Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies.

Andrea Pilotto, Alberto Romagnolo, Jasmine A Tuazon, Joaquin A Vizcarra, Luca Marsili, Maurizio Zibetti, Michela Rosso, Federico Rodriguez-Porcel, Barbara Borroni, Maria Cristina Rizzetti, Carlo Rossi, Darwin Vizcarra-Escobar, Jennifer R Molano, Leonardo Lopiano, Roberto Ceravolo, Mario Masellis, Alberto J Espay, Alessandro Padovani, Aristide Merola

Journal: Journal of neurology, neurosurgery, and psychiatry 2020;90(11):1257-1263

PMID: 31142660

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Abstract

OBJECTIVE

Review the effect of orthostatic hypotension (OH) and rapid-eye-movement sleep behavioural disorder (RBD) on survival, cognitive impairment and postural stability, and discuss pathogenic mechanisms involved in the association of these two common non-motor features with relevant clinical outcomes in α-synucleinopathies.

METHODS

We searched PubMed (January 2007-February 2019) for human studies of OH and RBD evaluating cognitive impairment, postural instability, and survival in Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Included studies were analysed for design, key results and limitations as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS

OH and RBD showed a positive association with cognitive impairment in PD and DLB, conflicting association in PAF, and no association in MSA. OH was correlated with incident falls and postural instability in PD and DLB but not in MSA. The association between RBD and postural instability was inconclusive; positive in five studies, negative in seven. OH, but not RBD, correlated with reduced survival in PD, DLB and MSA. The combination of OH and RBD was associated with cognitive impairment and more rapid progression of postural instability.

CONCLUSIONS

OH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a 'malignant' phenotype of PD with early cognitive impairment and postural instability. Underlying mechanisms may include involvement of selected brainstem cholinergic and noradrenergic nuclei.

Address: Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario(BG), Italy.; Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.; Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.; The Ohio State University College of Medicine, Columbus, Ohio, USA.; Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.; Department of Neurology, The State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, USA.; Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.; Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario(BG), Italy.; Unit of Neurology, "F. Lotti" Hospital, Pontedera, Italy.; Hypnos, Institutodel Sueño; Clinica San Felipe; Faculty of Medicine, Universidad PeruanaCayetano Heredia, Lima, Peru.; Department of Neurology and Rehabilitation Medicine, The University of Cincinnati, Cincinnati, Ohio, USA.; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.; Department of Medicine (Neurology) Hurvitz Brain Sciences Program, University of Toronto, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.; Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA [email protected].

DOI: 10.1136/jnnp-2019-320846

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MeSH Terms: Cognitive Dysfunction, Disease Progression, Humans, Hypotension, Orthostatic, Postural Balance, REM Sleep Behavior Disorder, Synucleinopathies