Progressive supranuclear palsy--20 years later

Reviewing the literature since recognition of progressive supranuclear palsy (PSP) as a clinicopathological entity 20 years ago, the present state of knowledge is delineated. The etiology of PSP is still unknown. The clinical hallmarks are supranuclear palsy of vertical gaze, axial dystonia in extension and pseudobulbar palsy with marked dysarthria and dysphagia. Accessory features include subcortical dementia, mental, extrapyramidal, pyramidal and cerebellar symptoms. PSP is a disease of the presenium (average age at onset, 59.6 years) with a male preponderance (60% men). The onset is insidious with vague complaints of dysequilibrium (60%), mental changes (46%) and disturbed vision (21%), often preceding abnormal neurological findings. The important borderland and main differential diagnosis is parkinsonism. However, in PSP, responsiveness to antiparkinsonian agents is poor and progression is rapid and fatal within few years (average survival time, 5.7 years). Promising diagnostic tools at present include CT-scanning and neuro-otologic and -ophthalmologic examination. Neuropathological findings, confined to specific diencephalic, brainstem and cerebellar nuclei, include neurofibrillary tangles (ultrastructurally different from those seen in other CNS disorders), neuron loss and gliosis. The importance of research on neurocytochemistry, brain ultrastructure and immunology in the current investigation of PSP is outlined.