Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia. Issue 7 (July 2017)

• Record Type: Journal Article
• Authors: Gueguen, Antoine; Jardel, Claude; Polivka, Marc; Tan, S. Veronica; Gray, Françoise; Vignal, Catherine; Lombès, Anne; Gout, Olivier; Bostock, Hugh
• Is Part Of: Clinical neurophysiology. Volume 128:Issue 7(2017:Jul.)
• Page Start: 1258
• Page End: 1263
• Publication Date: 2017-07
• Subjects: CPEO -- Mitochondrial disease -- Nerve excitability -- Myelin sheath -- Barrett-Barrett conductance; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2017.04.013
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: Patients with chronic progressive external ophthalmoplegia due to large size deletions of mtDNA were studied. Nerve excitability abnormalities were found that correlated with skeletal muscle weakness. Abnormalities suggested a spread of mitochondrial dysfunction to Schwann cells. 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.