Objective: To quantify the extent of dopaminergic loss in early clinically unilateral PD from studies using presynaptic dopamine imaging with either single photon emission computed tomography (SPECT) or positron emission tomography (PET). To define this loss in relation to normal values stratified by striatal region, and in relation to clinical lateralization.

Background: Neuropathological studies in Parkinson’s disease (PD) suggest that dopaminergic cell loss in the substantia nigra is at least 50% at the onset of motor symptoms, but loss of striatal dopaminergic activity is even greater (70-80%). However, such studies include very few cases of early disease. Neuroimaging can be applied in larger numbers at early clinical stages, but there is variation in case selection, especially disease duration.

Method: A systematic review of studies using presynaptic dopaminergic transporter imaging in early, clinically unilateral PD compared to matched controls was performed. Studies had to include a minimum of 5 cases, and to include data that allowed extraction of findings from the early, clinically unilateral stage. Standard errors for the percentage difference between cases and controls were derived using the delta method, and a random effects analysis was carried out with the I-squared as a measure of heterogeneity.

Results: 410 cases of early unilateral PD who underwent neuroimaging at a mean age of 57.4 (SD 10.4) years, and a disease duration of 1.9 (SD 1.5) years were included from 19 papers. Striatum loss was 41.2 % (95%CI 36.8-45.6) contralateral to the clinically affected side, and 32.2% (95%CI 26.9-37.5) ipsilateral to the affected side; contralateral putamen loss was 52.0% (95%CI 45.3-58.7) while ipsilateral putamen loss was 39.5% (95%CI 30.5-48.5); and contralateral caudate loss was 28.9% (95%CI 24.5-33.4) while ipsilateral caudate loss was 23.3% (95%CI 18.8-27.8).

Conclusion: Striatal dopaminergic loss in early motor PD at the clinically unilateral stage, as defined by dopamine transporter imaging, is around 40% for the clinically affected hemisphere, and so not as severe as neuropathology studies suggested. It ranges from around 30% in the affected caudate, to around 50% in the affected putamen. Given that there is downregulation of the dopamine transporter in PD, the true level of neurodegeneration in this subgroup of early PD cases is probably even lower than the imaging studies suggest.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/striatal-dopaminergic-loss-in-early-clinically-unilateral-parkinsons-disease-a-systematic-review/