Objective: To evaluate diagnostic criteria for corticobasal degeneration (CBD) in relation to pathology and disease course.

Background: The overlapping features of CBD and related conditions raise operational difficulties for applying diagnostic criteria. Even within a specific pathologically-defined disease, there is clinical heterogeneity which changes over time(1). The Armstrong criteria (2) define different CBD clinical phenotypes: CBD-corticobasal syndrome (CBS), CBD-nonfluent/agrammatic variant aphasia (NAV), CBD-progressive supranuclear palsy syndrome (PSPS) and CBD-frontal behavioural spatial (FBS). Patients presenting with one of the clinical phenotypes of CBD may have more than one overlapping CBD phenotype. The predominant phenotype may vary over time, and movement and cognitive disorders clinics evaluate and define a different disease spectrum.

Method: We identified 133 pathologically defined cases with a clinical diagnosis of CBS, CBD or an overlap syndrome during life. Using established criteria, each case was reviewed and assigned a syndromic diagnosis for (i) initial phenotype, (ii) early dominant phenotype (first 3 years), (iii) late dominant phenotype and (iv) greatest diagnostic certainty (clinically Probable CBD > Possible CBD).  Exclusion criteria were applied as available, the majority lacking Alzheimer biomarker studies. We also applied criteria for PSP, MSA and DLB.

Results: Across the group, 81% had more than one syndromic allocation, increasing with time (mean 2.4 <3 years, to 4.4 over disease course). 53 (40%) had confirmed CBD pathology. 23% met criteria for Probable PSP, MSA or DLB <3 years, 48% over disease course. Initial and early dominant phenotype was consistent in the majority (>95%). The positive predictive value for CBD pathology was 33% for clinically probable CBD and 51% for clinically possible CBD.  Language presentations (CBD-NAV) fitting clinically probable or possible CBD criteria had the highest predictive value for CBD pathology versus other phenotypes. CBD-PSP has a rapid disease course.

Conclusion: Armstrong criteria for CBD, irrespective of phenotype, have a low predictive value for CBD pathology in retrospective cohorts with incomplete clinical data.  More prospective data are needed with rigorous assessment of exclusion criteria, including AD biomarkers.  A biomarker for CBD as compared to PSP would improve diagnostic accuracy.

References: 1. Grimm MJ, Respondek G, Stamelou M, et al. How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy. Mov Disord. 2019;34(8):1228-1232. doi:10.1002/mds.27666 2. Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, Boxer AL, Dickson DW, Grossman M, Hallett M, Josephs KA, Kertesz A, Lee SE, Miller BL, Reich SG, Riley DE, Tolosa E, Tröster AI, Vidailhet M, Weiner WJ. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013 Jan 29;80(5):496-503. doi: 10.1212/WNL.0b013e31827f0fd1. PMID: 23359374; PMCID: PMC3590050.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-evaluation-of-the-application-of-clinical-research-criteria-for-corticobasal-degeneration-in-a-large-clinico-pathological-series/