Corticobasal syndrome / corticobasal degeneration

Note: corticobasal syndrome (CBS) refers to the constellation of symptoms reflective of a clinical phenotype. Corticobasal degeneration refers to the underlying neuropathology. Corticobasal syndrome is not exclusively the result of corticobasal degeneration, and similarly, corticobasal degeneration does not always present as corticobasal syndrome.

Diagnosis

CBS clinical criteria (Armstrong 2013) (note that other clinical phenotypes, including FBS, naPPA, and PSP may also have CBD pathology)

1) Probable CBS

a. Must have asymmetric presentation

b. Must have at least two of the following:

i. Limb rigidity or akinesia

ii. Limb dystonia

iii. Limb myoclonus

c. Must have at least two of the following:

i. Orobuccal or limb apraxia

ii. Cortical sensory deficit (i.e. agraphesthesia, astereognosis)

iii. Alien limb phenomena (more than simple levitation)

2) Possible CBS

a. Must have asymmetric presentation

b. Must have at least one of the following:

i. Limb rigidity or akinesia

ii. Limb dystonia

iii. Limb myoclonus

c. Must have at least one of the following:

i. Orobuccal or limb apraxia

ii. Cortical sensory deficit

iii. Alien limb phenomena (more than simple levitation)

- patients with CBS will often have deficits within domains of executive functioning, writing, as and visuospatial construction (Finger 2016)

- neuroimaging shows asymmetric frontal and parietal lobe atrophy (Finger 2016

Other possible presentations of underlying corticobasal degeneration pathology: (Armstrong 2013)

1) Frontal behavioral-spatial syndrome

a. Must have at least two of the following:

i. Executive dysfunction

ii. Behavioral or personality changes

iii. Visuospatial deficits

2) Nonfluent / agrammatic variant primary progressive aphasia

3) Progressive supranuclear palsy (Steele-Richardson-Olszewski)

Pathology

Proposed pathologic criteria for the diagnosis of CBD require: (Armstrong 2013)

a) The detection of characteristic tau-immunoreactive lesions in the neurons, glia, and cell processes of the cortex and striatum (caudate and putamen), particularly astrocytic plaques and thread-like lesions in both white matter and gray matter

b) In conjunction with neuronal loss in focal cortical regions and in the substantia nigra

c) Supportive features include ballooned cortical neurons, cortical atrophy, and tau-positive oligodendroglial coiled bodies

- pathology is typically 4R tau (CBD) > (Alzheimer’s pathology) > PSP, TDP-43 > 3R tau 92

References

Armstrong, M. J. et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 80, 496–503 (2013). https://pubmed.ncbi.nlm.nih.gov/23359374/

Finger, E. C. Frontotemporal Dementias. Contin. Minneap. Minn 22, 464–489 (2016). https://pubmed.ncbi.nlm.nih.gov/27042904/