Association of MRI Measures With Disease Severity and Progression in Progressive Supranuclear Palsy

Abstract

Objective: To verify the association of midbrain-based MRI measures as well as cortical volumes with disease core features and progression in patients with Progressive Supranuclear Palsy (PSP). Methods: Sixty-seven patients (52.2% with Richardson's syndrome) were included in the present analysis. Available midbrain-based MRI morphometric assessments as well as cortical lobar volumes were computed. Ocular, gait and postural involvement at the time of MRI was evaluated with the PSP rating scale. Specific milestones or death were used to estimate disease progression up to 72 months follow up. Hierarchical regression models and survival analysis were used for analyzing cross-sectional and longitudinal data, respectively. Results: Multivariate models showed vertical supranuclear gaze palsy was associated with smaller midbrain area (OR: 0.02, 95% CI 0.00–0.175, p = 0.006). Cox regression adjusted for age, disease duration, and phenotype demonstrated that lower midbrain area (HR: 0.122, 95% CI 0.030–0.493, p = 0.003) and diameter (HR: 0.313, 95% CI 0.112–0.878, p = 0.027), higher MR Parkinsonism Index (HR: 6.162, 95% CI 1.790–21.209, p = 0.004) and larger third ventricle width (HR: 2.755, 95% CI 1.068–7.108, p = 0.036) were associated with higher risk of dependency on wheelchair. Conclusions: Irrespective of disease features and other MRI parameters, reduced midbrain size is significantly associated with greater ocular motor dysfunction at the time of MRI and more rapid disease progression over follow up. This is the first comprehensive study to systematically assess the association of available midbrain-based MRI measures and cortical volumes with disease severity and progression in a large cohort of patients with PSP in a real-world setting.

Using Downgaze Palsy Progression Rate to Model Survival in Progressive Supranuclear Palsy–Richardson Syndrome

“…Survival in PSP‐Richardson syndrome can be predicted to some extent by the PSPRS total score and its progression rate early in the disease course 7,13 . Table 5 summarizes previous studies of factors associated with shorter survival in PSP 1,5,6,7,13,21,25‐31 . The present study does the same using a different methodology and further confirms the predicting value of the progression rate of downgaze palsy in survival.…”

“…Early urinary symptoms Cui et al, 2020 29 Greater midbrain atrophy and enlarged third ventricle on MRI Picillo et al, 2020 30 Golbe et al, 2020 13 Velocity of total PSPRS score from onset to first visit progression in PSPRS scores during that limited timespan. 8 To extend this analysis to a longer time period, we used our longer term data set to tabulate the median and 95% CI total PSPRS scores and downgaze palsy scores through the seventh year of disease.…”

Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy

“…The LRRK2 gene was associated with reduced survival ( 20 ). Atrophy in midbrain and larger third ventricle width were also associated with higher risk of death ( 21 , 22 ). We were unable to control all the factors in our study revealing that the rapid deterioration of the downgaze palsy could predict survival in an individual level, although we controlled other factors and also consistently found that older age of onset was also associated with a shorter disease duration to death.…”

Neuroimaging in Parkinson’s Disease: necessity or exaggeration?

“…Measurements of the SCP, MCP, pons area and midbrain area allow the calculation of the MRI parkinsonism index (MRPI), wherein a value of ≥13.55 or The MRPI and the P area/M area ratio have adequate diagnostic value to support the PSP-RS clinical diagnosis of PSP-RS, as opposed to PD and healthy controls, but they do not show an adequate sensitivity and specificity profile when differentiating PSP subtypes [54]. Midbrain area measurement is much easier for neuroradiologists to perform, has similar diagnostic potential to MRPI, and is significantly associated with greater ocular motor dysfunction at the time of MRI and more rapid disease progression at follow-up [62]. Callosal atrophy and mild cortical atrophy -usually restricted to the frontal lobes -are also observed [47].…”