New approaches to spasticity management after spinal cord injury: application of multilevel magnetic stimulation

Full Text

BACKGROUND

Annually, approximately 5–6 million nervous system injuries are reported worldwide, accounting for 5%–9% of all neurological conditions. Although spinal cord injuries (SCIs) represent only a small percentage of nervous system injuries, they pose significant social and medical challenges. However, diagnoses are often inaccurate, and treatments remain ineffective. Most patients (80%–100%) with SCIs become disabled or die [1]. SCIs are associated with complications that can negatively affect a patient’s performance status, rehabilitation potential, and time required to return to an active social life. In addition to motor disorders, neurogenic pelvic dysfunction, autonomic disorders, sensory disorders, and muscle spasticity may occur [2]. Spasticity is a common SCI complication. In a study of 884 patients with SCIs, Filatov reported spasticity in 74%. Spasticity is most often reported with cervical and upper thoracic injuries and is less common with lower thoracic and lumbar injuries [3]. Spasticity is caused by corticoreticulospinal tract damage, resulting in disinhibition of tonic reflexes in the absence of cortical inhibitory effects [4].

Spasticity can significantly affect patient quality of life following spinal surgery. In severe cases, contractures and pressure ulcers may develop, limiting the effectiveness of physical therapy, passive exercises, and other rehabilitation measures. This limitation results in slower recovery of functional capabilities and increased socioeconomic burden on healthcare institutions. Therefore, it is crucial to develop an optimal spasticity diagnosis and treatment strategy [5]. The Modified Ashworth Scale (MAS) is the standard tool for diagnosing and assessing spasticity severity. It is a 5-point numerical scale ranging from 0 to 4. This scale is suitable for the initial diagnosis of muscle hypertonia and evaluation of rehabilitation outcomes [6]. The Modified Tardieu Scale (MTS) is a less common tool for assessing muscle spasticity [7]. The key feature of MTS is its ability to evaluate changes in the muscle tone and joint range of motion, caused by spastic co-contraction (the involvement of antagonist muscles) and the stretch reflex (the response to tendon stretching). MTS assesses these changes at various passive movement speeds [8]. However, this scale has not been widely adopted in Russian neurological practice because of its time-consuming and complex testing process.

New reviews and studies on treatment options for spasticity in SCIs are regularly published, covering physical therapy, pharmacological therapy, and local injection therapy [9, 10]. However, most of these options have contraindications and may cause adverse effects.

Pharmacological treatment for spasticity includes systemic agents such as central muscle relaxants and benzodiazepines (diazepam). Oral muscle relaxants can significantly improve mild spasticity. However, severe cases often require high doses, which are associated with side effects such as drowsiness, dizziness, decreased blood pressure (which can lead to vascular collapse and loss of consciousness), and dyspeptic symptoms (which can exacerbate existing SCI-induced gastrointestinal disorders). The use of diazepam is limited by its potency as a sedative and its risk of addiction [11, 12].

Currently, botulinum toxin type A is used as a local injection therapy to treat isolated spasticity in individual muscles. The agent blocks acetylcholine release at the neuromuscular junction, which temporarily prevents signals from reaching the muscle. However, this treatment option has several disadvantages, including allergic reactions, the need for ultrasound guidance, and potential flu-like systemic reactions. Additionally, prolonged use may lead to drug tolerance [13].

Advances in physical therapy focus on neuromodulation techniques rather than symptomatic treatment. They address the underlying cause of spasticity by noninvasively modulating the nervous system at various levels [14]. The nervous system can be stimulated through electrical, mechanical, magnetic, or thermal exposure to alter the properties of neurons and interneuronal connections, such as electrical, magnetic, and ultrasound stimulations [15]. Magnetic stimulation is an advanced and promising treatment option with minimal contraindications (metal items in the exposure area and/or electromagnetic implants), few potential complications (rare headaches after transcranial exposure), and a wide range of applications; this variability is due to different coils providing exposure at different depths and a set of protocols capable of stimulating or inhibiting the nervous system [16–18].

Magnetic stimulation techniques are classified based on the level of the nervous system being exposed: transcranial (TMS), trans-spinal (TSMS), or peripheral (PMS). Studies showed that patients with SCIs experience statistically significant improvements after receiving treatment with several magnetic stimulation techniques such as repetitive TMS and TSMS of the primary motor cortex of the affected limb. A meta-analysis by Korzhova et al. (2018) identified 26 articles on TMS effectiveness in the treatment of spasticity. The meta-analysis included 6 studies with a total of 149 patients who underwent real or sham stimulation. In patients with stroke, no significant difference was found in the effects of real and sham stimulation. Patients with SCIs and spasticity showed significant improvements in spasticity after real stimulation (mean effect: –0.80; 95% confidence interval [CI]: –1.12 to –0.49; the true effect size is highly likely to be negative). Sham stimulation did not exhibit any significant improvements in spasticity (mean effect size: 0.15; 95% CI: –0.30 to 0.00, including the zero value). High-frequency repetitive TMS to the M1 area of the spastic leg demonstrated significant differences between the real and sham stimulation groups (p = 0.0002). The authors concluded that TMS had a significant effect on spasticity only in cases induced by lesions at the brainstem or spinal cord [19]. In a randomized, double-blind, placebo-controlled crossover study by Nardone et al. (2017), 10 patients with incomplete cervical or thoracic SCIs received daily real or placebo rhythmic TMS (rTMS) stimulation for 10 days. The following parameters were compared before and after stimulation: the amplitude ratio of the soleus H reflex, amplitude of motor evoked potentials at rest and during background contraction, MAS score, and Spinal Cord Assessment Tool for Spastic Reflexes score. Patients who received real rTMS demonstrated a significant increase in MEP amplitude both at rest and during active stimulation. Moreover, these patients showed a significant decrease in MAS and SCAT scores after treatment. These changes persisted for 1 week after the end of rTMS; however, they were not reported with sham TMS [20]. Other studies have confirmed the effectiveness of these techniques in humans and animals [21, 22].

PMS is no less effective. Many studies confirmed a decrease in spasticity (as measured by MAS scores) in patients with spastic paralysis and improvement in motor function of the affected limbs [23, 24]. A systematic review by Lomovtsev et al. (2023) included 10 clinical studies. The frequency ranged from 1 Hz to 150 Hz, with 25 Hz being the most common, and the intensity increased gradually but not consistently. Eighty percent of the studies demonstrated positive results regarding spasticity, including improvements in stretch reflex thresholds, self-reported decreases in spasticity-related difficulties, and decreases in clinical spasticity severity, performance scores, MAS scores, spastic tone, and active-to-passive dorsiflexion ratios [25]. Zschorlich et al. (2019) conducted a pilot study with 38 patients. Some received PMS using a 5 Hz posterior tibial nerve stimulation (n = 19), while others received sham stimulation (n = 19). The stimulation session lasted for 5 min. The study used a pre- and posttreatment design and divided patients into comparable groups. The parameters were evaluated at the start and end of the treatment period. The main result of the study was a significant decrease in soleus reflex activity. The PMS group showed a 23.7% decrease in the tendon reflex activity following treatment compared with pretreatment values (p < 0.001). The sham stimulation group exhibited no significant changes [26].

All of the above techniques improve spasticity in patients with SCIs, and using them in combination increases the overall effectiveness of therapy. Therefore, we combined three techniques that stimulate different levels of the nervous system into one technique called multilevel magnetic stimulation (MMS).

Aim

The study aimed to evaluate the effectiveness of MMS in improving spasticity in patients with poststroke spastic monoplegia or paraplegia.

METHODS

This controlled, randomized, open-label study included patients with SCIs aged 18–55 years (mean age: 36 ± 4 years) and divided them into two groups. The control group received standard therapy and basic rehabilitation, including pharmacological therapy, physiotherapy, and exercise therapy (n = 15). In contrast, the study group received standard therapy + MMS (n = 15). All patients were evaluated and treated at the Clinic of Nervous Diseases of the Kirov Military Medical Academy in Saint Petersburg, Russia.

Selection criteria:

• No history of traumatic brain injury, acute cerebrovascular accident within the past 2 years, or previous neuroinfections
• No contraindications to MS
• Presence of SCIs
• No compressive and ischemic complications of SCIs
• No contraindications to standard therapy and rehabilitation

All patients underwent standard clinical and neurological examinations to evaluate sensitivity impairment, motor dysfunction, and spasticity [27]. The SCI level was determined by diagnostic imaging and clinical examination using the American Spinal Injury Association Impairment Scale. Spasticity severity was assessed using the following MAS scoring system: 0, no increased tone; 1, slight increase in muscle tone, indicated by a catch when the limb is moved in flexion or extension, or slight increase in muscle tone, indicated by a catch followed by minimal resistance throughout range of motion; 2, more marked increase in tone throughout most of the range of motion, but the limb can be easily flexed; 3, considerable increase in tone, but passive movement is difficult; and 4, limb is rigid in flexion or extension [28].

The Neuro-MSX magnetic stimulator (Neurosoft, Russia) with a round coil was used for magnetic stimulation.

The therapeutic magnetic stimulation protocol was as follows:

1. TMS: the M1 stimulation point (lower limbs Cz). Frequency, 10 Hz; pause, 25 s; 50 pulses per train; total number of pulses, 500; duration, 4.08 min.
2. TSMS: the stimulation point at the mid-thoracic spine with a biphasic series of stimuli. Frequency, 1 Hz; 480 pulses per series; 50 series without pauses; duration, 7.59 min; total number of pulses, 24,000.
3. PMS: the stimulation points at the front and back of the thighs. Frequency, 10 Hz; pause, 3.5 s; stimuli in a series, 48; series duration, 4.7 s; series in a session, 74; duration, 10.03 min; total number of impulses, 3552 [29].

The treatment period lasted 3 weeks and comprised 15 procedures, performed daily for 5 days, followed by a 2-day break.

Statistical analysis was performed using StatTech v. 4.8.6 (StatTech LLC, Russia). The Shapiro–Wilk test was applied to test normality of data. The significance of changes in dependent samples was assessed using a parametric paired Student’s t-test for normal data and a nonparametric Wilcoxon test for non-normal data. The Mann–Whitney test was used to compare independent samples. Fisher’s exact test was employed to compare the percentages in a 2 × 2 contingency table. Moreover, the Pearson chi-square test was utilized to evaluate the differences in distributions of qualitative characteristics between groups. Cohen’s d was used to assess the size of the clinical effect. The patients were divided into groups and evaluated for homogeneous distribution of the primary characteristics (Tables 1 and 2). Differences were considered significant at p < 0.05. The sample size was not pre-calculated.

 

Table 1. Distribution of patients based on the presence of spasticity symptoms

Parameter	Categories	Spasticity		Fisher’s exact test	p
		Not present	Present
Group	Control group	4	11	1	1.000
	Study group	3	12

 

Table 2. Distribution of patients by level of spinal cord injury

Parameter	Categories	Level of spinal cord injury			χ2	p
		Cervical	Thoracic	Lumbar
Group	Control group	4	9	2	2.519	0.284
	Study group	1	10	4

 

Patients were stratified into three groups based on SCI level (Table 2). The Pearson chi-square test revealed no significant differences in patient distribution. Therefore, further comparisons were possible.

The subsequent analysis only included patients with spasticity (MAS > 0) at the initial examination.

RESULTS

Figure 1 shows the sampling sequence. We analyzed data from 23 patients who were diagnosed with spasticity during their initial examination. The Shapiro–Wilk test revealed the normal initial MAS scores in the study group and non-normal MAS scores in the control group. This helped determine which statistical tests to use for the intragroup analysis.

 

Fig. 1. Patient sampling diagram.

 

Table 3 presents the distribution of the mean MAS scores before and after treatment.

 

Table 3. Changes in spasticity severity by the Ashworth scores in groups

Group	Number of patients	MAS score, exam 1 (M ± SD)	MAS score, exam 2 (M ± SD)	Δ (M ± SD)
Control	12	3.58 ± 0.79	2.08 ± 1.16	1.50 ± 1.51
Study	11	3.73 ± 0.90	2.00 ± 1.10	1.73 ± 1.27

 

The mean pretreatment MAS scores were 3.73 ± 0.90 in the study group and 3.58 ± 0.79 in the control group. The mean posttreatment MAS scores decreased to 2.00 ± 1.10 in the study group and to 2.08 ± 1.16 in the control group. Therefore, both groups showed significant improvements in spasticity. The parametric paired Student’s t-test (t = 5.73; p = 0.0004) was used for the study group with normal differences and indicated the highly significant intervention effect. The nonparametric Wilcoxon test for dependent samples was used in the control group with non-normal differences (Z = –2.21; p = 0.0269), which showed a significant, though smaller, decrease.

The Mann–Whitney test was used to compare the size of the changes in spasticity index (Δ) between groups (U = 80.0; p = 0.3945). No significant differences were found between the groups. However, Cohen’s d revealed a large clinical effect in the control group (0.91) and an extremely large clinical effect in the study group (1.45). Although the difference between the groups was not significant, the MMS showed a clinically greater decrease in spasticity.

The t- and Z-scores used in the analysis are statistical measures describing the relationship between the size of the observed effect and degree of data scatter. The higher the absolute score, the less likely the observed effect is random. In the Mann–Whitney test, the U statistic quantifies the difference in ranks between two independent samples. Cohen’s d reflects the standardized effect size, which is approximately 0.2, 0.5, and 0.8 for small, medium, and large effects, respectively. The obtained values (0.91 and 1.45) confirm that both groups achieved clinically significant improvements in spasticity. However, the improvements were higher in the study group.

Patients were evaluated 3 months after treatment to determine if the decrease in spasticity was stable. Both groups partially returned to their initial MAS scores, but their mean scores remained significantly lower. The study group demonstrated better maintenance of effects compared with the control group (Table 4).

 

Table 4. Changes in Ashworth scores at posttreatment month 3

Group	Pretreatment (M ± SD)	Posttreatment (M ± SD)	At month 3 (M ± SD)	Δ from baseline (%)
Control	3.58 ± 0.79	2.08 ± 1.16	2.50 ± 1.20	–30.2
Study	3.73 ± 0.90	2.00 ± 1.10	2.20 ± 1.05	–41.0

 

At posttreatment month 3, the mean MAS score in the study group increased by only 0.20 compared with the scores obtained immediately after the end of treatment, while the control group demonstrated an increase by 0.42. This indicates a more lasting clinical effect of MMS (Fig. 2).

 

Fig. 2. Changes in Ashworth scores.

 

Analysis showed that both treatment regimens improved spasticity in patients with SCIs, but MMS induced a larger clinical effect. Additionally, at posttreatment month 3, the study group demonstrated a longer-lasting effect. Therefore, this option may be a promising addition to standard therapy.

No adverse events were reported during the study.

DISCUSSION

This study evaluated an MMS regimen that combined transcranial, trans-spinal, and peripheral magnetic stimulations. Both groups (the control group receiving standard therapy and the study group receiving standard therapy + MMS) demonstrated statistically significant improvements in spasticity as measured by MAS scores. Additionally, the study group exhibited a greater decrease in spasticity, as evidenced by the size of the intragroup statistical effect and clinical significance of the changes.

The mean MAS scores decreased from 3.73 ± 0.90 to 2.00 ± 1.10 in the study group and from 3.58 ± 0.79 to 2.08 ± 1.16 in the control group. Although no significant differences were found in the intergroup comparison (p = 0.3945), Cohen’s d indicated a greater clinical improvement in the study group (1.45 vs. 0.91). Additionally, at posttreatment month 3, the study group demonstrated a sustained effect.

These findings are consistent with those of other studies, which show the effectiveness of each MMS component. TMS decreases muscle tone and promotes neuroplasticity in patients with SCIs, multiple sclerosis, and stroke [30]. TSMS modulates spinal reflex circuits and improves conduction in descending pathways, which decreases the abnormal hyperactivity of alpha motor neurons [31, 32]. Furthermore, PMS improves the performance of peripheral nerves and muscles and decreases spasticity [33].

The combined use of all three types of stimulation in MMS showed a synergistic effect at various levels of the nervous system, including the cortical, spinal, and peripheral levels. This may explain the greater and more sustained decrease in spasticity observed in the study group compared to the control group.

However, the study had some limitations. The small sample size and lack of time stratification may have affected the interpretation of the results. Further evaluation is required in future studies.

Overall, our results confirm the clinical potential of MMS as a standard rehabilitation program for patients with SCIs, which provides better improvements in spasticity and longer-lasting effects.

CONCLUSION

The study found that MMS results in a more significant and long-lasting decrease in spasticity in patients with SCIs compared with standard therapy alone. Despite the small sample size, obtained data indicate the clinical effectiveness of MMS and its impact on the neurophysiological mechanisms that regulate muscle tone. Further clinical research is required to confirm the effectiveness of MMS in rehabilitation.

ADDITIONAL INFO

Author contributions: D.A. Solovev: conceptualization, methodology, investigation, formal analysis, writing—original draft; V.Yu. Lobzin, I.A. Lupanov — study concept and design, analysis of obtained data, final editing, approval of the manuscript for publication; D.N. Frunza, A.S. Rodionov, A.V. Ryabtsev, P.S. Dynin, K.M. Naumov, N.V. Tsygan, I.V. Litvinenko — study concept and design, approval of the manuscript for publication. All authors have read and approved the final version of the manuscript prior to publication.

Ethics approval: The conducted study was approved by the local ethics committee of the S.M. Kirov Military Medical Academy (protocol No. 324 dated June 11, 2025).

Disclosure of interests: The authors have no relationships, activities, or interests over the past three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Funding sources: The study was not supported by any external sources of funding.

Consent for publication: Written consent was obtained from the patients for publication of relevant medical information within the manuscript.

Statement of originality: The authors did not use previously published information (text, illustrations, data).

Data availability statement: All the data obtained in this study is available in the article.

Generative AI: Generative artificial intelligence technologies were not used in the creation of this article.

About the authors

Daniil A. Solovev

Military Medical Academy

Author for correspondence.
Email: dankrute@gmail.com
ORCID iD: 0009-0007-8821-348X
SPIN-code: 8592-5718

Resident

Russian Federation, Saint Petersburg

Vladimir Y. Lobzin

Military Medical Academy; Saint Petersburg State University

Email: dankrute@gmail.com
ORCID iD: 0000-0003-3109-8795
SPIN-code: 7779-3569

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

Ivan A. Lupanov

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0009-0008-7918-9227
SPIN-code: 2986-6679

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Daria N. Frunza

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0009-0004-6631-0420
SPIN-code: 7177-8195

Neurologist

Russian Federation, Saint Petersburg

Aleksandr S. Rodionov

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0002-7455-8600
SPIN-code: 4458-9650

Neurologist

Russian Federation, Saint Peterburg

Aleksandr V. Ryabtsev

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0002-3832-2780
SPIN-code: 9915-4960

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Pavel S. Dynin

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0001-5006-8394
SPIN-code: 8323-3951

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Konstantin M. Naumov

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0001-7039-2423
SPIN-code: 3996-2007

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, Saint Petersburg

Nikolay V. Tsygan

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0002-5881-2242
SPIN-code: 1006-2845

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Igor V. Litvinenko

Military Medical Academy

Email: dankrute@gmail.com
ORCID iD: 0000-0001-8988-3011
SPIN-code: 6112-2792

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

References

Supplementary files