Emerging strategies in the management of essential tremor

Abstract

Currently available therapies for essential tremor (ET) provide sufficient control only for less than a half of patients and many unmet needs exist. This is in part due to the empiric nature of existing treatment options and persisting uncertainties about the pathogenesis of ET. The emerging concept of ET as a possible neurodegenerative disorder, better understanding of associated biochemical changes, including alterations in the γ-aminobutyric acid (GABA)-ergic system and gap junctions, and the identification of the role of the leucine-rich repeat and immunoglobulin-like domain-containing 1 (LINGO-1) gene in ET pathogenesis suggest new avenues for more targeted therapies. Here we review the most promising new approaches to treating ET, including allosteric modulation of GABA receptors and modifications of the LINGO-1 pathway. Medically refractory tremor can be successfully treated by high-frequency deep brain stimulation (DBS) of the ventral intermediate nucleus, but surgical therapies are also fraught with limitations due to adverse effects of stimulation and the loss of therapeutic response. The selection of additional thalamic and extrathalamic targets for electrode placements and the development of a closed-loop DBS system enabling automatic adjustment of stimulation parameters in response to changes in electrophysiologic brain activity are also reviewed. Tremor cancellation methods using exoskeleton and external hand-held devices are also briefly discussed.

A meta-analysis of outcomes and complications of magnetic resonance–guided focused ultrasound in the treatment of essential tremor

“…10 The presence of ET can cause significant functional and psychological disability, and hence the term "benign" has largely been abandoned in its nomenclature. 14 The incidence is higher in the white than in the African American population. 24 Increasing age has been consistently associated with the incidence and prevalence of ET.…”

Cerebellar repetitive transcranial magnetic stimulation (rTMS) for essential tremor: A double-blind, sham-controlled, crossover, add-on clinical trial

“…Despite detrimental effects on quality of life of patients, medications traditionally used as the first-line treatment for ET are neither effective enough nor completely safe in a considerable number of patients [2,3]. Although deep brain stimulation (DBS) and other surgical procedures such as thalamotomy may provide better unilateral tremor control, they are invasive [4,5] and many patients prefer not to select surgical therapeutic options. Altogether, currently there are very few effective non-invasive safe therapeutic strategies for treatment of this common neurological disorder.…”

MRI‐guided laser interstitial thermal thalamotomy for medically intractable tremor disorders

“…Inclusion criteria were a clinical diagnosis of tremor-dominant PD, TiD, or ET following the Queen Square Brain Bank diagnostic criteria for PD 9 and the criteria of the consensus statement of the Movement Disorder Society on tremor for ET and TiD. 1 Tremor-dominant PD was defined as a MDS-UPDRS 10 resting tremor score of ≥2 for at least 1 hand. 11…”

“…© 2018 International Parkinson and Movement Disorder Society Key Words: brain iron accumulation; essential tremor; tremor-dominant Parkinson's disease; tremor in dystonia; R2 Star Diagnosing a tremor disorder accurately is challenging as similar clinical entities can be caused by different diseases. 1 Therefore, in the absence of biomarkers, misdiagnoses between tremor in Parkinson's disease (PD), tremor in dystonia (TiD), and essential tremor (ET) frequently occur. 2 Ioflupane-based single photon emission computed tomography ( 123 I-FP-CIT DAT-SPECT) can assist in differentiating PD from ET and TiD by detecting a presynaptic dopaminergic deficit.…”