Brain Network and Modulation

RESEARCH ARTICLE
Year
: 2022  |  Volume : 1  |  Issue : 1  |  Page : 31--38

Clinical effect of repetitive functional magnetic stimulation of sacral nerve roots on urinary retention after spinal cord injury: a case-control study


Jing-Jing Zhang1, Yan Chen1, Ling-Li Wu1, Fang Gao1, Yan Li1, Bing-Chen An2,  
1 Department of Rehabilitation, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 Department of Rehabilitation, Huadong Hospital Affiliated to Fudan University, Shanghai, China

Correspondence Address:
Bing-Chen An
Department of Rehabilitation, Huadong Hospital Affiliated to Fudan University, Shanghai
China
Yan Li
Department of Rehabilitation, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai
China

Abstract

Urinary retention is a serious complication of spinal cord injury. This study examined whether repetitive functional magnetic stimulation (rFMS) applied over the sacral nerve root affected bladder function or mood in patients with urinary retention after spinal cord injury. This single-center, case-control study included 32 patients with detrusor flaccid neurogenic bladder after spinal cord injury, who were randomly assigned to rFMS (n = 11), electroacupuncture pudinal nerve stimulation (EAPNS; n = 11), and control groups (n = 10). All groups received routine bladder function training. The S3 sacral nerve was stimulated at a frequency of 5 Hz, once per day for 4 consecutive weeks in the rFMS group. Electroacupuncture stimulation of the pudendal nerve was performed once daily for 4 weeks in the EAPNS group. The control group received bladder function retraining alone. After the 4-week treatment, there were significant improvements in all three groups (P < 0.05). Primary bladder sensation, maximum bladder volume, maximum bladder pressure, and residual urine were significantly higher in the rFMS group than in the other two groups (P < 0.05). Primary bladder sensation, maximum bladder volume, residual urine, and urinary leukocyte count were significantly different between the EAPNS and control groups (P < 0.05). The rFMS group had significantly lower scores in the self-rated anxiety scale and self-rated depression scale compared with those of the other two groups. The quality of life score significantly increased in all three groups. rFMS is conducive to the recovery of neurogenic function in patients with urinary retention. This study provides a scientific basis for the clinical application and promotion of rFMS.



How to cite this article:
Zhang JJ, Chen Y, Wu LL, Gao F, Li Y, An BC. Clinical effect of repetitive functional magnetic stimulation of sacral nerve roots on urinary retention after spinal cord injury: a case-control study.Brain Netw Modulation 2022;1:31-38


How to cite this URL:
Zhang JJ, Chen Y, Wu LL, Gao F, Li Y, An BC. Clinical effect of repetitive functional magnetic stimulation of sacral nerve roots on urinary retention after spinal cord injury: a case-control study. Brain Netw Modulation [serial online] 2022 [cited 2022 Jun 29 ];1:31-38
Available from: http://www.bnmjournal.com/text.asp?2022/1/1/31/340142


Full Text



 Introduction



Spinal cord injury (SCI) is a serious disease of the central nervous system that occurs because of various traumatic and non-traumatic causes (Hamid et al., 2018). Neurogenic bladder (NB) is a common clinical complication of SCI (Myers et al., 2016), with a prevalence of approximately 70–84% (Powell, 2016). NB can be divided into three types: urinary incontinence, urinary retention, and mixed urinary incontinence and urinary retention (Panicker, 2020). Clinicians should create different rehabilitation programs according to the different types of NB. At present, a significant proportion of cases of NB are of the urinary retention type. Urinary retention can cause hydronephrosis, urinary tract infection, and later chronic renal failure (Billet and Windsor, 2019). Renal failure due to bladder dysfunction is the leading cause of death in patients with SCI in the first few decades after injury (Chen et al., 2016). Therefore, the reconstruction of balanced bladder function and improvement of urinary control ability is an important part of rehabilitation treatment for SCI patients.

Current rehabilitation methods for urinary retention include pelvic floor muscle function training (Dumoulin and Hay-Smith, 2010), clean intermittent catheterization (Lucas, 2019), botulinum toxin injection (Jhang, 2019), electronic biofeedback (Dumoulin and Hay-Smith, 2010), and acupuncture (Wu et al., 2018). All of the above treatments have limited efficacy. Most are palliative and can only temporarily solve symptoms. Some require interventional therapy and have strict indications, so their clinical application is limited.

Increasing numbers of scientific studies have reported the use of electrical stimulation as a second- or third-line treatment for neurogenic lower urinary tract disease, and its use is now well-validated and accepted (Chari et al., 2017). A previous study (Yoo et al., 2008) showed that low frequency electrical stimulation of the pudendal nerve can inhibit bladder detrusor contraction, induce urethral sphincter contraction, and promote bladder filling; intermediate and high frequency electrical stimulation of the pudendal nerve can promote bladder detrusor contraction, inhibit urethral sphincter contraction, and promote bladder emptying. However, electrical stimulation of the pudendal nerve always uses surface electrodes, which causes contraction in the pelvic floor muscles primarily indirectly through multisynaptic reflexes (Kielb, 2005). Lv and Wang (2014) established electroacupuncture pudinal nerve stimulation (EAPNS, formerly known as “sacral four-needle” therapy), and proved that this treatment had both good short- and long-term efficacy for female stress urinary incontinence. However, there is insufficient evidence to prove the clinical effect of EAPNS on neurogenic bladder with detrusor retardation.

Magnetic stimulation is the use of a magnetic field of a certain intensity and frequency to stimulate nervous tissue to produce excitement in non-invasive diagnostic and treatment measures; it is non-invasive, safe, painless, and can reach deeper structures (Fernandes et al., 2021). High frequency repetitive transcranial magnetic stimulation can promote detrusor contraction and urethral sphincter relaxation in patients with multiple sclerosis (Nardone et al., 2019). Low frequency repetitive transcranial magnetic stimulation can effectively treat neurogenic lower urinary tract dysfunction caused by Parkinson’s disease and other neurodegenerative diseases (Brusa et al., 2009). Magnetic stimulation can also relieve some symptoms of bladder pain syndrome and chronic pelvic pain (Nizard et al., 2018). The targets of magnetic stimulation studied above are located in the right and left dorsolateral prefrontal cortices. As early as 1993, Brodak et al. (1993) used sacral nerve root magnetic stimulation to treat urinary retention after SCI, and found that the detrusor stimulation threshold increased with increased bladder volume. Tsai et al. (2014) found that magnetic stimulation of sacral nerve roots can increase bladder volume and reduced urination in women with stress incontinence. Bycroft et al. (2004) applied single and intermittent bursts of function magnetic stimulation on sacral nerve root to compare the bladder function between seven men with neurogenic detrusor overactivity and five healthy men. The study affirmed the ability of functional magnetic stimulation (FMS) to inhibit bladder contractions in both of these patient groups. However, most studies have focused on patients with urinary incontinence, and few studies have specifically examined the use of repetitive FMS (rFMS) for improving urinary retention.

At present, the clinical results of rFMS are quite different because of differences in the location and frequency of magnetic stimulation. Furthermore, there are no relevant studies on the treatment of urinary retention after SCI using rFMS. Therefore, we attempted to preliminarily explore the clinical efficacy and mechanisms of rFMS in patients with urinary retention after SCI and thus provide a scientific basis for the clinical application of rFMS.

 Subjects and Methods



This study was designed as a single-center, case-control study. Thirty-two patients with urinary retention after SCI who were admitted to the Department of Rehabilitation, Tongren Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2020 participated in the study. All participants provided written informed consent form. This study was approved by the Ethics Committee of the Tongren Hospital, Shanghai Jiao Tong University School of Medicine (approval No. 2020-082-01) on October 21, 2021 and registered at Chinese Clinical Trial Registry (Registration No. ChiCTR2000039625) on November 7, 2021. The procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 2000.

Subjects

A total of 32 patients with urinary retention after SCI who were admitted to the Rehabilitation Department of Shanghai Tongren Hospital from January 2020 to December 2020 were randomly divided into the rFMS group (n = 11), the EAPNS group (n = 11), and the control group (n = 10). Because of the sequential admission of patients, all patients were numbered using a random number table after admission.

Inclusion criteria

The inclusion criteria were as follows: International Standard for Neurological Classification of Spinal Cord Injury (ASIA and ISCoS International Standards Committee, 2019); residual urine (RU) ≥ 100 mL, abnormal bladder filling stage pressure test results (Amarenco et al., 2017); stable vital signs, good mental state, and good compliance; spinal cord injury above the sacral pulp, spinal shock phase has passed; and sensation present in the saddle area or contraction present in the anus.

Exclusion criteria

The exclusion criteria were as follows: presence of urinary tract infection, tumor, urinary calculi, or organic obstruction; metal implant within a 10-cm radius of the treatment site; and presence of a pacemaker or other sensitive medical electronic device.

Therapeutic methods

Prior to treatment, patients underwent urodynamic tests. Patients in all three groups received basic medication (anti-hypertensive drugs, hypoglycemic drugs), a regular and fixed water intake program, maintained a urine diary, and underwent routine physical therapy, bladder function training (use of postures, trigger urination, and increased abdominal pressure urination). The rFMS group received rFMS applied over sacral nerve root. The EAPNS group received electroacupuncture pudendal nerve stimulation. The control group only received routine bladder function training. All three groups were treated for 4 weeks.

The specific methods were as follows:

Bladder function training

Drinking water plan according to the patient’s drinking habit, drinking 125–200 mL water per hour, to a total of 1500–3000 mL every day. If the patient lacked a fairly accurate sense of bladder fullness and was completely unable to empty the bladder autonomously, the safe bladder capacity was estimated to be 300 mL and the daily intake of water was approximately 2000 mL.Urination diary: A frequency urine scale was used to record the volume of urination per time, and the number of urinations during the day and night.Timing urination: Urination or catheterization every 2–4 hours, 300–400 mL is appropriate, avoid more than 500 mL.Trigger urination: Patients were instructed to pay attention to the precursors of bladder filling, such as swelling and numbness in the bladder area, and encouraged to look for triggers, such as scratching the inner thigh and pulling pubic hair, to induce urination.

rFMS therapy

Magnetic stimulation therapy was applied using a magnetic stimulator with a circular stimulus coil (Ered Company, Wuhan, China). Metal and electronic devices were removed from the patient’s body, and the patient was asked to take and maintain a prone position. The position of the S3 sacral foramina was roughly ascertained: about a finger’s distance from the midpoint of the line between the upper margin of the sacrum and the coccyx. The center of the magnetic stimulation circular coil was aligned with the S3 foramina. First, a monopulse magnetic stimulation was used under magnetic stimulator, with the intensity of stimulation set at 80% of the maximum output intensity and with an output frequency of 5 Hz; continuous magnetic stimulation was applied for 20 minutes for a total of 1600 pulses. The stimulation was performed once a day, five times a week for 4 weeks during the course of treatment. The patients’ response to magnetic stimulation was observed and evaluated. When the S3 nerve root was effectively stimulated using magnetic stimulation, toe flexion could be seen, and the patients had an obvious sensation of anal contraction.

Electroacupuncture pudendal nerve stimulation

EAPNS therapy (originally known as “four sacral points” therapy) was adopted (Lv and Wang, 2014). According to the direction of the pudendal nerve, four acupuncture points in the sacrococcygeal region were selected: 1 cm laterally from the sacrococcyx joint (both sides) and 0.5 cm laterally from the tip of the coccyx (both sides).

The upper two acupuncture points were directly stimulated with 0.35 mm × 100 mm filiform needles at a depth of 80–95 mm, so that the needle sensation radiated to the urethra or anus. At the next two acupuncture points, a 0.40 mm × 100–125 mm filiform needle was used to obfuscate laterally (in the direction of the sciatic and rectal fossa near the perineal nerve) with a depth of 90–110 mm so the needle sensation radiated to the urethra.

The needle handle on each side of the needle was connected to a pair of electrodes from the KWD-808-I electroacupuncture instrument (Indi Electronic Medical Device Company, Suzhou, China) after the needle was inserted as detailed above. A continuous wave was used for electroacupuncture stimulation with a frequency of 2.5 Hz, and strong stimulation (45–55 mA) was used, set so that the patient did not feel uncomfortable, for 60 minutes each time. The patients were treated daily five times a week for 4 weeks during the course of treatment.

Outcome measures

Baseline data collection included age, sex, American Spinal Injury Association Impairment grade, and the course of the disease. Clinical outcomes were assessed by the changes manifested at the baseline and after the 4-week follow-up, using primary bladder sensation (PBS), maximum bladder volume (MBV), and maximum bladder pressure (MBP). Meanwhile, the RU, urinary leukocyte (UL), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and the quality of life (QOL) score.

Urodynamic indicators include PBS, MBV, and MBP. PBS is when the subject first feels the bladder filling. MBV refers to the volume of the bladder when the patient feels that they can no longer hold in urine. MBP is the maximum pressure the bladder can achieve as it gradually fills up. Urodynamic examination has been shown to be reliable and valid for evaluation of NB patients with SCI.

RU refers to the volume of urine remaining in the bladder at the end of urination. The value in normal healthy adults is generally less than 5 mL. If the RU gradually increases by more than 50 mL or even more than 100 mL, it is considered to be a pathological state.

The white blood cells in RT examination reflect the level of inflammation in urine. The positive white blood cells in RT examination consider the presence of urinary tract infection, and the degree of inflammation is related to the amount of white blood cells.

SAS and SDS were used to assess the anxiety and depression of the subjects, respectively. Each scale contains 20 items, and each item is divided into four grades. The subjects were required to answer the questions according to the situation in the previous week. The scales were used to assess mood changes before and after treatment.

The QOL score (0–6) is a measure of a patient’s lifetime subjective perception of their current level of lower urinary tract symptoms. The primary concern is the degree to which the patient was troubled by the lower urinary tract symptoms and whether they could be tolerated. It provides a platform for communication between doctors and patients, enabling doctors to have a good understanding of patients’ disease status.

Statistical analysis

The statistical analysis was performed using the Statistical Package for Social Science version 22® (IBM SPSS, Inc., Armonk, NY, USA). The level of significance for all hypothesis tests (P) was set at 0.05. A descriptive analysis was performed to describe the characteristics of age, sex, American Spinal Injury Association Impairment grade, and other clinical data in the three groups. Continuous variables are presented as mean ± standard deviation (SD). The chi-squared or Fisher’s exact test was performed to compare categorical variables among the three groups. Because of the small sample size, non-parametric tests were performed in the evaluation. The comparison during follow-up endpoints among three groups was performed using the Kruskal–Wallis test.

 Results



Baseline characteristics

Baseline sociodemographic and clinical characteristics of the three groups are summarized in [Table 1]. At baseline, the sample was homogeneous regarding sex, and age (P > 0.05; [Table 1]). No patient was lost or excluded during follow-up [Figure 1]. No adverse event was reported.{Table 1}{Figure 1}

Bladder urodynamics

After 4-week treatment, there were significant improvements in PBS, MBV, MBP and RU in the three groups. Compared with the other two groups, the rFMS group showed lower PBS (P = 0.005), MBV (P = 0.000), RU (P = 0.000) and higher MBP (P = 0.004). Compared with the control group, the EAPNS group showed significant improvements in PBS (P < 0.05) and MBV (P < 0.05), RU (P < 0.05), other than in MBP (P = 0.051; [Figure 2]).{Figure 2}

UL examination

After 4-week treatment, there was a significant reduction in the number of white blood cells in urine routine in the rFMS (P = 0.003) and EAPNS (P = 0.007) groups compared with the pretreatment value. Otherwise, the control group showed no significant decrease in white blood cells in urine routine compared with the pretreatment value (P = 0.058). Compared with the control group, the rFMS and EAPNS groups showed the lower number of white blood cells in urine routine (P = 0.008 and P = 0.017; [Figure 2]).

QOL

There were significantly higher QOL scores in the three groups when compared with the pretreatment value (all P = 0.000). There was no significant difference in QOL scores between the rFMS and control groups (P = 0.137) and between the EAPNS and control group (P = 0.485). However, the rFMS group showed significant higher QOL scores than the EAPNS group (P = 0.001; [Figure 2]).

SAS and SDS scales

There were significant lower SAS and SDS scores in three groups when compared with the pretreatment value (all P = 0.000). The SAS score in the rFMS group was not significantly higher than that in the EAPNS group (P = 0.402). Whereas the EAPNS and rFMS groups showed lower scores than the control group (P = 0.003 and P = 0.036). The SDS score in the rFMS group was significantly lower than that in the EAPNS and control groups (P = 0.017 and P = 0.012; [Figure 2]).

 Discussion



Urine storage in and excretion from the human bladder is a very complex neuroregulatory activity (Hamid et al., 2018). Urination and storage are accomplished under the control and coordination of central access, peripheral nerves (parasympathetic and sympathetic somatic nerves), and the urethral sphincter. Dysfunction of urination and storage because of central and/or peripheral nerve injury is called NB. At present, NB can be divided into three types: urinary incontinence, urinary retention, and urinary incontinence and urinary retention (Georgopoulos and Apostolidis, 2017). Urinary retention can be further divided into detrusor relaxation-type and urethral sphincter functional obstruction-type. Improving the status of bladder function is an important treatment for patients with NB after SCI (Stöhrer et al., 2009). Different types of NB require different treatments. Previous studies failed to classify the management and treatment of NB (Niu et al., 2018; Steadman and Grill, 2020). In this study, the patient population was restricted to those with detrusor retardation-type NB. Currently, there are many methods for treating detrusor retardation-type NB after SCI, including drug therapy, surgical therapy, electrical stimulation therapy, magnetic stimulation therapy, and bladder function retraining (Qiu et al., 2008). How to use currently available treatments to produce a better therapeutic effect remains an area of continued discussion and research in the medical field.

The pudendal nerve originates from the motoneurons of the anterior horn of the S2–S4 spinal cord, and it has both motor and sensory function. Electric stimulation of the pudendal nerve is a special electric stimulation therapy, targeting the pudendal nerve (Cvetanovich et al., 2018). The frequency, intensity, and pulse width of pudendal nerve electrical stimulation can be adjusted to regulate the synergy of bladder detrusor and urethral sphincter function, improve the compliance of the bladder wall, increase bladder capacity, improve urination disorder, and promote bladder function recovery (Xie et al., 2014). Hansen et al. (2005) reported that pudendal nerve electroacupuncture stimulation therapy can improve urination efficiency in patients with NB after SCI. Boggs et al. (2006) found that the micturition efficiency induced by intermittent pudendal nerve electroacupuncture stimulation therapy was significantly higher than that induced by perfusion expansion micturition and intermittent sacral nerve electroacupuncture stimulation therapy. A previous study has shown that superficial stimulation of the pudendal nerve at twice the threshold can significantly improve the bladder volume and urination rate (Zhang et al., 2019). Wang and Zhang (2013) found that electroacupuncture of the pudendal nerve and strong electroacupuncture stimulation can significantly improve symptoms and quality of life in women with stress urinary incontinence. Drawing lessons from the above studies, we used EAPNS to treat detrusor retardation-type NB after SCI. The results of this study show that urodynamic indicators significantly improved after 4 weeks of treatment.

Studies have shown that after SCI, the functions of human corticospinal tract, primary motor cortex (M1), and spinal cord recover to some extent. Magnetic stimulation can cause long-term changes in excitability in these anatomical regions, which can significantly improve the control of autonomic movement, and has the potential to restore bladder function (Bunday and Perez, 2012). Bemelmans et al. (1992) proposed a new technique to obtain pelvic floor motor evoked potentials after magnetic stimulation of the cauda equina. One study found that magnetic stimulation of S3 nerve roots can stimulate bidirectional release of different neurotransmitters to excite and inhibit the bladder detrusor and urethral sphincter, and coordinate the detrusor and urethral sphincter to form a normal urination reflex, thus improving urination and promoting nerve regeneration and recovery of motor function (Jiao et al., 2012). Magnetic stimulation of the sacral nerves is a bidirectional regulation, balancing the stimulation and inhibition of urination control, thus contributing to the improvement of the two polar disorders of urinary retention and urge incontinence (Savic et al., 2017). The mechanism by which magnetic stimulation excites peripheral nerves promotes nerve growth and synaptic formation. Brodak et al. (1993) and El-Habashy et al. (2020) found that magnetic stimulation of sacral nerve roots over a period of time can induce detrusor contraction. In addition, studies have found that magnetic stimulation can induce bladder contraction in patients with SCI (Yamanishi et al., 2015; Vadalà et al., 2018). As such, the RU volume of bladder in patients with NB after SCI can be reduced, the incidence of urinary tract infection can be reduced, the self-care ability of patients can be improved, and nursing cost can be reduced. Therefore, this study was conducted to observe the clinical effects of magnetic stimulation of the sacral nerves on flaccid detrusor function in NB and to compare it with electroacupuncture of the pudendal nerve alone. The results showed that magnetic stimulation combined with acupuncture improved patients’ bladder function and quality of life more than acupuncture alone.

This study confirmed that the clinical effect of sacral nerve magnetic stimulation was significantly better than that of electroacupuncture, providing theoretical support for the treatment of NB after SCI. However, this study still had the following limitations. First, the sample size was small, which may affect the accuracy of the research conclusion to some extent. Second, the study period was short and the long-term efficacy was not followed up. Third, a standardized method of magnetic stimulation of the sacral nerve roots has not yet been formulated. Therefore, further study and discussion are required.

Author contributions

Data search: BCA, LLW and FG; data collection: YC; data analysis: JJZ and YL; manuscript writing: JJZ; manuscript correction: BCA, JJZ and YL. All authors approved the final version of the manuscript.

Conflicts of interest

The authors declare no conflicts of interest.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.[2]

References

1Amarenco G, Sheikh Ismaël S, Chesnel C, Charlanes A, F LEB (2017) Diagnosis and clinical evaluation of neurogenic bladder. Eur J Phys Rehabil Med 53:975-980.
2ASIA and ISCoS International Standards Committee (2019) The 2019 revision of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)-What’s new? Spinal Cord 57:815-817.