Clinical and pathophysiological aspects of non-motor manifestations of Parkinson's disease
M. A. Nikitina,
N. G. Zhukova,
E. Yu. Bragina,
V. M. Alifirova,
I. A. Zhukova,
D. E. Gomboeva,
E. S. Kolupaeva,
I. Zh. Zhalsanova https://doi.org/10.20538/1682-0363-2019-4-222-232
Abstract
Non-motor symptoms are an essential manifestation of the clinical picture of Parkinson's disease (PD). This literature review is devoted to the study of recent advances in the field of clinical and pathophysiological aspects of the non-motor manifestations of Parkinson's disease.
Aim. The aim was to study and generalize the wide range of non-motor manifestations of PD and their features in this pathology, and to reveal the pathophysiological link between motor and non-motor manifestations of the disease and the role of the neurodegenerative process in the clinical picture of PD.
Materials and methods. Keywords (Parkinson's disease, non-motor symptoms, apathy, anxiety, depression, sleep disorder, pain) search in the Web of Science, Core Collection, Scopus, Pubmed databases.
Results. Knowledge about the presence of PD non-motor symptoms, characteristics of their manifestations improve their diagnosis and help to choose the correct treatment strategy. This survey comprises nonmotor manifestations of PD, such as: mood disorders (apathy, anxiety, depression), impulse control disorders (dopamine disregulation syndrome), sleep disorders (insomnia, excessive daytime sleepiness, bouts of sleepiness, conduct disorder in REM phase of sleep), autonomic disorders (constipation, enuresis, thermoregulatory dysfunction, cardiovascular disorders, orthostatic hypotension), and cognitive impairment.
About the Authors
M. A. Nikitina
Siberian State Medical University (SSMU)
Russian Federation
Russian Federation
PhD, Associate Professor, Department of Neurology and Neurosurgery,
2, Moscow Trakt, 634050, Tomsk
N. G. Zhukova
Siberian State Medical University (SSMU)
Russian Federation
Russian Federation
DM, Professor, Department of Neurology and Neurosurgery,
2, Moscow Trakt, 634050, Tomsk
E. Yu. Bragina
Research Institute of Medical Genetics, Tomsk National Research Medical center (NRMC) of the Russian Academy of Sciences
Russian Federation
Russian Federation
PhD, Senior Researcher, Laboratory of Population Genetics,
10, Naberezhnaya Ushayki Str., Tomsk, 634050
V. M. Alifirova
Siberian State Medical University (SSMU)
Russian Federation
Russian Federation
DM, Professor, Head of the Department of Neurology and Neurosurgery,
2, Moscow Trakt, 634050, Tomsk
I. A. Zhukova
Siberian State Medical University (SSMU)
Russian Federation
Russian Federation
PhD, Associate Professor, Department of Neurology and Neurosurgery,
2, Moscow Trakt, 634050, Tomsk
D. E. Gomboeva
Research Institute of Medical Genetics, Tomsk National Research Medical center (NRMC) of the Russian Academy of Sciences
Russian Federation
Russian Federation
Post-Graduate Student, Laboratory of Population Genetics,
10, Naberezhnaya Ushayki Str., Tomsk, 634050
E. S. Kolupaeva
Siberian State Medical University (SSMU)
Russian Federation
Russian Federation
Resident, Department of Neurology and Neurosurgery,
2, Moscow Trakt, 634050, Tomsk
I. Zh. Zhalsanova
Research Institute of Medical Genetics, Tomsk National Research Medical center (NRMC) of the Russian Academy of Sciences
Russian Federation
Russian Federation
Post-Graduate Student, Laboratory of Population Genetics,
10, Naberezhnaya Ushayki Str., Tomsk, 634050
References
1. Fenelon G., Alves G. Epidemiology of psychosis in Parkinson's disease. Journal of the Neurological Sciences. 2010; 289 (1–2): 12–17. DOI: 10.1016/j.jns.2009.08.014.
2. Tysnes O.B., Storstein A. Epidemiology of Parkinson’s disease. J. Neural. Transm. (Vienna). 2017; 124 (8): 901–905. DOI: 10.1007/s00702-017-1686-y.
3. Petrov V.A., Alifirova V.M., Saltykova I.V., Zhukova I.A., Zhukova N.G., Dorofeeva Y.B., Tyakht A.V., Altukhov I.A., Kostryukova E.S., Titova M.A., Mironova Y.S., Izhboldina O.P., Nikitina M.A., Perevozchikova T.V., Fait E.A., Sazonov A.E. Comparison study of gut microbiota in case of Parkinson’s disease and other neurological disorders. Bulletin of Siberian Medicine. 2016; 15 (5): 113–125. (in Russ.). DOI: 10.20538/1682-0363-2016-5-113-125.
4. Lang A. A critical appraisal of the premotor symptoms of Parkinson's disease: Potential usefulness in early diagnosis and design of neuroprotective trials. Mov. Disord. 2011: 26 (5): 775–783. DOI: 10.1002/mds.23609.
5. Rana A.Q., Ahmed U.S., Chaudry Z.M., Vasan S. Parkinson’s disease: a review of non-motor symptoms. Expert Rev. Neurother. 2015; 15 (5): 549–562. DOI: 10.1586/14737175.2015.1038244.
6. Pfeiffer R.F. Non-motor symptoms in Parkinson’s disease. Parkinsonism Relat. Disord. 2016; 22 (Suppl. 1): 119–122. DOI: 10.1016/j.parkreldis.2015.09.004.
7. Macleod A.D., Counsell C.E. Predictors of functional dependency in Parkinson’s disease. Mov. Disord. 2016; 31 (10): 1482–1488. DOI: 10.1002/mds.26751.
8. Weintraub D., Burn D.J. Parkinson's disease: the quintessential neuropsychiatric disorder. Mov. Disord. 2011; 26 (6): 1022–1031. DOI: 10.1002/mds.23664.
9. Bonnet A., Jutras M., Czernecki V., Corvol J., Vidailhet M. Nonmotor symptoms in Parkinson’s disease in 2012. Relevant Clinical Aspects. Parkinson’s Disease. 2012; 2012: 198316. DOI: 10.1155/2012/198316.
10. Bugalho P., Lampreia T., Miguel R., Mendonзa M.D., Caetano A., Barbosa R. Non-motor symptoms in Portuguese Parkinson’s disease. Sci. Rep. 2016; 6: 32267. DOI: 10.1038/srep32267.
11. Li H., Zhang M., Chen L., Zhang J., Pei Z., Hu A. et al. Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson’s disease. Mov. Disord. 2010; 25 (16): 2740–2746. DOI: 10.1002/mds.23368.
12. Merello M., Gerschcovich E., Ballesteros D., Cerquetti D. Correlation between the movement disorders society unified Parkinson’s disease rating scale (MDS–UPDRS) and the Uunified Parkinson’s disease rating scale (UPDRS) during l-dopa acute challenge. Parkinsonism & Related Disorders. 2011; 17 (9): 705–707. DOI: 10.1016/j.parkreldis.2011.07.002.
13. Gallagher D.A., Lees A.J., Schrag A. What are the most important non-motor symptoms in patients with Parkinson’s disease and are we missing them? Mov. Disord. 2010; 25 (15): 2493–500. DOI: 10.1002/mds.23394.
14. Liu W.M., Lin R.J., Yu R.L., Tai C.H., Lin C.H., Wu R.M. The impact of nonmotor symptoms on quality of life in patients with Parkinson’s disease in Taiwan. Neuropsychiatr. Dis. Treat. 2015; 11: 2865–2873. DOI: 10.2147/NDT.S88968.
15. Prakash K.M., Nadkarni N.V., Lye W.K., Yong M.H., Tan E.K. The impact of non-motor symptoms on the quality of life of Parkinson’s disease patients: a longitudinal. Eur. J. Neurol. 2016; 23 (5): 854–860. DOI: 10.1111/ene.12950.
16. Chaudhuri K., Schapira A. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. The Lancet Neurology. 2009; 8 (5): 464-474. DOI: 10.1016/S1474-4422(09)70068-7.
17. Schapira A. The measurement and importance of non-motor symptoms in Parkinson disease. Eur. J. Neurol. 2015; 22 (1): 2–3. DOI: 10.1111/ene.12523.
18. Liepelt-Scarfone I., Pilotto A., Muller K., Bormann C., Gauss K., Wurster I. et al. Autonomic dysfunction in subjects at high risk for Parkinson’s disease. J. Neurol. 2015; 262 (12): 2643–2652. DOI: 10.1007/s00415-015-7888-z.
19. Zhukova I.A., Zhukova N.G., Izhboldina O.P., Nikitin M.A., Alifirova V.M. Methods for assessing the olfactory function in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. Vol. 2: Neurology and psychiatry of advanced age. 2015; 115 (2): 47–52 (in Russ.). DOI: 10.17116/jnevro20151156244-49.
20. Cersosimo M.G., Raina G.B., Pecci C., Pellene A., Calandra C.R., Gutiйrrez C., Micheli F.E., Benarroch E.E. Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J. Neurol. 2013; 260 (5): 1332–1338. DOI: 10.1007/s00415-012-6801-2.
21. Peeraully T., Yong M.H., Chokroverty S., Tan E.K. Sleep and Parkinson’s disease: a review of case-control polysomnography studies. Mov. Disord. 2012; 27 (14): 1729–1737. DOI: 10.1002/mds.25197.
22. Mьller B., Assmus J., Herlofson K., Larsen J.P., Tysnes O.B. Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson’s disease. Parkinsonism Relat. Disord. 2013; 19 (11): 1027–1032. DOI: 10.1016/j.parkreldis.2013.07.010.
23. Hauser R., Auinger P. Determination of minimal clinically important change in early and advanced Parkinson’s disease. Mov. Disord. 2011; 26 (5): 813–818. DOI: 10.1002/mds.23638.
24. Qamhawi Z., Towey D., Shah B., Pagano G., Seibyl J., Marek K., Borghammer P., Brooks D.J., Pavese N. Clinical correlates of raphe serotonergic dysfunction in early Parkinson’s disease. Brain. 2015; 138 (Pt. 10): 2964–2973. DOI: 10.1093/brain/awv215.
25. Martнnez-Martнn P., Damiбn J. Parkinson disease: Depression and anxiety in Parkinson disease. Nature Reviews Neurology. 2010; 6 (5): 243–245. DOI: 10.1038/nrneurol.2010.49.26. Goldstein D.S. Dysautonomia in Parkinson disease. Compr. Physiol. 2014; 4 (2): 805–826. DOI: 10.1002/cphy.c130026.
26. Balestrino R., Martinez-Martin P. Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson’s disease. J. Neurol. Sci. 2017; 373: 173–178. DOI: 10.1016/j.jns.2016.12.060.
27. Iranzo A., Serradell M., Vilaseca I., Valldeoriola F., Salamero M., Molina C., Santamaria J., Tolosa E. Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. Parkinsonism Relat. Disord. 2013; 19 (6): 600–604. DOI: 10.1016/j.parkreldis.2013.02.009.
28. Visanji N.P., Brooks P.L., Hazrati L.N., Lang A.E. The prion hypothesis in Parkinson's disease: braak to the future. Acta Neuropathol. Commun. 2013; 1: 2. DOI: 0.1186/2051-5960-1-2.
29. Braak H., Rub U., Jansen Steur E.N., Del Tredici K., de Vos R.A. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology. 2005; 64 (8): 1404–1410. DOI: 10.1212/01.WNL.0000158422.41380.82.
30. Tomic S., Rajkovaca I., Pekic V., Salha T., Misevic S. Impact of autonomic dysfunctions on the quality of life in Parkinson’s disease patients. Acta Neurol. Belg. 2017; 117 (1): 207–211. DOI: 10.1007/s13760-016-0739-6.
31. De Luka S.R., Svetel M., Pekmezoviс T., Milovanoviс B., Kostiс V.S. When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson’s disease? Vojnosanit Pregl. 2014; 71 (4): 346–351. DOI: 10.2298/VSP1404346D.
32. Badri A.V., Purohit R.S., Skenazy J., Weiss J.P., Blaivas J.G. A review of lower urinary tract symptoms in patients with Parkinson’s disease. Curr. Urol. Rep. 2014; 15 (9): 435. DOI: 10.1007/s11934-014-0435-0.
33. Walker D.G., Lue L.F., Adler C.H., Shill H.A., Caviness J.N., Sabbagh M.N., Akiyama H., Serrano G.E., Sue L.I., Beach T.G. Arizona Parkinson disease consortium. Changes in properties of serine 129 phosphorylated a-synuclein with progression of Lewy-type histopathology in human brains. Exp. Neurol. 2013; 240: 190–204. DOI: 10.1016/j.expneurol.2012.11.020.
34. Heller J., Dogan I., Schulz J.B., Reetz K. Evidence for gender differences in cognition, emotion and quality of life in Parkinson’s disease? Aging Dis. 2013; 5 (1): 63–75. DOI: 10.14366/AD.2014.050063.
35. Dickson D.W., Braak H., Duda J.E., Duyckaerts C., Gasser T., Halliday G.M., Hardy J., Leverenz J.B., Tredici K.D., Wszolek Z.K., Litvan I. Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria. Lancet Neurol. 2009; 8 (12): 1150–1157. DOI: 10.1016/S1474-4422(09)70238-8.
36. Wolters E. Non-motor extranigral signs and symptoms in Parkinson's disease. Parkinsonism Relat. Disord. 2009; 15 (Suppl. 3): 6–12. DOI: 10.1016/S1353-8020(09)70770-9.
37. Kostryukova E.S., Alifirova V.M., Zhukova N.G., Zhukova I.A., Izhboldina O.P., Petrov V.A., Mironova Y.S., Latypova A.V., Nikitina M.A., Titova M.A., Tyakht A.V., Dorofeeva Y.B., Saltykova I.V., Sazonov A.E. Olfactory dysfunction and modification in microbiota as early non-motor manifestations of Parkinson’s disease. Bulletin of Siberian Medicine. 2016; 15 (5): 66–74 (in Russ.). DOI: 10.20538/1682-0363-2016-5-66-74.
38. Postuma R., Aarsland D., Barone P. et al. Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. Mov. Disord. 2012; 27: 617–626. DOI: 10.1002/mds.24996.
39. Cavaco S., Gonзalves A., Mendes A., Vila-Chг N., Moreira I., Fernandes J., Damбsio J., Teixeira-Pinto A., Bastos Lima A. Abnormal olfaction in Parkinson disease is related to faster disease progression. Behav. Neurol. 2015; 2015: 976589. DOI: 10.1155/2015/976589.
40. Valkovic P., Minar M., Singliarova H., Harsany J., Hanakova M., Martinkova J., Benetin J. Pain in Parkinson’s disease: a cross-sectional study of its prevalence, types, and relationship to depression and quality of life. PLoS One. 2015; 10 (8): e0136541. DOI: 10.1371/journal.pone.0136541.
41. Goldman J.G., Stebbins G.T., Leung V., Tilley B.C., Goetz C.G. Relationships among cognitive impairment, sleep, and fatigue in Parkinson’s disease using the MDS–UPDRS. Parkinsonism Relat. Disord. 2014; 20 (11): 1135–1139. DOI: 10.1016/j.parkreldis.2014.08.001.
42. Huber S.J., Paulson G.W., Shuttleworth E.C. Relationship of motor symptoms, Intellectual impairment, and depression in Parkinson's disease. J. Neurosurg. Psychiat. 1988; 51 (6): 855–858. DOI: 10.1136/jnnp.51.6.855.
43. Voon V., Fernagut P., Wickens J., Baunez C., Rodriguez M., Pavon N., Juncos J., Obeso J., Bezard E. Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders. The Lancet Neurology. 2009; 8 (12): 1140–1149. DOI: 10.1016/S1474-4422(09)70287-X.
44. Evans A.H., Katzenschlager R., Paviour D., O'Sullivan J.D., Appel S., Lawrence A.D., Lees A.J. Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome. Mov. Disord. 2004; 19 (4): 397–405. DOI: 10.1002/mds.20045.
45. Weintraub D., Koester J., Potenza M.N., Siderowf A.D., Stacy M., Voon V., Whetteckey J., Wunderlich G.R., Lang A.E. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch. Neurol. 2010; May; 67 (5): 589–595. DOI: 10.1001/archneurol.2010.65.
46. Tan L.C.S. Mood disorders in Parkinson’s disease. Parkinsonism Relat. Disord. 2012; 18: 1: S74–76. DOI: 10.1016/S1353-8020(11)70024-4. 48. Moore O., Kreitler S., Ehrenfeld M., Giladi N. Quality of life and gender identity in Parkinson’s disease. J. Neural. Transm. 2005; 112 (11): 1511–1522. DOI: 10.1007/s00702-005-0285-5.
47. Dogan V.B., Koksal A., Dirican A., Baybas S., Dirican A., Dogan G.B. Independent effect of fatigue on health-related quality of life in patients with idiopathic Parkinson’s disease. Neurol. Sci. 2015; 36 (12): 2221–2226. DOI: 10.1007/s10072-015-2340-9.
48. Schrempf W., Brandt M.D., Storch A., Reichmann H. Sleep disorders in Parkinson’s disease. J. Parkinsons Dis. 2014; 4 (2): 211–221. DOI: 10.3233/JPD-130301.
49. Ratti P.L., Negre-Pages L., Perez-Lloret S., Manni R., Damier P., Tison F. Subjective sleep dysfunction and insomnia symptoms in Parkinson’s disease: insights from a cross-sectional evaluation of the French CoPark cohort. Parkinsonism Relat. Disord. 2015; 21 (11): 1323–1329. DOI: 10.1016/j.parkreldis.2015.09.025.
50. Gaig C., Tolosa E. When does Parkinson's disease begin? Mov. Disord. 2009; 24 (Suppl. 2): S656–664. DOI: 10.1002/mds.22672.
51. Schulte E.C., Winkelmann J. When Parkinson’s disease patients go to sleep: specific sleep disturbances related to Parkinson’s disease. J. Neurol. 2011; 258 (Suppl. 2): S328–335. DOI: 10.1007/s00415-011-5933-0.
52. Tyakht A.V., Alifirova V.M., Zhukova N.G., Zhukova I.A., Latypova A.V., Izhboldina O.P., Petrov V.A., Mironova Y.S., Titova M.A., Nikitina M.A., Kostryukova E.S., Dorofeeva Y.B., Saltykova I.V., Sazonov A.E. Is gut microbiota associated with Parkinson’s disease? Bulletin of Siberian Medicine. 2016; 15 (5): 134–146 (in Russ.). DOI: 10.20538/1682-0363-2016-5-134-146.
53. Haehner A., Boesveldt S., Berendse H., Mackay-Sim A., Fleischmann J. Prevalence of smell loss in Parkinson's disease – a multicenter study. Parkinsonism & Related Disorders. 2009; 15 (7): 490–494. DOI: 10.1016/j.parkreldis.2008.12.005.
Review
For citations:
Nikitina M.A., Zhukova N.G., Bragina E.Yu., Alifirova V.M., Zhukova I.A., Gomboeva D.E., Kolupaeva E.S., Zhalsanova I.Zh. Clinical and pathophysiological aspects of non-motor manifestations of Parkinson's disease. Bulletin of Siberian Medicine. 2019;18(4):222-232. (In Russ.) https://doi.org/10.20538/1682-0363-2019-4-222-232
Views:
907
Email this article 