Non-motor Parkinson disease: new concepts and personalised management

Titova, Nataliya; Chaudhuri, K Ray

doi:10.5694/mja17.00993

ARTICLE
AUTHORS
REFERENCES

Topics

Nervous system diseases

Social determinants of health

Diagnostic techniques and procedures

Summary

Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms.
NMS dominate the prodromal phase of PD and some may serve as clinical biomarkers of PD.
NMS can be dopaminergic, non-dopaminergic, of genetic origin or drug induced.
Clinical assessment of NMS should include the NMS Questionnaire (completed by patients) for screening, as recommended by the International Parkinson and Movement Disorders Society and other international societies.
The total number of NMS in a patient with PD constitutes the NMS burden, which can be graded using validated cut-off scores on the NMS Questionnaire and Scale and can be used as an outcome measure in clinical trials.
Despite NMS burden having a major effect on the quality of life of patients and carers, a large European study showed that NMS are often ignored in the clinic.
The syndromic nature of PD is underpinned by non-motor subtypes which are likely to be related to specific dysfunction of cholinergic, noradrenergic, serotonergic pathways in the brain, not just the dopaminergic pathways.
NMS can be treated by dopaminergic and non-dopaminergic strategies, but further robust studies supported by evidence from animal models are required.
The future of modern treatment of PD needs to be supported by the delivery of personalised medicine.

1 Pirogov Russian National Research Medical University, Moscow, Russia
2 Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK

Correspondence: nattitova@yandex.ru

Acknowledgements:

We thank the National Institute of Health Research Biomedical Research Centre and the Institute of Psychiatry, Psychology and Neuroscience at Kings College London for supporting research cited in this article, and the MDS Non-Motor Parkinson’s Disease Study Group.

Competing interests:

No relevant disclosures.

1. Parkinson J. An essay on the shaking palsy. Lond Med Phys J 1817; 38.
2. Korczyn AD. Parkinson’s disease: one disease entity or many? J Neural Transm 1999; 56: 107-111.
3. Langston JW. The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006; 59: 591-596.
4. Titova N, Padmakumar C, Lewis SJG, et al. Parkinson’s: a syndrome rather than a disease? J Neural Transm (Vienna) 2017; 124: 907-914.
5. Chaudhuri, KR, Healy DG, Schapira AHV. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 2006; 5: 235-245.
6. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, NMSS Validation Group. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 2011; 26: 399-406.
7. Chaudhuri KR, Rojo JM, Schapira AHV, et al. A proposal for a comprehensive grading of Parkinson’s disease severity combining motor and non-motor assessments: meeting an unmet need. PLoS One 2013; 8: e57221.
8. Chaudhuri KR, Sauerbier A, Rojo J, et al. The burden of non-motor symptoms in Parkinson’s disease using a self-completed non-motor questionnaire: a simple grading system. Parkinsonism Relat Disord 2015; 21: 287-291.
9. Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: time to be precise. Mov Disord 2017; 32: 1147-1154.
10. Alves G, Forsaa E, Pedersen KF, et al. Epidemiology of Parkinson’s disease. J Neurol 2008; 255(Suppl 5): 18-32.
11. Titova N, Qamar MA, Chaudhuri KR. Biomarkers of Parkinson’s disease: an introduction. Int Rev Neurobiol 2017; 132: 183-196.
12. Chaudhuri KR, Odin P. The challenge of non-motor symptoms in Parkinson’s disease. Prog Brain Res 2010; 184: 325-341.
13. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015; 30: 1600-1611.
14. Doppler K, Jentschke HM, Schulmeyer L, et al. Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease. Acta Neuropathol 2017; 133: 535-545.
15. Katunina E, Titova N. The epidemiology of nonmotor symptoms in Parkinson’s disease (cohort and other studies). Int Rev Neurobiol 2017; 133: 91-110.
16. Todorova A, Jenner P, Chaudhuri KR. Non-motor Parkinson’s: integral to motor Parkinson’s, yet often neglected. Pract Neurol 2014; 14: 310-322.
17. Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 2009; 24: 1641-1649.
18. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79: 368-376.
19. Martinez-Martin P, Rodriguez-Blazquez C, Abe K, et al. International study on the psychometric attributes of the non-motor symptoms scale in Parkinson disease. Neurology 2009; 73: 1584-1591.
20. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry 2000; 69: 308-312.
21. Hagell P, Nordling S, Reimer J, et al. Resource use and costs in a Swedish cohort of patients with Parkinson’s disease. Mov Disord 2002; 17: 1213-1220.
22. Braak H, Del Tredici K, Rub U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211.
23. Braak H, Ghebremedhin E, Rub U, et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318: 121-134.
24. Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol 2015; 77: 830-839.
25. Hassan A, Wu SS, Schmidt P, et al. The profile of long-term Parkinson’s disease survivors with 20 years of disease duration and beyond. J Parkinsons Dis 2015; 5: 313-319.
26. Titova N, Martinez-Martin P, Katunina E, et al. Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed. J Neural Transm 2017; 124: 1529-1537.
27. Jellinger KA. Neuropathobiology of non-motor symptoms in Parkinson disease. J Neural Transm (Vienna) 2015; 122: 1429-1440.
28. Jellinger KA. Neuropathology of sporadic Parkinson's disease: evaluation and changes of concepts. Mov Disord 2012; 27: 8-30.
29. Titova N, Schapira AHV, Chaudhuri KR, et al. Nonmotor symptoms in experimental models of Parkinson’s disease. Int Rev Neurobiol 2017; 133: 63-89.
30. Chaudhuri KR, Martinez-Martin P, Schapira AHV, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 2006; 21: 916-923.
31. Chaudhuri KR, Martinez-Martin P, Brown RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 2007; 22: 1901-1911.
32. Martinez-Martin P, Chaudhuri KR, Rojo-Abuin JM, et al. Assessing the non-motor symptoms of Parkinson’s disease: MDS-UPDRS and NMS Scale. Eur J Neurol 2015; 22: 37-43.
33. Titova NV, Chaudhuri KR. Non-motor symptoms of Parkinson’s disease: the submerged part of the iceberg. Ann Clin Exp Neurol 2017; 11(4): 5-18.
34. Sauerbier A, Qamar MA, Rajah T, et al. New concepts in the pathogenesis and presentation of Parkinson’s disease. Clin Med (Lond) 2016; 16: 365-370.
35. Martinez-Martin P, Ray Chaudhuri K. Comprehensive grading of Parkinson’s disease using motor and non-motor assessments: addressing a key unmet need. Expert Rev Neurother 2018; 18: 41-50.
36. Storch A, Schneider CB, Wolz M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 2013; 80: 800-809.
37. Erro R, Vitale C, Amboni M, et al. The heterogeneity of early Parkinson’s disease: a cluster analysis on newly diagnosed untreated patients. PLoS One 2013; 8: e70244.
38. Pont-Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord 2015: 30; 229-237.
39. Sauerbier A, Jenner P, Todorova A, et al. Non motor subtypes and Parkinson’s disease. Parkinsonism Relat Disord 2016; 22(Suppl 1): 41-46.
40. Zis P, Martinez-Martin P, Sauerbier A, et al. Non-motor symptoms burden in treated and untreated early Parkinson’s disease patients: argument for non-motor subtypes. Eur J Neurol 2015; 22: 1145-1150.
41. Marras C, Chaudhuri KR. Nonmotor features of Parkinson’s disease subtypes. Mov Disord 2016; 31: 1095-1102.
42. Williams-Gray CH, Evans JR, Goris A, et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain 2009; 132(Pt 11): 2958-2969.
43. Weintraub D, Simuni T, Caspell-Garcia C, et al.; Parkinson’s Progression Markers Initiative Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov Disord 2015; 30: 919-927.
44. Shimada H, Hirano S, Shinotoh H, et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology 2009; 73: 273-278.
45. Gjerløff T, Fedorova T, Knudsen K, et al. Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain 2015; 138(Pt 3): 653-663.
46. O’Callaghan C, Lewis SJG. Cognition in Parkinson’s disease. Int Rev Neurobiol 2017; 133: 557-583.
47. Muralidharan V, Balasubramani PP, Chakravarthy VS, et al. A neurocomputational model of the effect of cognitive load on freezing of gait in Parkinson’s disease. Front Hum Neurosci 2017; 10: 649.
48. Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson’s disease: the case for noradrenergic enhancement. Mov Disord 2014; 29: 1710-1719.
49. Pavese N, Metta V, Bose SK, et al. Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain 2010; 133: 3434-3443.
50. Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society Evidence-Based Medicine Review Update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 2011; 26(Suppl 3): S42-80.
51. Schrag A, Sauerbier A, Chaudhuri KR. New clinical trials for nonmotor manifestations of Parkinson’s disease. Mov Disord 2015; 30: 1490-1504.
52. Titova N, Jenner P, Chaudhuri KR. The future of Parkinson’s treatment - personalised and precision medicine. Eur Neurol Rev 2017; 12: 15-16.

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Non-motor Parkinson disease: new concepts and personalised management

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