Improving the early diagnosis of corticobasal syndrome: a large clinico-pathological study

Abstract

BackgroundCorticobasal syndrome is associated with a heterogeneous spectrum of pathologies, with low predictive value for Corticobasal degeneration (CBD) pathology. Here, we validate the Armstrong criteria and interrogate clinical features to improve accurate diagnosis ante-mortem.MethodsWe applied Armstrong criteria to all archived cases with a clinical diagnosis of CBS or CBS- overlap syndrome over disease course. Clinical and radiological features were compared by pathologi- cal substrate.Results105 of 123 patients met diagnostic criteria for either Probable or Possible CBS/CBD of whom 38 (36%) had CBD and 79 (75%) had 4-repeat tauopathies (4RT). 3 years from onset, 8/22(36%) of those with Probable CBD and 19/48(40%) Possible CBD had pathology-confirmed CBD, whilst 11/35 (31%) were ‘Armstrong-negative”. Over disease course, PPV for CBD was similar (36%). Criteria were better at predicting 4RT, 82% and 75% within 3 years of onset and over disease course, respectively. Addition of specific language or behavioural abnormalities did not improve PPV. 46% patients met MDS PSP/CBS criteria over disease course, with 92% PPV for 4RT. No individual clinical feature was found to singularly predict underlying pathology.ConclusionThe Armstrong criteria have low predictive value for CBD both in early disease and over disease course. However, it has >80% prediction of 4RT. A combination of more specific biomarkers are required to improve diagnosis.d.lux@ucl.ac.uk