Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers

Abstract

Background: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic adult-onset primary tauopathies clinically classified among the atypical parkinsonian syndromes. They are intrinsically related with regard to their clinical features, pathology, biochemistry, and genetic risk factors. Objectives: This review highlights the current knowledge on PSP and CBD, focusing on evolving clinical concepts, new diagnostic criteria, and advances in biomarkers. Methods: We performed a non-systematic literature review through the PubMed database. The search was restricted to articles written in English, published from 1964 to date. Results: Clinicopathologic and in vivo biomarkers studies have broadened PSP and CBD clinical phenotypes. They are now recognized as a range of motor and behavioral syndromes associated with underlying 4R-tauopathy neuropathology. The Movement Disorders Society PSP diagnostic criteria included clinical variants apart from the classical description, increasing diagnostic sensitivity. Meanwhile, imaging biomarkers have explored the complexity of symptoms and pathological processes related to corticobasal syndrome and CBD. Conclusions: In recent years, several prospective or clinicopathologic studies have assessed clinical, radiological, and fluid biomarkers that have helped us gain a better understanding of the complexity of the 4R-tauopathies, mainly PSP and CBD.

Phenotypic and Positron Emission Tomography with [18F]fluordeoxyglucose (FDG PET) differences in corticobasal syndrome: comparison of two cases

“…Since PSP and CBS have significant phenotypic overlaps, another plausible possibility is that case 1 has a cortical variant of PSP, such as the corticobasal variant of PSP (PSP-CBS), a phenotype mostly linked to CBD pathology, although it might be found in cases with a PSP neuropathology 3 . Despite similar clinical manifestations between CBD and PSP, some clinical hints may favor CBD such as limb apraxia, asymmetrical bradykinesia, and increased saccadic latencies with preserved velocity in patients with CBD (as seen in our case).…”

“…Finally, FDG PET can help the distinction between PSP and CBD. While FDG PET in PSP typically shows a characteristic pattern of hypometabolism in the midbrain, basal ganglia, thalamus, and frontal lobes, CBD asymmetrically involves the frontal and parietal lobes, basal ganglia, and thalamus 3 .…”

“…The term CBS concerns a purely phenotypic description and may be caused by different underlying neurodegenerative pathologies, including Corticobasal Degeneration (CBD), Alzheimer's Disease (AD), or Progressive Supranuclear Palsy (PSP) 2 . On the other hand, CBD refers to the pathological entity originally characterized by asymmetrical frontoparietal cortical atrophy, loss of neurons in the substantia nigra, and swelling of the neuronal cell bodies with achromatic cells 3 .…”

Decoding Neurodegeneration: A Comprehensive Review of Molecular Mechanisms, Genetic Influences, and Therapeutic Innovations

“… Patients diagnosed with corticobasal degeneration (CBD) often display corticobasal syndrome (CBS), characterized by bradykinesia, rigidity, dystonia, apraxia, cortical sensory signs, alien limb phenomenon, and bradykinesia [ 16 ]. They may also show features of FTD (bvFTD or nfvPPA), displaying depigmentation in the substantia nigra, atrophy of globus pallidus, as well as focal and asymmetric cerebral cortical atrophy—histopathological features that overlap between PSP and CBD such as tau-immunoreactive glial cells as well as NCI histopathological features of both syndromes [ 17 ]. FTD caused by mutations of the MAPT gene is an autosomal dominant form linked to chromosome 17 (FTDP-17T) that accounts for roughly 10% of familial FTD cases.…”

“…They may also show features of FTD (bvFTD or nfvPPA), displaying depigmentation in the substantia nigra, atrophy of globus pallidus, as well as focal and asymmetric cerebral cortical atrophy—histopathological features that overlap between PSP and CBD such as tau-immunoreactive glial cells as well as NCI histopathological features of both syndromes [ 17 ].…”