Objective: Progressive Supranuclear Palsy (PSP) and Nonfluent Primary Progressive Aphasia (nfvPPA) are clinicopathological entities within the 4-repeat tauopathy (4R tauopathy) spectrum. Increasing evidence suggests that these disorders represent distinct phenotypic expressions along a shared pathological continuum rather than separate diseases.

Background: We report a case that initially presented with language-dominant symptoms and subsequently evolved into a typical PSP phenotype.

Method: An 82-year-old man presented with a six-year history of progressive cognitive decline. Initially, he developed memory impairment and difficulty with calculation. Four years prior to presentation, he exhibited progressive nonfluent speech characterized by reduced spontaneous output and effortful articulation, while comprehension was relatively preserved. Three years earlier, he was diagnosed with nfvPPA and initiated on medical treatment. Thereafter, articulation difficulties and global cognitive decline gradually worsened.

One year prior to evaluation, he developed recurrent falls and was hospitalized for aspiration pneumonia secondary to dysphagia. Urinary and fecal incontinence were also noted. Neurological examination revealed vertical supranuclear gaze palsy and a positive Rocket sign, leading to a diagnosis of PSP. During seven months of follow-up, bradykinesia, rigidity, and postural instability markedly progressed, resulting in loss of independent ambulation.

Results: Brain magnetic resonance imaging demonstrated diffuse cerebral atrophy and mild-to-moderate T2-weighted hyperintense lesions in the cerebral white matter. Dopamine transporter imaging using 18F-fluoropropyl-carbomethoxyiodophenylnortropane positron emission tomography showed decreased dopamine transporter uptake in the bilateral putamina. Serial cognitive assessments revealed significant deterioration over time.

Conclusion: This case illustrates the phenotypic evolution from language-predominant nfvPPA to classical PSP features, including recurrent falls, vertical gaze palsy, and axial parkinsonism. Rather than representing two independent disorders, these findings support the concept of a shared 4R tauopathy spectrum in which clinical manifestations expand and progress over time. Recognition of this continuum has important implications for early diagnosis, prognostication, and future disease-modifying therapeutic strategies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-evolution-from-nonfluent-ppa-to-psp/