ALTERAZIONI CLINICHE E STRUTTURALI CEREBELLARI IN PAZIENTI CON MALATTIA DI PARKINSON E FREEZING DEL CAMMINO

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CLINICAL AND CEREBELLAR STRUCTURAL ALTERATIONS IN PARKINSON’S DISEASE PATIENTS WITH FREEZING OF GAIT

Autori

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

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

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

Mariotto Sara (University of Verona, Verona, Italy); Di Vico Ilaria (University of Verona, Verona, Italy); Mantovani Elisa (University of Verona, Verona, Italy)

Canu Elisa (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); Bressan Miriana (University of Verona, Verona, Italy); Castelnovo Veronica (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Sibilla Elisa (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy); Tripodi Chiara (Vita-Salute San Raffaele University, Milan, Italy; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy); Freri Fabiola (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy)

Balestrino Roberta (Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurotech Hub, Vita-Salute San Raffaele University, Milan, Italy); Trentinaglia Milena (University of Verona, Verona, Italy); Maffei Francesco (University of Verona, Verona, Italy)

Chiodega Vanessa (University of Verona, Verona, Italy); Taburin Stefano (University of Verona, Verona, Italy)

Volontè Maria Antonietta (Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy); Tinazzi Michele (University of Verona, Verona, Italy)

Filippi Massimo (Vita-Salute San Raffaele University, Milan, Italy; 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); Agosta Federica (Vita-Salute San Raffaele University, Milan, Italy; 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

Cerebellum plays an increasingly recognized role in gait modulation and FoG in PD patients [1]. This study aimed at assessing clinical and cerebellar volume differences in Parkinson’s disease (PD) patients with and without freezing of gait (PD-FoG and PD-NOFoG).

Methods

Thirty-four PD-FoG, 35 PD-NOFoG, and 23 healthy controls underwent clinical assessment and structural MRI. Clinical evaluation included walking, balance, and a comprehensive neuropsychological battery. Grey matter cerebellar volumes were assessed using SUIT atlas. Analyses were Bonferroni-corrected for number of groups.

Results

Compared to healthy controls, both PD-FoG and PD-NOFoG groups showed reduced walking speed, lower balance confidence (ABC scale), impaired balance (MiniBESTest), and an increased number of steps to walk 10 meters both at comfortable and maximal speed. Additionally, they exhibited a worse performance in memory, attention, and executive functions. Only PD-FoG patients showed increased Timed-Up-and-Go test (TUG) completion time both with and without a cognitive dual-task, and a worse visuospatial performance, delayed recall of Rey’s word list, Trail-Making-Test B-A, and phonemic fluency. Both PD groups exhibited reduced cerebellar lobule X volumes, but only PD-FoG patients had a reduced vermis VIIb volume compared to controls. When directly compared, PD-FoG patients demonstrated a greater number of steps in the 10-meter walking test at maximal speed, lower balance confidence, and worse phonemic fluency relative to PD-NOFoG patients. Additionally, PD-FoG patients exhibited increased volumes in cerebellar lobules VIIIb and IX, as well as vermis crus II.

Conclusion

These findings suggest that structural alterations in specific cerebellar regions, involved in motor and cognitive control of movement, may be linked to the pathophysiology of FoG in patients with PD. Further research is needed to determine if these changes reflect compensatory mechanisms or contribute directly to the development of FoG.

REFERENCES

[1] Gardoni A, Agosta F, Sarasso E, Basaia S, Canu E, Leocadi M, Castelnovo V, Tettamanti A, Volontè MA, Filippi M. Cerebellar alterations in Parkinson’s disease with postural instability and gait disorders. J Neurol. 2023 Mar;270(3):1735-1744. doi: 10.1007/s00415-022-11531-y. Epub 2022 Dec 19. PMID: 36534200.

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