The pathophysiology of fatigue in Parkinson's disease

[Marco]

Needless to say they haven't cracked it but some interesting theories overlapping those around ME/CFS :

The Pathophysiology of Fatigue in Parkinson's Disease and its Pragmatic Management

[excerpt - my para breaks]

The perception of fatigue may represent a homeostatic mechanism to limit energy utilization and to prevent energy exhaustation.[7]

Among various peripheral and central contributors to the sensation of muscle fatigue and the perception of fatigue, respectively, inflammatory cytokines may also play a role.[24]

Patients suffering from neuroinflammatory and autoimmune diseases also frequently complain of severe, disabling fatigue.[24]

An association between PD and chronic inflammation has been revealed, together with elevated levels of activated CD4 and CD8 T cells, interleukin-1β, interleukin-2, and tumor necrosis factor-α in sera and cerebrospinal fluid from patients with PD. Recently, Lindqvist et al.[25] reported that increased levels of inflammatory markers in the cerebrospinal fluid of patients with PD were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition. After controlling for PD duration, age, gender, somatic illness, and dementia, high C-reactive protein levels were significantly associated with more severe symptoms of fatigue and depression.

The hypothesized roles of cytokines and chemokines in the generation of nonmotor symptoms of PD, including fatigue, may be mediated through their ability to promote microglial activation and induction of leukocyte chemotaxis,[26] which are closely associated with chronic neuroinflammation. However, they may also have direct effects on monoaminergic neurotransmission and the hypothalamic-pituitary-adrenal axis, which have been implicated in the pathophysiology of fatigue.[24]

There also seems to be quite a few studies using drug interventions (with few significant benefits unfortunately).

http://www.movementdisorders.org/MD...athophysiology-Fatigue-Parkinsons-Disease.htm

 

[Alvin2]

This reminds me of the Nilotinib drug trial, their study reported a fair amount of analysis that would do well combined with this paper.
That said i've also noticed a fair number of similarities with Parkinson's disease (and some clear differences of course).
I would be interested the analysis in this paper being repeated on some of the patients on the current Nilotinib drug trial.