Clinicopathological correlations in corticobasal degeneration
Article first published online: 5 AUG 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 2, pages 327–340, August 2011
How to Cite
Lee, S. E., Rabinovici, G. D., Mayo, M. C., Wilson, S. M., Seeley, W. W., DeArmond, S. J., Huang, E. J., Trojanowski, J. Q., Growdon, M. E., Jang, J. Y., Sidhu, M., See, T. M., Karydas, A. M., Gorno-Tempini, M.-L., Boxer, A. L., Weiner, M. W., Geschwind, M. D., Rankin, K. P. and Miller, B. L. (2011), Clinicopathological correlations in corticobasal degeneration. Ann Neurol., 70: 327–340. doi: 10.1002/ana.22424
- Issue published online: 5 AUG 2011
- Article first published online: 5 AUG 2011
- Accepted manuscript online: 16 MAR 2011 12:27PM EST
- Manuscript Accepted: 9 MAR 2011
- Manuscript Revised: 6 MAR 2011
- Manuscript Received: 26 MAY 2010
- NIH/NCRR UCSF-CTSI Grant. Grant Number: UL1 RR024131
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. ANN NEUROL 2011;