Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a rare brain disorder that causes serious and permanent problems with control of gait and balance. The hallmark of PSP is a visual disturbance, which results from a progressive inability to coordinate eye movements. PSP is related to both Parkinson’s disease and FTD.

Additional motor symptoms similar to those seen in Parkinson’s disease and other features of frontotemporal dementia such as behavioral and social dysfunction; cognitive decline may develop. Depression and apathy are common mood symptoms.

Key Clinical Features

Difficulty coordinating eye movements is the characteristic feature of PSP, the symptom that usually develops first, and the feature that is most useful in distinguishing PSP from similar neurodegenerative disorders such as Parkinson’s. Patients cannot coordinate their eyes to look up or down. Some patients experience this visual deficit as blurring.

  • Loss of balance and gait instability resulting in increased likelihood of falls.
  • Slowness and stiffness of movements, similar to that seen in Parkinson disease
  • Dysphagia – difficulty swallowing
  • Dysarthria – speech difficulties
  • Immobile, “masked face”
  • Forced laughing or crying is prolonged.

During the disease progression some PSP patients may experience cognitive symptoms similar to the behavioral variant of FTD, although the symptoms are usually milder than in FTD.

Behavioral and emotional symptoms that may occur in PSP:
A progressive deterioration in the patients’ ability to control or adjust his/her behavior appropriately in different social contexts is the hallmark of the behavior changes, and results in the embarrassing, inappropriate social situations that can be one of the most disturbing facets of FTD and related disorders.

In addition to the depression, apathy and inability to control emotions noted above, PSP patients may manifest emotional blunting or indifference toward others and a lack of insight into changes in their own behavior.

Cognitive symptoms
PSP patients may suffer increasing impairment in “executive functions,” such as distractibility, mental rigidity and inflexibility, impairments in planning and problem solving, and poor financial judgment. PSP patients may also have memory problems. They also develop progressive language disturbance.

Key Pathologic Features

Autopsy of the brain shows atrophy and loss of cells in the basal ganglia, the substantia nigra, the subthalamus and the brainstem–the portion of the brain responsible for balance and coordinating eye movements. Scientists have determined that these affected cells contain deposits of an abnormal form of the protein tau. Tau is present in all neurons, and it plays important roles in the structure and function (metabolism) of normal neuron function. Because of the accumulation of tau, PSP is said to be a tauopathy.

Genetics

PSP is usually a sporadic disease, meaning it is a disorder that develops by chance rather than being inherited. For the great majority of cases, the cause of PSP remains unclear. No specific environmental risk factors have been associated with the disease. However, in about 15% of cases, there is a family history of a neurodegenerative disease (not necessarily PSP). In a very few cases, mutations have been found in the microtubule associated protein tau (MAPT) gene. First degree relatives of a person with PSP and a known MAPT mutation are at 50% risk of inheriting the gene and therefore of developing PSP or FTD. Additionally, almost all people with PSP have a certain MAPT haplotype (group of genetic markers). Although this haplotype is also frequently found in people without PSP, it may influence how the MAPT gene works and therefore influence the risk of PSP.

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, 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. The most commonly used for PSP have been Prozac, Elavil and Tofranil. The anti-PSP benefit of these drugs seems to be unrelated to their ability to relieve depression.

Currently, clinical research trials with agents that impact tau protein pathophysiology, and with free radical scavengers (agents that can get rid of potentially harmful free radicals in the brain), are in progress or being planned for PSP. Ongoing research focusing on Parkinson and Alzheimer diseases should shed light on the disease process at work in PSP, as well as suggest effective therapies.

Management and Prognosis

Management of PSP symptoms can take many forms. Patients frequently use weighted walking aids to counteract their tendency to fall backward. Bifocals or special glasses called prisms are sometimes prescribed for PSP patients to remedy the difficulty of looking down. Although formal physical therapy is of no proven benefit in PSP, exercises can be done to keep the joints limber. Prevention of injuries related to recurrent falls is a major focus of physical therapy.

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. A surgical procedure involving a gastrostomy tube may be done when there are significant and severe swallowing disturbances. This surgery involves the placement of a tube through the skin of the abdomen into the stomach for feeding purposes. The most common cause of death is pneumonia. With good attention to medical and nutritional needs, however, most PSP patients live well into their 70s and beyond.

For additional information and support:

The Association for Frontotemporal Degeneration
Radnor Station #2, Suite 320
290 King of Prussia Rd.
Radnor, PA 19087
Toll free: 866-507-7222
E-mail: info@theaftd.org
www.theaftd.org

CurePSP (Foundation for PSP, CBD and Related Disorders)
30 E. Padonia Road, Suite 201
Timonium, MD 21093
Toll free: 800-457-4777
E-mail: info@curepsp.org
www.psp.org