Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be?

ABSTRACT

Background

PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. Our aim was to critically evaluate the degree to which structural, functional and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP.

Methods

We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English using postmortem diagnosis or NINDS-SPSP criteria as the diagnostic standard from 1996-2016. We define a five-level theoretical construct for the utility of neuroimaging biomarkers in PSP: group-level findings (level 1), biomarkers with demonstrable individual-level diagnostic utility (level 2), biomarkers for early disease (level 3), surrogate biomarkers of PSP pathology (level 4), and definitive biomarkers of PSP pathology (level 5).

Results

While many biomarkers show group-level abnormalities in Richardson's syndrome, brainstem measurements provide the best currently available level 2 biomarkers, with midbrain area, midbrain-pons ratio and MR Parkinsonism index providing high sensitivity and specificity. Some studies have also demonstrated diagnostic utility of diffusion weighted and tensor imaging, [18F]fluorodeoxyglucose PET and [18F]AV-1451 tau PET biomarkers. Only a few studies have assessed patients early in the disease course to suggest level 3 biomarkers, and there are currently no level 2 biomarkers available for variant PSP syndromes. No neuroimaging metrics have been shown to provide adequate biomarkers for autopsy-confirmed PSP.

Conclusion

While radiological biomarkers are available to aid in the clinical diagnosis of Richardson's syndrome, more work is needed to develop biomarkers for the other variant PSP syndromes and autopsy-confirmed PSP. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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