MPRI 2.0 Accurately Differentiates Parkinson Disease and Progressive Supranuclear Palsy

Aldo Quattrone, MD, a professor of neuroscience at Magna Graecia University and a member of the Neuroimaging Research Unit at the Institute of Molecular Bioimaging and Physiology, part of the National Research Council, in Catanzaro, Italy

Aldo Quattrone, MD

A precise measurement done by magnetic resonance imaging (MRI), called the Magnetic Resonance Parkinsonism Index (MRPI) 2.0, has been shown to accurately predict the clinical evolution toward a progressive supranuclear palsy (PSP) parkinsonism phenotype, differentiating it from Parkinson disease.¹

The 4-year prospective clinical study sought to investigate the appearance of vertical gaze abnormalities, a feature which is suggestive of PSP, in patients with Parkinson disease to determine a proper diagnosis for patients at the earliest stages, allowing for earlier intervention with promising disease-modifying treatments. The study was led by Aldo Quattrone, MD, a professor of neuroscience at Magna Graecia University and a member of the Neuroimaging Research Unit at the Institute of Molecular Bioimaging and Physiology, part of the National Research Council, in Catanzaro, Italy.

Ultimately, after the final follow-up, 100 patients out of the total cohort of 110 patients with Parkinson maintained their original Parkinson diagnosis, while 10 (9.1%) developed vertical gaze abnormalities. The MRPI 2.0 classified all 10 of these patients as probable PSP-parkinsonism with 100% sensitivity, specificity, positive and negative predictive values, and accuracy, with a cutoff value of ≥2.88.

In total, 5 of the 10 patients were classified as O1‐A2 (clear limitation of range of voluntary gaze in the vertical more than in the horizontal plane, affecting both up‐ and downgaze, coupled with levodopa-resistant parkinsonism), 4 as O2‐A2 (slowness of vertical greater than horizontal saccadic eye movements, coupled with levodopa-resistant parkinsonism), and 1 as O2‐A3 (slowness of vertical greater than horizontal saccadic eye movements, coupled with levodopa‐responsive parkinsonism).

“Our findings are consistent with previous studies that showed that a number of patients initially diagnosed as having [Parkinson] were later found to have an alternative diagnosis as a result of the development of atypical clinical features,” Quattrone and coauthors wrote.

The study evaluated the MRPI and the pons/midbrain (P/M) area ratio, as well as their respective 2.0 versions, which included the measurement of third ventricle width. All patients repeated the clinical evaluation, levodopa acute test, and MR imaging examination with the same protocol as the baseline at the end of the 4-year follow-up period.

Out of a total of 40 patients with an initial diagnosis of possible Parkinson who showed levodopa responsiveness of >30% at baseline, 19 established a good levodopa response at the end of follow‐up. These patients had less than 2 years of disease duration at baseline and had not had an adequate trial of levodopa or dopamine agonists. All 70 patients with probable Parkinson showed some levodopa responsiveness, with 51 displaying moderate responsiveness, 30 showing good responsiveness, and 10 showing excellent responsiveness. At baseline, 90% (n = 9) of patients who developed vertical gaze abnormalities during the follow‐up showed a moderate response to levodopa, while the remaining 1 showed good levodopa response.

At baseline, the measurement values of patients with Parkinson were not different between the P/M 2.0, the MRPI, and the MRPI 2.0 values of the controls, though the P/M values were significantly higher in the patients with Parkinson. Those with vertical supranuclear gaze palsy (VSGP) showed higher biomarker values (P/M mean, 6.01 ±0.9; P/M 2.0, 1.40 ±0.2; MRPI, 15.68 ±1.5; MRPI 2.0, 3.69 ±0.6) than those with slowness of vertical saccades (P/M, 5.69 ±0.8; P/M 2.0, 1.33 ±0.4; MRPI, 14.44 ±1.1; MRPI 2.0, 3.33 ±0.7).

“The between‐group comparison showed that all morphometric measures (P/M, P/M 2.0, MRPI, and MRPI 2.0) were significantly higher in patients with PSP‐parkinsonism than in those with [Parkinson], both at baseline and at follow‐up,” Quattrone and colleagues detailed. “MRPI 2.0 values showed no overlap between patients with PD and patients with PSP‐P at both evaluations.”

When disease-status-to-follow&#8208;up interaction was considered, there were significant differences between patients with Parkinson and patients with PSP&#8208;parkinsonism for all morphometric measurements (P <.001), suggesting that disease progression was more marked in patients with PSP&#8208;P than in those with Parkinson.

“At baseline, the MRPI 2.0 showed the highest accuracy in predicting the appearance of [vertical gaze abnormalities] in all patients with initial diagnosis of PD who later changed diagnosis from Parkinson disease to PSP&#8208;parkinsonism,” the investigators wrote. “At the end of follow&#8208;up, MRPI 2.0, MRPI, and P/M 2.0 showed an excellent performance (accuracy, 100%) in differentiating PSP&#8208;parkinsonism patients from those with [Parkinson].”

Additionally, the MRPI 2.0 performance was highly accurate in differentiating the PSP&#8208;parkinsonism group from the non&#8208;PSP&#8208;parkinsonism group, consisting of patients with Parkinson, multiple system atrophy, and dementia with Lewy bodies, at baseline. The investigators also observed an “excellent” correlation between intrarater (intraclass correlation coefficients: 3rdV width, 0.993; frontal horns (FH) width, 0.991; 3rdV/FH, 0.995) and interrater (intraclass correlation coefficients: 3rdV width, 0.982; FH width, 0.987; 3rdV/FH, 0.989) agreement.

Quattrone and colleagues noted that to date, a limited number of studies have focused on evaluating the accuracy of MRPI for the differentiation of patients with PSP&#8208;parkinsonism from those with Parkinson and some have reported low sensitivity, which was then confirmed in a larger cohort of patients with PSP&#8208;parkinsonism. “We demonstrated that a new version of MRPI (MRPI 2.0) was highly accurate in differentiating patients with PSP&#8208;parkinsonism from those with Parkinson and controls. This version included the measurement of the 3rdV width in the calculation, a brain structure that has been reported to be enlarged in patients with PSP,” they wrote.

The concluded that these findings demonstrate the usefulness of these new imaging biomarkers—specifically of the MRPI 2.0&mdash;in predicting the development of visual gaze abnormalities and the clinical evolution towards PSP phenotypes in patients with the initial diagnosis of Parkinson disease. They suggested further clinical evaluation is warranted.

“These biomarkers could help clinicians identify very early those patients who may change the initial diagnosis from [Parkinson disease] to PSP&#8208;parkinsonism, thus impacting on patient counseling, prognosis, and therapeutic strategies,” they concluded. “On this basis, the use of accurate biomarkers may enable clinical trials to be performed at early stages of disease when new therapies are most likely to be efficacious.”

REFERENCE

1. Quattrone A, Morelli M, Vescio B, et al. Refining initial diagnosis of Parkinson's disease after follow&#8208;up: A 4&#8208;year prospective clinical and magnetic resonance imaging study. Movement Disord. Published online February 13, 2019. doi: 10.1002/mds.27621.