Tremor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Tremor is an involuntary, rhythmic, oscillatory movement, and it is the most common involuntary movement disorder. Essential tremor, Parkinson’s disease and enhanced physiologic tremor are the common causes of tremors in a primary care setting. Essential tremor is the most common. Other causes are caffeine intake, excessive alcohol, hypoglycemia, stress, anxiety, depression, fatigue, Wilson’s disease, hyperthyroidism, multiple sclerosis, normal aging. Tremor can be classified into resting and action. Action tremor is further divided into postural, kinetic (simple or intentional), isometric and task-specific tremor. Tremor is thought to be the result of a combination of different mechanisms that could result in oscillatory/rhythmic movement. These mechanisms are mechanical oscillations, reflex oscillations, central oscillations, and cerebellar oscillation. Tremor must be differentiated from diseases that cause involuntary movement: myoclonus, clonus, asterixis, and epilepsia partialis continua. Essential tremor and Parkinson’s disease worsens with time, treatment helps minimizing symptoms. Physiologic tremor does not worsen with age.

James Parkinson, identified the tremor as “involuntary tremulous motion in parts not in action,” in his essay on the shaking palsy, in 1817. Orthostatic tremor was first described by Kenneth M Heilman in 1984. Pietro Burresi in 1874, used the term essential tremor.

Tremor may be classified into resting or action tremor. Action tremor further includes postural, kinetic (simple or intentional), isometric and task-specific tremor.

Tremor is thought to be the result of a combination of different mechanisms that could result in oscillatory/rhythmic movement. These mechanisms are mechanical oscillations, reflex oscillations, central oscillations, and cerebellar oscillation. These mechanisms differ on the basis of their origin. Mechanical oscillations occur in limbs, and can be limited to a particular joint. Reflex oscillations originate from afferent muscle spindles, while central neuronal pacemaker involves the thalamus, basal ganglia, and inferior olive. Cerebellar oscillations are due to disturbances in feedforward or feedback loops in the cerebellum.

Common causes of tremor in primary care include enhanced physiologic tremor, essential tremor, and Parkinson’s disease. Other causes are caffeine intake, excessive alcohol, hypoglycemia, stress, anxiety, depression, fatigue, Wilson’s disease, hyperthyroidism, multiple sclerosis, normal aging.

Tremor must be differentiated from diseases that cause involuntary movement: myoclonus, clonus, asterixis, and epilepsia partialis continua. The cause of tremor must also be differentiated from other conditions that cause tremor: essential tremor, physiological tremor, Parkinson’s disease, cerebellar tremor, orthostatic tremor.

The incidence and prevalence of tremor as a symptom are not determined. The incidence of essential tremor increases with age, it has bimodal incidence according to age. The prevalence of essential tremor is approximately 0.4% to 5.6%. The incidence of Parkinson’s disease is in the range of 8 to 18 per 100,000 people yearly. Seven million people worldwide, and one million people in the United States, are suffering from Parkinson’s disease. The rate of parkinson’s disease is higher in Caucasians as compared to black or oriental populations. Parkinson’s disease is more common in rural populations.

Common risk factors for essential Tremor include Family history, old age, Caucasian ethnicity, and male gender. Risk factors for physiologic Tremor include caffeine, stress, muscle fatigue, low blood sugar, and anxiety.

There is insufficient evidence to recommend routine screening for tremor.

Essential tremor and Parkinson’s disease worsen with time, but treatment helps to minimize symptoms. Physiologic tremor and drug induced tremor do not worsen with time and can be controlled. Tremors may be mild or can be very disabling for some patients. Patients with tremors have shown to have decrease quality of life physically and mentally as compared to healthy population.

Tremor is primarily diagnosed based on the clinical presentation. The clinical diagnosis is based upon detailed history and a focused physical exam.

Tremor is the most common involuntary movement disorder. In the primary care setting, the most common causes of tremors are essential tremors, Parkinson’s disease and enhanced physiologic tremor. Important features of tremor in patients history are mode of onset, unilateral or bilateral tremor, type of tremor (resting or action), symmetric or asymmetric, associated signs and symptoms, aggravating and relieving factors, medications, and family history. Essential tremor is diagnosed according to International Parkinson and Movement Disorder Society (IPMDS) guidelines including bilateral action tremor of upper limbs, absence of other neurological signs, long duration of symptoms at least more than 3 years and absence or presence of tremor in other locations.

Physical examination of patients with tremor varies depending on the cause of tremor. The basis of physical examination is to determine the type of tremor, phenomenological features of tremor, associated neurological signs.

Tremor is more of a clinical diagnosis. However, some causes of tremors can be identified through laboratory workup via hyperthyroidism, hypoglycemia, hepatic malfunction, renal impairment, and Wilsons disease.

Tremor can mimic ventricular tachycardia on ECG appearing as a broad QRS complex and cause an artifact. It must be differentiated by finding normal QRS complexes hidden between artifact waves and looking for an unstable baseline at the beginning of the ECG recording. Hyperthyroidism can appear as sinus tachycardia, atrial flutter or atrial fibrillation on ECG. Stress and anxiety can cause sinus tachycardia on ECG. It is important to obtain an ECG in patients diagnosed with tremor before starting medications like propranolol to investigate for bradycardia.

There are no x-ray findings associated with tremor.

There are no echocardiography findings associated with tremor. Magnetic resonance-guided focused ultrasound (MRgFUS), is a noninvasive focused ultrasound ablative thalamotomy procedure used to treat essential tremor.

Neuroimaging using CT scan may help determine if the tremor is the result of a structural defect or degeneration of the brain. ACT scan can be used to diagnose cerebellar causes of tremor or can identify stroke, multiple sclerosis, or Wilsons disease. SPECT of the nigrostriatal dopaminergic system can help distinguish essential and dystonic tremors in Parkinson’s disease from neurodegenerative Parkinson’s disease.

An MRI is not helpful in diagnosing most common causes of tremor, but it can help diagnose some less common causes of tremor including, cerebellar lesion, stroke, multiple sclerosis , Wilsons disease. It may help determine if the tremor is the result of a structural defect or degeneration of the brain. Magnetic resonance guided focused ultrasound (MRgFUS), is a noninvasive focused ultrasound ablative thalamotomy procedure used to treat essential tremor.

Tremors of all forms exhibit cerebellar activation on positron emission tomography studies.

Electromyography, accelerometers, potentiometers, handwriting tremor analysis and long-term tremor record.

Non-pharmacological Therapy: Lifestyle changes, physical therapy, psychological techniques (relaxation, biofeedback). First line medications for essential tremorare propranolol (40 to 240 mg/day) or primidone. Parkinson’s disease‘s first-line include Carbidopa–levodopa in combination, as carbidopa prevents conversion of levodopa into dopamine before reaching the brain, hence increasing efficacyFor physiologic Tremor: Factors that enhance a physiological tremor must be controlled. Propranolol can be taken prophylactically to prevent enhanced physiologic tremor in situations that trigger it. In tremor associated with Multiple Sclerosis, Beta-blockers, anxiolytics, anticonvulsants can help minimize the symptoms. For orthostatic Tremor, first line medication is clonazepam, should be started at 0.5mg and titrated up to 2mg thrice a day. Alcohol withdrawal tremor can be treated by Hydration, folate, thiamine, multivitamin, benzodiazepine.

Surgery is not first line treatment for any cause of tremor. It is opted when non-pharmacological and pharmacological therapy fails. Interventional procedures used to treat tremors include Botulinum neurotoxin injections, Thalamotomy, deep brain stimulation, Magnetic resonance-guided focused ultrasound, and radio-surgical gamma knife thalamotomy.

There are no established measures for the primary prevention of the majority of the underlying causes of tremor. However, tremor induced by stress, drugs, alcohol, caffeine, prolonged standing (orthostatic tremor) can be prevented by avoiding them. Pesticides, dairy products, β2-adrenoreceptor antagonists have shown to increase risk of developing Parkinson’s disease. Smoking, caffeine, tea, physical activity, gout, vitamin E, non-steroidal anti-inflammatory drugs, β2-adrenoreceptor agonists have shown to reduce the risk of developing Parkinson’s disease.

Effective measures for the secondary prevention of tremor vary according to the cause of tremor. Enhanced physiologic tremor and drug induced tremor can get better by avoiding tremor stimulating factors or drugs respectively. Essential tremor and Parkinson’s disease worsen with time. There has been no identified measure for secondary prevention of these causes, however, some improvement has been seen in Parkinson’s disease with caffeine intake and physical activity.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

James Parkinson identified the tremor as “involuntary tremulous motion in parts not in action,” in his essay on the shaking palsy in 1817. Orthostatic tremor was first described by Kenneth M Heilman in 1984. Pietro Burresi, in 1874, used the term essential tremor.

• James Parkinson identified the tremor as “involuntary tremulous motion in parts not in action,” in his essay on the shaking palsy in 1817. ^[1]
• Orthostatic tremor was first described by Kenneth M Heilman in 1984. ^[2].
• In 1874, Pietro Burresi used the term essential tremor.^[3]
• In 1904, Gordon Holmes first described Holmes tremor.^[4].

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Tremor may be classified into resting or action tremor. Action tremor includes postural, kinetic (simple or intentional), isometric and task-specific tremor.

Tremor may be classified into two main groups: ^[1][2]

• Resting tremor: Occurs when the body is not moving and is at rest, the muscle is relaxed and supported against gravity. It could occur in hands, legs, or arms. Resting tremor decreases in intensity with targeted movement. Parkinson’s disease and drug-induced parkinsonism exhibit resting tremors. Other causes of resting tremor are Wilson’s disease, dystonia, rubral tremor (brainstem lesion), and progressive supranuclear palsy.
• Action Tremor: Could occur with any voluntary movement. It is further classified into:
  • Postural Tremor: Increases with voluntary movement. Physiologic tremor, essential tremor, drug or alcohol withdrawal and metabolic changes in thyroid, kidney, liver may result in postural tremor.
  • Kinetic Tremor:
    • Simple kinetic: Not affected by targeted movement. Occurs with normal limb movement.
    • Intentional tremor: Increases in intensity by targeted movement. Observed in cerebellar lesion caused by stroke, multiple sclerosis or tumor, spinocerebellar ataxia, vitamin E deficiency and lithium or alcohol toxicity.
  • Isometric tremor: Voluntary contraction of muscle against a heavy/rigid/stationary object. For instance, making a fist, using one hand to hold a heavy object, or pushing against a wall.
  • Task-induced tremor: Occurs when performing a highly skilled task, handwriting tremor, or musicians tremor.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

It is thought that tremor is the result of a combination of different mechanisms that could result in oscillatory/rhythmic movement. These mechanisms are mechanical oscillations, reflex oscillations, central oscillations, and cerebellar oscillation. These mechanisms differ on the basis of their origin.

The normal physiology of tremor is based on the four oscillatory centers: ^[1][2][3]

• Mechanical oscillations: Occurs in limbs, could be limited to a particular joint
• Reflex oscillations: Originates from afferent muscle spindles
• Central neuronal pacemaker: Involves thalamus, basal ganglia, inferior olive.
• Cerebellar Oscillations: Disturbance in feedforward or feedback loops in cerebellum resulting in oscillations.

• It is understood that tremor is the result of oscillations produced by the above-mentioned mechanisms.
• The following are some common causes of tremor and the mechanisms from which they originate: ^[1]

Common Causes of Tremor	Predominant Mechanism
Physiological tremor	Mechanical and central
Psychogenic tremor	Reflex (clonus)
Symptomatic palatal tremor	Central (inferior olive)
Essential tremor	Central and cerebellar (olivocerebellar circuits)
Parkinson’s disease	Central (basal ganglia)
Toxic and drug‐induced tremors	Reflex

• Essential tremor is transmitted in an autosomal dominant pattern. So far, no particular genes have been identified as the cause. In Linkage study, three susceptible loci were mapped in families with pure monogenic essential tremor: ^[4]
  • 3q13
  • 2p25-p22
  • 6p23
• Wilson’s disease is transmitted in an autosomal recessive pattern. ^[5]
  • Mutation in the ATP7B gene on chromosome 13 (13q14.3)

Conditions associated with tremor include:

• Parkinson’s disease
• Drug-induced parkinsonism:Neuroleptics, metaclopromide,phenothiazines
• Wilson’s disease
• Metabolic disorders: Thyrotoxicosis, pheochromocytoma, hypoglycemia
• Alcohol withdrawal
• Peripheral Neuropathy
• Orthostatic tremor
• Essential tremor

On gross pathology, Parkinson’s disease has loss of dopamine pigment in the substantia nigra.

On microscopic histopathological analysis, Lewy bodies and Lewy neurites are found in neuronal cell bodies and neuronal cell processes, respectively in patients with Parkinson’s disease.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Common causes of tremor in primary care include enhanced physiologic tremor, essential tremor, and Parkinson’s disease.

Common causes include: ^[1][2]

• Enhanced physiologic tremor
• Essential tremor
• Parkinson’s disease
• Excessive caffeine
• Psychogenic due to stress,anxiety, and depression
• Hypoglycemia
• Fatigue
• Aging

Less common cause include:^[3]

• Wilson’s disease
• Multiple sclerosis
• Alcohol withdrawal tremor
• Hyperthyroidism
• Mercury poisoning
• Liver or kidney failure
• Drug Induced Tremors
• Orthostatic tremor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Tremor must be differentiated from diseases that cause involuntary movement: myoclonus, clonus, asterixis, and epilepsia partialis continua. The cause of tremor must also be differentiated from other conditions that cause tremor: essential tremor, physiological tremor, Parkinson’s disease, cerebellar tremor, orthostatic tremor.

• Tremor must be differentiated from diseases that cause involuntary movement: ^[1]
  • Myoclonus: Brief muscle twitches, limited to single limb or to adjacent parts.EEG shows association with spike-wave complexes.
  • Clonus: Rhythmic movement aggravated by muscle stretching.
  • Asterixis: On electromyographic, flapping/abduction of the upper extremities is indicated as prolong absence of EMG activity.
  • Epilepsia partialis continua: Regular jerks of the arm/hand.
• Differentiating the cause of tremor from other diseases on the basis of the type of tremor, associated signs, and symptoms.^[2][3][4]

Common Cause of Tremor	Differentiating Feature of Tremor	Main Feature of Disease
Essential tremor	Postural Tremor – Frequency 4–12 Hz, Bilateral onset	gait ataxia, vestibulo-cerebellar involvement, reduced by alcohol, family history, stress/fatigue can increase tremor amplitude, increases with voluntary movements
Parkinson’s disease	Resting Tremor – Unilateral onset	Bradykinesia, micrographia, stooped posture, ataxia, rigidity, imbalance, depression, apathy, decreases with voluntary movements
Physiologic Tremor	Postural tremor – High frequency 8–10 Hz, low amplitude, irregular oscillations	Tremor occurs while maintaining a posture and mostly disappears if eyes are closed or a load is placed on the muscles. Subtle innate tremor normally present in the general population.
Enhanced Physiologic Tremor	Increased amplitude	Physiologic tremor enhanced due to fatigue, sleep deprivation, drugs, endocrine disorders, caffeine, stress.
Cerebellar Tremor	Intention tremor – Low frequency <4 Hz	Occurs in multiple sclerosis, stroke, brainstem tumor, or cerebellar trauma. May feature ataxia, dysmetria, dysdiadochokinesia, and dysarthria.
Drug Induced Tremor	Can enhance rest, action, postural tremors	Amiodarone, bronchodilators, lithium, metoclopramide, neuroleptics, theophylline, valproate
Orthostatic Tremor	Essential tremor variant, high frequency 14 Hz-18 Hz	Occurs in the legs on standing and is relieved by sitting down
Holmes tremor	Combination of rest, action, and postural tremors, Frequency 2Hz-5Hz	Mostly due to vascular lesion in mesencephalic, thalamic or both regions.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

The incidence and prevalence of tremor as a symptom is not determined. The incidence of essential tremor increases with age and has bimodal incidence according to age. Prevalence of essential tremor is approximately 0.4% to 5.6%. The incidence of Parkinson’s disease is in the range of 8 to 18 per 100,000 people yearly. Seven million people worldwide, and one million people in the United States, are suffering from Parkinson’s disease. Parkinson’s disease is higher in Caucasians as compared to black or oriental populations. Parkinson’s disease is more common in rural populations.

• The incidence of essential tremor increases with age.
• Incidence of essential tremor is 23.7 per 100,000 annually. ^[1]
• The incidence of Parkinson’s disease is in the range of 8 to 18 per 100,000 people yearly. ^[2]

• The prevalence of essential tremor is approximately 0.4% to 5.6%. ^[3]
• Seven million people worldwide, and one million people in the United States, are suffering from Parkinson’s disease.
• Exact prevalence of psychogenic tremor had not been determined, but it is thought to be high. ^[4]

• Essential tremor has bimodal incidence according to age.
• Incidence of Parkinson’s disease increases with age. One percent of the population over the age of 60, and four percent of the population over the age of 80, are affected.
• Mean age-of-onset of Parkinson’s disease is 60 years. ^[5]
• Orthostatic tremor usually targets the population over 60 years of age.

• Prevalence of Parkinson’s disease is higher in Caucasians as compared to black or oriental populations. ^[6]

• Males are more commonly affected by Parkinson’s disease than females. The male to female ratio is approximately 3:2. ^[7]
• Females are more commonly affected by orthostatic tremor than males.

• Parkinson’s disease affects more Caucasians as compared to black or East and Southeast Asian populations. ^[6]
• Parkinson’s disease is more common in rural populations.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Common avoidable risk factors in the development of tremors include limiting caffeine, alcohol, managing stress, anxiety, depression, blood glucose level, minimizing fatigue.

Common risk factors in the development of tremor include:

• Essential Tremor:^[1]
  • Family history
  • Age: Forty and above
• Parkinson’s Disease:^[2]
  • Advancing age
  • Caucasian
  • Male gender
• Physiologic Tremor:^[3]
  • Caffeine
  • Stress
  • Muscle fatigue
  • Low blood sugar
  • Anxiety

• Orthostatic Tremor:^[4]
  • Standing
• Alcohol withdrawal^[5]
• Excessive alcohol intake

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

There is insufficient evidence to recommend routine screening for tremor.

There is insufficient evidence to recommend routine screening for tremor.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Essential tremor and Parkinson’s disease worsens with time, treatment helps to minimize symptoms. Physiologic tremors and drug-induced tremor do not worsen with time and can be controlled. Tremors may be mild or can be very disabling for some patients. Patients with tremors have shown to have decrease quality of life physically and mentally as compared to healthy population.

• Tremor is not a life-threatening condition. However, if not symptomatically treated it can cause severe physical, mental and social disabilities depending on the intensity of tremors.
• Essential tremor and Parkinson’s disease generally worsen with time. Physiologic tremor and drug induced tremor do not worsen with time and can be controlled.^[1]

• Reduces quality of life
• Can cause social disability.
• May limit their physical activity
• Patients with essential tremor have shown to have decrease quality of life physically and mentally as compared to healthy population. ^[2]
• Depression^[3]

• Tremors may be mild or can be very disabling for some patients.
• Essential tremor is a gradually progressing disease.The symptoms usually worsen with age.^[4]
• It has been observed that patients suffering from essential tremors are more likely to develop other forms of neurodegenerative disorders including, Parkinson’s disease, Alzheimer’s disease as compared to average population especially if age of onset is after 65 years.^[5]
• Physiologic and drug-induced tremor with time do not worsen, They can be completely controlled by eliminating the causative drug for drug-induced tremor or controlling the enhancing factors for physiologic tremors.^[1]

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