Background: Disorders arising from primary mitochondrial genetic defects are known to be associated with peripheral neuropathy. The mechanisms underlying this are poorly understood, and may be secondary to disordered oxidative phosphorylation and reduced energy-dependent maintenance of ionic gradients necessary for impulse propagation and neuronal cell integrity.
Methods: Fifteen patients with mitochondrial disorders ( MELAS 6, CPEO 5, MERRF 1, Pearson’s 1, undetermined 2) either confirmed by genetic characterisation or suspected on muscle biopsy were evaluated clinically and electrophysiologically. Axonal excitability was assessed in median motor nerves at the wrist and compared with 50 normal controls.
Results: As a group, there was no significant difference in excitability parameters. However, the MELAS subgroup (4 genetically confirmed) showed significant changes in 5 threshold electrotonus parameters that could result from membrane depolarisation (TEd peak and at 10-20ms, TEh at 10-20, 20-40, 90-100ms; p=0.02-0.03). In support of this interpretation, there were trends for appropriate changes in the relative refractory period, refractoriness and superexcitability. These trends were not significant, possibly because of the small sample size. Half the MELAS patients in the subgroup had diabetes or impaired glucose tolerance, and one had an axonal neuropathy on standard nerve conduction. None of the 15 had abnormal autonomic studies (RR interval with deep breathing, standing and Valsalva; SSR).
Conclusion: Even with these small numbers, the suggestive evidence for axonal depolarisation in patients with MELAS accords with the a priori hypothesis of respiratory chain abnormalities. The manifestations appear to be subclinical in most patients.