Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy

Pavone, Costanza; Weigand, Stephen W.; Ali, Farwa; Clark, Heather M.; Botha, Hugo; Machulda, Mary M.; Savica, Rodolfo; Pham, Nha Trang Thu; Grijalva, Rosalie M.; Schwarz, Christopher G.; Senjem, Matthew L.; Filippi, Massimo; Jack, Clifford R.; Lowe, Val J.; Josephs, Keith A.; Whitwell, Jennifer L.

doi:10.1016/j.parkreldis.2023.105290

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…Identifying the predominant subtype is clinically relevant, as it can provide information about the expected prognosis. For example, comparing PSP-RS and PSP variants affecting subcortical structures (PSP-P, PSP-PGF, PSP-PI) with PSP variants affecting cortical structures (PSP-CBS, PSP-SL, PSP-F) shows that patients with subcortical variants generally have a slower rate of progression compared with the other groups [12,13 ]. PSP-RS has the fastest progression and shortest survival [14,15].…”

Section: Defining Progressive Supranuclear Palsy Variantsmentioning

confidence: 99%

Progressive supranuclear palsy: current approach and challenges to diagnosis and treatment

Carpentier

McFarland

2023

Current Opinion in Neurology

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Purpose of review Since the original description of progressive supranuclear palsy (PSP) by Steele, Richardson and Olszewski, the clinical spectrum of PSP has expanded and now includes multiple phenotypic variants linked by a common disease. In this review, we discuss the evolution of the PSP syndrome and clinical criteria, with a particular focus on the 2017 Movement Disorders Society PSP criteria, its application and limitations. We also discuss our current approach to diagnosis and treatment. Recent findings There is a significant overlap between the different variants of PSP and multiple phenotypes that may be applied to the same patient simultaneously. Variant severity and predominance also evolve throughout the course of the disease. Each variant and level of certainty is associated with different specificity and sensitivity for underlying disease. The differential diagnosis of PSP is continuously evolving and includes other tauopathies, neurodegenerative, genetic, autoimmune and infectious disorders. MRI measurements can aid in the diagnosis. The first guidelines to help with clinical management of those patients have been recently published. Summary Although much improved, clinical PSP criteria alone remain insufficient and emphasize the need for improved biomarkers to identify patients at early stages to direct appropriate therapeutic strategies and target potential research.

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Section: Defining Progressive Supranuclear Palsy Variantsmentioning

confidence: 99%

Progressive supranuclear palsy: current approach and challenges to diagnosis and treatment

Carpentier

McFarland

2023

Current Opinion in Neurology

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“…Clinical heterogeneity has been assessed across PSP variants, particularly to compare disease severity and rates of progression. It is clear from several recent studies that the subcortical variants of PSP show the slowest progression in overall disease severity and motor disability [31,32], have the least ocular motor impairments [31], and show longer survival [33 ▪ ], compared with PSP-RS and cortical variants. The cortical variants of PSP show worse motor disability, cognitive impairment and activities of daily living compared with subcortical variants of PSP [31,33 ▪ ].…”

Section: Understanding Clinical and Anatomical Heterogeneitymentioning

confidence: 99%

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

Whitwell

2023

Current Opinion in Neurology

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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.

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Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials

Quattrone,

Franzmeier,

Huppertz

et al. 2024

Movement Disorders

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BackgroundSeveral magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed.ObjectiveComparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials.MethodsProgressive supranuclear palsy‐Richardson's syndrome (PSP‐RS) patients with one‐year‐follow‐up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age‐matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas‐based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data.ResultsOf 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems.ConclusionsThis evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas‐based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy

Cited by 4 publications

References 35 publications

Progressive supranuclear palsy: current approach and challenges to diagnosis and treatment

Progressive supranuclear palsy: current approach and challenges to diagnosis and treatment

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

Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials

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