Impaired oxidative metabolism in exercising muscle from ALS patients

The pathogenic mechanism of selective loss of motor neurones in amyotrophic lateral sclerosis (ALS) is still poorly understood. Recently, research evidence has suggested that mitochondrial dysfunction occurs in central nervous system as well as in peripheral tissues from ALS patients. The aim of our study was to indirectly investigate in vivo oxidative metabolism of exercising muscle in a case history of patients affected by ALS. To this purpose 11 patients, 8 male and 3 female, mean age+/-SD: 52.4+/-11.1 years, performed a bicycle incremental test for the assessment of lactate production. At rest, there was increased lactate concentration in patients: 2.77+/-0.79 vs. 1.48+/-0.49 mmol/l in normal controls (normal range: 0.67-2.47 mmol/l). Analysis of lactate curve during exercise showed a lactate production increase compared to controls. Furthermore, anaerobic lactate threshold was detected at 40-50% of the predicted normal power output, anticipated with respect to both normal subjects and non-ALS chronically denervated controls with comparable motor impairment (60-70%), suggesting that mitochondrial dysfunction can occur in exercising skeletal muscle from ALS patients.