Dovepress 3 – Tremor is of large amplitude (.2 cm), violent, and jerky, resulting in difficulty completing the task because of spilling or inability to hold a pen to paper. Tremor rating scales (TRS) are used to evaluate ET, particularly in clinical trials. A commonly used TRS is the Fahn–Tolosa–Marin rating scale,19 which is completed by health care providers. The FTM rating scale evaluates ET based on its appearance, tasks such as drawing lines, spirals, and pouring liquids, and effect on activities or daily living. Elble et al found that a 1-point change in TRS represents a substantial change in tremor amplitude in ET patients.20 Gironell et al evaluated the diagnostic potential of neu- rophysiologic analysis of tremor.21 Subjects included three hundred outpatients with postural tremor. Following the first clinic visit, accelerometry and surface electromyography was conducted, and patients were clinically diagnosed by two neurologists who were blinded to the results of neurophysi- olgoical testing. Neurophysiologic criteria for the diagnosis of ET required the presence of all of the following: 1. Rhythmic burst of postural tremor on EMG 2. Tremor frequency greater than or equal to 4 Hz 3. Absence of rest tremor or, if present, frequency 1.5 Hz lower than the postural tremor 4. Absence of tremor latency from rest to postural position 5. Changes of the dominant frequency peak less or equal to 1 Hz after the weight load test 6. No changes in tremor amplitude after mental concentration. The neurophysiologic criteria for ET showed a sensitivity of 98%, a specificity of 82%, a positive predictive value of 95%, a negative predictive value of 91%, and positive prob- ability ratio of 5.5. Genetics ET is commonly inherited by autosomal dominant trans- mission with incomplete penetrance. In some families, transmission appears to be polygenic.22 Identified suscepti- bility loci for ET include 3q13.1,23 2p22-p25,24 and 6p23.25 Approximately 50% of ET patients have an affected first- degree relative,11 and first-degree relatives of ET patients also appear to be five times more likely to develop ET than control subjects.26 A family history of ET appears to correlate with younger reported age of tremor onset. Not all cases of ET have a genetic etiology, however, and the disease may occur sporadically.27 Neuropsychiatric Disease and Treatment 2010:6 Overview of essential tremor Pathogenesis The exact pathogenesis of ET is unknown. The disease may be caused by a central oscillator originating in the Guillain Mollaret triangle located in the brainstem. Other areas of the brain that have been implicated in the pathogenesis of ET are the inferior olivary nucleus and the cerebellum.28 Evidence for cerebellar involvement includes the presence of “torpedos” or axonal swellings that have been identified in the Purkinje cells in some ET patients.29 One study also found a greater loss of Pukinje cells in the cerebellum of ET patients compared to normal controls.30 Whether ET is a neurodegenerative disorder or a non- degenerative disease remains controversial. The finding of Lewy body pathology in some ET patients and Purkinje cell loss in others points towards a neurodegenerative process. However, ET may be caused by abnormal oscillatory dys- function of the motor system, suggesting that it is not a pri- mary neurodegenerative disease, but one in which there may be secondary neuronal damage as the disease progresses.17 Increased membrane excitability in motor circuits may play a key role in the pathogenesis of ET.31 Several studies suggest that there may be a link between PD and ET, although this remains controversial. For example, one prospective study of patients with ET found a fourfold increase in the risk of developing PD compared to individuals without ET.2 Rest tremor, which is commonly found in PD patients, also appears to occur in a subset of ET patients, for reasons that are unknown. Another study compared 53 patients with combined ET and PD to patients with diagnoses of either PD or ET alone,33 and found that the gender distribution of patients with a combination of ET and PD (67.9% male) was identical to that of PD patients (67.9% male) but different from that of ET patients (50.0% male) (P = 0.02). Treatment of ET (pharmacotherapy) Pharmacologic treatment of ET should be considered when tremor interferes with activities of daily living. Proper treatment is contingent on a correct diagnosis, and other possible causes of tremor must be excluded. Patients need to be informed that treatment of ET does not cure the disease, but may offer tremor improvement. Medications that are used to treat ET are those that are used to treat other medical conditions, such as hypertension and seizures. It is estimated that medications improve tremor magnitude in ET by about 50%. Unfortunately, 30% to 50% of ET patients will not respond to medical therapy. submit your manuscript | www.dovepress.com Dovepress 403