Progressive supranuclear palsy (PSP) is an adult-onset, neurological disease that impacts movement, thinking, speech, and vision. PSP is commonly referred to as an “atypical parkinsonism,” or sometimes “Parkinson’s-plus” diagnosis, because of its overlap of certain symptoms with Parkinson’s disease. However it often progresses quite differently than Parkinson’s disease, and it shares similar pathology to Alzheimer’s and frontotemporal dementia.

PSP is considered rare. It is currently estimated that 10 to 12 people per 100,000 are living with PSP. About 30,000–40,000 people are diagnosed with PSP in the United States. The numbers for PSP are likely underestimates because many people with PSP are misdiagnosed with another condition, such as Parkinson’s disease or frontotemporal dementia.

The prevalence for PSP compares to about 1 million with Parkinson’s disease and 5 million with Alzheimer’s disease. PSP is slightly more common than amyotrophic lateral sclerosis (called ALS, or Lou Gehrig’s disease in the U.S. and motor neuron disease elsewhere), although ALS is better known than PSP in that it is easier to diagnose than PSP and often affects much younger people.

We recognize the extra layer of complexities and frustrations that can come along with a rare diagnosis, including healthcare providers who lack familiarity with the disease. One of CurePSP’s priority goals is to improve awareness of PSP and related diseases among medical professionals and the general public. Such awareness is critical to accurate diagnosis, which allows patients earlier access to specialized management and care, and stimulates interest among researchers, pharmaceutical companies and funding agencies to support the cause and cure of this unique and puzzling illness.

PSP is rare: no one even realized it existed until 1963, when several patients were first described at a national neurology research convention and the disease was given its name. In retrospect, at least 12 cases of PSP had appeared in the medical literature between 1909 and 1962, but because of its resemblance to Parkinson’s, it wasn’t recognized as a distinct disease. The brain under the microscope is almost identical to that of “post-encephalitic parkinsonism,” a common condition in the early 20th century but now nearly extinct, which also made for erroneous diagnoses during that era.

Although PSP is slightly more common than the well-known amyotrophic lateral sclerosis (called ALS, or Lou Gehrig’s disease in the U.S. and motor neuron disease elsewhere), ALS is easier to diagnose than PSP and often affects much younger people.

Each year an average of 1.1 people per 100,000 are newly diagnosed with PSP; five or six people per 100,000 are living with the disease. These figures are nearly identical wherever they have been carefully measured, which is in only three countries—the U.K., the U.S. and Japan

PSP can start differently for different people, but there are some commonalities. Balance difficulty, changes to walking, and frequent falls are often the first symptoms for the majority of people with PSP. Other common early symptoms include changes to vision and speech, mild shaking of the hands, difficulty driving a car, and difficulty finding words. Early forgetfulness or personality changes, such as loss of interest in ordinary pleasurable activities, impulsivity, or increased irritability, can also occur and may be misinterpreted as depression or early stage dementia.

Changes to vision can be an early symptom of PSP for many people, while for others it does not appear until a few years later. Abnormalities with eye movements is something that neurologists will assess, which is why they often have you follow their finger and move your eyes in different directions without moving your head.

The most common and characteristic eye movement problem in PSP is an impaired ability to move the eyes up or down. Although Parkinson’s disease, other conditions, and normal aging can sometimes cause difficulty moving the eyes up, PSP is nearly unique in also causing problems moving the eyes down. This problem often takes the form of eye movement apraxia, where the patient can move the eyes up or down only after several requests or with a delay after initiating the effort. This symptom can interfere with looking down at a plate while eating or with descending a flight of stairs, among other things.

Another eye movement problem that starts early in the illness is square wave jerks—rapid, involuntary, right-left movements that interfere with the ability to precisely aim the eyes at a target. Large eye movements can also become jerky rather than smooth.

Because aiming the eyes properly is the main difficulty, reading can become challenging, as a person with PSP may find it hard to automatically shift down from line to line. Some people also have difficulty maintaining eye contact during conversation.

Many people with PSP report double vision, which can look like two images of one object or the images may overlap. This can be an early symptom of PSP.

People with PSP can experience abnormal eyelid movement. One such problem is called blepharospasm, which can take the form either of forceful involuntary closing of the eyes for a few seconds or minutes at a time, or of difficulty opening the eyes, even though the lids seem to be relaxed. The person may try to use the muscles of the forehead, or even the fingers, in an effort to open the eyelids (“apraxia of lid opening”). Others may have trouble closing the eyes and blink very little. While about 15 to 25 blinks per minute are normal, people with PSP blink, on average, only about three or four times per minute. This can allow the eyes to become dry. Dry eyes can lead to blurred vision, production of extra tears, or a sensitivity to light called photophobia.

Not everyone with PSP gets all of these visual symptoms. Symptoms vary from person to person and in severity. If you experience changes to your vision, especially if they interfere with your daily functioning and quality of life, you can be assessed by a neuro-ophthalmologist. There may be treatment options and management techniques that can help, depending on the nature and severity of the vision symptoms, such as artificial tears for dry eyes, prism glasses or prism stickers for double vision, and Botox injections or eyelid crutches for forced eyelid closure. Occupational therapists can also provide recommendations for adaptations related to vision that can make daily life easier and the home environment safer.

The same general area of the brain that controls eye movement also controls movements of the mouth, tongue, and throat, and these movements also weaken in PSP. In Parkinson’s disease, the primary speech problem is characterized by soft volume. While this can occur in PSP, PSP can also cause the speech to have an irregular, explosive, or rubber band quality (called spastic speech) or a slurred, drunken quality (ataxic speech). These changes to speech and voice can be coupled with difficulty getting out thoughts or finding words, making communication quite challenging for many people with PSP. It can be helpful to work with a speech-language pathologist, especially one who is specialized in Parkinson’s disease and related disorders, to learn exercises and compensatory strategies to help people with PSP continue to communicate as much as possible.

Unfortunately, swallowing problems are common with PSP and are a leading cause of complications. PSP can cause weakness and incoordination of throat muscles, making it more difficult to swallow. This issue increases the risk of food or liquids going into the lungs, which is called aspiration, and can lead to pneumonia.

Changes to swallowing function, which can occur early in PSP, may include coughing on thin liquids or more particulate foods, such as salads or dry cereal. Other signs of swallowing dysfunction can include the sensation of food being caught in the throat, frequent runny nose, watery-sounding voice, occurrences of choking, and recurrent lung infections. Additionally, sometimes people with PSP can eat more impulsively, including large bites or very quickly, which can increase risk with swallowing.

Your doctor may recommend regular examinations of your swallowing function to make sure food and liquid are going down the right way. Additionally, speech-language pathologists can help assess swallowing function as well as provide recommendations for diet and lifestyle modifications and exercises for the throat in order to make swallowing easier and safer.

Dementia is a term that refers to the loss of cognitive functioning to the extent that it impacts a person’s daily life. There are different types of dementia, and different diseases can cause dementia. In Alzheimer’s disease, the most common cause of dementia, the cognitive impairment is primarily in the area of memory. People with PSP can experience changes to cognitive function, especially in more advanced stages of disease. This is usually in the areas of organization and processing of thoughts, planning, multitasking, attention, and word-finding. Sometimes people with PSP are initially misdiagnosed with Alzheimer’s disease, or may be diagnosed with frontotemporal dementia, which is a different type of dementia.

Aphasia is a cognitive deficit affecting communication, including finding words, expressing thoughts, and understanding language. Different neurological conditions can cause aphasia. Some people with PSP can experience aphasia. The severity can vary greatly, and for some, it can be an early symptom of PSP.

For many families of someone with PSP, the most challenging aspects of cognitive impairment with PSP are impulsivity, poor judgment, and lack of insight into their cognitive or physical challenges. As examples, someone may jump up from a chair quickly, without waiting for assistance or using a walker, or may eat large portions of food very quickly. Some families have also shared that their loved one with PSP developed a tendency for impulsive and compulsive shopping. A big point of contention for families and healthcare providers alike is when a person with PSP is adamant they can still drive or do other things safely when it is apparent to others that they are unsafe. Impulsivity coupled with imbalance is the primary reason that people with PSP fall.

Apathy can also be a cognitive symptom with PSP, causing people to have less motivation to partake in activities. Cognitive changes in PSP can lead to social withdrawal or irritability, especially when they make communicating thoughts and participating in conversations more difficult.

Even in later stages of PSP, a person can often still respond to a question with accuracy and detail, but because of slowed processing speed, it may take several seconds or minutes and great effort to get out a thought. People with PSP and families can ask people to be patient when communicating. It can also be helpful to work with a speech-language pathologist on strategies to compensate for and adapt to cognitive changes and make communication easier.

The name of the disease includes the word “progressive” because, unfortunately, early symptoms get worse and new symptoms develop over time. After five or six years, on average, the imbalance and stiffness worsen to make walking very difficult or impossible. Difficulty with eyesight, speech, and swallowing are additional important features of PSP that eventually occur in most patients. Not everyone experiences all of the symptoms of PSP, and the appearance and progression of these symptoms varies greatly among individuals.

Research has shown that someone with PSP lives, on average, about eight to ten years after the onset of symptoms. Injury from falling is one of the most common complications in PSP. Another is infection, particularly pneumonia and urinary tract infections. Your doctor may recommend regular evaluations of your swallowing function, assessments by a physical therapist and adaptive equipment to improve your safety with ambulation, a consultation with a urologist if challenges with urinary function arise, and other preventative measures.

We recognize this information is scary and overwhelming to learn and to think about. It can be helpful to talk this information through with your medical team and your family, including planning for the future and your wishes for quality of life. CurePSP and the rest of your support system are here to help.

PSP is occasionally referred to as Steele-Richardson-Olszewski syndrome after the three physicians who first described the disease in 1963. There are thought to be several different types of PSP.

About half of those with PSP have the Richardson’s syndrome type. The most common first symptom of this type of PSP is loss of balance while walking, which can take the form of unexplained falls. People may also experience stiffness or awkwardness when walking, while sometimes the falls are described as attacks of dizziness.

The second most common form of PSP, accounting for about a quarter of cases, is called PSP-parkinsonism. The PSP-parkinsonism type of PSP is more likely to have mild tremor as a symptom, to involve one side of the body more than the other, to have less of a problem with vision and swallowing, and to respond better to drugs for Parkinson’s disease.

There are other less common types that are characterized by their predominant clinical symptoms.

Some neurologists may share the diagnosis of a specific PSP type with you, but they likely will not. The different types may involve symptoms that require certain care considerations, but ultimately, PSP, regardless of the type, is treated similarly. Care, support, and management will be tailored to your unique needs.

To diagnose PSP, a neurologist will gather a person’s medical history, including neurological symptoms, when they started, and how they impact the person’s everyday functioning. They will also perform a physical examination where they will evaluate how a person walks, speaks, and moves their eyes, feet, and hands.

At this time, there is no specific test to diagnose PSP. Neurologists will often refer to magnetic resonance imaging (MRI) to look for changes in the brain. Midbrain atrophy found on a brain MRI can be suggestive of PSP and when viewed from a certain angle, this atrophy can resemble a hummingbird. The “hummingbird sign” on a MRI (sometimes called the “penguin sign”) can help to support a clinical diagnosis of PSP. A neurologist may decide to use other tests, such as blood tests, a neuropsychological evaluation, a DaTscan, or positron emission tomography (PET) scan to support the diagnosis of PSP or help rule out other causes of symptoms. Sometimes how someone responds to medications for Parkinson’s disease can also help a neurologist make a diagnosis of PSP.

Many people with PSP face a long and confusing diagnosis journey, including a number of tests, specialists, and diagnoses. It is our hope that better awareness of PSP, especially within the medical community, will lead to earlier and more accurate diagnosis.

At this time, there are no medications to cure PSP or to slow its progression. Some symptoms of PSP can be managed successfully with medications for the same symptoms in other conditions. Drugs for Parkinson’s disease that stimulate the brain’s dopamine system, particularly carbidopa-levodopa, can be effective in alleviating some of the parkinsonism symptoms in PSP, particularly slowness and stiffness. It has also been found to reduce some of the frequency of falling. Unfortunately, the response to carbidopa-levodopa in PSP is typically not as dramatic or long-lasting as in Parkinson’s disease. Sometimes having little to no response to carbidopalevodopa after a Parkinson’s diagnosis can be a sign of an atypical parkinsonism disease such as PSP. Amantadine is another medication often used in Parkinson’s disease that may have some benefit in PSP, particularly with freezing of gait.

Botox or Myobloc, two types of botulinum toxin, can be useful for people with PSP who experience blepharospasm (forced closure of the eyelids), excessive drooling, involuntary bending or turning of the neck muscles, jaw clenching, or other types of dystonia. Botox injections should be performed only by an experienced neurologist to minimize risks and side effects.

Other medications can be used to manage other symptoms of PSP, such as sleep, urinary, or mood changes. Your doctor will work with you closely to try different medications, timing, and dosages to maximize the benefits for your symptoms while also trying to minimize side effects.

Deep brain stimulation (DBS) is a brain surgery commonly offered to people with Parkinson’s disease. There have been only relatively small case series as examples of people with PSP undergoing DBS, and in most cases it was because they were misdiagnosed as having Parkinson’s disease. DBS worsens symptoms for people with PSP, and for this reason, DBS is not recommended for PSP at this time.

Allied health therapies are also important pillars of treatment to address many of the symptoms and challenges faced by people living with PSP. Occupational therapists can assess safety in the home environment and with driving and daily tasks, as well as provide recommendations for strategies and adaptive equipment to support independence and ease of daily activities. As research has shown repeatedly that cardiovascular exercise can slow down progression of motor decline in most neurodegenerative conditions, exercise remains a very important piece of disease management for people with PSP. Physical therapists can teach exercises that are safe to do and help to keep someone active, as well as provide recommendations for appropriate ambulatory equipment. Speech-language pathologists address speech, communication, cognition, and swallowing functions. Clinical social workers and nursing professionals are equally important members of a care team, offering resource connection, help with navigating the healthcare system, and support in decision-making. It is also important to treat anxiety or depression if it is impacting daily functioning and quality of life, which can be done through the use of mood medications and mental health therapy.

Both PSP and Parkinson’s disease cause parkinsonism (with a small p)—a combination of stiffness, slowness and clumsiness. This is why PSP may be difficult to distinguish from Parkinson’s disease early on. However, shaking (tremor), while prominent in about 70 percent of people with Parkinson’s disease, occurs in only about 10 percent of people with PSP. A more common type of tremor occurring in PSP is irregular, mild and present only when the hands are in use, not at rest as in Parkinson’s disease.

Patients with PSP usually stand up straight or occasionally even tilt the head backwards and tend to fall backwards, while those with Parkinson’s usually are bent forwards. The problems with vision, speech and swallowing are much more common and severe in PSP than in Parkinson’s. Parkinson’s causes more difficulty using the hands and more stiffness in the limbs than does PSP. Finally, the medications that are so effective for Parkinson’s disease offer much less benefit in PSP.

The PSP-parkinsonism variant of PSP is more likely than typical PSP to have a tremor, to involve one side of the body more than the other, to have less of a problem with vision and swallowing, and to respond better to drugs for Parkinson’s.

Most drugs for Parkinson’s disease enhance, replace or mimic a brain chemical called dopamine. Parkinson’s responds better to such drugs than does PSP because dopamine deficiency is by far Parkinson’s most important abnormality. In PSP, deficiencies of several other brain chemicals are at least as severe as the dopamine deficiency, and no good way exists to replace those. Also, in PSP, there is damage to the brain cells that receive the dopamine-encoded messages, while these remain intact in Parkinson’s.

“Progressive” is in the name because of how symptoms change and worsen over time. The term “supranuclear” refers to the area of the brain that is affected in PSP (at the base of the brain, in the brainstem), that causes the eye problems in PSP. In general, “palsy” means weakness or paralysis of a part of the body. People with PSP have often difficulty aiming the eyes properly because of weakness or paralysis (palsy) of the muscles that move the eyeballs.

Many people with PSP may be told, prior to a more definitive PSP diagnosis, that they have “parkinsonism.” They may hear the term “atypical parkinsonism” used as an umbrella term referring to PSP and other related diagnoses. Parkinsonism is a term that describes a constellation of symptoms similar to Parkinson’s disease, including tremor, imbalance, slowness of movement, and stiffness of muscles. Sometimes a provider will say someone has “parkinsonism” in very early stages of symptoms, when it is not yet clear what diagnosis someone has.

“Atypical parkinsonism” is a term frequently used to refer to diseases that look like Parkinson’s disease in many ways, and may even be initially diagnosed as Parkinson’s disease but then have other symptoms not as commonly seen in Parkinson’s disease. These “atypical” symptoms may include earlier and more profound changes to vision, balance, and speech as well as a lack of robust response to the Parkinson’s disease medication carbidopa-levodopa. Other diagnoses that are commonly referred to as atypical parkinsonism diseases include corticobasal degeneration (CBD) and multiple system atrophy (MSA). Because of the similarities of care journeys and needs of PSP, CBD, and MSA, it is not unusual for them to be served by the same healthcare providers, support groups, and organizations, including CurePSP.

The direct cause of PSP is not fully understood. However, we do know that it has to do with the clumps of tau protein. Tau is a normal protein found in brain cells and is currently thought to help maintain the microtubules, which are stiff rods that function as the brain cells’ internal transportation and skeletal system. In PSP, the tau seems to become abnormally folded, which causes it to stick together and become stuck inside the cell. The areas of the brain that have cells with tau inside of them also exhibit impaired neuron function and neuronal death. The clumps’ technical name is neurofibrillary tangles. Alzheimer’s disease and frontotemporal dementia also involve misfolding of the tau protein.

The symptoms of PSP are caused by a gradual deterioration of brain cells in a few places in the base of the brain. The most important such place, the substantia nigra, is also affected in Parkinson’s disease; damage to it accounts for the symptoms that PSP and Parkinson’s disease have in common. However, several important areas that are affected in PSP are normal in Parkinson’s disease, and vice versa. Additionally, Parkinson’s disease is caused by the misfolding of a different protein, called alpha synuclein, and under the microscope, the appearance of the damaged brain cells in PSP is quite different from those in Parkinson’s disease. Instead, it resembles the degeneration in Alzheimer’s disease and frontotemporal dementia, although the location of the damaged cells is quite different in PSP compared with these other tauopathies.

Genetic differences and exposure to certain chemicals are being explored as possible causes, but ultimately, we are not yet sure why tau misfolds or people get certain brain disorders like PSP. For someone who is personally impacted by PSP, we recognize that not knowing the cause can be extremely frustrating, confusing, and scary. Researchers and doctors are working hard to understand PSP and other related neurodegenerative diagnoses, and we hope their work will lead to more answers and treatment options soon.

PSP very rarely runs in families and is not considered a genetic disease. Fewer than one in 20 people with PSP knows of even one other family member with PSP, and detailed neurological exams of relatives of patients with PSP show no more definite abnormalities than exams of relatives of healthy people. 

However, two different variants in the gene on chromosome 17 that encodes the tau protein are more common in PSP than in the rest of the population. One of the variants is called the H1 haplotype. About 95% of people with PSP have this variant on both of their copies of chromosome 17, while this is true for only about 60% of people without PSP. So clearly, the H1 haplotype is (nearly) necessary but far from sufficient to cause the disease. We don’t yet know how that version of the tau gene actually affects brain cells. It may increase the amount of tau protein produced or it may change the chemical properties of the protein.

Over the past two decades, a handful of other gene variants not on chromosome 17 have been found to be more common in people with PSP than in people without PSP. These genes help control a variety of critical processes inside of brain cells. More research is needed to identify how these insights can translate into possible PSP prevention and treatment.

There is important research being done to look for genetic and environmental contributors to the cause of PSP, as well as research on tests that can lead to more accurate diagnosis and improved care of PSP. Many people with PSP find that participation in research is a meaningful way to help doctors and scientists understand, diagnose, and treat PSP and related diseases. Additionally, participants in clinical trials may benefit from a new treatment that is not generally available and may receive detailed care and attention that is not part of routine medical care.

Because of the rarity of PSP, there can sometimes be the challenge of not having enough eligible people to be included in drug trials. To properly test a drug and understand its impact, patients need to be recruited from a number of sites. CurePSP is working hard to build partnerships with pharmaceutical and biotechnology companies to develop interest and funding for the study of PSP and related diseases. Additionally, CurePSP funds research through various grant programs and supports collaborative research projects through its growing CurePSP Centers of Care network of medical centers across the United States and Canada.

In the United States, clinical trials are listed on a website maintained by the National Institutes of Health, www.clinicaltrials.gov. You can enter “progressive supranuclear palsy” into the search box. You can also ask your neurologist if they are aware of studies in PSP or consult curepsp.org for that information.

Donating your brain to science can be a powerful contribution to the understanding of PSP and other neurodegenerative conditions. Each donated brain is also evaluated by a trained neuropathologist to confirm that the diagnosis of PSP was correct. Setting up brain donation needs to occur early, ideally months or even years prior to someone passing away. Visit www.psp. org/ineedsupport/braindonation to learn about CurePSP’s Brain Donation Assistance Program.

Building a support team around you is foundational to quality of care and life with PSP. Your support team may consist of your partner, family, friends, support group, religious community, healthcare team, professional care, and others—people who care about you and show up for you.

When living with a chronic and progressive diagnosis, it is important to find the right medical team to support your needs with PSP over time. PSP needs to be managed by a neurologist. This could be a general neurologist, but, if available in your area, you may also choose to work with a neurologist who has gone through specific training in movement disorders or behavioral/cognitive neurology. Rehabilitation therapists (physical, occupational, and speech therapists) and clinical social workers also play important roles in the care of PSP. You may also benefit from adding other specialists to your team as symptoms and needs arise. These may include a urologist, sleep specialist, neuro-ophthalmologist, and palliative care specialist. Taking care of your emotional health, whether as a person diagnosed with PSP or as a carepartner, is also a priority, and working with a mental health professional to process the experience, foster coping skills, or address other emotional needs can be exceptionally beneficial. When building your care team, it is important you have providers that you have chemistry with and that you trust, and for you to know that you have the right and ability to change your providers if needed.

Completing health care advance directives is an excellent tool for sharing your wishes regarding care with your support team. Health care advance directives address topics such as how aggressive your medical care should be (for example, whether you would want a feeding tube or a machine for breathing, if the need arose) and how you define quality of life. These directives should be completed with your family and your doctor and should be reviewed at least annually in case your wishes change.

Many people living with PSP consider and explore professional care services, such as in-home care, adult day care, or long-term care, depending on their care needs and situation. These services can provide additional layers of support, including companionship or hands-on help for the person with PSP and assistance and respite for the family.

Additionally, there can be great value in connecting with other people affected by the same diagnosis as you and your family, through support groups or peer supporters. It can feel validating and uplifting to hear the experiences and insights on how others adjust to life with PSP. You can exchange helpful tips on ways to cope and adapt physically and psychologically with the diagnosis. CurePSP offers a variety of support groups for people affected by PSP. There are also many more for atypical parkinsonism (which can include PSP and other diseases, such as corticobasal degeneration and multiple system atrophy) in the United States and other countries. Visit www.psp.org/ineedsupport/supportgroups for a list of regional support groups as well as virtual, national and international support groups facilitated by or in collaboration with CurePSP. Additionally, many local Parkinson’s disease or frontotemporal dementia support groups welcome members with PSP. If you may be interested in starting your own PSP support group, contact CurePSP to learn more and for help in getting started. Additionally, CurePSP offers a peer support network, family conferences, and educational webinars where you can learn about PSP and connect to the community. We know that a diagnosis of PSP can bring up many emotions, changes, and considerations. No matter how you find support, please remember that you do not have to navigate the PSP journey alone.

Several prescription medications can help patients with PSP, in some cases.

Levodopa and carbidopa are the almost universally prescribed generic form of the brand name Sinemet. Levodopa is the component that helps the disease symptoms; carbidopa simply helps prevent the nausea that levodopa can cause. When levodopa came along in the late 1960s, it was a revolutionary treatment for Parkinson’s but it is of only modest benefit in PSP. It can help the slowness, stiffness and balance problems of PSP to a degree, but usually not the mental, speech, visual or swallowing difficulties. About 50 percent of those with PSP-parkinsonism respond to levodopa/ carbidopa, while the figure is only 14 percent for Richardson’s syndrome. The drug typically loses its benefit after two or three years, but a few patients with PSP continue to respond.

Some patients with PSP require large dosages to see an improvement—up to 1,200 milligrams of levodopa (with carbidopa) per day—so the dosage should generally be raised to at least that level under the close supervision of a physician, unless a benefit or intolerable side effects occur sooner. The most common side effects of this drug in PSP are confusion, hallucinations and dizziness. These typically disappear after the drug is stopped. The most common side effect in patients with Parkinson’s disease, involuntary writhing movements (chorea or dyskinesias), occur very rarely in PSP, even at high dosages.

Patients with PSP should generally receive the standard Sinemet or generic carbidopa/levodopa preparation rather than the controlled-release (Sinemet CR or generic carbidopa/levodopa ER) form. The CR or ER form is absorbed from the intestine into the blood slowly and can be useful for people with Parkinson’s disease who respond well to carbidopa/levodopa but need to prolong the number of hours of benefit from each dose. In PSP, however, such response fluctuations almost never occur. Because the CR or ER is sometimes absorbed very little or erratically, a poor response in a patient with PSP might be incorrectly blamed on the fact that the disease is usually unresponsive to the drug. Such a patient might actually respond to the standard form, which reaches the brain in a more predictable way.

For people with PSP who cannot swallow pills safely, a solution is to crush a regular levodopa-carbidopa tablet into a food or beverage that is easily swallowed. The drug dissolves best in acidic beverages such as juices or sodas.

Another formulation of levodopa-carbidopa combines those two drugs with a third drug, entacapone, in the same tablet called Stalevo. The entacapone slows the rate at which dopamine is broken down. It is useful for patients with Parkinson’s but rarely, if ever, in PSP.

There are three dopamine receptor agonists drugs on the market for Parkinson’s—Mirapex (pramipexole), Requip (ropinirole) and Neupro (rotigotine, which comes only as a skin patch). For PSP, these rarely give any benefit beyond that provided by carbidopa/levodopa and may cause hallucinations and confusion, excessive involuntary movements, dizziness and nausea.

Antidepressants have also had some modest success in PSP, sometimes relieving the depression that can be part of the disease. There are many antidepressants and none has been shown to be superior to any others. The older, tricyclic antidepressants seem to be no less effective in PSP than the newer reuptake blocker antidepressants.

Amantadine has been used for Parkinson’s since the 1960s. It can be effective against the PSP gait disorder even if Sinemet is not, possibly because it affects more than just the dopamine system. Its benefit generally lasts only a few months, however. Its principal potential side effects are dry mouth, constipation, confusion, swelling of the ankles and a pink skin discoloration in a lacy pattern called livedo reticularis. In people with PSP, the dosage should be kept low, generally no more than 200 mg per day, because of the potential for confusion or agitation.

Drugs for dementia, including Aricept (donepezil), Reminyl (galantamine) and Exelon (rivastigmine), enhance the activity of the brain chemical acetylcholine and are modestly useful against the dementia of Alzheimer’s disease. They can also be somewhat useful in Parkinson’s disease and other forms of dementia. None of them has been found helpful in PSP, but rivastigmine is probably worth trying. A fourth anti-Alzheimer drug, Namenda (memantine), acts on a different brain chemical, glutamate. It works no better for PSP than the others and can cause confusion and agitation in those patients.

One possible success story is the dietary supplement Coenzyme Q-10 (CoQ10), is which is available without a prescription, although the jury is still out. It helps the body’s cells produce energy from sugar and oxygen and is a normal constituent of the mitochondria, the tiny compartments in our cells where that chemical process occurs. One small study gave modestly favorable results. Another gave similar benefit, but was too small to be sure that its outcome was not just the result of chance. The required dosage of the standard formulation of CoQ10 is probably at least 1200 mg per day and perhaps as high as 2400 mg. The newer liposomal form probably gives the same benefit at 300 mg per day. As a nonprescription item, CoQ10 is not covered by drug insurance and costs $50 to $100 month. Therefore, people with PSP should carefully consider the meager evidence to date for the benefit of CoQ10 before taking that long-term financial plunge. Their neurologists should do a careful exam upon starting the drug and repeat it two months later to determine whether the treatment is working, and if not, discontinue it.

Botox or Myobloc, two types of botulinum toxin, are a different sort of drug that can be useful for people whose PSP is complicated by blepharospasm. A very dilute solution of the toxin, which is produced by certain bacteria that can contaminate food, can be carefully injected by a neurologist into the eyelid muscles as a temporary remedy for abnormal involuntary eyelid closure. Botox can also be used for involuntary turning or bending of the head that occurs in PSP, but injecting it into the neck muscles can sometimes cause slight weakness of the nearby swallowing muscles. In PSP, where swallowing is already impaired in many patients, caution should be used when considering use of Botox in neck muscles.

In the past 20 years, many drugs have been tested in patients with PSP. Some of these are intended to actually slow the long-term brain cell loss; i.e., slow progression of the disease. Unfortunately, none has helped. The most promising were riluzole, which modestly helps amyotrophic lateral sclerosis; davunetide, which is a fragment of a protein that helps maintain brain cells’ internal skeletons; and tideglusib, which prevents the abnormal attachment of phosphate to the tau protein, preventing it from clumping up in the brain cells. The last drug did show a glimmer of promise; MRI scans showed less loss of brain mass in the patients on tideglusib than in those on placebo. This may justify further study of the drug, but it is doubtful that any drug company will want to pursue it after it failed to slow progression of the actual symptoms of the disease.

Two other approaches to slowing the progression of PSP have just entered clinical trials. One gives antibodies designed to attack the abnormal tau protein as if it were an invading virus or bacterium. There are two such trials, sponsored by the companies Bristol-Myers Squibb and AbbVie, respectively. Another uses a version of the cancer drug Taxol to help maintain the brain cells’ inner skeletons, which break down in PSP.

Two current, small, preliminary trials use existing drugs that are marketed for other diseases. One uses Salsalate, a nonsteroidal anti-inflammatory drug, which may prevent the tau protein from aggregating via a mechanism unrelated to its anti-inflammatory effect. Another tests the drug methylene blue or LMT-X in Alzheimer’s disease, hoping that it will also be useful in PSP.

Two drugs that reduce the tendency of tau protein to aggregate by altering the ability of phosphate molecules to attach to it will enter trials in the next year or two. The two drug companies involved are Asceneuron and Merck.

Fortunately for PSP sufferers, drug companies have started to act on the realization that a prevention or disease-slowing treatment for PSP, where the market is tiny, could also work in Alzheimer’s disease, where the market is huge.

For extreme cases of poor swallowing where choking is a definite risk, the placement of a tube through the abdomen into the stomach (called gastrostomy or percutaneous endoscopic gastrostomy or PEG) may be advised. PEG feeding may allow patients to regain lost weight, avoid hunger and receive the nourishment they need to fight off other potential complications of PSP. A patient receiving the necessary nutrients and fluids is much happier and stronger overall and will probably find general movement, speech and thinking easier.

PEG placement may be considered when any of the following occur: a first episode of aspiration pneumonia; small amounts of aspiration with each swallow; significant weight loss from insufficient feeding; or when the prolonged time required for a meal disrupts the operation of the household.

The PEG tube can be inserted with the patient awake but sedated, often as an outpatient procedure. The tube is clamped shut and hidden under the clothes when not in use. The feeding can easily be managed at home by pureeing the family’s regular food in a blender and injecting it into the tube with what looks like a basting syringe. The skin site where the tube enters requires only a little care that can easily be provided by a family member or even by the patient in some cases. If the need for tube feeding abates (as through a new medication, for example), normal oral feeding can be resumed and the tube can be kept as a backup or removed.

One potential downside of tube feedings for some patients is a loss of feeling “whole” or part of humanity. The issue of how a feeding tube will affect a patient’s quality of life must be considered carefully by the family, physician and if possible, the patient and sometimes ethical or spiritual advisors. Some patients in the advanced stages of PSP may feel that their quality of life is so poor that prolonging that life by having a PEG installed is not what they want.

It’s important to note that some nursing homes will advise PEG placement because it reduces the personnel time needed to feed the patients and because third-party payers often will pay an additional fee for tube feeding but not for the time-consuming task of hand feeding a patient by mouth.

Not so far, unfortunately. The operations for Parkinson’s disease fall into two categories. One is based on the theory that the basal ganglia (the group of nuclei that control movement to the rest of the brain) is overactive. The most common operation to dampen down this overactivity at present is subthalamic nucleus stimulation. The previous approach, pallidotomy, is rarely performed now. In PSP, however, the output area of the basal ganglia is damaged, so its activity is already dampened. The operation would only make things worse.

There are, however, trials now in progress in people with PSP to test stimulation of the area of the brain that serves balance, the pedunculo-pontine nucleus (PPN). The PPN is in the brainstem, which is an area tightly packed with critical circuitry. The procedure seems to be acceptably safe and does seem to help the balance problem in some patients with Parkinson’s disease, but the overall improvement in patients is still undetermined.

In patients with Parkinson’s, there is also an operation that attempts to replace the lost dopamine-producing brain cells. This is unlikely to work for PSP because, while in Parkinson’s, most of the movement problem is caused by loss of the main dopamine-producing nucleus, the substantia nigra, the movement problems in PSP are caused by the loss of many additional nuclei. Many of those other nuclei receive their input from the substantia nigra, so replacing only the first link in the chain would not help much and, at this point, it would cause too much trauma to the brain to replace cells in all of the nuclei involved in PSP.

An exciting experiment in progress in Milan, Italy, but one that has only a slim chance of success, is the injection of stem cells directly into the arteries feeding the brain. This project is still in the very early phases designed to test its safety. If it succeeds, then a large project will test for benefit. The intent is not to replace lost cells, as the injections land in random spots, but to stimulate the brain to produce its own growth factors to repair the damage of PSP.

Formal physical therapy is worth a trial in PSP, especially with the goal of teaching the patient to use gait-assistive devices such as a walker. Certain exercises done in the home by oneself on a regular schedule can keep the joints limber. Exercise also has a clear psychological benefit that improves a sense of well-being for anyone with a chronic illness. For specific exercises, consult one of the books for patients with Parkinson’s disease or the pamphlets distributed by the national Parkinson organizations.

The special balance problems in PSP dictate caution in performing any exercises while standing. Many useful exercises can be performed seated in a chair or lying on a mat. Using a stationary bicycle is usually feasible as long as there is help in mounting and dismounting safely. The best strategy is to have an evaluation and treatment plan from a physical therapist or physiatrist (a physician specializing in rehabilitation of chronic conditions).

Probably the most important part of dealing with PSP is for the patient’s family to understand that the problems with visual inattention and personality changes are part of the illness. The patient is not lacking will power nor “faking.” Furthermore, many of the problems in PSP are intermittent and can be aggravated by the patient’s mental or emotional state. For example, walking, writing and eating may be poor one hour and better the next. The family should understand that these fluctuations are not under the patient’s control and that nagging and shouting usually just make matters worse. A wise policy is to be prepared to take advantage of the “good” periods to have an outing, a relaxing shower or some other activity that would be more difficult at another time.

Walking aids are often important for patients with PSP. Because of the tendency to fall backwards, if a walker is required it should be weighted in front with sandbags over the lower rung. A better but more expensive solution is a large, heavy walker resembling a small shopping cart with three or four fat, soft rubber wheels and a hand brake. The tendency to fall backwards can also be countered by the use of built-up heels. Leg braces are not helpful because the problem in PSP is coordination and balance rather than actual muscle weakness.

Shoes with smooth soles are often better than rubber-soled athletic shoes. In many people with PSP, the gait disorder includes some element of “freezing,” a phenomenon that makes it difficult to lift a foot from the ground to initiate gait. People with such symptoms can fall if they move their body forward before the foot moves. In these cases, smooth soles could make it easier to slide the first foot forward.

Handrails installed in the home, especially in the bathroom, may also be helpful. The difficulty looking down dictates that low objects such as throw rugs and low coffee tables be removed from the patient’s living space.

To remedy the difficulty of looking down, bifocals or special prism glasses are sometimes prescribed for people with PSP. These are worth trying, but can be of limited value because there is not only a problem moving the eyes in PSP, but also a problem directing the person’s attention (the “mind’s eye”) to objects located below the eyes.

The most common subtype of PSP is called PSP-Richardson's syndrome (PSP-RS), after the neurologists who first described PSP in the 1960s. PSP-RS is known as the classic type of PSP and is the most common of the ten subtypes.  

Although it’s known that PSP-RS is the most common, it’s difficult to estimate how many people with PSP have which subtype. It’s hard to know because:  

• Published statistics are based on people with PSP who are able to visit research institutions, which doesn't capture the whole picture of people with PSP. Many people can’t seek care at research institutions for reasons like cost or geographical location.  
• Many clinical trials and epidemiological studies only study people with PSP-RS. 
• PSP can sometimes look like other diseases, which makes it easy to misdiagnose. It’s difficult to know if a person truly has PSP without an autopsy of the brain.  
• As the disease progresses over time, the symptoms of the other subtypes often look more like PSP-RS.  
• There aren’t currently clear diagnostic distinctions between subtypes. At this time, a subtype is diagnosed only by presenting symptoms. Many patients could be categorized into one or more subtypes, especially in the earlier years of the disease. 

The most common initial symptom of PSP-RS is unexplained falls, but as the disease progresses, people might start to experience symptoms of other subtypes. Other common symptoms are issues with thinking and planning, controlling actions and speech, moving eyes up and down (supranuclear gaze palsy) and controlling the eyelids, swallowing, difficulty moving at a normal pace, ability to control the bladder and sleeping issues.  

PSP-Parkinsonism is the second most common subtype of PSP. Compared to PSP-RS, it has more asymmetry (one-sidedness), tremor and slowness. Compared to other types of PSP, PSP-P responds better to Parkinsonism medications, like levodopa. People with PSP-P tend to have fewer issues with thinking, behavior, balance and eye movement. It typically progresses the slowest of all the subtypes, averaging about nine years of survival after the first symptoms.  

PSP-P is often originally diagnosed as Parkinson’s disease because of the symptom similarities and the tendency for better and early responsiveness to Parkinson’s medications. It’s usually only when symptoms progress faster than expected that the medical team begins to rethink the Parkinson’s diagnosis. 

The main symptom of PSP-PGF is no longer being able to maintain an ongoing gait, or difficulty continuing walking after a step or two. This is especially true after pausing, turning or entering a doorway threshold. As the disease progresses, people with PSP-PGF usually can’t initiate walking at all. 

People with PSP-PGF may struggle with small handwriting and rapid speech. People that have issues with progressive gait freezing without other neurological symptoms are likely to eventually develop PSP.  

PSP-SL is a composite category, meaning that it is made up of other, smaller classifications that cover speech and language. Both subtypes in this category can have aphasia as a symptom. Aphasia is when someone has trouble mentally finding words, expressing thoughts or understanding language.   

People with PSP-SL experience a specific kind of aphasia, known as Primary Progressive Aphasia (PPA). This means that aphasia is caused by a progressive issue in the brain, rather than something like a stroke or a head injury. The two types of Progressive Aphasia in the PSP-SL category are:  

PSP-Nonfluent/Agrammatic variant of Primary Progressive Aphasia (PSP-nfaPPA): speech is halting with poor grammar and there is difficulty with syntax (sentence structure) and pronunciation. Comprehension and ability to name items and people are not affected.  

PSP-Semantic-Variant Primary Progressive Aphasia (PSP-svPPA): there is difficulty naming items and people but no issue with using proper grammar or syntax.  

PSP-CBS is highly asymmetric, meaning symptoms are usually only on one side of the body, or at least more prominent on one side. Symptoms tend to be rigidity, slowed movement and loss of skilled movement (called apraxia). It also features asymmetric fixed postures (called dystonia), weakness, abnormal reflexes (pyramidal findings) and small, rapid and irregular movements (known as myoclonus).  

People with PSP-CBS may also have a loss of visual perception, ability to identify familiar objects by touch or understanding where their body or limbs are in space. Aphasia, or difficulty understanding and pronouncing language, can sometimes happen.  

People with PSP-CBS have fewer issues with eyes, and less postural instability and cognitive loss than PSP-RS. CBS is a disease that is closely related to PSP, and it is sometimes given as a diagnosis by itself. 

PSP-F features some behavioral challenges, such as disinhibition, irritability, apathy and loss of empathy for others. It also is known for greater impairment in executive functions like maintaining attention, ability to follow instructions, changing tasks on command or stopping a behavior when attempting to.  

These specific cognitive and behavioral issues can be also found in PSP-RS but are usually milder than in PSP-F and only show up later in the disease. 

One of the main symptoms of PSP-RS is vision and eye symptoms. For people with PSP-OM, however, vision and eye trouble are one of the only features they experience. People with PSP-OM may have difficulty looking up or down, trouble tracking moving items with the eyes and other ocular problems. Issues with the eyes can sometimes cause falls in people with PSP-OM, because of problems in perception and sight.  

Another main symptom of PSP-RS is postural instability, which is trouble with balance, maintaining an upright posture and trouble walking. People with PSP-PI experience these parts of PSP-RS and might experience frequent falls due to these issues. Similarly to PSP-OM, this subtype features little else of the classic PSP-RS.  

PSP-PLS is a subtype of amyotrophic lateral sclerosis, known as ALS or Lou Gehrig disease. It can be difficult to tell ALS apart from PSP-PLS, but PSP-PLS is highly asymmetric and is similar to corticobasal syndrome (PSP-CBS). However, PSP-PLS rarely has the sensory loss, dystonia or the small and irregular movements that CBS is known for.  

The cerebellum is the area of the brain that’s located at the back of the head and helps control voluntary movement. PSP-C can cause balance and coordination problems and issues with vision and fine motor movements. Those with PSP-C have a lurching walk of PSP-RS (sometimes described as appearing as though the person is intoxicated), jerking movements of the eyes and slurred speech.  

It can be hard to tell PSP-C apart from PSP-RS while the person with the disease is still alive. When brain tissue is examined during autopsy, people with PSP-C are usually found to have shrunk cerebellums. 

For unclear reasons, this subtype is far more common in East Asia than elsewhere in the world. 

Currently, clinical trials are accepting people only with PSP-RS, but efforts are being made to include other subtypes. There are a few reasons that researchers are sticking to just PSP-RS for now:  

• We are not yet sure how the less common subtypes would react to drug trials, because of the small molecular differences between PSP-RS and other subtypes. 
• Because PSP-RS progresses faster than the other subtypes, a trial of just PSP-RS will have results in a shorter amount of time with fewer participants. 
• Most people who have early signs of PSP-RS are likely to be confirmed to have PSP at autopsy. However, with the other subtypes, there is a greater chance that people have other underlying conditions causing their symptoms, which could cloud the results of a drug study on PSP. 
• Almost all PSP trials measure outcomes using the PSP Rating Scale, which was designed to only measure PSP-RS. However, progression can vary widely for other subtypes, so including them in a trial could hide the benefit of a potential drug.  

There is active research going on regarding PSP subtypes.  Some goals of this research are to:

• Learn why the disease spreads through the brain in PSP-RS and other cortical subtypes faster than in sub-cortical subtypes. Learning this could help researchers better understand the way tau-based disorders work, which in turn would offer them opportunities to develop new medications.  
• Find new ways to identify non-PSP-RS subtypes and to enroll people with non-PSP-RS subtypes into clinical trials. New diagnostic tests are coming, such as a tau-based positron emission tomography (PET) scan. Measures of tau in the skin, blood or spinal fluid could also help identify people with non-PSP-RS subtypes. These tests would improve trials and make testing new drugs for PSP much quicker.