The present study demonstrated that the mean CCSI score was significantly greater in patients with DIP than in those with PD, suggesting that an olfactory function test may be useful for differentiating patients with DIP from those with PD. Additionally, one DIP patient with a lower CCSI score also had decreased cardiac MIBG uptake, indicating that the offending drug may have unmasked clinical manifestations of parkinsonism in this patient
Depending on the clinical outcome, the patients with DIP can be classified as DIP unrelated to PD, DIP unmasking PD and DIP antedating PD.15
According to previous reports,4,5,8
most patients with DIP (70–90%) showed permanent resolution of parkinsonism after withdrawal of the offending drug, consistent with DIP unrelated to PD. Interestingly, these patients had normal 18
F‐DOPA and cardiac MIBG uptakes, reflecting no nigrostriatal or cardiac sympathetic dysfunction, both of which are in PD. The present study demonstrated that most patients with DIP (93%) had CCSI scores within the normal range and above the range of PD patient scores, and showed marked improvement of the parkinsonian features after withdrawal of the offending drug, suggesting DIP unrelated to PD. Thus we propose that an olfactory function test may be a useful tool to detect patients with DIP who are unrelated to PD.
Although the number of subclinical PD cases in patients with DIP is small, it is important to detect them, from the viewpoint of disease prognosis and treatment strategies. It is difficult to detect a patient with DIP who has subclinical PD on the basis of the reversibility of the parkinsonian features. The 18
F‐DOPA positron emission tomography (PET) and cardiac MIBG scans may be useful for detecting subclinical PD in patients with DIP. Burn and Brooks5
studied 13 patients with DIP using 18
F‐DOPA PET and identified nigral dysfunction in three patients. Recently, we conducted cardiac MIBG scans in 20 patients with DIP and identified cardiac sympathetic dysfunction in two patients.8
All patients who had abnormal 18
F‐DOPA and cardiac MIBG uptakes showed persistent parkinsonism after withdrawal of the offending drug.
In the present study, one patient with DIP whose CCSI score lay within the PD range exhibited persistent parkinsonism after the offending drug was withdrawn. Interestingly, this patient showed decreased cardiac MIBG uptake, which fell within the range of PD patients. According to Braak's neuropathological staging system for PD,16
the olfactory system may represent one of the induction sites of neuropathological processes in PD. In fact, not only olfactory impairment but also cardiac sympathetic dysfunction were reported in incidental Lewy body disease,17,18
a presymptomatic phase of PD, and these two systems may be closely coupled in patients with PD.19
Thus this DIP patient may be in subclinical PD, and the offending drug may aggravate the potential dopaminergic defect, resulting in the unmasking of clinical manifestations of parkinsonism.
The olfactory function test is simpler to perform, less invasive and less expensive than cardiac MIBG or PET scanning. Our study suggests that an olfactory function test may be a useful tool to screen for patients with DIP unrelated to PD and to identify patients with DIP who have subclinical PD. Further study using functional imaging to detect nigrostriatal function and long term follow‐up are warranted to determine whether DIP patients with low CCSI scores may also have nigral pathology.