Progressive supranuclear palsy: clinico-pathological and biochemical studies.

Ten autopsy cases of Progressive Supranuclear Palsy (PSP) are reported. Age at onset ranged from 16 to 67 years and the duration of illness 3 to 24 years. The clinical features were aggressive mental retardation in 4 cases with early onset, paroxysmal dysequilibrium, ophthalmoplegia, rigidity and akinesia, pseudobulbar palsy and variable degrees of dementia. Neuropathology showed widespread neurofibrillary degeneration associated with system-bound neuronal loss and gliosis in subcortical areas, particularly affecting the subthalamic nucleus, substantia nigra, brainstem tegmentum and dentate nuclei, with no or little involvement of the cerebral cortex. The distribution of the lesions and the ultrastructure of the neurofibrillary tangles made of 15 nm straight filaments (seen in one case) in PSP are different from postencephalitic parkinsonism, Guam Parkinson-dementia complex and brainstem affection in (pre)senile dementia. Post-mortem biochemical analysis of two brains disclosed severe reduction of tyrosine hydroxylase, the key synthetic enzyme of the catecholamine pathway, not only in the nigrostriatal system as seen in Parkinson's disease, but in most areas of the brain-stem and limbic system. The implication and possible pathogenic and therapeutic significance of these biochemical findings are discussed. The etiology of PSP and its nosological position within the degenerative extrapyramidal disorders remain unknown.