Pathology and sensitivity of current clinical criteria in corticobasal syndrome

Abstract

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four-repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p-CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr-CBD) at the later stage. Only two patients fulfilled the criteria for either p-CBD or cr-CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset.

Eyelid Dysfunction in Neurodegenerative, Neurogenetic, and Neurometabolic Disease

“…Furthermore, AEO typically coincides with or precedes the onset of parkinsonism in PSP, whereas it is a much later manifestation of PD. AEO is also seen in MSA and corticobasal syndrome, though in the latter the underlying pathology at autopsy is one of PSP rather than true corticobasal ganglionic degeneration (128). It has also been described in cases of amyotrophic lateral sclerosis (ALS) with or without frontotemporal disease, HD, SCA2 (129), SCA3 (130), Wilson’s disease, chorea-acanthocytosis, and others.…”

Key emerging issues in progressive supranuclear palsy and corticobasal degeneration

“…Unfortunately, one study assessing the validity of the CBD criteria for research concluded that the new probable criteria was not specific as many of patients in their study met criteria for possible or probable CBD, yet did not have CBD pathology [11]. A second study also demonstrated that the clinical criteria for possible CBD were not very sensitive within the first two years of disease onset [12]. …”

Cognitive dysfunction in corticobasal degeneration

“…For instance, only 25% to 56.25% of patients with pathologically-confirmed CBD had previously presented with symptoms of CBS 4,5,6 . On the other hand, the proportion of patients diagnosed with CBS presenting with the histologic hallmarks of CBD is highly variable, ranging from 23.8% to 100% 4,5,6,7 . Considering the enormous difficulty in accurately diagnosing CBD during life, it is clear that current epidemiological estimates hold substantial uncertainty.…”

“…These new criteria have expanded the recognized clinical phenotypes, reflecting current knowledge. Still, it seems to lack specificity for the clinical diagnosis 11 and sensitivity within the first two years of disease onset 7 .…”