Resting-state Functional MRI and Motion Analysis Characteristics in Patients with Isolated REM Sleep Behavior Disorder
Elisabetta Sarasso1, Andrea Gardoni2, Sara Marelli3, Roberta Balestrino4, Lucia Zenere2, Silvia Basaia2, Alessandra Castelnuovo3, Andrea Tettamanti5, Luigi Ferini-Strambi6, Massimo Filippi7, Federica Agosta8
1Neuroimaging Research Unit, Division of Neuroscience; and Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, IRCCS San Raffaele Scientific Institute; and University of Genoa, 2Neuroimaging Research Unit, Division of Neuroscience, 3Division of Neuroscience, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, 4Neurorehabilitation Unit; and Neurosurgery and Gamma Knife Radiosurgery Unit, 5Department of Rehabilitation and Functional Recovery, 6Division of Neuroscience, Sleep Disorders Center, 7Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, 8Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University
Objective:
To assess clinical, motion analysis and resting-state functional MRI (RS-fMRI) functional connectivity (FC) alterations in iRBD patients relative to healthy subjects and the correlations between clinical features and RS-fMRI changes in iRBD.
Background:
Isolated REM sleep behavior disorder (iRBD) might represent an early manifestation of α-synucleinopathies. Indeed, most patients with iRBD develop neurodegenerative parkinsonism over time.
Design/Methods:
Thirty-eight patients with a polysomnography-confirmed iRBD and 28 age/sex-matched healthy controls underwent clinical, motion analysis, and RS-fMRI evaluations. Motion analysis was performed using a stereophotogrammetric system to assess spatio-temporal parameters during single and dual-task gait/mobility conditions. RS-fMRI images were analyzed using an Independent Component Analysis to obtain FC maps of the main RS networks.
Results:
IRBD patients relative to healthy controls showed a worse manual dexterity at 9-hole pegboard test (9HPT). Both iRBD patients and healthy controls worsened the spatio-temporal motion parameters during dual-task relative to single-task gait/mobility tests. However, iRBD patients showed a higher asymmetry of arm swing amplitude during 4-meter walking test (4MWT) and a higher stride length variability during 4MWT with cognitive dual-task relative to healthy subjects. Moreover, iRBD patients showed a decreased FC of pallidum within the basal ganglia network and of occipital and temporal areas within the visuo-associative network compared to healthy controls. Correlation analyses showed that the decreased FC in the basal ganglia network correlated with a worse manual dexterity and with an increased asymmetry of arm swing amplitude during 4MWT in iRBD subjects.
Conclusions:
This study suggested that RS-fMRI, clinical and motion analysis features could help to identify early subtle movement disorders in a subclinical phase, being promising biomarkers for early alpha-synucleinopathy detection in iRBD. Longitudinal data will allow to test a multifactorial prediction model combining fMRI, clinical and motion analysis data to predict the conversion from iRBD to parkinsonian syndromes.