Objective: Fatigue is a commonly reported symptom in amyotrophic lateral sclerosis (ALS), although the underlying mechanisms appear complex, with dysfunction of central and peripheral nervous systems reported. Consequently, the present study utilized novel threshold tracking transcranial magnetic stimulation (TMS) techniques to determine the contribution of central mechanisms to development of fatigue in ALS.
Methods: Studies were undertaken in 9 ALS patients and 19 normal controls using a 90 mm circular coil. TMS studies were performed at baseline, immediately after a voluntary contraction (VC) period of 120 second duration (three VC periods), and at 5, 10 and 20 minutes after last VC.
Results: There was significant reduction of short interval intracortical inhibition (SICI) in controls, peaking after the second VC period (SICI baseline 17.0±1.7%; SICI 11.5±2.1%, P<0.05). Although SICI was significantly reduced in ALS patients at baseline (2.2±4.4%, P<0.01), there was no significant reduction of SICI during or after VC (SICI2ndvc 1.4±3.7%, P=0.4). Furthermore, there was a reduction of the motor evoked potential (MEP) amplitude, peaking at the end of the first VC period, being greater in ALS patients (MEP reduction ALS 26%; controls 15%) and accompanied by significant reduction in peak force generated by thumb abduction in ALS patients (peak force baseline 31.1±4.1 Nm; Peak force during 3rdVC 19.3±2.7 Nm, P<0.05).
Conclusion: These studies suggest that cortical adaptive processes are dysfunctional in ALS, thereby suggesting a significant contribution of central processes to development of fatigue in ALS. Therapeutic interventions aimed at modulating central dysfunction may improve fatigue in ALS.