Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome

Abstract

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Keywords: clinical course; corticobasal degeneration; corticobasal syndrome; diagnosis; pathology.

Graphical Abstract

Figure 1

Analytic flow and background pathology in CBS. (A) Analytic flow for CBD and CBD mimics. CBD–PSPS, corticobasal degeneration (CBD) presented progressive supranuclear palsy (PSP) syndrome; CBD–CBS, CBD presented corticobasal syndrome (CBS); PSP–CBS, PSP presented CBS; AD–CBS, Alzheimer’s disease (AD) presented CBS. (B) The background pathology of CBS. CBS, corticobasal syndrome; CBD, corticobasal degeneration; PSP, progressive supranuclear palsy; FTLD-TDP, frontotemporal dementia (FTLD) with TDP-43 pathology; DLB, dementia with Lewy bodies; GGT, globular glial tauopathy. The background pathology of CBS includes various tauopathies. CBD was most common, followed by PSP, AD FTLD-TDP, DLB, and GGT. Others included FTLD fused in sarcoma (FUS) (n = 1), glioblastoma (n = 1), Pick’s disease (n = 1), prion disease (n = 1) and non-specific pathological changes (n = 1).

Figure 2

Interval from the initial symptom to key milestones in CBD. (A) Patients with CBD. (B) Patients with CBD–CBS. (C) Patients with CBD–PSPS. (D) Patients with CBD–dementia. CBD, corticobasal degeneration; CBS, corticobasal syndrome; PSPS, progressive supranuclear palsy syndrome.

Figure 3

Combination of clinical phenotype in CBD. Each number is a number of patients who met the item of Armstrong’s criteria. The most common clinical type was PSPS (48 or 84% at the presentation or during the entire course, respectively), followed by FBS (48 or 64%) and possible CBS (32 or 46%) using Armstrong’s criteria. Many patients with CBD met the multiple clinical phenotypes of the Armstrong criteria. Conversely, 11 patients at presentation and four during the course did not meet any clinical criterion. One patient data during the entire course were unavailable. CBD, corticobasal degeneration; PSPS, progressive supranuclear palsy syndrome; FBS, frontal behavioural–spatial syndrome; naPPA, non-fluent/agrammatic variant of primary progressive aphasia; Possi CBS, possible corticobasal syndrome; Prob CBS, probable corticobasal syndrome.

Figure 4

Interval from the initial symptom to key milestones in CBD mimics. (A) Patients with CBD mimics. (B) Patients with PSP–CBS. (C) Patients with AD–CBS. CBD, corticobasal degeneration; CBS, corticobasal syndrome; PSP, progressive supranuclear palsy.

Figure 5

Decision tree analysis for background pathology of CBS. A decision tree analysis was performed using the classification and regression tree method with CBD, PSP and AD as the dependent variables and sex, age at onset and significant findings (freezing at onset, tremor at onset, dysarthria at onset, dysarthria at presentation, pyramidal signs at presentation, pyramidal signs during the entire course, myoclonus during the entire course, personality change during the entire course and supranuclear gaze palsy during the entire course) as the independent variables, and cross-validation was performed. (A) Clinical findings suggestive of CBD pathology. ‘Freezing at onset’ or ‘no dysarthria at presentation and age at onset <66 years in the case without freezing at onset’ predicted CBD pathology with a sensitivity of 81.3%, specificity of 84.4%, PPV of 72.3% and NPV of 90%. (B) Clinical findings suggestive of PSP pathology. ‘Dysarthria at presentation and age at onset older than 61 years’ suggested PSP pathology, with a sensitivity of 64.3%, specificity of 85.3%, PPV of 64.3% and NPV of 85.3%. (C) Clinical findings suggestive of AD pathology. ‘Pyramidal sign at presentation and personality change during the entire course’ implied AD pathology with a sensitivity of 66.7%, specificity of 95.2%, PPV of 66.7% and NPV of 95.2%. n, number of patients; CRT, classification and regression tree method; CBS, corticobasal syndrome; CBD, corticobasal degeneration; PSP, progressive supranuclear palsy; AD, Alzheimer's disease; PPV, positive predictive value; NPV, negative predictive value.