Distinct Patterns in Midbrain Structures Elucidate Pathophysiology of Parkinson Disease

Findings from an imaging study published in Movement Disorders reveal that the substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr) demonstrate significant patterns of Parkinson disease (PD) progression as reflected by increased relaxation rate (R2*) and quantitative susceptibility mapping, providing further insight into the mechanisms driving the progression of this disease.

A total of 72 patients with PD were compared with 62 non-PD controls in terms of their baseline and 18-month (18.8±0.8 months) MRI findings. The investigators segmented and analyzed 3 midbrain structures — SNc, SNr, and red nucleus — and calculated R2* and quantitative susceptibility mapping values for the SNc and SNr. Additionally, the study investigators compared controls with specific PD subgroups, based on the time following PD diagnosis. Patients were categorized into subgroups according to stage of disease: early-stage PD (<1 year), middle-stage PD (<5 years), and later-stage PD (>5 years).

Significantly higher R2* and quantitative susceptibility mapping values were observed in the SNc and SNr of patients with PD compared with controls at baseline (P ≤.003). The investigators also observed a more rapid R2* increase in the SNc among PD patients vs controls at 18-month follow-up (P =.002); however, there were no between-group differences in quantitative susceptibility mapping values at this same time point (P =.668).

In addition, all PD subgroups had higher baseline SNc R2* (P ≤.006), with a significantly faster increase observed in later-stage PD (P <.0001) that was associated with nonmotor symptom changes (r=0.746, P =.002). At baseline, quantitative susceptibility mapping values in the SNr were higher among patients with middle-stage and later-stage PD patients (P ≤.002); however, only patients with later-stage PD demonstrated a long-term decrease in these values (P =.004) that was associated with motor sign changes (r=0.837, P <.001).

The lack of reliable and objective measures for clinical progression of PD as well as the performance of MRIs in the on-drug state represent possible limitations of this study.

Findings from this study integrate “stage, location, and biological dependencies of different neuroimaging measures and provides a straw man for possibly reconciling apparently contradictory findings in biomarker research, as well as helping to understand the pathophysiology of PD progression.”

Reference

Du G, Lewis MM, Sica C, et al. Distinct progression pattern of susceptibility MRI in the substantia nigra of Parkinson’s patients [published online May 14, 2018]. Mov Disord. doi:10.1002/mds.27318