Clinical Pearls & Morning Reports
Recently, a task force of the International Parkinson and Movement Disorder Society proposed a new formal definition of essential tremor as a syndrome of isolated tremor of both upper limbs with a duration of at least 3 years, with or without tremor in other locations, such as head, voice, or lower limbs. Read the latest NEJM Clinical Practice here.
Q: What are some of the features of essential tremor?
A: Essential tremor is one of the most common movement disorders and affects approximately 1% of the population worldwide. The incidence increases with advancing age, with the majority of population-based studies showing no difference in prevalence between men and women. The age of onset can be as early as childhood and has a bimodal distribution, with age peaks in the second and sixth decades of life.
Q: Describe an approach to the diagnosis of essential tremor.
A: A comprehensive medical history and neurologic examination are often sufficient to make a diagnosis. The history taking should include information about age of onset, family history, temporal evolution, and any exposure to potentially tremor-inducing drugs (e.g., valproate, selective serotonin-reuptake inhibitors, sympathomimetic agents, or lithium) and toxins (e.g., mercury, lead, or manganese). The neurologic examination should assess the distribution of tremor and activation condition (i.e., whether tremor appears during rest, posture [defined as isometric extension of a body part, such as a limb, against gravity], or goal-directed movement), include a visual estimation of the tremor frequency range (low [<4 Hz], medium, [4 to 8 Hz], or high [>8 Hz]), and assess any signs to suggest systemic illness or neurologic disease.
A: Propranolol and primidone are the two compounds with the highest level of evidence to treat essential tremor by reducing the severity of upper-limb symptoms. The nonselective beta-blocker propranolol has been shown to be an effective treatment in randomized, controlled trials at doses ranging from 120 to 240 mg per day. Across randomized, controlled trials, tremor amplitudes that were measured by accelerometry were reduced by a mean of 55%. Primidone, which is metabolized to phenylethylmalonamide and phenobarbital, has been effective in doses ranging from 250 to 750 mg per day, with reductions of 60% in tremor amplitudes, similar to reductions observed with propranolol monotherapy. Limited data from randomized, controlled trials are available to support the use of other medications in essential tremor, including topiramate, alprazolam, gabapentin, and other beta-blockers besides propranolol (e.g., atenolol, nadolol, and sotalol).
A: Deep-brain stimulation (unilateral and bilateral) and thalamotomy (only unilateral) targeting the thalamic nucleus ventralis intermedius are used for the treatment of medically intractable upper-limb tremor in essential tremor. Although conventional stereotactic thalamotomy was the first available interventional treatment of tremor, its application is limited to unilateral interventions owing to the high risk of irreversible dysarthria or ataxia after bilateral thalamotomy. In 2016, the Food and Drug Administration approved a focused ultrasound device to treat essential tremor that is refractory to medical therapy. The approval was based on the results of a randomized, controlled trial involving 76 participants with essential tremor, in which unilateral thalamic thermoablation using focused ultrasound with magnetic resonance imaging guidance resulted in a significantly greater reduction in hand tremor and better quality of life over a period of 12 months than a sham intervention.