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Neuroimage Clin. 2019;22:101722. doi: 10.1016/j.nicl.2019.101722. Epub 2019 Feb 19.

Atrophy in midbrain & cerebral/cerebellar pedunculi is characteristic for progressive supranuclear palsy - A double-validation whole-brain meta-analysis.

Author information

1
Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany. Electronic address: falbrecht@cbs.mpg.de.
2
Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany. Electronic address: bisenius@cbs.mpg.de.
3
Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany; Department of Medical Engineering and Biotechnology, University of Applied Science, Jena, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, Germany. Electronic address: neumann@cbs.mpg.de.
4
Department of Radiology, Mayo Clinic, Rochester, MN, United States. Electronic address: Whitwell.Jennifer@mayo.edu.
5
Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany; Clinic of Cognitive Neurology, University of Leipzig & FTLD Consortium Germany, Germany. Electronic address: schroet@cbs.mpg.de.

Abstract

OBJECTIVE:

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome characterized by vertical gaze palsy and postural instability. Midbrain atrophy is suggested as a hallmark, but it has not been validated systematically in whole-brain imaging.

METHODS:

We conducted whole-brain meta-analyses identifying disease-related atrophy in structural MRI. Eighteen studies were identified (N = 315 PSP, 393 controls) and separated into gray or white matter analyses (15/12). All patients were diagnosed according to the National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP criteria, Litvan et al. (1996a)), which are now considered as PSP-Richardson syndrome (Höglinger et al., 2017). With overlay analyses, we double-validated two meta-analytical algorithms: anatomical likelihood estimation and seed-based D mapping. Additionally, we conducted region-of-interest effect size meta-analyses on radiological biomarkers and subtraction analyses differentiating PSP from Parkinson's disease.

RESULTS:

Whole brain meta-analyses revealed consistent gray matter atrophy in bilateral thalamus, anterior insulae, midbrain, and left caudate nucleus. White matter alterations were consistently detected in bilateral superior/middle cerebellar pedunculi, cerebral pedunculi, and midbrain atrophy. Region-of-interest meta-analyses demonstrated that midbrain metrics generally perform very well in distinguishing PSP from other parkinsonian syndromes with strong effect sizes. Subtraction analyses identified the midbrain as differentiating between PSP and Parkinson's disease.

CONCLUSIONS:

Our meta-analyses identify gray matter atrophy of the midbrain and white matter atrophy of the cerebral/cerebellar pedunculi and midbrain as characteristic for PSP. Results support the incorporation of structural MRI data, and particularly these structures, into the revised PSP diagnostic criteria.

KEYWORDS:

Anatomical likelihood estimation; Cerebellar pedunculi; Cerebral pedunculi; Imaging biomarker; Meta-analysis; Midbrain; Progressive supranuclear palsy; Seed-based D mapping

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