Quick Conclusions From Slowed Saccades: When Progressive Supranuclear Palsy Overshadows Lewy Body Disease

Antemortem prediction of dementia-causing neurodegenerative disease is challenging, in part due to the frequency of co-occurring diseases. Etiologic diagnosis may be aided by the identification of highly specific clinical features or available biomarkers. Here we present an educational case of an individual with a primary neuropathological diagnosis of lewy body disease (LBD) and contributing progressive supranuclear palsy (PSP). He was clinically diagnosed only with PSP-Richardson syndrome based on ocular motor findings. LBD was not considered despite several inconsistent clinical features. Neuropathological examination showed well-developed transitional/limbic LBD and a very mild burden of PSP. Diagnostic criteria for PSP were just met based on semiquantitative ratings and affected neuroanatomy. No amyloid plaques of Alzheimer disease (AD) were identified, but AD-tau tangles reached Braak stage 4. Postmortem analysis of cerebrospinal fluid showed alpha-synuclein seeding amplification, but no clear evidence for AD. However, plasma biomarkers P-tau181 and P-tau217 suggested AD neuropathological change. Biomarkers may assist in the assessment of multiple etiologies, but they are imperfect and require expert interpretation within clinical contexts. Accurate etiologic prediction requires an understanding of common co-occurring neurodegenerative diseases, cautious interpretation of biomarkers, and knowledge of clinicopathological relationships.