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Last updated:
February 01, 2021
Years published: 1986, 1987, 1988, 1990, 1992, 1996, 1997, 1998, 1999, 2000, 2005, 2008, 2011, 2014, 2017, 2021
NORD gratefully acknowledges Rodger J. Elble, MD, PhD, Professor of Neurology, Director, Parkinson Disease and Movement Disorders Center, Southern Illinois University School of Medicine, for assistance in the preparation of this report.
Summary
Progressive supranuclear palsy (PSP) is an uncommon degenerative neurological disorder that causes progressive impairment of balance and walking; impaired eye movement, especially in the downward direction; abnormal muscle tone (rigidity); speech difficulties (dysarthria); and problems related to swallowing and eating (dysphagia). Affected individuals frequently experience personality changes and cognitive impairment. Symptoms typically begin after age 60 but can begin earlier. The exact cause of PSP is unknown. PSP is often misdiagnosed as Parkinson disease, Alzheimer disease, corticobasal degeneration and other neurodegenerative disorders.
Introduction
Drs. John C. Steele, J.C. Richardson and J. Olszewski identified progressive supranuclear palsy as a distinct neurological disorder in 1963.
The signs and symptoms of PSP vary from person to person, but patients generally fall into one of four clinical syndromes (phenotypes): Richardson syndrome, atypical Parkinsonism, corticobasal syndrome, and pure akinesia and gait freezing. Less commonly, patients present with cognitive loss and no motor signs.
The most common presentation is the Richardson syndrome, consisting of gait and balance impairment, a wide-eyed staring facial expression, abnormal speech, memory and cognitive impairment and a slowing or loss of voluntary eye movement, particularly in the downward direction (supranuclear ophthalmoplegia). Cognitive symptoms include forgetfulness and personality changes, such as loss of interest in formerly pleasurable activities (apathy), impaired attention and concentration, depression, and increased irritability.
Fewer than half of all PSP patients are initially diagnosed correctly because many patients do not present with the classic Richardson syndrome. Many of these patients are initially slow and have muscle rigidity and occasionally tremor, resembling Parkinson disease, and they may initially respond somewhat to levodopa. Other patients present with bizarre stiffening (rigidity and dystonia) and loss of voluntary function in one upper limb, as is seen in corticobasal degeneration.
Some patients exhibit a syndrome of progressive gait freezing. These patients exhibit hesitant initiation of gait and a tendency to freeze or stop when turning and when crossing thresholds (doorways). Their eye movements and cognition are normal. Small handwriting and low-volume rapid, mumbling speech (tachyphemia or cluttered speech) are typical and are similar to that which occurs in Parkinson disease, but in contrast to Parkinson disease, there is no slowness (bradykinesia) or muscle stiffness (rigidity). Finally, some patients with PSP present with cognitive impairment and personality change (frontotemporal dementia), progressive speech and language impairment, generalized ataxia, or generalized spasticity. Most patients with these atypical presentations ultimately develop abnormalities of eye movement, speech, swallowing and gait (Richardson syndrome) in a few years. Thus, the diagnosis of PSP typically becomes more certain as the disease progresses.
The challenge is to diagnose the disease in the very early stages, and this is very difficult in patients that do not have the classic Richardson syndrome. There is no diagnostic laboratory or radiologic test for PSP. Therefore, most patients are diagnosed fairly late in the course of the illness. PSP culminates in death at a median of 6 to 9 years after diagnosis, and those with the Richardson syndrome and dementia progress most rapidly. Death from PSP is most often caused by pneumonia or other infections.
Impaired eye movements eventually make reading, driving, and interpersonal eye contact difficult or impossible. Abnormal eyelid control causes the eyes to close involuntarily (blepharospasm) for seconds or more, and some affected individuals may have difficulty opening their eyes after closure (eye opening apraxia), even though the muscles around the eyes appear relaxed. Patients often blink less than normal, causing the eyes to become dry and red.
Muscles of the body may contract involuntarily, causing the affected body part (e.g., the upper or lower limbs) to assume bizarre postures. This is called dystonia. Blepharospasm is a form of dystonia affecting the muscles around the eyes.
A mild or moderate degree of mental impairment eventually occurs in most patients, and this may be misdiagnosed as Alzheimer disease when it occurs early in the illness, before significant difficulties with speech, balance and eye movements appear.
Some patients experience sleep disturbances such as frequent awakenings and changes in sleeping patterns. Sleep disturbances may be a sign of depression or may be a side effect of a medication. REM (rapid eye movement) sleep behavior disorder is not a characteristic of PSP but is a characteristic of dementia with Lewy bodies, Parkinson disease and multiple system atrophy. In REM sleep behavior disorder, patients talk and move during dream sleep, and the movement can result in personal injury or injury to a bed partner.
The cause of PSP is not known, but it is a form of tauopathy, in which abnormal phosphorylation of the protein tau is associated with destruction of vital protein filaments in nerve cells. This “neurofibrillary” degeneration is hypothesized to cause the death of nerve cells, and most experimental treatments are aimed at preventing tau pathology. The signs and symptoms of PSP are determined by the distribution of tau pathology in the brain. Recent work suggests that the disease is at least partly genetic. Many researchers now believe that various genetic and environmental factors interact to produce this disorder.
In the medical literature, the word “tauopathy” is used to refer to several neurodegenerative disorders including PSP, in which tau are mishandled. Other neurodegenerative disorders classified as tauopathies include corticobasal degeneration and Pick disease. Alzheimer disease also produces tau pathology.
Genetics plays an important role in PSP even though most patients have no family history of PSP. Rare mutations in the gene for the microtubule-associated protein tau (MAPT) appear to cause PSP in rare patients, and risk of PSP is determined to some extent by genetic variation in this gene. Variants of least three other genes (STX6, EIF2AK3, and MOBP) are also associated with an increased the risk of developing PSP. The study of genetic mechanisms should eventually lead to effective medical therapies.
PSP is under-diagnosed, so it is difficult to know how many people are affected. This disorder is believed to affect at least 20,000 people in the United States. According to some reports, PSP is estimated to affect as many as 5-17 in 100,000 people, but recent autopsy studies found PSP pathology in 2-6% of elderly people that had no diagnosis of PSP before death. The onset of this disorder occurs between 45 and 75 years of age, with the average age of onset at about 63 years. Men and women are affected more or less equally.
The diagnosis of progressive supranuclear palsy may be suspected based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic physical findings.
Treatment
Treatment of progressive supranuclear palsy is symptomatic and supportive. There is no cure at the present time. In some cases, drugs used to treat Parkinson disease (antiparkinsonian agents), such as levodopa, are beneficial in relieving symptoms of slowness, but the effect is usually limited and temporary. Antidepressant medications are of some benefit in some cases. The use of these drugs should be monitored carefully by a neurologist experienced in their administration.
Walking aids such as a walker weighted in front and wearing shoes with built-up heels may help in preventing affected individuals from falling backwards. Periodic evaluations by physical therapy, occupational therapy and speech therapy are helpful in maximizing quality of life. Bifocals or special glasses with prisms may be prescribed for some individuals with PSP to treat certain difficulties in eyesight (i.e., difficulty looking down). Botulinum toxin injections are helpful in treating blepharospasm.
When a patient can no longer swallow, a surgical procedure known as percutaneous gastrostomy can be performed, depending upon the patient’s wishes and quality of life. In this procedure, a tube is placed through the skin of the abdomen into the stomach to allow sufficient feeding.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
REVIEW ARTICLES
Coughlin DG, Litvan I. Progressive supranuclear palsy: advances in diagnosis and management. Parkinsonism Relat Disord 2020;73:105-116.
Wen Y, Zhou Y, Jiao B, Shen L. Genetics of progressive supranuclear palsy: a review. J Parkinsons Dis 2020:1-13.
Shoeibi A, Olfati N, Litvan I. Frontrunner in translation: progressive supranuclear palsy. Front Neurol 2019;10.
Boxer AL, Yu JT, Golbe LI, Litvan I, Lang AE, Hoglinger GU. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Lancet Neurol 2017;16:552-563
INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Microtubule-Associated Protein Tau; MAPT. Entry No: 157140. Last Updated08/14/2020. Available at: https://omim.org/entry/157140 Accessed Jan 26, 2021.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Supranuclear Palsy, Progressive; 1; PSNP1. Entry No: 601104. Last Updated02/14/2019. Available at: https://omim.org/entry/601104?search=601104&highlight=601104 Accessed Jan 26, 2021.
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