The first clinicopathologic descriptions of progressive supranuclear palsy (PSP) to draw widespread attention were published in 1963 and 1964.1–3 The full-blown, typical case is at once unusually complex in its combination of motor and behavioral features and so distinctive that the diagnosis is unmistakable at a glance. Lack of objective diagnostic markers and poor response to treatment make PSP a challenge for the clinician and a trial for the patient and family. But recent progress in understanding its genetic, molecular, and cellular pathology offer hope that PSP will become more easily diagnosed and treated in the near future.
Presenting Features and Clinical Course
Three retrospective studies found gait disturbance, often unheralded falls, to be a presenting feature in 90%, 62%, and 61%, respectively.4–6 In contrast, Parkinson's disease (PD) presents with gait disturbance in only 11% of cases.7 The falls may prompt a workup for vestibulopathy, myelopathy, basilar artery ischemia, cardiac syncope, or epilepsy. However, in most cases, the gait disturbance is accompanied by enough bradykinesia and/or rigidity to prompt an initial diagnosis of PD.
The next most common presenting feature is a nonspecific mental and physical slowness, irritability, social withdrawal, or fatigability8 that is usually interpreted by the patient as normal aging. If medical attention is sought at this point, a diagnosis of primary depression or Alzheimer's disease (AD) is common.
In the minority of cases that present with gaze palsy, dysarthria or dysphagia, the initial workup may embark on a search for myasthenia gravis, progressive bulbar palsy, or local causes of esophageal dysmotility. Cataract extraction may be performed in a futile effort to correct the nonrefractible visual deficit of early, unrecognized supranuclear gaze fixation instability. Gaze palsy is often absent until the middle of the illness and is only rarely the presenting symptom (Table 21–1). In one series of autopsy-confirmed patients, gaze palsy failed to appear during life in half of cases.9 Yet many physicians fail to consider the diagnosis of PSP until vertical gaze restriction occurs.
Table 21–1. Symptoms at Onset of PSP |Favorite Table|Download (.pdf)
Table 21–1. Symptoms at Onset of PSP
|Symptom||Percentage of Cases (N = 187)|
|Reduced speech output||3|
|Blurring or diplopia||10|
|Other visual symptom||3|
In its full-blown clinical state, PSP will not be confused with other illnesses. There can be little diagnostic doubt in a patient with a progressive syndrome of gait instability with early falls, bradykinesia, disproportionately nuchal rigidity ...