Can drug-induced Parkinsonism reveal pre-motor Parkinson disease? (P6.054)

OBJECTIVE: To characterize underlying striatal dopaminergic denervation in patients with presumed drug-induced Parkinsonism (DIP) and investigate its relationship to olfactory impairment (OI), a common pre-motor finding in Parkinson disease (PD). BACKGROUND: DIP associated with dopamine receptor-blocking antipsychotic (AP) drugs is common and can be clinically indistinguishable from idiopathic PD. Symptoms sometimes do not improve or worsen after AP withdrawal suggesting that DIP may represent “unmasking” of pre-motor PD. We have previously reported that OI was significantly more common in patients who did not recover from DIP. DESIGN/METHODS: We reviewed Ioflupane I123 SPECT scans (DaTI) that label striatal presynaptic dopaminergic neurons from 14 consecutive patients (13 male) with DIP. Scans were read as normal or abnormal by a nuclear medicine physician. Semi-quantitative analysis of uptake in the caudate, anterior putamen and posterior putamen was performed by a separate observer blinded to clinical and olfactory data. Olfactory scores below the 10th percentile normalized for age and gender were considered abnormal. RESULTS: DaTI was abnormal in 4/14 (29[percnt]) of DIP subjects. Olfactory testing was available for 9 subjects and was concordant with DaTI result in 8/9 (89[percnt]) of cases. In semi-quantitative DaTI, minimal uptake in the posterior putamen was significantly lower in DIP/OI (N=3) compared to those with normal olfaction (N=4) (1.1±0.5 vs 2.3±0.3, p=0.04). Posterior putamen uptake in DIP/OI was similar to a PD group (p=0.43, N=4) whereas DIP subjects with normal olfaction were similar to tremor patients (p=1.0, N=4). Average posterior putamen uptake was strongly correlated with olfactory score, adjusting for age (r=0.92, p=0.03). CONCLUSIONS: Olfactory testing may be a simple, inexpensive screen to help identify DIP subjects with underlying dopaminergic denervation, consistent with pre-motor PD. Identification of cohorts with pre-motor PD offers opportunities to study and intervene at the earliest stages of disease. Disclosure: Dr. Morley has nothing to disclose. Dr. Cheng has nothing to disclose. Dr. Dubroff has nothing to disclose. Dr. Wilkinson has nothing to disclose. Dr. Duda holds stock and/or stock options in General Electric and Celgene, Inc.