What is progressive supranuclear palsy?
Progressive supranuclear palsy (PSP) is a rare neurological disorder that affects body movements, walking and balance, and eye movements. PSP is caused by damage to nerve cells in areas of the brain that control thinking and body movements. It is one of a family of neurological conditions called atypical parkinsonism and belongs to the category of frontotemporal disorders.
PSP is different from Parkinson's disease, although some of their symptoms are similar. PSP typically begins in a person’s mid- to late-60s, later than when Parkinson’s disease symptoms typically develop.
The disorder usually worsens rapidly and most people with PSP develop severe disability within three to five years of when symptoms start. PSP can lead to serious complications such as pneumonia, choking, or head injuries from falls.
Symptoms of PSP
PSP affects a person’s movements, and can lead to loss of balance, difficulty walking or swallowing, slurred speech, problems with eye movements. PSP can also affect a person’s mood, behavior, and thinking. The most frequent first symptom of PSP is a loss of balance while walking which can lead to abrupt and unexplained falls. People with PSP may also have stiffness and slow movement.
As the disease progresses, most people develop eye problems. Eye and vision symptoms may include:
- Slow eye movements
- Trouble looking up or down
- Trouble controlling eyelids, involuntary closing of the eyes, decreased blinking, or difficulty opening the eyes
- Tendency to move the head rather than just the eyes to look in different directions
People with PSP and their loved ones may notice changes in mood or behavior. These may include:
How is progressive supranuclear palsy different from Parkinson's disease?
PSP is often misdiagnosed as Parkinson's disease, especially early in the disorder. The two disorders share many symptoms, but PSP progresses more rapidly than Parkinson's.
There are several key differences between PSP and Parkinson's:
- People with PSP tend to lean backwards and extend their neck. The unexplained falls that accompany PSP usually happen from falling backward. This is called “axial rigidity.” People with Parkinson's tend to bend forward rather than backward.
- Problems with speech and swallowing are much more common and severe in PSP than in Parkinson's and usually show up earlier in the disease.
- People with PSP develop unique eye movement problems with looking up and down.
- Tremor (shaking) is rare in PSP but very common in people with Parkinson's.
- People with Parkinson’s disease often show great benefit from levodopa therapy, while people with PSP have minimal or no response.
- A signature of PSP is the build-up in affected brain cells of a protein known as tau. But in Parkinson's, a different protein called alpha-synuclein builds up in diseased brain cells.
Who is more likely to get progressive supranuclear palsy?
The exact cause of PSP is unknown, but research suggests that it involves progressive damage to cells in a few specific areas in the brain, mainly in the brain stem. The death of brain cells in one of these areas, the substantia nigra, accounts in part for the motor symptoms that PSP and Parkinson's have in common.
The tau protein deposits that build up in nerve cells in PSP appear to spread to different regions of the brain and cause cells to stop working and die. This in turn destroys the neuronal connections that underlie healthy brain function.
PSP is usually sporadic, meaning that it happens randomly without a known cause. In very few cases, the disease results from variations (mutations) in the MAPT gene. This variation provides faulty instructions for making tau in brain cells. For most people with PSP, no known genetic factor is found.
Several theories suggest that PSP might be caused by:
- Random genetic changes that happen in particular cells or genes in a specific combination that injures these cells.
- Exposure to some unknown environmental factor (such as chemicals in food, air, or water), which slowly damages certain vulnerable areas of the brain.
- Cellular damage caused by free radicals, which are reactive molecules produced continuously by all cells during normal metabolism. Although the body has built-in ways to clear free radicals from the body, scientists suspect that—under certain circumstances—free radicals can react with and damage other molecules.
How is progressive supranuclear palsy diagnosed and treated?
Diagnosing PSP
Currently there are no tests or brain imaging techniques to definitively diagnose PSP. A doctor will review medical history and perform a physical and neurological exam.
It’s important to identify problems with gait, eye movements, speech, and swallowing early. Exams can help rule out other similar disorders. An MRI (magnetic resonance imaging) may show shrinkage at the top of the brain stem and help doctors examine brain activity in certain areas.
Learn more about neurological tests and procedures.
Treating PSP
There is currently no treatment that effectively stops or slows the progression of PSP, and symptoms usually don’t respond well to medicines. But a doctor may recommend trying these medicines:
- Parkinson's disease medicines rarely help people with PSP. In some people, levodopa can treat the slowness, stiffness, and balance problems associated with PSP, but the effect is usually minimal and short-lasting.
- Injections of botulinum toxin into muscles around the eyes can help with PSP-associated eye closing.
- Some antidepressant medicines may offer some benefits beyond treating depression, such as pain relief and decreasing drooling.
There are also non-medicine treatment options for PSP symptoms, such as:
- Weighted walking aids can reduce the risk of falling backward.
- Bifocals or special glasses called prisms can help reduce difficulty looking down.
- Exercise and physical activity (supervised by a healthcare professional) can keep joints limber.
- People who have significant trouble swallowing and are at risk of serious choking may have a surgical procedure to place a tube into the stomach to allow the person to get nutrients without having to chew and swallow.
What are the latest updates on progressive supranuclear palsy?
The National Institutes of Health (NIH), which includes NINDS, is the primary funder of research on the brain and nervous system.
PSP is one of the disorders being studied as part of the Parkinson's Disease Biomarkers Program. This initiative is aimed at discovering ways to identify people at risk for developing Parkinson's and related disorders, and to track the progression of these diseases. NIH also supports clinical research studies to develop brain imaging that may allow for earlier and more accurate diagnosis of PSP.
Understanding genetics and the tau protein
Researchers hope to identify specific gene changes that cause PSP and are also studying how genetics and the environment interact to make people more susceptible to the disease. Previous studies have linked multiple genes, including the gene for making the tau protein (MAPT), with PSP.
Scientists hope to understand the mechanisms involving tau that lead to PSP and its symptoms. NIH supports research to characterize and distinguish the different formations of the tau protein and to better understand the role of tau protein build-up in PSP. Other studies are exploring ways to improve how to image or visualize tau in the brain.
Understanding the underlying disease mechanisms
Animal or cell models may identify how PSP happens and progresses, and this knowledge may lead to the discovery of potential therapies. Other studies in animal models and patients focus on learning about the parts of the brain affected by PSP, such as those involved in motor control and thinking, which can also help us better understand the disease mechanisms.
Developing treatments
There have been significant efforts to develop new therapies for PSP to slow down or stop the disease progression. Many of these studies focus on developing anti-tau therapy to stop the build-up and spread of the tau protein. Other studies have focused on different PSP-related changes in the nervous system, including inflammation and problems with mitochondria (the energy factories in cells). Other studies hope to find ways to improve brain activity using a special type of brain stimulation that does not involve surgery. Some researchers are exploring stem cell-based therapies to help symptoms of PSP.
The Rare Diseases Clinical Research Network, led by NIH's National Center for Advancing Translational Sciences (NCATS), is designed to facilitate research collaboration, study enrollment, and data sharing among rare diseases researchers. The Rare Diseases Clinical Research Network funded under this project studies neurological disorders, including PSP.
For more information on research about PSP, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also has links to publications and resources from these projects.
For research articles and summaries on PSP, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one improve care for someone with PSP?
Consider participating in a clinical trial, so clinicians and scientists can learn more about PSP and related disorders. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to detect, treat, or prevent disease safely.
All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities. This makes sure that study results apply to as many people as possible and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research, visit the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with PSP at ClinicalTrials.gov, a searchable database of current and past clinical studies and research results.
Where can I find more information about PSP?
Information may be available from the following sources: