer A MacLean; Jordan Davies; Joshua Kurtz; Amanda Salisbury; Mark A Liker; Terence D Sanger; Joffre Olaya

doi:10.3389/fneur.2023.1307595

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

Front Neurol. 2024 Jan 24:14:1307595. doi: 10.3389/fneur.2023.1307595. eCollection 2023.

Authors

Jaya Nataraj^{1

2}, Jennifer A MacLean^{2

3}, Jordan Davies^{4

5}, Joshua Kurtz⁶, Amanda Salisbury², Mark A Liker^{4

7}, Terence D Sanger^{1

2

3

8}, Joffre Olaya^{4

5}

Affiliations

¹ Samueli School of Engineering, University of California Irvine, Irvine, CA, United States.
² Research Institute, Children's Hospital of Orange County, Orange, CA, United States.
³ Department of Neurology, Children's Hospital of Orange County, Orange, CA, United States.
⁴ Division of Neurosurgery, Children's Hospital of Orange County, Orange, CA, United States.
⁵ Department of Neurological Surgery, School of Medicine, University of California Irvine, Irvine, CA, United States.
⁶ School of Medicine, University of California Irvine, Irvine, CA, United States.
⁷ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁸ Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, CA, United States.

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.

Keywords: MECR; MEPAN; deep brain stimulation; dystonia; pediatrics.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.