Pathology Postmortem examinations have disclosed a bilateral loss of neurons and gliosis in the periaqueductal gray matter, superior colliculus, subthalamic nucleus, red nucleus, pallidum, dentate nucleus, and pretectal and vestibular nuclei, and to some extent in the oculomotor nucleus. The expected loss of the myelinated fiber bundles arising from these nuclear structures has also been commented upon. The remarkable finding has been the neurofibrillary degeneration of many of the residual neurons. The neurofibrillary tangles are thick and often composed of single strands, either twisted or in parallel arrangement. The neurons of the cerebral cortex have been involved in some cases (shown by staining of tau protein), but these changes do not correlate with dementia. The cerebellar cortex is usually spared.
The cause and nature of this disease remain obscure. Though some clinical and pathologic heterogeneity is seen, the majority of cases of PSP conform to the typical pattern as we have just described. These interesting diagnostic and clinicopathologic aspects are summarized by Williams and Lees. Studies with PET demonstrate a decrease in blood flow, most marked in the frontal lobes, and a lesser extent of oxygen utilization in central structures (Leenders et al). Striatal dopamine formation and storage are significantly decreased when compared with control values. Much current interest has been directed to the neurofibrillary tangles and tau deposition in PSP and a potential link to the tau pathology displayed in frontotemporal dementia and in corticobasalganglionic degeneration (see in the following text). Certain tau gene (MAPT) haplotypes on chromosome 17p (the same site implicated in familial frontotemporal dementia) are more often associated with PSP than in unaffected individuals. A recent investigation into the mechanism of postural instability using functional imaging, showed a correlation between gait instability and decreased thalamic glucose metabolism and activation (Zwergal).
PSP should be suspected whenever an older adult inexplicably develops a state of imbalance, frequent falls with preserved consciousness, and variable extrapyramidal symptoms, particularly dystonia of the neck, ocular palsies, or a picture resembling pseudobulbar palsy. If the typical abnormalities of eye movements are present, the diagnosis is not difficult. When only a parkinsonian syndrome without tremor is apparent the main diagnostic consideration is striatonigral degeneration or the corticobasalganglionic syndrome, described below.
Treatment l-Dopa has been of slight and unsustained benefit in some of our patients, and combinations of l-dopa and anticholinergic drugs have been entirely ineffective in others. A marked response to these drugs should, of course, suggest the diagnosis of Parkinson disease. Recently, the drug zolpidem, a gabanergic agonist of benzodiazepine receptors, has been reported to ameliorate the akinesia and rigidity of PSP (Daniele et al); however, these observations require corroboration. Benztropine or trihexyphenidyl has been somewhat helpful in reducing dystonia but botulinum injections may be a better alternative if there are focal signs. Treatments of the sleep difficulties and urinary incontinence are of great assistance to the patient and family. A feeding tube becomes necessary in advanced cases. Observing the decline of these patients and the limitations of treatment is a frustrating ordeal for all involved.