Is Transcranial Sonography Useful to Distinguish Drug-Induced Parkinsonism From Parkinson ’ s Disease ?

Recent studies have suggested differential diagnostic utility of transcranial sonography (TCS) assessing the echogenic sign in the area of the substantia nigra (SN) in parkinsonian disorders. SN hyperechogenicity (SNþ) is defined as its enlargement and is present in at least 82% of Parkinson’s disease (PD) cases, but only in approximately 10% of healthy controls. The present study was performed to assess the diagnostic accuracy of TCS in distinguishing PD from drug-induced parkinsonism (DIP) using a community-based prospective study cohort representing a typical western population with respect to demographic characteristics and prevalence of these disorders in the elderly population (Bruneck study, approved by the local ethics committee). Five hundred and seventy-four men and women 55 to 94 years in age gave written informed consent. All TCS examinations and SN segmentations were performed by the same experienced ultrasound (US) examiner with a 2.5-MHz transducer (Logiq 7; General Electric, Milwaukee, WI), as described recently. The clinical investigators were blinded to the US results and vice versa. A clinical follow-up of the DIP cases was performed after 3 years. The side of greater SN echogenicity was used for statistical analysis, and SNþ was defined as an area of 0.18 cm based on a receiver operating characteristic analysis between PD subjects and healthy controls, corresponding to the 75th percentile of the larger SN side of the healthy controls, as suggested previously. Eighty-nine participants were excluded because of missing TCS information. Of the remaining 485 subjects, 17 had a diagnosis of definite PD according to UK Brain Bank criteria (3.5%; 7 female; mean age, 79.2 6 8.1 years) and 8 had a diagnosis of DIP (1.7%; 6 female; 68.5 6 9.7 years), according to published criteria. Area of SN echogenicity in the PD group (0.23 cm; standard deviation [SD], 0.07) was significantly increased, compared to the DIP group (0.16 cm; SD, 0.07; Mann-Whitney’s U test, P 1⁄4 0.026). Characteristics of DIP subjects and distribution of the SN values with respective diagnostic accuracy values are demonstrated in Figure 1. These values are similar to those reported in the only imaging study assessing the diagnostic accuracy of [123]I-FPCIT single-photon emission computed tomography in distinguishing DIP patients from PD patients. Other radiotracer studies in DIP subjects have also demonstrated that abnormal binding is associated with incident PD after discontinuation of the offending drug. Previous studies in young psychiatric patients have found significant positive correlations of the SN echogenic area and the prevalence, as well as the severity, of DIP, and it is tempting to speculate whether TCS could be helpful in identifying patients presenting with DIP, but who have an underlying nigrostriatal dysfunction. In line with this possibility is the finding of the only hyperechogenic DIP subject in our sample, in whom parkinsonism progressed slightly, even after discontinuation of the offending drug. In contrast, the only other DIP subject in whom the medication was stopped was normoechogenic and his parkinsonism completely resolved. In summary, our results suggest that TCS might offer an easyto-use, cost-effective aid in the distinction between PD and DIP, and larger, prospective studies are needed to validate its role.