Spastic hypertonia is a common complication after central nervous system injury affecting 30–40% of people with impaired limb function after stroke (Watkins et al., 2002; Dajpratham et al., 2009). With the population living with chronic stroke in the US expected to double from 2010 to 2050, spastic hypertonia is also a growing problem (Ovbiagele et al., 2013; Mozaffarian et al., 2016).

Spastic hypertonia (hyperreflexia called “spasticity” and elevated involuntary muscle tone) can cause patient discomfort, impair sleep, and make activities like dressing the upper body difficult (Patel et al., 2019). Spastic hypertonia can increase when the limb is in use or when medication treatments, like Botulinum toxin, are wearing off (Sommerfeld et al., 2004). Over time, spastic hypertonia can impair cleaning the hand, cause skin breakdown, and lead to contractures that permanently limit joint mobility (Thompson et al., 2005).

For many patients, current treatment options are inadequate. The most common therapies for spastic hypertonia are intramuscular injection of botulinum neurotoxin type A (BTX-A) and oral antispasmotics like Baclofen. BTX-A injections are typically repeated every three months, with 83–88% of patients reporting relapse of symptoms of spastic hypertonia between injections (Jacinto et al., 2020; Comella et al., 2021). Moreover, treatment does not fully abolish symptoms, even at peak effect (Comella et al., 2021). Baclofen is associated with side effects such as drowsiness (Ertzgaard et al., 2017), and BTX-A is associated with side effects such as weakness (Yaraskavitch et al., 2008; Crowner et al., 2010). Splinting is used to immobilize and stretch the limb to prevent contractures, but does not relieve spastic hypertonia (Lannin and Herbert, 2003).

Research has provided promising preliminary evidence that vibratory or vibrotactile stimulation may help relieve spastic hypertonia symptoms (Ness and Field-Fote, 2009; Noma et al., 2009, 2012; Marconi et al., 2011; Murillo et al., 2011; Caliandro et al., 2012; Casale et al., 2014; Costantino et al., 2017). Vibration can provide strong afferent input through both muscle sensory receptors (Ia) (Roll et al., 1989) and cutaneous mechanoreceptors (Verrillo et al., 1969; Johansson and Vallbo, 1979). However, the dominant mechanism acting to provide spastic hypertonia relief is unknown. In this prior research, three approaches to afferent stimulation for spasticity relief have emerged, including, stimulation to (1) the spastic (agonist) muscle (Noma et al., 2009, 2012; Marconi et al., 2011; Caliandro et al., 2012; Costantino et al., 2017; Won and Park, 2018), (2) the antagonist to the spastic muscle (Hagbarth and Eklund, 1968; Ageranioti and Hayes, 1990; Binder et al., 2009; Cordo et al., 2009; Murillo et al., 2011; Casale et al., 2014), and (3) the skin (Levin and Hui-Chan, 1992; Dewald et al., 1996; Cho et al., 2013; Seim et al., 2021b). No prior work has tested these different approaches in the same participant group. To address this question, we performed a controlled experiment comparing all three approaches to vibration therapy and a sham in a group of patients with post-stroke spastic hypertonia. Spasticity symptoms were measured before, during, and after stimulation to provide data on the time course of symptom changes. We hypothesize that measures of spastic hypertonia will be reduced during stimulation (τ1−τ0) for all conditions. We expect there to be some reduction in spastic hypertonia in the control condition due to relaxation of the participant while sedentary.

We conducted a randomized sham-controlled crossover study of vibrotactile stimulation in patients with spasticity after stroke. This study was reviewed and approved by the Stanford University Institutional Review Board and was registered at ClinicalTrials.gov (Identifier: NCT03814889).

The participant mean age was 60 years (33–75 years). The biological sex distribution was five females and nine males. The race and ethnicity distribution was: seven Asian, six Caucasian, and one Hispanic or Latino.

Table 1 shows Modified Ashworth Scale ratings and Modified Tardieu values for all time points and all conditions. Figure 2 shows the difference from baseline at each time point for all conditions. Trends over all time points are also plotted in Supplementary Figures S1, S2. Only cutaneous simulation resulted in significant reductions in Modified Ashworth ratings (Mean change −1.11 at τ1, p = 0.001; −1.25 at τ2, p = 0.001; and −0.75 at τ3, p = 0.011), Modified Tardieu ratings (Mean change −0.75 at τ1, p = 0.003; −0.71 at τ2, p = 0.003; and −0.21 at τ3, p = 0.1), and Modified Tardieu angle (Mean change −12.68° at τ1, p = 0.002; −9.54° at τ2, p = 0.007). MAS ratings are presented on a scale of 0–5.

We conducted a Friedman's test to assess whether baseline spasticity scores differed significantly between conditions. For the MAS baseline values, the test showed no significant difference between conditions (p = 0.051, Friedman's statistic = 7.7786, N = 14). Similarly, for the MTS baseline scores, there was no statistically significant difference between conditions (p = 0.126, Friedman's statistic = 5.7214, N = 14).

The MTS angle was also measured using 3D motion capture. 3D motion capture data showed that the catch angle was measured at a mean joint movement speed of 132 degrees per second, and the passive range of motion was measured at a mean of 22 degrees per second. The motion capture measures of MTS angle are graphed alongside the manual measurements in the Supplementary material. Values using 3D motion capture were similar to values taken by hand with a digital goniometer for all conditions. Precision of measures taken by hand was also similar to 3D motion capture measures (average SD difference = 5°). The Isometric Force Pillow data is reported in the Supplementary material.

There are multiple approaches to vibratory stimulation in the context of spastic hypertonia, and the work here is the first to compare multiple approaches in the same population. This comparison is important to provide more data on both the underlying mechanisms and optimal approach.

Results indicate that 20 min of skin stimulation, here applied to the fingertips, was associated with a significant reduction in measures of spastic hypertonia. Measures were still significantly different from baseline after stimulation was removed. Peripheral effects, like inhibitory postsynaptic potentials triggered by a volley of sensory input, would be expected to last only during stimulation (Dideriksen et al., 2015). This data thus supports to the idea that cutaneous stimulation could interact with mechanisms with longer time scales. Dewald et al. (1996) discussed a similar finding when using cutaneous electrical stimulation: They found reductions in spastic reflex torque that lasted 15 min after removal of stimulation. They discuss that synaptic effects like reciprocal and recurrent inhibition, as well as presynaptic inhibition are known to last less than a second after the stimulation input. They suggest that long-term potentiation (LTP) or depression (LTD) mediated via primary afferents at the dorsal horn could be at work. “Given that we observe a reduction in stretch reflex responsiveness after cutaneous stimulation, LTP would presumably operate at a convergent inhibitory interneuron, while LTD would operate at a presynaptic excitatory neuron” (Dewald et al., 1996).

Mean difference in Modified Ashworth Scale ratings of 1.1-1.25 points during and after cutaneous finger stimulation also surpass a clinically meaningful difference. The minimal clinically important difference (MCID) in Modified Ashworth for the upper limb is between 0.45 and 0.73 points (Chen et al., 2019).

Though not statistically significant, non-zero changes were also found during both conditions of muscle stimulation. The reason that muscle stimulation was not associated with a significant change in spastic hypertonia could be due to several factors. In prior work, the limb was sometimes in a stretched position e.g., Noma et al. (2009)—which keeps muscles long for increased Ia receptor discharge and keeps the hand loose for measurement. Muscle vibration thus may be best combined with splinting to keep the muscles in a stretched position—a potential avenue for future work. Prior work in muscle stimulation (including both whole body vibration and focal muscle vibration targeted to a specific muscle group) also likely activated multiple agonist and antagonist pathways partly due to the apparatus used in prior work. For example, if our focal stimulation apparatus applies 0.6 mm vibration that transmits ~0.18 mm to non-targets, prior work that applied 1 mm vibration or greater (Casale et al., 2014; Alashram et al., 2019), even using a rounded probe, could experience significant transmission to non targets (e.g., antagonists) (Guang et al., 2018). More than 0.3 mm has been reported to show significant effects in spastic hypertonia (Seo et al., 2016). Of course, stimulation at any muscle group will produce some effect in both agonist and antagonist circuits. Perhaps a higher amplitude of vibration would improve muscle stimulation for spastic hypertonia. Though such stimulation could not be isolated to a particular muscle group, the increased spread of higher-amplitude vibration could increase afferent discharge or muscle fiber recruitment.

The gripping exercise, adapted from the Jendrassik maneuver (Zehr and Stein, 1999), was intended to increase excitatory drive to the impaired limb. Though activities such as walking may provide more drive, our exercise appears to be a useful and accessible procedure. The data at τ3 serve as an effective addition to our repeated measurements in a given visit. Our hypothesis that measures of spastic hypertonia increase after an excitatory activity in all conditions was confirmed. Change in Modified Ashworth measures for the skin stimulation condition increased after the gripping exercise, but did remain significantly below baseline. This finding provides more support that muscle tone inhibition in this condition is not solely supported by an inflow of inhibitory postsynaptic potentials.

Our hypothesis that measures of spastic hypertonia would decrease during the control condition was not confirmed. Measures during the control condition were more consistent that we expected—enabling a clear comparison between conditions. We understood that participants may exhibit some relaxation (leading to decreased spastic hypertonia) after sitting and watching videos during the visit. We provided an adjustment period after their arrival to the lab for the explicit purpose of allowing the participant to stabilize, which appears to have been effective.

The results here inform the development and future research into vibratory and vibrotactile stimulation for spastic hypertonia relief. If a wearable device is created, this stimulation could be applied at intervals throughout the day to help relieve elevated spastic hypertonia during therapy or activities, in the morning, or as-needed. It could be used to help relax the limb for splinting, or between pharmaceutical doses (e.g., Botox or Baclofen). Stimulation is also accessible to those with limited residual motor function who cannot perform exercises.

No non-invasive apparatus can fully exclude activation of non-target muscles and overlying skin. The stimulation conditions used here were designed and validated to provide minimal stimulation of the non-target zones. In addition to amplitude choices, the stimulation's location and frequency support the difference in stimulation methods. The skin of the forearm contains significantly fewer cutaneous receptors than the fingertips. In fact, even individuals without stroke are unable to perceive vibrations at up to 1.5 g amplitude on the arm (Seim et al., 2021a). Some cutaneous activation will still occur during the muscle stimulation conditions; however, this is further mitigated by the use of a 70 Hz stimulation frequency, which is 1/4th the frequency at which Pacinian corpuscles preferentially respond to vibration [250 Hz (Johansson and Vallbo, 1979)]. In contrast, 70 Hz elicits near the peak response from Ia muscle spindles (Roll et al., 1989). Finally, this work focused on short term effects and patients in the chronic stage of stroke. Future work should further evaluate the potential clinical impacts of stimulation approaches long term.

Cutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation.

The datasets presented in this article are not readily available because patient data cannot be shared publicly. Requests to access the datasets should be directed to cseim@stanford.edu.

The studies involving humans were approved by Stanford University Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

BC and DV administered the study and supervised data entry. CS, CH, and LW engineered study devices. CS, AO, and ML designed the study protocol, analysis, and reporting. All authors contributed to the article and approved the submitted version.