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Abstract: Increased metabolic muscle fatigue is caused by some but not all mitochondrial mutations

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www.ProHealth.com • January 29, 2003


Arch Neurol 2003 Jan;60(1):50-8

Schulte-Mattler WJ, Muller T, Deschauer M, Gellerich FN, Iaizzo PA, Zierz S.

Klinik und Poliklinik fur Neurologie, Universitat Regensburg, Im Bezirksklinikum, Universitatsstrasse 84, 93053 Regensburg, Germany. wilhelm.schulte-mattler@klinik.uni-regensburg.de

CONTEXT: Excessive muscle fatigue occurs in patients with a mitochondrial encephalomyopathy (MEM), but it is also a frequent problem in patients with other neuromuscular disorders (ONMD).

OBJECTIVE: To determine whether, and to what extent, metabolic muscle fatigue specifically occurs in patients with an MEM.

DESIGN: Metabolic muscle fatigue was assessed in a series of 21 patients with an MEM, including 13 patients with chronic progressive external ophthalmoplegia and 8 patients with various mitochondrial point mutations; 27 patients with ONMD; and 25 healthy controls. Isometric twitch force of the ankle dorsiflexors was measured after supramaximal stimulation of peroneal nerves. Six trains of stimuli (of 1 minute's duration with rates from 0.2 to 5 stimuli per second) were given to each subject.

RESULTS: An abnormal decrement of the twitch amplitude that occurred during a stimulation train was found in patients with MEM and in those with ONMD. The decrement of the twitch amplitude of controls and of patients with ONMD was strongly influenced by their muscle force (P<.001). After subtraction of the influence of the muscle force, specific fatigue was notably higher in patients with chronic progressive external ophthalmoplegia than in patients with ONMD and in controls, and it correlated well with elevations of serum lactate. Specific fatigue was also abnormal in a patient with a mitochondrial G7497A mutation, but normal in patients with an A3243G or a G11778A mutation. The heteroplasmy of mitochondrial DNA in muscle correlated neither with the force measures nor with the serum lactate levels.

CONCLUSIONS: Generally, metabolic muscle fatigue accompanies muscular weakness. Specifically, some but not all mitochondrial mutations cause excessive metabolic muscle fatigue.

PMID: 12533088 [PubMed - in process]




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