Multiple sclerosis (MS) is a chronic disease of the nervous system that pathologically characterized by multiple areas of inflammation, demyelination, and glial scarring (sclerosis) in the white matter of the central nervous system (Harbo et al., 2013; Ghasemi et al., 2017). The clinical course of this disease varies from a benign and asymptomatic disease to a rapidly progressive and debilitating disease. MS commonly occurs at young age, and its peak is around 20–30 years of age.

The symptoms of this disease rarely start before the age of 10 years or after 60 years (Goldenberg, 2012; Harbo et al., 2013; Ghasemi et al., 2017). The main characteristic of this disease is the variability of symptoms; it also tends to change in terms of nature and severity over time (4). The common signs and symptoms of MS include muscle weakness, spasticity, reflex changes, sensory disorders, ataxia, nystagmus, vision disorders, autonomic symptoms (e.g., bladder, intestinal, and sexual disorders), and psychological symptoms. The McDonald diagnostic criteria are the best tool for a definitive diagnosis of this disease (Harbo et al., 2013). According to the McDonald diagnostic criteria, the presence of two or more attacks (dissemination in time), along with the clinical evidence and presence of two or more lesions in different parts of the central nervous system (dissemination in place), is necessary for a definite diagnosis of MS. Therefore, the criteria for the diagnosis of MS are based on the patient’s history, clinical examination findings, MRI findings of the brain and spinal cord, and examination of the cerebrospinal fluid.

Bladder and urinary disorders are the common symptoms of MS patients. Bladder care is essential to prevent disabilities, life-threatening infections, and stone formation in these patients. The bladder is probably the only visceral organ with smooth muscles, which is completely controlled by the cerebral cortex. A normal bladder function requires coordination between the sensory and motor components of both autonomic and somatic nervous systems.

Recent advanced studies on neural pathways and neurotransmitters have implicated the presence of neural pathways in the bladder function; therefore, many neurological diseases, including MS, can cause bladder dysfunction (Mahadeva et al., 2014; Khalaf et al., 2015).

The most common bladder dysfunction in MS is excessive bladder contraction. For the treatment of bladder disorders, anticholinergic antimuscarinic agents, such as solifenacin succinate can be used (Ragab et al., 2021). Also, posterior tibial nerve stimulation (PTNS) that involves the stimulation of lower urinary tract nerves often uses to stimulate the nervous pathway of bladder reflex (Staskin et al., 2012). The posterior tibial nerve consists of sensory and motor nerves that directly participates in controlling the sensations and movements of the bladder and pelvic floor muscles (Burks et al., 2010). In PTNS, depolarization of sacral somatic fibers and lumbar afferents indirectly inhibits the activity of the bladder, and can lead to the cessation of bladder contractions (Klingler et al., 2000; Amarenco et al., 2003). Indeed, the PTNS method is based on ancient Chinese acupuncture, which uses acupuncture points on the common peroneal or posterior tibial nerves to inhibit the bladder activity (Geirsson et al., 1993). In spite of available findings, it seems that there is still a need to conduct further research on PTNS. De Gennaro et al. (2011), study highlighted the need for further research on the PTNS. It may be one of the factors which limits the generalizability of previous studies is the selection of samples among patients with a specific disease (Fjorback et al., 2007). Overall, based on previous studies, urinary dysfunctions strongly affect the patient’s mental and psychological health, as well as quality of life (QOL) (Olujide and O’Sullivan, 2005; Mayer and Howard, 2008). According to new reference books, solifenacin succinate is the drug of choice for reducing the symptoms of overactive bladder (OAB). However, due to its side effects and high cost, physiotherapy has been also suggested. Therefore, the present study aimed to investigate and compare the effects of solifenacin succinate and PTNS on the treatment of OAB and improvement of QOL in patients with MS.

This clinical trial was conducted on MS patients with OAB in 2019. It was approved by the ethics committee of Ahvaz Jundishapur University of Medical Sciences (code: IR.AJUMS.HGOLESTAN.REC.1399.127) and registered in the Iranian Registry of Clinical Trials (code: IRCT20210207050277N1). Patients with MS, referred to the MS Association of Khuzestan, Iran, were first examined for OAB after confirming the absence of a urinary tract infection via urinalysis. This was achieved using the actionable questionnaire, which is an eight-item tool for screening MS patients with OAB. In this method, MS patients with OAB (with scores ≥3) were screened and diagnosed. Finally, according to the inclusion criteria, 70 patients were examined in this study.

The objectives of the study and the benefits of its results were explained to the patients, and they were ensured that they could withdraw from the study at any time. An informed consent form was obtained from all the patients. The volunteers were randomly divided into two groups (35 patients per group). Randomization was carried out by the random block method, where two patients were randomly assigned to each block, and a random code sequence was generated. For the first group, a drug treatment (solifenacin) was applied, while for the second group, PTNS was performed. The solifenacin group consisted of 28 female and 7 male patients, while the PTNS group consisted of 25 female and 10 male patients.

The mean age of the patients was 39.82 ± 9.088 years in the solifenacin group and 42.41 ± 9.175 years in the PTNS group; however, there was no significant difference between the two groups (p = 0.249). Two patients from the solifenacin group were excluded due to severe constipation. Also, one patient from the PTNS group was excluded due to death because of coronavirus disease. In the solifenacin group, 7 patients (21.2%) were male, and 26 patients (78.8%) were female, while in the PTNS group, 10 patients (29.4%) were male, and 24 patients (70.6%) were female; nevertheless, there was no significant difference regarding the distribution of patients in terms of gender (p = 0.441). Urinary incontinence due to solifenacin treatment increased from 2.97 ± 16.33 on the first day to 3.06 ± 5.97 in the 12th week; other findings are presented in Table 1.

Based on the results of GEE models, there was no significant difference between males and females for any dependent variables (p > 0.05). The findings showed that the trend of changes during the follow-up was not statistically significant for “physical health” and “Mental health” between the two groups (p > 0.05). Also, this result was established for other variables except for “urinary incontinence” and “Suffering from micturition during the day” (Table 1). The results showed that there were significant interactions between time and group for two factors, including “urinary incontinence” (p ≤ 0.001) and “suffering from micturition during the day” (p ≤ 0.001). In other words, there was a statistically significant difference in the urinary incontinence variable between the two groups over time (Figure 1). Based on the findings, the mean of urinary incontinence in the Solifenacin group was 1.41 units less than another group (β = −1.406, p < 0.001).

Also, the trend of changes in the variable suffering from micturition frequency during the day in the two groups over time was accompanied by a statistically significant difference (β = 0.884, p < 0.001). Based on the results, the patients in the Solifenacin group expressed less dissatisfaction with the number of urinations during the day compared to the patients in the PTNS group (Figure 2).

In the present study, the effect of surface electrical stimulation of the posterior tibial nerve and drug therapy (solifenacin) on the treatment of OAB and improvement of the QOL of patients with MS was investigated. To the best of our knowledge, comparison of solifenacin and PTNS therapeutic effects has not been performed on the MS patients in previous studies. The results showed significant between-group differences in the severity of urinary incontinence and the level of inconvenience due to the decrease in frequency of urination at night (for 12 weeks), while there were no significant differences regarding other variables. Also, the findings demonstrated no significant difference in the treatment effects between males and females in this study.

The present results are consistent with some previous studies examining the effects of drug therapy (solifenacin) and PTNS (Al-Danakh et al., 2022). In a study by van Rey and Heesakkers (2011), using 8.8 mg of solifenacin for 8 weeks led to a significant decrease in the number of pads used per day in the MS patients with OAB. Also, the intensity of urinary urgency decreased significantly.

Twenty out of 30 patients chose to continue solifenacin treatment after completing the study. The majority of the patients reported improved QOL. They concluded that solifenacin is effective in the treatment of patients with OAB symptoms (van Rey and Heesakkers, 2011). Besides, Chapple et al. (2006) studied the effects of solifenacin in 2,800 patients with symptoms of OAB, and the findings of this clinical trial showed that a solifenacin dose of 5 mg can be increased to 10 mg once a day. Compared to the placebo, it was effective in reducing incontinence, anxiety, and frequency of urination and increasing the volume of bladder emptying each time; the results of this clinical trial confirmed the use of solifenacin in the treatment of OAB (Chapple et al., 2006).

Additionally, Olujide and O’Sullivan (2005) evaluated the effect of internal stimulation of the posterior tibial nerve by passing a needle through the skin in 37 patients with OAB symptoms and 12 patients with non-obstructive urinary retention problems in 12 weeks. The QOL questionnaire and daily urinary excretion registration forms were used to evaluate the patients. The symptoms improved in 60% of the patients, although QOL improved more significantly in patients with OAB, which is consistent with the results of the present study. The findings of a study by Amarenco et al. (2003) also showed the positive effect of PTNS, which is in line with the current results. In their study, 44 patients with urgent and frequent urinary incontinence and emergencies, caused by an overworked bladder, were selected among patients without any specific neurological diseases, as well as patients with MS, spinal cord injuries, and Parkinson’s disease. Their bladder capacity was compared before and after electrical PTNS. The bladder capacity of 22 patients increased by about 100 ml, which indicates the immediate effect of this intervention; however, in their study, no control group was included to determine the effect of stimulation more precisely, and the participants included both neurological and non-neurological patients. Also, the final results of these two groups were not compared to determine the effect of this intervention more accurately.

Also, Finazzi Agrò et al. (2005) investigated the effect of PTNS over 4 weeks (three sessions every week, 30 min per session) in women with OAB and incontinence. In their study, PTNS was the only intervention used for the treatment group. For the control group, placebo stimulation was performed, and no other intervention with proven effectiveness was used to treat these patients. The results showed that in 71% of the patients in the treatment group, PTNS was an effective intervention. Therefore, similar to the results of the current study, the QOL score increased, and the frequency of urination decreased, whereas in the control group with placebo stimulation, no therapeutic effects were observed.

The results of the current study showed that both drug therapy with solifenacin and PTNS for OAB reduced the severity of urinary symptoms (e.g., urinary incontinence) and improved the QOL of patients with MS.

The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

NM and NO wrote the manuscript and contributed in conceptualization of the work. LK, GS, and MS collected the samples. MJ provided the ideas and critically edited the entire composition of the manuscript. All authors contributed to the article and approved the submitted version.