This study was approved by the local ethics committee, and each patient provided written informed consent. All patients were prospectively recruited, and the study was conducted between December 2012 and October 2013. In this study there were 17 patients with ET (17 males, mean age 67.3 ± 4.8 years) and 11 age-sex matched healthy control male subjects (mean age 67.2 ± 1.5 years). The seventeen patients with ET were categorized according to their response to propranolol, which is a representative beta blocker. Group A included patients with ET that responded to propranolol, whereas group B included patients who did not respond to propranolol. The healthy subjects did not have any history or symptoms of movement disorders, such as Parkinson's disease, tremor, dystonia, or other cognitive dysfunction, according to a dementia screening questionnaire. Neurologists, specializing in movement disorders at the Veterans Health Service Medical Center and Incheon St. Mary's Hospital (Korea), examined all patients exhibiting tremor. Patients with ET had postural and action tremor without Parkinsonism or other neurologic signs, and were diagnosed as having either definite or probable ET, as based on the National Institutes of Health diagnostic criteria (7). For all patients with ET, a tremor affecting the right arm was dominant. The severity of tremor symptoms was measured according to the Fahn-Tolosa-Marin tremor rating scale (FTM), which was done twice before propranolol therapy and 6 months after the initiation of propranolol therapy. The evaluation consisted of a detailed medical history, physical and neurological examinations, laboratory tests, and neuroimaging studies (MRI or CT) of the brain. None of the patients had any history or symptoms of memory impairment or other cognitive dysfunction (according to the dementia screening questionnaire), nor did they have any cerebrovascular lesions (as demonstrated on neuroimaging). In addition to the aforementioned exclusion criteria, we also excluded patients with secondary causes of tremor (e.g., Wilson's disease, thyroid disease, electrolyte imbalance, neuroleptic drug users, and psychiatric diseases) that would, in the expert opinion of the investigators, interfere with the safe conduct of the study.

For F-18 FDG-PET scans, all subjects were on nil per os for at least 4 hours and their pre-injection blood glucose levels were confirmed to be below 180 mg/dL. The images were obtained approximately 45 minutes after FDG injection (185-222 MBq), using a Discovery STE PET/CT scanner (GE Healthcare, Milwaukee, WI, USA). All studies were done in 3-dimensional acquisition mode. A 16-slice CT scan was performed for tissue attenuation correction prior to the FDG-PET scan. Imaging data were analyzed using SPM 8 (Wellcome Trust Centre for Neuroimaging, University College London, London, UK) and implemented using MATLAB software (MathWorks Inc., Natick, MA, USA). Differences in glucose metabolism between group A and B of ET were estimated on a voxel-by-voxel basis using t tests. Additionally, differences in glucose metabolism between group A and B of ET and healthy control were estimated. The resultant set of t-values constituted the SPM (t) map. The t-statistic image was thresholded at a > 3.93, corresponding to a uncorrected p value < 0.001 in conjunction with a cluster filter of 50 voxels. For purposes of visualization and anatomic localization, the t-score clusters were projected onto a standard high-resolution scalp-extract MRI.

All statistical analyses were performed using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). The Mann-Whitney test and Kruskal-Wallis test were used for comparison of continuous variables, and chi-square analyses were used for comparison of categorical variables. Values are expressed as means and standard deviations. Statistical significance was assumed at a false detection rate of less than 5% (i.e., p < 0.05).