Essential tremor

Although essential tremor (ET) is the most common movement disorder, it is frequently misdiagnosed and, as yet, there is no entirely satisfactory treatment.1S2 Termed “benign,” it can produce significant functional disability and embarrassment.3 Several epidemiologic studies have been conducted4-8 (table l), and it is reasonable to estimate in excess of one million cases in the United States, with no gender or racial differences. About 50% of cases are familial. It is transmitted as an autosomal dominant with variable penetran~e. ~ ET is monosymptomatic postural/action tremor, without parkinsonian, cerebellar, or other neurologic signs. ’OJl It can occur at any age, though incidence increases with age. Onset is often insidious with variable progression over time. The hands are most commonly affected, but other body parts may be involved. Usually, the tremor is most evident with the hands held in posture and attenuates during voluntary movement (as in finger-to-nose testing); however, in some patients tremor is most marked during movement.12 When tremor is severe, the tremor may persist a t rest, thus making distinction from Parkinson’s disease difficult . 13J4 The frequency of ET is typically between 4 and 8 Hz and tends to be inversely related to amp1it~de.l~ The tremor may result from synchronous or alternating activity in antagonistic muscle groups.16 Many authors have recognized that E T is a heterogenous condition. Differences in pharmacologic responsiveness have suggested subtypes.17J8 The most useful system of classification is that of Marsden et all9 (see table 2), based on frequency and the contribution of feedback around the peripheral stretch reflex. Type I is considered to be indistinguishable from enhancedphysiologic tremor (peripheral reflex dependent) and type I1 is largely dependent upon an oscillator within the central nervous system. Elble16 has demonstrated several different mechanisms that could form the basis for further subdivision of type I ET. Head tremor, commonly associated with hand tremor, can occur in isolation and may show a different pharmacologic response to hand tremor.20,21 Speech invol~ement22~~3 can result from tremor of the muscles of phonation, respiration, or other muscles of the head and neck. A severe, generalized tremor state involving limbs, head, and trunk may occur in some patients and could be classified as type TI1 by the Marsden et all9 scheme. Variants of ET12 include primary writing tremor, a selective action tremor in which pronation of the forearm during writing elicits a pronation/supination tremor not seen during other arm m o ~ e m e n t s ~ ~ , ~ ~ and orthostatic tremor, a lower limb tremor present on standing and absent during sitting, walking, or when leaning against a firm supp0rt.2~ In spite of clear definitions of ET, it is commonly misdiagnosed as Parkinson’s disease (PD) . 27 Parkinsonian signs such as cogwheel rigidity and tremor at rest may be seen in ET,14 and postural tremor is common in PD.28 Most epidemiologic studies have failed to find a relationship between PD and ET although the debate has recently been re-opened by Geraghty et al,29 who found that 25 of 130 consecutive patients with ET had concurrent PD. Barbeau and Pourcher30 suggest that patients with early onset PD have a high incidence of E T in their families. ET may be associated with other movement disorders such as focal dy~tonias ,~~ dystonia musculorum deformans and torsion d y ~ t o n i a , ~ ~ essential myocl~nus,~~ and inherited or acquired peripheral ne~ropathies.3~ Morphologic studies of autopsy cases have found no significant path0logy.3~ No abnormality of muscle spindle feedback or sensitivity of peripheral beta receptors has been d e t e ~ t e d . 3 ~ ~ ~ ~ ET of large amplitude and low (and invariant) frequency (Marsden type 11) appears to be dependent upon an oscillator within the central nervous system. In view of the rhythmic neuronal bursts that have been recorded in the thalamic nucleus ventralis in ETF8 and the response of ET to thalam~tomy,~g such an oscillator, in common with other pathologic tremors, must be closely associated with the cerebellorubral-thalamo-cortical circuit. Rhythmicity in the inferior olive40 may offer clues to the origin of ET, but as ElbleI6 has emphasized, the final expression of tremor depends on complex, and as yet poorly understood, interactions between a central “generator” and the peripheral system, in particular the stretch reflex.