A rare neurodegenerative disease with symptoms that are similar to those of Parkinson’s disease. However, PSP has enough distinctive features that misdiagnosis is uncommon or short-lived. Early in the onset of PSP, symptoms such as tremors, bradyki-nesia (slowed movement), postural instability (balance and equilibrium problems), and gait disturbances (difficulty in starting, stopping, and changing direction when walking) often are prominent; postural instability is rarely a prominent sign in the first few years of Parkinson’s disease. Another distinctive sign of PSP is difficulty with vertical eye movements, especially looking down. People with PSP also have more severe and earlier problems with swallowing and speaking than is typical for Parkinson’s. Personality changes, sleep disturbances, and cognitive problems are also usually earlier and more severe in PSP compared to Parkinson’s. As PSP almost always develops in people older than age 50, the combination of age and slowness with which neurologic symptoms develop frequently leads to an inaccurate diagnosis of Parkinson’s disease. Because many symptoms and a portion of the disease process are Parkinson-like, PSP is considered one of the Parkinson’s plus syndromes (conditions that have Parkinson’s symptoms as well as other distinctive symptoms).
Though it is a more aggressive disease than Parkinson’s, PSP is still fairly slowly progressive, with patients surviving years, often well over a decade. Although pneumonia, often from aspirating food or liquids due the swallowing difficulties, is the most common causes of death in PSP, people with PSP often do not die from their PSP and eventually succumb to unrelated causes. The loss of other brain cells causes PSP’s other symptoms, which include visual disturbances such as double vision or blurred vision, difficulty in breathing, personality changes, and dementia.
PSP is sometimes misdiagnosed as creutzfeldt-jakob disease (CJD), an even more rare neurodegenerative disease in which there is widespread tissue loss in the brain. Such misdiagnosis is most likely when the primary symptoms of PSP are dementia and personality changes, which are hallmarks of CJD. Differential diagnosis often does not occur until autopsy after death. Because there is no adequate treatment for either disease (though some experimental treatments for CJD hold some promise), misdiagnosis has little or no therapeutic consequence.
AMYOTROPHIC LATERAL SCLEROSIS (ALS), also widely known as Lou Gehrig’s disease, is also a potential misdiagnosis in people with PSP, due to the fact that problems with swallowing, keeping the airway open (so called stridor from involuntary closure of the vocal cords), and producing speech can be fairly early and prominent in both diseases. As with CJD, the consequences of such a misdiagnosis are small because ALS lacks an effective treatment as well.
Pathology of PSP
PSP primarily affects the structures of the brain-stem that regulate coordination, in particular the pons and thalamus, and the subcortical nuclei that regulate voluntary movement, in particular the subthalamic nucleus (STN), pallidum, and sub-stantia nigra. Scientists do not know how the deterioration that leads to PSP starts. Although this deterioration causes symptoms similar to those of Parkinson’s widespread death of both subcortical neurons and glial cells (specialized brain cells that support and protect neurons) occurs throughout the subcortex. Glial cells acquire a characteristic “tufted” appearance that results from the accumulation of TAU-based neurofibrillary tangles similar to those found in Alzheimer’s disease. These are distinguishing factors apparent only at autopsy after death, although functional imaging STUDIES SUCH AS POSITRON EMISSION TOMOGRAPHY (PET) and single photon emission computed tomography (SPECT) often can detect atrophy (loss of tissue) in the subcortical nuclei in the mid to late stages of the disease. The MRI often develops characteristic abnormalities by the mid to late stages as well. The neurologist may order one of these studies if questions remain about diagnosis as the disease progresses; although the findings are not conclusive, they help to distinguish PSP from
Parkinson’s because such atrophy does not occur with Parkinson’s.
Diagnosis of PSP is primarily clinical as there are no definitive tests. Differentiating PSP from Parkinson’s disease and other neurodegenerative conditions often is a matter of time. The most significant differentiating factor is that Parkinson’s disease responds to treatment with levodopa or dopamine agonist medications and PSP does not. However, tremors in both conditions respond to treatment with ANTICHOLINERGIC MEDICATIONS. This common response can perpetuate an incorrect diagnosis when tremor is the predominant symptom until symptoms worsen. As establishing a medication regimen that effectively relieves the symptoms of Parkinson’s disease requires up to several months, the lack of response of motor symptoms to treatment with anti-Parkinson’s medications may not be immediately apparent. Indeed, it is not uncommon for fine-tuning a medication regimen to take as long as a year. However, there is usually a noticeable improvement even if incomplete, and improvement this does not occur, the Parkinson’s diagnosis is questionable.
Visual disturbances often are overlooked or misunderstood in early PSP yet provide distinctive diagnostic clues. Vision problems in older people are fairly common, and blurred vision can occur in both PSP and Parkinson’s. However, the person with PSP often has significant difficulty in controlling eye movements and aiming the eyes. This is a consequence of cell loss in areas of the brainstem that coordinate vision and probably reflects damage to the optic tract and possibly the third, fourth, and sixth cranial nerves, which originate in the midbrain and the pons (structures of the brain-stem). The person with Parkinson’s who has visual symptoms may have a problem in moving the eyes downward but has control over other eye movements. This problem is a consequence of the loss of dopaminergic neurons in the areas of the basal ganglia that regulate voluntary movement.
Unfortunately, there are few effective treatments for PSP. Anti-Parkinson’s medications sometimes help to control tremors or, other motor symptoms, but usually only incompletely and temporarily; as symptoms progress past the mild stages, usual Parkinson’s treatments are rarely effective. Treatment is primarily palliative, aiming to maintain comfort as much as possible. PSP does not cause pain, although its dyskinEsias and dystonia can cause uncomfortable postures and positions. Muscle relaxants sometimes relieve these discomforts. Medications used to improve cognitive function in people who have Alzheimer’s disease are largely ineffective in those who have PSP, although many physicians would try them in people with PSP and cognitive decline.
Why PSP Interests Parkinson’s Researchers
PSP interests Parkinson’s researchers because part of the disease process is the same in PSP and Parkinson’s the loss of dopaminergic neurons. Yet the motor symptoms of PSP do not respond to dopamine replacement strategies as they do in Parkinson’s disease. As well, there are intriguing differences, such as the loss of nigrostriatal fibers that occurs in Parkinson’s disease but not in PSP, that raise questions about how the disease processes evolve. PSP’s cognitive and personality changes support the premise that functions in the brain are linked in ways that researchers do not yet understand; unraveling these connections will provide greater insights into brain function as well as dysfunction.