In 1963, Richardson, Steele, and Olszewski crystallized medical thought about a clinicopathologic entity—progressive supranuclear palsy (PSP)—to which there had been only ambiguous reference previously. The condition is not rare and examples are seen in every neurologic practice. By 1972, when Steele reviewed the subject, 73 cases (22 with postmortem examinations) had been described in the medical literature. Most cases are sporadic but familial clusters have been described in which the pattern of inheritance is compatible with autosomal dominant transmission (Brown et al; de Yébenes et al). Rojo and coworkers described 12 pathologically confirmed pedigrees and made note of the variable phenotypical expression of the disease even within a single pedigree. No toxic, encephalitic, racial, or geographic factor has been incriminated.
The disease has its onset typically in the sixth decade (range: 45 to 75 years), with some combination of difficulty in balance, abrupt falls, visual and ocular disturbances (giving the syndrome its name), slurred speech, dysphagia, and sometimes vague changes in personality, including apprehensiveness and fretfulness suggestive of an agitated depression. The most common early complaint is unsteadiness of gait and unexplained falling without loss of consciousness. The patient has difficulty in describing his imbalance, using terms such as “dizziness,” “toppling,” or an ambiguous problem with walking. The falls are frequently backward. At first, the neurologic and ophthalmologic examinations may be unrevealing, and it may take a year or longer for the characteristic syndrome comprising supranuclear ophthalmoplegia, pseudobulbar palsy, and axial dystonia to develop fully.
Difficulty in voluntary vertical movement of the eyes, often downward but sometimes only upward, and later impairment of voluntary saccades in all directions are characteristic. A related but more subtle sign has been the finding of hypometric saccades in response to an optokinetic drum or striped cloth moving vertically in one direction (usually best seen with stripes moving downward). Later, both ocular pursuit and refixation movements are delayed and diminished in amplitude and eventually all voluntary eye movements are lost, first the vertical ones and then the horizontal ones as well. However, if the eyes are fixated on a target and the head is turned slowly, full movements can be obtained, demonstrating the supranuclear, nonparalytic character of paralysis of ocular pursuit. Other prominent oculomotor signs are sudden jerks of the eyes during fixation, “cogwheel” or saccadic choppiness of pursuit movements, and hypometric saccades of long duration (Troost and Daroff). The Bell phenomenon (reflexive upturning of eyes upon forced closure of the eyelids) and the ability to converge are also lost eventually, and the pupils become small but remain round and reactive to both light and to accommodative stimuli. The upper eyelids may be retracted, and the wide-eyed, unblinking stare imparts an expression of perpetual surprise. Blepharospasm and involuntary eye closure are prominent in some cases. In the late stages, the eyes may be fixed centrally and all oculocephalic and vestibular reflexes are lost. It should be emphasized again that a proportion of patients do not demonstrate these eye signs for a year or more after the onset of the illness. We have also followed several patients who had no disorder of eye movement during life but in whom the typical pathologic changes of PSP were found at autopsy. In one such patient, there was a subcortical type of dementia; in another, focal limb dystonia and parkinsonism. Furthermore, other degenerative conditions can manifest a supranuclear vertical gaze disorder, although never to the extent seen in PSP; these include corticobasal-ganglionic degeneration, Lewy body disease, Parkinson disease, and Whipple disease.