Transcranial Sonography in Differential Diagnosis of Parkinson Disease and Other Movement Disorders
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremor, rigidity, bradykinesia, and postural instability. Despite advances in diagnostic techniques, the clinical diagnosis of PD remains challenging, particularly in its early stages, due to overlapping symptoms with other movement disorders such as essential tremor (ET), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Accurate diagnosis is crucial for appropriate therapeutic management, and transcranial sonography (TCS) has emerged as a promising tool for differentiating PD from other movement disorders. This study evaluates the efficacy of TCS in the differential diagnosis of PD, ET, MSA, and PSP in a Chinese population, providing valuable insights into its diagnostic utility.
Introduction
The clinical diagnosis of PD is often complicated by its similarity to other movement disorders in the early stages. Approximately 80% of PD cases are accurately diagnosed, but the remaining 20% may be misdiagnosed due to overlapping symptoms with conditions such as dementia with Lewy bodies, MSA, PSP, corticobasal degeneration, ET, drug-induced Parkinsonism, and vascular Parkinsonism. Accurate diagnosis is essential for proper therapeutic management, as misdiagnosis can lead to inappropriate treatment and poor outcomes.
Magnetic resonance imaging (MRI) is commonly used in neurological diseases, but its sensitivity is insufficient, particularly in the early stages of PD. Functional imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have shown promise but are expensive, require radioactivity, and are difficult to popularize. In contrast, TCS offers several advantages, including low cost, wide availability, short exam time, non-invasiveness, repeatability, and bedside availability. TCS is based on a different imaging principle than other neuroimaging modalities, providing high-resolution real-time dynamic imaging of deep brain structures.
Since its first application in 1995 to detect substantia nigra (SN) hyperechogenicity in PD patients, TCS has gained attention for its potential in diagnosing PD and differentiating it from other movement disorders. However, most studies on TCS have been conducted in Europe, America, Japan, and Korea, with limited reports from China. This study aims to evaluate the application of TCS for the differential diagnosis of PD, ET, MSA, and PSP in Chinese individuals.
Methods
The study was conducted from December 2017 to December 2019 at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University. A total of 500 inpatients were selected for the study and underwent routine transcranial ultrasound examination. Inclusion criteria included patients older than 18 years of age with complete clinical scores (e.g., Unified PD Rating Scale Part III [UPDRS-III], Hoehn and Yahr [H&Y] scale scores). Exclusion criteria included Parkinson syndrome caused by encephalitis, cerebrovascular disease, craniocerebral tumors, trauma, or drugs, as well as poor sound transmission through the temporal window.
Diagnosis and grouping were based on clinical diagnostic criteria. PD was diagnosed using the UK Parkinson Disease Society Brain Bank Clinical Diagnostic Criteria, ET was diagnosed according to the International Movement Disorders Association’s tremor consensus statement, MSA was diagnosed based on the second edition of the MSA diagnostic criteria, and PSP was diagnosed using the Clinical Diagnostic Criteria of the National Institute of Neurological Disease and Stroke and the Society for PSP. The diagnosis was made by two neurologists with more than five years of experience in handling patients with movement disorders. In cases of disagreement, a third expert with more than ten years of experience was consulted.
TCS was performed using a Philips IU22 color Doppler ultrasound system equipped with an S5-1 broadband sector array transducer. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of SN positivity and lenticular hyperechoic area were recorded. The echo of the SN was manually measured, and the ratio of the high echo areas of the bilateral SN to the total area of the midbrain (hyper-substantia nigra/midbrain [S/M]) was calculated. SN area ≥0.25 cm² and/or S/M ≥7% indicated SN positivity.
Results
Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 patients with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ² = 121.061, P < 0.001). The PD group showed a higher SN positivity rate than the ET (χ² = 94.898, P < 0.017), MSA (χ² = 57.619, P < 0.017), and PSP (χ² = 37.687, P < 0.017) groups.
SN positivity had a sensitivity of 81.0%, specificity of 75.4%, and positive and negative predictive values of 79.0% and 77.6%, respectively, in the differential diagnosis of PD from ET, PSP, and MSA. Specifically, SN positivity had a sensitivity of 81.0%, specificity of 78.9%, positive predictive value of 89.5%, and negative predictive value of 65.1% in differentiating PD from ET. For differentiating PD from MSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 81.0%, 74.0%, 92.5%, and 49.3%, respectively. In differentiating PD from PSP, the sensitivity, specificity, positive predictive value, and negative predictive value were 81.0%, 68.6%, 93.6%, and 38.7%, respectively.
The incidence rates of lenticular hyperechoic area also differed significantly among the four patient groups (χ² = 38.904, P < 0.001). The lenticular hyperechoic area was higher in the PD group than in the ET (χ² = 6.714, P < 0.017) and MSA (χ² = 18.680, P 0.017).
Discussion
This study demonstrates that TCS-derived SN positivity can effectively differentiate PD from ET, PSP, and MSA in a Chinese population. The incidence of lenticular hyperechoic areas is relatively low in PD and other movement disorders, suggesting that it may also be useful in differential diagnosis.
The human brain structure differs considerably across different ethnic groups, which may affect the results of TCS. In this study, 25% of patients were excluded due to poor sound transmission through the temporal window, highlighting the importance of evaluating TCS in different populations. The study found no significant differences in UPDRS-III and H&Y scale scores among the PD, MSA, and PSP groups, indicating clinical similarities of movement disorders in the current population.
SN positivity was significantly higher in the PD group than in the ET, MSA, and PSP groups, demonstrating its diagnostic utility. The sensitivity and specificity of SN positivity in differentiating PD from other movement disorders were consistent with previous studies, further supporting the use of TCS in PD diagnosis. The origin of SN hyperechogenicity is still unclear, but animal studies suggest an association with increased iron levels and decreased neuromelanin levels in the SN.
The lenticular hyperechoic area was higher in the PD group than in the ET and MSA groups but lower than in the PSP group, indicating its potential role in differential diagnosis. Trace metal accumulation and calcification are the most frequent causes of lenticular hyperechogenicity, and differences in iron deposition patterns may account for the observed differences among the groups.
TCS offers several advantages over other imaging techniques, including low cost, wide availability, short exam time, non-invasiveness, and repeatability. It provides high-resolution real-time dynamic imaging and is not adversely affected by patient movements. These features make TCS a valuable tool for the early diagnosis and differential diagnosis of PD and other movement disorders.
Limitations
This study has several limitations. It was a single-center study with a relatively small sample size of 375 patients, which may limit the generalizability of the findings. Additionally, the study did not include healthy controls, which could have provided further insights into the diagnostic utility of TCS. Future multicenter studies with larger sample sizes are needed to confirm these findings.
Conclusion
In conclusion, TCS-derived SN positivity can effectively differentiate PD from ET, PSP, and MSA in a Chinese population. The lenticular hyperechoic area may also be useful in differential diagnosis, although its incidence is relatively low in PD and other movement disorders. TCS offers several advantages over other imaging techniques and should be considered a valuable tool for the early diagnosis and differential diagnosis of PD and other movement disorders.
doi.org/10.1097/CM9.0000000000001503
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