Is the Pathology of Corticobasal Syndrome Predictable in Life?

Prince of Wales Medical Research Institute, Barker Street, Randwick, New South Wales, Australia
Movement Disorders (Impact Factor: 5.68). 08/2009; 24(11):1593 - 1599. DOI: 10.1002/mds.22558
Source: PubMed


Corticobasal syndrome (CBS) has been associated with a heterogeneous spectrum of pathologies with an increasing number of reports of Alzheimer's type pathology. There is, however, no means of predicting pathology of CBS in vivo at present. We compared the clinical features of patients presenting with CBS who have either pathologic changes of classic corticobasal degeneration (CBD) or Alzheimer's disease (AD) at post-mortem to identify predictors of the specific pathological processes in life. Twelve patients with CBS were followed prospectively; six had AD and six had classic CBD neuropathology. After review of the presenting clinical features, we identified nine potential predictor variables, compared their frequency in the two groups, and performed a discriminant function analysis. Initial episodic memory complaints and poor performance on the combined orientation-memory subtest of the Addenbrooke's Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal-lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante-mortem. CBS is frequently associated with Alzheimer's disease pathology. Early episodic memory impairment versus early behavioral symptomatology appears to best predict AD or CBD pathology in life. © 2009 Movement Disorder Society

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Available from: Thomas H Bak, Dec 19, 2013
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    • "The bulk of these observations suggest that most phenotypes are in general poorly predictive of the underlying pathology (Josephs et al. 2006b). CBS can include a diverse, non-CBD range of neuropathologies including PSP and most notably AD (Shelley et al. 2009), particularly when episodic memory complaints are prominent (see Bradley Boeve's, " The multiple phenotypes of corticobasal syndrome and corticobasal degeneration, " this issue). "
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    Journal of Molecular Neuroscience 09/2011; 45(3):343-9. DOI:10.1007/s12031-011-9632-1 · 2.34 Impact Factor
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    • "So far, normal dopamine transporter density has been reported only sporadically in CBS [19], [45], while none of the few systematic imaging studies in consecutive cohorts ever documented any normal scan [40]–. To our knowledge, there are only few reports of patients with clinical diagnosis of CBD with preserved SNc neuronal density at post-mortem, and most of them displayed either Alzheimer's or Pick's disease pathology [2], [3], [5], [7], [9], [10], [14], [15], [46]–[48]. The first possible explanation would come from a possible pathological involvement of the downstream postsynaptic neurons, even though the pathological involvement of postsynaptic striatal neurons in CBD is variable and unpredictable [17], [49]. "
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    ABSTRACT: To investigate dopaminergic function in a large cohort of patients with corticobasal syndrome (CBS) and describe its relationship with clinical features in comparison to Parkinson's disease and healthy control subjects. In addition, we assessed prevalence and features of individuals with CBS and in vivo evidence of preserved nigral neuronal density. Substantia nigra pars compacta (SNc) neuronal degeneration is a mandatory pathological criterion for definite corticobasal degeneration, though sporadic autopsy-proven cases with ante-mortem imaging evidence of preserved nigral terminals have been recently described. In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for "probable corticobasal degeneration" (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans. FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake. Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD.
    PLoS ONE 05/2011; 6(5):e18301. DOI:10.1371/journal.pone.0018301 · 3.23 Impact Factor
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    • "It is less common, however, for subjects presenting with CBS or bvFTD to show underlying AD pathology (Johnson et al., 1999; Alladi et al., 2007; Hu et al., 2009; Shelley et al., 2009), and neither syndrome is typically associated with predominant temporoparietal atrophy. Corticobasal syndrome is characterized by insidious onset and a progressive course of asymmetric cortical dysfunction, for example, ideomotor apraxia, cortical sensory loss or myoclonus, and asymmetric extrapyramidal dysfunction reflected by at least levodopa unresponsive appendicular rigidity or dystonia (Boeve et al., 2003; Litvan et al., 2003). "
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