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Abstract
Background and Objectives Corticobasal syndrome (CBS) is a clinical phenotype characterized by asymmetric parkinsonism, rigidity, myoclonus, and apraxia. Originally believed secondary to corticobasal degeneration (CBD), mounting clinicopathologic studies have revealed heterogenous neuropathologies. The objectives of this study were to determine the pathologic heterogeneity of CBS, the clinicoradiologic findings associated with different underlying pathologies causing CBS, and the positive predictive value (PPV) of current diagnostic criteria for CBD among patients with a CBS.
Methods Clinical data, brain MRI, and neuropathologic data of patients followed at Mayo Clinic and diagnosed with CBS antemortem were reviewed according to neuropathology category at autopsy.
Results The cohort consisted of 113 patients with CBS, 61 (54%) female patients. Mean ± SD disease duration was 7 ± 3.7 years; mean ± SD age at death was 70.5 ± 9.1 years. The primary neuropathologic diagnoses were 43 (38%) CBD, 27 (24%) progressive supranuclear palsy (PSP), 17 (15%) Alzheimer disease (AD), 10 (9%) frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP) inclusions, 7 (6%) diffuse Lewy body disease (DLBD)/AD, and 9 (8%) with other diagnoses. Patients with CBS-AD or CBS-DLBD/AD were youngest at death (median [interquartile range]: 64 [13], 64 [11] years) while CBS-PSP were oldest (77 [12.5] years, p = 0.024). Patients with CBS-DLBD/AD had the longest disease duration (9 [6] years), while CBS-other had the shortest (3 [4.25] years, p = 0.04). Posterior cortical signs and myoclonus were more characteristic of patients with CBS-AD and patients with CBS-DLBD/AD. Patients with CBS-DLBD/AD displayed more features of Lewy body dementia. Voxel-based morphometry revealed widespread cortical gray matter loss characteristic of CBS-AD, while CBS-CBD and CBS-PSP predominantly involved premotor regions with greater amount of white matter loss. Patients with CBS-DLBD/AD showed atrophy in a focal parieto-occipital region, and patients with CBS-FTLD-TDP had predominant prefrontal cortical loss. Patients with CBS-PSP had the lowest midbrain/pons ratio (p = 0.012). Of 67 cases meeting clinical criteria for possible CBD at presentation, 27 were pathology-proven CBD, yielding a PPV of 40%.
Discussion A variety of neurodegenerative disorders can be identified in patients with CBS, but clinical and regional imaging differences aid in predicting underlying neuropathology. PPV analysis of the current CBD diagnostic criteria revealed suboptimal performance. Biomarkers adequately sensitive and specific for CBD are needed.
Glossary
- AD=
- Alzheimer disease;
- AGD=
- argyrophilic grain disease;
- ARTAG=
- aging-related tau astrogliopathy;
- CBS=
- corticobasal syndrome;
- CBD=
- corticobasal degeneration;
- CJD=
- Creutzfeldt-Jakob disease;
- DLBD=
- diffuse Lewy body disease;
- FDG=
- 18F fluorodeoxyglucose;
- FTLD=
- frontotemporal lobar degeneration;
- FUS=
- fused in sarcoma;
- IQR=
- interquartile range;
- LBD=
- Lewy body dementia;
- NIBD=
- neurofilament inclusion body disease;
- PCA=
- posterior cortical atrophy;
- PPA=
- primary progressive aphasia;
- PPV=
- positive predictive value;
- PSP=
- progressive supranuclear palsy;
- RBD=
- REM sleep behavior disorder;
- SPM=
- statistical parametric mapping;
- STMS=
- Short Test of Mental Status;
- TDP=
- TAR DNA-binding protein 43;
- VBM=
- voxel-based morphometry
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.
- Received January 18, 2023.
- Accepted in final form March 23, 2023.
- © 2023 American Academy of Neurology
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