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.

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.

We reviewed DAT-SPECT scans from 34 patients with DIP to identify those with underlying nigrostriatal degeneration. Scans were read as normal or abnormal by two nuclear medicine physicians without knowledge of clinical status. Motor function was assessed using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-3), gait data were collected using an instrumented Timed Up and Go (TUG) test, and non-motor assessments included the Non-Motor Symptoms Questionnaire (NMSQ), RBD Screening Questionnaire (RBDSQ), and University of Pennsylvania Smell Identification Test (UPSIT).

The cohort was 94% male with a mean age of 64.5±7.1 years. 35% had underlying neurodegeneration. Comparing subjects with normal and abnormal imaging, there were no differences in age, sex, race, psychiatric diagnosis, or total UPDRS-3 and RBDSQ scores. Those with underlying neurodegeneration had greater turn steps (6.9±0.8 vs. 5.3±1.0 steps, p<0.001), turning duration (3.8±0.7 vs. 3.0 ± 0.7 seconds, p=0.005), lower UPSIT age/sex adjusted percentile scores (27.6±22.1 vs. 46.2±23.4, p=0.031), and more NMS overall (16.5±5.7 vs. 11.4±6.8, p=0.033). AUC for turn steps was 0.91 (CI 0.81-1.00), while AUC for a measure combining turn steps, turn duration, poor olfaction, and high NMS burden was 0.92 (0.83-1.00).

Many subjects with clinically presumed DIP had evidence of underlying DAT-SPECT abnormalities. Gait impairment, poor olfaction, and a higher burden of non-motor symptoms may be useful alone and in combination to identify DIP patients with underlying dopaminergic degeneration.