Does normal substantia nigra echogenicity make a difference in Parkinson's disease diagnosis? A real clinical practice follow-up study.

OBJECTIVES: Substantia nigra hyperechogenicity (SN+) detected by transcranial ultrasound (TUS) is useful for Parkinson's disease (PD) diagnosis. Approximately 15% false negative results of unknown significance are reported. However, most TUS studies are transversal, and diagnosis of PD may change during follow-up. METHODS: Analysis of our prospective registry of TUS in clinical practice, selecting patients with sufficient bone window, to whom TUS was performed because of suspected PD, and a minimum of 3-year follow-up. Subjects were classified regarding SN echogenicity (SN+/SN-). RESULTS: 172 patients (122 SN+, 50 SN-), mean age 71 years (25-90), were included. At the end of follow-up, PD diagnosis was retained by 91% SN+ vs. 54% SN- subjects (p < 0.0001), while final diagnosis of atypical parkinsonism (3%SN+ vs. 16%SN-, p:0.0059) was more frequent in SN-. Dopaminergic therapy response was associated with SN+ (88% SN+ vs. 50% SN-, p < 0.0001), as were abnormal DaTSCANs (90%SN+ vs. 56%SN-, p 0.0027). SN echogenicity had 80% sensitivity and 68% specificity for PD diagnosis, while SPECT had 91% and 73%, respectively. SN+ was the only baseline predictor of keeping PD diagnosis at the end of follow-up, with an odds ratio of 12 (95% CI 3-42) (p < 0.001). CONCLUSIONS: In our sample of patients with suspected PD, SN hyperechogenicity predicted PD diagnosis in the long term with a high odds ratio. Conversely, a baseline normal SN echogenicity was associated with a poorer response to PD therapy and change to a different diagnosis from PD. Normal SN appears to be a caveat for clinicians to check for atypical parkinsonism features during follow-up.

Substantia Nigra Echogenicity Predicts Response to Drug Withdrawal in Suspected Drug-Induced Parkinsonism.

INTRODUCTION: Response to drug withdrawal in patients with suspected drug-induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients. METHODS: Patients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure (PFNE). Transcranial sonography (TCS) findings were compared with the clinical diagnosis. RESULTS: Sixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one-way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism-inducing drug (P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%. CONCLUSIONS: We believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions.

Sonography for diagnosis of Parkinson disease-from theory to practice: a study on 300 participants.

OBJECTIVES: Hyperechogenicity of the substantia nigra on transcranial sonography is used for diagnosing Parkinson disease (PD). Cutoff values for the substantia nigra echogenic area, defining substantia nigra hyperechogenicity, vary among ultrasound systems from different manufacturers. In this study we wanted to determine the cutoff criterion for a Toshiba (Tokyo, Japan) system and to assess its diagnostic value. METHODS: Three hundred participants (controls, n = 138; patients with PD, n = 105; and patients with essential tremor, n = 57) underwent transcranial sonography following a standardized protocol. RESULTS: The substantia nigra was assessable in 92.7% of all participants. The substantia nigra echogenic area (larger of bilateral measurements) was larger in patients with PD (mean ± SD, 0.24 ± 0.05 cm(2)) than controls (0.14 ± 0.05 cm(2); P < .001) and patients with essential tremor (0.14 ± 0.04 cm(2); P < .001). Substantia nigra echogenicity was larger in male participants (0.20 ± 0.07 cm(2)) than female participants (0.15 ± 0.06 cm(2); P< .001). Age did not correlate with substantia nigra echogenicity in any group. Frontal horn width was larger and lenticular nucleus hyperechogenicity and a discontinuous raphe were more frequent in the PD group than the other groups. On multivariate analysis, only substantia nigra hyperechogenicity was associated with the diagnosis of PD. The 90th-percentile substantia nigra echogenic area in the control group, which defined marked substantia nigra hyperechogenicity, also represented the optimum cutoff value for discrimination of PD from non-PD participants on receiver operating characteristic curve analysis (area under the curve, 0.913; Youden index, 0.73). This cutoff value (≥0.21 cm(2), larger of bilateral measurements) yielded sensitivity of 83% and specificity of 90% for the diagnosis of PD. CONCLUSIONS: Transcranial sonography shows good diagnostic validity for diagnosis of PD when implemented according to a strictly standardized protocol.