Tremor overview

# Overview
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.

# Historical Perspective
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.

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

# Pathophysiology
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.

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

# Differentiating Tremor from other Diseases
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.

# Epidemiology and Demographics
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.

# Risk Factors
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.

# Screening
There is insufficient evidence to recommend routine screening for tremor.

# Natural History, Complications and Prognosis
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.

# Diagnosis

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

## History and Symptoms
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
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.

## Laboratory Findings
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.

## Electrocardiogram
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.

## X-ray
There are no x-ray findings associated with tremor.

## Echocardiography and Ultrasound
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.

## CT
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.

## MRI
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.

## Other Imaging Findings
Tremors of all forms exhibit cerebellar activation on positron emission tomography studies.

## Other Diagnostic Studies
Electromyography, accelerometers, potentiometers, handwriting tremor analysis and long-term tremor record.

# Treatment

## Medical Therapy
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
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.

## Primary Prevention
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, 2-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, 2-adrenoreceptor agonists have shown to reduce the risk of developing Parkinson's disease.

## Secondary Prevention
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.