Definition
Progressive supranuclear palsy (PSP) is a rare degenerative disorder that causes serious and permanent deficits in movement and cognitive function.
Description
Progressive supranuclear palsy is also known as Steele-Richardson-Olszewski syndrome, reflecting the names of persons who discovered the syndrome. PSP is a neurodegenerative disease (symptoms worsen with time) first described as a distinct disorder in 1964. Characteristics of PSP include slow movement and stiffness, which are also seen similarly in Parkinson's Disease (PD). Persons affected by PSP tend to have more postural imbalance with falls than patients with PD. Additionally tremor is usually absent in PSP patients, while those with PD have tremor. PSP is an uncommon disorder and initially it may be difficult to clinically distinguish between PSP and PD. PSP usually begins to produce symptoms in the sixth decade (50–59 years of age) of life and the disorder progressively worsens more quickly than PD. Patients with PSP typically become disabled within five to ten years after diagnosis (PD has a slower progression and typically persons can become disabled 20 years after onset). PSP is the most common Parkinson-like or Parkinson-plus disease.
Demographics
The estimated prevalence (number of existing cases) among persons older than 55 years is approximately seven per 100,000 persons. Studies indicate that there may be a slightly higher male prevalence (1.53), than female prevalence (1.23) per 100,000. In Perth, Australia, the incidence (number of new cases) is estimated at three to four per million cases. The incidence rate for ages 50-99 is 5.3 per 100,000. The peak incidence (the peak age range for new cases) is in the early sixties. PSP is not thought to be genetically transmitted in families, but there are some reported cases of inherited transmission. Survey research (using a questionnaire) in 1996 revealed that patients with PSP were less likely than controls to have completed 12 years of education, which suggests that education level is a marker for direct risk factors which can include chemical exposure or nutritional problems. In 1999 a high prevalence of PSP was found in Guadeloupe (French West Indies) which is related to ingestion of certain teas that are forms of custard apple (called "soursop" and "sweetsop").
Causes and symptoms
The cause of degeneration of nerve cells is unknown. Patients affected with PSP have a gradual and progressive damage to cells in the midbrain, which eventually leads to atrophy (shrinkage and loss of normal cell architecture). Patients have neuronal loss and neurofibrillary tangles in the diencephalon, brain stem and basal ganglia. Several theories have been proposed as potential causes. Initially, the main causes of PSP was thought to be due to a virus (possibly related to the influenza virus) or to a slow acting toxin (i.e. "MPTP", a drug of abuse contaminant, herbal Caribbean teas, Cycad nut poisoning in Guam).
However, recent genetic research as of 1999 suggests PSP may be a genetic disorder transmitted with autosomal recessive transmission. The gene implicated with the condition is called the tau gene. Analysis of the tau gene using molecular biology techniques indicate that the tau gene in PSP is different from genes observed in Alzheimer disease patients. Studies indicate that the tau gene in PSP is similar to the gene in another disease (Cortico basal degeneration). These genetic studies indicate that some nerve cells may be partially controlled by genetic susceptibility and also related to other environmental stressors/triggers such as viruses and/or toxins.
The symptoms of PSP are insidious and typically there is a prolonged phase of headaches, dizziness, fatigue, arthralgias and depression. The most common symptoms include postural instability and falls (seen in 63% of patients) and dyarthria (a symptom expressed in 35% of patients). Other important symptoms include bradykinesia and visual disturbance (diplopia, burning eyes, blurred vision and sensitivity to light) in 13% of affected PSP patients. The front neck muscles or back neck muscles may be affected. The rigidity of the spine is characterized by a stiff extended spine. PSP patients also exhibit eye movement paralysis. The eye lids may be held wide open with eye movement paralysis resulting in a facial expression that can be described as "staring," "astonished," or "puzzled."
Eye movement difficulties usually begin with difficulty looking up or down. There may be difficulty looking right or left. These eye abnormalities may cause difficulty during driving and reading. There is no treatment for eye movement abnormalities. Patients with PSP do not have eye muscle or eye nerve problems; the problem originates in the brain stem area.
Diagnosis
Lab tests and neuroimaging can be performed to eliminate other possible causes. One specific high resolution neuroimaging study called PET (positron emission tomography) scan can provide information about blood flow and oxygen supply to the brain. PET scan analysis has revealed a decrease in blood flow and oxygen metabolism in areas of the brain thought to degenerate in PSP patients (i.e. caudate, putamen and thalamus). Sleep patterns in PSP affected patients are often abnormal and demonstrated increased awakenings, diminished total sleep time, and progressive loss of REM sleep. Patients can also develop REM sleep behavior disorder consisting of abnormal motor activity with vivid dreams during REM sleep.
Autopsy results after examination of brain tissue reveals neuronal loss and neurofibrillary tangles and gliosis in the reticular formation and ocular (eye) motor nuclei, as well as neuronal pathology in the midbrain. MRI neuroimaging studies can detect abnormal patterns in affected areas within the brain.
Treatment team
As the disease progresses, specialists are required as part of the treatment team. Consultation with rehabilitation medicine specialist may help with walking stability and safety. A speech therapist may modify diet if swallowing is impaired. Consultation with an eye specialist (ophthalmologist) may be indicated for the treatment of eye problems.
Treatment
There is no effective therapy for PSP. Mediation generally has little or short term effects. Treatment is supportive (palliative) until the person dies. Supportive treatment can include speech therapy, walkers, antidepressants, artificial tears (to avoid drying of eyes from excess exposure) and caregiver support. Only few persons demonstrate benefit with medication that increases the neurotransmitters dopamine (dopaminergic) or acetylcholine (cholinergic drugs). A well balanced diet is recommended and gastrostomy (a surgical procedure to redirect bowels to pass through an opening in the stomach) is performed when feeding becomes problematic due to dysphagia (difficulty swallowing), or risk of bronchoaspiration (food lodging in the lungs due to abnormal swallowing) is possible.
Recovery and rehabilitation
PSP is a chronic and progressive disorder which means that symptoms worsen with the passing of time. Close follow-up care is advisable, and during visits it is necessary to provide family with direction and education. If the patient opts for experimental treatment protocols, it is mandatory to inform all concerned about potential side effects. Physical therapy involvement can help to maximize safety at home and provide instruction in the use of walking aids (i.e. wheelchair, walker).
Clinical trials
The National Institute of Neurological Disorders and Stroke (NINDS) are currently sponsoring research concerning diagnosis, treatment and causes of PSP. Additionally, studies concerning Parkinson's and Alzheimer's disease are being performed since a better understanding of related diseases may provide valuable information concerning PSP.
Prognosis
In most patients the disease is fatal within six to 10 years. Complications of PSP are related to abnormal balance, immobility (a late feature of PSP) and decreased cognition. Falls may cause patients to injure bones. Late onset immobility can cause infectious complications (pneumonia, urinary tract infection, or sepsis).
Special concerns
A well balanced diet is recommended and physical therapy may help with walking problems and falls which are the two major causes of disability. Educational concerns are important and should be directed to the patient, family members and caregivers. Education includes an understanding of the natural history of PSP and should include information concerning prognosis, complications, supportive therapy. Patients and families may benefit from PSP support group involvement.
Resources
BOOKS
Goetz, Christopher G., et al., eds. Textbook of Clinical Neurology, 1st ed. Philadelphia: W. B. Saunders Company, 1999.
Goldman, Lee, et al. Cecil's Textbook of Medicine, 21st ed. Philadelphia: W. B. Saunders Company, 2000.
PERIODICALS
Litvan, Irene. "Diagnosis and Mangement of Progressive Supranuclear Palsy." Seminars in Neurology 21 (2001).
WEBSITES
Hain, Timothy C. Progressive Supranuclear Palsy.http://neuronwu.edu/meded/MOVEMENT/psp2.htm.
Progrssive Supranuclear Palsy.http://healthlink.mcw.edu/article.922569615.html.
Progressive Supranuclear Palsy.http://health.allrefer.com.
Progressive Supranuclear Palsy Fact Sheet.http://www.ninds.nih.gov/health_and_medical/pubs/psp.htm.
Progressive Supranuclear Palsy.http://www.cmdg.org.
ORGANIZATIONS
Society for Progressive Supranuclear Palsy, Executive Plaza III, 11350 McCormick Road, Suite 906, Hunt Valley, MD 21031. toll free: 800-457-4777, phone: 410-785-7004, fax: 410-785-7009. e-mail: info@curepsp.org. http://www.psp.org.
The PSP Association, The Old Rectory, Wappenham, Towcester, Northants NN12 8SQ, United Kingdom. 011-44-1327-860299; Fax: 011-44-1327-861007. psp.eur@virgin.net. http://www.pspeur.org.
Laith Farid Gulli, MD
Nicole Mallory, MS, PA-C
