Research theme 2: Exploring the Post-Exertional Exacerbation of Fatigue (PEEF)

The biological basis of the chronic fatigue states (CFS, PCF, PVFS, PIFS), remains largely unknown, but multiple lines of evidence point to the central nervous system (CNS – that is the brain) as the primary site of the pathophysiology.¹ The cardinal symptom of profound fatigue is typically exacerbated by physical and cognitive activities previously achieved with ease, followed by delayed recovery over hours or even days. This post-exertional exacerbation of fatigue (PEEF) is also referred to as ‘post-exertional malaise’ and is the dominant function-limiting symptom of the illness.²

A new approach to improve understanding of the disease mechanisms of chronic fatigue states, is through physical and cognitive provocation studies which induce the characteristic post-exertional exacerbation of fatigue in a controlled fashion, offering the opportunity to seek biological correlates, and interventions that modify the phenomenon. Our team has developed and utilised standardised provocation paradigms that induce a reproducible pattern of fatigue exacerbation following either physical (exercise),^2-5 or cognitive (simulated driving) challenges,^2,4 captured by a validated self-report instrument recording the conscious sensation of fatigue in real time - the Fatigue and Energy Scale (FES).²

The current research focus is investigation of the potential effectiveness of centrally-active drugs such as modafinil on the severity and duration of PEEF induced under controlled experimental conditions.

¹  _{Sandler CX, Lloyd AR. Chronic fatigue syndrome: progress and possibilities? Medical Journal of Australia 2020; in press. Accepted mja19.00733.R2 (21.11.2019).}

²  _{Keech A, Sandler CX, Vollmer-ConnaU, Cvejic E, Lloyd AR, Barry BK. Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. Journal of Psychosomatic Research 2015; 79(6): 537-49.}

³  _{Sandler CX, et al. Fatigue exacerbation by interval or continuous exercise in chronic fatigue syndrome. Medicine and Science in Sports and Exercise 2016; 48(10): 1875-85.}

⁴  _{Cvejic E, et al. Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome. Journal of Psychosomatic Research 2017; 103: 91-4.}

⁵  _{Keech A, et al. Gene expression in response to exercise in patients with chronic fatigue syndrome: a pilot study. Front Physiol 2016; 7: 421.}