Office of Rare Diseases Neuropathologic Criteria for Corticobasal Degeneration

Abstract

A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis.

[18F]AV‐1451 PET in behavioral variant frontotemporal dementia due to MAPT mutation

“…The morphology and distribution of these inclusions appeared similar to sporadic frontotemporal lobar degeneration cases with CBD pathological subtype 12, 13. Immunostaining with 4‐repeat tau and p62 labeled a similar number of ballooned neurons, astrocytic plaques, and coiled bodies.…”

“…1C). Their morphology and distribution appeared typical for sporadic frontotemporal lobar degeneration with Corticobasal degeneration (CBD) pathology,12, 13 in keeping with MAPT mutation 14…”

Novel CSF biomarkers to discriminate FTLD and its pathological subtypes

“…FTLD cases with tau neuropathology (FTLD‐Tau, n  = 20) were selected based on autopsy ( n  = 2), MAPT mutations ( n  = 2),6 and familial history of autopsy confirmed FTLD‐Tau ( n  = 1). The FTLD‐Tau group was also enriched with CSF from patients with FTLD‐Plus syndromes related to tau pathology such as progressive supranuclear palsy (FTLD‐PSP, n  = 10) or corticobasal syndrome (FTLD‐CBS, n  = 5) 16, 17. Noteworthy, six FTLD‐Tau and six FTLD‐TDP patients had a positive AD CSF biomarker profile (low CSF β ‐amyloid 1–42 (A β 42) and high p or t‐Tau level, applying local laboratory standards), suggesting potential AD copathology in those cases.…”

Clinical, Cognitive and Anatomical Evolution from Nonfluent Progressive Aphasia to Corticobasal Syndrome: A Case Report

“…Recent reports stress the presence of significant frontal involvement in CBS, including posterior frontal regions (inferior frontal gyrus and motor and premotor cortices) and extending to the medial wall and the supplementary motor regions (Garraux et al, 2000;Kitagaki et al, 2000;Peigneux et al, 2001). Pathologically, CBS is characterized by neuronal loss and gliosis in the cortex, basal ganglia and substantia nigra and by the presence of ballooned neurons, and argyrophilic and tau-immunoreactive astrocytic plaques (Dickson et al, 2002). The clinical, anatomical and neuropathological similarities between FTLD, PPA, CBD and Pick's disease have led to the introduction of the concept of "Pick complex" disorder to subsume these overlapping syndromes (Kertesz et al, 1994).…”