The question of the existence and locus of a generator for essential tremor as opposed to the unbalancing of a feedback loop system, is unresolved. As indicated by McAuley, various studies demonstrate that rhythmic tremor activity is not primarily generated in the cortex. Based on electrophysiologic recordings in patients, two likely origins of oscillatory activity are the olivocerebellar circuits and the thalamus. Whether a particular structure possesses intrinsic rhythmicity or, as currently favored, the tremor is an expression of reciprocal oscillations in circuits of the dentato–brainstem–cerebellar or thalamic–tegmental systems is not at all clear. Studies of blood flow in patients with essential tremor by Colebatch and coworkers affirm that the cerebellum is rhythmically activated; on this basis they argue that there is a release of an oscillatory mechanism in the olivocerebellar pathway. Dubinsky and Hallett demonstrated that the inferior olives also become hypermetabolic when essential tremor is activated, but this has been questioned by Wills and colleagues who recorded increased blood flow in the cerebellum and red nuclei, but not in the olive. These proposed mechanisms of tremor are reviewed by Elble and also by Hallett.
Although this disorder is familial, almost always autosomal dominant, a single genetic site has not yet been established; several candidate polymorphisms have been tentatively proposed.
Treatment A curious fact about essential tremor of the typical (non–alternate-beat) type is that it can be suppressed by a small amount of alcohol in more than 75 percent of patients; but once the effects of the alcohol have worn off, the tremor returns and may even worsen for a time. Of more therapeutic interest, essential tremor is inhibited by the beta-adrenergic antagonist propranolol (between 80 and 200 mg per day in divided doses or as a sustained-release preparation) taken orally, usually remaining effective over a long period of time. Often it takes several days or weeks for the effect to be evident. The benefit is variable and often incomplete; most studies indicate that 50 to 70 percent of patients have some symptomatic relief but may complain of side effects such as fatigue, erectile dysfunction, and bronchospasm (see Young and colleagues). Several but not all of the other beta-blocking drugs are similarly effective: metoprolol and nadolol, which may be better tolerated than propranolol, are the ones most extensively studied, but they have yielded less consistent results compared to propranolol. The relative merits of different drugs in this class are discussed by Louis and by Koller et al.
The mechanism and site of action of beta-blocking agents is not known with certainty. It is blockade of the beta-2 adrenergic receptor that is most closely aligned with reduction of the tremor. Young and associates have shown that neither propranolol nor ethanol, when injected intraarterially into a limb, decreases the amplitude of essential tremor. These findings, and the delay in action of medications, suggest that their therapeutic effect is due less to blockade of the peripheral beta-adrenergic receptors than to their action on structures within the central nervous system. This is in contrast to the earlier mentioned muscle receptor-mediated effect of adrenergic compounds in physiologic tremor. It is possible that ambiguity regarding the action of beta-blocking drugs is the result of their effect on physiological tremor that is superimposed on essential tremor.