Progressive Supranuclear Palsy Syndrome Associated With a Novel Tauopathy: Case Study.

Abstract

To report a novel tauopathy in a patient with protracted course progressive supranuclear palsy (PC-PSP). This was a clinical follow-up, gene analysis, neuropathologic study. A 73-year-old man presented with diplopia, slowness, shuffling gait, and falls. Neurologic examination revealed slowed saccades, restricted up-gaze, and mild parkinsonism. Three years after onset, he developed personality changes. Slowly progressive parkinsonism was associated with memory and executive deficits. MRI showed subtle bilateral hippocampal and midbrain tegmentum atrophy and hyperintensity in the brainstem tegmentum and white matter of the medial temporal lobe. The duration of illness was 11 years. There were no pathogenic mutations in 80 genes known to be involved in neurodegeneration, including <i>MAPT</i> (H1/H1 haplotype) and <i>APOE</i> (ε3/ε3 genotype). Neuropathology revealed PSP type pathology together with the pathology described in the novel limbic-predominant neuronal inclusion body 4-repeat tauopathy (LNT) correlating well with the signal alterations seen in MRI. Our observation broadens the spectrum of tau pathology associated with PC-PSP and suggests that memory deficit and hippocampal atrophy may be suggestive of non-Alzheimer disease pathology, including LNT. Understanding the diverse range of tau morphologies may help explain phenotypic heterogeneity seen in PSP.