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

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Albrecht,  Franziska
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Bisenius,  Sandrine
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Neumann,  Jane
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Department of Medical Engineering and Biotechnology, University of Applied Sciences, Jena, Germany;
Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany;

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Schroeter,  Matthias L.
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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Citation

Albrecht, F., Bisenius, S., Neumann, J., Whitwell, J., & Schroeter, M. L. (2019). Atrophy in midbrain & cerebral/cerebellar pedunculi is characteristic for progressive supranuclear palsy: A double-validation whole-brain meta-analysis. NeuroImage: Clinical, 22: 101722. doi:10.1016/j.nicl.2019.101722.


Cite as: http://hdl.handle.net/21.11116/0000-0003-246D-B
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.