Suppression orthoses efficacy
For this review different efficacy analysis methods were used. The efficacy for most of the considered orthoses was analysed with PSD, whereas the remaining orthoses analysed the beneficial change with the RMS of the tremor amplitude, the average tremor acceleration (AA), or deflection amplitude (AD). Even though different analysis methods may have an impact on the efficacy outcome, it can be assumed that there is a similarity between these values as the analysed variables are co-dependent (distance, acceleration, energy).
In general, the efficacy of suppression is dependent on the mechanical system, but it is also reliant on the sensors, control strategies and human factors. Human factors include the individual adaptation of the subject to the orthoses, the individual characteristics of the disease and/or the individual biomechanical properties, like soft tissue characteristics. The influence of the individual can be seen in Fig.
3. The range of efficacy for tremor subjects is the largest, which can be ascribed to the different interactions of the orthoses with the human. Furthermore, the efficacy varies within one orthosis. One subject out of 10 reached an efficacy of 80% for orthosis #4 WOTAS, whereas the average was 40% (PSD) [
52]. Efficacy can also be found to vary within one subject, for instance with different arm postures (orthosis #3) [
45]. Furthermore, tremor-affected subjects suffered from different diseases including ET, PD, multiple sclerosis, post-traumatic tremor or mixed tremor. However, most studies focused on ET and PD as the most common movement disorder diseases. In some of the examined literature, subject populations comprised mixed disease diagnoses, whilst other studies considered individuals of only one condition. This disparity led to a large fluctuation in the efficacy of the studied orthoses. The efficacy for studies in tremor subjects ranges from 30% (AA) to 98% (PSD), with an average cross-method efficacy of 63%, which is in the range of medication efficacy (39 – 68% tremor amplitude improvement for ET) [
3]. Orthosis #12, DVB Orthosis, reached the highest suppression efficacy (98% PSD). However, the orthosis also suppresses 17% of voluntary movements (magnitude change). Furthermore, tremor subjects usually continue their medication therapy during the studies, which means that the suppression benefit of the orthoses is supplementary to the medication treatment. Neither pharmaceutical long-term studies nor orthotic long-term studies were sufficiently performed for comparison. However, tremor intensity increases over the progress of the disease, whereas the performed studies indicate that the efficacy of medication decreases over time. We assume that the efficacy performance of orthoses increases with more severe tremor, because most tremor suppression mechanisms reduce tremor to a certain baseline and are thereby independent from the severity of the tremor. It is unclear how tremor reacts to long-term mechanical suppression. Increase of tremor by muscle training due to resistance force by the orthosis, as well as decrease of tremor by the mechanical interruption of the sensory feedback of the nervous system, are possible effects. Furthermore, unknown side-effects and phenomena could appear and/or intensify, such as the Distal to Proximal Tremor Shift.
For the experiments with healthy subjects, tremorous movements were stimulated by either electricity or the subject imitating the movement. The properties of the soft tissues were included in these experiments, but it is unknown how comparable tremor simulation and stimulation are to condition-induced tremor. Furthermore, the retrieved studies used a small number of subjects, most often only one subject; as a result, the experiments are more a proof of concept than representative of a complete quantitative study on efficacy. Future evaluations need to aim for clinical trials with a statistically reliable number of subjects, while at the same time a placebo group should be included. The development of placebo-controlled trials is necessary because the mind-set might have a positive impact on the human control system, which reinforces the human motor control and reduces tremor. Placebo-controlled trials are a challenge, since a placebo orthosis itself will always have an impact on the wearer, as even just the weight of the placebo orthosis has a tremor suppression effect. Due to technical limitations, an orthosis will always have some resistance force and interaction with the wearer, especially in passive but also in semi-active and even active systems. A suitable approach for a placebo-controlled trial needs to be developed to account for the placebo effect.
Applying an external force to the human musculoskeletal system introduces further difficulties, as the involuntary muscle activity applies the force directly onto the skeletal system and therefore requires the orthosis to suppress this movement through the soft tissues (skin, fat, muscles, etc.). The stiffness between an orthosis and the human body is a key factor for tremor suppression as joint movement areas, surface tendons and surface nerves or vessels need to be avoided to prevent harm when applying force to the human system. Furthermore, the stiffness of the tissues increases with the applied pressure [
32,
55]. Besides the flux of force, soft tissues also influence sensory information, which are needed among other for a closed feedback loop. In order to optimise the system, soft tissues can be modelled with viscoelastic or elastic properties [
87]. The viscoelastic soft tissue model acts as a parallel non-linear spring-damper-system in the flux of force (Voight element) [
88].
Although most test bench experiments used recorded tremor data, they use a simplified and idealised system, not considering the potential influence of soft tissues or human factors. These simplifications, as expected, lead to the highest efficacies, up to 99.8% (PSD) with a small variation. The distribution of the efficacies shows the impact of soft tissues and the human factors, including the special biomechanics of the diseases. The biggest challenge for the design of an effective orthosis is the human-machine interface. In this field improvements are necessary, even though there is a mechanical limit due to soft tissues.
In order to put the orthosis efficacy in relation, the efficacy of other alternative and supplementary treatments is of interest. The management of tremor through functional electrical stimulation by Rocon’s group reduced the tremor power by 52% (PSD), which was their second approach after the orthosis WOTAS (#4) [
25]. However, rapid fatigue of the stimulated muscle, discomfort due to strong stimulation, and interference with voluntary movements are drawbacks affecting the wearers’ acceptance and the long-term effectiveness of functional electrical stimulation. The third approach of Rocon was sensory electrical stimulation, muscle stimulation below the functional activation threshold, which reached 52% reduction of tremor power on average (with individual parameter optimisation), which is in both cases an improvement compared to the 40% WOTAS (#4) efficacy. The variability in suppression in sensory electrical stimulation was high, with one third of the patients not responding to the therapy. Furthermore, over long-term use the efficacy may be impaired by neural adaptation [
89]. Dideriksen et al. showed that the state-of-the-art in suppression of tremor using electrical stimulation does not transcend 67% on average [
89], whereas tremor suppression orthoses have the potential to achieve higher suppression magnitudes as the semi-active DVB Orthosis (#12) did, with 98%.
Suppression mechanisms and properties
Active mechanisms are theoretically more advantageous than passive mechanisms because they do not generate resistance force for voluntary movements of the user. In reality, correct recognition of a user’s voluntary and involuntary movements by the control system presents a great challenge. The majority of the suppression orthoses rely on electric motors which need a transmission system in order to actuate the limb in the correct manner. These transmission systems are associated with additional weight and installation space, which results in a bulkier mechanism. Additionally, a high specific power and energy efficiency are beneficial for the orthosis’ performance and weight. The rotary motor with transmission exceeds the human muscle regarding the specific power and efficiency. Even though the requirements of the actuation system vary from those of the human muscle, the human muscle can serve as a point of orientation. Orthoses with a linear actuator need to be evaluated individually because the attachment of the orthosis to the human limb affects the resulting torque in the limb joint.
Semi-active mechanisms can minimise the resistance for voluntary movements and maximise it for involuntary movements. Most of the semi-active mechanisms use a magnetic field and magnetorheological fluid to tune the suppression system. Like the linear actuators, a quantitative comparison of the linear damper is difficult because the orthoses are attached differently to the limb. Their rotary damping coefficient is unknown and may have different proportions to that of the linear damping coefficient. The passive suppression mechanisms are not tuneable and are therefore lightweight. With a constant damping coefficient there is a compromise between suppressing voluntary movements in some parts and allowing involuntary movements in others. However, the advantage is the simplicity and lightweight design of such a system. Despite this, only a few papers about passive orthoses have been published, probably because of the disadvantages of such simple mechanisms.
The soft tissue pressure threshold and pressure discomfort threshold differ for each individual subject, through both inter-subject and intra-subject variation. In general, areas of the human body show a lower or higher pressure pain and discomfort threshold at different locations [
90]. It is therefore important where and how an orthosis is attached to the human body. Skin properties may also vary within a day and with age. Furthermore, mechanical properties of the skin like stiffness, friction and thickness change with its hydration and climate conditions [
91,
92]. A potential source of harm for the skeletal system is a misalignment with rigid actuators and structures, for which the inter-subject anatomical variation would consequently require an orthosis, which can adapt to a user’s anthropometry. A further safety hazard is the misalignment of the orthoses hinge and the human joint, where typically a slight human joint axis displacement is observed during rotation, such as the wrist [
93].
Soft mechanisms show a high potential for wearable robotic devices, as they are less bulky and especially visually more appealing. Current users of conventional rigid robotic orthoses claim that these are too bulky, which can lead to negative effects in activities of daily living or in the worst case to social exclusion [
52]. Out of the 21 retrieved orthoses, only 5 are soft orthoses without rigid structures or a suppression mechanism. Among the 16 prototypes, three orthoses propose a soft system. Veale et al. propose to direct research towards compliant robotic orthoses [
94].
Suppression mechanisms and properties
The main components of tremor orthoses are their suppression mechanisms, with the three most common mechanisms currently being electrical motors, pneumatic systems, and viscous/hydraulic configurations. The majority of the suppression orthoses are active with 52% prevalence, of which 73% (38% of all orthoses) rely on electrical motors. The majority (63%) use the electric motor directly (with transmission) to control the human joint. The other motors are used for tendons or alternative mechanisms to transfer the force to the body. Semi-active orthoses account for 29% of the selected papers. Four out of the six semi-active mechanisms are magnetically activated. All magnetically activated semi-active mechanisms are viscous/hydraulic based, with the exception of #10’s electromagnetic friction brake. Passive mechanisms are the least represented suppression type in the literature (19%). No intersection of passive mechanisms was found, since the orthoses use different approaches, like a pneumatic piston-coil (#14) and shear resistance orthosis (#13).
Another aspect of the suppression mechanism is its rigidity. Most of the orthoses rely on rigid suppression mechanisms, whereas only five orthoses integrated a non-rigid mechanism (#6, #11, #17, #18, #21).
In comparison to the human muscle, the specific power and energy efficiency of the mechanisms are shown in Table
3. The efficiency of linear motors and pneumatic piston-coil actuators was taken from external literature, not related to the review, since it was not provided in the retrieved publications. The linear motor has the highest specific power with 387.3 W/kg and the highest energy efficiency with 85% [
85]. The pneumatic mechanism shows the lowest specific power with 76.3 W/kg and an energy efficiency of 20% [
86]. The average specific force of the linear actuators of this review is 228.10 N/kg (±15.40 N/kg), whereas the rotary motor tendon transmission orthosis (#6) was excluded because it uses a transmission system to transfer the motor torque to linear force.
An active suppression mechanism is characterised by the torque or force. The average torque is 2.3 Nm (±0.73 Nm) excluding one outlier (#4 WOTAS – 8 Nm). The average force of the linear actuators is 15.6 N (±0.6 N), excluding also one outlier (#7 PMLM – 67 N).
Passive and semi-active tremor-suppression orthoses were characterised with the damping coefficient. In damping orthoses, the damping force depends on the velocity and for semi-active mechanisms also on the tuning, the adjustment of the damping coefficient by an additional editable input. One of the two semi-active mechanisms, with given parameters, has a low damping coefficient of 8.9 Ns/m, and can be tuned through adjustment of the magnetic field in the piston-coil for the magnetorheological fluid, to the high damping coefficient of 186.7 Ns/m (#9 MR Damper). The other semi-active mechanism has a larger range from 6.5 Ns/m to 25.0 Ns/m (#12 DVB Orthosis). The passive mechanism #7 PMLM has a constant damping coefficient of 400 Ns/m, whereas #14 Air Dashpot has a damping coefficient of 1800 Ns/m. Two other damping orthoses have a rotary damping coefficient of 2*10− 3 Nms/deg. (#13, #16).
Degrees of freedom
For the ergonomics of an orthosis, the DOF are relevant. A locked DOF restricts the natural workspace of the user. Such restrictions lead to discomfort and limited acceptance by the orthosis user. The review of the current literature shows that many orthoses lock the wrist deviation, a movement which can be compensated by the user’s shoulder movement, but this can lead to an overload and/or false posture of the shoulder in everyday usage [
46]. Most orthoses concentrate on suppressing tremor in one DOF, like the elbow or wrist (flexion and extension), whereas only one group investigated the biomechanical kinematics of tremor (#4 WOTAS) [
31]. However, for postural tremor of ET patients, the WFE and FPS are the kinematics with the highest measured tremorous impact in the upper limb [
30]. Many orthoses considered the WFE but only seven orthoses suppress involuntary movements of the FPS, a reason being the mechanical complexity of FPS intervention [
32]. Regardless, the exact biomechanical processes and origins of tremor are still unclear and there is a need for further investigations to achieve an optimal suppression [
95]. In general, it can be assumed that WFE and FPS suppression are sufficient for an adequate physical intervention in tremor because those are the most affected DOF in PD, ET and cerebellar tremor [
96].
Weight of the orthoses
The weight of a wearable orthosis is also an essential factor for its ergonomics. Additional weight at the arm can lead to muscle fatigue and discomfort and is one of the most important design factors [
97]. The average weight of an orthosis which suppresses involuntary movements in the elbow is 580 g, corresponding to a 19% increase in the weight of an average user’s arm (average forearm weight of 2.3% and arm weight of 5% from average body weight of 62 kg [
98,
99]). Comparatively, an orthosis attached to the forearm and/or hands may average 231 g for a 16% increase in the weight of the forearm. In both calculations, the weight of the energy source and control unit were not considered as these additional components will further increase the total weight of the orthoses. To keep the total weight at the arm, these components could be attached decentralized, e.g. like a backpack, instead of being integrated into the orthoses. Furthermore, the results of the specific weight show a high standard deviation because it is influenced by many factors, like the actuation system, cuff system, and lightweight design and development status, respectively. Too heavy orthoses can be an exclusion criterion for the wearer’s everyday usage. Users of the WOTAS (#4) claimed that the orthosis is too bulky and leads to muscle fatigue [
52]. This led to a cessation of the research on this wearable orthosis as it was not an acceptable solution for the patients [
100]. Instead, the group investigated taking a different approach (functional electrical stimulation). This shows the importance of the weight and the need for improvement.
Future research and development
Most of the prototypes did not reach the market due to the low wearability, leading to a lack of acceptance by the user. Here, wearability is the comfort and ergonomics in contrast to the performance. The high weight and the rigid structures lead to low ergonomics and comfort. Especially elder patients are more sensitive to weight due to sarcopenia, the degenerative loss of skeletal muscle mass associated with aging. Furthermore, older people often have a negative attitude towards technology, especially towards gerontechnology [
101]; therefore a high wearability and an unobtrusive design are required improvements.
In order to develop appropriate tremor-suppression orthoses, the biomechanics of the tremorous movement need to be characterized, as proposed by Charles et al. [
95]. Further investigations for the human-machine interface are needed, to improve the connection of a wearable device to the human body with an ideal force transmission. For this, an improvement in the understanding of tremorous movements and influencing factors of soft tissues are crucial.. Future research probably needs to focus on soft suppression mechanisms with improved efficacy for tremor suppression to attain higher rates of patient acceptance. To this end, a future orthosis needs to be less obtrusive and more visually appealing, as well as to incorporate more biomimetic design features, inspired by nature’s functions and mechanisms. Such suppression orthoses could rely on proposed mechanisms like hydraulically amplified soft actuators, Peano-HASEL [
102], dielectric elastomers, low melting point alloys, shape memory alloys or other mechanisms reviewed by Chen and Pei [
103]. This higher patient acceptance combined with improved efficacy could be achieved by the improved wearability along with such soft mechanisms and the new possibilities of an unobtrusive design. A new orthosis with a soft suppression system and improved suppression efficacy needs to have enough variability to accommodate all patients and different tremor types. Such an orthosis could be used in future to investigate the effect of such tremor-suppression orthosis on the subject and its involuntary movement in short- and long-term use, like the Distal to Proximal Tremor Shift phenomenon.