Progressive Supranuclear Palsy
NORD is very grateful to Rodger J. Elble, MD, PhD, Professor and Chair of Neurology, Director, Parkinson Disease and Movement Disorders Center, Neurology Residency Director, Southern Illinois University School of Medicine, for assistance in the preparation of this report.
Synonyms of Progressive Supranuclear Palsy
- nuchal dystonia dementia syndrome
- Steele-Richardson-Olszewski syndrome
- No subdivisions found.
Progressive supranuclear palsy (PSP) is a rare degenerative neurological disorder characterized by loss of balance and impaired walking; loss of control of voluntary 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 progressive supranuclear palsy is unknown. PSP is often misdiagnosed as Parkinson disease, Alzheimer disease, or other neurodegenerative disorders.
Symptoms associated with progressive supranuclear palsy vary from case to case, but patients generally fall into one of four clinical syndromes (phenotypes): Richardson variant, atypical parkinsonism, corticobasal variant, and pure akinesia and gait freezing.
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 and loss of voluntary eye movement, particularly in the downward direction. The next most common type is atypical parkinsonism, in which rest tremor is usually absent and patients have early impairment of balance and cognition. 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.
The so-called corticobasal variant is rare and may be indistinguishable from corticobasal degeneration, which typically presents with a bizarre stiffening (rigidity and dystonia) and loss of voluntary function in one upper limb. Similar impairment gradually spreads to the other limbs. Speech and cognitive function are usually impaired, particularly in the late stages of the disease. The least common form of PSP is the syndrome of primary akinesia and 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 occur in Parkinson disease, but in contrast to Parkinson disease, there is no slowness (bradykinesia) or muscle stiffness (rigidity).
Involuntary eye closure (blepharospasm), impaired ability to open the eyes (eye opening apraxia), and impaired articulation of speech (dysarthia) and/or swallowing difficulties (dysphagia) are common in PSP. New symptoms can develop during the course of PSP, and previously mild problems tend to become more severe with time. With progression, one variant of PSP typically develops features of the other three variants. Inability to walk, very impaired swallowing and unintelligible speech are common in the late stages of this disease.
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 not be able to open their eyes (eye opening apraxia), even when a spasm stops. Other patients have trouble closing their eyes or may blink less than normal, causing the eyes to become dry and red.
Muscles of the body may contract involuntarily, causing the affect 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 (AD) when it occurs early in the illness, before significant difficulties with speech, balance and eye movements appear. (For more information on Alzheimer disease, please choose "Alzheimer" as your search term in the Rare Disease Database.)
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.
The cause of progressive supranuclear palsy is not known, but it is a form of tauopathy, in which abnormal phosphorylation of the protein tau leads to destruction of vital protein filaments in nerve cells, causing their death. Recent work suggests that the disease is at least partly genetic. Many researchers now believe that various genetic and environmental factors contribute to the development of this disorder.
In the medical literature, the word "tauopathies" is used to refer to several neurodegenerative disorders, including PSP, in which tau is mishandled. Other neurodegenerative disorders classified as tauopathies include corticobasal degeneration, Pick's disease, and frontotemporal dementia.
At least some cases of PSP are thought to be linked to a mutation in the gene MAPT, which helps to produce (codes for) the tau protein. This gene resides on chromosome 17 (17q21.1). In such cases, PSP may be inherited as an autosomal dominant trait, in which each child has a 50:50 chance of inheriting the genetic defect from the affected parent.
PSP is under-diagnosed, so it is difficult to know how many people are affected. This disorder is believed to affect approximately 20,000 people in the United States. However, far fewer cases have been diagnosed. According to some reports, PSP is estimated to affect 1.4 in 100,000 people. The onset of this disorder occurs between 45 and 75 years of age, with the average age of onset at about 63 years. Males are affected more often than females.
Drs. John C. Steele, J.C. Richardson and J. Olszewski identified progressive supranuclear palsy as a distinct neurological disorder in 1963.
Symptoms of the following disorders can be similar to those of progressive supranuclear palsy. Comparisons may be useful for a differential diagnosis.
Corticobasal degeneration (CBD) is a rare progressive neurological disorder characterized by cell loss and shrinkage (atrophy) in certain areas of the brain (cerebral cortex and basal ganglia). The symptoms and signs of this disease resemble some patients with PSP, and many experts believe that CBD and PSP are variations of the same disease.
Multiple system atrophy (MSA) is a rare progressive neurological disorder characterized by a varying combination of parkinsonism and cerebellar ataxia (poorly coordinated limb movement, unsteady gait and dysarthria). Many patients with MSA also develop impaired function of the autonomic nervous system, which controls blood pressure, heart rate, sweating, the bowels and the urinary bladder. The exact cause of multiple system atrophy is unknown. (For more information, choose "multiple system atrophy" as your search term in the Rare Disease Database.)
Shy-Drager syndrome is simply multiple system atrophy with autonomic failure. Most experts no longer use this term (For more information on this disorder, choose "Shy-Drager" as your search term in the Rare Disease Database.)
Parkinson disease is a slowly progressive neurologic condition characterized by involuntary trembling (rest tremor), muscular stiffness or inflexibility (rigidity), slowness of movement (bradykinesia) and difficulty carrying out voluntary movements (akinesia). Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented regions of the brain), causing a decrease in dopamine levels in the brain. Dopamine is a neurotransmitter, which is a chemical that sends a signal from one nerve cell to another in the brain. Parkinson disease progresses much more slowly than PSP and usually is not incapacitating for a decade or more. (For more information on this disorder, choose "Parkinson's" as your search term in the Rare Disease Database.)
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 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, may be of some benefit in relieving symptoms the 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. 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).
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 (intestine) to allow for sufficient feeding.
A study sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) examined the effectiveness and safety of an experimental drug delivered through an investigational device in treating PSP. The drug is called Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (GDNF). It is administered directly into the brain through catheters attached to an infusion pump implanted in the patient’s abdomen. This study has been completed. For more information, go to http://clinicaltrials.gov/ct2/show/NCT00005903.
In the August 12, 1999, issue of the New England Journal of Medicine, Italian researchers reported that a preliminary study on 10 people with progressive supranuclear palsy treated with a short-acting hypnotic drug, Zolpidem, showed improvement of symptoms for a short period of time (i.e., up to two hours). The major side effect of this drug in this study was drowsiness. More research is necessary to determine the long-term safety and effectiveness of this treatment for individuals with PSP. The drug's initial, limited effectiveness may give clues to researchers about the brain chemicals involved with PSP. It may then be possible to study other possible drugs that may have a long lasting therapeutic effect. A 2002 study of Zolpidem indicated that the drug had only a transient effect on symptoms of PSP, yet was promising enough for further investigation.
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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Contact for additional information about progressive supranuclear palsy:
Rodger J. Elble, MD, PhD
Professor and Chair of Neurology
Director, Parkinson Disease and Movement Disorders Center
Neurology Residency Director
Southern Illinois Univeristy School of Medicine
PO Box 19643
Springfield, IL 62794-9643
Phone: (217) 545-7182
FAX: (217) 545-1903
email: firstname.lastname@example.org or email@example.com
Organizations related to Progressive Supranuclear Palsy
Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009;8:270-279.
Williams DR, Lees AJ, Wherrett JR, Steele JC. J. Clifford Richardson and 50 years of progressive supranuclear palsy. Neurology 2008;70:566-573.
Goedert M, Jakes R. Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta. 2005;1739:240-50.
Pelak VS, Hall DA. Neuro-ophthalmic manifestations of neurodegenerative disease. Ophthalmol Clin North Am. 2004;17:311-20.
FROM THE INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Microtubule-Associated Protein Tau; MAPT. Entry No: 157140. Last Updated February 3, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed April 19, 2011.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Supranuclear Palsy, Progressive; 1; PSNP1. Entry No: 601104. Last Updated December 15, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed April 19, 2011.
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Report last updated: 2011/04/19 00:00:00 GMT+0
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