Stroke is one of the most common neurological diseases worldwide, especially in the elderly. Limb dysfunction is one of the main causes of disability in stroke, which seriously affects patients' activities of daily living (1). It has been reported that nearly 70.0% of stroke patients suffer from limb dysfunction (2). Lower limb motor function is a prerequisite for daily activities and is often impaired after stroke, resulting in limited functional activities (3, 4). Lower limb spasm is a common symptom of stroke (5) and a result of upper motor neuron syndrome (UMNS) (6). Approximately 30% of stroke patients experience spasms that require intervention (7), which, if not actively treated, may lead to high muscle tone, joint contracture, and abnormal movement patterns of the affected limb, resulting in impaired weight-bearing capacity of the limb, affecting the patient's balance and walking ability. Lower limb spasm and motor dysfunction seriously affect the quality of life of patients, and ways to effectively control lower limb spasm and improve lower limb motor function represent important issues that are actively discussed in rehabilitation medicine.

From minutes to months after brain injury, other brain regions may undergo changes due to afferent nerve block, release of inhibition, activity-dependent synapse changes, membrane excitability changes, and formation of new synaptic connections or exposure of existing connections (8, 9). The naturally occurring functional reorganization of the cerebral cortex is limited, and functional training is one of the most important factors to improve patients' functional recovery and enable them to adapt to the environment and live independently (10). To achieve functional reorganization, patients need to practice specific activities, and the more they practice, the easier the reorganization becomes. In the facilitation model, the hierarchical structure of the brain was used to explain abnormal movement patterns and spasms after brain injury. Various studies have confirmed that normal movement patterns can be included in rehabilitation therapy to promote the formation of normal motor functions. Motor relearning techniques, including drafting training, muscle strength training, and correct posture guidance training, can correct lower limb spasm in stroke patients.

Transcranial magnetic stimulation (TMS) is a non-invasive nerve modulation and stimulation technique that uses electromagnetic induction properties to modulate cerebral cortical excitability for short or long periods by applying locally time-varying magnetic pulses. TMS includes three stimulus paradigms: single-pulse TMS (sTMS), double-pulse TMS (pTMS), and repetitive TMS (rTMS). sTMS and pTMS are mainly used as research tools to locate cortical function and measure cortical excitability. rTMS is a sequence of TMS pulses delivered at the same intensity to a single cortical region, which is used to regulate brain activity and can induce long-term effects (facilitation or inhibition). Motor relearning procedure (MRP) regards the recovery of motor function after stroke as a process of relearning or retraining. Through visual, auditory, and tactile feedback, the normal motor mode is constantly strengthened and the abnormal motor mode is corrected, so the patients can constantly cooperate with the treatment to promote functional recovery.

The current rehabilitation methods for post-stroke spasm and limb movement disorders include rTMS and MRP (11, 12). rTMS can influence the function and behavior of the cortex by safely modifying neuronal activity in certain brain areas (13). TMS uses Faraday's electromagnetic induction principle to generate an induced current in the brain. Faraday discovered that a pulsed current through a coil creates a magnetic field and that the rate of change of this magnetic field determines the secondary current induced in the nearby conductor. Regarding TMS, the electrical pulse passing through the conducting coil increases to peak intensity for a short time (<1 ms) before decreasing back to zero. The transient current creates a magnetic field perpendicular to the plane of the coil that increases as fast as the current (up to ~2.5 T) and then drops rapidly. This transient magnetic field passes unhindered through the subject's scalp and skull, creating an induced current in the brain that is parallel to the plane of the stimulation coil but in the opposite direction of the coil current (14).

To create an electric field in the brain using electromagnetic induction, rTMS delivers a brief, strong pulsed current to a coil placed on the subject's head. The generated electric field then modulates neuron transmembrane potential, hence modulating neural activity (15, 16). Studies have shown that rTMS may be effective in treating lower limb spasms and in regulating cortical excitability in the leg motor region (17). MRP is mainly applied in rehabilitation therapy for the recovery of motor function after stroke in adults. This method considers the restoration of motor function after a stroke as a process of retraining or relearning. Through constant reinforcement of appropriate movement patterns and correction of incorrect movement patterns, as well as collaboration with therapy, MRP may help patients achieve functional recovery (18).

The main objectives of this research are (1) to investigate the improvement of lower limb spasm, motor function, and cortical function of patients with prolonged treatment of stroke with rTMS combined with MRP, and (2) to further determine whether combined rTMS and MRP therapy is more effective than MRP alone on lower limb spasm, motor function, and cortical excitability in stroke patients.

rTMS has been reported to treat muscle spasticity in stroke patients (24–29). The purpose of our study was to explore whether the efficacy of rTMS combined with MRP was better than that of MRP alone in 60 stroke patients with hemiplegia. To evaluate patient recovery, it is necessary to investigate whether the motor function of lower limbs can be restored (19). MRP treatment significantly improves motor function and alleviates spastic disorders in stroke patients. Although traditional rehabilitation therapy can relieve the symptoms of limb spasm to a certain extent, it cannot improve the excitability of the cerebral cortex on the affected side of the patient, and the therapeutic effect is limited. In our study, low-frequency rTMS was used to inhibit the M1 region of the non-involved side. After 4 weeks of treatment, the rTMS combined with MRP can increase cerebral cortex excitability on the affected side or decrease it on the healthy side, effectively enhancing the motor function (e.g., Fugl-Meyer lower limb motor function and Fugl-Meyer balance function) and muscle spasticity (lower modified Ashworth score) of affected limbs in stroke patients and show a more obvious effect (higher extraction rate and lower threshold and CMCT) than exercise relearning therapy alone.

According to the principle of hemispheric competitive inhibition (25, 30, 31), hemispheric cortical excitability in the afflicted area decreases after stroke, and the healthy hemisphere presents an increase in cortical excitability due to the transcallosal inhibition loss of the affected hemisphere, thus aggravating the inhibition of the affected hemisphere by the healthy hemisphere. Therefore, improving cerebral cortex excitability on the affected side or decreasing it on the healthy side can promote the recovery of limb function after stroke (32, 33). Our study found that 1 Hz rTMS treatment on the healthy side of the cerebral hemisphere can significantly improve limb spasm after stroke and promote limb functional rehabilitation, which may be related to the fact that low-frequency rTMS can inhibit the excitability of the M1 region on the healthy side, reduce its inhibitory effect on the affected cortex, and indirectly enhance the excitability of the M1 cortex on the affected side (29, 34, 35). In other words, after inhibiting the non-affected side, the affected side's velocity-dependent stretch reflex was enhanced, tendon hyperreflexia was relieved, the balance of bilateral cerebral hemisphere functions was restored, and muscle tension was reduced. Meanwhile, the cortical excitability cerebral hemisphere of the affected person was further improved (36). Lin et al. (24) found that rTMS can effectively improve the motor function of the impacted limb in stroke patients. rTMS can stimulate the excitability of the cerebral cortex and promote synaptic activity and remodeling, thus accelerating the recovery of cognitive impairment and enhancing the motor function and spasticity of stroke patients (37). Rastgoo et al. (27) found that low-frequency rTMS over the M1 of unaffected lower limbs can reduce lower limb spasticity and improve motor dysfunction caused by lower limb spasticity in stroke patients. This result is consistent with the findings of Li et al. (26), which showed that low-frequency rTMS stimulation of the contralateral side decreased the MAS score and increased the FMA score in stroke patients after therapy, suggesting that low-frequency rTMS reduced patients' muscle spasticity and limb dyskinesia.

This study has several limitations. First, we did not conduct long-term observation and follow-up on the subjects; therefore, long-term efficacy needs to be observed in further studies. Second, the number of cases included in this study was small. Third, due to equipment configuration, the YRD CCY-I magnetic stimulation instrument uses a circular coil instead of the commonly used figure-eight transcranial magnetic stimulation coil.

In conclusion, rTMS combined with MRP showed better efficacy than MRP in treating muscle spasticity and limb dyskinesia in stroke patients. The combination of rTMS and MRP may be a beneficial adjunctive technique for motor neurorehabilitation in stroke patients with muscle spasticity and limb dyskinesia.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University. The patients/participants provided their written informed consent to participate in this study.

YL and PW: conceptualization. YZhang: methodology. XW: formal analysis. YZhao: investigation. SF: data curation. RC: writing—original draft preparation. YL: funding acquisition. RC, YL, and PW: writing—review and editing. YX and JZ: project administration. All authors have read and agreed to the published version of the article.