Differentiating Parkinson’s Disease from Essential Tremor Using Transcranial Sonography: A Systematic Review and Meta-Analysis

Abstract

Background: Essential tremor (ET) and the tremor of Parkinson’s disease (PD) are the most common tremors encountered in clinical practice. Especially in early disease stages, discrimination between the tremors of ET and PD can be challenging. Objective: The aim of this study was to evaluate the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra echogenicity for differential diagnosis of PD versus ET. Methods: A systematic PubMed search identified 512 studies. Sensitivity and specificity of substantia nigra hyperechogenicity was estimated. Data synthesis was carried applying a random effects bivariate binomial model. To assess study quality and risk of bias, the QUADAS-2 tool was used. Results: Eighteen studies were suitable for analysis including 1,264 PD and 824 ET patients. The meta analysis showed a pooled sensitivity and specificity for TCS in the differential diagnosis of PD versus ET of 84.6% (95% CI, 79.4–88.6%) and 83.9% (95% CI, 78.4–88.2%), respectively. Furthermore, we found similar results in sensitivity and specificity comparing TCS and DaTSCAN in a subgroup-analysis of three studies using both diagnostic tools including 107 patients with PD and 62 patients with ET. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection. Conclusion: Substantia nigra hyperechogenicity yield high diagnostic accuracy for the discrimination of PD from ET. TCS is a low cost, widely available, non-invasive marker without radiation Therefore, a diagnostic algorithm based on presence or absence of substantia nigra hyperechogenicity is highly warranted.

Transcranial ultrasonography to detect intracranial pathology: A systematic review and meta‐analysis

“…We focused the search on ICH, tumors, and neurodegenerative diseases to assess the accuracy of TCU in the evaluation of brain parenchyma due to the significant number of studies done in these diseases. Our analysis of neurodegenerative diseases showed an overall lower pooled sensitivity and specificity for the diagnosis of intracranial pathology by TCU in comparison to prior systematic reviews evaluating the utility of TCU for the detection of Parkinson's disease 62–64 . Overall, the accuracy of TCU in neurodegenerative diseases was too low for clinical application in initial triage, due to its much lower image resolution for brain parenchyma compared to computer tomography and magnetic resonance imaging.…”

“…Moreover, several neurodegenerative diseases cause functional changes detectable on a positron emission tomography scan before gross structural changes are visible in neuroimaging. A recent review highlighting the detection of substantia nigra echogenicity by TCU suggested possible clinical applications in distinguishing Parkinson's disease from essential tremors with similar sensitivity and specificity but these applications are suitable for diagnosed parkinsonian symptoms requiring further delineation of differential diagnosis 64 . We focused our review on information to help with accuracy of TCU in the initial diagnosis of intracranial pathology.…”

“…Our analysis of neurodegenerative diseases showed an overall lower pooled sensitivity and specificity for the diagnosis of intracranial pathology by TCU in comparison to prior systematic reviews evaluating the utility of TCU for the detection of Parkinson's disease. [62][63][64] Overall, the accuracy of TCU in neurodegenerative diseases was too low for clinical application in initial triage, due to its much lower image resolution for brain parenchyma compared to computer tomography and magnetic resonance imaging. Moreover, several neurodegenerative diseases cause functional changes detectable on a positron emission tomography scan before gross structural changes are visible in neuroimaging.…”

“…A recent review highlighting the detection of substantia nigra echogenicity by TCU suggested possible clinical applications in distinguishing Parkinson's disease from essential tremors with similar sensitivity and specificity but these applications are suitable for diagnosed parkinsonian symptoms requiring further delineation of differential diagnosis. 64 We focused our review on information to help with accuracy of TCU in the initial diagnosis of intracranial pathology. Lastly, despite sample size limitations, the pooled accuracy in this disease population showed a difference between the 95% confidence boundaries of 10%, lending no further utility to pursuing the diagnostic application of ultrasound in this population.…”

“…The eligibility criteria for our systematic review were more making the meta-analysis more informative. [62][63][64] We also focused on the initial diagnosis of intracranial pathology using TCU rather than the use of ultrasound image features to narrow differential diagnosis. We found one previous systematic review investigating the role of intraoperative ultrasound in the detection of brain tumors, but the limited number of studies assessing this pathology did not allow assessment of its applicability to clinical use.…”