Clinical Application of Repetitive Peripheral Magnetic Stimulation in Rehabilitation

Abstract

Repetitive peripheral magnetic stimulation (rPMS) is a noninvasive method involving the repetitive magnetic stimulation of peripheral nerves and muscles. Recently, its potential as a new neuromodulation technique for sensory motor disorders has been recognized. Its advantages include less pain than with electrical stimulation and that neuromuscular stimulation can be performed over clothing. These advantages make it a practical and straightforward adjunct tool widely used in clinical practice. In particular, the combination of rPMS and general rehabilitation reportedly promotes functional improvement in stroke patients with difficult involuntary contractions. This chapter reviews rPMS and its potential clinical applications in rehabilitation.

1. Introduction

Magnetic stimulation is the application of “electrode-free electrical stimulation” using induced current from a pulsed magnetic field. The magnetic field generated by the stimulation coil induces an electromagnetic-induced overcurrent in the body that resultantly depolarizes nerves and muscles’ cell membranes, thereby stimulating the brain, nerves, and muscles. Repetitive peripheral magnetic stimulation (rPMS) is applied as a treatment method that noninvasively delivers repetitive magnetic stimulation to peripheral nerves and muscles. It has attracted attention as a new means of rehabilitation, especially for sensory and motor disorders [1].

To date, neuromuscular electrical stimulation (NMES) has been widely used as a similar tool. NMES is an electrical stimulation therapy primarily performed to improve motor function, such as suppressing muscle hypertonia associated with upper-motor neuron damage, preventing and improving muscle atrophy associated with peripheral neuropathy, and increasing muscle strength. However, this therapy is associated with pain and discomfort caused by electrical stimulation. Compared with NMES, rPMS does not cause discomfort due to pain and can stimulate deep muscles [2]. NMES evokes cutaneous receptors and may generate noisy signals, whereas rPMS generates intrinsic receptive information during muscle contraction that affects brain reversibility [3].

Furthermore, rPMS does not require the application of electrodes and can be stimulated over clothing. Similar to NMES, however, rPMS is contraindicated for pacemakers and implantable medical devices. In addition, rPMS is larger in size and more expensive than NMES, making its widespread use a challenge. However, rPMS is expected to improve functional recovery in stroke patients because of its ability to safely stimulate deeper layers and improve muscle areas without pain [4].

2. rPMS studies in healthy subjects

2.1 Physiological changes in rPMS

rPMS can improve motor function in central nervous system (CNS) diseases. How, then, would the induction of CNS plasticity be altered by the parameters of rPMS? Nito et al. [5] studied the effects of rPMS on wrist extensor muscles in terms of neuroplasticity and motor performance in 26 healthy subjects (HS). Motor-evoked potential (MEP), intracortical inhibition (ICI), intracortical facilitation (ICF), M-wave, and Hoffman reflex were measured before and after the application of rPMS, and the effects of rPMS on wrist extensor movements were examined.

First, rPMS was applied to the wrist extensor muscles at different frequencies (50, 25, and 10 Hz), with the total number of stimuli set constant to examine the physical effects of stimulus frequency. MEPs of the wrist extensors increased significantly with rPMS at 50 and 25 Hz but remained unchanged at 10 Hz. In the next experiment, in which the number of stimuli was increased and the time required to induce plasticity was examined, at least 15 minutes of rPMS were required for 50- and 25-Hz rPMS. Based on these parameters, the sustained effect of 50- or 25-Hz rPMS was evaluated after 15 minutes of rPMS. Significant increases in MEP were observed up to 60 minutes after 50- and 25-Hz rPMS were administered. Similarly, attenuation of ICI and enhancement of ICF were also observed.

In addition, the maximal M-wave and Hoffman reflex were unchanged, suggesting that the imposition of rPMS does not directly stimulate the centrifugal nerves and excite the muscles but that the increase in MEP is caused by the plastic changes in the motor cortex. In addition, an increase in force and EMG during wrist extension movements was observed after the application of rPMS at 50 and 25 Hz. These results suggest that the application of rPMS at 25 Hz or higher for 15 minutes can increase cortical excitability at the irradiated site and improve motor output from the motor cortex, rather than changing the excitability of the spinal cord circuitry.

Recent studies have also reported the effects of rPMS in combination with noninvasive brain stimulation techniques and on regions other than the periphery. Kumru et al. [6] examined the effects of paired associative stimulation (PAS), in which paired stimuli of repetitive transcranial magnetic stimulation (rTMS) and rPMS are repeatedly applied. PAS is an effective method to induce plasticity in the human motor cortex. Three stimulus conditions were applied to 11 HS for 10 minutes each. In the rPMS alone condition, rPMS at 10 Hz was applied to the extensor carpi radialis (ECR) five times every 10 seconds for 60 trials. In the rTMS alone condition, rTMS was applied to the contralateral primary motor cortex region of the ECR at a frequency of 0.1 Hz (60 stimuli) and an intensity of 120% of the ECR threshold. In the PAS condition, rPMS and rTMS described above were performed with paired stimuli. The results showed that the PAS condition increased MEP amplitude and decreased ICI in the ECR. This suggests that PAS stimulation effectively increases corticospinal tract excitability and decreases ICI. Krause et al. [7] studied the effects of repetitive magnetic stimulation (rMS) to the right cervical nerve root (C7/C8) on corticospinal excitability in HS. The right cervical nerve root (C7/C8) innervating the test muscle, the right first dorsal interosseous muscle, was stimulated at a frequency of 20 Hz for 10 seconds with an intensity of 120% of resting motor threshold for a total of 10 trials. The results showed that rMS caused a significantly longer cortical silent period, increased ICI, and increased MEP amplitude. These changes were not confirmed contralaterally. This study confirmed that rMS increased MEP amplitude in the right first dorsal interosseous muscle without altering the left dorsal interosseous muscle. These results indicate that rMS affects motor cortex excitability similar to electrical stimulation; this suggests that rMS is applicable in spastic and central paraplegia rehabilitation.

As described above, physiological changes in rPMS have been reported in HS, and based on these studies, various clinical application studies have been conducted in the recent years.

2.2 Changes in rPMS and motor imagery in combination

Motor imagery (MI) is the simulation of movement in the brain without actual movement and is widely used in clinical practice as a tool for evaluation and treatment. Recently, the combined effects of MI and rPMS have been reported.

Asao et al. [8] examined the effects of rPMS combined with MI (rPMS+MI) on corticospinal excitability. The rPMS+MI condition and rPMS alone condition were performed on HS. In the rPMS+MI condition, rPMS was administered simultaneously with a cue for a MI task of dorsiflexion of the right wrist joint. The test muscle was the right ECR. The rPMS frequency was 25 Hz, stimulus duration was 2 s, and stimulus intensity was 1.5 times the motor threshold. In the rPMS alone condition, rPMS was administered under the same stimulation conditions as in the rPMS+MI condition. The results showed that the pre- and post-stimulus MEP ratios were more significant in the rPMS+MI condition than in the rPMS alone-intense condition, which was associated with Movement Imagery Questionnaire-Revised scores. This study suggests that an intervention combining rPMS and MI can induce more corticospinal excitation than rPMS alone.

The studies above did not clarify the effective length of intervention period for the combination of rPMS and MI to promote corticospinal excitability. Therefore, the time course changes in corticospinal excitability when rPMS and MI are used in combination have been examined [9]. rPMS alone, MI alone, and rPMS and MI combination conditions have been performed on HS. In the rPMS alone and rPMS+MI conditions, the ECR was stimulated with rPMS at 25 Hz for 2 seconds at a stimulus intensity of 1.5 times the motor threshold. In addition, the MI and rPMS+MI groups were asked to perform MI of wrist dorsiflexion for 2 seconds.

Consequently, the MEP amplitude increase of the ECR in the rPMS+MI group was observed after 10 minutes. In addition, the MEP amplitude after 20 minutes was more significant in the rPMS+MI group than in the rPMS alone group. This study suggests that the combination of rPMS and MI over 10 minutes increases corticospinal excitation and that the combined effect is more significant than rPMS alone. Overall, the combination of rPMS and MI may induce plasticity in the CNS and promote motor function recovery.

3. Clinical applications of rPMS

3.1 Muscle-strengthening effects of rPMS

One of the clinical applications of rPMS is its muscle-strengthening effect. It has been reported that rPMS promotes muscle strengthening in animals and humans without causing pain.

Yang et al. [10] investigated the effects of neuromuscular magnetic stimulation (NMMS) on strength, cross-sectional area, and thickness of the quadriceps muscle in HS. NMMS was performed on the quadriceps femoris muscle at a frequency of 10 Hz and at the maximum tolerable intensity that could be tolerated for 15 minutes, thrice weekly for 5 weeks. The results showed that maximal isometric torque and mean peak torque increased significantly after intervention, but there was no change in cross-sectional area or thickness. This study suggests that NMMS effectively trains large or skeletal muscles such as the quadriceps.

Stolting et al. [11] showed that magnetic stimulation of a mouse muscle injury model caused post-traumatic muscle hypertrophy, but the effects of rPMS on human subjects remained unclear. Therefore, Hirono et al. [12] examined the acute changes in skeletal muscle thickness induced by rPMS after low-intensity exercise for clinical application of rPMS. rPMS was applied to the vastus lateralis muscle at the maximum intensity of the rPMS device after an HS performed three sets of 10 isometric knee extension exercises at 30% of maximum muscle strength. The results showed that the muscle thickness of the rectus femoris and vastus lateralis muscles after exercise increased over baseline values, with significant increases only in the vastus lateralis after rPMS. This study suggests that post-exercise rPMS induces muscle expansion via repetitive muscle contractions. Acute changes such as skeletal muscle expansion that occur immediately after exercise also reportedly play a significant role in subsequent muscle hypertrophy [13, 14].

rPMS has the advantage of not causing pain and has been used in clinical practice with the expectation of functional recovery in some cases. Beck et al. [15] studied the effect of early intervention with rPMS on the vastus lateralis muscle after hip replacement surgery. The subjects were patients who underwent hip replacement after a proximal femur fracture. The experimental group received 10 Hz rPMS on the vastus lateralis muscle for 15 sessions daily, five times weekly for 3 weeks, whereas the control group received sham stimulation. The results showed that the root-mean-square value of the electromyogram during the maximum voluntary contraction of the vastus lateralis muscle after rPMS was significantly improved. Tandem rise time and normal walking speed in the rPMS group also improved. This study suggests that early intervention with rPMS on the lateral vastus muscle after hip arthroplasty improves muscle strength, standing balance, and gait function. This study also indicates that rPMS can be applied to patients with pain and wounds and is expected to be widely applied in clinical practice in the future.

As described above, rPMS, which promotes muscle strengthening without causing pain, has excellent potential for clinical applications.

3.2 Application of rPMS in stroke rehabilitation

Post-stroke hemiplegia occurs in more than 85% of individuals and 55–75% have residual upper limb dysfunction [16]. After stroke, the recovery rate to a practical level is approximately 60% for lower limb function and approximately 20% for upper limb function [17]. The effectiveness of rehabilitation and physical therapy for stroke has been reported in many cases. In this context, the effectiveness of rPMS for stroke has been reported in recent years.

rPMS is a noninvasive method of activating peripheral nerves at the stimulation site and improving muscle strength and has the advantage of being performed without causing pain. Jiang et al. [18] applied rPMS in the early subacute phase of stroke and studied its effect on severe upper limb disability. In the intervention group, rPMS of 20 Hz, totaling 2400 pulses, was applied daily for 2 weeks to the triceps brachii and extensor digitorum brevis muscles. The results showed that the rPMS group showed significant improvements in the upper limb, Barthel Index, upper limb muscle strength, and root mean square on the Fugl-Meyer Assessment compared with those in the control group. This study demonstrates that rPMS for the upper extremity after stroke improves upper extremity function and muscle strength.

Fernandez-Lobera et al. [19] studied the efficacy of rPMS as a tool to assess wrist spasticity in stroke patients. The subjects were HS, acute stroke patients without spasticity (AS), and chronic stroke patients with spasticity (CS). Spasticity was assessed by calculating the index of movement restriction (iMR) from the difference between the maximum passive movement range of the wrist joint and the evoked movement range by rPMS. The stimulation intensity of rPMS was set at 70% of the maximum output of the stimulator, frequency at 25 Hz, and stimulation duration at 2 seconds. The results showed that the amplitude, velocity, and acceleration of rPMS-induced movements were reduced in the CS compared with those in the HS and AS. The iMR values were 2.8 for HS, 13.0 for AS, and 59.2 for CS, with CS having the highest iMR value. Furthermore, the iMR value for CS decreased to 41.1 after treatment with botulinum neurotoxin.

Shoulder joint subluxation is one of the many complications following stroke and is an inhibitor of motor function recovery [20]. In particular, shoulder joint subluxation causes pain in the shoulder joint and has a significant impact on activities of daily living. Therefore, Fujimura et al. [21] investigated the effect of rPMS on shoulder joint dislocation caused by stroke. The subjects were patients who presented with shoulder joint subluxation after stroke. rPMS was performed repetitively on the supraspinatus, posterior deltoid, and infraspinatus muscles. Stimulation intensity was the maximum tolerable intensity and was performed at 30 Hz for 2 seconds for 100 sessions. Results showed that the acromion-humerus interval was significantly reduced after treatment. That shoulder joint pain, shoulder abduction range of motion, and upper extremity scores on the Fugl-Meyer Assessment also improved. This study demonstrates that rPMS for post-stroke shoulder dislocation decreases the degree of shoulder subluxation and pain and improves upper extremity motor function.

Krewer et al. [22] examined the short- and long-term effects of rPMS on spasticity and motor function in stroke patients. rPMS involved a total of 5000 stimuli at 25 Hz and a stimulus intensity of 110% of the resting motor threshold. Stimulation was applied to the extensor and flexor muscles of the upper arm and forearm twice daily for 2 weeks. Results showed short-term effects on wrist flexor spasticity (immediately after the intervention) and long-term effects on elbow extensor spasticity (2 weeks after the intervention) in the rPMS group. In addition, the rPMS group showed an improvement in sensory function. This study demonstrates that rPMS reduces spasticity and improves sensory function in stroke patients in both short and long terms.

Kinoshita et al. [23] investigated the effects of rPMS on the lower limb of chronic stroke patients on gait function. The subjects were stroke patients with lower limb hemiplegia and gait disturbance. The stimulation sites of rPMS were the gluteus maximus, vastus medialis, hamstrings, quadriceps, gastrocnemius, and soleus muscles of the paralyzed lower limb. rPMS was performed twice daily for 15 days at a frequency of 20 Hz for 3 s, 4800 pulses, and a stimulus intensity of 110% of the motor threshold. The results showed that walking speed, walking ability, and balance ability were significantly improved after the intervention. This study suggests that rPMS effectively restores gait function in stroke patients with gait disturbance.

Beaulieu et al. [24] studied the effect of rPMS on lower limb dysfunction in chronic stroke. The stimulation site of rPMS was the anterior tibialis muscle of the paralyzed lower extremity. rPMS was performed at a theta-burst frequency (three 50 Hz pulses each, delivered in 5-Hz bursts) for 190 s at 42% of maximum stimulation intensity. The results showed that the rPMS group increased ankle dorsiflexion range of motion and maximum isometric muscle strength after the intervention and decreased resistance to ankle flexor stretch. The results also suggested that these changes are related to residual corticospinal tracts. This study demonstrates that rPMS improves lower limb dysfunction in chronic stroke patients.

In conclusion, rPMS improves upper and lower limb dysfunction in stroke patients. Therefore, we believe that rPMS is a highly effective tool for evaluation and treatment in stroke rehabilitation.

4. Conclusion

This chapter outlines the physiological changes, combined effects of MI, muscle strengthening, and effects on stroke patients in rPMS. The rPMS parameters used in studies are listed in Tables 1 and 2. rPMS has attracted attention as a new neuromodulation technique that can noninvasively deliver repetitive magnetic stimulation to peripheral nerves and muscles using induced current from a pulsed magnetic field. Unlike NMES, rPMS is painless and has excellent potential for application in clinical settings. In particular, many clinical studies for stroke rehabilitation have been reported in recent years. Further development of rPMS research is expected, including its effectiveness when combined with other therapies and its integration with technology.

	Stimulation site	Stimulation frequency	Stimulation intensity
Nito et al. [5]	Wrist extensor muscles	50 Hz, 25 Hz, 10 Hz	120% of the motor threshold
Kumru et al. [6]	Extensore carpi radialis muscle	rPMS: 10 Hz; rTMS: 0.1 Hz	rPMS: 70% of motor threshold; rTMS: 120% of motor threshold
Krause et al. [7]	Cervical nerve roots (C7/C8) (First dorsal interosseous)	20 Hz	120% of motor threshold
Asao et al. [8]	Extensore carpi radialis muscle	25 Hz	150% of motor threshold
Asao et al. [9]	Extensore carpi radialis muscle	25 Hz	150% of motor threshold
Yang et al. [10]	Quadriceps muscle	10 Hz	Maximum tolerable intensity
Hirono et al. [12]	Vastus lateralis muscle	50 Hz	Maximum intensity of the device

Table 1.

rPMS parameters in basic research on healthy subjects.

	Patients	Stimulation site	Stimulation frequency	Stimulation intensity
Beck et al. [15]	After hip replacement surgery	Vastus lateralis muscle	10 Hz	Level where the visible movement of the knee is triggered
Jiang et al. [18]	Early subacute stroke	Triceps brachii and extensor digitorum muscles	20 Hz	Triceps brachii muscle: Intensity to induce 30° of elbow extension; Extensor digitorum muscle: Intensity to induce 45° of wrist extension
Fernandez-Lobera et al. [19]	Acute stroke without/with spasticity	Wrist extensor muscles	25 Hz	70% of the maximum stimulator power
Fujimura et al. [21]	Shoulder subluxations caused by stroke	Supraspinatus and posterior deltoid/infraspinatus muscles	30 Hz	Intensity until patients indicates that any further increase would become uncomfortable
Krewer et al. [22]	Severe hemiparesis and mild to moderate spasticity resulting from a stroke or a traumatic brain injury	Extensors and flexors of the upper and lower arm.	25 Hz	110% of motor threshold
Kinoshita et al. [23]	Hemorrhagic stroke with lower limb hemiparesis and gait disturbance	Gluteus maximus muscle, gluteus medius, hamstring muscle, musculus quadriceps femoris, gastrocnemius, soleus	20 Hz	110% of motor threshold
Beaulieu et al. [24]	Chronic stroke	Tibialis anterior muscle	Theta-burst frequency (5-Hz bursts of three 50 Hz pulses each)	42% of the maximal stimulator output

Table 2.

rPMS parameters in clinical research.

Acknowledgments

This work was supported by the Yuumi Memorial Foundation for Home Health Care and JSPS KAKENHI Grant Number JP20K11173.

Conflict of interest

The authors declare no conflict of interest.

Appendices and nomenclature