Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson’s Disease: A 7 Tesla Imaging Study

Abstract

Background: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. Objective: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. Methods: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). Results: We found that smaller SN correlated with longer disease duration (r =-0.49, p = 0.004), more severe MDS-UPDRS motor score (r =-0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r =-0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. Conclusions: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and lateralitydependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

Substantia Nigra Integrity Correlates with Sequential Working Memory in Parkinson's Disease

“…Earlier clinicopathological studies have shown that the akinetic-rigid subtype exhibited more neuronal loss in the SN than the tremor-dominant subtype of PD (Paulus and Jellinger, 1991;Jellinger, 1999). A recent 7T MRI study confirmed this observation, showing that smaller SN areas correlated with higher bradykinesia-rigidity scores but not tremor scores (Poston et al, 2020). As we also observed a correlation between the SN area and the ordering-related caudate activation, it raises the question whether PD patients with less severe bradykinesia and rigidity would show greater ordering-related caudate activation and better sequencing performance.…”

Predicting the progression of Parkinson's disease using conventional MRI and machine learning: An application of radiomic biomarkers in whole‐brain white matter

“…In recent years, radiomics has been widely used in the field of oncology as an emerging discipline to predict treatment responses and survival outcomes for different cancers. 11 Radiomics is also used in PD, but most of this work constrains usable information to specific brain regions, such as the substantia nigra, 12 or uses other imaging modalities, such as neuromelanin imaging or DTI. 13,14 However, when considering the prevalence of PD and the need for cost-effective and relatively easy-to-use technologies, the applicability of these techniques may be limited.…”

Stem cell in neurodegenerative disorders; an emerging strategy

“…Another well‐known neurodegenerative disease, PD, is described by tremor, rigidity, and bradykinesia in concomitant with postural shakiness looking in some patients since the disease advancements (Poston et al., 2020). It is pathologically identified through the loss of nigrostriatal dopaminergic innervation, while the neurodegeneration is recognized in both dopaminergic neurons and cells situated in other districts of the neural network (Li et al., 2020).…”