Behind the mirror: clinical and neuroradiological significance of mirror movements in idiopathic REM sleep behavior disorder

Autori

Elisabetta Sarasso (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy)

Roberta Balestrino (Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy)

Silvia Basaia (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Andrea Gardoni (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Saverio Sangermano (Vita-Salute San Raffaele University, Milan, Italy)

Sara Marelli (Sleep Disorders Center, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy)

Alessandra Castlenuovo (Sleep Disorders Center, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy)

Andrea Grassi (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Elisa Canu (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Luigi Ferini-Strambi (Sleep Disorders Center, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy)

Massimo Filippi (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy) – Federica Agosta (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Background and aims

Idiopathic REM Sleep Behavior Disorder (iRBD) is a recognized prodromal stage of synucleinopathies such as Parkinson’s disease (PD). Mirror movements (MM), involuntary contralateral mirroring of voluntary motor actions, are paraphysiological phenomena present in childhood and minimally in elder healthy subjects. Their re-emergence is documented in a wide range of diseases such as stroke, multiple sclerosis and movement disorders. They have been observed in PD, where they may reflect a compensatory cortical activation. In this context, MM appear as an epiphenomenon, whose expression is amplified by impaired interhemispheric inhibition. To our knowledge their presence and significance in iRBD have not been explored.

Methods

We enrolled 49 polysomnography-confirmed iRBD patients, divided into MM-positive (n=33) and MM-negative (n=16) groups. MM were phenotyped as monolateral (n=10) or bilateral (n=23). All underwent neurological, cognitive (MMSE, FAB, Rey and Benson figures, Rey Word List, Corsi, Token Test), motor (UPDRS I–III, 9HPT, 5TSTS, 10MWT), and MRI evaluations. FLAIR, 3DT1, 3DT2 sequences were used to assess hyperintense lesions (juxtacortical lesions, deep grey matter (DGM) lesions, periventricular lesions, infratentorial lesion) via volumetric and lesion count analyses. This study was funded from the Italian Ministero della Salute (grant number RF-2018-12366746).

Results

MM-positive patients showed lower upper limb dexterity (9HPT: 24.16±3.38 s vs 22.43±3.05 s, p=0.029) and reduced visuospatial-executive function (Corsi: 4.97±0.64 vs 5.63±1.03, p=0.004; Rey copy: 32.58±2.41 vs 34.13±1.71, p=0.01). Monolateral MM had younger age and more pronounced cognitive impairment in visuospatial, memory, and language tasks. Bilateral MM presented significantly increased DGM lesion volume (32.00±39.28 mm³ vs 11.00±19.00 in monolateral MM, p=0.049) and lesion number (1.45±1.64 vs 0.22±0.44, p=0.029), as well as greater periventricular hyperintense lesions burden (p=0.071 trend). Correlation analyses revealed that periventricular lesion volume and number were significantly associated with worse visuospatial performance (e.g. Rey copy: p=0.002, r=–0.668), mood symptoms (BDI-II: p=0.013, r=0.572), and gait impairment (N° of steps at 10MWT: p=0.014, r=0.555).

Conclusion

MM are common in iRBD but display distinct clinical and radiological profiles. Monolateral MM may reflect more closely early neurodegenerative processes and initial cognitive changes, while bilateral MM may reflect a more aspecific pattern, potentially driven by vascular burden. MM assessment may help identifying subgroups with different trajectories and risk profiles in the prodromal phase of synucleinopathies: longitudinal analysis is warranted to explore this hypothesis.

REFERENCES

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