The barbiturate drug primidone has also been effective in controlling essential tremor and may be tried in patients for whom beta-blocking medications and not effective or tolerated. The side effects may be drowsiness, nausea, and slight ataxia. Treatment should be initiated at 25 mg twice or three times per day and increased slowly in order to minimize these effects. Gabapentin, topiramate (see Connor), mirtazapine, a variety of benzodiazepines and a large number of other drugs have been used generally without success, and should be considered second-line therapies; these alternatives are discussed by Louis. Amantadine also has a modest effect on tremor and may be used as an adjunct.
The alternate-beat, slow, high-amplitude, kinetic-predominant type of essential tremor is more difficult to suppress but has reportedly responded to clonazepam (Biary and Koller); in our experience, however, this approach has not been as successful. Alcohol and primidone have less effect than they do in typical essential tremor. Indeed, the tremor has often been resistant to most attempts at suppression, for which reason surgical approaches are now being used (see further on).
Injections of botulinum toxin into a portion of a limb can reduce the severity of essential tremor locally, but the accompanying weakness of arm and hand muscles often proves unacceptable to the patient. The same medication injected into the vocal cords can suppress severe voice tremor as described in a series of cases by Adler and colleagues as well as by others, but caution must be exercised to avoid paralyzing the cords. Doses as low as 1 U of toxin injected into each cord may be effective, with a latency of several days. The long-term repeated use of this treatment has not been adequately studied for essential-type limb or voice tremor.
In resistant cases of essential tremor of the fast or slow variety, stimulation by electrodes implanted or ablative lesions in the ventral medial nucleus of the thalamus or the internal segment of the globus pallidus (of the same type used to treat Parkinson disease) has produced a response over many years; details can be found in the small study reported by Sydow and colleagues.
Tremor of Polyneuropathy
Adams and coworkers described a disabling action tremor in patients with chronic demyelinating and paraproteinemic polyneuropathies. It is a particularly prominent feature of the polyneuropathy caused by immunoglobulin M (IgM) antibodies to myelin-associated glycoprotein (MAG). The movements simulate a coarse essential, or ataxic, tremor and typically worsen if the patient is asked to hold his finger near a target. The EMG pattern is more irregular than that in essential (familial) tremor (Fig. 4-7C). Pedersen and colleagues have found it to vary greatly in amplitude with considerable side-to-side oscillation, which is induced by co-contracting muscle activity; they also found little suppression of the tremor with loading of the limb, unlike most other organic tremors. It is hypothesized that there is a disturbance of muscle spindle afferents.
Some cases of acute or chronic inflammatory neuropathy or ganglionopathy may be marked by a similar and prominent ataxic tremor and a faster action tremor. A special type of Guillain-Barré syndrome (Fisher variant) is characterized by a tremor that is indistinguishable from the ataxic type but probably has a peripheral basis. Also, the inherited disease, peroneal muscular atrophy (Charcot-Marie-Tooth disease), may be associated with tremor of the essential type but the two may be coincident rather than directly related; this combination of symptoms was the basis on which Roussy and Levy incorrectly set it apart as a distinct disease. Chapter 43 discusses these polyneuropathies.
Parkinsonian (Repose, Rest) Tremor