Objective: This study reviewed and compared evidence of nonmotor symptoms in prodromal phases in movement disorders including Parkinson disease, Atypical Parkinsonism (MSA, DLB, PSP), Huntington Disease and Spinocerebellar Ataxias.

Background: A prodromal disease phase refers to the stage in which early symptoms or signs of neurodegeneration are present, but clinical diagnostic criteria are not yet fulfilled. Identifying prodromal stages is difficult and most markers are nonspecific. Known prodromal markers of neurodegenerative diseases (e.g: RBD, cognitive decline, cerebral atrophy) may overlap between diseases. Hence, the investigation of the specificity of prodromal markers is pivotal for an accurate early detection of specific diseases and recruitment for neuroprotective trials.

Methods: PubMed search for studies on prodromal marker was conducted using the search terms of, e.g. (Parkinson disease OR Parkinson’s disease) AND (longitudinal OR cohort OR prospective) AND (prodromal OR premotor OR presymptomatic OR preclinical OR prediagnostic). We included only studies in English. Experts for each neurodegenerative disease entity were invited to review the search and to add other publications not identified by the primary search.

Results: Among the 381 studies initially identified, we included 25 PD, 51 HD,19 DLB, 7 MSA, 10 PSP, 24 SCA, which fulfilled the inclusion criteria. The most common nonmotor symptom found in commonality between diseases was REM sleep Behaviour Disorder (RBD) detected in the prodromal phases of in PD, DLB, MSA and SCA, but not described in prodromal HD or PSP. Also, autonomic dysfunction was reported in prodromal PD, HD, DLB, MSA and SCA; including cardiovascular dysregulation, constipation and urinary dysfunction.

Conclusions: Nonmotor symptoms occurring in the prodromal phases of different movement disorders may indicate common pathophysiological, systemic and progression characteristics in early disease stages. Differences and commonalities of prodromal markers in the prodromal phase of different movement disorders should be considered for improving the early and specific detection of specific movement disorders. Further prospective studies are necessary in this field.

References: Iranzo A, Fernandez-Arcos A, Tolosa E, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One 2014;9(2):e89741. Schrag A, Horsfall L, Walters K, Noyce A, Petersen I.Prediagnostic presentations of Parkinson’s disease in primary care: a case-control study.Lancet Neurol. 2015 Jan;14(1):57-64. doi: 10.1016/S1474-4422(14)70287-X. Epub 2014 Nov 27. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J.Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord. 2013 May;28(5):597-604. Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF.REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century.Neurology. 2010 Aug 10;75(6):494-9. Velazquez-Perez L, Rodriguez Labrada R, Laffita-Mesa M.Prodromal Spinocerebellar Ataxia Type 2: Prospects for Early Interventions and Ethical Challenges.Movement Disorders, Vol. 00, No. 00, 2017 Montes-Brown J, Machado A ,EstØvez M, Carricarte C,Velazquez-Perez L.Autonomic dysfunction in presymptomatic spinocerebellar ataxia type-2.Acta Neurol Scand 2012: 125: 24–29. Kaufmann H, Norcliffe-Kaufmann L, Palma JA, et al. The Natural History of Pure Autonomic Failure: a U.S. Prospective Cohort.Ann Neurol. 2017 February; 81(2): 287–297. Kobal J, Melik Z, Cankar K,Strucl M.Cognitive and autonomic dysfunction in presymptomatic and early Huntington’s disease.J Neurol (2014) 261:1119–1125.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/commonalities-of-prodromal-non-motor-symptoms-between-movement-disorders/