Dentate nucleus iron deposition is a potential biomarker for tremor‐dominant Parkinson's disease

Abstract

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic-rigid dominant (AR)] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0 T MR system. Inter-group susceptibility differences in bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast to the AR group, the TD group was found to have increased susceptibility in the bilateral DN, when compared to healthy controls. In addition, susceptibility was positively correlated with tremor score in drug naive PD patients. These findings indicate that iron load within DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR phenotypes of PD can be differentiated on the basis of the susceptibility of the DN at least on the group level.

Influence of regional iron on the motor impairments of Parkinson's disease: A quantitative susceptibility mapping study

“…Furthermore, we also observed that increasing dentate iron positively correlated with increasing tremor severity. This finding was supported by a recent study that was solely focused on the role of DN in PD . To date, a growing body of evidence demonstrated the abnormal status of the cerebellum in parkinsonian tremor patients because increased blood flow and metabolism, as well as increased neuronal activity, was commonly reported, indicating the possibility of involvement in DN, as it is the biggest subcortical nucleus in cerebellum.…”

“…Third, for smaller concentration of iron, Haacke et al suggested that there may be little noticeable effect on , even in the presence of what could be physiologically a dangerously high level of iron. On the contrary, QSM seems to be more sensitive in quantifying iron content in the small iron‐rich regions, such as RN, and DN in the present study and previously . In brief, with extensive practice of QSM so far, QSM is demonstrated to be more sensitive in the quantification of regional iron content than R2* and with a great potential in future applications.…”

“…On the contrary, QSM seems to be more sensitive in quantifying iron content in the small iron-rich regions, such as RN, 15,27 and DN in the present study and previously. 35 In brief, with extensive practice of QSM so far, QSM is demonstrated to be more sensitive in the quantification of regional iron content than R2* and with a great potential in future applications.…”

Iron deposition quantification: Applications in the brain and liver

“…All these studies show the value of QSM but one in particular notes that QSM is better than for finding the subthalamic nucleus (STN) . Work by He et al, suggests that the iron in the dentate nucleus increases in tremor‐dominated PD (Fig. ), while another study shows iron in the dentate goes down for a general idiopathic PD cohort .…”

“…QSM is able to visualize the basal ganglia, midbrain, and dentate nucleus structures very well . Several articles note that there are variabilities spatially in iron build‐up .…”