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Tremor is the involuntary, rhythmic movement of muscles, causing movement of a body part. Effective treatment of tremor requires distinguishing this type of movement disorder from other movement disorders. Rhythmicity distinguishes tremor from disorders in which tremor may be a component, such as choreoathetosis and dystonia, and its biphasic nature distinguishes tremor from clonus. The frequency and amplitude of a tremor vary to the degree that the tremor may be hardly noticeable or severely disabling. Tremor may be classified as fine, medium or coarse.
Classification: Postural, Rest and Action Tremors
Tremor is primarily classified on the basis of when it occurs, either with a certain posture, at rest or during action. A resting tremor occurs when the patient is attempting to maintain the position of a body part at rest (e.g., when the patient's hands exhibit a tremor as they are resting in the patient's lap). Postural tremor is observed when the patient tries to maintain a posture against gravity, such as holding the arms out in front of the body. An action tremor (kinetic or intention tremor) occurs during.
Tremor may be either physiologic or pathologic. Physiologic tremor is a normal variant, occurring at a frequency of 8 to 12 Hz in the hands yet as slow as 6.5 Hz in other body parts during maintenance of a posture. It can be increased by emotions such as anxiety, stress or fear, by exercise and fatigue, hypoglycemia, hypothermia, hyperthyroidism and alcohol withdrawal. When such an increase occurs, physiologic tremor is then called enhanced or exaggerated physiologic tremor. Certain drugs can also exacerbate physiologic tremor. Pathologic tremor is either idiopathic or occurs secondary to some disorders. Essential tremor and parkinsonian tremor are two common types of pathologic tremor.
Identification of the type of tremor depends on keen observation. The location of the tremor or the patient's position when it occurs should be identified first, and special attention must be paid to other signs of illness.
Tremor Types Based on Etiology
Parkinsonian Tremor
The tremor in Parkinson's disease occurs at rest and is characterized by a frequency of 4 to 6 Hz and a medium amplitude. It is classically referred to as a "pill rolling" tremor of the hands but can also affect the head, trunk, jaw and lips. Although rare, a rest tremor may also be found in patients with other neurodegenerative diseases, such as multiple-systems atrophy and progressive supranuclear palsy.
Parkinson's disease results from a slow degeneration of a small area in the midbrain, called the substantia nigra. Specifically, excitatory and inhibitory dopaminergic neurons degenerate in the substantia nigra pars compacta. These neurons project to the striatum and then to the globus pallidus. From there, multiple connections in the basal ganglia project to one another, to the thalamus and, finally, to the cortex, which makes up the extrapyramidal system. This system regulates the initiation.
Essential Tremor
Essential tremor is the most common movement disorder. This postural tremor may have its onset anywhere between the second and sixth decades of life and its prevalence increases with age. It is slowly progressive over a period of years.
The specific pathophysiology of essential tremor remains unknown. Essential tremor occurs sporadically or can be inherited. While the exact genetic defect has not been identified, familial transmission seems to be autosomal dominant.
The frequency of essential tremor is 4 to 11 Hz, depending on which body segment is affected. Proximal segments are affected at lower frequencies, and distal segments are affected at higher frequencies. Although typically a postural tremor, essential tremor may occur at rest in severe and very advanced cases. It most commonly affects the hands but can also affect the head, voice, tongue and legs. In some patients essential tremor is alleviated by small amounts of alcohol, an effect not found.
Cerebellar Tremor
The most common type of cerebellar tremor is kinetic, or goal directed. Cerebellar tremors are due to lesions of the lateral cerebellar nuclei or superior cerebellar peduncle, or its connections. Classically, a lesion within a cerebellar hemisphere or nuclei leads to an action tremor on the ipsilateral side of the body. Midline cerebellar disease may cause tremor of both arms, the head and the trunk.2 Lesions in the location of the red nucleus produce a wing-beating type of tremor (called rubral tremor).
During examination, a cerebellar tremor increases in severity as the extremity approaches its target. Other signs of cerebellar pathology, such as abnormalities of gait, speech and ocular movements, and the ability to perform rapidly alternating movements.
Another type of tremor may also be associated with damage to the cerebellum. Termed "cerebellar postural tremor," it is prominent with both action and posture.4 In its most severe form, cerebellar postural tremor has a frequency of 2.5 to 4 Hz.
Multiple sclerosis is the most common cause of the cerebellar postural tremor. Other causes of this tremor include tumors.
Alcohol Withdrawal Tremor
Alcohol withdrawal tremor is similar to essential tremor on examination but with subtle differences. Alcohol withdrawal tremor has a frequency between 6 and 10.5 Hz. In one study,10 74 percent of the patients with alcohol withdrawal tremors had tremors.
Psychogenic Tremor
Psychogenic tremor is a complex tremor that can occur at rest, during postural movement and during kinetic movement. The etiology and pathophysiology of psychogenic tremor are likely to differ from patient to patient, and the main focus of treatment.
Other Tremors
Other types of tremor occur much less commonly than the previously described tremors. Orthostatic tremor is defined as a postural tremor of the legs, occurring at a frequency of 13 to 18 Hz, initiated on standing and alleviated by walking or sitting.12 It is more readily noticeable during palpation than by sight and is not influenced by peripheral feedback.
Drug Treatment of Tremor
Parkinsonian Tremor
Treatment of Parkinson's disease includes both medical and surgical intervention. Dopamine replacement therapy by means of levodopa clearly revolutionized the treatment of Parkinson's disease. Levodopa is almost exclusively given in combination with the peripheral decarboxylase inhibitor carbidopa (Sinemet). Carbidopa blocks the peripheral metabolism of levodopa to dopamine, decreasing the peripheral adverse effects of levodopa, such as nausea and vomiting, while increasing levodopa's availability in the brain.15,16 In addition to modulating the tremor associated with Parkinson's disease, levodopa improves bradykinesia, rigidity and other commonly associated symptoms. Carbidopalevodopa is available in formulations of
When tremor is the predominant presenting symptom of Parkinson's disease or when tremor persists despite adequate control of other parkinsonian symptoms with low dosages of levodopa, an anticholinergic agent such as trihexyphenidyl (Artane) or benztropine (Cogentin) may be the
Trihexyphenidyl dosages necessary to improve tremor are between 4 and 10 mg per day (maximum: 32 mg), and useful benztropine dosages range from 1 to 4 mg per day. The side effects of these agents are their limiting factor, particularly in the
Other antiparkinsonian drugs--for example, amantadine (Symmetrel), tolcapone (Tasmar) and dopamine agonists such as pergolide (Permax), bromocriptine (Parlodel), ropinirole (Requip) and pramipexole (Mirapex)--are most helpful in
Essential Tremor
As with other tremors, effective treatment of essential tremor is not found in a single, universal agent. Some therapies may be satisfactory in some patients and ineffective in others. The most widely used drugs for essential tremor are the beta-adrenergic blocker propranolol (Inderal) and the anticonvulsant primidone (Mysoline).
Other beta-adrenergic receptor antagonists used in the treatment of essential tremor include metoprolol (Lopressor) and nadolol (Corgard).
In our experience, propranolol and primidone are equally effective in the treatment of essential tremor. Patients who do not respond to one medication after a few weeks of therapy should be tried on the other one.
Surgical Treatment of Tremor
Thalamotomy
Surgical therapy for tremor should only be considered if drug therapy fails to produce adequate relief. Stereotactic thalamotomy is the surgical procedure most often used to quell essential tremor. Before the introduction of levodopa, thalamotomy was an often-selected option in the treatment of Parkinson's disease. Because the benefits of levodopa wane after four to seven years of therapy, this procedure remains an option in some patients with severe parkinsonian tremor refractory to drug therapy. However, problems associated with bilateral thalamotomy, such as dysphagia and dysarthria, limit.
Pallidotomy
Producing lesions in the globus pallidus by means of pallidotomy is an alternative to thalamotomy in the treatment of parkinsonian tremor. Pallidotomy also improves other symptoms of Parkinson's disease, such as bradykinesia and levodopa-induced
In a series of 259 patients who underwent pallidotomy for parkinsonian tremor, complete relief . If the pallidal lesion is large enough and placed at the posteroventral margin of the lateral pallidum, it abolishes the tremor.
Thalamic Stimulation
During physiologic localization in preparation for thalamotomy, the observation that high-frequency stimulation of the ventral intermediate nucleus of the thalamus abolished tremor led to investigation of thalamic stimulation as a treatment for tremor. Thalamic stimulation involves implanting an electrode in the thalamic area found to be responsible for the tremor.
Promising Surgical Approaches
At the forefront of new surgical therapies for tremor are pallidal stimulation and subthalamic nucleus stimulation. With new advances in deep brain stimulation, procedures can be performed bilaterally to relieve tremor in patients with bilateral involvement. Either a combination of thalamotomy and stimulation or bilateral stimulation without ablation is now a possibility. Targets in the brain that are too dangerous to approach for producing a lesion by means of thalamotomy may be treated.