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

Abstract

PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five-level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group-level findings, level 2 representing biomarkers with demonstrable individual-level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field.

Clinical utility of FDG PET in Parkinson’s disease and atypical parkinsonism associated with dementia

“…These may be characterized by less severe or incomplete patterns, compared with typical and full-blown PSP. The panellists’ decision was consistent with both the EANM procedural guidelines [72] and the more recent diagnostic criteria of the Movement Disorder Society [5, 73], which support the use of FDG PET for discriminating PD from atypical parkinsonian syndromes.…”

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study

“…At baseline, patients with PSP-RS showed a typical pattern of brain damage, including midbrain atrophy, prominent frontal cortical thinning (extended minimally to temporoparietal regions) and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage 3. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, while midbrain atrophy and WM damage significantly progressed with a substantial impact on clinical decline.…”

“…Remarkable midbrain and cortical atrophy, usually involving the premotor and prefrontal regions, are typically observed in PSP-RS 3. More recently, extensive cortical thinning was found in the frontal, temporal, parietal and occipital cortex, cingulum, and insula in patients with PSP-RS compared with controls 4–6.…”

How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy

“…Biomarkers (eg, genetic, epigenetic, or biochemical attributes) and imaging support 7 currently only serve to support a diagnosis of PSP and to exclude differential diagnoses. 4,7 Biomarkers and imaging may become available in the near future to define PSP subgroups on a neurobiological basis. Future insights in these areas may allow us to revise our proposed guidelines and maybe even the overall MDS-PSP criteria.…”