Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia.

Abstract

OBJECTIVE:

To explore potential spreading to peripheral nerves of the mitochondrial dysfunction in chronic progressive external ophthalmoplegia (CPEO) by assessing axonal excitability.

METHODS:

CPEO patients (n=13) with large size deletion of mitochondrial DNA and matching healthy controls (n=22) were included in a case-control study. Muscle strength was quantified using MRC sum-score and used to define two groups of patients: CPEO-weak and CPEO-normal (normal strength). Nerve excitability properties of median motor axons were assessed with the TROND protocol and changes interpreted with the aid of a model.

RESULTS:

Alterations of nerve excitability strongly correlated with scores of muscle strength. CPEO-weak displayed abnormal nerve excitability compared to CPEO-normal and healthy controls, with increased superexcitability and responses to hyperpolarizing current. Modeling indicated that the CPEO-weak recordings were best explained by an increase in the 'Barrett-Barrett' conductance across the myelin sheath.

CONCLUSION:

CPEO patients with skeletal weakness presented sub-clinical nerve excitability changes, which were not consistent with axonal membrane depolarization, but suggested Schwann cell involvement.

SIGNIFICANCE:

This study provides new insights into the spreading of large size deletion of mitochondrial DNA to Schwann cells in CPEO patients.

• Authors: Antoine Gueguen, Claude Jardel, Marc Polivka, S Veronica Tan, Françoise Gray, Catherine Vignal, Anne Lombès, Olivier Gout, Hugh Bostock
• Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology (Clin Neurophysiol) Vol. 128 Issue 7 Pg. 1258-1263 (07 2017) ISSN: 1872-8952 [Electronic] Netherlands
• PMID: 28535487 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Chemical References

• DNA, Mitochondrial

Topics

• Adolescent
• Case-Control Studies
• Child
• DNA, Mitochondrial (genetics)
• Female
• Humans
• Male
• Middle Aged
• Muscle Weakness (diagnosis, genetics, physiopathology)
• Neural Conduction (physiology)
• Ophthalmoplegia, Chronic Progressive External (diagnosis, genetics, physiopathology)
• Prospective Studies
• Young Adult