An important research objective in the field of movement disorders has been the development of effective criteria for differentiating Parkinson’s disease (PD) from other conditions with similar symptoms. Essential tremor (ET) is frequently misdiagnosed as PD because of its close resemblance to the latter disorder. Such mistaken diagnoses lead to frustration on the part of both the patient and the neurologist, as ET does not respond to treatments for PD. This consideration underscores the importance of close examination of tremor manifestation, which can differentiate ET from PD. Also, early PD can be misdiagnosed as ET, with similar untoward impact on management. Although the diagnosis of both PD and ET remains based on the clinical history and neurologic exam, diagnostic tests (such as olfactory assessments and imaging incorporating the use of radioactive tracers) have also shown promise in distinguishing between the 2 disorders.

Essential tremor (ET), characterized by postural tremor of the arms or head, is one of the most common movement disorders.^1,2 The age of onset is bimodal, peaking in the early twenties and again during the sixth decade of life.³ The prevalence increases with advancing age, as reflected in studies that have reported rates of 4% among individuals ≥40 years old and nearly 5% in populations ≥65 years old—the latter being substantially higher than rates of all types of parkinsonism in the elderly (2.2%).^1-5 Moreover, the presence of ET among individuals ≥65 years of age nearly doubles the risk of dementia compared to population norms.⁶ Even in the absence of dementia, patients with ET may exhibit deficits across a wide range of cognitive functions, as well as psychiatric manifestations such as anxiety and depression.^7-9 Some studies but not others have reported an increased incidence of sensory abnormalities (including olfactory deficits and hearing loss) in patients with ET compared to the incidence in age-matched controls.^10-13

A familial pattern of occurrence has been observed in approximately 50% of young-onset cases of ET from population-based samples and >80% of young-onset cases from clinical series, implying a genetic component.¹⁴ Several candidate susceptibility loci have been identified, but their relative contributions to the risk of ET remain to be more fully defined.^3,15-19 In certain families, ET appears to be related to an autosomal dominant variant with high but not complete penetrance, suggesting an additional influence of environmental factors in the etiology of the disorder.^17,20 Interest in the independent effects of nongenetic risk factors, including possible environmental causes, has also been prompted by the fact that some cases of ET are sporadic.²¹ Recent studies have explored a host of possible environmental contributors (most notably harmane [a tremor-producing neurotoxin], lead, and agricultural exposures or pesticides), but further work is required to confirm associations with ET.²²

Imaging studies have revealed cerebellar participation in ET, with the tremor itself believed to be mediated by a neuronal loop involving cerebellothalamocortical fibers.^7,23 Recent pathologic studies using magnetoencephalography have provided the first direct evidence that patients with ET have alterations in communication within a network of brain areas, including the primary motor cortex, premotor cortex, thalamus, cerebellum, and brainstem.²⁴ Postmortem analyses have found that the cerebella of some ET brains contain significantly larger numbers of Bergmann glial cells and torpedoes (swellings of the proximal portion of the Purkinje cell axon) than control brains.^25,26 The number of torpedoes is 10 times higher than in control brains and 2 to 3 times higher than in brains from patients with Parkinson’s disease (PD) or Alzheimer’s disease (AD).^25-27 Studies have also documented a distinctive pattern of Lewy bodies in the brainstems of some patients with ET.^25,28 This pattern of Lewy body distribution, characterized by confinement primarily to the locus coeruleus, has not been observed in PD.^25,28 The mechanism by which confinement of Lewy bodies mainly to the locus coeruleus might result in kinetic tremor in ET remains unclear.⁷

Patterns of functional and cognitive decline have also been documented in ET that are different from those seen in PD and AD.²⁹ A recent study found that among patients with PD or AD, scores on the Minimum Data Set—Activities of Daily Living (MDS-ADL) section correlated significantly with scores on both the Unified Parkinson’s Disease Rating Scale part III and the Mini-Mental State Examination (MMSE).²⁹ In contrast, patients with ET exhibited a different pattern of functional disability, wherein MDS-ADL scores correlated significantly only with MMSE scores, specifically subscores related to orientation in time and space.²⁹ The investigators concluded that these findings highlight the need for greater attention to the nonmotor aspects of ET (eg, cognitive deficits), which may be more functionally disabling than motor dysfunction in some patients.²⁹

As knowledge continues to accumulate, the traditional view of ET as a benign, familial, monosymptomatic disorder is evolving into the perspective that this entity may actually represent a distinct neurodegenerative disease or family of such diseases, marked by a variety of motor and nonmotor features as well as by etiologic, clinical, and pathologic heterogeneity.^17,30