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

Overview

Journal Mov Disord Clin Pract

Publisher Wiley

Specialty Neurology

Date 2018 Oct 27

PMID 30363584

Citations 27

Authors

Vladimir S Kostic

Aleksandra Tomic

Milica Jecmenica-Lukic

Affiliations

Soon will be listed here.

Abstract

Background: Fatigue is 1 of the most common and most disabling symptoms among patients with Parkinson's disease (PD) and has a significant impact on their quality of life. Yet the pathophysiology of fatigue is poorly understood, while its treatment is "limited to an empirical approach based on plausible hypotheses."

Methods: PubMed was searched for articles with the key words "Parkinson's disease" or "parkinsonism" and "fatigue" that were published by or before August 2015. The analysis of articles, which were selected on subjective grounds, was used to review the current knowledge of pathophysiology and treatment outcomes in studies focused on fatigue in PD.

Conclusions: 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.

Citing Articles

Contribution of fatigue experienced by Parkinson's Disease patients on caregiver burden.

Landolfo S, Urso D, Santoro C, Batzu L, Gnoni V, Giugno A J Neurol. 2025; 272(4):264.

PMID: 40072620 DOI: 10.1007/s00415-025-12962-z.

Exploring the layers of fatigue in Parkinson's Disease: A comprehensive analysis of its prevalence and contributing factors.

Sarmento F, Lamp G, Srikar Lavu V, Madamangalam A, Dwarampudi J, Yuan Q Clin Park Relat Disord. 2024; 11:100288.

PMID: 39654952 PMC: 11626731. DOI: 10.1016/j.prdoa.2024.100288.

Golexanolone reduces glial activation in the striatum and improves non-motor and some motor alterations in a rat model of Parkinson's disease.

Izquierdo-Altarejos P, Arenas Y, Martinez-Garcia M, Vazquez L, Mincheva G, Doverskog M Front Aging Neurosci. 2024; 16:1417938.

PMID: 38974902 PMC: 11224447. DOI: 10.3389/fnagi.2024.1417938.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

Terra M, Lopes J, Bueno M, Trinca L, Smaili S Neurol Sci. 2024; 45(9):4309-4321.

PMID: 38528282 DOI: 10.1007/s10072-024-07466-z.

Transcranial brain parenchyma sonographic findings in patients with myotonic dystrophy type 1 and 2.

Mijajlovic M, Bozovic I, Pavlovic A, Rakocevic-Stojanovic V, Gluscevic S, Stojanovic A Heliyon. 2024; 10(5):e26856.

PMID: 38434309 PMC: 10907768. DOI: 10.1016/j.heliyon.2024.e26856.

References

Kang S, Wasaka T, Shamim E, Auh S, Ueki Y, Lopez G . Characteristics of the sequence effect in Parkinson's disease. Mov Disord. 2010; 25(13):2148-55. PMC: 4782591. DOI: 10.1002/mds.23251. View

Saez-Francas N, Hernandez-Vara J, Corominas Roso M, Martin J, Casas Brugue M . The association of apathy with central fatigue perception in patients with Parkinson's disease. Behav Neurosci. 2013; 127(2):237-44. DOI: 10.1037/a0031531. View

Chaudhuri K, Martinez-Martin P, Antonini A, Brown R, Friedman J, Onofrj M . Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER. Parkinsonism Relat Disord. 2013; 19(7):660-5. DOI: 10.1016/j.parkreldis.2013.02.018. View

Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H . Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004; 15(17):2571-4. DOI: 10.1097/00001756-200412030-00002. View

Pavese N, Metta V, Bose S, Chaudhuri K, Brooks D . Fatigue in Parkinson's disease is linked to striatal and limbic serotonergic dysfunction. Brain. 2010; 133(11):3434-43. DOI: 10.1093/brain/awq268. View

Postuma R, Lang A, Munhoz R, Charland K, Pelletier A, Moscovich M . Caffeine for treatment of Parkinson disease: a randomized controlled trial. Neurology. 2012; 79(7):651-8. PMC: 3414662. DOI: 10.1212/WNL.0b013e318263570d. View

Schenkman M, Butler R . A model for multisystem evaluation, interpretation, and treatment of individuals with neurologic dysfunction. Phys Ther. 1989; 69(7):538-47. DOI: 10.1093/ptj/69.7.538. View

Saez-Francas N, Hernandez-Vara J, Corominas-Roso M, Alegre J, Jacas C, Casas M . Relationship between poor decision-making process and fatigue perception in Parkinson's disease patients. J Neurol Sci. 2013; 337(1-2):167-72. DOI: 10.1016/j.jns.2013.12.003. View

Ghahari S, Packer T, Passmore A . Effectiveness of an online fatigue self-management programme for people with chronic neurological conditions: a randomized controlled trial. Clin Rehabil. 2010; 24(8):727-44. DOI: 10.1177/0269215509360648. View

10.

Kluger B, Krupp L, Enoka R . Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology. 2013; 80(4):409-16. PMC: 3589241. DOI: 10.1212/WNL.0b013e31827f07be. View

11.

Stocchi F, Abbruzzese G, Ceravolo R, Cortelli P, DAmelio M, De Pandis M . Prevalence of fatigue in Parkinson disease and its clinical correlates. Neurology. 2014; 83(3):215-20. DOI: 10.1212/WNL.0000000000000587. View

12.

Abe K, Takanashi M, Yanagihara T, Sakoda S . Pergolide mesilate may improve fatigue in patients with Parkinson's disease. Behav Neurol. 2002; 13(3-4):117-21. PMC: 5507127. DOI: 10.1155/2002/473140. View

13.

Kostic V, Covickovic-Sternic N, Beslac-Bumbasirevic L, Ocic G, Pavlovic D, Nikolic M . Dexamethasone suppression test in patients with Parkinson's disease. Mov Disord. 1990; 5(1):23-6. DOI: 10.1002/mds.870050106. View

14.

Stevens-Lapsley J, Kluger B, Schenkman M . Quadriceps muscle weakness, activation deficits, and fatigue with Parkinson disease. Neurorehabil Neural Repair. 2011; 26(5):533-41. DOI: 10.1177/1545968311425925. View

15.

. A controlled trial of rotigotine monotherapy in early Parkinson's disease. Arch Neurol. 2003; 60(12):1721-8. DOI: 10.1001/archneur.60.12.1721. View

16.

Havlikova E, Rosenberger J, Nagyova I, Middel B, Dubayova T, Gdovinova Z . Clinical and psychosocial factors associated with fatigue in patients with Parkinson's disease. Parkinsonism Relat Disord. 2007; 14(3):187-92. DOI: 10.1016/j.parkreldis.2007.07.017. View

17.

Beiske A, Svensson E . Fatigue in Parkinson's disease: a short update. Acta Neurol Scand Suppl. 2010; (190):78-81. DOI: 10.1111/j.1600-0404.2010.01381.x. View

18.

Oved D, Ziv I, Treves T, Paleacu D, Melamed E, Djaldetti R . Effect of dopamine agonists on fatigue and somnolence in Parkinson's disease. Mov Disord. 2006; 21(8):1257-61. DOI: 10.1002/mds.20929. View

19.

Jang W, Park J, Shin K, Kim J, Kim J, Youn J . Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease. J Neurol Sci. 2013; 337(1-2):47-54. DOI: 10.1016/j.jns.2013.11.015. View

20.

Abe K, Takanashi M, Yanagihara T . Fatigue in patients with Parkinson's disease. Behav Neurol. 2001; 12(3):103-6. DOI: 10.1155/2000/580683. View