Objective: To correlate anatomical changes with time to death in PSP.

Background: Many advances have been made in progressive supranuclear palsy (PSP) since it was first described in 1964.  Despite improved understanding of the pathological, genetic and imaging markers of the disease, prognostication remains challenging for clinicians and triallists.  Age and clinical features such as dysphagia, weight loss and the PSP rating scale (PSP-RS) are associated with shorter survival, but do not provide insights into associated brain states or structural changes.  

Methods: Fifty one participants were recruited from a specialist clinic for PSP for structural brain imaging, assessment of severity (PSP-RS), and cognitive testing [Addenbrooke’s Cognitive Examination – revised].  T1-weighted MPRAGE images were acquired on a Siemens Magnetom Tim Trio at 3T, between 133 and 1727 days before death.  Twenty one patients donated their brains to the Cambridge Brain Bank for post mortem examination.  A date of onset was estimated from the history given at first assessment. 

The dates of onset, scanning and death allowed calculation of two variables; (1) the disease stage at time of scanning expressed as a proportion of the total duration of a participant’s illness and (2) absolute time from scan to death.  The MPRAGE images were pre-processed for a Voxel-Based Morphometry (VBM) analysis using a general linear model using either stage or time to death as the principal variate of interest, with age, total intracranial volume (TIV) and gender as covariates. The significance of clusters was tested using threshold-free cluster enhancement (TFCE) and 5000 permutations.

Results: A significant subcortical cluster (p<0.05, TFCE corrected) correlated with stage of disease, centred on the thalamus.  The correlation between grey matter volumes and time from scan to death was not significant, reflecting the heterogeneity of PSP survival. 18/21 patients had typical PSP pathology, 2/21 had pathology that was intermediate between PSP and CBD tauopathy, while one case had dual pathology with PSP tauopathy and Lewy bodies. 

Conclusions: The data confirm progressive atrophy of the thalamus in PSP, but go further in indicating a relationship between focal thalamic atrophy and survival. We postulate thalamic ‘collapse’ as a critical process which adversely influences prognosis, and which may inform stratification and outcome in future trials of disease modifying therapies. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/anatomical-predictors-of-survival-in-psp-thalamic-collapse-towards-the-end-of-life/