Objective: The aim of this study is to explore whether monogenic PD (due to parkin or DJ-1 homozygous mutations) can be subtyped as “brain-first” by imaging the dopaminergic innervation of striatum and heart with F-DOPA PET, hypothesizing that it is devoid of peripheral α-synuclein pathology.

Background: The recent efforts for subtyping PD as “body-first” or “brain-first” depending on clinical features (motor and non-motor symptomatology) need to be confirmed by practical imaging tools examining the distribution of possible α-synuclein pathology. In this regard, F-DOPA PET imaging for brain and cardiac dopaminergic innervation at same session may provide valuable insights for subtyping monogenic PD (MPD) in comparison to idiopathic PD (IPD).

Method: A total of 23 patients (15 PARK2, 2 PARK7, 6 IPD shown to have no known PD mutations) were included and phenotypical features were noted. Both cardiac and brain F-DOPA PET-CT were acquired. Myocardium F-DOPA was considered to be reduced if the heart/mediastinum<1.5. Striatal F-DOPA uptake was evaluated visually(0=normal;1=mild;2=moderate;3=severe).

Results: 17 MPD (age 44.35±9.51) and 6 IPD (age 48.17±11.95) were similar for age and gender (p=0.47 and 0.17) but mean disease duration was longer in MPD (13.88±6.14 years vs 4.83±2.13 years; p<0.001). In MPD group, F-DOPA uptake tended to be more decreased in all the striatal regions except for the left putamen when compared to IPD group. This reduction was most significant for left caudate corpus (p<0.018). Myocardial F-DOPA uptake was reduced in 4 of 17 MPD and 4 of 6 IPD, showing less cardiac denervation in MPD but not reaching statistical significance(p=0.13) possibly due to limited number of patients in IPD group. Mean disease duration was similar between patients with normal and reduced myocardial F-DOPA uptake (12.2±7.0 and 10.1±6.1 years, p=0.59), while F-DOPA uptake reduction was higher in all the striatal regions in patients with normal myocardial F-DOPA uptake. MPD with/without cardiac denervation did not differ in terms of having constipation or RBD.

Conclusion: This preliminary study showed that reduction in striatal F-DOPA uptake is more severe in MPD patients, although myocardial dopaminergic innervation is preserved. These results support the “brain-first” pathogenetic characteristic of MPD as expected and suggest that F-DOPA PET may be used as a practical tool for evaluating dopaminergic innervation of brain and heart together.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/does-autosomal-recessive-parkinsons-disease-behave-as-brain-first-subtype/