Essential tremor: A heterogenous disorder

Although essential tremor (ET) has been well characterized since 1887, there is still considerable controversy about the definition of ET, and there is no agreement among the experts as to whether ET is a symptom, a syndrome, or a specific disease entity. Some experts, including my esteemed colleague, Dr. Elble, have concluded that ET “may not be a single entity.” As I agree with this view, there seems to be no need for any debate. Nevertheless, I will briefly review the evidence to support the argument that ET is not a monosymptomatic disorder, but a heterogenous disorder probably caused by different pathogenic mechanisms. I will discuss the evidence based on clinical, physiological, metabolic, genetic, and therapeutic studies. The uncertainty about the nosology of ET is partly due to a lack of a disease-specific diagnostic marker for ET and an absence of specific pathological changes in the brains of ET patients. Until such a biological, physiological, or genetic marker or markers are identified, the operational diagnostic criteria must rely on the presence or absence of certain clinical characteristics that may be used to categorize ET as definite, classic, probable, or possible (Table 1). The diagnostic criteria may be modified according to specific needs. For example, in genetic linkage studies, only definite ET may be acceptable, whereas in studies designed to explore the clinical spectrum of ET, including associated features, the possible ET category may be more appropriate (Table 2). More recently, core and secondary criteria were proposed to facilitate a practical approach to the diagnosis of ET. Core criteria include bilateral action tremor of the hands and forearms (but not rest tremor), absence of other neurological signs (except Froment’s sign), and isolated head tremor without signs of dystonia. Secondary criteria include long duration (>3 years), positive family history, and beneficial response to alcohol. There are diagnostic red flags that indicate diagnosis other than ET, such as unilateral tremor, leg tremor, rigidity, bradykinesia, rest tremor, gait disturbance, focal tremor, isolated head tremor with abnormal posture (head tilt or turning), sudden or rapid onset, and drug treatment that may cause or exacerbate tremor. For the purposes of this review, I will define ET operationally as a predominantly postural tremor of sporadic or genetic origin producing oscillatory movement of the hands, head, or both, without other known causes of tremor, such as drugs, metabolic or endocrine disorders, structural metabolic central nervous system lesions, or peripheral injury. Family history, alcohol sensitivity, and propranolol responsiveness, while characteristic of ET, should not be considered necessary for the diagnosis. Similarly, the presence of PD, dystonia, and other movement disorders should not necessarily preclude the diagnosis of ET. Typically described as a postural tremor, ET often has a marked kinetic component suggesting cerebellar involvement in the pathophysiology of ET. Thus, patients with otherwise typical (classic) ET often exhibit kinetic tremor when the voluntary movement starts (initial tremor), during the course of the movement (dynamic tremor), and as the affected body part approaches the target, e.g., while performing the finger-to-nose or the toe-to-finger maneuver (terminal tremor, also called intention tremor). In one study, 25% of ET patients were found to have moderate or severe kinetic tremor and other physiological evidence of cerebellar dysfunction. Cerebellar dysfunction in ET is also suggested by abnormalities in tandem gait, noted in 50% of ET patients and by mild postural instability. That the cerebellum may be involved in ET is also supported by the report of a 71-year-old man with ET in whom postural tremor disappeared on the right side after an ipsilateral cerebellar infarct. Correspondence to: Joseph Jankovic, MD, Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030. E-mail: josephj@bcm.tmc.edu Received 17 December 2001; Accepted 19 February 2002 Published online 15 April 2002 in Wiley InterScience (www. interscience.wiley.com). DOI 10.1002/mds.10221 Movement Disorders Vol. 17, No. 4, 2002, pp. 638–644 © 2002 Movement Disorder Society