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

Clinical and experimental findings support the view that fatigue is a primary manifestation of PD. The main hypothesized pathophysiological mechanisms include abnormal basal ganglia (BG)-cortical mechanisms, particularly frontal loops, and an imbalance between neurotransmitters (e.g., dopamine [DA] and serotonin), along with an altered hypothalamus-pituitary-adrenal axis, neuroinflammation, cardiac sympathetic denervation, etc. Pragmatic treatment of fatigue in patients with PD includes various pharmacological (dopaminergic and psychostimulant drugs, antidepressants) and nonpharmacological strategies, although current knowledge suffers from insufficient evidence to support the use of any drug or nondrug therapy.