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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Movement disorders with parkinsonian features are common, and in recent years imaging has assumed a greater role in diagnosis and management. Thus, it is important that radiologists become familiar with the most common imaging patterns of parkinsonism, especially given the significant clinical overlap and diagnostic difficulty associated with these disorders. The authors review the most common magnetic resonance (MR) and molecular imaging patterns of idiopathic Parkinson disease and atypical parkinsonian syndromes. They also discuss the interpretation of clinically available molecular imaging studies, including assessment of cerebral metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET), cortical amyloid deposition with carbon 11 ((11)C) Pittsburgh compound B and fluorine 18 ((18)F) florbetapir PET, and dopaminergic activity with iodine 123 ((123)I) ioflupane single photon emission computed tomography (SPECT). Although no single imaging test is diagnostic, a combination of tests may help narrow the differential diagnosis. Findings at (123)I ioflupane SPECT can confirm the loss of dopaminergic neurons in patients with parkinsonism and help distinguish these syndromes from treatable conditions, including essential tremor and drug-induced parkinsonism. FDG PET uptake can demonstrate patterns of neuronal dysfunction that are specific to a particular parkinsonian syndrome. Although MR imaging findings are typically nonspecific in parkinsonian syndromes, classic patterns of T2 signal change can be seen in multiple system atrophy and progressive supranuclear palsy. Finally, positive amyloid-binding PET findings can support the diagnosis of dementia with Lewy bodies. Combined with a thorough clinical evaluation, multimodality imaging information can afford accurate diagnosis, allow selection of appropriate therapy, and provide important prognostic information. ©RSNA, 2014.
    Radiographics 09/2014; 34(5):1273-1292. · 2.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by impaired higher visual processing skills, however motor features more commonly associated with corticobasal syndrome (CBS) may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-Motor subgroup. 30% (13) had PCA-Motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-Motor, as was myclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or Apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-Motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen and thalamus. The nine patients (including four PCA-Motor) with pathology or CSF all showed evidence of AD. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying AD.
    Neurobiology of Aging 12/2014; · 4.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities. Prospectively recruited case-control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them. The Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer's disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups. Reduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.
    Alzheimer's Research and Therapy 12/2014; 6(9):71. · 3.50 Impact Factor

Full-text (2 Sources)

Available from
Jun 3, 2014

Suzee E Lee