Cerebellar, Not Nigrostriatal Degeneration Impairs Dexterity in Multiple System Atrophy

Abstract

BackgroundMultiple 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.ObjectiveThe aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA.MethodsWe 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.ResultsNigrostriatal 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.ConclusionCerebellar 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.

Complemental Value of Microstructural and Macrostructural MRI in the Discrimination of Neurodegenerative Parkinson Syndromes

“…For example, an elevated nigral mean diffusivity and reduced fractional anisotropy were observed compared to healthy subjects; however, the interpretability of DTI metrics is constrained as they are limited to information on the orientation and isotropy of diffusivity [ 15 ]. Compared to DTI, biophysically motivated models, such as neurite orientation dispersion and density imaging (NODDI) and diffusion microstructure imaging (DMI) provide a more specific and interpretable approximation of the microstructure [ 16 – 18 ], e.g., observing an increased nigral-free water fraction in neurodegenerative Parkinson syndromes [ 19 , 20 ]. In contrast to NODDI, DMI is not restricted to hard a priori assumptions, therefore is more suitable to assess pathologically altered microstructures [ 17 ] and has already been successfully applied in clinical research [ 14 , 20 – 23 ].…”