Essential tremor (ET) is a neurological movement disorder characterised by bilateral limb kinetic/postural tremor, with or without tremor in other body parts including head, voice and lower limbs. Since no causative genes for ET have been identified, it is likely that the disorder occurs as a result of complex genetic factors interacting with various cellular and environmental factors that can result in abnormal function of circuitry involving the cerebello–thalamo–cortical pathway. Genetic analyses have uncovered at least 14 loci and 11 genes that are related to ET, as well as various risk or protective genetic factors. Limitations in ET genetic analyses include inconsistent disease definition, small sample size, varied ethnic backgrounds and many other factors that may contribute to paucity of relevant genetic data in ET. Genetic analyses, coupled with functional and animal studies, have led to better insights into possible pathogenic mechanisms underlying ET. These genetic studies may guide the future development of genetic testing and counselling, and specific, pathogenesis-targeted, therapeutic strategies.

Background: Essential tremor (ET) is reported to have a bimodal distribution of age at onset (AAO) with phenotypic variability based on the AAO. This study aims to explore the distribution of AAO based on mathematical modeling and ascertain the differences, if any, in the clinical features of groups. Methods: A chart review was conducted for 252 patients with ET diagnosed based on the Consensus statement of the Movement Disorder Society on Tremor. Finite mixture modeling was performed to identify groups of the cohort based on the AAO. Results: Three groups were defined: early onset (EO): AAO ≤ 22 years, n = 63, intermediate onset (IO): 23 ≤ AAO ≤ 35 years, n = 43, and late onset (LO): AAO ≥ 36 years, n = 146. There were no significant differences related to family history or responsiveness to alcohol. The EO group had significantly higher prevalence of upper limb and lower limb tremor. Head tremor and voice tremor was more prevalent in the IO and LO groups. Cerebellar signs showed a significant increase with an increase in AAO. Conclusions: ET shows significant phenotypic variability based on the AAO. Patients with an early AAO are more likely to develop an appendicular tremor, whereas the probability of axial tremor and cerebellar signs increases with increasing AAO.

Background: There is a significant need for a targeted therapy for essential tremor (ET), as medications have not been developed specifically for ET, and the ones prescribed are often not well-tolerated, so that many patients remain untreated. Recent work has shown that, unlike previous experience, kinematically guided individualized botulinum toxin type A (BoNT-A) injections provide benefit along with minimal weakness. Ours is the first long-term (96-week) safety and efficacy study of BoNT-A as monotherapy for ET using kinematically driven injection parameters. Methods: Ten ET patients were administered six serial BoNT-A treatments every 16 weeks and were assessed at 6 weeks following treatment. During each study visit, the Fahn–Tolosa–Marin (FTM) scale, the Unified Parkinson’s Disease Rating Scale, and the Quality of Life for Essential Tremor Questionnaire (QUEST) were administered along with kinematic assessment of the treated limb. Participants performed scripted tasks with motion sensors placed over each arm joint. Dosing patterns were determined using the movement disorder neurologist’s interpretation of muscles contributing to the kinematically analyzed upper limb tremor biomechanics. Results: There was a 33.8% (p<0.05) functional improvement (FTM part C) and a 39.8% (p<0.0005) improvement in QUEST score at week 96 compared to pretreatment scores at week 0. Although there was a 44.6% (p<0.0005) non-dose-dependent reduction in maximal grip strength, only 2 participants complained of mild weakness. Following the fourth serial treatment, mean action tremor score was reduced by 62.9% (p=0.001) in the treated and by 44.4% (p=0.03) in the untreated arm at week 96 compared to week 48. Conclusions: Individualized BoNT-A dosing patterns to each individual’s tremor biomechanics provided an effective monotherapy for ET as function improved without functionally limiting muscle weakness.

During the “DBS Canada Day” symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to share their knowledge regarding deep brain stimulation (DBS) management of movement disorders in three domains: (1) the programming algorithms, (2) the necessary team to run a neurosurgery program, and (3) the appropriate scales to better define in a more comprehensive fashion the effect of the brain surgery. Each presentation was followed by an open discussion, and this article reports on the conclusions of this meeting on these three questions. Concerning programming, the role of the pulse width and the switching off of the stimulation at night for thalamic stimulation for the control of tremor have been discussed. The algorithms proposed in the literature for programming in Parkinson’s disease (PD) need validation. In dystonia, the use of monopolar vs bipolar parameters, the use of low vs high frequencies and the use of smaller versus larger pulse widths all need to be examined properly. Concerning the necessary team to run a neurosurgical program, recommendations will follow the suggestions for standardized outcome measures. Regarding the outcome measures for DBS in PD, investigations need to focus on the non-motor aspects of PD. Identifying which nonmotor symptoms respond to DBS would allow a better screening before and satisfaction postoperatively. There is an important need for more data to determine the optimal programming protocol and the standard measures that should be performed routinely by all centers.

In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated—Parkinson’s disease (PD), tremor, and dystonia—is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies.

Background: Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT−) are few. Methods: To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. Results: HT was present in 44.4% of the patients. Comparison between HT+ and HT− showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. Conclusions: Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

We review the Saskatchewan Movement Disorders Program, which started in 1968 and has had the dual goals of patient care and research. The clinics are structured to collect research-worthy data including videos, longitudinal follow-up, and autopsy studies of patients seen in the clinics. At every clinic visit, the patient is evaluated by one or both authors. A total of 25% to 30% of the deceased come to autopsy. Frozen half-brain and formalin-fixed remnants from autopsy are preserved in our laboratories. Patients not seen in our clinic are not included in research, which makes it different from brain banks. So far, 515 cases have come to autopsy. So far, there have been 17 collaborating scientific teams from Canada, the United States, Europe, and Japan. The collaborators are not charged for access to our resources. This program offers a unique opportunity to study multiple aspects of movement disorder patients seen in clinical practice.

Background: Treatment options for essential (ET) and Parkinson disease (PD) tremor are suboptimal, with significant side effects. Botulinum toxin type A (BoNT A) is successfully used in management of various focal movement disorders but is not widely used for tremor. Method: This study examines complexity of wrist tremor in terms of involvement of its three anatomical degrees of freedom (DOF) in two common situations of rest and posture. The study examines tremor in 11 ET and 17 PD participants by kinematic decomposition of motion in 3-DOF. Results: Tremor decomposition showed the motion involved more than one DOF (<70% contribution in one DOF) in most ET (rest: 100%, posture: 64%) and PD (rest: 77%, posture: 77%) patients. Task variation resulted in change in both amplitude and composition in ET, but not in PD. Amplitude significantly increased from rest to posture in ET. Directional bias was observed at the wrist for ET (pronation), and PD (extension, ulnar deviation, pronation). Average agreement between clinical visual and kinematic selection of muscles was 55% across all subjects. Conclusion: This study shows the complexity of tremor and the difficulty in visual judgment of tremor, which may be key to the success of targeted focal treatments such as BoNT A.

Essential tremor (ET) is the most common type of movement disorder, although its etiology and neurophysiological substrates remain unclear. While thought to be a benign condition, it has yet to be studied from a neuropsychological perspective. We examined the neurocognitive functioning of 13 nondemented subjects with severe ET, including aspects of memory, cognitive flexibility, and attention. Results revealed that 12/13 subjects demonstrated impairment on 1 or more cognitive measures in comparison with published normative data. The pattern of findings was suggestive of relative dysfunction of frontal-mediated processes not unlike that seen in Parkinson's disease. These deficits were found in subjects irrespective of the presence of cognitive complaints, depression, or the existence of other potential neurocognitive risk factors. These findings suggest that mild cognitive deficits are not uncommon in association with severe ET and may be related to subcortical systems. (JINS, 2002, 8, 125–129.)