Clinical and neuroimaging features of the progressive supranuclear palsy- corticobasal degeneration continuum

Abstract

Purpose of review: The aim of this study was to discuss how recent work has increased our understanding of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The investigation of large and autopsy-confirmed cohorts, imaging modalities to assess different aspects of pathophysiology, clinical phenotypes and the application of advanced machine learning techniques, have led to recent advances in the field that will be discussed.

Recent findings: Literature over the past 18 months will be discussed under the following themes: studies assessing how different neuroimaging modalities can improve the diagnosis of PSP and CBD from other neurodegenerative and parkinsonian disorders, including the investigation of pathological targets such as tau, iron, neuromelanin and dopamine and cholinergic systems; work improving our understanding of clinical, neuroanatomical and pathological heterogeneity in PSP and CBD; and work using advanced neuroimaging tools to investigate patterns of disease spread, as well as biological mechanisms potentially driving spread through the brain in PSP and CBD.

Summary: The findings help improve the imaging-based diagnosis of PSP and CBD, allow more targeted prognostic estimates for patients accounting for phenotype or disease, and will aid in the development of appropriate and better-targeted disease biomarkers for clinical treatment trials.

Figure 1:. Brainstem and cortical findings across PSP clinical variants

Left panel shows boxplots of MRI parkinsonism index (MRPI) values across PSP variants, highlighting abnormal MRPI values in all PSP variants, except for PSP-gait freezing which did not differ from controls. Right panel shows group-level SPM maps of cortical grey matter loss, highlighting relative absence of cortical volume loss in PSP-Richardson, PSP-parkinsonism and PSP-gait freezing compared to PSP-speech/language, PSP-corticobasal and PSP-frontal.

Figure 2:. Patterns of anatomical spread in machine learning identified MRI-subcortical and MRI-cortical variants of PSP.

The spatial distribution and severity of atrophy are shown for each subtype at each SuStaIn stage at which brain volumes in PSP cases reach different z-scores relative to controls (49). The The earliest SuStaIn stages in the ‘MRI-subcortical’ subtype (75% of cases) involved the midbrain followed by other brainstem structures (medulla, pons, and superior cerebellar peduncle) and ventral diencephalon. Atrophy then progressed to the dentate nucleus of the cerebellum, thalamus, globus pallidus and putamen before spreading to cortex after stage 13. Cortical atrophy progressed from the insula and posterior frontal lobe to the temporal, parietal, and occipital lobe. The earliest SuStaIn stages in the ‘cortical’ subtype involved the midbrain and insula, followed by the frontal lobes (posterior > anterior), thalamus, ventral diencephalon, and the basal ganglia which were all affected at a similar time (before stage 13). Only 5% of cases were not able to be subtyped.