Clinicopathological correlations in corticobasal degeneration

TLDR

Antemortem prediction of corticobasal degeneration remains difficult without redefined clinical features and specific biomarkers. The study aims to characterize cognitive, behavioral, physical findings, and brain atrophy patterns in pathology‑proven corticobasal degeneration and corticobasal syndrome. The authors reviewed clinical and MRI data from 18 autopsy‑confirmed CBD patients and 40 CBS patients with known histopathology, comparing atrophy patterns via voxel‑based morphometry. CBD patients show early behavioral or cognitive symptoms, dorsal prefrontal and perirolandic atrophy, and are linked to four clinical syndromes, whereas CBS is characterized by perirolandic atrophy regardless of pathology, with FTLD‑associated CBS extending to prefrontal cortex and AD‑associated CBS extending to temporoparietal cortex.

Abstract

To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology.We reviewed clinical and magnetic resonance imaging data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n = 18) or clinical CBS at first presentation with known histopathology (n = 40). Atrophy patterns were compared using voxel-based morphometry.CBD was associated with 4 clinical syndromes: progressive nonfluent aphasia (n = 5), behavioral variant frontotemporal dementia (n = 5), executive-motor (n = 7), and posterior cortical atrophy (n = 1). Behavioral or cognitive problems were the initial symptoms in 15 of 18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and perirolandic cortex, striatum, and brainstem (p < 0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p < 0.001 uncorrected).Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia, symptoms dominate early stage disease. CBS is driven by medial perirolandic dysfunction, but this anatomy is not specific to a single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified.