In some cases, tremors occur only during a particular task, such as writing, or while holding limbs in certain position such as when bring a glass to the mouth. These task- and position-specific tremors may be variants of ET but they have unique features. In some cases, the clinical features overlap with another movement disorder, called dystonia. Dystonia is an involuntary sustained contraction of muscles producing abnormal movements or postures. Examples of dystonia include writer’s cramp, torticollis or wry neck (cervical dystonia), and involuntary eye closure (blepharospasm). In some patients, dystonia produces rhythmical movements resembling ET, but in contrast to ET, dystonic tremor is more irregular, jerky, and is more influenced by the position of the affected body part.
Another variant of ET is orthostatic tremor. This is a very fine and rapid tremor in the legs only when patients are standing. It resolves with sitting or walking. It is so small that it often is not seen, and the actual complaint is poor balance while standing that improves while walking. Patients, despite their intense feeling of imbalance usually do not fall.
Essential tremor is called “essential” because it was thought to be the single symptom of the disorder. However, patients with ET have higher rates of hearing loss, restless legs syndrome, balance difficulties, and possibly Parkinson’s disease (PD). The PD association is controversial; as some patients with ET simply develop features of parkinsonism, and it is not clear whether this is simply part of ET or truly a variant of PD. There is now a brain scan test (DaTScan) that measures dopamine cells in the brain that can help sort this out. Dopamine cells are lost in PD but normal in ET. There is no actual test for ET itself. The diagnosis is based on examination, and eliminating other possibilities.
What causes essential tremor?
Frequently misdiagnosed as a stress-related condition or a natural consequence of aging, ET is actually a neurological disorder probably originating in the brain. A family history of tremor is present in the majority of patients. Despite the overwhelming evidence that ET is a genetic disorder, the gene or genes for ET have not yet been fully identified, although several genes that increase the likelihood of having tremor are identified. Currently there is no definitive DNA test for ET. These increased risk genes can be obtained in special laboratories, but there is no reason to obtain these since they only modestly increase the risk. Usual imaging studies such as MRIs are usually normal. A SPECT test that measures the amount of dopamine is also normal in ET, and contrast to Parkinson’s where it is abnormal.
Evidence points to two main types of pathology (abnormalities) when the brain is evaluated at autopsy, although some patients with ET have no clear abnormality at autopsy. Some patients show cell loss and “torpedo” type of swelling of specialized cells in the cerebellum (brain area that deals with coordination) called Purkinje cells. There is also some evidence the there are altered connections of neurons in this part of the brain. Other cases show brainstem “Lewy bodies” which are pathological features usually seen in Parkinson’s disease. The distribution of these, however, is different from PD. Although not caused by stress, either physical or emotional stress can worsen ET, as can lack of sleep, low blood sugar, overactive thyroid and certain drugs. In short, anything that increases adrenalin in the body temporarily worsen tremor, even beneficial things like physical excersise.
How is essential tremor treated?
The treatment of tremor depends largely on its severity; many patients with mild tremor require nothing more than simple reassurance. Positioning of the arms closer to the body can lessen tremor. There are also devices that sense the tremor, then move a utensil (fork/spoon) in the opposite direction to dampen the functional tremor. Most patients who are referred to a neurologist, however, have troublesome tremors that require pharmacologic or surgical treatments. The larger amplitude and slow frequency postural tremors usually do not respond as well to pharmacologic therapy.
Alcohol reduces the amplitude of ET in about 2/3 of patients. Some patients use it regularly for its “calming” effect and some use it before an important engagement where the presence of tremor could be a source of embarrassment. The majority of evidence suggests that alcohol abuse is not more common in patient with ET but tremor is sometimes incorrectly ascribed to the effects of alcohol in those who do drink heavily. Propranolol (Inderal), a beta-adrenergic blocker, remains the most commonly used drug for the treatment of ET and enhanced physiologic tremors, but other similar beta blockers, especially nadolol, may also help. The major side effects of propranolol and other beta blockers include fatigability, sedation, depression and erectile dysfunction. The effects on tremor, and on side effects, are dose dependent. Propranolol can also be used on an as needed basis. The anti-tremor effect of primidone (Mysoline) has been confirmed by multiple clinical trials. If experienced, side effects are usually felt with the first dose and include nausea, vomiting, sedation, confusion and loss of balance. Usually these resolve after a few days. A combination of the two drugs, propranolol and primidone, may be more efficacious than either drug alone. Topiramate (Topamax) often improves tremor symptoms about equally well, but often has a variety of side effects included memory problems, tingling, altered taste, weight loss (not always a problem), and increased risk for kidney stones.
Other medications may less consistently help ET. The benzodiazepine drugs, such as lorazepam (Ativan) and clonazepam (Klonopin) also may also improve ET and its variants. They usually cause sedation and may worsen balance. Other medications include gabapentin (Neurontin), pregabalin (Lyrica), zonisamide (Zonegram), and levetiracetam (Keppra) are drugs approved for the treatment of epilepsy, may be also useful in the treatment of tremors. Gabapentin, topiramate, levodopa, primidone, clonazepam, and phenobarbital may be useful in patients with orthostatic tremor, a possible variant of ET. Task specific tremors usually do not respond as well to medications. Patients with head tremor often do not respond to medications, but can be effectively treated with botulinum toxin (BoNT) injections into the neck muscles. BoNT is also effective in the treatment of hand tremor. Usually well tolerated, BoNT can produce transient weakness of the injected muscles. The overall benefit depends on which muscle are actually causing the tremor, as some are more safely injected than others. High cost is often a problem with this treatment.
Neurosurgical treatments, such as deep brain stimulation (DBS), are generally reserved for patients whose tremors continue to interfere with work or activities of daily living despite optimal medical therapy. DBS involves an incision in the scalp and drilling a hole in the skull. The surgeon then uses a “probe”, a wire electrode, and advances the electrode into the portion of the brain that is thought to be functioning abnormally. The DBS lead, which actually contains multiple electrodes, is surgically inserted into the desired target and fixed to the skull with a ring and cap. An extension wire passes from the scalp area under the skin to the chest and is connected to an implantable pulse generator (IPG), a pacemaker-like device, which can deliver pulses with a variety of parameters, modes, and polarities into the target brain area. The patient can activate or deactivate the DBS system by placing a hand-held device over the chest area that contains the IPG. The major advantage of DBS over the traditional ablative procedures (thalamotomy, where a hole is made in the same area) is that the stimulating electrodes and parameters (frequency of stimulation, pulse width, and voltage) can be adjusted and “customized” to the needs of the individual patients. Potential risks, such as hemorrhage, stroke or infection, are uncommon, but should be considered when making a final decision about this treatment option. Side effects, if they occur, are usually reversible, but may include weakness, speech and swallowing difficulties, and abnormal sensations. Newer methods for thalamotomy and new DBS devises are under development. Of note, focused ultrasound, where a lesion can be made in the thalamus without actually drilling a hole through the skull, has been FDA approved to treat ET on one side of the body. Results of those studies are fairly similar to DBS studies.
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