Introduction
Recent clinical trials in Parkinson's disease (PD) using dopaminergic imaging methods (DAT imaging with SPECT and F-dopa imaging with PET) have revealed that about 10–15% of parkinsonian patients have scans without evidence of dopaminergic deficit (SWEDD). Little is known about the neural mechanisms of the parkinsonism in these subjects. The objective of this study is to elucidate the neurophysiology underlying parkinsonian patients with SWEDD using PET imaging markers of metabolic and dopaminergic functions.
Methods
We examined our collections of F-dopa scans from patients referred for the clinical diagnosis of parkinsonism. 29 patients (16 % of the total) were found to have normal striatal F-dopa uptake (not significantly different from the normal mean and within 2 standard deviations); 10 of them (6 women, 5 men; age 38.8 ± 10.8 years) were also scanned with fluorodeoxyglucose (FDG) PET. We compared these FDG scans to those of an age-matched control group with SPM99 and assessed whether the SWEDD subjects express a previously identified PD-related covariance pattern (PDRP). Finally we performed a separate principal component (PC) analysis on the combined group of SWEDDs and controls to identify a pattern of abnormal brain metabolism specifically related to this condition.
Results
SPM analysis showed no areas of significant metabolic difference between the SWEDD group and the controls. Brain network analysis revealed that PDRP was not expressed the SWEDD subjects. An additional network analysis on the combined SWEDD and control group identified a pattern (PC 1, accounting for 37% of variance) that distinguished the SWEDD group from the controls (p < 0.04). This pattern was characterized by hypometabolism in bilateral prefrontal cortices and caudate, covarying with relative hypermetabolism in pons, midbrain, cerebellar vermis, and bilateral medial temporal cortex.
Conclusion
Patients with SWEDD account for approximately 15% of subjects referred for diagnostic imaging for parkinsonism. In our cohort, these subjects tended to be young compared to typical parkinsonian patients. Although the regional metabolism appeared to be normal we found that these subjects express a specific abnormal brain network characterized by hypometablism in prefrontal cortex and caudate. This pattern suggests that some parkinsonian subjects with SWEDD may be characterized by abnormalities in striato-cortical connections in the setting of apparent normal dopaminergic function.