Anwar Ahmed, MD
DESCRIPTION 
Tremor is the most common movement disorder. It is defined as a rhythmic, involuntary, oscillating movement of a body part occurring in isolation or as part of a clinical syndrome. In clinical practice, characterization of tremor is important for etiologic consideration and treatment.
- Terminology
- Resting tremor occurs when a body part is at complete rest against gravity. Tremor amplitude decreases with voluntary activity.
- Postural tremor occurs during maintenance of a position against gravity.
- Action or kinetic tremor occurs during voluntary movement.
- Task-specific tremor emerges during a specific activity.
- Intention (or terminal) tremor manifests as a marked increase in tremor amplitude during a terminal portion of targeted movement.
EPIDEMIOLOGY
Prevalence
- Essential tremor (ET) prevalence rate 0.4–5.6%. Family history + in 60% of patients, autosomal dominant.
- Approximately 60% of patient experience tremor in Parkinson's disease (PD). PD prevalence 56–234 per 100,000.
RISK FACTORS
- Genetic and environmental factors
- The risk of ET in a first-degree relative is 5 times greater than the risk in control cases
- Exposure to certain drugs
Genetics
- The inheritance of ET is autosomal dominant, with incomplete penetrance.
- Specific genes for ET have been linked to chromosomes 2p, 3q, and 4p.
- In ET, onset younger with family history positive.
GENERAL PREVENTION
Drug-induced tremor may be prevented by avoiding certain drugs.
PATHOPHYSIOLOGY
Four basic mechanisms are linked to the production of tremor. It is likely that combinations of these mechanisms produce tremor in different diseases.
- Mechanical oscillations of the limb can occur at a particular joint; this mechanism applies in cases of physiologic tremor.
- Reflex oscillation is elicited by afferent muscle spindle pathways and is responsible for stronger tremors by synchronization. This mechanism is a possible cause of tremor in hyperthyroidism or other toxic states.
- Central oscillators are groups of cells in the CNS present in the thalamus, basal ganglia, and inferior olive. These cells have the capacity to fire repetitively and produce tremor. Parkinsonian tremor might originate in the basal ganglia, and ET might originate within the inferior olive and thalamus.
- Abnormal functioning of the cerebellum can produce tremor.
ETIOLOGY
Tremor can be classified on a clinical and etiologic basis. Signs and symptoms depend on tremor type and cause. Multiple etiologies have been identified including neurodegenerative diseases, brain ischemia or demyelination, metabolic derangements, drugs and toxic states.
COMMONLY ASSOCIATED CONDITIONS
- Physiologic tremor: Low-amplitude tremor (6–12 Hz); neurological examination normal.
- Drugs and toxins may induce an enhanced physiological tremor.
- ET frequency of 7–10 Hz; predominantly postural- or action-type tremor; drinking alcohol temporarily reduces the tremor. Other associated symptoms can include mild gait difficulty.
- PD tremor is a low-frequency 4–6 Hz rest tremor typically defined as a pill-rolling tremor. Some patients also have postural and action tremors.
- Cerebellar tremor is a low-frequency (<4 Hz) intention tremor often unilateral. Signs and symptoms of cerebellar dysfunction may be present, including ataxia, dysmetria, dysdiadochokinesia, and dysarthria.
- Dystonic tremor is predominantly postural in nature often irregular in rhythm.
- Holmes’ tremor or rubral tremor is a combination of rest, postural, and action tremors due to midbrain lesions in the vicinity of the red nucleus. This type of tremor is irregular and low frequency (4.5 Hz).
- Common tremor-inducing drugs include neuroleptics, lithium, divalproex sodium (Depakote), amiodarone, metoclopramide, theophylline, and bronchodilators.
- Tremor can occur in diseases such as thyrotoxicosis and hepatic failure and in drug withdrawal.
- Psychogenic tremor can involve any part of the body, but it most commonly affects the extremities. Usually, tremor onset is sudden and begins with an unusual combination of postural, action, and resting tremors. Psychogenic tremor decreases with distraction and is associated with multiple other psychosomatic complaints.
- Orthostatic tremor occurs in the legs immediately on standing and is relieved by sitting down. Orthostatic tremor is usually high frequency (14–18 Hz), and no other clinical signs or symptoms are present.
- Essential palatal tremor is an uncommon disorder, characterized by rhythmic movements of the soft palate.
[Outline]
Diagnostic evaluation of the tremor should include a thorough clinical history, clinical examination (including tremor rating), and differential diagnosis
HISTORY
The clinical history must detail tremor onset, duration, severity, affected area, activating factors, relieving factors, effect of alcohol, family history, and associated symptoms
PHYSICAL EXAM
- The clinical examination should determine a tremor rating and tremor frequency.
- The patient should be examined during rest, when assuming various positions, and when moving.
- An examination of gait, muscle tone, facial expressions, and dexterity is also important, particularly in differentiating ET from PD.
- Tremor in each affected body part can be rated as resting, kinetic, or postural and with a scale developed by Kahn and colleagues as follows: (1) No tremor; (2) slight tremor; (3) moderate tremor (less than 2 cm excursion); (4) marked tremor (2–4 cm excursion); and (5) severe tremor (more than 4 cm excursion).
DIAGNOSTIC TESTS AND INTERPRETATION
A laboratory workup is not necessary for most tremor patients.
- Thyroid function test.
- In young patients with parkinsonism or tremor, serum copper, serum ceruloplasmin, 24-hour urinary copper, and slit-lamp examination (Wilson's disease).
- To rule out systemic causes of tremor, such as hypoglycemia, liver disease, electrolyte imbalance, or drug abuse, appropriate tests should be ordered.
- An MRI or computed tomography scan of the brain is needed in some patients if tremor onset is acute, progression is rapid, and cerebellar signs suggest stroke, demyelinating disease, or structural lesion.
- In difficult cases FDA-approved FP-CIT SPECT Scan (DaTscan) can differentiate Parkinsonism from ET.
- Tremor also can be analyzed and diagnosed with the help of accelerometers and surface electromyogram recordings (tremor analysis).
DIFFERENTIAL DIAGNOSIS
Differential diagnosis of tremor include the following:
- Myoclonus is irregular or rhythmic brief muscle jerks that can mimic tremor.
- Clonus is a rhythmic movement around joints that is stimulated through stretch reflex.
- Asterixis is a type of myoclonus that can cause a flapping tremor of the extremities.
- Epilepsia partialis continua can cause rhythmic jerks in the extremities.
[Outline]
Dependent on the type of tremor:
- Treatment of ET usually begins with primidone or propranolol monotherapy. The dosages are gradually increased to achieve optimal response. They may be combined.
- Primidone can gradually be increased to a range of 150 mg/day to 250 mg/day and a maximum of 750 mg/day.
- Propranolol can gradually be increased over several weeks to 240 mg/day or as high as 320 mg/day.
- Relative contraindications to use propranolol include asthma, diabetes,congestive heart failure, and bradycardia.
- Common side effects of primidone and propranolol include dizziness, tiredness, and depression.
- Second-line medications: Topiramate, gabapentin, clonazepam can be used for ET after trial of propranolol and primidone.
- PD tremor usually improves with dopaminergic and anticholinergic medications (see Parkinson's disease).
- Orthostatic tremor may respond to clonazepam treatment.
- Psychogenic tremor requires early psychiatric intervention and psychotherapy.
- Drug-induced tremor improves after stopping the offending agent.
- Tremor caused by metabolic or toxic states responds to the treatment of underlying conditions.
SURGERY/OTHER PROCEDURES
- For patients with severe, disabling, medication-refractory ET and PD tremor, surgery is a reasonable treatment option.
- Surgical management includes ablative therapy through stereotactic thalamotomy or chronic thalamic deep brain stimulation. The ventral intermediate nucleus of the thalamus is the best target for both ablative and deep brain stimulation surgeries for ET.
- Similarly in PD, tremor improves significantly after subthalamic nucleus deep brain stimulation surgery. Although these surgical techniques are widely available, they should be used with caution and only after exhausting all possible pharmacologic treatment options.
- Contraindications for surgical management of tremor include unstable medical illnesses, swallowing difficulty, and marked cognitive problems.
IN-PATIENT CONSIDERATIONS
N/A
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Periodic follow-up is helpful to check the medication response and progression of disease.
PATIENT EDUCATION
- Community support groups for ET, PD, and dystonia
- National organizations:
- International Essential Tremor Foundation (IETF), 7046 West 105th Street, Overland Park, KS 66212-1803; Tel: 913-341-3880; website: www.essentialtremor.org
- WE MOVE, 204 West 84th Street, New York, NY 10024; Tel: (US): 800-437-MOV2; (outside US): 212-875-8312, www.wemove.org
PROGNOSIS
- PD is a chronic progressive neurodegenerative disease that leads to worsening of cognitive and motor symptoms particularly gait and balance.
- ET course is benign and remains mild for years, but tremor worsens with age.
[Outline]
