Spasticity: Non-pharmacological Rehabilitation Interventions

Backus D, Williams J, Mirkowski M, Morrow S, Short C, Donkers SJ, Bruno T, on behalf of the MSBEST Team. (2019). Spasticity: Non-pharmacological Rehabilitation Interventions. Multiple Sclerosis Best Evidence-Based Strategies and Treatment/Therapies for Rehabilitation. Version 1.0: p. 1-59.

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Key Points

• Group exercise training targeting flexibility, strength, and balance may improve spasticity in persons with MS.
• Locomotor training using body weight supported treadmill training may reduce lower extremity spasticity in persons with secondary progressive MS.
• It is unclear if unloaded leg cycling alone improves clinical measures of spasticity in persons with MS; however, it may have a positive impact on subjective measures of spasticity.
• Unloaded leg cycling may improve spasticity in combination with pharmacological management.
• Participation in recreational sports activities such as sports climbing or yoga may not reduce spasticity in persons with MS.
• Hydrotherapy may improve subjective measures of spasticity more than land-based exercise in persons with MS.
• Cryotherapy may not reduce clinical measures of spasticity in persons with MS; however, cryotherapy may have a positive impact on subjective measures of spasticity.
• Repetitive transcranial and trans-spinal magnetic stimulation may reduce spasticity in persons with MS.
• Intermittent theta-burst stimulation may be an effective intervention to reduce spasticity in persons with relapsing-remitting MS.
• Transcranial direct current stimulation may not improve spasticity in persons with relapsing-remitting MS.
• Transcutaneous electrical nerve stimulation may not reduce spasticity in persons with MS.
• Subcutaneous nerve stimulation (SCNS) may reduce spasticity in persons with MS. SCNS does not seem to be harmful and may temporarily reduce clonus at the ankle.
• Spinal cord stimulation may be a beneficial modality for treating spasticity in persons with MS.
• Hip flexion assist orthoses may not be an effective intervention to reduce lower limb spasticity in persons with MS. There is no evidence related to the utility of other types of orthoses for reducing spasticity in persons with MS.
• Radial shock wave therapy may be effective for reducing spasticity in persons with MS.
• Reflexology may reduce spasticity in persons with MS.
• Acupuncture may reduce spasticity in ambulatory persons with MS.
• It is unclear if massage therapy improves spasticity in the lower extremities of persons with MS.
• Intermittent theta-burst stimulation, in combination with exercise therapy, may reduce spasticity in persons with relapsing-remitting MS.
• Combining massage therapy with exercise therapy may not reduce spasticity in persons with MS more than either therapy alone.
• The use of supported standing may not improve spasticity more than a home exercise program in persons with secondary progressive MS.
• Whole body vibration, in combination with exercise, may not reduce clinical measures of spasticity in persons with MS; however, it may have a positive impact on subjective measures of spasticity.
• Functional electrical stimulation-supported lower extremity cycling may reduce spasticity immediately following treatment in persons with chronic progressive MS.
• Multidisciplinary inpatient rehabilitation may not improve subjective measures of spasticity in clinically stable persons with MS.
• Both orthopedic surgical and neurosurgical interventions may be effective for reducing severe spasticity in persons with MS.
• Transcutaneous electrical nerve stimulation may reduce lower extremity spasticity in persons with MS to a greater degree than oral baclofen.
• Oral baclofen in combination with a stretching program may reduce spasticity more than placebo in persons with MS, but may not be more effective than baclofen alone.
• A combination of oral dantrolene sodium and physical therapy interventions following surgical management of contractures may improve spasticity in persons with severe MS.
• Botulinum toxin, when followed by early physiotherapy, may provide greater reduction in spasticity than botulinum toxin alone in persons with secondary progressive MS.
• Segmental muscle vibration, or a combination of segmental muscle vibration with botulinum toxin, may provide greater reduction in spasticity in persons with secondary progressive MS compared to botulinum toxin alone.

2017 literature search

Module to be updated

Abbreviations

Introduction

Individuals with multiple sclerosis (MS) experience a variety of impairments depending on the location and extent of the lesions and neural damage from the disease. Spasticity is frequently reported as one of the most disruptive symptoms, and in some, may lead to impaired mobility affecting transfers and ambulation, and can impact activities of daily living and social participation. Spasticity has also been reported to significantly decrease quality of life and may even be considered a health issue (Arroyo, Massana, & Vila, 2013; Flachenecker, Henze, & Zettl, 2014; Svensson, Borg, & Nilsson, 2014). Spasticity often leads to a decrease in range of motion, pain or discomfort, and poor positioning, with secondary effects on health and hygiene.

Spasticity is traditionally challenging to define. The Lance definition of spasticity (1980) is a well-accepted one: “…a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflexes, as one component of the upper motoneuron syndrome” (Lance, 1980). However, the word “spasticity” clinically often refers to the spasticity syndrome, which is far more complicated. The spasticity syndrome includes hyperactive tendon reflexes, clonus, and spasms (Katz, Rovai, Brait, & Rymer, 1992; O'Dwyer, Ada, & Neilson, 1996). The National Institutes of Health Task Force definition (Sanger et al., 2003) attempts to further define spasticity as a type of hypertonia in which one or both of the following signs are present: 1) resistance increases with externally imposed movement and with increasing speed of stretch, and varies with the direction of joint movement, and/or 2) there is a threshold speed or joint angle above which the resistance to externally imposed movement rises rapidly. Thus, it is critical that when communicating about or reading literature related to spasticity, one is clear about how it is being defined.

A variety of approaches exist to help manage spasticity in persons with MS (PwMS). These include pharmacological as well as non-pharmacological approaches. Pharmacological treatments include medications that act within the nervous system (e.g., baclofen), at the neuromuscular junction (e.g., botulinum toxin), or directly on skeletal muscle (e.g., dantrolene). Non-pharmacological rehabilitation approaches, such as physical or occupational therapy, may utilize any combination of prolonged stretching and range of motion exercises, casting/splinting, and electrical stimulation to help minimize the detrimental effects of spasticity. Exercise may include weight bearing (e.g., locomotor training) or non-weight bearing (e.g., cycling) activities. Alternative approaches can include acupuncture and massage. Often, treatment for spasticity will be some combination of pharmacological and non-pharmacological approaches and requires a team-based approach for effective management. Surgical approaches may be utilized for sub-optimal response to these pharmacological and non-pharmacological approaches.

This module provides an overview of the available evidence for non-pharmacological interventions for spasticity rehabilitation in PwMS.

Non-pharmacological Interventions: Exercise

Various types of exercise can yield benefits for reduction of spasticity. Exercise modalities include interventions targeting flexibility, range of motion, strengthening and balance exercises, progressive resistance training, leg cycling, and body weight supported treadmill training. A few studies have investigated the effects of different types of exercise-programming on spasticity in PwMS.

Group Exercise Training

Group exercise training can be one mechanism to accomplish exercise interventions, whereby individuals participate in a training program together with other individuals.

Discussion

Tarakci et al. (2013) evaluated 99 MS participants who were ambulatory with or without an assistive device (Expanded Disability Status Scale (EDSS) 2.0-6.5) and randomized them to either a group exercise training program or a control group (no intervention) and evaluated lower extremity spasticity as a secondary outcome measure, using the Modified Ashworth Scale (MAS). The exercise intervention, 60 minutes three times per week for 12 weeks, was performed in a group setting led by a physical therapist with a variety of exercises targeting flexibility, strengthening, balance, coordination, and functional activities. The intervention group showed statistically significant (p<0.01) improvements in all MAS measures compared to the control group.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Tarakci et al. 2013) that a group exercise training program targeting lower extremity flexibility, strength, and balance may improve spasticity compared to no intervention in persons with MS.

Locomotor Training

Locomotor training involves specific walking training either over-ground or using a treadmill system, with or without body weight support, to help address components of an individual's walking ability, including underlying impairments (e.g., spasticity), balance, endurance, as well as adapting to real-life contexts.

Discussion

Giesser et al. (2007) evaluated the impact of locomotor training using body weight support on a treadmill on the functional mobility of four participants with secondary progressive MS (SPMS), and measured spasticity as a secondary outcome. This study involved participants with an average EDSS score of 7.25 and primarily spinal cord presentations of their MS. All four participants completed an average of 40 sessions (2 times per week for 20 weeks), consisting of 60 minutes of weight bearing with 20 minutes of stepping activity. Following intervention, three of the four participants demonstrated a reduction in their spasticity as measured by MAS scores.

Conclusion

There is level 4 evidence (from one pre-post study; Giesser et al. 2007) that locomotor training using body weight supported treadmill training may improve spasticity in persons with secondary progressive MS.

Unloaded Cycling

Cycling, as a therapeutic intervention, is believed to modulate spasticity via the influence of pre-synaptic mechanisms leading to a decrease in excitation of excitatory neurotransmitter release resulting in diminished activation (Frigon, Collins, & Zehr, 2004; Grey et al., 2008).

Discussion

Three studies examined the effects of unloaded leg cycling on MS-related spasticity. Motl et al. (2007) recruited six participants with MS (EDSS 0.5-4.5) with mild to moderate spasticity taking oral baclofen and evaluated spasticity via H-reflex measurements and MAS scores. Participants underwent an exercise condition (20 minutes of unloaded leg cycle ergometry) or a control condition (20 minutes of sitting quietly). Both the H-reflex and MAS scores were significantly reduced 10 and 30 minutes after exercise and the H-reflex remained reduced 60 minutes after exercise. The results of this study suggest that unloaded leg cycling may be an effective adjuvant to pharmacological spasticity management in PwMS. A similar study by Sosnoff et al. (2009) assigned 22 participants with MS (relapsing-remitting (RRMS), primary progressive (PPMS), or SPMS) to either an exercise condition (unloaded leg cycling 30 minutes per session, 3 times per week for 4 weeks) or a control condition and evaluated spasticity using the H-reflex, MAS, and Multiple Sclerosis Spasticity Scale (MSSS-88). The study found neither an improvement or worsening in long term clinical or neurophysiological measures of spasticity apart from the effect of the exercise condition being significantly associated with lower Hmax/Vmax ratio values four weeks following intervention. However, a significant improvement in the participants' perception of spasticity (MSSS-88) was noted.

Another study by Sosnoff et al. (2010) compared the effects of acute unloaded arm cycling versus acute unloaded leg cycling on lower extremity spasticity in PwMS. Ten participants with RRMS and slight to moderate spasticity of the lower extremities participated in three separate sessions evaluating acute unloaded arm cycling or acute unloaded leg cycling as compared to a control condition of quiet sitting. Spasticity was evaluated as the primary outcome measure and measured clinically using the MAS and electrophysiologically via electromyography and H-reflex measurements. After acute unloaded arm cycling, a small, statistically significant reduction in Hmax/Mmax amplitude – indicative of decreased spasticity – was measured in addition to a moderate to large, statistically significant reduction in MAS scores. After acute unloaded leg cycling, a moderate, statistically significant reduction in Hmax/Mmax amplitude was measured along with large, statistically significant decreases in MAS scores. While the current study found statistically significant changes in both cycling conditions, it is important to note that there were greater reductions of the soleus H-reflex and MAS scores in unloaded leg cycling as compared to arm cycling. Furthermore, the study also demonstrated a statistically significant increase in spasticity over time as seen in the control session. Overall, this study demonstrated clinical and neurophysiological reductions in spasticity with unloaded cycling, with a greater effect when the muscles tested were activated by the cycling activity.

Conclusion

There is conflicting evidence (from two prospective controlled trials; Sosnoff et al. 2010; Sosnoff et al. 2009) regarding whether or not unloaded leg cycling reduces spasticity compared to quiet sitting in persons with MS.

There is level 2 evidence (from one prospective controlled trial; Sosnoff et al. 2010) that unloaded leg cycling may reduce spasticity more as compared to unloaded arm cycling in persons with relapsing-remitting MS.

There is level 2 evidence (from one prospective controlled trial; Motl et al. 2007) that unloaded leg cycling may be an effective adjuvant to pharmacological spasticity management compared to quiet sitting in persons with MS.

Mixed Fitness Recreational Activities

Participation in mixed fitness recreational activities such as yoga and sports climbing may provide potential opportunities for fun and alternative exercise options while improving symptoms of MS. However, there is a lack of evidence regarding the incorporation of recreational physical activities and the impact of the activity on MS symptoms.

Discussion

A study by Velikonja et al. (2010) examined the influence of mixed fitness recreational activity participation on various symptoms of MS. Twenty subjects with RRMS, PPMS, or SPMS (EDSS<6.0) were randomized to either sports climbing or yoga, once a week for a period of 10 weeks. Spasticity was a primary outcome measure and was evaluated using the MAS. The sports climbing group participated in wall climbing activities that provided functional opportunities for whole body strengthening, balance, and coordination, depending on the ability level of the participant. The yoga group participated in yoga exercises requiring postural control, body awareness, and isometric muscle contraction and relaxation. The study found no reduction in MAS scores after either intervention; however, neither intervention increased spasticity in the affected muscle groups. There was a statistically significant improvement in EDSS pyramidal scores in the sports climbing group (p=0.046), which indirectly measures muscle strength and flexibility in conjunction with muscle spasticity.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Velikonja et al. 2010) that mixed fitness recreational activities such as sports climbing or yoga may not reduce spasticity in persons with MS.

Hydrotherapy

Hydrotherapy is a modality which utilizes the therapeutic benefits of water to promote healing and restore function. Aquatic therapy programs may offer benefits including gravity reduced exercise and increased freedom of movement in individuals with cerebral palsy (Dimitrijevic et al., 2012) and post stroke (Zhang et al., 2016).

Discussion

One study has examined the effect of an aquatic exercise program compared to land-based exercises for reducing spasticity in PwMS. Castro-Sanchez et al. (2012) investigated the efficacy of a hydrotherapy Ai-Chi program for PwMS and evaluated spasms (as a component of the spasticity syndrome) as a secondary outcome. It would be important to note that Ai-Chi is an aquatic therapy grounded in Tai chi chuan and qigong principles thus emphasizing the importance of the breath as well as progressive resistance training. In this study, 73 PwMS were randomized to a control group consisting of land-based breathing and relaxation exercises, or to an experimental group which received Ai-Chi exercises in a swimming pool. Each group participated in hour long biweekly sessions over 20 weeks with a focus on deep breathing and relaxation for both the control and experimental groups. The study found a significant difference in spasm visual analog scale (VAS) scores at the termination of the study (week 20), with the hydrotherapy group demonstrating a significant decrease in spasms which was maintained at week 24 (four week follow up), but not at week 30 (10 week follow up), which is suggestive of a temporarily maintained effect following the conclusion of the aquatic therapy program. Furthermore, the authors hypothesized that the beneficial effects of an aquatic therapy program are due in part to the gravity reducing environment allowing for greater voluntary movements and overall exercise capability as compared to land-based therapies. While there is insufficiently powered evidence to definitively conclude that aquatic exercise is an effective intervention for MS-related spasticity, the initial evidence is favourable.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Castro-Sanchez et al. 2012) that an aquatic Ai-Chi exercise program may reduce spasticity compared to land-based breathing and relaxation exercises in persons with MS.

Non-pharmacological Interventions: Cryotherapy

It is well known that many PwMS have altered signs and symptoms due to temperature fluctuations, with function tending to deteriorate with increases in ambient or core temperature (Uhtoff's phenomenon) and tending to improve with cooling. Typically, changes associated with exposure to cooling include reduced fatigue as well as possible positive impacts on spasticity, strength, sensation, and mobility (Mead, 1966). The presumed mechanism of action may relate, in part, to improvements in neural transmission within demyelinated circuits with changes in core body temperature that enhance axonal transmission properties and minimize instances of conduction block (Frohman et al., 2013). Limited literature exists regarding the effect of cold on functional mobility, specifically the impact of cold on MS-related spasticity.

Discussion

Three studies have examined the effects of prolonged cryotherapy on MS-related spasticity. Two studies (Kinnman et al., 1997; Nilsagard et al., 2006) evaluated the use of a specialized cooling garment on motor function in PwMS. Nilsagard et al. (2006) recruited 43 temperature-sensitive PwMS (RRMS, PPMS, and SPMS, EDSS 3.0-6.0) in a randomized crossover study and compared the effect of a cooling garment with a placebo garment on physical functioning. This study examined various functional mobility outcomes before and after wearing a cooling vest (-20°C) or placebo vest (22°C) for 45 minutes, including spasticity (assessed using the MAS). While the study found no statistically significant differences in changes on the MAS between groups, there were statistically significant subjective improvements in patients' perception of their spasticity. In contrast, Kinnman et al. (1997) studied the repeated use of a cooling suit on motor function – with spasticity evaluated as a secondary measure – in 14 participants who were ambulatory (EDSS 2.0-6.5) and six participants who were wheelchair dependent (EDSS 7.0-7.5) in addition to eight healthy controls. Spasticity was present in six of the 14 participants who were ambulatory; five of the six had improved spasticity after using the cooling suit. Furthermore, all six participants who were wheelchair dependent demonstrated improved spasticity following use of the cooling suit.

Interestingly, Chiara et al. (1998) examined the effect of a cold bath on MS-related spasticity in 14 ambulatory MS participants (EDSS<5.0). All participants underwent 20 minutes of rest in a “cold” bath (24°C /75°F) in a hydrotherapy tank and 20 minutes of rest in ambient room temperature (24°C+ /-0.6/76°F). While the temperature difference between the control and experimental conditions was negligible, the study noted increased spasticity under the experimental condition. As a result, the study found that cooling by immersion does not reduce mild to moderate spasticity in PwMS and may result in increased spasticity. This finding would support the notion that certain instances of cooling may act as a noxious stimulus and lead to a hypertonicity wind-up phenomenon in addition to negatively impacting visco-elastic properties of connective tissues. In clinical practices located in regions with extreme winter weather, it would not be uncommon to hear complaints of worsening spasticity with cold exposure in some persons living with MS.

Conclusion

There is level 1b evidence (from two randomized controlled trials; Nilsagard et al. 2006; Chiara et al. 1998) that cryotherapy may not reduce spasticity compared to ambient temperature in persons with MS.

Non-pharmacological Interventions: Electrical Stimulation

Electrical stimulation is a well-known therapeutic modality that is widely used in several forms and has been shown to have positive effects on spasticity in spinal cord injury and acquired brain injury populations (Fernández-Tenorio, Serrano-Munoz, Avendano-Coy, & Gomez-Soriano, 2016; Khan, Amatya, Bensmail, & Yelnik, 2017; Sadowsky et al., 2013). Multiple studies have examined a variety of stimulation modalities and their effects on MS-related spasticity. Electrical stimulation can be delivered at any point along the neural axis; stimulation interventions of the brain include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and theta-burst stimulation (TBS), whereas stimulation delivered peripherally includes transcutaneous electrical nerve stimulation (TENS), neuromuscular electrical stimulation, functional electrical stimulation (FES), spinal cord stimulation (SCS), and subcutaneous nerve stimulation (SCNS). Several of these have been evaluated for the management of spasticity in PwMS. Though a full discussion of the safety and tolerability of these various modalities is beyond the scope of this module, caution should be exercised in using modalities that stimulate the central neuraxis (especially brain) in those persons with a history of seizure. For modalities stimulating elements of the peripheral neuraxis (especially peripheral nerve and muscle), caution should be exercised in using these modalities on persons with comorbid neuronopathy, polyneuropathies, or relevant focal neuropathies/active motor radiculopathies. In the same vein, caution must be exercised in using peripherally stimulating modalities in persons suffering from a comorbid primary muscle condition. Pre-treatment evaluations via electroencephalogram or electrodiagnosis (nerve conduction studies and electromyography) may be prudent.

Repetitive Transcranial Magnetic Stimulation

rTMS is a form of noninvasive brain stimulation that has been used therapeutically since 1985. rTMS involves the use of a magnet to stimulate targeted areas of the brain to elicit a specific response, such as modulating cortical excitability (Hallett, 2000). One theory suggests that stimulation of the motor cortex with rTMS will increase inhibitory input through the corticospinal tract to ultimately reduce muscle spasticity (Mori, Koch, Foti, Bernardi, & Centonze, 2009; Valle et al., 2007).

Discussion

Two studies examined the effects of rTMS on treating spasticity in PwMS. This modality delivers a stimulus over the primary motor cortex and has previously been shown to modulate corticospinal tract excitability and the spinal H-reflex, a known measure of spasticity. Centonze et al. (2007) examined two rTMS protocols (within four separate experimental designs) in 19 subjects with RRMS (EDSS 3.0-6.0) with unilateral or predominantly unilateral lower limb spasticity. Clinical (MAS) and electrophysiological (H-reflex) measures of spasticity were used. Overall, the primary study findings indicated that rTMS over the primary motor cortex modulates spasticity and corticospinal tract excitability. In PwMS, a single session of rTMS did not have any clinical effect (decrease in MAS scores) on spasticity (Experiment A). A two-week, ten session series of 5Hz rTMS (Experiment D) did demonstrate a reduction in lower extremity spasticity as indicated by a reduction in MAS and H-reflex values. Furthermore, the reduction in H-reflex ratio was maintained one week after the intervention ended, indicating a beneficial prolonged reduction in spasticity. Abdelkader et al. (2013) also evaluated the use of rTMS and its effect on MS-related spasticity based on the results from Centonze et al. (2007). In this study, 21 subjects with RRMS (EDSS 3.0-5.5) and lower extremity spasticity underwent a two-week treatment series of both high frequency (5Hz) and low frequency (1Hz) rTMS protocols as described by Centonze et al. (2007). Spasticity was assessed clinically using the MAS and Tardieu scales and physiologically using the spinal H-reflex. Abdelkader et al. (2013) found statistically significant improvement on the MAS, Tardieu scales, and H-reflex in participants after treatment with 5Hz rTMS, and no improvement on spasticity after 1Hz rTMS, validating the findings previously reported by Centonze et al. (2007).

Nielsen et al. (1996) examined the effect of repetitive trans-spinal magnetic stimulation on spasticity as measured by the AS and H-reflex in 38 individuals with MS. The individuals were randomized to receive either active treatment or sham stimulation twice daily for one week. Stimulation was delivered across the thoracic spinal cord as determined by investigators. Following the intervention, individuals receiving stimulation demonstrated statistically significant improvements in measures of spasticity including the AS and ankle stretch reflex as compared to controls. Interestingly, both the control (sham stimulation) and treatment stimulation groups reported significant improvement in self-reported spasticity compared to baseline (as measured by ease of activities of daily living) despite only the treatment group demonstrating clinical differences, leading to question a potential placebo effect.

Conclusion

There is level 2 evidence (from one prospective controlled trial; Centonze et al. 2007) that high frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) may reduce spasticity compared to sham rTMS in persons with relapsing-remitting MS.

There is level 2 evidence (from one prospective controlled trial; Abdelkader et al. 2013) that high frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) may reduce spasticity compared to low frequency (1 Hz) rTMS in persons with relapsing-remitting MS.

There is level 1b evidence (from one randomized controlled trial; Nielsen et al. 1996) that trans-spinal magnetic stimulation may reduce spasticity compared to sham stimulation in persons with MS.

Theta-Burst Stimulation

TBS is a form of transcranial magnetic stimulation first described in 2005. Originally used for stimulation of the motor cortex (Huang, Edwards, Rounis, Bhatia, & Rothwell, 2005), TBS may be a suitable intervention for reducing spasticity in people with MS (Di Lazzaro et al., 2005).

Discussion

Only one prospective controlled trial has evaluated the effects of 10 sessions of intermittent TBS (iTBS) over two weeks in PwMS compared to sham iTBS. There was a subsequent decrease in spasticity post treatment as measured with the H/M ratio and the MAS scores (see Table 7). However, this trial had several limitations. First, it was carried out in only 20 participants with MS, 10 each in the intervention and sham groups; second, the level of severity was not specified. These limitations make it difficult to ascertain if these findings are indeed generalizable to the MS population.

Conclusion

There is level 2 evidence (from one prospective controlled trial; Mori et al. 2010) that intermittent theta-burst stimulation may reduce spasticity compared to sham stimulation in persons with relapsing-remitting MS.

Transcranial Direct Current Stimulation

tDCS is another form of non-invasive brain stimulation employing a constant, low current to the brain through electrodes on the scalp (Nitsche et al., 2008). Similar to rTMS, tDCS activates neurons in the stimulated area of the brain, and may have therapeutic benefits for people with neurological injury or disease (Stagg & Nitsche, 2011).

Discussion

One study by Iodice et al. (2015) evaluated the effectiveness of anodal tDCS on lower extremity spasticity in MS. This study randomized 20 subjects with RRMS (EDSS 3.0-6.0) and lower extremity spasticity to an anodal tDCS or sham tDCS group. Each group underwent five daily tDCS sessions, with the anodal group receiving 2mA intensity for 20 minutes once a day. Spasticity was evaluated using the MAS and MSSS-88. The study did not find statistically significant changes for any outcome measures between the anodal and sham tDCS groups. These results contrast with previously reported findings regarding rTMS as demonstrated by Centonze et al. (2007) and Abdelkader et al. (2013); however, the authors hypothesized that the effect difference was due to the mechanism of action as tDCS alters the resting membrane potential of a nerve whereas rTMS triggers action potential propagation.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Iodice et al. 2015) that transcranial direct current stimulation (tDCS) may not reduce spasticity compared to sham tDCS in persons with relapsing-remitting MS.

Transcutaneous Electrical Nerve Stimulation

TENS is an electromodality that delivers an electrical current to excite nerves via surface electrodes. While commonly used to modulate pain, TENS has been recently studied for potential application regarding spasticity.

Discussion

Two studies have examined the effects of TENS on spasticity in PwMS. A study by Armutlu and colleagues (2003) enrolled 10 participants with progressive MS (EDSS<6.0) and mild to moderate ankle plantar flexor spasticity. Each participated in daily TENS sessions (pulse width 300us, pulse frequency 100Hz), 20 minutes a day for four weeks; the TENS was placed over the same spinal cord level as the spastic muscle group. The study found statistically significant reductions (p<0.05) in myoelectric activity and MAS scores in both lower extremities after four weeks of treatment. While this study provides initial evidence that TENS has a positive effect on MS-related spasticity, further research is warranted. Miller and colleagues (2007) also assessed the impact of TENS on MS-related spasticity, specifically comparing the effect of two different application times. One treatment protocol administered 60 minutes of daily high frequency TENS (pulse frequency 100 Hz, pulse width 125us), while the second treatment protocol administered eight hours of the same high frequency TENS (pulse frequency 100Hz, pulse width 125us); both were applied directly over the affected quadriceps muscle at a “strong, but comfortable” sensation below motor threshold. Knee extensor spasticity was evaluated on the most affected limb using the Global Spasticity Scale (GSS) – a composite of the Ashworth Scale, Clonus score, and Patellar Tendon Reflex score – and Penn Spasm Scale (PSS). The study found reductions in mean GSS scores after both treatment protocols. A small, nonsignificant reduction was found after two weeks of 60-minute TENS application and a larger, but still nonsignificant, reduction was found after the eight-hour applications. The study also found a small, non-significant reduction in the PSS after the 60-minute protocol and a statistically significant reduction in PSS scores after the eight-hour applications.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Miller et al. 2007) that electrical nerve stimulation using either a one-hour or eight-hour protocol may not reduce spasticity in persons with MS.

Subcutaneous Nerve Stimulation

SCNS, also known as peripheral nerve stimulation, involves implanting an electrode to deliver peripheral nerve stimulation directly. SCNS has been demonstrated to reduce neuropathic pain (de Leon-Casasola, 2009), and may be beneficial for reducing spasticity along similar pathways.

Discussion

In one study by Walker (1982), the effect of SCNS on upper extremity spasticity and ankle clonus was examined in individuals with upper motor neuron disorders. Of 13 participants, nine were diagnosed with MS, and four with post-laminectomy irritability resulting in ankle clonus that lasted for 40-60 beats as triggered by stretch. Nine participants underwent SCNS for one hour twice daily for one week while four participants underwent placebo stimulation at points distal to the tested nerves. The author noted that SCNS delivered to the radial, median (at the level of the wrist), and saphenous nerves resulted in inhibited ankle clonus. In 100% of individuals receiving SCNS, a slight inhibition of ankle spasticity was noted with maximal reflex suppression occurring one hour following treatment, with treatment effects lasting three hours. The author reports that the clonus reflex was inhibited contralaterally to the side stimulated in all cases.

Conclusion

There is level 2 evidence (from one prospective controlled trial; Walker 1982) that subcutaneous nerve stimulation may reduce spasticity compared to sham stimulation in persons with MS.

Spinal Cord Stimulation

SCS involves delivering electrical stimulation to the spinal cord using an implanted device, often called a pacemaker (Oakley & Prager, 2002). SCS of the dorsal columns of the spinal cord has been used as a treatment for chronic pain and may also be an intervention useful for reducing spasticity.

Discussion

Five studies examined the use of SCS on a variety of symptoms including the reduction of spasticity in PwMS.

In a study by Read et al. (1980), the authors examined 16 ambulatory patients with chronic static or progressive spinal MS. All participants underwent a procedure to implant electrodes in the conus medullaris. There was continuous stimulation for two weeks with the intensity adjusted by each subject to maintain a comfortable paresthesia. Cord stimulation resulted in reduced tone in nine subjects, increased tone in two subjects, and there was no change in tone in two subjects. Additionally, the authors noted that one subject had normal leg tone throughout the study. Additionally, two participants who were wheelchair dependent were able to walk for short distances (20m and 50m) during the stimulation period.

Dimitrijevic et al. (1980) examined the neurophysiologic effects of chronic SCS in participants with upper motor neuron disorders. Eleven individuals were followed over the course of 18 months; six subjects had a diagnosis of MS and five had a chronic spinal cord injury. Spasticity was measured via subjective patient report and polyelectromyography (PEMG) of muscle activity were recorded over each subject's lower trunk and lower limb muscles. PEMG analysis demonstrated consistent repeatable and definitive changes in motor control in all subjects following continuous stimulation. The authors reported that the most noticeable results included a reduction in tonic responses to various passive stretch as well as less overflow to other local muscles.

Siegfried, Lazorthes, and Broggi (1981) examined 53 subjects with spastic movement disorders who underwent chronic spinal electrical stimulation over a period of one to five years. Of the 53 participants studied, 37 of the candidates who underwent the implantation procedures were diagnosed with MS and all had severe to very severe lower extremity spasticity. Motor function assessments were performed one to five years post electrical stimulator placement. Of those individuals, two subjects showed no change in spasticity, 12 with fair improvement in spasticity, 18 with good improvement, and three with very good improvement.

Koulousakis et al. (1987) investigated the impact of SCS on clinical and subjective reports of spasticity and quality of life in 20 subjects with movement disorders. Of those, 12 were diagnosed with MS; four had quadriparesis/tetraparesis and eight had paraparesis. Each of the participants underwent placement of multipolar electrodes implanted in the spinal canal via laminectomy. Continuous stimulation was provided, and subjects were monitored three, six, and 12 months post implantation and annually for an additional three years. Investigators examined muscle tone, gait pattern (if ambulatory), and subjective and clinical improvements of movement disorder although the assessments used were not disclosed. Of the four subjects with MS with quadriparesis/tetraparesis, one noted improvement in standing and walking although they only had a slight increase in tone initially. One subject was found to demonstrate a decrease in clinically measured spasticity and improvements in speech and nursing care, however subjectively reported “no improvement” due to an unreasonable expectation of study findings as reported by the authors. Two others with quadriparesis/tetraparesis were noted to have no improvement in spasticity or quality of life. Of the eight subjects with paraparesis, seven were followed for the study duration; six of seven subjects had a slight to distinct decrease in spasticity with reports of improved mobility including sitting, transfers, standing and walking. All seven reported increased endurance noted clinically by investigators.

In one small study, Scerrati and colleagues (1982) investigated the effects of SCS on the H-reflex in five subjects with spinal spasticity; four of the participants were diagnosed with MS. Each subject underwent placement of the stimulation electrodes via epidural at the T9-10 or T1 level with the stimulation level between 50-120Hz in three subjects and 33Hz in two subjects; the stimulation was intended to provoke a non-painful paresthesia in all subjects. H-reflex was obtained by measuring percutaneous stimulation of the posterior tibial nerve. During SCS, three of the subjects reported a subjective feeling of relaxation and improvement in spasticity and two subjects reported no impression of effectiveness. Clinically, no objective changes were observed upon examination or in motor ability other than one subject who was able to move the right foot during stimulation. During SCS, the H-reflex threshold was reduced to 7.5% (from 16%) in four participants (three with MS) and enhanced to 9% in the fifth (MS) participant. Furthermore, the Hmax/Mmax ratio was decreased by approximately 20% in three subjects and unchanged in two subjects. As a result, the heterogeneity of the subjects studied, and non-uniformity of the results leads to an inconclusive decision regarding the effectiveness of SCS in persons with MS.

Conclusion

There is level 4 evidence (from four pre-post studies; Koulousakis et al. 1987; Siegfried et al. 1981; Dimitrijevic et al. 1980; Read et al. 1980) that spinal cord stimulation may reduce spasticity in persons with MS.

Non-pharmacological Interventions: Orthoses

Many individuals with MS may, at some point in their disease course, adopt the use of some type of lower limb orthosis as an assistive device during transferring, standing, and walking activities or to improve seated positioning. The orthosis serves to protect an individual's joints and maintain biomechanical alignment as well as offer support to PwMS who have weaker trunks and legs (Lehman, 1979). In general, lower limb orthoses tend to be prescribed to PwMS to achieve the following goals: to assist in compensating for fatigable weakness with the view to improve walking endurance, to reduce the energy-cost of walking by improving gait parameters and reducing biomechanical disadvantages (decreasing the excursion of the centre of mass during the gait cycle), and to reduce the risk of falls. Some orthoses afford an individual to weight-bear on the lower extremities and ambulate, which may decrease muscle tone and spasticity.

Discussion

One study by Sutliff et al. (2008) examined the efficacy and safety of a hip flexion assist orthosis (HFAO) on spasticity in ambulatory MS patients. The study examined 21 ambulatory PwMS (EDSS not specified) with unilateral or predominantly unilateral hip flexor weakness in a pre-post study design where spasticity, as measured by the MAS, was a secondary outcome measure. After an initial evaluation, each participant was fitted and trained to use a semi-custom novel lightweight active HFAO and instructed on a wear schedule. Each participant wore the HFAO during ambulation activities (daily duration not specified) daily over the course of 12 weeks. The study found no significant effect of the HFAO on spasticity.

Many factors must be considered when choosing an appropriate orthosis, including cosmesis. In the case of hip flexion assist devices, the only device which has been studied in PwMS with the view to assessing impact on spasticity, these are the most commonly used orthotic strategy to compensate for pure proximal lower limb weakness or a combination of weakness and tone-inhibited hip flexion from severe quadriceps spasticity. Given that these devices are typically worn over clothing and highly visible leading to poor cosmesis, require some effort to don, and may be costly, many eligible users decline a trial. More typically, PwMS are prescribed ankle-foot orthoses, which help compensate for distal lower limb weakness.

Conclusion

There is level 4 evidence (from one pre-post study; Sutliff et al. 2008) that hip flexion assist orthoses may not improve spasticity in persons with MS.

Non-pharmacological Interventions: Radial Shock Wave Therapy

Radial shock wave therapy (RSWT) is a modality which utilizes kinetic energy generated by a ballistic source to create pressure waves over a given target tissue. The pressure waves then cause cavitation bubbles within the target tissue producing a biological response thought to influence pathways in pain and hypertonicity (Ueberle, 2007). RSWT has been successfully used in rehabilitation to treat pain and muscle hypertonicity in persons with cerebral palsy (Gonkova, Ilieva, Ferriero, & Chavdarov, 2013; Vidal, Morral, Costa, & Tur, 2011) and stroke (Kim, Shin, Yoon, Kim, & Lee, 2013).

Discussion

One randomized controlled trial (RCT) by Marinelli and colleagues (2015) examined the effects of RSWT on pain and muscle hypertonia in PwMS. Sixty-eight subjects participated, with 34 receiving active RSWT and 34 receiving sham RSWT as the control group. The investigators administered RSWT once weekly for four weeks. Spasticity of the lower limbs were assessed at baseline, one week after the initial treatment session, one week following the final treatment session, and one month following the treatment session. In those participants who received the active treatment, investigators examined the H/M ratio which did not change over the course of treatment. However, mean MAS scores were significantly reduced over the course of the treatment series in those who received active treatment as compared to the control group.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Marinelli et al. 2015) that radial shock wave therapy may reduce spasticity compared to sham stimulation in persons with MS.

Non-pharmacological Interventions: Complementary and Alternative Treatment

Complementary and alternative medicine (CAM) approaches have been used as an adjunct to traditional therapies in Western medicine for many years (Jonas, Eisenberg, Hufford, & Crawford, 2013). CAM interventions include a heterogeneous mix of practices, such as acupuncture, reflexology, massage therapy, dietary modification, and the use of herbal medicines; however, there is limited data regarding the safety or effectiveness of these modalities. Although people with MS report use of CAM to manage symptoms (Olsen, 2009; Schwarz, Knorr, Geiger, & Flachenecker, 2008), few have been effectively evaluated for the management of spasticity.

Reflexology

Reflexology is a treatment modality involving manual stimulation of reflex points on the feet that are presumed to correspond to various areas of the body whereby treatment to those areas may positively influence the target tissues (Ernst & Köder, 1997). Reflexology has become a popular CAM treatment in the last century (Ernst & White, 2000). However, there has been little research regarding the safety or efficacy of this modality in individuals with MS.

Discussion

A study conducted by Siev-Ner et al. (2003) examined the impact of reflexology treatment on MS symptoms. In this study, 53 PwMS were randomized to either a sham treatment group or a reflexology group with participants receiving weekly treatment sessions for 45 minutes over 11 weeks. Muscle tone, as measured by Ashworth scores, was evaluated as a primary outcome. The control group received non-specific calf massage (to control for touch therapy) while the experimental group received manual stimulation of reflex points on the feet. The study found a statistically significant decrease in Ashworth scores in the experimental group as compared to the control group at the end of the treatment period. However, one might question whether specific calf massage was an effective sham control and whether non-specific foot massage would have been superior. This must be considered a significant limitation in study design.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Siev-Ner et al. 2003) that reflexology may reduce spasticity compared to a sham control (non-specific calf massage) in persons with MS.

Acupuncture

Acupuncture, similar to reflexology, is a treatment modality originating in Eastern medicine that incorporates the use of specific pressure points on the body that correspond somatotopically to various body areas and target tissues. Classically, these points are accessed by specifically designed needles. In contrast to reflexology, substantially more is known about the pathophysiologic mechanisms involved in acupuncture induced analgesia. Reduction of nociceptive inputs may be crucial to improvement in spasticity. Historical research has reported that an “intact nervous system” is necessary for the anti-nociceptive effects (Levy & Matsumoto, 1975). Thus, total lesion burden and/or lesion location in PwMS may impact acupuncture efficacy. Previous research has demonstrated the benefits of acupuncture in stroke rehabilitation (Park, Hopwood, White, & Ernst, 2001; Vados, Ferreira, Zhao, Vercelino, & Wang, 2015).

Discussion

One study has evaluated acupuncture as a complimentary modality for reducing MS-related spasticity (Miller, 1996). Four participants (no disease course or severity noted) received usual care and acupuncture, in a randomized order, to their lower extremities. Two of the four were ambulatory and two said to be 'wheelchair-bound/confined to their wheelchairs'. Spasticity, as measured by the MAS, was noted to improve in ambulatory participants receiving acupuncture compared to their counterparts receiving usual care. However, wheelchair-bound participants did not show measurable improvement in spasticity following treatment with acupuncture. One could speculate that the ability to adequately transmit along nociceptive pathways by virtue of a more intact central nervous system may be a key factor in being able to mount a response to acupuncture but the authors themselves make no hypotheses regarding the failure of the acupuncture treatment in the non-ambulatory ('wheelchair-bound') patients. More research would be necessary to draw further conclusions regarding the efficacy, tolerability, and safety of acupuncture in PwMS across the disease continuum.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Miller 1996) that acupuncture may reduce spasticity compared to usual care in ambulatory persons with MS.

Massage Therapy

Massage involves the manual manipulation of muscle, connective tissue, tendons, and ligaments, and is generally thought of as a modality to enhance a person's health and well-being. Recent evidence suggests that massage may impact factors that influence the experience of anxiety and depression, such as cortisol, serotonin, and dopamine (Field, Hernandez-Reif, Diego, Schanberg, & Kuhn, 2005). Massage therapy is the therapeutic application of massage with the goal of achieving a structural or physiological change in the body (Moyer, Rounds, & Hannum, 2004), such as increasing circulation, improving lymphatic drainage, lengthening shorted soft tissue, or reducing pain. Massage therapy has been evaluated related to the effectiveness for reducing spasticity in people with neurological conditions such as spinal cord injury (Manella & Backus, 2011) and cerebral palsy (Hernandez‐Reif et al., 2005).

Discussion

Two studies employed a pre-post design to evaluate the effectiveness of massage therapy for reducing spasticity in persons with MS. Backus et al. (2016) evaluated the impact of massage therapy delivered for 30 minutes a week for six weeks on spasticity in the lower extremities in 28 people with MS. They found that a defined routine consisting of a combination of effleurage, petrissage, friction, and static compression strokes did not lead to significant changes, and specifically did not reduce spasticity, as measured with the MAS. The authors reported that spasticity was not a primary outcome measure for this study, and the intervention was not focused specifically on extremities in which there was increased tone or spasticity. They also stated that some participants in the study did not have spasticity at the start of the study, and thus, a decrease in spasticity was not anticipated.

In contrast to the Backus et al. (2016) study, all participants in the Brouwer and de Andrade (1995) study had mild to moderate spasticity in their lower extremities, as this was an inclusion criterion. In this study, investigators used electrophysiological measures, i.e., the H-reflex, to determine whether the excitability of the alpha-motor neuron pool and pre-synaptic inhibition could be acutely modified in the plantar flexor muscles with three minutes of slow stroking. While participants reported that they felt more relaxed, and the H-reflex amplitude and alpha motoneuron excitability were significantly decreased for up to 30 minutes after the intervention, neither the pre-synaptic inhibition nor the mechanically induced stretch reflex changed significantly. This was a small study, without a control group, and thus further research is warranted.

Conclusion

There is conflicting evidence (from two pre-post studies; Backus et al. 2016; Brouwer & de Andrande 1996) regarding whether or not massage therapy improves spasticity in the lower extremities of persons with MS.

Combining or Comparing Non-pharmacological Modalities

In the management of spasticity in PwMS, multiple interventions are often trialed, either in combination or comparatively. While the previous sections have evaluated the effect of independent treatment modalities to improve spasticity in PwMS, several studies have examined the use of multiple non-pharmacological interventions for MS-related spasticity.

Exercise and Theta-Burst Stimulation

Discussion

One study has examined the use of exercise and TBS as a combined intervention to treat MS-related spasticity. Mori et al. (2011) examined the benefits of iTBS alone and combined with exercise therapy, with spasticity as a primary outcome of the study. Thirty participants with RRMS (EDSS 2.0-6.0) with unilateral or predominantly unilateral lower extremity spasticity were randomly assigned to one of three groups: 1) iTBS alone, 2) iTBS plus exercise therapy, and 3) sham iTBS plus exercise therapy. The high frequency (theta frequency 5Hz) iTBS (or sham stimulation) was delivered for approximately three minutes (200 seconds) daily for five consecutive days for two weeks. The study found that iTBS alone and iTBS together with exercise therapy produced positive effects on spasticity, while exercise therapy alone did not. While both groups receiving iTBS saw a significant reduction in lower extremity spasticity, the group receiving iTBS and exercise therapy saw a reduction in both MAS and MSSS-88 scores while the iTBS alone group noted only a reduction in MAS scores. As a result, this study demonstrates that the combined modalities have a greater beneficial effect than iTBS alone.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Mori et al. 2011) that intermittent theta-burst stimulation (iTBS) in combination with exercise therapy may reduce spasticity compared to iTBS alone in persons with relapsing-remitting MS.

Exercise and Massage Therapy

Discussion

Negahban et al. (2013) evaluated the comparative effectiveness of massage and exercise therapies alone or in combination for reducing a variety of symptoms, including spasticity, in PwMS. Forty-eight participants with RRMS or SPMS (EDSS 2.0-6.0) were randomized to one of four groups including 1) massage therapy alone, 2) exercise therapy alone, 3) massage and exercise therapy, and 4) control group (standardized medical care). Each group received interventions in 30-minute sessions three times per week for five weeks. The massage therapy group received the massage therapy to their bilateral lower extremities for 30 minutes. The exercise therapy group participated in a 30-minute standardized program consisting of stretching, strengthening, balance, and endurance training for their lower extremities. The combined therapy group received 15 minutes of active exercise in addition to 15 minutes of passive massage to the bilateral lower extremities. Spasticity was measured by the MAS. The massage and exercise groups demonstrated significant reductions in spasticity compared to baseline (p=0.006 and p=0.031, respectively). Additionally, the combined intervention group experienced a smaller reduction that was not statistically significant compared to baseline (p=0.530). The lack of significant change in the combination group may be due to less time spent on either intervention alone, with the participants receiving half the dosage of each modality. The massage and exercise groups demonstrated significantly better MAS change scores compared to the control group (p<0.001 and p=0.002, respectively). However, the combined intervention group did not have significantly different MAS change scores compared to the control group (p=0.015). Furthermore, no significant differences in spasticity were observed between the exercise, massage, and combined intervention groups.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Negahban et al. 2013) that massage therapy in combination with exercise therapy may not reduce spasticity compared to standard medical care in persons with MS.

There is level 1b evidence (from one randomized controlled trial; Negahban et al. 2013) that massage therapy, exercise therapy, and combined massage-exercise therapy may not be more effective compared to one another for spasticity in persons with MS.

Therapeutic Standing and Exercise

The effect of therapeutic static weight bearing has been demonstrated to reduce spasticity in individuals with cerebral palsy (Pin, 2007) and spinal cord injury (Bohannon, 1993).

Discussion

A single randomized controlled trial by Baker et al. (2007) examined the efficacy of a home exercise program and therapeutic standing (via Oswestry standing frame support) on range of motion, spasticity, and spasm outcomes in PwMS. Six participants with SPMS (EDSS 7.0) and Ashworth scores of at least greater than or equal to two in their lower extremities participated in this randomized crossover study. Statistically significant improvements were noted in range of motion in participants' hips and knees with the standing intervention as compared to the exercise group. Additionally, there were downward trends in the reduction of Ashworth scores for knee flexion and ankle dorsiflexion in standing as well as a reduction in spasm frequency (although not severity) as measured by the Penn Spasm Frequency Scale in both the exercise and standing programs. Although the study did not demonstrate statistically significant between-group changes in measures of spasticity and spasms, improvements were noted, indicating that further research is warranted.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Baker et al. 2007) that supported standing may not improve spasticity compared to a home exercise program in persons with secondary progressive MS.

Vibration and Exercise

Vibration is a modality delivered while a participant is sitting, standing, or lying on a large vibrating platform. Whole body vibration involves stimulating the entire body with the body situated in some fashion over a vibrating surface (Dolny & Reyes, 2008), and may be beneficial for reducing spasticity in people with neurological injury or disease (Huang, Liao, & Pang, 2017).

Discussion

One study by Schyns et al. (2009) evaluated the use of whole body vibration as an adjunct to traditional exercise programming. In this study, 16 participants with MS were randomly assigned to either an exercise program performed with whole body vibration or the same exercise program without whole body vibration. Both groups of participants then underwent the alternate condition with a two-week rest period in between programs. Spasticity was measured before and after each intervention series using the MAS and MSSS-88. The vibration was delivered at 40Hz for 30 seconds (specific manufacturers' recommendations for stretching and strengthening exercises) while each participant was performing a series of 10 lower body exercises. The study found that MAS scores were unchanged after either intervention in both groups. MSSS-88 scores showed a statistically significant reduction in spasms after the combined exercise program with whole body vibration versus the exercise program alone. While there is insufficient evidence to conclude whether whole body vibration provides additional improvements in tone reduction, vibration did not have a deleterious effect on MS-related spasticity. The authors suggest that vibration may potentially be used as an adjunct to an exercise program for the reduction of spasticity given that there was a reduction in the MSSS-88 scores.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Schyns et al. 2009) that whole body vibration in combination with exercise may not be more effective for improving spasticity compared to exercise alone in persons with MS.

Functional Electrical Stimulation-Supported Lower Extremity Cycling

Functional electrical stimulation (FES)-supported lower extremity cycling is a modality using electrical stimulation to support an individual's lower extremity muscle contraction throughout a cycling motion. The use of FES cycling has been previously demonstrated to be effective to improve muscle function and cycling mobility in persons with spinal cord injury (Hunt et al., 2004; Petrofsky & Phillips, 1984) and stroke (Szecsi, Krewer, Muller, & Straube, 2008). Consequently, the use of FES may have beneficial applications in the treatment of MS-related spasticity.

Discussion

Szecsi et al. (2009) performed a pilot studying evaluating the effects of FES assisted lower extremity cycling on various biomechanical and functional outcomes in PwMS. Twelve participants (EDSS scores 4.0-8.0) with ‘chronic progressive' MS (term not defined by authors) participated in six FES-supported cycling training sessions over two weeks. During the sessions, each participant completed 12-18 minutes of total training time with only six minutes of FES-supported pedaling, with the patient physically controlling the stimulation intensity delivered via a throttle mechanism. Spasticity was measured using the MAS. A statistically significant reduction in spasticity was noted immediately following the intervention (pre and post daily training sessions), however there was no significant longer term reduction in spasticity (before and after the two-week training period).

Conclusion

There is level 4 evidence (from one pre-post study; Szecsi et al. 2009) that spasticity may be acutely reduced following functional electrical stimulation-assisted lower extremity cycling in persons with chronic progressive MS.

Multidisciplinary Rehabilitation

Multidisciplinary or interdisciplinary rehabilitation is a model of care that involves the input of a variety of medical specialists and allied health professionals working together for the purposes of minimizing the participant's symptom burden and improving all facets of independent functioning at the activity and social participation levels. This may be delivered as inpatient or outpatient care depending on the complexity of the rehabilitation needs of the individual. In the context of MS, inpatient care may be the preferred delivery model following an acute and debilitating relapse or for periods of transition from ambulatory to non-ambulatory status. Increasingly, outpatient programs to assist in the development of self-management skills are gaining traction in the field of MS. For more information on team rehabilitation, see Team-Based Rehabilitation: Functional and Quality of Life Outcomes.

Discussion

Storr et al. (2006) evaluated the efficacy of a multidisciplinary inpatient rehabilitation program in stable PwMS. Ninety participants were randomized into either a control group or intervention group. The control group remained in their homes and was given no study-related treatment while the intervention group was admitted to a comprehensive multidisciplinary inpatient rehabilitation program lasting, on average, 35 days. Spasticity was measured subjectively as a secondary outcome via a VAS for spasticity. The intervention group received individualized 45-minute physical therapy sessions four to five times per week, 30-minute occupational therapy sessions three times per week, and 30 minutes of daily self-directed exercise training over three to five weeks. The study did not demonstrate any beneficial effect of the rehabilitation program on any study related outcome measures. The authors hypothesized that this effect was due to a short duration intervention in clinically stable individuals for sustained exercise as compared to rehabilitating specific impairments. Additionally, the generalized nature of the rehabilitative programs may have contributed to a smaller effect. A highly personalized program directed towards specific rehabilitative needs may yield better results.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Storr et al. 2006) that multidisciplinary inpatient rehabilitation may not improve spasticity compared to no treatment in clinically stable persons with MS.

Surgery

In some individuals with spasticity, hypertonia may be so severe that contractures develop and can drastically impair functional positioning, mobility, and lead to harmful skin breakdown. When an individual develops severe spasticity that fails conventional conservative treatments, surgery may be necessary to prevent increasingly severe abnormal postures. Surgical options for the treatment of severe spasticity and contractures in PwMS include both orthopedic and neurological approaches, including multiple tenotomy, and longitudinal myelotomy, selective posterior rhizotomy, microsurgical dorsal root entry zone (DREZ)-otomy (MDT), and intrathecal injections, respectively. Intrathecal baclofen pump treatment is discussed in a separate module focusing exclusively on evidence for the pharmacological management of spasticity.

Discussion

Several studies have investigated a wide range of surgical interventions for severe spasticity management in PwMS. Pope et al. (1991) examined the effect of surgery (tenotomy) and post-operative stretching and immobilization for the management of knee contractures in six cases of MS. Following surgery, bilateral knee contractures in all subjects were significantly reduced with a statistically significant increase in hip range of motion which was maintained at reassessment at two weeks, three months, and nine months postoperatively. Furthermore, a post-surgical stretching regimen using either continuous passive motion or plaster of Paris serial casting showed no statistically significant differences in maintaining gains. Functionally, the authors found no significant improvement in transfer time following surgery. As such, tenotomies to address contracture management is a viable option if the individual is no longer able to be managed by conservative care.

Laitinen and Singounas (1971) investigated lower extremity spasticity and lower extremity mobility in response to longitudinal myelotomy in nine participants, five of whom were diagnosed with MS. All patients except one had complete paraplegia with spasticity preoperatively. In all participants, severe spasticity and associated pain was immediately relieved postoperatively. Five patients experienced a recurrence of distal spasticity in the Achilles reflex without recurrence of hip or knee spasticity which the author attributed to the fact that the "lower end of the [surgical] incision had been made higher than it should have been.” Postoperatively, two patients with MS regained some volitional movement in both limbs. A third patient (with MS) had been completely bedridden with paraplegia for eight years prior to the longitudinal myelotomy and was able to walk with the help of a knee supporting splint three months post surgery. As a result, myelotomy may be a viable option for treatment of severe spasticity of the lower extremities.

Glazer and Mooney (1970) reported on a retrospective case series of 249 patients with MS who underwent various surgical procedures including tenotomies, neurectomies, spinal fusions, tendon releases, and tendon transfers. Of the 231 procedures performed, only 61 extremity procedures in 42 participants (surgery or nerve block) were performed to alleviate MS-related issues. Spasticity was relieved to an extent in 44 extremity procedures; of the procedures performed, spasticity was greatly relieved by 35 operations, partially relieved by seven operations, and slightly relieved by two operations. Additionally, fixed contractures were relieved by 41 operations, partially relieved by eight operations, and slightly relieved by two operations. Overall, retrospective analysis demonstrated effective relief of spasticity and decrease in contractures leading to improved quality of life for PwMS.

Sindou and colleagues (1982) evaluated the effectiveness of selective posterior rhizotomy (SPR) in 15 subjects with advanced MS. All subjects demonstrated hypertonicity with irreducible abnormal postures in lower extremity triple flexion and adduction with significant associated pain that had been resistant to conservative treatments. Following SPR, 12 of the 15 subjects has significant improvement in spastic flexion of the hips and knees allowing for an improved spontaneous posture. Additionally, all but one participant demonstrated good improvements in flexion spasms. Given the result that 80% (12 out of 15) of participants experienced positive outcomes, SPR may be considered a valuable method for the treatment of paraplegia with significant hypertonicity and postural dysfunction.

Sindou and Jeanmonod (1989) evaluated the long-term effects of MDT to treat harmful spasticity in one or both lower extremities in 53 bedridden patients with intractable spasticity; 28 of the 53 study participants were diagnosed with MS. All patients underwent surgical procedures via microsurgical laminectomy to access the appropriate rootlets within the conus medullaris. Spasticity was measured on a scale developed by the authors ranging from zero (best – normal tone) to four (severe), similar to the MAS. Preoperatively, severe flexor spasticity was present in 49 out of 53 subjects and severe extensor spasticity in three out of 53 subjects. Additionally, 38 of the participants had severe flexion spasms. Postoperatively, 75% of the subjects had good or excellent outcomes for resolution of their spasticity with mean scores at baseline of 3.6/4 reduced to follow up scores of 1.04 (one month post), 1.56 (six months post) and 1.58 (one year post) with no significant changes noted in continued follow up to 13 years post-operatively. Additionally, 82.2% of subjects experienced good or excellent outcomes for reduction of flexion spasms. Regarding flexion spasms, these subjects had mean scores at baseline of 2.52/4 reduced to follow up scores of 0.93 (one month post), 0.97 (six months post) and 1.03 (one year post) with no significant changes noted in continued follow up to 13 years post-operatively. Given these results, MDT is potentially a viable option for managing severe spasticity that is not responsive to more conservative treatments.

Conclusion

There is level 4 evidence (from four pre-post studies and one case series; Pope et al. 1991; Sindou & Jeanmonod 1989; Sindou et al. 1982; Laitinen & Singounas 1971; Glazer & Mooney 1970) that orthopedic surgical interventions and neurosurgical interventions involving the spinal cord may reduce spasticity in persons with MS.

Combining or Comparing Pharmacological and Non-pharmacological Modalities

In the management of spasticity in PwMS, multiple interventions are often trialed, either in combination or comparatively. Several studies have examined the use of various combinations of pharmacological and non-pharmacological interventions for MS-related spasticity.

Baclofen and Transcutaneous Electrical Nerve Stimulation

Discussion

One RCT compared the effects of baclofen and TENS on lower extremity spasticity in PwMS (Shaygannejad et al., 2013). Fifty-two patients (EDSS≤6.0 and MAS scores of ≤3) were randomized to a four-week course of oral baclofen (10mg bid titrated up to 25mg bid) or four-week course of self-applied TENS to the gastrocnemius daily for 20-30 minutes any time a spasm occurred. Spasticity was measured with the MAS. Both groups demonstrated a statistically significant reduction in lower extremity spasticity following treatment, with the TENS group demonstrating a greater reduction in MAS scores (mean decrease of 1.04 points (95% CI, 0.81, 1.28)) compared to the baclofen group (mean decrease of 0.58 points (95% CI, 0.37, 0.78)). The mean difference in MAS scores at follow-up was significantly lower in the TENS group compared to the baclofen group (p<0.05), in both legs. Furthermore, the TENS group maintained a greater reduction in spasticity after the four-week follow up as noted by a lower mean difference in scores compared to baseline.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Shaygannejad et al. 2013) that transcutaneous electrical nerve stimulation may lead to greater reductions in spasticity compared to oral baclofen in persons with MS.

Baclofen and Exercise

Discussion

Brar et al. (1991) examined three treatment regimens involving baclofen and exercise for MS-related spasticity. Thirty PwMS (EDSS≤5.5 with mild to moderate lower extremity spasticity) participated in a randomized crossover study with the following treatment groups: baclofen alone, a stretching program with placebo, a stretching program with baclofen, and placebo alone. Participants' spasticity, as a primary outcome measure, was measured using Cybex isokinetic knee flexion scores and MAS scores. The authors found that spasticity significantly decreased in the baclofen and combination therapy groups compared to placebo (flexion scores). A trend toward decreased spasticity was noted in the combination therapy group compared to the baclofen only group, although this was not statistically significant.

Conclusion

There is level 2 evidence (from one randomized controlled trial; Brar et al. 1991) that oral baclofen combined with a stretching program may reduce spasticity compared to placebo in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Brar et al. 1991) that oral baclofen combined with a stretching program may not reduce spasticity compared to baclofen alone in persons with MS.

Dantrolene Sodium, Physical Therapy, and Surgery

Discussion

Reyes et al. (1978) investigated the effect of a combined program for MS-related spasticity, including anti-spasticity medication (dantrolene sodium), surgical procedures (tenotomy and plastic surgery to close pressure wounds), and physical therapy (passive range of motion exercises to manage lower extremity spasticity and contractures). Five participants were included who had severe lower extremity spasticity in hip flexors, adductors, and knee flexors, contracture formation, and pressure sores due to spasticity-related positioning challenges. The primary objective of the study was life-preserving medical management given the extent of tissue breakdown in these individuals. Spasticity, as a contributory factor, was only measured as a secondary outcome subjectively (no outcome measure noted), with subjective improvement alongside improved passive range of motion scores following surgical procedures. After each patient underwent tenotomies of their adductors and hamstrings, therapy programs consisted of daily passive range of motion two-three times per day in conjunction with oral dantrolene sodium (75-125mg four times daily). Upon long term follow up (three years), all patients had maintained positive changes in muscle tone with continued daily passive range of motion and dantrolene sodium, which allowed for improved positioning in bed as well as in wheelchairs.

Conclusion

There is level 4 evidence (from one pre-post study; Reyes et al. 1978) that a combination of oral dantrolene sodium and physical therapy interventions following surgical management of contractures may improve spasticity in persons with MS.

Botulinum Toxin and Physical Therapy

Discussion

Giovanelli et al. (2007) examined the benefits of early physical therapy programming after local upper and lower extremity botulinum toxin type A injections. The study randomized 38 participants with SPMS (EDSS unspecified, MAS scores of at least 3) to either a control group of botulinum toxin only or a treatment group consisting of botulinum toxin followed by active and passive exercise and stretching programs. The exercise and stretching programs were performed daily for 15 consecutive days immediately following injection with botulinum toxin. Spasticity measures, MAS and VAS, were assessed at baseline, and at two, four, and 12 weeks after injection. The study found statistically significant decreases in both groups after botulinum toxin. The experimental group was found to have a significantly better combined positive effect as the group was noted to have a reduction in spasticity that remained at four and 12 weeks whereas the control group was noted to have an initial reduction in spasticity that increased at four and 12 weeks. Indeed, post-procedure instructions to persons receiving botulinum toxin for the purposes of spasticity management/hypertonicity that include post-injection stretching, especially between days 3-21 post injection, would be considered standard of care by most injectors.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Giovannelli et al. 2007) that early physiotherapy following botulinum toxin type A may be more effective for reducing spasticity compared to botulinum toxin alone in persons with secondary progressive MS.

Botulinum Toxin and Segmental Muscle Vibration

Segmental muscle vibration is a modality in which specific target muscles are placed under vibratory stimulation to inhibit muscle activation via the surface placement of a mechanical device producing low amplitude/high frequency bursts presumed to stimulate muscle spindle afferents, with effectiveness noted in stroke (Noma, Matsumoto, Etoh, Shimodozono, & Kawahira, 2009).

Discussion

Paoloni et al. (2013) examined the effect of segmental muscle vibration after botulinum toxin injection for the treatment of spasticity in PwMS. In this study, 42 participants with SPMS (EDSS 2.0-6.0) were randomized to one of three groups: 1) segmental vibration to lower extremity muscles three times per week for four weeks, 2) botulinum toxin followed by segmental vibration, or 3) botulinum toxin alone. All groups also participated in general physical therapy sessions three times per week for four weeks. The study found that all three groups demonstrated statistically significant decreases in both knee and ankle MAS scores over time compared to baseline. Furthermore, the group that received a combination of botulinum toxin and vibration therapy demonstrated statistically significant decreases in knee and ankle spasticity scores that continued at 10 weeks and 22 weeks following treatment. The group receiving botulinum toxin alone demonstrated the shortest effects of any group, as indicated by higher MAS scores at 22 weeks post intervention, suggesting an unsurprising re-increase in muscle tone known to occur given the typical efficacy period of botulinum toxin injections. However, no significant differences were observed between groups in both knee and ankle MAS scores at any time point.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Paoloni et al. 2013) that segmental muscle vibration, and combined segmental muscle vibration and botulinum toxin, may be more effective compared to botulinum toxin type A for spasticity in persons with secondary progressive MS.

Summary

There is level 1b evidence (from one randomized controlled trial; Tarakci et al. 2013) that a group exercise training program targeting lower extremity flexibility, strength, and balance may improve spasticity compared to no intervention in persons with MS.

There is level 4 evidence (from one pre-post study; Giesser et al. 2007) that locomotor training using body weight supported treadmill training may improve spasticity in persons with secondary progressive MS.

There is conflicting evidence (from two prospective controlled trials; Sosnoff et al. 2010; Sosnoff et al. 2009) regarding whether or not unloaded leg cycling reduces spasticity compared to quiet sitting in persons with MS.

There is level 2 evidence (from one prospective controlled trial; Sosnoff et al. 2010) that unloaded leg cycling may reduce spasticity more as compared to unloaded arm cycling in persons with relapsing-remitting MS.

There is level 2 evidence (from one prospective controlled trial; Motl et al. 2007) that unloaded leg cycling may be an effective adjuvant to pharmacological spasticity management compared to quiet sitting in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Velikonja et al. 2010) that mixed fitness recreational activities such as sports climbing or yoga may not reduce spasticity in persons with MS.

There is level 1b evidence (from one randomized controlled trial; Castro-Sanchez et al. 2012) that an aquatic Ai-Chi exercise program may reduce spasticity compared to land-based breathing and relaxation exercises in persons with MS.

There is level 1b evidence (from two randomized controlled trials; Nilsagard et al. 2006; Chiara et al. 1998) that cryotherapy may not reduce spasticity compared to ambient temperature in persons with MS.

There is level 2 evidence (from one prospective controlled trial; Centonze et al. 2007) that high frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) may reduce spasticity compared to sham rTMS in persons with relapsing-remitting MS.

There is level 2 evidence (from one prospective controlled trial; Abdelkader et al. 2013) that high frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) may reduce spasticity compared to low frequency (1 Hz) rTMS in persons with relapsing-remitting MS.

There is level 1b evidence (from one randomized controlled trial; Nielsen et al. 1996) that trans-spinal magnetic stimulation may reduce spasticity compared to sham stimulation in persons with MS.

There is level 2 evidence (from one prospective controlled trial; Mori et al. 2010) that intermittent theta-burst stimulation may reduce spasticity compared to sham stimulation in persons with relapsing-remitting MS.

There is level 1b evidence (from one randomized controlled trial; Iodice et al. 2015) that transcranial direct current stimulation (tDCS) may not reduce spasticity compared to sham tDCS in persons with relapsing-remitting MS.

There is level 1b evidence (from one randomized controlled trial; Miller et al. 2007) that electrical nerve stimulation using either a one-hour or eight-hour protocol may not reduce spasticity in persons with MS.

There is level 2 evidence (from one prospective controlled trial; Walker 1982) that subcutaneous nerve stimulation may reduce spasticity compared to sham stimulation in persons with MS.

There is level 4 evidence (from four pre-post studies; Koulousakis et al. 1987; Siegfried et al. 1981; Dimitrijevic et al. 1980; Read et al. 1980) that spinal cord stimulation may reduce spasticity in persons with MS.

There is level 4 evidence (from one pre-post study; Sutliff et al. 2008) that hip flexion assist orthoses may not improve spasticity in persons with MS. 

There is level 1b evidence (from one randomized controlled trial; Marinelli et al. 2015) that radial shock wave therapy may reduce spasticity compared to sham stimulation in persons with MS.

There is level 1b evidence (from one randomized controlled trial; Siev-Ner et al. 2003) that reflexology may reduce spasticity compared to a sham control (non-specific calf massage) in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Miller 1996) that acupuncture may reduce spasticity compared to usual care in ambulatory persons with MS.

There is conflicting evidence (from two pre-post studies; Backus et al. 2016; Brouwer & de Andrande 1996) regarding whether or not massage therapy improves spasticity in the lower extremities of persons with MS.

There is level 1b evidence (from one randomized controlled trial; Mori et al. 2011) that intermittent theta-burst stimulation (iTBS) in combination with exercise therapy may reduce spasticity compared to iTBS alone in persons with relapsing-remitting MS.

There is level 1b evidence (from one randomized controlled trial; Negahban et al. 2013) that massage therapy in combination with exercise therapy may not reduce spasticity compared to standard medical care in persons with MS.

There is level 1b evidence (from one randomized controlled trial; Negahban et al. 2013) that massage therapy, exercise therapy, and combined massage-exercise therapy may not be more effective compared to one another for spasticity in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Baker et al. 2007) that supported standing may not improve spasticity compared to a home exercise program in persons with secondary progressive MS.

There is level 2 evidence (from one randomized controlled trial; Schyns et al. 2009) that whole body vibration in combination with exercise may not be more effective for improving spasticity compared to exercise alone in persons with MS.

There is level 4 evidence (from one pre-post study; Szecsi et al. 2009) that spasticity may be acutely reduced following functional electrical stimulation-assisted lower extremity cycling in persons with chronic progressive MS.

There is level 1b evidence (from one randomized controlled trial; Storr et al. 2006) that multidisciplinary inpatient rehabilitation may not improve spasticity compared to no treatment in clinically stable persons with MS.

There is level 4 evidence (from four pre-post studies and one case series; Pope et al. 1991; Sindou & Jeanmonod 1989; Sindou et al. 1982; Laitinen & Singounas 1971; Glazer & Mooney 1970) that orthopedic surgical interventions and neurosurgical interventions involving the spinal cord may reduce spasticity in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Shaygannejad et al. 2013) that transcutaneous electrical nerve stimulation may lead to greater reductions in spasticity compared to oral baclofen in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Brar et al. 1991) that oral baclofen combined with a stretching program may reduce spasticity compared to placebo in persons with MS.

There is level 2 evidence (from one randomized controlled trial; Brar et al. 1991) that oral baclofen combined with a stretching program may not reduce spasticity compared to baclofen alone in persons with MS.

There is level 4 evidence (from one pre-post study; Reyes et al. 1978) that a combination of oral dantrolene sodium and physical therapy interventions following surgical management of contractures may improve spasticity in persons with MS.

There is level 1b evidence (from one randomized controlled trial; Giovannelli et al. 2007) that early physiotherapy following botulinum toxin type A may be more effective for reducing spasticity compared to botulinum toxin alone in persons with secondary progressive MS.

There is level 1b evidence (from one randomized controlled trial; Paoloni et al. 2013) that segmental muscle vibration, and combined segmental muscle vibration and botulinum toxin, may be more effective compared to botulinum toxin type A for spasticity in persons with secondary progressive MS.