Pathologic heterogeneity in clinically diagnosed corticobasal degeneration

Background: Early reports suggested that corticobasal degeneration (CBD) is a distinct clinicopathologic entity. Because patients have had a fairly consistent constellation of clinical and laboratory findings, many have proposed that the pathologic diagnosis can be surmised with confidence during life. Objective: To analyze the pathologic findings in a large series of cases with clinically diagnosed CBD. Methods: Using the medical research linkage system of the Mayo Clinic for the period January 1990 to December 1997, we identified cases diagnosed during life with CBD who subsequently underwent autopsy. All patients had progressive asymmetric rigidity and apraxia (except one with rigidity but no apraxia) with other findings, suggesting additional cortical and basal ganglionic dysfunction. All cases underwent standardized neuropathologic examination with the distribution and severity of the pathologic changes determined for each case and the pathologic diagnoses based on currently accepted criteria. Results: Thirteen cases were identified. The pathologic diagnoses were CBD in seven, AD in two, and one each for progressive supranuclear palsy, Pick's disease, nonspecific degenerative changes, and Creutzfeldt-Jakob disease. Two cases had negligible basal ganglia and nigral degeneration despite previously having obvious extrapyramidal signs. However, all patients had focal or asymmetric cortical atrophy with coexisting neuronal loss and gliosis with or without status spongiosis, which was maximal in the parietal and frontal cortical regions. Conclusions: The constellation of clinical features considered characteristic of CBD is associated with heterogeneous pathologies. Furthermore, this syndrome can occur in the absence of basal ganglia and nigral degeneration. The one invariable pathologic abnormality in patients with this syndrome, however, is asymmetric parietofrontal cortical degeneration. At present, accurate diagnosis of CBD requires tissue examination.