Progressive Supranuclear Palsy (PSP): All you need to know

Progressive supranuclear palsy (PSP) is a serious disease of the brain. 

It can progress rapidly and lead to problems with balance, mobility, vision, speech, and swallowing.

In this article, we will explain what PSP is, how to identify the symptoms, and what different treatment options are available.

What is Progressive Supranuclear Palsy (PSP)?

PSP is one of a group of diseases known as atypical parkinsonisms.

These diseases share many of the symptoms of Parkinson’s, but they originate from different causes.

Progressive supranuclear palsy is less prevalent than Parkinson’s and it affects around three to six people in every 100,000 worldwide. It is more commonly diagnosed in men than women, and symptoms usually occur after the age of 60. (1)

Other examples of atypical parkinsonisms include Lewy body dementia (LBD), multiple system atrophy (MSA), and corticobasal degeneration (CBD).

If you notice any changes in mobility or cognitive function in yourself, or someone else, and you suspect something is wrong, you should see a doctor right away.

Early diagnosis can be the key to slowing down the progression of neurological diseases and maintaining your quality of life and independence for as long as possible.

The first step to getting a PSP diagnosis is to rule out Parkinson’s disease.

What Causes Progressive Supranuclear Palsy?

The symptoms of PSP are caused by harmful buildups of a protein called tau, the same protein which is present in Alzheimer’s disease. (2)

Tau occurs naturally in the brain, however, in people with progressive supranuclear palsy it is not broken down properly and forms clumps in brain cells, mostly at the base of the brain. These clumps cause the brain cells to stop working correctly and eventually die. (3)

However, the exact reason why this happens remains unknown. There is a hypothesis that neurodegenerative diseases such as PSP develop because when abnormal protein clumps form in a cell, they affect nearby connected cells, allowing the disease to progress through the brain. (3)

Other theories regarding the cause of PSP include genetic mutations, bacterial infections entering the nervous system, or free radicals which cause cell malfunction in the brain. (3)  (4)

Another line of thinking is that PSP and other neurological diseases may be triggered by continued exposure to environmental toxins, such as carbon monoxide or pesticides. Some evidence supports this theory. (5) (6)

For example, researchers in France identified a high number of PSP cases in an industrial town. The area was highly polluted with toxic chemicals and waste. (7)

Additionally, scientists spent many years researching neurological diseases on the Pacific Island of Guam. There was a high prevalence of a disease very similar to PSP. Although they suspected that poisonous seeds of a local plant, the cycad, were the cause, they were not able to find definitive proof. (8)

Signs and Symptoms of PSP

The symptoms of PSP can be similar to Parkinson’s. One of the most common first symptoms is sudden stiffness and losing your balance while walking. (9)

Early symptoms

Here are some early signs and symptoms to watch out for:

• Loss of balance when walking, which can lead to falls, often falling backward
• Generally stiff or clumsy movements
• Blurred or double vision, inability to control eye movements, difficulty moving your eyes up and down and controlling eyelids
• Fatigue
• Changes in behavior or personality: becoming irritable or apathetic, having mood swings (laughing or crying for no reason)
• Difficulties with problem-solving, reasoning, and decision making
• Aversion to bright lights (photophobia)

Subsequently, as the disease progresses, initial symptoms may become more severe. It becomes more difficult to control the eye muscles, and patients may require assistance when walking or a wheelchair.

Mid-stage symptoms

In the middle stage of progressive supranuclear palsy, the following symptoms may arise:

• Slow, quiet or slurred speech
• Loss of facial expression
• Trouble swallowing (dysphagia)
• Reduced blink reflex which leads to dry and irritated eyes
• Involuntary closing of the eyes (blepharospasm)
• Disturbed sleep or insomnia
• Slowness of thought and some memory problems
• Neck or back pain, joint pain, headaches

Late-stage symptoms

In the advanced stages, PSP can lead to:

• Increased difficulty controlling muscles of mouth, throat, and tongue. This means speech becomes increasingly slow, slurred, and harder to understand.
• Severe swallowing problems which result in a high risk of choking or chest infections.
• Problems with thinking, concentration, and memory (dementia) though these are generally milder than in the case of Alzheimer’s.
• Problems with bowel or bladder control such as constipation, difficulty passing urine, or needing to urinate several times during the night.

PSP vs Parkinson’s

There are a few main differences between the symptoms of Parkinson’s and PSP.

• Tremors are characteristic of Parkinson’s disease and are often the first symptom. They are less frequent and milder in patients with PSP.
• Both conditions cause eye problems. However, people with PSP are much more likely to struggle with looking up and down.
• Patients with Parkinson’s usually bend forwards, but PSP results in a backwards tilted posture, which leads to falling backwards.
• Speech and swallowing difficulties are more pronounced in PSP than in Parkinson’s.

(10) (11) (12)

How is Progressive Supranuclear Palsy Diagnosed?

It can take time to diagnose progressive supranuclear palsy because it closely resembles Parkinson’s and other atypical parkinsonism diseases in the beginning stages. (13)

There are many possible symptoms, and each individual case is different.

Furthermore, there is no definitive test for PSP. Instead, diagnosis is based on an evaluation of the symptoms and ruling out other conditions such as Parkinson’s and stroke.

Someone with symptoms of PSP will usually be referred to a neurologist, who will arrange various brain scans which are able to rule out strokes or brain tumors. An MRI can also detect abnormal changes to the brain which indicate PSP.

One way to rule out Parkinson’s is to prescribe a course of a drug called levodopa. This medication is very effective at improving the symptoms of Parkinson’s but is less beneficial for patients with PSP. (14)

Another aspect of the process is psychological testing, such as tests to evaluate memory, concentration, understanding of language, and processing visual information.

People with PSP often have a pattern of poor concentration, low attention span, problems with spoken language, and visual processing. However, unlike typical dementia, the memory is not so significantly affected.

How is PSP Treated?

Sadly, there is currently no cure for PSP.

The gradual worsening of symptoms cannot be entirely prevented.

Treatments focus on managing the symptoms and improving quality of life for patients.

Medication

There are no specific medications for PSP. However, in the early stages, patients may derive some benefit from medications used to treat Parkinson’s. These may improve balance and stiffness, though they are not highly effective and the impact is short-lived.

Botox is sometimes administered to help with muscle stiffness and eye spasms.

Antidepressants may also be prescribed as depression is common in people diagnosed with PSP. (15)

Physiotherapy

A physiotherapist will aim to help patients make the most of their remaining mobility through gentle exercise. The priority will be to improve balance and posture and minimize falls.

They may recommend special equipment such as a walking frame or shoes to help with mobility.

Speech and language therapy

Speech and language therapy can help patients learn techniques to overcome communication difficulties and swallowing techniques to reduce the risk of choking or inhaling food.

They can also help to make speech clearer and offer advice about communication aids as the condition progresses.

What is the Outlook for Someone with PSP?

There is no cure for PSP, and existing treatments have limited benefits.

The disease progresses rapidly and life expectancy after a diagnosis of PSP is around 6-9 years. (16)

Within a few years, patients may be confined to a wheelchair and be very limited in their ability to communicate. Someone in the advanced stage of PSP will require round-the-clock care.

Difficulties swallowing may mean they require a feeding tube, as in many cases, the cause of death in people with PSP is choking, or pneumonia caused by inhalation of food due to problems with swallowing.

Advances in Research and Treatment for PSP

There is a wealth of ongoing research into neurological diseases such as progressive supranuclear palsy.

According to a recent article in Scientific American, deeper knowledge about tau may be key to making significant progress in understanding degenerative diseases of the brain and developing more effective treatments. (17)

Specifically, scientists are interested in tau-targeting therapies that may be able to reduce toxic levels of tau or compensate for brain function. These treatments would likely be most effective in the early onset of the disease. (18)

Organizations such as CurePSP focus on a broad spectrum of research into diagnostic markers, genetics, and tau strains. They are also studying interactions between genetic and environmental risk factors. (19)

Ultimately there is still a long way to go before better treatments or a cure for progressive supranuclear palsy are found. Hopefully, new discoveries will lead to longer, more fulfilling lives for patients.

References

(1) Höglinger, G. U., Respondek, G., Stamelou, M., Kurz, C., Josephs, K. A., Lang, A. E., Mollenhauer, B., Müller, U., Nilsson, C., Whitwell, J. L., Arzberger, T., Englund, E., Gelpi, E., Giese, A., Irwin, D. J., Meissner, W. G., Pantelyat, A., Rajput, A., van Swieten, J. C., Troakes, C., … Movement Disorder Society-endorsed PSP Study Group (2017). Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Movement disorders: official journal of the Movement Disorder Society, 32(6), 853–864. https://doi.org/10.1002/mds.26987

(2) Koga, S., Parks, A., Kasanuki, K., Sanchez-Contreras, M., Baker, M. C., Josephs, K. A., Ahlskog, J. E., Uitti, R. J., Graff-Radford, N., van Gerpen, J. A., Wszolek, Z. K., Rademakers, R., & Dickson, D. W. (2017). Cognitive impairment in progressive supranuclear palsy is associated with tau burden. Movement disorders : official journal of the Movement Disorder Society, 32(12), 1772–1779. https://doi.org/10.1002/mds.27198

(3) National Institute of Neurological Disorders and Stroke: Progressive Supranuclear Palsy Fact Sheet. Retrieved on 1 July 2020 from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Progressive-Supranuclear-Palsy-Fact-Sheet

(4) Tetz, G., Pinho, M., Pritzkow, S. et al. Bacterial DNA promotes Tau aggregation. Sci Rep 10, 2369 (2020). https://doi.org/10.1038/s41598-020-59364-x

(5) Golbe LI, Rubin RS, Cody RP, et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology. 1996;47(1):148-154. doi:10.1212/wnl.47.1.148

(6) Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci. 2000;3(12):1301-1306. doi:10.1038/81834

(7) Caparros-Lefebvre, D., Golbe, L. I., Deramecourt, V., Maurage, C. A., Huin, V., Buée-Scherrer, V., Obriot, H., Sablonnière, B., Caparros, F., Buée, L., & Lees, A. J. (2015). A geographical cluster of progressive supranuclear palsy in northern France. Neurology, 85(15), 1293–1300. https://doi.org/10.1212/WNL.0000000000001997

(8) Andy Coghlan: First clue to treating mystery disease of US Pacific island. New Scientist, 20 January 2016. Retrieved on 1 July 2020 from https://www.newscientist.com/article/2073942-first-clue-to-treating-mystery-disease-of-us-pacific-island/#ixzz6QfSylhBA

(9) Litvan, I., Mangone, C. A., McKee, A., Verny, M., Parsa, A., Jellinger, K., D’Olhaberriague, L., Chaudhuri, K. R., & Pearce, R. K. (1996). Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. Journal of neurology, neurosurgery, and psychiatry, 60(6), 615–620. https://doi.org/10.1136/jnnp.60.6.615

(10) Vidailhet M, Rivaud S, Gouider-Khouja N, et al. Eye movements in parkinsonian syndromes. Ann Neurol. 1994;35(4):420-426. doi:10.1002/ana.410350408

(11) Alvarez MV, Evidente VG, Driver-Dunckley ED. Differentiating Parkinson’s disease from other parkinsonian disorders. Semin Neurol. 2007;27(4):356-362. doi:10.1055/s-2007-985336

(12) Tysnes OB, Vilming ST. Atypisk parkinsonisme [Atypical parkinsonism]. Tidsskr Nor Laegeforen. 2008;128(18):2077-2080.

(13) Frank C, Pari G, Rossiter JP. Approach to diagnosis of Parkinson disease. Can Fam Physician. 2006;52(7):862-868.

(14) Constantinescu R, Richard I, Kurlan R. Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord. 2007;22(15):2141-2295. doi:10.1002/mds.21578

(15) Esmonde, T., Giles, E., Gibson, M. et al. Neuropsychological performance, disease severity, and depression in progressive supranuclear palsy. J Neurol 243, 638–643 (1996). https://doi.org/10.1007/BF00878659

(16) Agarwal S, Gilbert R. Progressive Supranuclear Palsy. [Updated 2020 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526098/

(17) Karen Weintraub: Tau Shows Promise as Achilles’ Heel for Alzheimer’s and Similar Diseases. Scientific American, 2 March 2020. Retrieved on 1 July 2020 from https://www.scientificamerican.com/article/tau-shows-promise-as-achilles-heel-for-alzheimers-and-similar-diseases/

(18) Congdon, E. E., & Sigurdsson, E. M. (2018). Tau-targeting therapies for Alzheimer disease. Nature reviews. Neurology, 14(7), 399–415. https://doi.org/10.1038/s41582-018-0013-z

(19) Cure PSP: Research. Retrieved on 1 July 2020 from https://www.psp.org/iwanttolearn/research/