Progressive Supranuclear Palsy
Progressive supranuclear palsy
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, Woodholme Medical Building. 1838 Greene Tree Road, #515, Baltimore, MD 21208. (410) 486-3330 or 800-457-4777; Fax: (410) 486-4383. spsp@psp.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
Progressive Supranuclear Palsy
Progressive Supranuclear Palsy
Definition
Progressive supranuclear palsy (PSP; also known as Steele-Richardson-Olszewski syndrome) is a rare disease that gradually destroys nerve cells in the parts of the brain that control eye movements, breathing, and muscle coordination. The loss of nerve cells causes palsy, or paralysis, that slowly gets worse as the disease progresses. The palsy affects ability to move the eyes, relax the muscles, and control balance.
Description
Progressive supranuclear palsy is a disease of middle age. Symptoms usually begin in the 60s, rarely before age 45 or after age 75. Men develop PSP more often than women do. It affects three to four people per million each year.
Causes and symptoms
PSP affects the brainstem, the basal ganglia, and the cerebellum. The brainstem is located at the top of the spinal cord. It controls the most basic functions needed for survival-the involuntary (unwilled) movements such as breathing, blood pressure, and heart rate. The brainstem has three parts: the medulla oblongata, the pons, and the midbrain. The parts affected by PSP are the pons, which controls facial nerves and the muscles that turn the eye outward, and the midbrain, the visual center. The basal ganglia are islands of nerve cells located deep within the brain. They are involved in the initiation of voluntary (willed) movement and control of emotion. Damage to the basal ganglia causes muscle stiffness (spasticity) and tremors. The cerebellum is located at the base of the skull. It controls balance and muscle coordination.
Vision is controlled by groups of cells called nuclei in the brainstem. In PSP, the nuclei continue to function, but the mechanisms that control the nuclei are destroyed. The term supranuclear means that the damage is done above (supra ) the nuclei. Patients with PSP have difficulty with voluntary (willed) eye movement. At first, the difficulty only occurs in trying to look down. As the disease progresses, ability to move the eyes right and left is also affected. However, reflex or unwilled eye movements remain normal. Thus, when the patient's head is tilted upwards, the eyes move to look down. These reflex movements remain normal until late in the course of the disease. The upper eyelids may be pulled back, the eyebrows raised, and the brow wrinkled, causing a typical wide-eyed stare. Rate of blinking may decrease from the normal 20-30 per minute to three to five per minute. It becomes difficult to walk downstairs, to maintain eye contact during conversation, or to move the eyes up and down to read.
The earliest symptoms of PSP may be frequent falls or stiff, slow movements of the arms and legs. These symptoms may appear as much as five years before the characteristic vision problems. Walking becomes increasingly awkward, and some patients tend to lean and fall backward. Facial muscles may be weak, causing slurred speech and difficulty swallowing. Sleep may be disturbed and thought processes slowed. Although memory remains intact, the slowed speech and thought patterns and the rigid facial expression may be mistaken for senile dementia or Alzheimer's disease. Emotional responses may become exaggerated and inappropriate, and the patient may experience anxiety, depression, and agitation.
The cause of PSP is not known. Most people who develop PSP come from families with no history of the disease, so it does not seem to be inherited, except in certain rare instances. People who have PSP seem to lack the neurotransmitters dopamine and homovanillic acid in the basal ganglia. Neurotransmitters are chemicals that help carry electrical impulses along the nervous system. Transmitting structures in brain cells called neurofibrils become disorganized (neurofibrillary tangles). Neurofibrillary tangles are also found in Alzheimer's disease, but the pattern is somewhat different.
Diagnosis
PSP is sometimes mistaken for Parkinson's disease, which is also associated with stiffness, frequent falls, slurred speech, difficulty swallowing, and decreased spontaneous movement. The facial expression in Parkinson's, however, is blank or mask-like, whereas in PSP it is a grimace and wide-eyed stare. PSP does not cause the uncontrolled shaking (tremor) in muscles at rest that is associated with Parkinson's disease. Posture is stooped in Parkinson's disease, but erect in PSP. Speech is of low volume in both diseases, but is more slurred and irregular in rhythm in PSP.
Multiple strokes or abnormal accumulations of fluid within the skull (hydrocephalus ) can also cause balance problems similar to PSP. Magnetic resonance imaging (MRI) scans of the brain may be needed to rule out these conditions. In advanced cases, MRI shows characteristic abnormalities in the brainstem described as "mouse ears."
Treatment
PSP cannot be cured. Drugs are sometimes given to relieve symptoms, but drug treatment is usually disappointing. Dopaminergic medications used in Parkinson's disease, such as levodopa (Sinemet), sometimes decrease stiffness and ease spontaneous movement. Anticholinergic medications, such as trihexyphenidyl (Artane), which restore function to neurotransmitters, or tricyclic drugs, such as amitriptyline (Elavil) may improve speech, walking, and inappropriate emotional responses.
Speech therapy may help manage the swallowing and speech difficulty in PSP. As the disease progresses, the difficulty in swallowing may cause the patient to choke and get small amounts of food in the lungs. This condition can cause aspiration pneumonia. The patient may also lose too much weight. In these cases, a feeding tube may be needed. The home environment should be modified to decrease potential injury from falls. Walkers can be weighted in front, to prevent backward falls and handrails can be installed in the bathroom. Because the patient cannot look down, low objects like throw rugs and coffee tables should be removed. Dry eyes from infrequent blinking can be treated with drops or ointments.
KEY TERMS
Basal ganglia— Brain structure at the base of the cerebral hemispheres, involved in controlling movement.
Brainstem— Brain structure closest to the spinal cord, involved in controlling vital functions, movement, sensation, and nerves supplying the head and neck.
Cerebellum— The part of the brain involved in coordination of movement, walking, and balance.
Magnetic resonance imaging (MRI)— An imaging technique that uses a large circular magnet and radio waves to generate signals from atoms in the body. These signals are used to construct images of internal structures.
Parkinson's disease— A slowly progressive disease that destroys nerve cells. Parkinson's is characterized by shaking in resting muscles, a stooping posture, slurred speech, muscular stiffness, and weakness.
Prognosis
The patient's condition gradually deteriorates. After about seven years, balance problems and stiffness make it nearly impossible for the patient to walk. Persons with PSP become more and more immobile and unable to care for themselves. Death is not caused by the PSP itself. It is usually caused by pneumonia related to choking on secretions or by starvation related to swallowing difficulty. It usually occurs within 10 years, but if good general health and nutrition are maintained, the patient may survive longer.
Prevention
PSP cannot be prevented.
Resources
ORGANIZATIONS
American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. 〈http://www.aan.com〉.
Society for Progressive Supranuclear Palsy, Inc. Suite #5065 Johns Hopkins Outpatient Center, 601 N. Caroline St., Baltimore, MD 21287. (800) 457-4777. 〈http://www.psp.org〉.