Objective: To examine a cohort of Veterans with drug-induced parkinsonism (DIP) using [123I]Ioflupane single photon emission computed tomography (DAT-SPECT) to identify those with nigrostriatal degeneration and compare differences between subjects with and without underlying neurodegeneration.

Background: DIP is common and can be clinically indistinguishable from idiopathic Parkinson’s disease (PD). When symptoms persist after drug withdrawal, DIP may represent “unmasking” of prodromal PD. We explored the prevalence of abnormal DAT-SPECT and features associated with underlying neurodegeneration.

Method: We reviewed DAT-SPECT scans from 35 patients with DIP. Scans were read as normal or abnormal by a radiologist without knowledge of clinical status. Semi-quantitative analysis of uptake in the caudate, anterior and posterior putamen, and striatum was performed using software. Motor function was assessed with the Unified Parkinson’s Disease Rating Scale Part III (UPDRS3). Non-motor assessments included University of Pennsylvania Smell Identification Test (UPSIT), Non-Motor Symptoms Questionnaire (NMSQ) and RBD Screening Questionnaire (RBDSQ).

Results: The cohort was comprised of 91% men with a mean age of 64.4±7.1 years. Comparing subjects with normal vs. abnormal imaging, there were no differences in age, sex, race, UPDRS3 or RBDSQ.  However, those with neurodegeneration had lower UPSIT age/sex adjusted percentile scores (29.5±22.3 vs. 46.2±23.4, p=0.047) and reported more NMS overall (16.2±5.6 vs. 11.4±6.8, p=0.035). UPSIT and NMSQ were both significant predictors of scan result in multivariate models controlling for age. AUC for UPSIT percentile and NMS as a predictor of DAT-SPECT result were 0.72 (CI 0.53-0.89) and 0.70 (0.59-0.89). AUC for a measure combining poor olfaction and high NMS burden was 0.77 (0.60-0.92). Age-adjusted Z-scores for DAT uptake were lower for abnormal scans in all regions (striatum p=0.006, caudate p=0.016, anterior putamen p=0.009, posterior putamen p<0.001) but decreased uptake was most prominent in the posterior putamen.

Conclusion: Many subjects with clinically presumed DIP had evidence of underlying DAT-SPECT abnormalities in a pattern consistent with early PD. Poor olfaction and higher burden of non-motor symptoms, both associated with prodromal PD, may be useful alone and in combination to identify DIP patients with underlying dopaminergic degeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/predictors-of-underlying-neurodegeneration-in-drug-induced-parkinsonism/