Clinicopathological correlations in corticobasal degeneration

Memory and Aging Center, University of California San Francisco, San Francisco, CA 94143, USA.
Annals of Neurology (Impact Factor: 11.91). 08/2011; 70(2):327-40. DOI: 10.1002/ana.22424
Source: PubMed

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.

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Available from: Eric Huang, Aug 15, 2015
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    • "Other localizations of AD neuropathology cause atypical manifestations: early behavioral changes in a frontal variant of AD, and massive visuospatial dysfunction in posterior cortical atrophy (Alladi et al, 2007). Up to 23% of patients with CBS have AD pathology (Lee et al, 2011), and we recently described focal AD with signs and symptoms of CBS (Johanidesova et al, 2012). "
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    Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 12/2013; 26(4):189-94. DOI:10.1097/WNN.0000000000000011 · 1.14 Impact Factor
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    • "We did not test him for driving abilities, but according to his wife's description, we inferred it had to do with his attentional and executive dysfunction, for instance, difficulties to manage dual tasks, slowness of information processing, planning, and using strategies to reach the end point. Executive functions seem to follow the same pattern of decline as episodic memory along with SD or CBD progression and severity (Graham et al., 2003; Kelley et al., 2009; Lee et al., 2011; Matuszewski et al., 2009; Rohrer et al., 2010). These results point to frontal lobe dysfunction, including not only SD, but also CBD Downloaded by [Universitaire De Lausanne] at 07:24 29 October 2013 TABLE 4 Summary of reports of fluent aphasia in CBD/CBS patients "
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    ABSTRACT: A 57-year-old male with no family history was diagnosed with semantic dementia. He also showed some unusual cognitive features such as episodic memory and executive dysfunctions, spatial disorientation, and dyscalculia. Rapidly progressive cognitive and physical decline occurred. About 1.5 years later, he developed clinical features of a corticobasal syndrome. He died at the age of 60. Brain autopsy revealed numerous 4R-tau-positive lesions in the frontal, parietal and temporal lobes, basal ganglia, and brainstem. Neuronal loss was severe in the temporal cortex. Such association of semantic dementia with tauopathy and corticobasal syndrome is highly unusual. These findings are discussed in the light of current knowledge about frontotemporal lobar degeneration.
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    • "It should be noted though that the underlying pathology in these subjects could be progressive supranuclear palsy, since limb apraxia was previously reported in subjects with AOS and progressive supranuclear palsy pathology (Josephs et al., 2006a). This would be in keeping with the fact that while only about half of subjects with corticobasal syndrome have corticobasal degeneration pathology (Josephs et al., 2006b; Ling et al., 2010; Lee et al., 2011), many also have progressive supranuclear palsy pathology (Josephs et al., 2006b; Ling et al., 2010; Lee et al., 2011). Regardless, the evidence indirectly suggests that the underlying pathology associated with PPAOS is likely to be tau, either progressive supranuclear palsy or corticobasal degeneration (Josephs et al., 2006a; Josephs and Duffy, 2008; Deramecourt et al., 2010). "
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