Early progressive supranuclear palsy: pathology and clinical presentation.

Progressive supranuclear palsy (PSP) is a syndrome of supranuclear ophthalmoplegic palsy, pseudobulbar palsy, rigidity of the limbs, nuchal dystonia, and dementia in which the gaze palsy is the hallmark of the disease. Most neurologists are reluctant to consider the diagnosis unless visual problems exist. Since the earliest complaints of PSP are said to be variable and subtle, accurate diagnosis is often delayed and initial pathologic changes of the disease not well studied. Two patients came to autopsy with dementia, gait disturbances, and/or dysarthria but no eye findings by history or physical exams. Symptoms had been attributed to metastatic cancers. At autopsy prominent globose neurofibrillary tangles with variable cell loss, microglial nodules, and neuronophagia were found in the locus ceruleus, third cranial nerve complex, nucleus supratrochlearis, nucleus centralis superior, and nucleus basalis of Meynert with mild pallor of the globus pallidus, mild cell loss in the dentate nucleus of the cerebellum, and sparing of the superior colliculus. The diagnosis of early PSP was made. These cases serve to 1) detail the more limited neuropathologic changes in early PSP, 2) reemphasize that the earliest clinical symptoms of PSP are not gaze palsies, and 3) remind clinicians to consider PSP in their differential diagnosis in patients with gait disturbances, dementia, and/or dysarthria, and 4) document PSP in association with carcinoma in two cases.