Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

C Guevara,K Bulatova,M J Kempton,G J Barker,N Crossley,G Gonzalez

doi:10.1155/2016/9631041

C Guevara, K Bulatova + Show 4 more

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https://doi.org/10.1155/2016/9631041

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Journal: Parkinson's disease	Publication Date: Jan 1, 2016
Citations: 11	License type: CC BY 4.0

Affiliation: University of Chile, King's College London

Abstract

In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17–0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32–0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95–1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71–2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.

Highlights

There is a need to characterize disease progression in idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) to test the effectiveness of disease-modifying interventions
PSP and MSA can be misdiagnosed with IPD or vice versa at the initial stages of the disease and differential diagnosis can be challenging, a number of neuroimaging techniques allow a partial distinction among the diseases [1]
Established operational criteria were used to assess the diagnoses of MSA, PSP, and IPD [8,9,10]

Summary

Introduction

There is a need to characterize disease progression in idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) to test the effectiveness of disease-modifying interventions. PSP and MSA can be misdiagnosed with IPD or vice versa at the initial stages of the disease and differential diagnosis can be challenging, a number of neuroimaging techniques allow a partial distinction among the diseases [1]. Clinical trials for these disorders are hampered by the lack of surrogate endpoints and the unknown tempo of neuronal destruction. While clinical scales have been largely used to measure disease progression in therapeutic trials, they have a number of inherent limitations that reduce their sensitivity for tracking disease progression They may show nonlinearity, floor and ceiling effects, or an inability to differentiate symptomatic changes from disease modification changes. These factors may increase the variability of clinical data and limit both their effectiveness as outcome measures and their utility as inputs to power calculations when generating sample size estimates for clinical trials

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