# Medical Devices for Tremor Suppression: Current Status and Future Directions
## 1 Introduction
Currently, propranolol and primidone are the two first-line therapies [15; 16; 17; 18; 19; 21]. Across randomized controlled trials (RCTs), propranolol and primidone monotherapy produce a mean reduction in the tremor amplitude of 54.1% and 59.9%, respectively, as measured by accelerometry [22]. Nonetheless, 56.3% of patients eventually discontinued the use of either medications [23]. Topiramate is also recommended as a first-line therapy by the guidelines of the Italian Movement Disorders Association (IMDA) [24] and is considered clinically useful at higher doses by the IPMDS task force [19]. However, it is recommended by the AAN guidelines as a second-line therapy [17; 18]. Second-line medications have been reported to be less efficacious in reducing the amplitude of tremors. These include alprazol, atenol, gabapentin, and sotalol, as well as the aforementioned topiramate [17; 18]. In contrast, there is no consensus in the management of PD tremors. The current NICE guidelines recommend levodopa as the first-line therapy for management of all motor symptoms in patients in the early stages of PD [5]. Deep brain stimulation (DBS), whose efficacy has been demonstrated through closed loop approaches [25; 26] and interleaving stimulation [27], is the most common surgical treatment to date, providing durable tremor control, especially for patients with medically refractory ET or advanced PD. The effectiveness of DBS in ET and PD tremor is thought to be due to the direct electrical stimulation to the ventral intermediate nucleus (VIM) possibly disrupting the synchronous firing of thalamic neurons [28; 29]. In addition to the VIM, the subthalamic nucleus, internal globus pallidus, and pedunculopontine nucleus are also effective targets for DBS in patients with PD tremors [30]. The use of DBS was approved by the Food and Drug Administration (FDA) for ET in 1997, for advanced PD in 2002, and for mid-stage PD in 2016. As of late, radiofrequency thalamotomy has become less favored. An RCT comparing DBS with thalamotomy in 68 patients with tremor due to ET, PD, or multiple sclerosis found that DBS results in fewer adverse effects (\(p\) = 0.024) and a greater increase in the Frenchay Activities Index score, which assess 15 ADLs. This suggests a greater improvement in the functional status when compared to thalamotomy [31]. Although surgical treatments for tremors, including DBS, stereotactic radiosurgery (SRS), and magnetic resonance-guided focused ultrasound (MRgFUS), are more efficacious than pharmacotherapy [32], the utilization of these procedures remains low. Limiting factors may include high surgical costs [33; 34], access to care [35; 36], and patient preference [35]. Other perceived barriers to DBS include practitioner preference [34; 37], high resource and labor intensity [34; 38], and perceptions of serious surgical risk [34; 39; 38]. Thus, a growing unmet need for safe and effective tremor control and suppression sets the stage for a range of therapies to bridge this gap between lifestyle modifications, pharmacotherapy, and surgical treatment. Using a variety of noninvasive suppression mechanisms, medical devices fit within this gap to provide effective tremor suppression at a lower risk than surgery. The increasing interest in this area has led to the birth of a new classification of external upper limb tremor stimulators. In 2018, the de novo classification request of Cala ONE (Cala Health, Burlingame, CA, USA) received FDA approval [40]. Herein, we focus on the mechanisms of action, safety and efficacy profiles, and clinical applications of different categories of medical devices that are available clinically or previously investigated for tremor suppression. Furthermore, we highlight the limitations of these devices. Such information may then be translated biomechanically and clinically for potential future advancements of medical device for tremor suppression.