Abstract Details

Corticobasal syndrome (CBS) is characterized by asymmetric parkinsonism, rigidity, myoclonus, and apraxia. While originally considered primarily a motor disorder secondary to corticobasal degeneration (CBD), its effects on cognition, behavior, and language are now well-recognized - as well as its heterogenous underlying neuropathologies.  

The objectives of this study were to determine the pathologic heterogeneity, the clinico-radiological findings associated with different underlying pathologies, and the positive predictive value (PPV) of current diagnostic criteria for CBD amongst patients with CBS.

Clinical, neuropathologic, brain MRI and FDG-PET imaging data of patients clinically diagnosed with CBS were reviewed according to neuropathology determined at autopsy.

The cohort included 113 patients, 61 (54%) females. Primary neuropathologic diagnoses were: 43 (38%) CBD, 27 (23.9%) progressive supranuclear palsy (PSP), 17 (15%) Alzheimer’s disease (AD), 10 (8.8%) frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), 7 (6.2%) diffuse Lewy body disease/AD (DLBD/AD), and 9 (7.9%) with other diagnoses. CBS-AD or CBS-DLBD/AD patients were youngest at death (median [IQR]: 64[13], 64[11] years) while CBS-PSP patients were oldest (77[12.5], P=0.024). CBS-DLBD/AD patients had the longest disease duration (9[6] years) while CBS-other subgroup had the shortest (3[4.25], P=0.04). Posterior cortical signs and myoclonus were more characteristic of CBS-AD and CBS-DLBD/AD patients.

Voxel-based morphometry revealed that widespread cortical loss was characteristic of CBS-AD, while CBS-CBD and CBS-PSP predominantly involved premotor regions with greater white matter loss. CBS-DLBD/AD showed atrophy in a focal parieto-occipital region, and CBS-FTLD-TDP had predominant prefrontal cortical loss. For cases with CBS-PSP pathology, midbrain/pons ratio was lowest (P=0.012).

Of the 67 cases who met criteria for possible CBD at presentation, 27 were pathology-proven CBD cases, yielding PPV of 40.3%.

A variety of neurodegenerative disorders can be identified in CBS patients, but clinical and regional imaging differences may aid in predicting underlying neuropathology. Biomarkers that are sensitive and specific for underlying CBD are needed.