Progressive supranuclear palsy (PSP) is a rare brain disorder that causes serious and permanent problems with control of gait and balance. The most obvious sign of the disease is an inability to aim the eyes properly, which occurs because of lesions in the area of the brain that coordinates eye movements. Some patients describe this effect as a blurring. PSP patients often show alterations of mood and behavior, including depression and apathy as well as progressive mild dementia.

As the name suggests, the disease begins slowly and grows worse over time, causing weakness (palsy) by damaging certain parts of the brain above pea-sized structures (nuclei) that control eye movements (supranuclear).

Approximately 20,000 Americans - or one in every 100,000 people over the age of 60 - have PSP, making it much less common than Parkinson's disease, which affects more than 500,000 Americans. Patients are usually middle-aged or elderly, and men are affected more often than women.

Causes

PSP is caused by a gradual deterioration of brain cells in a few tiny but important places at the base of the brain, in the region called the brainstem. One of these areas, the substantia nigra, is also affected in Parkinson's disease, and damage to this region of the brain accounts for the motor symptoms that PSP and Parkinson's have in common.

Scientists do not know what causes these brain cells to degenerate but there are several theories about PSP's cause:

• Viral. One possibility is that an unconventional virus-like agent infects the body and takes years or decades to start producing visible effects. Creutzfeldt-Jakob disease is one disease known to be caused by such an agent.
• Genetic mutations. Another possibility is that random genetic mutations, of the kind that occur in all of us all the time, happen to occur in particular cells or certain genes, in just the right combination to injure these cells.
• Chemical. A third possibility is that there is exposure to some unknown chemical in the food, air, or water which slowly damages certain vulnerable areas of the brain. This theory stems from a clue found on the Pacific island of Guam, where a common neurological disease occurring only there and on a few neighboring islands shares some of the characteristics of PSP, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease). Its cause is thought to be a dietary factor or toxic substance found only in that area.
• Free radicals. Another possible cause of PSP is cellular damage caused by free radicals, reactive molecules produced continuously by all cells during normal metabolism. Although the body has built-in mechanisms for clearing free radicals from the system, scientists suspect that, under certain circumstances, free radicals can react with and damage other molecules. A great deal of research is directed at understanding the role of free radical damage in human diseases.

Symptoms

Initial complaints in PSP are typically vague and an early diagnosis is always difficult. The primary complaints fall into these categories:

• Symptoms of dysequilibrium, such as unsteady walking or abrupt and unexplained falls without loss of consciousness;
• Visual complaints, including blurred vision, difficulties in looking up or down, double vision, light sensitivity, burning eyes, or other eye trouble;
• Slurred speech; and
• Various mental complaints such as slowness of thought, impaired memory, personality changes, and changes in mood.

Diagnosis

PSP is often difficult to diagnose because its symptoms can be very much like those of other, more common movement disorders, and because some of the most characteristic symptoms may develop late or not at all. Some of its symptoms closely resemble those of Parkinson's disease, Alzheimer's disease, and rarer neurodegenerative disorders, such as Creutzfeldt-Jakob disease. The key to diagnosing PSP is identifying early gait instability and difficulty moving the eyes, the hallmark of the disease, as well as ruling out other similar disorders, some of which are treatable.

• PSP is most often misdiagnosed as Parkinson's disease early in the course of the illness.
• Memory problems and personality changes may also lead a physician to mistake PSP for depression, or even attribute symptoms to some form of dementia.
• PSP resembles Parkinson's disease in that it can cause stiffness, movement difficulties, and clumsiness. However, patients with PSP usually stand straight or occasionally even tilt their heads backward (and tend to fall backward), while those with Parkinson's disease usually bend forward.
• Problems with speech and swallowing are much more common and severe in PSP than in Parkinson's disease, and tend to show up earlier in the course of the disease.
• Both diseases share other features: onset in late middle age, bradykinesia (slow movement), and rigidity of muscles.
• Tremor, almost universal in Parkinson's patients, is rare in PSP.
• Although Parkinson's patients markedly benefit from the drug levodopa, patients with PSP respond poorly and only transiently to this drug.

Prognosis

PSP gets progressively worse but is not itself directly life-threatening. It does, however, predispose patients to serious complications such as pneumonia secondary to difficulty in swallowing (dysphagia). The most common complications are choking and pneumonia, head injury, and fractures caused by falls. The most common cause of death is pneumonia. With good attention to medical and nutritional needs, it is possible for most PSP patients to live a decade or more after the first symptoms of the disease.

Treatment

There is currently no effective treatment for PSP, although scientists are searching for better ways to manage the disease. In some patients the slowness, stiffness, and balance problems of PSP may respond to anti-parkinsonian agents such as levodopa, or levodopa combined with anticholinergic agents or amantadine, but the effect is usually temporary. The speech, vision, and swallowing difficulties usually do not respond to any drug treatment. Another group of drugs that has been of some modest success in PSP are antidepressant medications.

Non-drug treatment for PSP can take many forms. Patients frequently use weighted walking aids because of their tendency to fall backward. Bifocals or special glasses called prisms are sometimes prescribed for PSP patients to remedy the difficulty of looking down. Formal physical therapy is of no proven benefit in PSP, but certain exercises can be done to keep the joints limber. At some point, when swallowing disturbances make severe choking a definite risk, it may become necessary to perform a gastrostomy (or a jejunostomy), a minimally invasive surgical procedure. This surgery involves the placement of a tube through the skin of the abdomen into the stomach (intestine) for feeding purposes. Pallidotomy and other surgical procedures used in Parkinson's patients have not been proven effective in PSP.