CHAPTER 119
Movement Disorders
Every body movement, from raising a hand to smiling, involves a complex interaction between the central nervous system (brain and spinal cord), nerves, and muscles. Damage to or malfunction of any of these components may result in a movement disorder.
Different types of movement disorders can develop, depending on the nature and location of the damage or malfunction, as in the following:
Damage to the parts of the brain that control voluntary movement or the connections between the brain and spinal cord: Weakness or paralysis of the muscles involved in voluntary movements and exaggerated reflexes
Damage to the basal ganglia (collections of nerve cells located at the base of the cerebrum, deep within the brain): Involuntary or decreased movements, but not weakness or changes in reflexes
Damage to the cerebellum: Loss of coordination
Some movement disorders, such as hiccups, are temporary, usually causing little inconvenience. Others, such as Parkinson’s disease, are serious and progressive, impairing the ability to speak, use the hands, walk, and maintain balance when standing.
Myoclonus
Myoclonus refers to quick, lightning-like jerks (contractions) of a muscle or a group of muscles.
Myoclonus may involve only one hand, a group of muscles in the upper arm or leg, or a group of facial muscles. Or it may involve many muscles at the same time. Hiccups are a type of myoclonus that involves only the diaphragm, the muscle that separates the chest from the abdomen.
Myoclonus may occur normally, often when a person is falling asleep. Or it may result from a disorder, such as the following:
Hiccups: Spasms of the Diaphragm
Almost everyone has had hiccups, so hiccups are hardly thought of as a movement disorder. But they are. They occur when there are spasms of the diaphragm, followed by quick, noisy closings of the glottis. (The diaphragm is the muscle that separates the chest from the abdomen and that is responsible for each breath. The glottis is the opening between the vocal cords, which closes to stop the flow of air to the lungs.) Hiccups are more likely to occur when carbon dioxide levels in the blood decrease. Such a decrease can occur when people hyperventilate.
Most bouts of hiccups have no obvious cause. They usually start in a social situation, perhaps triggered by some combination of laughing, talking, eating, and drinking. Sometimes hot or irritating food or liquids are the cause. Some less common causes of hiccups are more serious. For example, the diaphragm may become irritated because of pneumonia, chest or stomach surgery, or waste products that accumulate in the blood when the kidneys malfunction. Rarely, hiccups develop when a brain tumor or stroke interferes with the breathing center in the brain.
Hiccups usually begin suddenly and stop after several seconds or minutes, but occasionally, they persist for some time, even in healthy people. When the cause is serious, hiccups tend to persist until the cause is corrected. Hiccups due to a brain tumor or stroke may be very hard to stop and may become exhausting.
Many home remedies have been used to cure hiccups. Most involve ways to raise the level of carbon dioxide in the blood, such as the following:
Holding the breath
Breathing into a paper (not plastic) bag
Stimulating the vagus nerve, which runs from the brain to the stomach, may stop the hiccups. The following can stimulate this nerve:
Drinking water quickly
Swallowing dry bread or crushed ice
Gently pulling on the tongue
Gently rubbing the eyeballs
For most people with hiccups, any of these remedies work.
For persistent hiccups, treatment is needed, particularly when the cause cannot be easily corrected. Several drugs have been used with varying success. They include scopolamine, prochlorperazine, chlorpromazine, baclofen, metoclopramide, and valproate.
Liver failure
Kidney failure
Cardiac arrest (when the heart’s pumping stops suddenly)
Brain damage due to a virus (viral encephalopathy)
Metabolic disorders (such a high or low blood sugar level)
Oxygen deprivation
Head injuries
Alzheimer’s disease (occasionally)
Creutzfeldt-Jakob disease
Juvenile myoclonic epilepsy (which causes seizures)
Myoclonus can occur after a person takes high doses of certain drugs such as antihistamines, some antidepressants (such as amitriptyline), bismuth, levodopa, or opioids (narcotics).
Symptoms
Myoclonus can be mild or severe. Muscles may jerk quickly or slowly, rhythmically or not. Myoclonus may occur once in a while or frequently. It may occur spontaneously or be triggered by a stimulus, such as a sudden noise, light, or a movement. For example, reaching for an object or taking step may trigger jerks that disrupt the movement. In Creutzfeldt-Jacob disease (a rare degenerative brain disorder—see page 766), myoclonus becomes more obvious when people are suddenly startled. If myoclonus is due to a metabolic disorder, it may persist and affect muscles throughout the body, sometimes leading to seizures.
Did You Know…
Some types of myoclonus—hiccups and the quick twitches of muscles as a person falls asleep—are normal.
Diagnosis and Treatment
The diagnosis is based on symptoms. Other tests may be done to identify the cause.
The cause is corrected if possible. For example, drugs that can cause myoclonus are stopped. A high or low blood sugar level is corrected, and kidney failure is treated with hemodialysis. If the cause cannot be corrected, valproate or levetiracetam (anticonvulsants—see table on page 716) or clonazepam (a mild sedative) sometimes helps. When given with carbidopa, the dietary supplement 5-hydroxytryptophan (which is produced by the brain) may also help.
Tremor
A tremor is an involuntary, rhythmic, shaking movement produced when muscles repeatedly contract and relax.
Everyone has a tremor to some degree. For example, when held outstretched, the hands usually tremble slightly. Such slight, rapid tremor, called physiologic tremor, is normal and reflects the precise moment-by-moment control of muscles by nerves. In most people, the tremor is too slight to be noticed.
Factors that can make a normal tremor more noticeable include stress, anxiety, fatigue, withdrawal of alcohol or certain other drugs (such as opioids), an overactive thyroid gland (hyperthyroidism), consumption of caffeine, and use of certain drugs, including theophylline and beta-adrenergic agonists such as albuterol (which are used to treat asthma), corticosteroids, and valproate (an anticonvulsant).
Types of Abnormal Tremors
There are several types of abnormal tremor. Tremors are classified according to the following:
How fast the shaking movements are (frequency)
How wide (amplitude) they are, ranging from fine to coarse
How often the tremors occur
How severe they are
What triggers them, such as rest or movement
What causes them
Tremors triggered by rest are called resting tremors. Tremors triggered or made worse by movement are called action tremors. Action tremors can be classified as intention tremors (triggered by aiming for a target) or postural tremors (triggered by holding a limb in one position). Causes are classified as physiologic, essential, cerebellar, or secondary. Secondary tremors are caused by disorders or drugs.
Resting Tremor: This tremor occurs when muscles are at rest, making an arm or a leg shake even when a person is completely relaxed. The tremor becomes less noticeable or disappears when the person moves the affected muscles. Resting tremors are often slow and coarse.
These tremors develop when collections of nerve cells at the base of the cerebrum (including the basal ganglia) are disturbed. Such disturbances usually result from Parkinson’s disease. Antipsychotic drugs are another common cause of resting tremors.
Resting tremors may be socially embarrassing but typically do not interfere with daily activities, such as drinking a glass of water.
Intention Tremor: This tremor occurs when a person ends a purposeful movement (such as pressing a button) or aims for a target (as when reaching for an object with the hand). The person may miss the targeted object because of the tremor. Intention tremors are relatively slow and coarse.
These tremors may result from damage to the cerebellum or its connections. Thus, cerebellar tremors and intention tremors may be used synonymously. Multiple sclerosis is a common cause. Stroke, Wilson’s disease, alcoholism, and overuse of sedatives or anticonvulsants can cause the cerebellum to malfunction, resulting in an intention tremor.
Postural Tremor: This tremor occurs when an arm or a leg is held in one position against gravity, as when a person holds the arms outstretched in front of the body.
If the tremor develops gradually, it is usually a physiologic or essential tremor. If a postural tremor starts more suddenly, the cause may be a toxin, a disorder (such as hyperthyroidism), withdrawal of alcohol or a drug, or use of certain drugs.
Essential Tremor: This tremor usually begins in early adulthood but can begin at any age. The tremor slowly becomes more obvious and becomes more noticeable as people age. Thus, it is sometimes incorrectly called senile tremor. It is usually rapid and fine but may be slow, coarse, or both.
Some forms of essential tremor, called benign hereditary tremor, run in families. What causes essential tremors is unknown, but these tremors (while they can be disabling if severe) do not indicate a serious disorder.
Essential tremor can affect the hands, head, and voice. Usually, the tremor stops during rest and worsens when the limbs are held in uncomfortable positions. The tremor often becomes obvious when the limbs are outstretched. For example, a tremor of the hand or wrist may become obvious when the wrist is bent upward and the fingers are spread apart. The tremor typically affects both sides of the body but may affect one side more than the other. Sometimes the head trembles and bobs, and the voice becomes shaky.
Any factor that makes normal (physiologic) tremors worse (such as stress, fatigue, or consumption of caffeine) can make essential tremors more noticeable. Drinking alcohol usually makes the tremor less noticeable.
Usually, essential tremor remains mild. However, it can be troublesome and embarrassing. It can affect handwriting and make using utensils difficult. In some people, the tremor gradually worsens over time, eventually resulting in disability.
Asterixis: Asterixis resembles a tremor but is not one. Asterixis occurs when a group of contracted muscles suddenly and temporarily goes limp. For example, when the arms and hands are outstretched, the hands suddenly drop, then resume their original position. The movements are repetitive, coarse, slow, and not rhythmic.
Asterixis commonly results from liver failure and so has been called liver flap. Asterixis may also result from kidney failure, use of certain drugs, or brain damage (encephalopathy) due to a metabolic disorder. It is often accompanied by tremors and myoclonus (see page 768).
Did You Know…
Everyone has tremors to some degree.
Simple, common-sense measures can make functioning with noticeable tremors easier.
Diagnosis
If a noticeable tremor develops, it should be evaluated by a doctor. A doctor can usually identify the type of tremor by its characteristics. The type of tremor determines which diagnostic tests are done.
Resting tremor: A complete neurologic evaluation is done to check for Parkinson’s disease. Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain may be done.
Intention tremor: An imaging procedure, such as CT or MRI, is often done to look for damage to the brain, especially the cerebellum.
Postural tremor: If symptoms develop suddenly, the doctor asks about the drugs the person is taking, and tests may be done to check for other disorders, such as thyroid disorders. CT or MRI may also be done.
Essential tremor: The doctor asks what drugs the person is using, whether the person is experiencing anxiety or stress, and whether an alcoholic beverage makes the tremor less noticeable. A blood test to check for hyperthyroidism is done.
Asterixis: Blood tests are done to determine whether a liver, kidney, or metabolic disorder is the cause.
Treatment
For mild tremor, no treatment is needed. If tremors become bothersome, some simple measures can help:
Grasping objects firmly and holding them close to the body to avoid dropping them
Avoiding uncomfortable positions
Not eating soup in public
Using assistive devices, as instructed by an occupational therapist
Assistive devices may include rocker knives, utensils with large handles, and, particularly if the tremor is severe, button hooks, Velcro fasteners (instead of buttons or shoe laces), zipper pulls, straws, and shoe horns.
For physiologic or essential tremor, eliminating or minimizing the trigger may lessen the tremor. For example, treating hyperthyroidism may help. Drinking alcohol in moderation may lessen the tremor. However, heavy drinking followed by stopping it suddenly makes the tremor worse. If many daily activities (such as using utensils and drinking from a glass at mealtime) become difficult or if the person’s work requires steady hands, drugs are used. Treatment may include a beta-blocker (such as propranolol), the anticonvulsant primidone, or both.
If due to Parkinson’s disease, a resting tremor is treated as part of that disease. Drugs with anticholinergic effects such as trihexyphenidyl and benztropine usually help control the tremor.
Intention tremors are difficult to treat, but if the condition affecting the cerebellum can be corrected, the tremor may resolve. If the condition cannot be corrected, a therapist may put wrist and ankle weights on the affected limb to reduce the tremor. Or people may be taught to brace the limb during activity. These measures sometimes help.
Deep Brain Stimulation: Tiny electrodes are placed in the area of the brain involved in tremors. The electrodes deliver a painless shock to block the impulses causing tremors. Deep brain stimulation is sometimes done when drugs cannot control a severe, disabling essential tremor or a resting tremor. For essential tremors, the thalamus (a collection of nerve cells at the base of the brain) is stimulated. For resting tremors, the thalamus or subthalamic nucleus (located below the thalamus) is stimulated. Such procedures are available only at special centers.
Parkinson’s Disease
Parkinson’s disease is a slowly progressive degenerative disorder of the central nervous system. It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone (rigidity), slowness of voluntary movements, and difficulty maintaining balance (postural instability). Many people develop dementia.
Parkinson’s disease results from degeneration in the part of the brain that helps coordinate movements.
Usually, the most obvious symptom is tremors that occur when muscles are relaxed.
Muscles become stiff, movements become slow and uncoordinated, and balance is easily lost.
Doctors base the diagnosis on symptoms.
Changes in lifestyle, drugs (such as levodopa plus carbidopa), and sometimes surgery help lessen symptoms, but the disease is progressive, eventually causing severe disability and immobility.
Parkinson’s disease affects about 1 of 250 people older than 40, about 1 of 100 people older than 65, and about 1 of 10 people older than 80. It commonly begins between the ages of 50 and 79. Rarely, Parkinson’s disease occurs in children or adolescents.
When the brain initiates an impulse to move a muscle (for example, to lift an arm), the impulse passes through the basal ganglia (collections of nerve cells located deep within the brain). The basal ganglia help smooth out muscle movements and coordinate changes in posture. Like all nerve cells, those in the basal ganglia release chemical messengers (neurotransmitters) that trigger the next nerve cell in the pathway to send an impulse. A key neurotransmitter in the basal ganglia is dopamine. Its overall effect is to increase nerve impulses to muscles. In Parkinson’s disease, nerve cells in part of the basal ganglia (called the substantia nigra) degenerate, reducing the production of dopamine and the number of connections between nerve cells in the basal ganglia. As a result, the basal ganglia cannot smooth out movements as they normally do, leading to tremor, loss of coordination, slow movement (bradykinesia), and a tendency to move less (hypokinesia).
Did You Know…
Symptoms of Parkinson’s disease can be caused by many other disorders and drugs.
Parkinson’s disease is sometimes hard to diagnose in older people because aging causes some of the same symptoms.
Early in Parkinson’s disease, delaying levodopa (the most useful treatment) is sometimes the best approach.
What causes Parkinson’s disease is unclear. According to one theory, Parkinson’s disease may result from abnormal deposits of synuclein (a protein in the brain that helps nerve cells communicate). These deposits, called Lewy bodies, can accumulate in several regions of the brain, particularly in the substantia nigra (deep within the cerebrum) and interfere with brain function. Lewy bodies often accumulate in other parts of the brain and nervous system, suggesting that they may be involved in other disorders. In Lewy body dementia, Lewy bodies form throughout the outer layer of the brain (cerebral cortex). Lewy bodies may also be involved in Alzheimer’s disease.
About 15 to 20% of affected people have relatives who have had Parkinson’s disease. Thus, genetics may play a role.
Parkinsonism refers to symptoms of Parkinson’s disease (such as slow movements and tremors) when they are caused by another condition. Various conditions can cause parkinsonism (see page 777).
Symptoms
Usually, Parkinson’s disease begins subtly and progresses gradually. In about two thirds of people, tremors are the first symptom. In others, the first symptom is usually problems with movement or a reduced sense of smell.
Parkinson’s disease typically causes the following symptoms:
Tremors: Tremors are coarse and rhythmic. They usually occur in one hand while the hand is at rest (a resting tremor). The tremor is called a pill-rolling tremor because the hand moves as if it is rolling small objects around. The tremor decreases when the hand is moving purposefully and disappears completely during sleep. Emotional stress or fatigue may worsen the tremor. The tremor may eventually progress to the other hand, the arms, and the legs. A tremor may also affect the jaws, tongue, forehead, and eyelids, but not the voice. In some people, a tremor never develops.
Stiffness (rigidity): Muscles become stiff, impairing movement. When the forearm is bent back or straightened out by another person, the movement may feel stiff and ratchet-like (called cogwheel rigidity).
Slowed movements: Movements become slow and difficult to initiate, and people tend to move less. Thus, mobility decreases.
Difficulty maintaining balance and posture: Posture becomes stooped, and balance is difficult to maintain, leading to a tendency to fall forward or backward. Because movements are slow, people often cannot move their hands quickly enough to break a fall.
Walking becomes difficult, especially taking the first step. Once started, people often shuffle, taking short steps, keeping their arms bent at the waist, and not swinging their arms. While walking, some people have difficulty stopping or turning. When the disease is advanced, some people suddenly stop walking because they feel as if their feet are glued to the ground (called freezing). Other people unintentionally and gradually quicken their steps, breaking into a stumbling run to avoid falling. This symptom is called festination.
Stiffness and decreased mobility can contribute to muscle ache and fatigue. Because the small muscles of the hands are often impaired, daily tasks, such as buttoning a shirt and tying shoelaces, become increasingly difficult. Most people with Parkinson’s disease have shaky, tiny handwriting (micrographia) because initiating and sustaining each stroke of the pen is difficult. Sensation and strength are usually normal.
The face becomes less expressive (masklike) because the facial muscles that control expression do not move. This lack of expression may be mistaken for depression, or it may cause depression to be overlooked. (Depression is common among people with Parkinson’s disease.) Eventually, the face can take on a blank stare with the mouth open, and the eyes may not blink often. Often, people drool or choke because muscle rigidity in the face and throat makes swallowing difficult. People with Parkinson’s disease often speak softly in a monotone and may stutter because they have difficulty articulating words.
Parkinson’s disease also causes other symptoms:
Insomnia is common, often because people need to urinate frequently or because symptoms worsen during the night, making turning over in bed difficult. Rapid-eye-movement (REM) sleep behavior disorder commonly develops. In this disorder, the limbs, which normally do not move in REM sleep, may move suddenly and violently, sometimes injuring a sleep partner. Lack of sleep may contribute to depression and drowsiness during the day.
Urination may be difficult to start and to maintain (called urinary hesitancy).
Constipation can develop because the intestine may move its contents more slowly. Inactivity and levodopa, the main drug used to treat Parkinson’s disease, can worsen constipation.
A sudden, excessive decrease in blood pressure may occur when a person stands up (orthostatic hypotension).
Scales (seborrheic dermatitis) develop often on the scalp and face and occasionally in other areas.
Dementia develops in about half the people with Parkinson’s disease. In many people, intellect remains normal.
Diagnosis
The diagnosis is likely if the person has fewer, slow movements and either the characteristic tremor or muscle rigidity. Mild, early disease may be difficult for doctors to diagnose because it usually begins subtly. Diagnosis is especially difficult in older people because aging can cause some of the same problems as Parkinson’s disease, such as loss of balance, slow movements, muscle stiffness, and stooped posture. To exclude other causes of the symptoms, doctors ask about previous disorders, exposure to toxins, and use of drugs that could cause parkinsonism.
No tests or imaging procedures can directly confirm the diagnosis. However, computed tomography (CT) and magnetic resonance imaging (MRI) may be done to look for a structural disorder that may be causing the symptoms. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) can detect brain abnormalities typical of the disease. However, SPECT and PET are currently used only in research facilities.
If the diagnosis is unclear, doctors may give the person levodopa, a drug used to treat Parkinson’s disease. If levodopa results in clear improvement, Parkinson’s disease is likely.
Treatment
General measures used to treat Parkinson’s disease can help people function. Many drugs (such as levodopa-carbidopa) can make movement easier and enable people with Parkinson’s disease to function effectively for many years. But no drug can cure the disease. Two or more drugs may be needed. For older people, doses are often reduced. Drugs that cause or worsen symptoms, particularly antipsychotics, are avoided. If the disease is advanced and drugs are ineffective or cause severe side effects, surgery is considered.
General Measures: Various simple measures can help people with Parkinson’s disease maintain mobility and independence:
Continuing to do as many daily activities as possible
Following a program of regular exercise
Simplifying daily tasks—for example having buttons on clothing replaced with Velcro fasteners or buying shoes with Velcro fasteners
Using assistive devices, such as zipper pulls and button hooks
Physical therapists (see page 48) and occupational therapists (see page 50) can help people learn how to incorporate these measures into their daily activities, as well as recommend exercises to improve muscle tone and maintain range of motion. Therapists may also recommend mechanical aids, such as wheeled walkers, to help people maintain independence.
Simple changes around the home can make it safer for people with Parkinson’s disease:
Removing throw rugs to prevent tripping
DRUGS USED TO TREAT PARKINSON’S DISEASE
| DRUG | SOME SIDE EFFECTS | COMMENTS |
| Dopamine precursor | ||
| Levodopa (given with carbidopa) | For levodopa: Involuntary movements (of the mouth, face, and limbs), nightmares, low blood pressure when a person stands up (orthostatic hypotension), constipation, nausea, drowsiness, confusion, hallucinations, palpitations, and flushing If these drugs are suddenly stopped, neuroleptic malignant syndrome (with high fever, high blood pressure, rigidity, muscle damage, and coma), which can be life threatening |
This combination is the mainstay of treatment. Carbidopa helps increase the effectiveness of levodopa and reduce its side effects. After several years, the effectiveness of the combination may lessen. |
| Dopamine agonists | ||
| Bromocriptine Pramipexole Ropinirole |
Drowsiness, nausea, orthostatic hypotension, involuntary movements, confusion, and hallucinations When these drugs are suddenly stopped, neuroleptic malignant syndrome |
Early in the disease, these drugs may be used alone or with small doses of levodopa to possibly delay levodopa’s side effects. Later in the disease, dopamine agonists are useful when the on-off effects of levodopa make it less effective. |
| Apomorphine | Severe nausea, vomiting, and lumps (nodules) under the skin at the injection site | This quick-acting drug is injected under the skin. It is used as rescue therapy to reverse the off effect of levodopa. |
| Rotigotine | Drowsiness, nausea, orthostatic hypotension, confusion, hallucinations, weight gain (possibly due to fluid retention), and sometimes irritation at the application site | This drug is available as a skin patch. It is used alone early in the disease. The patch is worn continuously for 24 hours, then removed and replaced. The patch should be placed in different locations each day to reduce the risk of skin irritation. |
| MAO-B inhibitors | ||
| Rasagiline | Nausea, insomnia, drowsiness, and swelling due to fluid accumulation (edema) If people take doses that are higher than those usually used to treat Parkinson’s disease and consume foods or beverages that contain tyramine (such as certain cheeses and red wine) or take certain other drugs, hypertensive crisis (a severe headache and a potentially fatal increase in blood pressure) |
Rasagiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, rasagiline is modestly effective. |
| Selegiline | Worsening of nausea, confusion, and involuntary movements due to levodopa | Selegiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, selegiline is modestly effective. |
| COMT inhibitors | ||
| Entacapone Tolcapone |
Nausea, involuntary movements, confusion, diarrhea, back pain, and discoloration of the urine | These drugs can be used to supplement levodopa late in the disease and to extend the interval between doses of levodopa. |
| Anticholinergic drugs | ||
| Benztropine Trihexyphenidyl Tricyclic antidepressants (such as amitriptyline), used if depression also needs to be treated Some antihistamines (such as diphenhydramine) |
Drowsiness, confusion, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, loss of bladder control, and impaired regulation of body temperature | These drugs may be given alone in the early stages of the disease or as a supplement to levodopa in the later stages. They can reduce tremor but do not affect slow movements or muscle rigidity. |
| Antiviral drug | ||
| Amantadine | Nausea, dizziness, insomnia, anxiety, confusion, edema, difficulty urinating, worsening of glaucoma, and mottled discoloration of the skin due to dilated blood vessels (livedo reticularis) Rarely, when the drug is stopped or the dose is reduced, neuroleptic malignant syndrome | Amantadine is used alone in the early stages for mild disease but may become ineffective after several months. Later, it is used to supplement levodopa and to lessen involuntary movements due to levodopa. |
| Beta-blocker | ||
| Propranolol | Spasm of the airways (broncho-spasm), an abnormally slow heart rate (bradycardia), heart failure, possible masking of low blood sugar levels after insulin injections, impaired peripheral circulation, insomnia, fatigue, shortness of breath, depression, Raynaud’s phenomenon, vivid dreams, hallucinations, and sexual dysfunction | Propranolol can be used to reduce the severity of tremors. |
| MAO-B = monoamine oxidase type B; COMT = catechol O-methyltransferase. | ||
Installing grab bars in bathrooms and railings in hallways and other locations to reduce the risk of falling
For constipation, the following can help:
Consuming a high-fiber diet, including such foods as prunes and fruit juices
Exercising
Drinking plenty of fluids
Using stool softeners (such as senna concentrate), supplements (such as psyllium), or stimulant laxatives (such as bisacodyl taken by mouth) to keep bowel movements regular
Difficulty swallowing may limit food intake, so the diet must be nutritious. Making an effort to sniff more deeply may improve the ability to smell, enhancing the appetite.
Levodopa-Carbidopa: Traditionally, levodopa, which is given with carbidopa, is the first drug used. These drugs, taken by mouth, are the mainstay of treatment for Parkinson’s disease. However, some experts think that using levodopa early in the disease may cause side effects to develop more quickly, and people may stop responding to the drug sooner. Thus, a drug with anticholinergic effects, amantadine, or a drug that mimics the action of dopamine (a dopamine agonist) may be used first.
Levodopa reduces muscle rigidity, improves movement, and substantially reduces tremor. Taking levodopa produces dramatic improvement in people with Parkinson’s disease. The drug enables many people with mild disease to return to a nearly normal level of activity and enables some people who are confined to bed to walk again. However, levodopa usually does not help people with parkinsonism (which is due to another disorder).
Levodopa is a dopamine precursor, which means that the body can convert it to dopamine. Conversion may occur in the basal ganglia, thus compensating for the decrease in dopamine production. But levodopa can also be converted to dopamine early, on its way to the brain. When levodopa is converted early, the amount of dopamine available for controlling symptoms is reduced. Also, dopamine levels in the blood increase, increasing the risk of side effects such as nausea and flushing. Giving carbidopa with levodopa prevents this early conversion of levodopa. When the two drugs are given together, a lower dose of levodopa can be used, and nausea and flushing occur less often and are less severe.
To determine the best dose of levodopa for a particular person, doctors must balance control of the disease with the development of certain side effects, which may limit the amount of levodopa the person can tolerate. These side effects include involuntary movements (of the mouth, face, and limbs), nightmares, hallucinations, and changes in blood pressure.
After taking levodopa for 5 or more years, more than half the people begin to alternate rapidly between a good response to the drug and no response—an effect called the on-off phenomenon. Within seconds, they may change from being fairly mobile to being severely impaired and immobile. The periods of mobility after each dose become shorter and may be accompanied by involuntary movements (dyskinesias) due to levodopa use, including writhing or hyperactivity. Taking lower, more frequent doses controls these effects for a while. Other options are switching to a controlled-release formulation or adding a dopamine agonist or amantadine. However, after 15 to 20 years, these effects become hard to suppress. Surgery is then considered.
Other Drugs: Other drugs are generally less effective than levodopa, but they may benefit some people, particularly if levodopa is not tolerated or is insufficient.
Dopamine agonists (such as pramipexole and ropinirole), which mimic the action of dopamine, may be useful at any stage of the disease. Another dopamine agonist, rotigotine, is available as a skin patch. Apomorphine, a quick-acting dopamine agonist injected under the skin (subcutaneously), is used to reverse the off part of levodopa’s on-off phenomenon—when movement is difficult to initiate. Thus, this drug is called rescue therapy. It is usually used when people freeze in place, preventing them, for example, from walking. Affected people or another person (such as a family member) can inject the drug up to 5 times a day as needed.
Rasagiline and selegiline belong to a class of drugs called monoamine oxidase inhibitors (MAO inhibitors—see table on page 868). They prevent the breakdown of dopamine, thereby prolonging dopamine’s action in the body. If taken with certain foods (such as certain cheeses), beverages (such as red wine), or drugs, MAO inhibitors can have a serious side effect called hypertensive crisis (see table on page 92). However, this effect is unlikely when Parkinson’s disease is being treated because the doses used are low and the type of MAO inhibitor used (MAO type B inhibitors) is less likely to have this effect.
Entacapone prevents the breakdown of dopamine and appears to be a useful supplement to levodopa. Tolcapone works similarly to entacapone but is rarely used because it can damage the liver.
Some drugs with anticholinergic effects (see box on page 1897), such as benztropine and trihexyphenidyl, are effective in reducing the severity of a tremor and can be used in the early stages of Parkinson’s disease. They can also be used in the later stages to supplement levodopa. These drugs may reduce tremor because they block the action of acetylcholine, and tremor is thought to be caused by an imbalance of acetylcholine (too much) and dopamine (too little). Other drugs with anticholinergic effects, including some antihistamines and tricyclic antidepressants, are mildly effective and may be used to supplement levodopa. However, many anticholinergic effects are troublesome, especially in older people. These effects include confusion, drowsiness, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, and loss of bladder control.
Amantadine, a drug sometimes used to treat influenza, may be used alone to treat mild Parkinson’s disease or as a supplement to levodopa. Amantadine probably has many effects that make it work. For example, it probably stimulates nerve cells to release dopamine.
Propranolol, a beta-blocker, may be used to reduce the severity of a tremor.
Deep Brain Stimulation: People with involuntary movements due to long-term use of levodopa may benefit from deep brain stimulation. Tiny electrodes are surgically implanted in part of the basal ganglia. By stimulating this part, deep brain stimulation often greatly reduces the involuntary movements and tremors and shortens the off part of the on-off phenomenon.
Stem Cells: Transplantation of stem cells to treat Parkinson’s disease has received much publicity. Theoretically, stem cells, such as those derived from bone marrow or embryos, could be transplanted into the brain and become capable of producing dopamine. However, studies to determine whether this treatment is effective and safe in people will take many years.
Caregiver and End-of-Life Issues: Because Parkinson’s disease is progressive, people eventually need help with normal daily activities, such as eating, bathing, dressing, and toileting. Caregivers can benefit from learning about the physical and psychologic effects of Parkinson’s disease and about ways to enable people to function as well as possible. Because such care is tiring and stressful, caregivers may benefit from support groups.
Eventually, most people with Parkinson’s disease become severely disabled and immobile. They may be unable to eat, even with assistance. Dementia develops in about half the people. Because swallowing becomes increasingly difficult, death due to aspiration pneumonia is a risk. For some people, a nursing home may be the best place for care. Before people with this disease are incapacitated, they should establish advance directives, indicating what kind of medical care they want at the end of life (see page 69).
Parkinsonism
Parkinsonism refers to symptoms of Parkinson’s disease (such as slow movements and tremors) that are caused by another condition.
Various conditions can cause parkinsonism:
Viral encephalitis, a rare brain inflammation that follows a flu-like infection
Other degenerative disorders, such as dementia, multiple system atrophy, corticobasal ganglionic degeneration, and progressive supranuclear palsy
Structural brain disorders, such as brain tumors and strokes
Head injury, particularly the repeated injury that occurs in boxing (making a person punch-drunk)
Drugs, such as antipsychotics and the antihypertensives methyldopa and reserpine
Toxins, such as manganese, carbon monoxide, and methanol
Certain drugs and toxins interfere with or block the action of dopamine and other neurotransmitters. For example, antipsychotic drugs, used to treat paranoia and schizophrenia, block dopamine’s action. Use of the substance MPTP (which was produced accidentally when illicit drug users tried to synthesize the opioid meperidine) can cause sudden, severe, irreversible parkinsonism in young people.
Symptoms
Parkinsonism causes the same symptoms as Parkinson’s disease (see page 771). They include a resting tremor, stiff muscles, slow movements, and difficulty maintaining balance and walking.
The disorders that cause parkinsonism may also cause other symptoms or variations of parkinsonian symptoms, as in the following:
Prominent memory loss due to dementia
Symptoms of parkinsonism on only one side of the body due to certain brain tumors
Low blood pressure and urinary problems due to multiple system atrophy
Inability to express or understand spoken or written language (aphasia), inability to do simple skilled tasks (apraxia), and inability to associate objects with their usual role or function (agnosia) due to corticobasal ganglionic degeneration
In corticobasal ganglionic degeneration, symptoms begin after age 60. People become immobile after about 5 years, and death typically occurs after about 10 years.
Diagnosis
Doctors ask about previous disorders, exposure to toxins, and use of drugs that could cause parkinsonism. Brain imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be done to look for a structural disorder that may be causing the symptoms.
If the diagnosis is unclear, doctors may give the person levodopa, a drug used to treat Parkinson’s disease, to rule out Parkinson’s disease. If the drug results in clear improvement, Parkinson’s disease is the likely cause.
Treatment
The cause is corrected or treated if possible. If a drug is the cause, stopping the drug may cure the disorder. Symptoms may lessen or disappear if the underlying disorder can be treated. The drugs used to treat Parkinson’s disease (such as levodopa) are often not effective in people with parkinsonism but can sometimes offer modest improvement.
Drugs are used if symptoms are bothersome. If the cause is use of antipsychotic drugs, amantadine or a drug with anticholinergic effects, such as benztropine, may relieve symptoms.
The same general measures used to help people with Parkinson’s disease maintain mobility and independence are useful (see page 773). For example, people should remain as active as possible, simplify daily tasks, use assistive devices as needed, and take measures to make the home safe (such as removing throw rugs to prevent tripping). Physical and occupational therapists can help people implement these measures. Good nutrition is also important.
Progressive Supranuclear Palsy
Progressive supranuclear palsy is characterized by muscle stiffness (rigidity), inability to move the eyes, weakness of the throat muscles, and a tendency to fall backward.
Progressive supranuclear palsy, which is much rarer than Parkinson’s disease, affects many parts of the brain, particularly the basal ganglia and the brain stem. (The basal ganglia help smooth out muscle movements and coordinate changes in posture. The brain stem regulates critical body functions, such as breathing, heart rate, and swallowing, and helps adjust posture.) Brain cells in these areas degenerate, but why they do is unknown.
Symptoms usually begin in late middle age. The first symptom may be difficulty looking up without bending the neck or difficulty climbing up and down stairs. People with the disorder cannot roll their eyes downward, fix their eyes on a stationary object, or follow a moving object. They may have blurred or double vision. The upper eyelids may pull back, producing a look of astonishment. Muscles become rigid, and movements are slow. Walking is unsteady, with a tendency to fall backward. Speaking and swallowing are difficult. Other symptoms include insomnia, agitation, irritability, apathy, and rapid changes in emotion.
In the late stages, depression and dementia are common. Like Parkinson’s disease, progressive supranuclear palsy results in severe muscle rigidity and disability, usually within 5 years. Usually, death, often due to infection, occurs within 10 years after symptoms begin.
The diagnosis is based on symptoms. No effective treatment exists. The drugs used to treat Parkinson’s disease provide some relief.
Multiple System Atrophy
Multiple system atrophy is a progressive, fatal disorder that makes muscles stiff (rigid) and causes problems with movement, loss of coordination, and malfunction of internal body processes (such as blood pressure and bladder control).
The parts of the brain that control movements and many internal body processes degenerate.
Some symptoms resemble those of Parkinson’s disease, but internal body processes also malfunction.
Doctors base the diagnosis on symptoms.
Simple measures and drugs can help lessen symptoms, but the disorder is progressive and ultimately fatal.
Multiple system atrophy usually begins when people are in their 50s. It affects about twice as many men as women. It results from degeneration of several parts of the brain and spinal cord:
The basal ganglia (collections of nerve cells at the base of the cerebrum, deep within the brain), which help control voluntary muscle movements by balancing the actions of muscle groups that move the same muscles in opposite ways (for example, a group that bends an arm and a group that straightens the arm)
The cerebellum, which coordinates voluntary movements (particularly complex movements done simultaneously) and helps maintain balance
Areas that control the autonomic nervous system, which regulates involuntary body processes, such as how blood pressure changes in response to changes in posture
Nerve cells that stimulate muscle action (motor neurons) in the cerebellum, basal ganglia, and spinal cord
The cause of the degeneration is unknown. Multiple system atrophy includes three disorders previously thought to be separate disorders:
Olivopontocerebellar atrophy, which is characterized by symptoms similar to those of Parkinson’s disease (called parkinsonism) and difficulty maintaining balance
Striatonigral degeneration, which is very similar to Parkinson’s disease except that levodopa often does not relieve symptoms
Shy-Drager syndrome, which is characterized by parkinsonism and problems with urination, blood pressure control, and some other internal body processes
Symptoms
Multiple system atrophy is a progressive disorder. Early symptoms vary, depending on which part and how much of the brain is affected first. The disorder causes three groups of symptoms.
Parkinsonism—symptoms that resemble those of Parkinson’s disease—may occur early. These symptoms result from degeneration in the basal ganglia. Muscles are stiff (rigid), and movements become slow, shaky, and difficult to initiate. When walking, people may shuffle and not swing their arms. People feel unsteady and off balance, making them more likely to fall. Posture may be stooped. Limbs may tremble jerkily, usually when they are held in one position. But people with multiple system atrophy are less likely to have tremors during rest than people with Parkinson’s disease. Articulating words is difficult, and the voice may become high-pitched and quaver.
Loss of coordination may also occur early. It results from degeneration in the cerebellum. People may be unable to control movements of their arms and legs. Consequently, they have difficulty walking and take wide, irregular steps. When reaching for an item, they may reach beyond it. When sitting, they may feel unstable. People may have difficulty focusing their eyes on and following objects. Tasks that require rapidly alternating movements, such as turning a door knob or screwing in a light bulb, also become difficult.
Malfunction of internal body processes, controlled by the autonomic nervous system, may also occur early. Blood pressure may decrease dramatically when a person stands up, causing dizziness, light-headedness, or fainting—a condition called orthostatic hypotension. Blood pressure may increase when a person lies down. People may need to urinate urgently or frequently or may pass urine involuntarily (urinary incontinence). They may have difficulty emptying the bladder (urinary retention). Constipation is common. Vision becomes poor. Men may have difficulty initiating and maintaining an erection (erectile dysfunction).
Other symptoms of autonomic malfunction may occur early or late. Less sweat, tears, and saliva are produced. As a result, people may become intolerant of heat and have dry eyes and mouth. People may have difficulty swallowing and breathing. Breathing may be noisy and high-pitched. During sleep, breathing may stop repeatedly or become inadequate (sleep apnea). People may lose control of bowel movements (fecal incontinence).
Many people are confined to a wheelchair or are otherwise severely disabled within 5 years after symptoms begin. The disorder results in death 9 to 10 years after symptoms begin.
Diagnosis
The diagnosis is based on symptoms. However, symptoms may resemble those of other disorders, making the disorder difficult to diagnose.
The only sure way to diagnose multiple system atrophy is to examine brain tissue after death. Nonetheless, some tests help with the diagnosis. For example, if levodopa relieves parkinsonism, the cause is probably Parkinson’s disease. Levodopa has little or no lasting effect on similar symptoms due to multiple system atrophy. Magnetic resonance imaging (MRI) of the brain may help rule out other neurologic disorders. Tests to evaluate the autonomic nervous system may be done. For example, blood pressure may be measured while the person is sitting and after the person stands to check for orthostatic hypotension. The presence of orthostatic hypotension supports the diagnosis of multiple system atrophy.
Treatment
No treatment can cure multiple system atrophy. However, a combination of simple measures and drugs may help relieve symptoms.
Parkinsonism: Continuing to do as many daily activities as possible helps maintain muscle strength and flexibility. Stretching and exercising regularly may also help. Drugs used to treat Parkinson’s disease, such as levodopa plus carbidopa or pergolide, taken by mouth, may be tried, but these drugs usually have little effect or are effective for only a few years.
Orthostatic hypotension: Measures are taken to stabilize the sudden changes in blood pressure. Consuming more salt and water may increase the volume of blood and thus help increase blood pressure. Standing up slowly may help prevent blood pressure from decreasing too much when a person stands, as may wearing an abdominal binder or compression stockings. These garments help maintain blood pressure by promoting blood flow from the legs to the heart and thus prevent too much blood from staying (pooling) in the legs. Raising the head of the bed by about 4 inches (10 centimeters) can help prevent blood pressure from increasing too much when the person lies down. If blood pressure does increase, an antihypertensive drug (such as propranolol) may be taken at night. Fludrocortisone may be taken by mouth. It helps the body retain salt and water and thus may increase blood pressure as needed when a person stands. Other drugs, such as midodrine or pyridostigmine, taken by mouth, may also help.
Decreased production of body fluids: If sweating is reduced or absent, people should avoid warm environments to avoid overheating the body. Good dental care and regular check-ups are essential for people with dry mouth. Artificial tears (eye drops containing substances that resemble real tears) applied every few hours may relieve dry eyes.
Urinary retention: If needed, people can learn to insert a catheter into the bladder themselves. They insert it several times a day. It is inserted through the urethra, allowing urine in the bladder to drain out. People remove the catheter after the bladder is empty. This measure helps prevent the bladder from stretching and urinary tract infections from developing. Washing the hands, cleansing the area around the urethra, and using a sterile or clean catheter also help prevent infections. Inserting a catheter becomes more difficult as coordination deteriorates. Doctors may prescribe bethanechol, which increases the tone of bladder muscles and sometimes makes emptying the bladder easier.
Urinary incontinence: Oxybutynin or tolterodine, taken by mouth, may be used to relax the muscles of an overactive bladder. If incontinence persists, using a catheter inserted into the bladder may help. Some people learn to insert it themselves.
Constipation: A high-fiber diet and stool softeners are recommended. If constipation persists, enemas may be necessary.
Erectile dysfunction: Usually, treatment consists of drugs such as sildenafil, tadalafil, or vardenafil, taken by mouth.
As the disorder progresses, people may need a breathing tube, a feeding tube (usually surgically inserted), or both. Physical, occupational, and speech therapists can teach people ways to compensate when walking, doing daily activites, and speaking become difficult. Social workers can help people find support groups and, when symptoms become disabling, home health care or hospice services.
End-of-Life Issues: Because the disorder is progressive and ultimately fatal, people should prepare advance directives soon after the disorder is diagnosed. These directives should indicate what kind of medical care people want at the end of life (see page 69).
Tics
Tics are rapid, purposeless, repetitive but not rhythmic involuntary movements that are virtually identical to one another. They can be suppressed but only for a short time and only with conscious effort.
Tics may occur on their own or be caused by a disorder or drug.
People feel an irresistible urge to blink, grimace, jerk their head, or move in some other way.
Many tics disappear on their own, but if they are troublesome or severe, mild sedatives or antipsychotic drugs may help.
Tics may be simple or complex. Simple tics, such as excessive blinking, grimacing, or head jerking, may begin as nervous mannerisms. Complex tics, such as those that occur in Tourette’s syndrome, often resemble fragments of normal behavior.
Tics, especially simple tics, can occur on their own. Many of these tics begin during childhood and disappear without treatment. Or tics can occur as part of another disorder, such as Huntington’s disease, obsessive-compulsive disorder, some infections, or a stroke. Some drugs and toxins cause tics.
Symptoms
Before a tic occurs, people may feel an urge to do the tic. This urge is similar to the need to sneeze or scratch an itch. Tension builds up, usually in the affected body part. When people give in to the tic, they feel relief briefly.
The tic can sometimes be postponed for seconds to minutes, but usually it eventually becomes irresistible. Most people have trouble controlling tics, especially during times of emotional stress. However, some people can suppress some tics, usually with difficulty. Calling attention to a tic, particularly in children, may make the tic worse.
Treatment
For people with a simple tic (particularly children), reassurance is often best, with as little attention paid to the tic as possible.
If tics are particularly troublesome, they can be treated with drugs. For simple tics, benzodiazepines, such as clonazepam and diazepam, may help. These drugs are mild sedatives taken by mouth. Clonidine, a drug used to treat high blood pressure, occasionally helps. It blocks the action of norepinephrine, a neurotransmitter that is thought to contribute to tics. Side effects may include excessively low blood pressure.
For severe tics, antipsychotic drugs may be effective even though psychosis is not the cause of tics (see page 781). Or botulinum toxin can be injected into the affected muscle, paralyzing it and thus preventing the tic.
TOURETTE’S SYNDROME
Tourette’s syndrome is a hereditary disorder characterized by simple and complex muscle and vocal tics that occur frequently throughout the day for at least one year.
Tourette’s syndrome is common, affecting possibly as many as 1 of 100 people. It is 3 times more common among men than among women. It often begins in early childhood. In most people, symptoms are so mild that the disorder is not recognized.
The cause is unknown.
The disorder often begins with simple tics, such as blinking, grimacing, or head jerking, followed by such movements as hitting and kicking and vocal outbursts, including cursing.
Doctors base the diagnosis on symptoms.
Drugs may not be needed, but clonidine, mild sedatives, antipsychotics, or botulinum toxin may help.
The cause is unknown but is thought to be an abnormality in dopamine or another brain neurotransmitter (a chemical messenger that nerve cells use to communicate). Genes are involved, but their precise role and the specific genes involved are unknown.
Symptoms
Tourette’s syndrome often begins with simple muscle tics, such as grimacing, head jerking, and blinking. Simple tics may be only a nervous habit and may disappear with time. Such tics do not necessarily lead to Tourette’s syndrome, which involves more than a simple tic. For example, people with Tourette’s syndrome may repeatedly move their head from side to side, blink their eyes, open their mouth, and stretch their neck.
Did You Know…
Most people with Tourette’s syndrome do not randomly shout out obscenities.
The disorder may progress to bursts of complex tics, including vocal tics, hitting, kicking, and sudden, irregular, jerky breathing. Vocal tics may start as grunting, snorting, humming, or barking noises and progress to compulsive, involuntary bouts of cursing. For no apparent reason and often in the midst of conversation, some people with Tourette’s syndrome may call out obscenities or words related to feces (called coprolalia). These vocal outbursts are sometimes mistakenly thought to be intentional, especially in children. Although coprolalia is a well-known feature of Tourette’s syndrome, at least 85% of people with Tourette’s syndrome do not have coprolalia. People may also repeat words immediately after hearing them (called echolalia).
People with Tourette’s syndrome often have difficulty functioning and experience considerable anxiety in social situations. In the past, they were shunned, isolated, or even thought to be possessed by the devil. Impulsive, aggressive, and self-destructive behaviors develop in many people, and obsessive-compulsive behavior develops in about half. Children with Tourette’s syndrome often have difficulty learning. Many also have attention-deficit/hyperactivity disorder. Whether Tourette’s syndrome itself or the extraordinary stresses of living with the disorder cause these problems is unclear.
Diagnosis
The diagnosis is based on symptoms. Early diagnosis can help parents understand that the tics their children have are not voluntary and that punishment cannot stop the tics and may even make them worse.
Treatment
If symptoms are mild, drugs may not be needed.
Simple Tics: Doctors often first try clonidine or guanfacine. Clonidine, a drug used to treat high blood pressure, occasionally helps and is particularly useful in controlling anxiety and obsessive-compulsive behavior. Benzodiazepines, such as clonazepam and diazepam, may help. These drugs are mild sedatives taken by mouth.
Severe Symptoms: Antipsychotic drugs may be used to help suppress the tics, even though psychosis is not the cause. The lowest dose needed to make tics tolerable is used, and doses are decreased as tics lessen. Haloperidol, the most commonly used anti-psychotic drug, is effective but is more likely to have side effects than other antipsychotic drugs, such as olanzapine, pimozide, and risperidone.
Side effects of antipsychotics (see table on page 894) may include symptoms similar to those of Parkinson’s disease (parkinsonism), restlessness, muscle stiffness, sustained involuntary muscle contractions (dystonias), weight gain, blurred vision, sleepiness, and dulled, slowed thinking. Tardive dyskinesia, which consists of repetitive involuntary movements, may develop and persist even after the drug is stopped. Uncontrollably, the arms or legs writhe, the tongue protrudes, and the lips pucker, purse, and smack. A rare but more serious side effect called neuroleptic malignant syndrome consists of high fever, high blood pressure, muscle damage, and coma.
Injecting botulinum toxin into the muscles producing the tics may decrease the abnormal movements as well as the urge that precedes them. Botulinum, the bacterial toxin that causes botulism, is used to paralyze muscles (and to treat wrinkles).
Deep brain stimulation is considered an experimental treatment for Tourette’s syndrome, but it is sometimes done in special centers when the disorder is severe and drugs have been ineffective. Electrodes are placed in the parts of the brain thought to be involved in tics.
Chorea, Athetosis, and Hemiballismus
Chorea is repetitive, brief, jerky, rapid involuntary movements that start in one part of the body and move abruptly, unpredictably, and often continuously to another part. Athetosis is a continuous stream of slow, flowing, writhing involuntary movements. Hemiballismus is a type of chorea, usually involving violent, flinging involuntary movements of one arm.
Chorea and athetosis are usually symptoms of another disorder, although chorea may develop on its own in older people or in pregnant women.
Chorea and athetosis usually cause slow, writhing, and dance-like, jerky movements.
Hemiballismus is flinging movements of one side of the body, usually the arm.
For chorea and athetosis, treating the cause may help, as may antipsychotic drugs.
Chorea and athetosis, which may occur together as choreoathetosis, are not disorders. Rather, they are symptoms that can result from several very different disorders. Chorea and athetosis result from overactivity in the basal ganglia, the part of the brain that helps smooth out and coordinate movements initiated by nerve impulses from the brain. In most forms of chorea, an excess of dopamine, the main neurotransmitter used in the basal ganglia, prevents the basal ganglia from functioning normally. Drugs and disorders that increase dopamine levels or increase the sensitivity of nerve cells to dopamine tend to worsen chorea and athetosis.
Chorea and athetosis occur in Huntington’s disease, a hereditary degenerative disorder. Chorea may occur in Sydenham’s chorea (also called St. Vitus’ dance or Sydenham’s disease), a complication of rheumatic fever (a childhood infection caused by certain streptococci). Sydenham’s chorea is characterized by jerky, uncontrollable movements and can last for several months.
Chorea sometimes develops in older people for no apparent reason. This chorea, called senile chorea, tends to affect the muscles in and around the mouth. Chorea can also affect women during the first 3 months of pregnancy (a condition called chorea gravidarum), but it disappears without treatment shortly after they give birth. Rarely, a similar chorea develops in women taking oral contraceptives. Chorea can also result from lupus (systemic lupus erythematosus), overactivity of the thyroid gland (hyperthyroidism), a tumor or stroke affecting a part of the basal ganglia called the caudate nucleus, and certain drugs such as antipsychotic drugs.
Symptoms
Chorea typically involves the hands, feet, and face. The jerky movements seem to flow from one muscle to the next and may seem dancelike. The movements may merge imperceptibly into purposeful or semipurposeful acts, sometimes making the chorea hard to identify.
Athetosis usually affects the hands and feet. The slow writhing movements often alternate with holding parts of the limbs in certain positions (postures) to produce a continuous, flowing stream of movement.
Hemiballismus affects one side of the body. The arm is affected more often than the leg. It is usually caused by a stroke affecting a small area just below the basal ganglia called the subthalamic nucleus. Hemiballismus may be temporarily disabling because when a person tries to move the limb, it may fling out uncontrollably.
Treatment
Chorea due to hyperthyroidism usually lessens when that disorder is treated. Sydenham’s chorea and chorea caused by a stroke often gradually subside without treatment. If chorea is caused by a drug, stopping the drug may help, but the chorea does not always disappear. Pregnant women with chorea may be treated with barbiturates during the pregnancy.
Drugs that block dopamine’s action may help control the abnormal movements. These drugs include antipsychotic drugs (see table on page 894), such as fluphenazine, haloperidol, and risperidone. Drugs that reduce the amount of dopamine released, such as reserpine and tetrabenazine, may also help. However, improvement may be limited.
Hemiballismus usually goes away on its own after several days, but it sometimes lasts for 6 to 8 weeks. Antipsychotic drugs may help suppress hemiballismus.
Huntington’s Disease
Huntington’s disease (Huntington’s chorea) is a hereditary disease that begins with occasional involuntary jerking or spasms, then progresses to more pronounced involuntary movements (chorea and athetosis), mental deterioration, and death.
Part of the brain that smooths and coordinates movements degenerates.
Movements become slow and uncoordinated, and mental function, including self-control and memory, deteriorates.
Doctors base the diagnosis on symptoms, family history, imaging of the brain, and gene testing.
Drugs can help relieve the symptoms, but the disorder is progressive, ultimately ending in death.
Huntington’s disease affects fewer than 1 of 10,000 people. It affects both sexes equally. The gene for Huntington’s disease is dominant. Therefore, children of a person who has this disease have a 50% chance of developing it (see page 12). Symptoms usually develop subtly, beginning between the ages of 35 and 50 but can develop before adulthood. Huntington’s disease is caused by gradual degeneration of small parts of the basal ganglia called the caudate nucleus and corpus striatum. The basal ganglia help smooth out and coordinate movements.
Symptoms
During the early stages of Huntington’s disease, people can blend the involuntary abnormal movements into purposeful ones so that the abnormal movements are barely noticeable. However, with time, the movements become more obvious. People may walk in a lilting or exaggeratedly jaunty way, like a puppet. They may grimace, flick the limbs, and blink more often. Movements become uncoordinated and slow. Eventually, the entire body is affected, making walking, sitting still, eating, speaking, and dressing extremely difficult.
Genetic Testing for Huntington’s Disease
The genetic mutation that causes Huntington’s disease is located on chromosome 4. It involves repetition of a particular section of the genetic code in the DNA.
The gene for Huntington’s disease is dominant. Thus, having only one copy of the abnormal gene, inherited from one parent, is sufficient to cause the disease. Almost all people with the disease have only one copy of the abnormal gene. Children of such people have a 50% chance of inheriting the abnormal gene and thus the disease.
People who have a parent or grandparent with Huntington’s disease can find out whether they have inherited the gene for the disease by taking a genetic test. For the test, a blood sample is taken and analyzed. Such people may or may not want to know whether they have inherited the gene. This issue should be discussed with an expert in genetic counseling before genetic testing.
Mental changes frequently occur before or as the abnormal movements develop. These changes are subtle at first. People may gradually become irritable and excitable. They may lose interest in their usual activities. They may be unable to control their impulses, losing their temper, having fits of despondency, or becoming promiscuous. As the disease progresses, people may behave irresponsibly and often wander aimlessly. Over years, they lose their memory and their ability to think rationally. They may become severely depressed and attempt suicide.
In advanced disease, dementia is severe, and people are confined to bed. Full-time assistance or nursing home care is needed. Death usually occurs 13 to 15 years after symptoms begin. The cause is usually pneumonia or coronary artery disease.
Diagnosis
Huntington’s disease may be difficult to recognize in the early stages because symptoms are subtle. The disease may be suspected based on symptoms and a family history. Doctors should be told about relatives who have had mental problems or have been diagnosed as having a neurologic or psychiatric disorder (such as Parkinson’s disease or schizophrenia) because they may have had Huntington’s disease that was not diagnosed. Computed tomography (CT) or magnetic resonance imaging (MRI) is done to check for the degeneration of the basal ganglia characteristic of the disease and to rule out other disorders.
Genetic testing is done to confirm the diagnosis. Genetic testing and counseling are important for people who have a family history of the disease but no symptoms because people are likely to have children before symptoms appear. For such people, genetic counseling should precede genetic testing. They are referred to centers that have expertise in dealing with the complex ethical and psychologic issues involved.
Treatment
As soon as possible after the diagnosis is made, people with Huntington’s disease should establish advance directives, indicating what kind of medical care they want at the end of life (see page 69).
No cure exists for Huntington’s disease. However, drugs, such as the sedative chlorpromazine, the anti-psychotic haloperidol, and the antihypertensive reserpine, can help relieve symptoms and control behavior.
Dystonia
Dystonia is characterized by involuntary sustained muscle contractions that may make people freeze in the middle of an action or make the entire body, the trunk, or another part of the body twist or turn.
Dystonia may result from a genetic mutation, a disorder, or a drug.
Spasms occur in the affected part of the body, distorting the position of that body part.
The cause is corrected if possible, but drugs, such as mild sedatives, levodopa plus carbidopa, and botulinum toxin, may help.
Causes
Dystonia seems to result from overactivity in several areas of the brain—the basal ganglia, thalamus, cerebellum, and cerebral cortex. Dystonia may result from a genetic mutation (called primary dystonia) or from a disorder or drug (called secondary dystonia). Antipsychotic drugs can cause various types of dystonia, including shutting of the eyelids, twisting of the neck (spasmodic torticollis) or back, grimacing, puckering of the lips, protrusion of the tongue, and writhing of the arms or legs.
Types and Symptoms
Dystonias may affect one part (focal dystonias) or several parts (segmental dystonias) of the body. Sometimes they affect the whole body (generalized dystonias).
CAUSES OF DYSTONIAS
| TYPE | EXAMPLES |
| Disorders | Cerebral palsy Genetic disorders, such as generalized dystonia and doparesponsive dystonia Multiple sclerosis A severe lack of oxygen to the brain (which may occur at birth or later in life) Stroke Toxicity due to accumulation of certain metals (such as copper in Wilson’s disease) |
| Drugs | Antiemetics (such as metoclopramide and prochlorperazine) Antipsychotic drugs (such as chlorpromazine, fluphenazine, haloperidol, and thiothixene) |
Focal and Segmental Dystonias: Dystonias that affect one or several body parts typically start in a person’s 30s or 40s and affect women more often. Initially, spasms may occur randomly or only during stress. Certain movements of the affected body part may trigger the spasms, which may disappear during rest. Over days, weeks, or many years, spasms may become more frequent and may continue during rest. Eventually, the affected body part remains distorted, sometimes in a painful position. Severe disability results. The following are examples of focal and segmental dystonias:
Blepharospasm: This dystonia affects mainly the eyelids. The eyelids are repeatedly and involuntarily forced shut. Occasionally, only one eye is affected at first, but ultimately, the other eye is also affected. It usually begins as excessive blinking, eye irritation, or extreme sensitivity to bright light. Many people with blepharospasm find ways to keep their eyes open, such as yawning, singing, or opening the mouth wide. These techniques become less effective as the disorder progresses. Blepharospasm can severely impair vision.
Spasmodic torticollis: Torticollis specifically affects the muscles of the neck. It is one of the most common focal dystonias in adults. The cause is often unknown but, in some cases, is probably genetic. Torticollis can also be caused by drugs that block dopamine, such as haloperidol. Rarely, torticollis is present at birth (called congenital torticollis). In adults, it often begins with a pulling sensation of the neck. The head, neck, and shoulders can twist into a distorted position that persists. Early in the disorder the spasm can sometimes be suppressed with effort. Or people sometimes discover tricks that make the spasm stop temporarily. For example, they may touch their face in a particular spot (usually on the side opposite the twisting).
Spasmodic dysphonia: The muscles of the vocal cords, which control speech, contract involuntarily. Speech may be impossible or may sound strained, quavery, hoarse, whispery, jerky, creaky, staccato, or garbled and be difficult to understand.
Occupational dystonias: These dystonias, also called task-specific dystonias, affect one part of the body and often result from overuse. For example, golfers may have involuntary muscle spasms in the hands and wrists (called the yips). The yips may make putting nearly impossible. What is supposed to be a 3-foot putt can become a 15-foot putt when a golfer loses control because of the yips. Similarly, musicians, especially concert pianists, may have bizarre spasms of the fingers, hands, or arms that prevent them from performing. Musicians who play wind instruments may have spasms of the mouth. Persistent writer’s cramp may be dystonia.
Meige’s disease: This dystonia combines involuntary blinking with jaw grinding and grimacing. Thus, it is also called blepharospasm-oromandibular dystonia. (“Blepharo” refers to the eyelids, “oro” refers to the mouth, and “mandibular” refers to the jaw.) It usually begins in late middle age.
Generalized Dystonias: Dystonias that affect the whole body include the following:
Generalized dystonia: This rare dystonia, also called idiopathic torsion dystonia, is progressive and often hereditary. In many cases, specific genetic mutations have been identified. The gene most commonly affected is the DYT1 gene. The resulting dystonia is called DYT1 dystonia. Involuntary movements result in sustained, often bizarre postures. Typically, symptoms begin during childhood, often with turning the foot in during walking. The dystonia may affect only the trunk or a leg but sometimes affects the whole body, ultimately confining children to a wheelchair. When this dystonia develops in adults, it usually begins in the face or arms and usually does not affect other parts of the body. Mental function is not affected.
Dopa-responsive dystonia: This rare form of dystonia is hereditary. Symptoms usually begin during childhood. Typically, one leg is affected first. As a result, children tend to walk on tiptoes. Symptoms worsen at night. Walking becomes progressively more difficult, and both arms and legs are affected. However, some children have only mild symptoms, such as muscle cramps after exercise. Sometimes symptoms appear later in life and resemble those of Parkinson’s disease. Movements may be slow, balance may be difficult to maintain, and a tremor may occur in the hands during rest. Symptoms lessen dramatically when people are given low doses of levodopa. If levodopa relieves the symptoms, the diagnosis is confirmed.
Treatment
Correcting or eliminating the cause of dystonia, if known, usually reduces the spasms. For example, drugs used to treat multiple sclerosis may reduce spasms related to that disease. When dystonia is due to use of an antipsychotic drug, promptly taking diphenhydramine by injection or by mouth usually stops the spasms quickly, and the antipsychotic is stopped.
For generalized dystonia, a drug with anticholinergic effects (such as trihexyphenidyl or benztropine) is most commonly used. These drugs reduce spasms by blocking specific nerve impulses involved in causing the spasms. However, anticholinergic effects also include confusion, drowsiness, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, loss of bladder control, and tremor, which are troublesome, especially in older people. A benzodiazepine (a mild sedative) such as clonazepam, baclofen (a muscle relaxant), or both are also usually given. Baclofen may be given by mouth or by a pump implanted in the spinal canal. If generalized dystonia is severe or does not respond to drugs, tiny electrodes may be surgically implanted in the basal ganglia (a procedure called deep brain stimulation).
Did You Know…
Drugs used to treat nausea or psychosis sometimes cause abnormal sustained muscle contractions (dystonias).
Botulinum toxin, also used to treat facial wrinkles, is used to treat some dystonias.
Some people, especially children with doparesponsive dystonia, improve dramatically when they are treated with levodopa plus carbidopa.
If one or a few body parts are affected, botulinum toxin (a bacterial toxin used to paralyze muscles or to treat wrinkles) is injected into the overactive muscles. Botulinum weakens the muscle contraction but does not affect the nerves. These injections are particularly useful for blepharospasm and spasmodic torticollis.
Physical therapy helps some people, especially those who are treated with botulinum.
Coordination Disorders
Coordination disorders result from malfunction of the cerebellum, the part of the brain that coordinates voluntary movements.
The cerebellum malfunctions, causing loss of coordination.
Often, people cannot control their arms and legs, making them take wide, unsteady steps when they walk.
Doctors base the diagnosis on symptoms, family history, and magnetic resonance imaging of the brain.
The cause is corrected if possible, and if it cannot be, treatment focuses on relieving symptoms.
The cerebellum is the part of the brain most involved in coordinating sequences of movements. It also controls balance and posture. Anything that damages the cerebellum can lead to loss of coordination (ataxia).
Prolonged, excessive alcohol use permanently damages the cerebellum and is the leading cause of coordination disorders. Less commonly, other disorders, such as an underactive thyroid gland (hypothyroidism), vitamin E deficiency, and brain tumors, cause coordination disorders. Some hereditary disorders, such as Friedrich’s ataxia, cause loss of coordination. Certain drugs (such as anticonvulsants), especially when they are given in high doses, can cause coordination disorders. In such cases, the disorder may disappear when the drug is stopped.
Symptoms
People with ataxia cannot control the position of their arms and legs or their posture. Thus, when they walk, they take wide steps and stagger and make broad, zigzag movements with their arms.
Coordination disorders can cause other abnormalities, such as the following:
Dysmetria: People cannot control the range of body movements. For example, in attempting to reach for an object, people with dysmetria may reach beyond the object.
Dysarthria: Speech is slurred, and fluctuations in volume cannot be controlled because speech muscles are uncoordinated. Movement of the muscles around the mouth may be exaggerated.
Scanning speech: People speak in a monotone with staccato-like hesitation.
Nystagmus: When glancing at an object, the eyes may overshoot their target, and nystagmus may occur. In nystagmus, the eyes repeatedly move rapidly in one direction, then drift slowly back to their original position.
Tremor: Damage to the cerebellum can also cause a tremor when people end a purposeful movement or try to reach a target (intention tremor) or when people try to hold their body in a certain position (postural tremor). Muscle tone may decrease.
Friedreich’s Ataxia: In this progressive disorder, walking becomes unsteady between the ages of 5 and 15. Then arm movements become uncoordinated, and speech becomes slurred and hard to understand. Many children with the disorder are born with a clubfoot, curved spine (scoliosis), or both. People with Friedreich’s ataxia cannot sense vibrations, cannot sense where their arms and legs are (lose their position sense), and no longer have reflexes. Mental function may deteriorate. Tremor, if present, is slight.
Did You Know…
The most common cause of coordination disorders is prolonged, excessive alcohol use.
By their late 20s, people with this disorder may be confined to a wheelchair. Death, often due to an abnormal heart rhythm or heart failure, usually occurs by middle age.
Diagnosis and Treatment
The diagnosis is based on symptoms. Doctors also ask about relatives who have had similar symptoms (family history) and about conditions that could cause the symptoms. Magnetic resonance imaging (MRI) of the brain is usually done. Genetic testing is done if people may have a family history of coordination disorders. If possible, the cause is eliminated or treated. For example, if the coordination disorder is due to use of alcohol, alcohol is stopped. If the disorder is caused by a high dose of a drug (such as phenytoin), the dose is reduced. Some underlying disorders, such as hypothyroidism and vitamin E deficiency, can be treated. Surgery may help some people with brain tumors. For hereditary coordination disorders, there is no cure. In such cases, treatment focuses on relieving symptoms.
CAUSES OF COORDINATION DISORDERS
| TYPE | EXAMPLES |
| Brain disorders | Birth defects of the brain |
| Bleeding (hemorrhage) in the brain | |
| Brain tumors, particularly in children | |
| Head injuries (repeated) | |
| Strokes | |
| Hereditary disorders | Spinocerebellar ataxias |
| Friedreich’s ataxia | |
| Ataxia-telangiectasia | |
| Other disorders | Heatstroke or extremely high fever |
| Multiple sclerosis | |
| Multiple system atrophy | |
| Underactive thyroid gland (hypothyroidism) | |
| Vitamin E deficiency | |
| Drugs and toxic substances | Alcohol use (excessive and prolonged) |
| Anticonvulsants such as phenytoin, particularly at high doses | |
| Carbon monoxide | |
| Heavy metals such as mercury or lead |
Fragile X-Associated Tremor/Ataxia Syndrome
Fragile X-associated tremor/ataxia syndrome is a genetic disorder that affects mostly men and causes tremor, loss of coordination, and dementia.
The disorder results from a genetic mutation.
In men over 50, tremors in the hands develop first, followed by loss of coordination, slowed movements, decreased facial expression, and sometimes memory loss.
Genetic testing can confirm the diagnosis.
Drugs used to treat Parkinson’s disease can often relieve the tremors.
Fragile X-associated tremor/ataxia syndrome, a newly recognized disorder, may affect as many as 1 of 3,000 men over 50.
Fragile X-associated tremor/ataxia syndrome results from a less extensive abnormality (called a premutation) in a gene on the X chromosome (men have an X and a Y chromosome, and women have 2 X chromosomes). A more extensive (full) mutation in this gene causes fragile X syndrome (which causes mental retardation) in children. People with the premutation are considered carriers. Men with the premutation pass it to their daughters (but not to their sons). Most women with the premutation are unaffected and thus may unknowingly pass the gene on to their sons (grandsons of affected men). Children of such a woman have a 50% chance of inheriting the premutation. When the premutation is passed from mother to child, it sometimes changes into a full mutation, causing fragile X syndrome in the child.
Did You Know…
Some cases of Alzheimer’s disease or Parkinson’s disease are actually a newly recognized disorder called fragile X-associated tremor/ataxia syndrome.
About 30% of men with the premutation and fewer than 5% of women with the premutation develop fragile X-associated tremor/ataxia syndrome as adults. The risk of developing the disorder increases as people age.
Symptoms
Symptoms usually develop later in life. The first symptom is often tremors in the hands, typically when people try to do a task. Other symptoms include loss of coordination, slow movements, stiffness, and decreased facial expression.
People may have problems remembering recent events and solving problems. They may think more slowly. These problems often progress to dementia. People may also have personality changes. They may become depressed, anxious, impatient, hostile, and moody.
Sensation in the feet may be lost. Internal organs may malfunction. Affected people may feel lightheaded when they stand because blood pressure does not increase as it normally does (called orthostatic hypotension). They may have to urinate more frequently. Eventually, they may lose control of the bladder and bowel movements.
After symptoms appear, people may live from about 5 to 25 years.
In women with the premutation, symptoms are usually less severe, possibly because they have another X chromosome, which seems to protect against the effects of the X chromosome with the premutation. Also, women with the premutation are more likely to have early menopause, infertility, and ovarian dysfunction than women without it.
Diagnosis and Treatment
Because this disorder is newly recognized, the diagnosis is sometimes missed or mistaken for disorders that cause similar symptoms, such as Parkinson’s disease or Alzheimer’s disease.
Genetic testing can confirm the diagnosis. Magnetic resonance imaging (MRI) may be done to check for characteristic abnormalities in the brain.
Grandfathers of children with fragile X syndrome should be asked whether they have symptoms suggesting fragile X-associated tremor/ataxia syndrome. Daughters and grandsons of affected men should have genetic counseling. They can be tested for the premutation so that they can make decisions about whether or not to have children and whether or not to have prenatal testing if pregnancy occurs.
Tremors can often be relieved by many of the drugs used to control tremors due to Parkinson’s disease (see table on page 774).