Enhanced fatigue during motor performance in patients with Parkinson's disease

Objective: To measure fatigue quantitatively during continuous motor performance in patients with PD. Background: Enhanced fatigue on performance of motor tasks is a very frequent and disabling complaint of PD patients, and is poorly characterized and understood. Recent evidence suggests a role for mitochondrial dysfunction in the pathogenesis of PD. Reduced exercise capacity is one of the hallmarks of systemic mitochondrial impairment. Methods: The authors used an automated system to measure muscle fatigue during a continuous (30-second), maximal, isometric forearm flexion in 17 PD patients and 10 age-matched control subjects. A fatigue index (FI) was then calculated. Peak force (PF) was measured as an internal standard of the examination. Measurements were performed before and 2 hours after an oral dose of levodopa/carbidopa (125 mg/12.5 mg). Results: In PD patients there was a 50% increase in Fl. The increased Fl was often asymmetric and more pronounced on the side more affected by the disease. FI was significantly responsive to, and improved after, an oral dose of levodopa. The rate of improvement in Fl induced by levodopa correlated with disease severity, as measured by the Unified Parkinson's Disease Rating Scale. No significant alterations in PF were observed. Conclusions: Enhanced muscle fatigue should be recognized as an integral part of the spectrum of motor impairment of PD. However, our data argue for its association with a central dopamine deficiency rather than with a muscle mitochondrial abnormality.