Cerebellar, Not Nigrostriatal Degeneration Impairs Dexterity in Multiple System Atrophy

• Published in: Movement disorders Vol. 39; no. 1; pp. 130 - 140
• Main Authors: Rau, Alexander, Hosp, Jonas A., Rijntjes, Michel, Weiller, Cornelius, Kellner, Elias, Berberovic, Emir, Oikonomou, Panteleimon, Jost, Wolfgang H., Reisert, Marco, Urbach, Horst, Schröter, Nils
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-01-2024; Wiley Subscription Services, Inc
• Subjects: Atrophy; Axons; Basal ganglia; Central nervous system diseases; cerebellar dysfunction; Cerebellum; Cerebellum - diagnostic imaging; dexterity; diffusion microstructure imaging; diffusion multicompartment imaging; Humans; Movement disorders; multiple system atrophy; Multiple System Atrophy - complications; Multiple System Atrophy - diagnostic imaging; Neurodegeneration; Neurodegenerative diseases; Parkinson Disease - complications; Parkinson Disease - diagnostic imaging; Parkinson's disease; Phenotypes; putamen; Substantia nigra; Substantia Nigra - diagnostic imaging; dexterity; substantia nigra; diffusion microstructure imaging; putamen; multiple system atrophy; cerebellar dysfunction; diffusion multicompartment imaging
• DOI: 10.1002/mds.29661
• EISSN: 1531-8257
• ISSN: 0885-3185

Background
Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA‐P [multiple system atrophy‐parkinsonian subtype]) and one with predominant cerebellar deficits (MSA‐C [multiple system atrophy‐cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA.
Objective
The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA.
Methods
We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA‐P and 17 patients with MSA‐C compared to 31 healthy controls (HC). Dexterity was assessed using the 9‐Hole Peg Board (9HPB) performance.
Results
Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free‐fluid compartment, was present in MSA‐P and MSA‐C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA‐P showed more pronounced putaminal degeneration than MSA‐C. In contrast, a cerebellopontine axonal degeneration was observed in MSA‐P and MSA‐C, with stronger effects in MSA‐C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration.
Conclusion
Cerebellar dysfunction contributes to impaired dexterity not only in MSA‐C but also in MSA‐P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.