Unusual phenotype of pathologically confirmed progressive supranuclear palsy with autonomic dysfunction and cerebellar ataxia: Case report

Abstract

Background: Based on the results of recent multicenter clinical-pathological studies, it seems that the clinical heterogeneity of progressive supranuclear palsy (PSP) is much broader than previously thought. We will report 2 cases of patients with unusual manifestation of pathologically confirmed PSP.

Methods: Two female patients were diagnosed with the parkinsonian phenotype of multiple system atrophy (MSAP) according to current clinical diagnostic criteria at the ages of 55 and 60 years, respectively. The patients were followed up for the next 5 and 7 years. In both cases, a detailed neuropathological examination of the brain was conducted postmortem.

Results: In the first case, the overall pathological picture corresponded with the diagnosis of 4R tauopathy. In the second case, the brain pathology corresponded with a combination of 4R tauopathy and neocortical amyloidopathy.

Conclusion: Some of the main symptoms of MSA, such as cerebellar ataxia and orthostatic hypotension, are not rare parts of the clinical picture of PSP. PSP can thus be mistakenly diagnosed as MSA. In order to determine the most accurate clinical diagnosis of PSP, a revision of its current clinical diagnostic criteria seems appropriate.

Figure 1

Case 1. Horizontal FLAIR sequence showing rare small nonspecific (probably postischemic) white matter lesions (A). Sagittal T1-weighted MRI, showing near-normal shape of the brainstem (B). FLAIR = fluid-attenuated inversion recovery, MRI = magnetic resonance imaging.

Figure 2

Case 2. Horizontal FLAIR sequence showing mild supratentorial changes in the white matter of both hemispheres (A). Sagittal T1-weighted MRI showing the normal shape of the brain stem (B). FLAIR = fluid-attenuated inversion recovery, MRI = magnetic resonance imaging.

Figure 3

Case 1. Atrophy of the subthalamic nucleus (A). Spectrum of tau pathology in different brain regions: numerous threads, coiled bodies, and neurofibrillary tangles in the subthalamic region (AT8; B). A few tufted astrocytes in the basal ganglia (AT8; C). Neurofibrillary tangles in pigmented neurons of the substantia nigra (4RD; D). Original magnification: 100×.

Figure 4

Case 2. Numerous deposits of hyperphosphorylated tau protein positive with monoclonal antibody against DR4 subtype of tau protein in the substantia nigra, proving progressive supranuclear palsy (A). Neurofibrillary degenerative structures stained with monoclonal antibody against hyperphosphorylated tau protein showing Alzheimer disease–related neuropathology (B). Numerous deposits of hyperphosphorylated tau protein positive with monoclonal antibody against DR4 subtype of tau protein in the substantia nigra, original magnification 200× (C). Different morphology of amyloid plaques and cerebral amyloid angiopathy positive in immunohistochemical reaction with monoclonal antibody against amyloid-β-peptide (D).