Tremor – Causes, Symptoms, Diagnosis, Treatment

Tremor is defined as an involuntary rhythmic and oscillatory movement of a body part with a relatively constant frequency and variable amplitude. Alternating contractions of antagonistic muscles cause it. Tremor is the most common of all movement disorders, and essential tremor is the most common neurologic cause of postural or action tremor. It usually presents as a bilateral postural 6 to 12 Hz tremor of the hands, followed by a kinetic and resting component. The upper limbs are often symmetrically involved, but with disease progression, the head and voice (less commonly legs, jaw, face, and trunk) may be involved. Although benign regarding its effect on life expectancy, it often causes embarrassment and, in a small percentage of patients, also serious disability. Symptoms are typically progressive and potentially disabling, often forcing patients to change jobs or seek early retirement.

Types of Tremor

The most common postural tremors are as follows:

  • Anxiety and fatigue tremors –  fine, rapid tremors involving the fingers. The injection of epinephrine into normal individuals produces tremors identical to those seen in anxiety or with fatigue.
  • Thyrotoxicosis – a fine, rapid tremor of the fingers identical to the tremors listed above.
  • Essential (benign familial) tremor – a coarse, irregular tremor that usually starts in the hands and fingers and eventually involves the voice, head, and neck. Usually it becomes worse with goal-directed movements. Difficulty with handwriting, piano playing, typing, or drinking coffee is often the most prominent complaint. Drinking alcohol diminishes the tremor. There is a strong heritable tendency. Onset is in early adult life. Treatment with propranolol is efficacious in some patients.
  • Cerebellar tremor – a coarse, irregular tremor involving the shoulder girdle and neck, seen in patients with diseases of the cerebellum. A prime example is alcoholic cerebellar cortical degeneration. When quite severe, it can be present at rest also.
  • Lithium tremor – seen in individuals being treated with lithium. It is quite similar to essential tremor.
  • Physiologic tremor – Predominantly bilateral, symmetrical action tremor. High frequency (10 to 12 Hz), the presence of known cause (e.g., medications, hyperthyroidism, hypoglycemia)
  • Parkinson’s Disease Tremor – Predominantly at rest, asymmetrical.  Usually does not produce head tremor. Frequency 4 to 6 Hz.
  • Orthostatic tremor – Postural tremor in the torso and lower limbs while standing; may also occur in the upper limbs. Suppressed by walking. Tremor is high frequency (14 to 20 Hz) and synchronous among ipsilateral and contralateral muscles.
  • Cerebellar tremor – Postural, intention, or action tremor. Relatively low frequency (3 to 4 Hz). Associated with ataxia and dysmetria
  • Writing tremor (task-specific) – Not evident in other tasks requiring coordination, only during writing. Is considered a variant of focal hand dystonia (Writer’s cramp).
  • Psychogenic tremor – It is not an exclusion diagnosis. Symptoms vary in severity, depending on the subject’s emotional state associated with stressful life events. Several clues are helpful to differentiate the psychogenic nature and include sudden onset and spontaneous remission, larger variations of amplitude and frequency, and less severity. The tremors disappear with distractions such as alternate finger tapping, mental concentration on serial 7s, or the healthcare professional applying a vibrating tuning fork to a patient’s forehead and informing the patient (wrongly) that this can stop the tremor and entrainment. Entrainment is a change in frequency of the tremor in adaptation to voluntary movements such as a regular movement in the contralateral limb.
  • Postural tremors – are also seen in Wilson’s disease, acquired hepatocerebral degeneration, and certain poisons, especially mercury. Mercury poisoning was known as the “hatter’s shakes” because workers involved in the manufacture of felt hats were exposed to mercury.
  • Kinetic tremor – is associated with any voluntary movement, such as moving the wrists up and down or closing and opening the eyes.
  • Intention tremor – is produced with the purposeful movement toward a target, such as lifting a finger to touch the nose.  Typically the tremor will become worse as an individual gets closer to their target.
  • Task-specific tremor – only 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 such as holding a heavy book or a dumbbell in the same position.

What are the different categories or types of tremor?

Tremor is most commonly classified by its appearance and cause or origin.  There are more than 20 types of tremor.  Some of the most common forms of tremor include:

Essential tremor

Essential tremor (previously also called benign essential tremor or familial tremor) is one of the most common movement disorders.  The exact cause of essential tremor is unknown.  For some people this tremor is mild and remains stable for many years.  The tremor usually appears on both sides of the body, but is often noticed more in the dominant hand because it is an action tremor.

The key feature of essential tremor is a tremor in both hands and arms, which is present during action and when standing still.  Additional symptoms may include head tremor (e.g., a “yes” or “no” motion) without abnormal posturing of the head and a shaking or quivering sound to the voice if the tremor affects the voice box.  The action tremor in both hands in essential tremor can lead to problems with writing, drawing, drinking from a cup, or using tools or a computer.

Tremor frequency (how “fast” the tremor shakes) 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 tremor and/or increase its severity.  Though the tremor can start at any age, it most often appears for the first time during adolescence or in middle age (between ages 40 and 50).  Small amounts of alcohol may help decrease essential tremor, but the mechanism behind this is unknown.

About 50 percent of the cases of essential tremor are thought to be caused by a genetic risk factor (referred to as familial tremor).  Children of a parent who has familial tremor have greater risk of inheriting the condition.  Familial forms of essential tremor often appear early in life.

For many years essential tremor was not associated with any known disease.  However, some scientists think essential tremor is accompanied by a mild degeneration of certain areas of the brain that control movement.  This is an ongoing debate in the research field.

Dystonic tremor

Dystonic tremor occurs in people who are affected by dystonia—a movement disorder where incorrect messages from the brain cause muscles to be overactive, resulting in abnormal postures or sustained, unwanted movements.  Dystonic tremor usually appears in young or middle-aged adults and can affect any muscle in the body.  Symptoms may sometimes be relieved by complete relaxation.

Although some of the symptoms are similar, dystonic tremor differs from essential tremor in some ways.  The dystonic tremor:

  • is associated with abnormal body postures due to forceful muscle spasms or cramps
  • can affect the same parts of the body as essential tremor, but also—and more often than essential tremor—the head, without any other movement in the hands or arms
  • can also mimic resting tremor, such as the one seen in Parkinson’s disease.
  • Also, the severity of dystonic tremor may be reduced by touching the affected body part or muscle, and tremor movements are “jerky” or irregular instead of rhythmic.

Cerebellar tremor

Cerebellar tremor is typically a slow, high-amplitude (easily visible) tremor of the extremities (e.g., arm, leg) that occurs at the end of a purposeful movement such as trying to press a button.  It is caused by damage to the cerebellum and its pathways to other brain regions resulting from a stroke or tumor.  Damage also may be caused by disease such as multiple sclerosis or an inherited degenerative disorder such as ataxia (in which people lose muscle control in the arms and legs) and Fragile X syndrome (a disorder marked by a range of intellectual and developmental problems).  It can also result from chronic damage to the cerebellum due to alcoholism.

Psychogenic tremor

Psychogenic tremor (also called functional tremor) can appear as any form of tremor.  It symptoms may vary but often start abruptly and may affect all body parts.  The tremor increases in times of stress and decreases or disappears when distracted.  Many individuals with psychogenic tremor have an underlying psychiatric disorder such as depression or post-traumatic stress disorder (PTSD).

Physiologic tremor

Physiologic tremor occurs in all healthy individuals.  It is rarely visible to the eye and typically involves a fine shaking of both of the hands and also the fingers.  It is not considered a disease but is a normal human phenomenon that is the result of physical properties in the body (for example, rhythmical activities such as heart beat and muscle activation).

Enhanced physiologic tremor

Enhanced physiological tremor is a more noticeable case of physiologic tremor that can be easily seen.  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.

Parkinsonian tremor

Parkinsonian tremor is a common symptom of Parkinson’s disease, although not all people with Parkinson’s disease have tremor.  Generally, symptoms include shaking in one or both hands at rest.  It may also affect the chin, lips, face, and legs.  The tremor may initially appear in only one limb or on just one side of the body.  As the disease progresses, it may spread to both sides of the body.  The tremor is often made worse by stress or strong emotions.  More than 25 percent of people with Parkinson’s disease also have an associated action tremor.

Orthostatic tremor

Orthostatic tremor is a rare disorder characterized by rapid muscle contractions in the legs that occur when standing.  People typically experience feelings of unsteadiness or imbalance, causing them to immediately attempt to sit or walk.  Because the tremor has such a high frequency (very fast shaking) it may not visible to the naked eye but can be felt by touching the thighs or calves or can be detected by a doctor examining the muscles with a stethoscope.  In some cases the tremor can become more severe over time.  The cause of orthostatic tremor is unknown

Causes of Tremor

The etiology of essential tremor is mostly unexplained. About half of the cases of essential tremor appear to result from a genetic mutation; although, a specific gene has not been identified. This form is referred to as familial tremor and is an autosomal dominant disorder. The variability in age of onset, the presence of sporadic cases, and incomplete concordance of essential tremor among monozygotic twins suggest that environmental factors play a role.

The Movement Disorders Society diagnostic criteria include:

  • Neurologic disorders, including multiple sclerosis, Parkinson’s disease, stroke, and traumatic brain injury
  • Certain medicines, such as asthma medicines, amphetamines, caffeine, corticosteroids, and medicines used for certain psychiatric and neurological disorders
  • Alcohol use disorder or alcohol withdrawal
  • Mercury poisoning
  • Hyperthyroidism (overactive thyroid)
  • Liver or kidney failure
  • Anxiety or panic
  • Tremor is bilateral, symmetrical and postural
  • The tremor involves the forearms and hand
  • Is persistent and visible
  • May be associated with isolated head tremor

What causes tremors?

Generally, tremor is caused by a problem in the deep parts of the brain that control movements.  Most types of tremors have no known cause, although there are some forms that appear to be inherited and run in families.

Tremor can occur on its own or be a symptom associated with a number of neurological disorders, including:

  • multiple sclerosis
  • stroke
  • traumatic brain injury
  • neurodegenerative diseases that affect parts of the brain (e.g.,  Parkinson’s disease).
  • the use of certain medicines (particular asthma medication, amphetamines, caffeine, corticosteroids, and drugs used for certain psychiatric and neurological disorders)
  • alcohol abuse or withdrawal
  • mercury poisoning
  • overactive thyroid
  • liver or kidney failure
  • anxiety or panic.

Symptoms of Tremor

Symptoms of tremor may include:

  • Begin gradually, usually more prominently on one side of the body
  • Worsen with movement
  • Usually occur in the hands first, affecting one hand or both hands
  • Can include a “yes-yes” or “no-no” motion of the head
  • May be aggravated by emotional stress, fatigue, caffeine or temperature extremes
  • a rhythmic shaking in the hands, arms, head, legs, or torso
  • shaky voice
  • difficulty writing or drawing
  • problems holding and controlling utensils, such as a spoon.

Some tremor may be triggered by or become worse during times of stress or strong emotion, when an individual is physically exhausted, or when a person is in certain postures or makes certain movements.

Diagnosis of Tremor

Diagnosing essential tremor involves reviewing your medical history, family history and symptoms and conducting a physical examination.

There are no medical tests to diagnose essential tremor. Diagnosing it is often a matter of ruling out other conditions that could be causing your symptoms. To do this, your doctor may suggest the following tests:

Neurological examination

In a neurological examination, your doctor tests your nervous system functioning, including checking your:

  • Tendon reflexes
  • Muscle strength and tone
  • Ability to feel certain sensations
  • Posture and coordination
  • Gait

Laboratory tests

Your blood and urine may be tested for several factors, including:

  • Thyroid disease
  • Metabolic problems
  • Drug side effects
  • Levels of chemicals that may cause tremor

Performance tests

To evaluate the tremor itself, your doctor may ask you to:

  • Drink from a glass
  • Hold your arms outstretched
  • Write
  • Draw a spiral

If your doctor is still unsure if your tremor is essential tremor or Parkinson’s disease, he or she might order a dopamine transporter scan. This scan can help your doctor tell the difference between the two types of tremor.

Treatment of Tremor

Less impaired patients may choose to skip treatment altogether. Some patients that are not functionally impaired desire treatment because their tremor is a significant source of embarrassment. Options for patients with significant functional impairment include non-medical, medical, or interventional therapy.

Non-Medical Therapy

  • In some patients, tremors can be reduced by weighting the limb, usually by applying wrist weights. In a small proportion of patients, this can dampen down the tremor enough to provide some relief or improve functioning. Since anxiety and stress classically make the tremor worse, non-medical relaxation techniques and biofeedback can be effective in some patients. Medications known to make tremors worse should be eliminated or minimized when possible. People with tremors also may benefit from avoiding dietary stimulants, such as caffeine. There are several commercially available technologies to help stabilize the use of utensils, like weighted utensils, or active cancelation of tremor technology to dampen tremors, which could be helpful for some patients.
  • Physical, speech-language, and occupational therapy –  which may help to control tremor and deal with the daily challenges caused by the tremor

Medical Therapy

The therapeutic approach to essential tremors many times follows a trial and error approach, and patients should be challenged by several medications if the first choice is ineffective or associated with debilitating adverse effects. Medical therapy can be divided into first, second, and third-line therapies.

First-line therapy

  • It is either approved by the FDA or supported by double-blinded, placebo-controlled studies that meet criteria for the class I evidence. This class of medications includes propranolol and primidone. If both primidone and propranolol are not effective alone, combinations of both may provide relief in selected patients.

Second-line therapy

  • Second-line therapy is supported by double-blinded, placebo-controlled trials that do not meet other requirements for the class I evidence studies. This includes gabapentin, pregabalin, topiramate, benzodiazepines (clonazepam, alprazolam), beta-blockers (atenolol and metoprolol) and zonisamide.

Third-line therapy

These therapies are based on open-label studies or case series. Drugs in this class include nimodipine and clozapine.

  • Beta-blocking drugs – such as propranolol are normally used to treat high blood pressure but they also help treat essential tremors.  Propranolol can also be used in some people with other types of action tremor.  Other beta-blockers that may be used include atenolol, metoprolol, nadolol, and sotalol.
  • Anti-seizure medications – such as primidone can be effective in people with essential tremor who do not respond to beta-blockers.  Other medications that may be prescribed include gabapentin and topiramate.  However, it is important to note that some anti-seizure medications can cause tremors.
  • Tranquilizers (also known as benzodiazepines) – such as alprazolam and clonazepam may temporarily help some people with tremors.  However, their use is limited due to unwanted side effects that include sleepiness, poor concentration, and poor coordination.  This can affect the ability of people to perform daily activities such as driving, school, and work.  Also, when taken regularly, tranquilizers can cause physical dependence and when stopped abruptly can cause several withdrawal symptoms.
  • Parkinsonian tremor – drug treatment involves L-DOPA or dopamine-like drugs such as pergolide, bromocriptine, and ropinirole; They can be dangerous, however, as they may cause symptoms such as tardive dyskinesia, akathisia, clonus, and in rare instances tardive (late-developing) psychosis. Other drugs used to lessen parkinsonian tremor include amantadine and anticholinergic drugs like benztropine

Interventional Therapy

  • For patients who fail pharmacologic treatment with the above drugs or are unable to tolerate the side effects, surgical options include deep brain stimulation (DBS), focused ultrasound, or radio-surgical gamma knife thalamotomy to treat persistently disabling limb tremor, and botulinum toxin injections to treat persistently disabling head or vocal cord tremor.

Botulinum neurotoxin (BoNT) injections:

  • In some patients with severe head or hand tremors, injection with botulinum toxins can be helpful. BoNT should be considered as a treatment option for essential hand tremor in those patients who fail treatment with oral agents (Level B). A recent evidence-based review reported insufficient evidence to conclude the use of BoNT in the treatment of head and voice tremor.

Deep-brain stimulation

  • This is the most common surgical treatment for essential tremor. Most series report 70% to 90% hand tremor control. In deep-brain stimulation, electrical stimulation is delivered to the brain through an electrode implanted deep into the ventral intermediate nucleus (VIM) of the thalamus. This is typically done by implanting 4 electrodes in the VIM using stereotactic methods.
  • Computerized programming of the pulse generator is most commonly done with a handheld device after the patient leaves the hospital to optimize the electrode montage, voltage, pulse frequency, and pulse width. Deep-brain stimulation can be done unilaterally or bilaterally depending on patients symptoms. There is an increased risk of speech and balance difficulties with bilateral procedures. If the tremor significantly affects both hands, the dominant hand is targeted, bilateral procedures may be considered.

Thalamotomy

  • Stereotactic surgical techniques can be used to create a lesion in the ventral intermediate (VIM) nucleus of the thalamus.

Focused ultrasound

  • Approved by the FDA in 2016, magnetic resonance imaging-guided, high-intensity, focused ultrasound thalamotomy is an innovative method for the treatment of essential tremor. Although it is transcranial and does not require an incision, skull penetration, or an implanted device, it is an invasive therapy that produces a permanent thalamic lesion.

Radio-surgical gamma knife thalamotomy

  • Gamma-knife thalamotomy fo­cuses high-energy gamma rays on the ventral intermediate resulting in the death of neurons. It is an unproven treatment that has not generally been adopted due to concerns about potential radiation side effecs, including a theoretical, long-term risk of secondary tumor formation.

Surgery

When people do not respond to drug therapies or have a severe tremor that significantly impacts their daily life, a doctor may recommend surgical interventions such as deep brain stimulation (DBS) or very rarely, thalamotomy.  While DBS is usually well-tolerated, the most common side effects of tremor surgery include dysarthria (trouble speaking) and balance problems.

  • Deep brain stimulation (DBS) – is the most common form of surgical treatment of tremor.  This method is preferred because it is effective, has low risk, and treats a broader range of symptoms than thalamotomy.  The treatment uses surgically implanted electrodes to send high-frequency electrical signals to the thalamus, the deep structure of the brain that coordinates and controls some involuntary movements.  A small pulse generating device placed under the skin in the upper chest (similar to a pacemaker) sends electrical stimuli to the brain and temporarily disables the tremor.  DBS is currently used to treat parkinsonian tremor, essential tremor, and dystonia.
  • Thalamotomy – is a surgical procedure that involves the precise, permanent destruction of a tiny area in the thalamus.  Currently, surgery is replaced by radiofrequency ablation to treat severe tremor when deep brain surgery is contraindicated—meaning it is unwise as a treatment option or has undesirable side effects.  Radiofrequency ablation uses a radio wave to generate an electric current that heats up a nerve and disrupts its signaling ability for typically six or more months.  It is usually performed on only one side of the brain to improve tremor on the opposite side of the body.  Surgery on both sides is not recommended as it can cause problems with speech.

Lifestyle changes

  • Physical, speech-language, and occupational therapy – may help to control tremors and meet daily challenges caused by the tremor.  A physical therapist can help people improve their muscle control, functioning, and strength through coordination, balancing, and other exercises.  Some therapists recommend the use of weights, splints, other adaptive equipment, and special plates and utensils for eating.  Speech-language pathologists can evaluate and treat speech, language, communication, and swallowing disorders.  Occupational therapists can teach individuals new ways of performing activities of daily living that may be affected by the tremor.
  • Eliminating or reducing tremor-inducing substances such as caffeine and other medication –  (such as stimulants) can help improve tremor. Though small amounts of alcohol can improve tremors for some people, tremor can become worse once the effects of the alcohol wear off.

References

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