Researchers developed the biomarker in hopes of simplifying the recent MRPI 2.0 measurement for use in clinical practice.
Aldo Quattrone, MD
A new study published in Movement Disorders suggests that third ventricle/internal skull diameter ratios (3rd V/ID) allow for the early differentiation of Parkinson disease (PD) and progressive supranuclear palsy (PSD) and are sufficiently simple and generalizable to be used in most routine clinical practices and in patient selection for a variety of clinical trials.
In both the local “training” and the international “testing” cohorts analyzed, 3rd V/ID values were significantly lower in patients with PD than in patients with PSD. The mean 3rd V/ID was 3.57 (standard deviation [SD], ±1.43) in PD and 7.23 (SD, ±1.79) in PSP in the “training” cohort (P <.001), and 3.80 (SD, ±1.60) in PD and 7.10 (SD, 1.81) in PSP in the “testing” cohort (P <.001). In patients with PD compared to the control group, there was no significant difference in 3rd V/ID values.1
Senior author Aldo Quattrone, MD, Neuroscience Centre and Neuroimaging Research Unit, National Research Council, Magna Graecia University, stated that “the 3rd V/ID coupled simplicity with generalizability and good accuracy, thus enabling patients with PD or PSP to also be correctly classified in everyday clinical practice worldwide.”
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The training cohort consisted of 269 patients, 96 with treated PD, 73 with late-stage PD, and 98 controls. The testing cohort consisted of 291 participants, 81 with de novo PD and 133 controls from the Parkinson’s Progression Markers Initiative, and 76 with early-stage PSP from an international research group. Quattrone and colleagues found that 3rd V/ID values were strongly associated with the probability of having PSP—for each 1-unit increase in 3rd V/ID values, the odds ratio (OR) for having PSP was 4.0 (95% CI, 2.8–6.5) in the training cohort and 3.1 (95% CI, 2.3–4.5) for the testing cohort.
The 3rd V/ID is calculated by hand; using 3-D T1-weighted images at the midsagittal plane, the subcallosal line is used to generate an axial slice to measure the 3rd ventricle width. The use of the subcallosal line is common in radiological routine and is therefore easily reproducible yet still accurate without any special qualifications or technology, unlike other studies that have studied the 3rd ventricle width using low-sense transcranial sonography or specialized automated ventricular volumetry, or the current calculations of the Magnetic Resonance Parkinsonism Index (MRPI).
Quattrone and colleagues previously defined MRPI 2.0 as an accurate measure to distinguish between the 2 diseases by measuring the 3rd ventricle on an axial slice generated at the level of both the anterior and posterior commissures, normalized by the largest width of the frontal horns.2 With the use of 3rd V/ID, they have now defined a simpler biomarker for use in clinical practice.
The diagnostic performance between the 2 cohorts did not differ according to the De Long test (D = .99; P = .32). The training cohort showed an area under the curve (AUC) of 0.94 (95% CI, 0.91–0.98) and the testing cohort confirmed this performance with an AUC of 0.91 (95% CI, 0.87–0.96).
The optimal cutoff values generated for each cohort were also tested against the other cohorts to confirm the validity of these findings. The authors determined this ratio value to be 5.88, above which supports the clinical diagnosis of PSP and below which supports a diagnosis of PD.
The patients enrolled in the study did not undergo pathologic examinations, so some clinical diagnoses may have been in error. Future studies may want to conduct their own pathologic examinations, as well as use larger cohorts to further investigate the efficacy of the 3rd V/ID biomarker.
Quattrone and colleagues suggest implementing this additional screen when selecting patients for clinical trials to avoid the potential confounding factor of patients with possible diagnosis confusion between PSP and PD, stating that “the use of our new MR biomarker could positively impact the enrollment of PD and PSP patients in clinical trials still based on clinical criteria.”