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What is Parkinson's disease?
Parkinson's disease is the second most common neurodegenerative disorder and the most common
movement disorder. It is characterized by progressive loss of muscle control, which leads to trembling
of the limbs and head while at rest, stiffness, slowness, and impaired balance. As symptoms worsen, it
may become difficult to walk, talk, and complete simple tasks.
The progression of Parkinson's disease and the degree of impairment vary from individual to individual.
Many people with Parkinson's disease live long productive lives, whereas others become disabled
much more quickly. Premature death is usually due to complications such as falling-related injuries or
In the United States, about 1 million people are affected by Parkinson's disease and worldwide about
5 million. Most individuals who develop Parkinson's disease are 60 years of age or older. Parkinson's
disease occurs in approximately 1% of individuals aged 60 years and in about 4% of those aged 80
years. Since overall life expectancy is rising, the number of individuals with Parkinson's disease will
increase in the future. Adult-onset Parkinson's disease is most common, but early-onset Parkinson's
disease (onset between 21-40 years), and juvenile-onset Parkinson's disease (onset before age 21)
also exist.
Descriptions of Parkinson's disease date back as far as 5000 BC. Around that time, an ancient Indian
civilization called the disorder Kampavata and treated it with the seeds of a plant containing
therapeutic levels of what is today known as levodopa. Parkinson's disease was named after the
British doctor James Parkinson, who in 1817 first described the disorder in great detail as "shaking
What causes Parkinson's disease?
A substance called dopamine acts as a messenger between two brain areas - the substantia nigra and
the corpus striatum - to produce smooth, controlled movements. Most of the movement-related
symptoms of Parkinson's disease are caused by a lack of dopamine due to the loss of dopamineproducing cells in the substantia nigra. When the amount of dopamine is too low, communication
between the substantia nigra and corpus striatum becomes ineffective, and movement becomes
impaired; the greater the loss of dopamine, the worse the movement-related symptoms. Other cells in
the brain also degenerate to some degree and may contribute to non-movement related symptoms of
Parkinson's disease.
Although it is well known that lack of dopamine causes the motor symptoms of Parkinson's disease, it
is not clear why the dopamine-producing brain cells deteriorate. Genetic and pathological studies have
revealed that various dysfunctional cellular processes, inflammation, and stress can all contribute to
cell damage. In addition, abnormal clumps called Lewy bodies, which contain the protein alphasynuclein, are found in many brain cells of individuals with Parkinson's disease. The function of these
clumps in regards to Parkinson's disease is not understood. In general, scientists suspect that
dopamine loss is due to a combination of genetic and environmental factors
What genes are linked to Parkinson's disease?
In most individuals, Parkinson's disease is idiopathic, which means that it arises sporadically with no
known cause. However, about 15% of individuals have family members with Parkinson's disease. By
studying families with hereditary Parkinson's disease, scientists have identified several genes that are
associated with the disorder. Studying these genes helps understand the cause of Parkinson's
disease and may lead to new therapies. So far, five genes have been identified that are definitively
associated with Parkinson's disease.
1. SNCA (synuclein, alpha non A4 component of amyloid precursor): SNCA makes the protein
alpha-synuclein. In brain cells of individuals with Parkinson's disease, this protein aggregates
in clumps called Lewy bodies. Mutations in the SNCA gene are found in early-onset
Parkinson's disease.
2. PARK2 (Parkinson's disease autosomal recessive, juvenile 2): The PARK2 gene makes the
protein parkin. Mutations of the PARK2 gene are mostly found in individuals with juvenile
Parkinson's disease. Parkin normally helps cells break down and recycle proteins.
3. PARK7 (Parkinson's disease autosomal recessive, early onset 7): PARK7 mutations are
found in early-onset Parkinson's disease. The PARK7 gene makes the DJ-1 protein, which
may protect cells from oxidative stress.
4. PINK1 (PTEN-induced putative kinase 1): Mutations of this gene are found in early-onset
Parkinson's disease. The exact function of the protein made by PINK1 is not known, but it may
protect structures within the cell called mitochondria from stress.
5. LRRK2 (leucine-rich repeat kinase 2): LRRK2 makes the protein dardarin. Mutations in the
LRRK2 gene have been linked to late-onset Parkinson's disease.
Several other chromosome regions and the genes GBA (glucosidase beta acid), SNCAIP (synuclein
alpha interacting protein), and UCHL1 (ubiquitin carboxyl-terminal esterase L1) may also be linked to
Parkinson's disease.
Who is at risk for Parkinson's disease?
Age is the largest risk factor for the development and progression of Parkinson's disease.
Most people who develop Parkinson's disease are older than 60 years years of age.
Men are affected about 1.5 to 2 times more often than women.
A small number of individuals are at increased risk because of a family history of the disorder.
Head trauma, illness, or exposure to environmental toxins such as pesticides and herbicides
may be a risk factor.
What are the symptoms of Parkinson's disease?
The primary symptoms of Parkinson's disease are all related to voluntary and involuntary motor
function and usually start on one side of the body. Symptoms are mild at first and will progress over
time. Some individuals are more affected than others. Studies have shown that by the time that
primary symptoms appear, individuals with Parkinson's disease will have lost 60% to 80% or more of
the dopamine-producing cells in the brain. Characteristic motor symptoms include the following:
Tremors: Trembling in fingers, hands, arms, feet, legs, jaw, or head. Tremors most often
occur while the individual is resting, but not while involved in a task. Tremors may worsen
when an individual is excited, tired, or stressed.
Rigidity: Stiffness of the limbs and trunk, which may increase during movement. Rigidity may
produce muscle aches and pain. Loss of fine hand movements can lead to cramped
handwriting (micrographia) and may make eating difficult.
Bradykinesia: Slowness of voluntary movement. Over time, it may become difficult to initiate
movement and to complete movement. Bradykinesia together with stiffness can also affect the
facial muscles and result in an expressionless, "mask-like" appearance.
Postural instability: Impaired or lost reflexes can make it difficult to adjust posture to
maintain balance. Postural instability may lead to falls.
Parkinsonian gait: Individuals with more progressive Parkinson's disease develop a
distinctive shuffling walk with a stooped position and a diminished or absent arm swing. It may
become difficult to start walking and to make turns. Individuals may freeze in mid-stride and
appear to fall forward while walking.
Secondary symptoms of Parkinson's disease
While the main symptoms of Parkinson's disease are movement-related, progressive loss of muscle
control and continued damage to the brain can lead to secondary symptoms. These vary in severity,
and not every individual will experience all of them. Some of the secondary symptoms include:
anxiety, insecurity, and stress
confusion, memory loss, and dementia (more common in elderly individuals)
difficulty swallowing and excessive salivation
diminished sense of smell
increased sweating
male erectile dysfunction
skin problems
slowed, quieter speech, and monotone voice
urinary frequency/urgency
What other conditions resemble Parkinson's disease?
In its early stages, Parkinson's disease can resemble a number of other conditions with Parkinson-like
symptoms known as Parkinsonism. These conditions include multiple system atrophy, progressive
supranuclear palsy, corticobasal degeneration, Lewy body dementia, stroke, encephalitis
(inflammation of the brain), and head trauma. Alzheimer's disease and primary lateral sclerosis can
also be mistaken for Parkinson's disease. Other similar conditions include essential tremor, dystonic
tremor, vascular Parkinsonism, and drug-induced Parkinsonism.
How is Parkinson's disease diagnosed?
An early and accurate diagnosis of Parkinson's disease is important in developing good treatment
strategies to maintain a high quality of life for as long as possible. However, there is no test to
diagnose Parkinson's disease with certainty (except after the individual has passed away). A diagnosis
of Parkinson's disease - especially in the early phase - can be challenging due to similarities to related
movement disorders and other conditions with Parkinson-like symptoms. Individuals may sometimes
be misdiagnosed as having another disorder, and sometimes individuals with Parkinson-like
symptoms may be inaccurately diagnosed as having Parkinson's disease. It is therefore important to
re-evaluate individuals in the early phase on a regular basis to rule out other conditions that may be
responsible for the symptoms.
A neurologist who specializes in movement disorders will be able to make the most accurate diagnosis.
An initial assessment is made based on medical history, a neurological exam, and the symptoms
present. For the medical history, it is important to know whether other family members have
Parkinson's disease, what types of medication have been or are being taken, and whether there was
exposure to toxins or repeated head trauma in the past. A neurological exam may include an
evaluation of coordination, walking, and fine motor tasks involving the hands.
Several guidelines have been published to assist in the diagnosis of Parkinson's disease. These
include the Hoehn and Yahr scale and the Unified Parkinson's Disease Rating Scale. Tests are used
to measure mental capacity, behavior, mood, daily living activities, and motor function. They can be
very helpful in the initial diagnosis, to rule out other disorders, as well as in monitoring the progression
of the disease to make therapeutic adjustments. Brain scans and other laboratory tests are also
sometimes carried out, mostly to detect other disorders resembling Parkinson's disease.
The diagnosis of Parkinson's disease is more likely if:
1. at least two of the three major symptoms are present (tremor at rest, muscle rigidity, and
2. the onset of symptoms started on one side of the body;
3. symptoms are not due to secondary causes such as medication or strokes in the area
controlling movement; and
4. symptoms are significantly improved with levodopa (see below).
What is the treatment for Parkinson's disease?
There is currently no treatment to cure Parkinson's disease. Several therapies are available to delay
the onset of motor symptoms and to ameliorate motor symptoms. All of these therapies are designed
to increase the amount of dopamine in the brain either by replacing dopamine, mimicking dopamine,
or prolonging the effect of dopamine by inhibiting its breakdown. Studies have shown that early
therapy in the non-motor stage can delay the onset of motor symptoms, thereby extending quality of
The most effective therapy for Parkinson's disease is levodopa (Sinemet), which is converted to
dopamine in the brain. However, because long-term treatment with levodopa can lead to unpleasant
side effects (a shortened response to each dose, painful cramps, and involuntary movements), its use
is often delayed until motor impairment is more severe. Levodopa is frequently prescribed together
with carbidopa (Sinemet), which prevents levodopa from being broken down before it reaches the
brain. Co-treatment with carbidopa allows for a lower levodopa dose, thereby reducing side effects.
In earlier stages of Parkinson's disease, substances that mimic the action of dopamine (dopamine
agonists), and substances that reduce the breakdown of dopamine (monoamine oxidase type B
(MAO-B) inhibitors) can be very efficacious in relieving motor symptoms. Unpleasant side effects of
these preparations are quite common, including swelling caused by fluid accumulation in body tissues,
drowsiness, constipation, dizziness, hallucinations, and nausea.
For some individuals with advanced, virtually unmanageable motor symptoms, surgery may be an
option. In deep brain stimulation (DBS), the surgeon implants electrodes to stimulate areas of the
brain involved in movement. In another type of surgery, specific areas in the brain that cause
Parkinson's symptoms are destroyed.
An alternative approach currently being explored is the use of dopamine-producing cells derived from
stem cells. While stem cell therapy has great potential, more research is required before such cells
can become of therapeutic value in the treatment of Parkinson's disease.
In addition to medication and surgery, general lifestyle changes (rest and exercise), physical therapy,
occupational therapy, and speech therapy may be beneficial.
How can people learn to cope with Parkinson's disease?
Although Parkinson's disease progresses slowly, it will eventually affect every aspect of life - from
social engagements, work, to basic routines. Accepting the gradual loss of independence can be
difficult. Being well informed about the disease can reduce anxiety about what lies ahead. Many
support groups offer valuable information for individuals with Parkinson's disease and their families on
how to cope with the disorder. Local groups can provide emotional support as well as advice on where
to find experienced doctors, therapists, and related information. It is also very important to stay in
close contact with health care providers to monitor the progression of the disease and to adjust
therapies to maintain the highest quality of living.
Can Parkinson's disease be prevented?
Scientists currently believe that Parkinson's disease is triggered through a complex combination of
genetic susceptibility and exposure to environmental factors such as toxins, illness, and trauma. Since
the exact causes are not known, Parkinson's disease is at present not preventable.
What is the prognosis of Parkinson's disease?
The severity of Parkinson's disease symptoms vary greatly from individual to individual and it is not
possible to predict how quickly the disorder will progress. Parkinson's disease itself is not a fatal
disease, and the average life expectancy is similar to that of people without the disease. Secondary
complications, such as pneumonia, falling-related injuries, and choking can lead to death. There are
many treatment options that can reduce some of the symptoms and can prolong the quality of life of
an individual with Parkinson's disease.
Parkinson's disease at a glance
Parkinson's disease is a neurodegenerative disorder which leads to progressive deterioration
of motor function due to loss of dopamine-producing brain cells.
Primary symptoms include tremor, stiffness, slowness, impaired balance, and later on a
shuffling gait.
Some secondary symptoms include anxiety, depression, and dementia.
Most individuals with Parkinson's disease are diagnosed when they are 60 years old or older,
but early-onset Parkinson's disease also occurs.
With proper treatment, most individuals with Parkinson's disease can lead long, productive
lives for many years after diagnosis.
What is tremor?
Tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements
(oscillations) of one or more parts of the body. It is the most common of all involuntary movements and
can affect the hands, arms, head, face, vocal cords, trunk, and legs. Most tremors occur in the hands.
In some people, tremor is a symptom of another neurological disorder. The most common form of
tremor, however, occurs in otherwise healthy people. Although tremor is not life-threatening, it can be
embarrassing to some people and make it harder to perform daily tasks.
What causes tremor?
Tremor is generally caused by problems in parts of the brain that control muscles throughout the body
or in particular areas, such as the hands. Neurological disorders or conditions that can produce tremor
include multiple sclerosis, stroke, traumatic brain injury, and neurodegenerative diseases that damage
or destroy parts of the brainstem or the cerebellum. Other causes include the use of some drugs (such
as amphetamines, corticosteroids, and drugs used for certain psychiatric disorders), alcohol abuse or
withdrawal, mercury poisoning, overactive thyroid, or liver failure. Some forms of tremor are inherited
and run in families, while others have no known cause.
What are the characteristics of tremor?
Characteristics may include a rhythmic shaking in the hands, arms, head, legs, or trunk; shaky voice;
difficulty writing or drawing; or problems holding and controlling utensils, such as a fork. Some tremors
may be triggered by or become exaggerated during times of stress or strong emotion, when the
individual is physically exhausted, or during certain postures or movements.
Tremor may occur at any age but is most common in middle-aged and older persons. It may be
occasional, temporary, or occur intermittently. Tremor affects men and women equally.
A useful way to understand and describe tremors is to define them according to the following types.
Resting or static tremor occurs when the muscle is relaxed and the limb is fully supported against
gravity, such as when the hands are lying on the lap. It may be seen as a shaking of the limb, even
when the person is at rest. This type of tremor is often seen in patients with Parkinson's disease. An
action tremor occurs during any type of movement of an affected body part. There are several
subclassifications of action tremor. Postural tremor occurs when the person maintains a position
against gravity, such as holding the arms outstretched. Kinetic (or intention) tremor occurs during
purposeful voluntary movement, such as touching a finger to one's nose during a medical exam. Taskspecific tremor appears when performing highly skilled, goal-oriented tasks such as handwriting or
speaking. Isometric tremor occurs during a voluntary muscle contraction that is not accompanied by
any movement.
What are the different categories of tremor?
Tremor is most commonly classified by clinical features and cause or origin. Some of the better known
forms of tremor, with their symptoms, include the following:
Essential tremor (sometimes called benign essential tremor) is the most common of the more than
20 types of tremor. Although the tremor may be mild and nonprogressive in some people, in others,
the tremor is slowly progressive, starting on one side of the body but affecting both sides within 3
years. The hands are most often affected but the head, voice, tongue, legs, and trunk may also be
involved. Head tremor may be seen as a "yes-yes" or "no-no" motion. Essential tremor may be
accompanied by mild gait disturbance. Tremor frequency may decrease as the person ages, but the
severity may increase, affecting the person's ability to perform certain tasks or activities of daily living.
Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremors and/or
increase their severity. Onset is most common after age 40, although symptoms can appear at any
age. It may occur in more than one family member. Children of a parent who has essential tremor
have a 50 percent chance of inheriting the condition. Essential tremor is not associated with any
known pathology.
Parkinsonian tremor is caused by damage to structures within the brain that control movement. This
resting tremor, which can occur as an isolated symptom or be seen in other disorders, is often a
precursor to Parkinson's disease (more than 25 percent of patients with Parkinson's disease have an
associated action tremor). The tremor, which is classically seen as a "pill-rolling" action of the hands
that may also affect the chin, lips, legs, and trunk, can be markedly increased by stress or emotions.
Onset of parkinsonian tremor is generally after age 60. Movement starts in one limb or on one side of
the body and usually progresses to include the other side.
Dystonic tremor occurs in individuals of all ages who are affected by dystonia, a movement disorder
in which sustained involuntary muscle contractions cause twisting and repetitive motions and/or
painful and abnormal postures or positions. Dystonic tremor may affect any muscle in the body and is
seen most often when the patient is in a certain position or moves a certain way. The pattern of
dystonic tremor may differ from essential tremor. Dystonic tremors occur irregularly and often can be
relieved by complete rest. Touching the affected body part or muscle may reduce tremor severity. The
tremor may be the initial sign of dystonia localized to a particular part of the body.
Cerebellar tremor is a slow, broad tremor of the extremities that occurs at the end of a purposeful
movement, such as trying to press a button or touching a finger to the tip of one's nose. Cerebellar
tremor is caused by lesions in or damage to the cerebellum resulting from stroke, tumor, or disease
such as multiple sclerosis or some inherited degenerative disorder. It can also result from chronic
alcoholism or overuse of some medicines. In classic cerebellar tremor, a lesion on one side of the
brain produces a tremor in that same side of the body that worsens with directed movement.
Cerebellar damage can also produce a "wing-beating" type of tremor called rubral or Holmes' tremor a combination of rest, action, and postural tremors. The tremor is often most prominent when the
affected person is active or is maintaining a particular posture. Cerebellar tremor may be accompanied
by dysarthria (speech problems), nystagmus (rapid, involuntary rolling of the eyes), gait problems, and
postural tremor of the trunk and neck.
Psychogenic tremor (also called hysterical tremor) can occur at rest or during postural or kinetic
movement. The characteristics of this kind of tremor may vary but generally include sudden onset and
remission, increased incidence with stress, change in tremor direction and/or body part affected, and
greatly decreased or disappearing tremor activity when the patient is distracted. Many patients with
psychogenic tremor have a conversion disorder (defined as a psychological disorder that produces
physical symptoms) or another psychiatric disease.
Orthostatic tremor is characterized by rhythmic muscle contractions that occur in the legs and trunk
immediately after standing. Cramps are felt in the thighs and legs and the patient shakes
uncontrollably when asked to stand in one spot. No other clinical signs or symptoms are present and
the shaking ceases when the patient sits or is lifted off the ground. Orthostatic tremor may also occur
in patients who have essential tremor.
Physiologic tremor occurs in every normal individual and has no clinical significance. It is rarely
visible to the eye and may be heightened by strong emotion (such as anxiety or fear), physical
exhaustion, hypoglycemia, hyperthyroidism, heavy metal poisoning, stimulants, alcohol withdrawal, or
fever. It can be seen in all voluntary muscle groups and can be detected by extending the arms and
placing a piece of paper on of the hands. Enhanced physiologic tremor is a strengthening of
physiologic tremor to more visible levels. It is generally not caused by a neurological disease but by
reaction to certain drugs, alcohol withdrawal, or medical conditions including an overactive thyroid and
hypoglycemia. It is usually reversible once the cause is corrected.
Tremor can result from other conditions as well. Alcoholism, excessive alcohol consumption, or
alcohol withdrawal can kill certain nerve cells, resulting in tremor, especially in the hand. (Conversely,
small amounts of alcohol may help to decrease familial and essential tremor, but the mechanism
behind this is unknown. Doctors may use small amounts of alcohol to aid in the diagnosis of certain
forms of tremor but not as a regular treatment for the condition.) Tremor in peripheral neuropathy may
occur when the nerves that supply the body's muscles are traumatized by injury, disease, abnormality
in the central nervous system, or as the result of systemic illnesses. Peripheral neuropathy can affect
the whole body or certain areas, such as the hands, and may be progressive. Resulting sensory loss
may be seen as a tremor or ataxia (inability to coordinate voluntary muscle movement) of the affected
limbs and problems with gait and balance. Clinical characteristics may be similar to those seen in
patients with essential tremor.
How is tremor diagnosed?
During a physical exam a doctor can determine whether the tremor occurs primarily during action or at
rest. The doctor will also check for tremor symmetry, any sensory loss, weakness or muscle atrophy,
or decreased reflexes. A detailed family history may indicate if the tremor is inherited. Blood or urine
tests can detect thyroid malfunction, other metabolic causes, and abnormal levels of certain chemicals
that can cause tremor. These tests may also help to identify contributing causes, such as drug
interaction, chronic alcoholism, or another condition or disease. Diagnostic imaging using
computerized tomography or magnetic resonance imaging may help determine if the tremor is the
result of a structural defect or degeneration of the brain.
The doctor will perform a neurological exam to assess nerve function and motor and sensory skills.
The tests are designed to determine any functional limitations, such as difficulty with handwriting or
the ability to hold a utensil or cup. The patient may be asked to place a finger on the tip of her or his
nose, draw a spiral, or perform other tasks or exercises.
The doctor may order an electromyogram to diagnose muscle or nerve problems. This test measures
involuntary muscle activity and muscle response to nerve stimulation.
Are there any treatments?
There is no cure for most tremors. The appropriate treatment depends on accurate diagnosis of the
Some tremors respond to treatment of the underlying condition. For example, in some cases of
psychogenic tremor, treating the patient's underlying psychological problem may cause the tremor to
Symptomatic drug therapy is available for several forms of tremor. Drug treatment for parkinsonian
tremor involves levodopa and/or dopamine-like drugs such as pergolide mesylate, bromocriptine
mesylate, and ropinirole. Other drugs used to lessen parkinsonian tremor include amantadine
hydrochloride and anticholinergic drugs.
Essential tremor may be treated with propranolol or other beta blockers (such as nadolol) and
primidone, an anticonvulsant drug.
Cerebellar tremor typically does not respond to medical treatment. Patients with rubral tremor may
receive some relief using levodopa or anticholinergic drugs.
Dystonic tremor may respond to clonazepam, anticholinergic drugs, and intramuscular injections of
botulinum toxin. Botulinum toxin is also prescribed to treat voice and head tremors and several
movement disorders.
Clonazepam and primidone may be prescribed for primary orthostatic tremor.
Enhanced physiologic tremor is usually reversible once the cause is corrected. If symptomatic
treatment is needed, beta blockers can be used.
Eliminating tremor "triggers" such as caffeine and other stimulants from the diet is often recommended.
Physical therapy may help to reduce tremor and improve coordination and muscle control for some
patients. A physical therapist will evaluate the patient for tremor positioning, muscle control, muscle
strength, and functional skills. Teaching the patient to brace the affected limb during the tremor or to
hold an affected arm close to the body is sometimes useful in gaining motion control. Coordination and
balancing exercises may help some patients. Some therapists recommend the use of weights, splints,
other adaptive equipment, and special plates and utensils for eating.
Surgical intervention such as thalamotomy and deep brain stimulation may ease certain tremors.
These surgeries are usually performed only when the tremor is severe and does not respond to drugs.
Thalamotomy, involving the creation of lesions in the brain region called the thalamus, is quite
effective in treating patients with essential, cerebellar, or parkinsonian tremor. This in-hospital
procedure is performed under local anesthesia, with the patient awake. After the patient's head is
secured in a metal frame, the surgeon maps the patient's brain to locate the thalamus. A small hole is
drilled through the skull and a temperature-controlled electrode is inserted into the thalamus. A lowfrequency current is passed through the electrode to activate the tremor and to confirm proper
placement. Once the site has been confirmed, the electrode is heated to create a temporary lesion.
Testing is done to examine speech, language, coordination, and tremor activation, if any. If no
problems occur, the probe is again heated to create a 3-mm permanent lesion. The probe, when
cooled to body temperature, is withdrawn and the skull hole is covered. The lesion causes the tremor
to permanently disappear without disrupting sensory or motor control.
Deep brain stimulation (DBS) uses implantable electrodes to send high-frequency electrical signals to
the thalamus. The electrodes are implanted as described above. The patient uses a hand-held magnet
to turn on and turn off a pulse generator that is surgically implanted under the skin. The electrical
stimulation temporarily disables the tremor and can be "reversed," if necessary, by turning off the
implanted electrode. Batteries in the generator last about 5 years and can be replaced surgically. DBS
is currently used to treat parkinsonian tremor and essential tremor.
The most common side effects of tremor surgery include dysarthria (problems with motor control of
speech), temporary or permanent cognitive impairment (including visual and learning difficulties), and
problems with balance.
What are the dystonias?
The dystonias are movement disorders in which sustained muscle contractions cause twisting and
repetitive movements or abnormal postures. The movements, which are involuntary and sometimes
painful, may affect a single muscle; a group of muscles such as those in the arms, legs, or neck; or the
entire body. Those with dystonia usually have normal intelligence and no associated psychiatric
What are the symptoms of dystonias?
Dystonia can affect many different parts of the body. Early symptoms may include a deterioration in
handwriting after writing several lines, foot cramps, and/or a tendency of one foot to pull up or drag;
this may occur "out of the blue" or may occur after running or walking some distance. The neck may
turn or pull involuntarily, especially when the patient is tired or stressed. Sometimes both eyes will
blink rapidly and uncontrollably, rendering a person functionally blind. Other possible symptoms are
tremor and voice or speech difficulties. The initial symptoms can be very mild and may be noticeable
only after prolonged exertion, stress, or fatigue. Over a period of time, the symptoms may become
more noticeable and widespread and be unrelenting; sometimes, however, there is little or no
How are the dystonias classified?
One way to classify the dystonias is according to the parts of the body they affect:
Generalized dystonia affects most or all of the body.
Focal dystonia is localized to a specific part of the body.
Multifocal dystonia involves two or more unrelated body parts.
Segmental dystonia affects two or more adjacent parts of the body.
Hemidystonia involves the arm and leg on the same side of the body.
Some patterns of dystonia are defined as specific syndromes:
Torsion dystonia, previously called dystonia musculorum deformans or DMD, is a rare, generalized
dystonia that may be inherited, usually begins in childhood, and becomes progressively worse. It can
leave individuals seriously disabled and confined to a wheelchair. Genetic studies have revealed an
underlying cause in many patients - a mutation in a gene named DYT1. And it has been discovered
that this gene is related not only to generalized dystonia, but also to some forms of focal dystonia.
Note, however, that most dystonia, of any type, is not due to this gene and has an unknown cause.
Cervical dystonia, also called spasmodic torticollis, or torticollis, is the most common of the focal
dystonias. In torticollis, the muscles in the neck that control the position of the head are affected,
causing the head to twist and turn to one side. In addition, the head may be pulled forward or
backward. Torticollis can occur at any age, although most individuals first experience symptoms in
middle age. It often begins slowly and usually reaches a plateau. About 10 to 20 percent of those with
torticollis experience a spontaneous remission, but unfortunately the remission may not be lasting.
Blepharospasm, the second most common focal dystonia, is the involuntary, forcible closure of the
eyelids. The first symptoms may be uncontrollable blinking. Only one eye may be affected initially, but
eventually both eyes are usually involved. The spasms may leave the eyelids completely closed
causing functional blindness even though the eyes and vision are normal.
Cranial dystonia is a term used to describe dystonia that affects the muscles of the head, face, and
neck. Oromandibular dystonia affects the muscles of the jaw, lips, and tongue. The jaw may be pulled
either open or shut, and speech and swallowing can be difficult. Spasmodic dysphonia involves the
muscles of the throat that control speech. Also called spastic dysphonia or laryngeal dystonia, it
causes strained and difficult speaking or breathy and effortful speech. Meige's syndrome is the
combination of blepharospasm and oromandibular dystonia and sometimes spasmodic dysphonia.
Spasmodic torticollis can be classified as a type of cranial dystonia.
Writer's cramp is a dystonia that affects the muscles of the hand and sometimes the forearm, and
only occurs during handwriting. Similar focal dystonias have also been called typist's cramp, pianist's
cramp, and musician's cramp. Dopa-responsive dystonia (DRD), of which Segawa's dystonia is an
important variant, is a condition successfully treated with drugs. Typically, DRD begins in childhood or
adolescence with progressive difficulty in walking and, in some cases, spasticity. In Segawa's dystonia,
the symptoms fluctuate during the day from relative mobility in the morning to increasingly worse
disability in the afternoon and evening as well as after exercise. The diagnosis of DRD may be missed
since it mimics many of the symptoms of cerebral palsy.
What do scientists know about the dystonias?
Investigators believe that the dystonias result from an abnormality in an area of the brain called the
basal ganglia where some of the messages that initiate muscle contractions are processed. Scientists
suspect a defect in the body's ability to process a group of chemicals called neurotransmitters that
help cells in the brain communicate with each other. Some of these neurotransmitters include:
GABA (gamma-aminobutyric acid), an inhibitory substance that helps the brain maintain
muscle control.
Dopamine, an inhibitory chemical that influences the brain's control of movement.
Acetylcholine, an excitatory chemical that helps regulate dopamine in the brain. In the body,
acetylcholine released at nerve endings causes muscle contraction.
Norepinephrine and serotonin, inhibitory chemicals that help the brain regulate acetylcholine.
Acquired dystonia, also called secondary dystonia, results from environmental or disease-related
damage to the basal ganglia. Birth injury (particularly due to lack of oxygen), certain infections,
reactions to certain drugs, heavy-metal or carbon monoxide poisoning, trauma, or stroke can cause
dystonic symptoms. Dystonias can also be symptoms of other diseases, some of which may be
About half the cases of dystonia have no connection to disease or injury and are called primary or
idiopathic dystonia. Of the primary dystonias, many cases appear to be inherited in a dominant
manner; i.e., only one carrier parent need contribute the dystonia gene for the disease to occur, each
child having a 50/50 chance of being a carrier. In dystonia, however, a carrier may or may not develop
a dystonia and the symptoms may vary widely even among members of the same family. The product
of one defective gene appears to be sufficient to cause the chemical imbalances that may lead to
dystonia; but the possibility exists that another gene or genes and environmental factors may play a
Some cases of primary dystonia may have different types of hereditary patterns. Knowing the pattern
of inheritance can help families understand the risk of passing dystonia along to future generations.
When do symptoms of dystonias occur?
In some individuals, symptoms of a dystonia appear in childhood, approximately between the ages of
5 and 16, usually in the foot or in the hand. In generalized dystonia, the involuntary dystonic
movements may progress quickly to involve all limbs and the torso, but the rate of progression usually
slows noticeably after adolescence.
For other individuals, the symptoms emerge in late adolescence or early adulthood. In these cases,
the dystonia often begins in upper body parts, with symptoms progressing slowly. A dystonia that
begins in adulthood is more likely to remain as a focal or segmental dystonia.
Dystonias often progress through various stages. Initially, dystonic movements are intermittent and
appear only during voluntary movements or stress. Later, individuals may show dystonic postures and
movements while walking and ultimately even while they are relaxed. Dystonic motions may lead to
permanent physical deformities by causing tendons to shorten.
In secondary dystonias due to injury or stroke, people often have abnormal movements of just one
side of the body, which may begin at the time of the brain injury or sometime afterward. Symptoms
generally plateau and do not usually spread to other parts of the body.
Are there any treatments for dystonias?
No one treatment has been found universally effective. Instead, physicians use a variety of therapies
aimed at reducing or eliminating muscle spasms and pain.
Medication. Several classes of drugs that may help correct imbalances in neurotransmitters have
been found useful. But response to drugs varies among patients and even in the same person over
time. The most effective therapy is often individualized, with physicians prescribing several types of
drugs at different doses to treat symptoms and produce the fewest side effects. Note that not all of the
medications mentioned below are currently available for patients in the United States.
Frequently, the first drug administered belongs to a group that reduces the level of the
neurotransmitter acetylcholine. Drugs in this group include trihexyphenidyl, benztropine (Cogentin),
and procyclidine HCl. Sometimes these medications can be sedating, especially at higher doses, and
this can limit their usefulness.
Drugs that regulate the neurotransmitter GABA may be used in combination with these drugs or alone
in patients with mild symptoms. GABA-regulating drugs include the muscle relaxants diazepam
(Valium), lorazepam (Ativan), clonazepam (Klonopin), and baclofen (Lioresal).
Other drugs act on dopamine, a neurotransmitter that helps the brain fine-tune muscle movement.
Some drugs which increase dopamine effects include levodopa/carbidopa (Sinemet) and
bromocriptine (parlodel). DRD has been remarkably responsive to small doses of this dopamineboosting treatment. On the other hand, patients have occasionally benefited from drugs that decrease
dopamine, such as reserpine or the investigational drug tetrabenazine. Once again, side effects can
restrict the use of these medications.
Anticonvulsants including carbamazepine (Tegretol), usually prescribed to control epilepsy, have
occasionally helped individuals with dystonia.
Botulinum toxin (Botox). Minute amounts of this familiar toxin can be injected into affected muscles
to provide temporary relief of focal dystonias. First used to treat blepharospasm, such injections have
gained wider acceptance among physicians for treating other focal dystonias. The toxin stops muscle
spasms by blocking release of the excitatory neurotransmitter acetylcholine. The effect lasts for up to
several months before the injections have to be repeated.
Surgery and other treatments. Surgery may be recommended for some patients when medication is
unsuccessful or the side effects are too severe. In selected cases, advanced generalized dystonias
have been helped, at least temporarily, by surgical destruction of parts of the thalamus, a structure
deep in the brain that helps control movement. Speech disturbance is a special risk accompanying this
procedure, since the thalamus lies near brain structures that help control speech. Surgically cutting or
removing the nerves to the affected muscles has helped some focal dystonias, including
blepharospasm, spasmodic dysphonia and torticollis. The benefits of these operations, however, can
be short-lived. They also carry the risk of disfigurement, can be unpredictable, and are irreversible.
Some patients with spasmodic dysphonia may benefit from treatment by a speech-language
pathologist. Physical therapy, splinting, stress management, and biofeedback may also help
individuals with certain forms of dystonia.
Tardive dyskinesia: A neurological syndrome characterized by repetitive, involuntary, purposeless
movements caused by the long-term use of certain drugs called neuroleptics used for psychiatric,
gastrointestinal and neurological disorders such as Parkinson's disease. Features may include
grimacing, tongue protrusion, lip smacking, puckering and pursing, and rapid eye blinking. Rapid
movements of the arms, legs, and trunk may also occur. Impaired movements of the fingers may
appear as though the patient is playing an invisible guitar or piano. The incidence of the syndrome
rises with the dose and duration of drug treatment. The treatment of tardive dyskinesis is usually to
stop or minimize the use of the offending drug. However, for some patients with a severe underlying
condition this may not be a feasible option. Replacing the offending drug with substitute drugs may
help. Other drugs such as benzodiazepines, adrenergic antagonists, and dopamine agonists may also
be beneficial. In an individual case, the symptoms of tardive dyskinesia may remain long after
discontinuation of the offending drug or the symptoms may improve or disappear with time.
Spasmodic dysphonia: A voice disorder caused by involuntary movements of one or more muscles
of the larynx or voice box. People who have spasmodic dysphonia may have occasional difficulty
saying a word or two or they may experience sufficient difficulty to interfere with communication.
Spasmodic dysphonia causes the voice to break or to have a tight, strained, strangled or effortful
quality. Spasmodic dysphonia can affect anyone. It most often becomes evident between 30 and 50
years of age. More women are affected by spasmodic dysphonia than men. Also called spastic
dysphonia and laryngeal dystonia.
There are three different types of spasmodic dysphonia: adductor spasmodic dysphonia, abductor
spasmodic dysphonia and mixed spasmodic dysphonia:
Adductor spasmodic dysphonia -- A form of spasmodic dysphonia in which sudden involuntary
muscle movements or spasms cause the vocal folds (or vocal cords) to slam together (adduct)
and stiffen. These spasms make it difficult for the vocal folds to vibrate and produce voice.
Words are often cut off or difficult to start because of the muscle spasms. Therefore, speech
may be choppy and sound similar to stuttering. The voice of an individual with adductor
spasmodic dysphonia is commonly described as strained or strangled and full of effort.
Surprisingly, the spasms are usually absent while whispering, laughing, singing, speaking at a
high pitch or speaking while breathing in. Stress, however, often makes the muscle spasms
more severe.
Abductor spasmodic dysphonia -- A form of spasmodic dysphonia in which sudden involuntary
muscle movements or spasms cause the vocal folds to open (abduct). The vocal folds can not
vibrate when they are open. The open position of the vocal folds also allows air to escape
from the lungs during speech. As a result, the voices of these individuals often sound weak,
quiet and breathy or whispery. As with adductor spasmodic dysphonia, the spasms are often
absent during activities such as laughing or singing.
Mixed spasmodic dysphonia -- A form of spasmodic dysphonia involving the muscles that
open the vocal folds as well as the muscles that close the vocal folds. Mixed spasmodic
dysphonia therefore has features of both adductor and abductor spasmodic dysphonia.
The basic cause of spasmodic dysphonia is unknown. Because the voice can sound normal or near
normal at times, spasmodic dysphonia was once thought to be psychogenic. While psychogenic forms
of spasmodic dysphonia exist, there is increasing evidence that most cases of spasmodic dysphonia
are neurogenic (of neurologic origin).
Spasmodic dysphonia may co-occur with other movement disorders such as blepharospasm
(excessive eye blinking and involuntary forced eye closure), tardive dyskinesia (involuntary and
repetitious movement of muscles of the face, body, arms and legs), oromandibular dystonia
(involuntary movements of the jaw muscles, lips and tongue), torticollis (involuntary movements of the
neck muscles), or tremor (rhythmic, quivering muscle movements).
Spasmodic dysphonia runs in some families and is thought to be inherited. Research has identified a
possible gene on chromosome 9 that may contribute to the spasmodic dysphonia that is common to
certain families. In some individuals the voice symptoms begin following an upper respiratory infection,
injury to the larynx, a long period of voice use, or stress.
The diagnosis of spasmodic dysphonia is usually made based on identifying the way the symptoms
developed as well as by careful examination of the individual. Most people are evaluated by a team
that usually includes an otolaryngologist (an ear, nose and throat physician), a speech-language
pathologist (a professional trained to diagnose and treat speech, language and voice disorders) and a
neurologist. The otolaryngologist examines the vocal folds to look for other possible causes for the
voice disorder. Fiberoptic nasolaryngoscopy, a method whereby a small lighted tube is passed
through the nose and into the throat, is a helpful tool that allows the otolaryngologist to evaluate vocal
cord movement during speech. The speech-language pathologist evaluates the patient's voice and
voice quality. The neurologist evaluates the patient for signs of other muscle movement disorders.
Spasmodic dysphonia (cont.)
There is presently no cure for spasmodic dysphonia. Current treatments only help reduce the
symptoms of this voice disorder. Voice therapy may reduce some symptoms, especially in mild cases.
An operation that cuts one of the nerves of the vocal folds (the recurrent laryngeal nerve) has
improved the voice of many for several months to several years but the improvement is often
temporary. Others may benefit from psychological counseling to help them to accept and live with their
voice problem. Still others may benefit from job counseling that will help them select a line of work
more compatible with their speaking limitations.
The most promising treatment to relieve the symptoms of spasmodic dysphonia currently appears to
be injections of very small amounts of botulinum toxin (botox) directly into the affected muscles of the
larynx. Botox injections generally improve the voice for a period of three to four months after which the
voice symptoms gradually return. Reinjections are necessary to maintain a good speaking voice. Initial
side effects that usually subside after a few days to a few weeks may include a temporary weak,
breathy voice or occasional swallowing difficulties. Botox may relieve the symptoms of both adductor
and abductor spasmodic dysphonia.