Objective: The aim of this study was to investigate the role of substantia nigra microstructural integrity in parkinsonian gait impairments.

Background: Gait impairments are common in Parkinson’s disease (PD). However, quantitative and objective parameters describing gait biomechanical characteristics are needed because the pathological mechanisms are complex and not thoroughly elucidated. As a central structure within the basal ganglia-brainstem loops, the substantia nigra is involved in gait modulation.

Method: Participants (N = 38 PD-patients; N = 33 age-matched controls) walked on a treadmill at fixed speeds of 0.5 and 1.0 km/h. We analyzed biomechanical gait parameters separately and performed a principal component analysis (PCA) to delineate relevant features. As an advanced marker of microstructural integrity, the extracellular water within the substantia nigra was calculated based on participants’ diffusion-weighted MR-images applying the NODDI model. We performed permutation tests using FSL’s randomise tool (5000 permutations) to test microstructural associations with the identified gait components.

Results: PD-patients had increased duration of stance phase, load response, pre-swing, and double support time, and reduced duration of single support and swing time (all P < 0.005). Step and stride length, step and stride times, and cadence were not significantly different between the groups (all P > 0.05). PCA identified two components that were assigned to length and time characteristics and the rhythmic organization of gait, respectively. In PD, the rhythmic component was positively correlated with the amount of extracellular water in the right substantia nigra (r = 0.48; P < 0.005), indicating that patients with increased water extend the duration of stance phase, load response, and pre-swing.

Conclusion: By fixing the gait speed we provide evidence that alterations in the rhythmic organization of gait are not simply a byproduct of bradykinesia-related reduced walking speed. Moreover, the close association between gait rhythmic alterations and extracellular water content in the substantia nigra indicates that patients with more severe neurodegeneration exhibit greater impairments. These results highlight the potential of substantia nigra microstructure imaging to measure gait-dysfunction and disease-progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gait-abnormalities-relate-to-increased-extracellular-water-in-the-substantia-nigra-in-parkinsons-disease-patients/