Autopsy-proven progressive supranuclear palsy presenting as behavioral variant frontotemporal dementia

Abstract

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder pathologically characterized by neuronal loss, gliosis and tau-positive neurofibrillary tangles in basal ganglia, brainstem and cerebellar nuclei. Five presenting clinical syndromes of PSP are well-described: (i) the classic Richardson's syndrome; (ii) asymmetric parkinsonism with tremor; (iii) freezing of gait; (iv) asymmetric limb apraxia, and (v) apraxia of speech. Aim: To determine whether autopsy-proven PSP cases may present with another clinical phenotype. Methods: Medical records of 66 autopsy-proven PSP cases between 1973 and 2010 were reviewed to determine whether all could be classified into one of five well-defined syndromes listed above. Three cases presented with prominent behavioral and personality changes, meeting diagnosis of behavioral variant frontotemporal dementia. MRI midbrain and pons volumes and pons/midbrain ratios were compared to healthy controls and typical PSP cases. Results: All three bvFTD cases developed at least one PSP symptom or sign that emerged up to 5 years after initial presentation. One case was re-diagnosed as PSP 6 years after presentation as bvFTD. Compared to controls, midbrain volume was significantly smaller in both bvFTD (p = .03) and PSP cases (p = .008), without significant difference between PSP and bvFTD cases (.44). However pontine volumes were similar across all three groups. Conclusions: While most autopsy-confirmed PSP cases present with one of the five well-described syndromes, there are cases that may present as bvFTD. In these, at least one cardinal symptom or sign of PSP later emerges, associated with smaller midbrain volume and increased pons/midbrain ratio. Thus underlying PSP pathology should be considered in these cases.