Physiotherapy intervention on monosymptomatic nocturnal enuresis: a systematic review

Abstract

INTRODUCTION

Monosymptomatic nocturnal enuresis is the most common voiding disorder and is associated with a decrease in the well-being and quality of life. Physiotherapy intervention has emerged as a second line treatment, and the treatment strategies that have been most commonly used to treat children and adolescents with monosymptomatic nocturnal enuresis are electrostimulation, magnetotherapy, biofeedback, behavioral therapy and pelvic floor muscle training. Establishing the efficacy of these physiotherapy strategies in children and adolescents up to 16 years is the aim of this Systematic Review.

EVIDENCE ACQUISITION

Research was conducted from December 2022 to November 2023 in five databases: PubMed, Web of Science, Academic Search Complete, CINAHL Plus, and PEDro and two independent reviewers assessed titles and abstracts and judged each article for eligibility. Ten randomized-controlled trials written in English remained for analysis. PRISMA guidelines were followed, and the protocol was registered in PROSPERO database.

EVIDENCE SYNTHESIS

Electrostimulation was the most studied therapeutic modality and the one that showed better results, with significant improvements on bladder volumes and wet nights frequency, especially when used in association with Behavioral Therapy, Biofeedback and Pelvic Floor Muscle Training. Magnetotherapy presented less evidence.

CONCLUSIONS

The obtained results demonstrated that physiotherapy treatment strategies may be of added value in clinical practice, as they were well tolerated, and provided a safe and effective contribution to second line treatment options for children and adolescents with refractory Monosymptomatic Nocturnal Enuresis to first line treatments.

Introduction

The International Children’s Continence Society (ICCS) defines enuresis as an intermittent and involuntary loss of urine during sleep time, after the age of five years.^{1, 2} Studies report a significant number of children experiencing difficulty in attaining dry nights, with negative impact on their psychosocial and emotional well-being.^{1, 3-8} Approximately 15% to 20% of five-year-old children suffer from this condition. At the age of seven years the prevalence is around 10%, at ten years around 5%, and in teenagers and young adults the prevalence drops to 1% to 3%.^{1, 2, 6-10} If the child does not have any other lower urinary tract symptom, enuresis can be classified as monosymptomatic nocturnal enuresis (MNE) and accounts for 80% to 85% of the cases,^{1, 6, 10} being the most common voiding disorder encountered by pediatricians.¹ Enuresis can also be classified as primary and secondary. If the child has not been dry for a period greater than six months, is defined as primary, and secondary if it happens after a six month dry period.^{1, 2, 10, 11} Three mechanisms of MNE are described in the literature: small functional bladder capacity, nocturnal polyuria and sleep arousal dysfunction.^{1-3, 6, 7, 11} Although without treatment and per year, 15% of those affected, are expected to have a spontaneous cure rate, the chance of becoming dry is lower if the enuresis is frequent.^{2, 7, 8, 10} Current first line treatments target the underlying physiopathology of MNE and include enuresis alarm training and desmopressin.^{2, 6, 7, 9} Even though, with unclear or lower evidence, behavioral therapy (BT) can also be included in these first line treatments.^{1, 2, 4, 7, 8} However, a third of all these children remain refractory or quit treatments, so new treatment options are needed.^{6, 9} Several studies are starting to recognize physiotherapy as a solid second line treatment, with promising results, and without side effects.^{3-6, 11} Physiotherapy has been widely used in adults and children with daytime urinary incontinence with high evidence levels.^{3, 6, 12, 13} Physiotherapy includes strategies like different types of electrostimulation (ES), magnetotherapy (MGT), biofeedback (BF), BT and pelvic floor muscle training (PFMT). Establishing the efficacy of these strategies in children with MNE is the aim of this Systematic Review (SR).

Evidence acquisition

Design

This SR is reported as per PRISMA guidelines.¹⁴ The protocol was published and registered in the PROSPERO database (CRD42022314390).

Information sources and literature search strategy

Five databases were searched from December 2022 to November 2023: PubMed, Web of Science, Academic Search Complete, CINAHL Plus and PEDro. The overall search strategy was developed by two independent reviewers. The search terms used were (“Nocturnal Enuresis” or “Enuresis”) AND (“Physiotherapy” or “Physical Therapy”) AND (“Treatment”).

Inclusion and exclusion criteria

The present SR focuses on original full-length articles published in English, in scientific journals that contained physiotherapy intervention strategies used to treat children and adolescents with MNE. No restrictions occurred regarding type of timeframe for completing the interventions or type of study settings in which interventions were conducted. The following inclusion criteria were applied to retrieved studies: 1) randomized controlled trials (RCT); 2) original research articles written in English; 3) participants diagnosed with MNE; 4) children and adolescents up to 16 years; 5) physiotherapy treatment strategies. The exclusion criteria defined were: 1) animal studies; 2) unavailable full-text studies.

Study selection

Two independent reviewers assessed all remaining titles and abstracts and judged each article for eligibility. If this was insufficient for determining eligibility, then the full-text articles were retrieved. Full-text articles were obtained from the remaining eligible abstracts. One reviewer independently screened the references lists of all included articles for any additional relevant studies. During each review phase, regular meetings were held to discuss criteria. Discussion and consensus resolved disagreements among reviewers.

Methodological quality assessment

The methodological quality of included studies was evaluated by two independent reviewers, using PEDro Scale.^{15, 16} PEDro Scale was developed by Moseley et al. in 1999,¹⁷ and it aims, through 11 items, to evaluate whether the criteria of an RCT were followed under ideal conditions, and to assess methodological quality of studies. Eight domains (2-9) evaluate internal validation and two (10-11) evaluate statistical information so that the results can be interpreted. There is an additional item (item 1) that evaluate external validation or the applicability of the trial, but it is not used to calculate the scale final score.^14-16 It is a practical tool, but knowledge of the scientific methodology is required, therefore it has to be used by a trained examiner, with the requirements demanded by the PEDro steering group.¹⁴

Evidence synthesis

Study selection results are documented with the PRISMA flow diagram (Figure 1). A total of 965 articles were identified, of which 139 were immediately excluded (duplications). After revision of the titles and abstracts more 686 articles were excluded for not meeting the inclusion criteria and 11 were not retrieved. From the 129 articles that remained, 119 were excluded for having a different study design from the intended in this SR and, at the end, 10 articles were included in this SR.

Figure 1.

—Flow diagram of the selected studies (PRISMA).

Supplementary Digital Material 1 (Supplementary Table I)^{3-5, 9, 11-13, 18-20} presents a summary of the analysis of the selected articles. Samples were recruited in urological clinical departments and comprised children and adolescents of both sexes, from 5 to 16 years. Study 4 did not present the age range of their subjects. All subjects had primary monosymptomatic enuresis (PMNE). Concerning outcome measures all studies evaluated the number of wet nights and study 4, 5 and 9 also studied the clinical response outlined by the ICSS. The studies 3, 6, 7, 8 and 10 collected data about bladder volumes, mainly first morning voided volume (FMV) and maximum voided volume (MVV). Study 10 complemented its assessment with the recording of pelvic floor electromyographic activity and study 6 also assessed quality of life.

From the ten studies selected six studies (study 4, 5, 6, 7, 8 and 10) applied different types of ES as treatment strategy. The types of ES implemented were posterior tibial nerve stimulation (study 4 and 6), intra-anal ES (study 10) and transcutaneous electrical ES (study 5, 7 and 8). Four studies researched the effects of BT on MNE (study 1, 2, 5, 7, 9 and 10). All of them applied simple behavioral interventions like reward systems, fluid restriction, scheduled voiding and wakening, toilet training and diet. Study 3 used MGT as treatment strategy and study 10 also used intra-anal biofeedback (BF) and PFMT. The achieved results of each treatment strategy can be seen in Supplementary Table I and organized by therapy in the following text.

Electrostimulation

ES was the most often applied strategy, although different kinds of ES and methodologies were used.

Posterior tibial nerve stimulation (PTNS) was evaluated in two studies (Study 4⁵ and 6).¹² It was observed significant positive results in terms of number of wet nights (the average number of wet nights per week decreased from 4.7 to 2.6, P=0.002 and from 5.90±0.41 to 1.20±0.14, P=0.001, respectively), ICSS clinical response (28.6% had a complete response and 50% had a partial response in study 4), MVV (increased from a mean of 266.57±82 to 280.14±71.81 cc, P=0.022 in study 4; and from a mean of 160±15 to 192±12 cc, P=0.001, in study 6) and quality of life (increased from a mean of 1.80±0.04 to 3.90±0.73, P=0.001 in study 6). Nevertheless, the results of study 4 showed some deterioration in the follow-up.¹²

Transcutaneous Electrical Nerve Stimulation (TENS) was evaluated in three studies (Study 5,¹³ 7³ and 8).⁹ It was observed significant positive results in terms of number/percentage of wet nights in study 5 and 7 (from 78.3% to 31.2%, P=0.0038 in study 5; from 5.7±2 to 3.1±2.9 and 1.5±2, P=0.004, after 2 months and at the 1-year follow-up, respectively in study 7) but it was not found a significant difference in the number of wet nights after treatment with TENS (P value not declared) in study 8. According to ICCS standardization criteria, in study 5, 15% responded to treatment and 56% had a partial response but no patient had complete resolution of symptoms; in study 7, 67% had a complete response, 25% had a partial response; and in study 8 no children experienced a full response. It was observed significant positive results in the MVV in study 7 and 8 (from 163±61 to 326±126, P=0.03 at the 2-month follow-up; and from -16±56 mL to 28±70 mL, P<0.05, respectively).

In study 10¹¹ it was evaluated Intra-anal Electrical Stimulation (IAES). It was observed a statistically significant improvement on the post-treatment mean values of nocturnal bladder capacity on dry and wet nights (increased from 120±14.14 to 364.4±48.05, and from 108.84±30.63 to 322±23.87, P=0.037), an increased PFMs activity peak (from 95.6±8.1 to 174.5±10.2, P<0.05), an increased PFMs activity speed (from 12.2±0.8 to 36±4.6, P<0.05) and decreased frequency of wet nights (from 93.4 to 14.3, P<0.05). According to clinical response, 86,7% of the sample became partial responders and 13,3% complete responders.

Behavioral therapy

Study 1²⁰ named BT as Dry-Bed Training and performed 2 experiments. The second one consisted of 6 groups, but only one evaluated BT alone (scheduled voiding and awakening). Progress was monitored at 3, 6 and 12 months after reaching the success criterion. The Dry-Bed procedure without urine-alarm treatment was markedly less effective than the other strategies, since only 5 of the 20 children reached the dryness criterion of 14 consecutive dry nights, and since the mean number of days to last wet night and of wet nights were much higher (116 and 78, respectively) than in the other groups. On the other hand, alarm therapy in conjunction with BT achieves higher efficacy values compared to alarm therapy alone (20 vs. 16 cases reaching dryness criterion; 32, 40 and 34 vs. 63 mean number of days to last wet night; 14 and 11 vs. 26 mean number of wet nights).

Study 2¹⁹ evaluated the effectiveness of desmopressin, BT and their combination. The BT consisted of a 4 stages program, performed once a week for 8 weeks and then once a month during the 2-month follow-up period. A substantial reduction was observed, from 5.5 to 3.0 nights per week (45% reduction). Desmopressin alone or in combination with BT doubled the rate of total dryness compared with BT, however the latter achieved significantly more permanent results, since the percentage of relapse was lower (50%) than group A (82%) and group C (90%). More than half the parents expressed satisfaction with BT procedure.

In study 4,⁵ in addition to the application of active and sham PTNS in the EG and CG, respectively, both groups maintained BT. Since BT was evaluated together with sham PTNS and since sham therapy has the ability to change the physiological response of a subject, it is not possible to ascertain the effectiveness of BT alone. Even so, the mean number of wet nights decreased from 5.1±1.4 to 4.7±2.1, P=0.041 and there were two patients (14.3%) with a partial response, while the remaining individuals did not get any response. This allows us to speculate that BT was not very effective in reducing MNE otherwise, even with a sham therapy at the same time, the results would be much more favorable. The same happened in study 8,⁹ but with TENS.

As for in study 5,¹³ BT was evaluated in the CG and the EG applied BT along with TENS. Both groups had significant results in reducing the rate of wet nights but there was a significantly greater increase in dry nights in the EG. Study 7³ had a very similar methodology and results. BT was evaluated alone in the CG and together with TENS in EG. In the CG, the mean number of wet nights per week decreased from 5.4±2 to 3.3±3 and 1.1±2, P=0.003 after 2 months and at 1-year follow-up, with an improvement score of 46%. However, the improvement score in the EG was significantly higher (78%).

Differently to the other studies, in study 6¹² all participants were instructed to perform certain functions throughout the treatment without calling it BT, despite being so. However, similarly to study 4,⁵ the CG is tested with another therapy (bedwetting alarm) in addition to BT. There was a decrease in the frequency of NE from 6.30±0.23 to 3.40±0.35, P=0.001, an increase in MVV from 155±14 to 176±10, P=0.001, and an increase in quality of life assessment score from 1.56±0.09 to 2.80±0.05, P=0.001. Although the results were significantly positive, the EG had higher scores and moreover it is not possible to conclude the effectiveness of BT alone in reducing MNE.

Study 9 exclusively investigated BT.⁴ The study divided the sample in three groups and each group was instructed to perform BT differently - as a written guideline, with a parental control checklist, and as an oral guideline together with desmopressin. Results showed that the compliance and treatment response was lower in the written guideline group (54.5% compliant, 22.7% partial compliant; 9.09% responder and 45.5% partial responder, P=0.001) and higher in the other two groups (80% compliant and 10% partial compliant; 60% responder and 15% partial responder in group II; 66.7% compliant and 23.8% partial compliant; 76.2% responder and 9.5% partial responder in group III). No significant difference was determined in the compliance rates of groups II and III (P=0.12) however group II was determined to be highly compliant to behavioral therapy compared to the other groups.

Study 10¹¹ evaluated BT together with PFMT in the CG. The EGs, in addition to the same therapies as the CG, also applied IAES and BF. The CG obtained some significant results in the increased PFMs activity peak (from 93±7.6 to 93.7±9.1, P=0.018), increased PFMs activity speed (from 11.8±1.4 to 12.8±1.7, P=0.017) and decreased frequency of wet nights (from 94.1 to 66.1, P=0.000), however the score was lower when compared to the other two groups. The mean values of nocturnal bladder capacity on dry and wet nights was not significantly different (P=0.531).

Intra-anal biofeedback

Intra-anal BF (IABF) was evaluated in study 10¹¹ along with other therapeutic modalities. It presented significant results related to the increase of nocturnal bladder capacity on dry and wet nights (from 122±16.43 to 202.22±33.87, and from 111.2±29.48 to 180.83±28.74, P<0.05 respectively), increased PFMs activity peak (from 93.2±7.1 to 160.2±7, P<0.05), increased PFMs activity speed (from 12±1.4 to 30.1±4.5, P<0.05) and decreased frequency of wet nights (from 92.4 to 51.6, P<0.05), however not so expressive as IAES.

Pelvic floor muscular training

As already mentioned above, PFMT was also evaluated in study 10¹¹ along with BT as the CG, compared to IAES and IABF. The results are the same as presented in the BT section.

Magnetotherapy

MGT was only investigated in study 3¹⁸ and the results of this pilot study point to a significant reduction in wet nights (from 3.1 to 1.3, P=0.028) and increase in bladder volume at the strong desire to void (from 215.3 to 264.3, P=0.022). The increase in bladder volume at the first desire to void was marginally significant (from 106.3 to 140.5, P=0.059) and the increase in bladder capacity was not statistically significant (P=0.11). These scores were much higher compared to the CG, which were not statistically significant (P=0,35; P=0,17; P=0.74; P=0.068, respectively).

A lack of homogeneity between intervention methodologies was seen through the ten studies and only study 1, 2, 5 and 7 presented long term follow-up results. Studies 4, 8 and 10 worked with refractory MNE while the other studies did not mention that information or only worked with first time treated children.

Risk of bias of the included studies was analyzed and represented in Figure 2.

Figure 2.

—Representation of bias assessment risk of the included studies.

Discussion

The purpose of this SR was to evaluate the effectiveness of physiotherapy strategies in children and adolescents with MNE. While there is some evidence of high methodological quality for first line treatments of MNE (enuresis alarm training and desmopressin), there is limited evidence about second line treatments. Second-line treatments are an emerging need since both enuresis alarm training, and desmopressin have limitations and side effects.^{6, 8} It is also consensual that some of these children and adolescents are resistant to this type of treatments.⁸ To date, no treatment proposed for resolution of EN has been observed to be completely effective, with more than a third of patients exhibiting an unsatisfactory response to first-line treatments.¹³

Considering the reality that this clinical condition faces, studies about the effect of physiotherapy on MNE, as second line-treatment, have been progressing steadily. This SR identified 10 studies that applied different therapeutic modalities – ES, BT, BF, PFMT and MGT that presented different outcomes and evidence levels.

Electrostimulation

Studies have been showing promising results on children and adolescents with MNE, regarding ES.^{1, 3, 5, 6, 11-13, 21-30} Of all the strategies included in this SR this is the most studied therapeutic modality. It can be applied through invasive methods (vaginally or intra-anally) and through non-invasive methods (percutaneous and transcutaneous). It’s painless, safe and well-tolerated by the different samples.^{3, 6, 9} Few side effects were reported.^{6, 9}

With regard to invasive techniques, one study evaluated the effect of intra-anal electrostimulation. Taking into account the context and population under study, it is natural that the scientific community gives preference to non-invasive methods. Nevertheless, the results showed that intra-anal ES was the more effective therapeutic modality applied in study 10, ¹¹ obtaining statistically significant improvement on bladder volumes, wet nights frequency and PFMs electromyographic activity. Besides intra-anal ES, the experimental group also performed BT and PFM training that was also applied to the control group. The significant improvement in all measured outcomes in the ES group might be attributed to the pudendal nerve stimulation, which improves the PFMs contraction ability, the bladder capacity, the reduction in wet nights and the normalization of the voiding pattern in children with MNE.^{3, 11, 13} ES helps to reestablish the balance between facilitatory and inhibitory control by means of enhancing peripheral and central neuroplasticity.²¹ Furthermore, direct stimulation of the nerve was more beneficial than stimulation of the muscle. A wide and synchronous stimulation pattern and an increased conduction velocity was already reported in favor of ES.^{21, 28} It nonspecifically stimulates both fast, and slow fibers at either low, or high intensity and allows the activation of smooth muscle fibers, which are difficult to reach by active exercises.^{21, 26}

Percutaneous ES is also becoming a viable non-invasive method applied to children and adolescents with MNE. It has been successfully used for overactive bladder syndrome and lower urinary tract in adults.¹² PTNS was researched in study 4 and 6, with both studies presenting similar methodologies (although not equal) concerning PTNS application. There was a significant improvement in recovery rate, a significant reduction in the frequency of nocturnal enuresis and an increase in bladder volumes. Participants’ quality of life and self-esteem also improved as seen in Nuhoglu’s study.⁵ Nevertheless, the results of study 4 showed some deterioration in the follow-up,¹² suggesting that PTNS may have temporary efficacy and the need for maintenance treatment which was already reported by Van der Pal.²⁵ That effect was not reported by Capitanucci et al., that found that the improvement persisted at 2-year follow-up.²⁹ It is important to note that study 6 did not perform follow-up and that both the experimental group and the control group underwent enuresis bedwetting alarm and unspecified medical treatment. Despite the good outcomes, the mode of action of PTNS is still unknown.^{5, 12} Some authors hypothesize that the tibial nerve stimulation contributes directly to sensory and motor control of the urinary bladder and pelvic floor, inhibits the detrusor, increases bladder capacity and improves cortical organization triggered by peripheral neuromodulation.^{22-24, 30}

Considering the results that transcutaneous ES already achieved in daytime overactive bladder symptoms it was expected that this type of ES would be applied and studied in MNE obtaining good results.^{3, 13} It is assumed that nerve ES is more efficient in the pediatric age group since children have higher neural plasticity.^{2, 3} Neurophysiological and neuroimaging evidence suggest that transcutaneous ES acts directly on the neurological system, resulting in physiological changes with consequent neural reconditioning. Therapeutic effects work both peripherally by affecting muscle fibers and micturition reflexes and centrally by the restoration of brainstem and cortical activities.^{2, 3, 9, 13} Although the results described in the literature were consistent, data presented in the three studies analyzed were not consensual. Significant decrease in the number of wet nights and ICSS clinical response was reported in study 5 and 7^{3, 13} that used respectively an interferential current and TENS as forms of ES, associated with BT. The resolution rate was higher with the use of interferential current. However, exclusive treatment with TENS, used in study 8,⁹ did not lead to significant changes on the number of wet nights and on bladder volumes. It can be hypothesized that the results of study 5 and 7 were due to the combination of the two therapies that acted on different etiological factors.¹³ All children received BT, which makes impossible to differentiate between the effect of BT and the actual effect of transcutaneous ES. Nevertheless, this option of including both therapies on the study designs was considered by the authors as a must have, because BT always has a role on MNE management.^{3, 13}

Behavioral therapy

Only one study exclusively investigated BT. The findings showed that the written checklist method increased the success rate up to 60%, creating a positive atmosphere and improving communication within the family, even if they had a low socio-economic status.⁴ BT is a safe method, however requires a high level parental involvement.^{1, 7} Older publications also studied the effectiveness of BT in studies with first line treatments. Despite not being as effective as first-line treatments, it has always been shown to produce positive and significant effects in reducing the frequency of wet nights. The other studies obtained results considering BT as a control group.^{3, 11, 13} This option of considering BT as the intervention to be included in the control groups was in fact transversal to the majority of studies and the results were very similar. The BT group obtained some significant results but with lower scores when compared to the experimental groups. So, it appears that simple behavioral interventions seem to be more effective than no active treatment.⁷ Nevertheless some authors continue to contest the true effect of this therapy when applied alone, stating that the results are still controversy, unclear or insufficient, due to lack of randomized, controlled studies.^{2, 11} The success rate of BT ranges between 18 and 22%⁴ and the main problem with many of the simple behavioral strategies are the high dropout and non-compliance rates.^{4, 7} However, for some authors the use of BT is indispensable and unavoidable, being an asset when combined with other strategies.^{3, 11, 13} The combined effect of BT with other techniques, play an essential role enhancing urinary function in children with MNE.¹³ It is believed that the results observed at the end of treatment are due to the fact that the combination of the two therapies benefits children with enuresis by acting on different etiological factors.¹¹ It’s already clear that the pathophysiology of MNE is multifactorial. Sleep arousal difficulties, polyuria and bladder dysfunction are the three suggested etiologies for MNE. Therefore, treatment should be based on the specific underlying etiologies of each patient.³ BT helps to correct the extrinsic body mechanism, enhancing children’s awareness of their pelvic components and their physiological functions and stimulating the active participation of children in correcting their habits, while the other techniques act directly on the neurological system, resulting in physiological changes with consequent neural reconditioning.^{11, 13}

Study 7 was the only one that referred to this therapy as standard urotherapy instead of BT. Although there is still some heterogeneity with regard to terminology and its protocols, all previously mentioned studies presented the same instructions. The common instructions across all studies were about decreasing evening liquid intake and avoiding liquids 2/3 hours before bedtime, restraining foods and liquids intake containing caffeine, adopting a high-fiber diet, keeping a diary of dry nights, use of rewards for dry nights and bladder training consisting of emptying the bladder before going to bed, immediately after waking up and every 3 to 4 hours during the day. In addition to these, study 7³ provided simple explanations of urinary and gastrointestinal tract function, instructed to an optimal toilet posture/frequency, to sitting on the toilet three times a day after mealtime in a relaxed position for five minutes and to avoid, in addition caffeine, tea, citric fruits, soft drinks, chocolate and irritating foods. Study 8⁹ did not mention what the BT consisted of. Study 9⁴ also added instructions to wake and lift the child for voiding during the night, to drink a sufficient amount of water, and to avoid holding urine.

Biofeedback

Only one study reported data about BF.¹¹ As it is an invasive technique, in this age group, the feasibility of carrying out experimental studies is reduced. The experimental BF group also performed BT and PFMT, that was also applied to the control group. Results were significant concerning bladder volumes, wet nights frequency and PFMs electromyographic activity and BF group presented better results than the control group. BF improves PFMs function in children with enuresis more rapidly than PFM training alone. BF training enhances the ability to contract and relax PFMs and sphincters and to recognize and make voluntary use of the PFMs¹¹ in an entertaining environment that plays an essential role in this population. Furthermore, BF modulates bladder instability by stimulating the detrusor inhibitory reflex.³¹

Pelvic floor muscle training

PFMT was also researched in study 10¹¹, along with BT as the control group and obtained some significant results, however, with lower scores when compared to the other two experimental groups that applied intra-anal ES and BF.

PFMT have a significant impact on improving children’s urinary functions, voiding muscle control, and bladder capacity.¹¹ They also are a fundamental part of the treatment for urinary incontinence^32-36 but in this age group it is difficult to voluntarily induce the contraction of PFMs, as well as to monitor and control the quality of the contraction. In this way, it seems safe to say that the use of other techniques that help to induce this contraction may be a path that produces better results.

Magnetotherapy

The preliminary results reported by study 3¹⁸ were promising but lack validation with larger samples. No more studies were carried out with this strategy which makes the evidence level low. It seems that MGT induces inhibitory effects on detrusor overactivity in a similar manner to electrical stimulation.²⁷ MGT has been reported to be safe, non-invasive, painless and easy to use, and without adverse effects.^{18, 27}

Limitations of the study

Although the articles included in the study were all RCTs, we must take into account its limitations (Figure 2) so that the analysis of the results is done accordingly, but also because they end up influencing the quality of the presented systematic review.

The first limitation identified was the diversity of terminologies existing for the same function or treatment strategy, such as urotherapy. Urotherapy can also be referred to as behavioral therapy, however, different treatment protocols were also found for the same intervention strategies.

This systematic review contained ten studies with different intervention strategies and different treatment protocols in the experimental groups. Control groups also did not show uniformity and few studies used placebo groups.

Some of the studies did not use double-blind methodology in the sample selection and randomization phase, increasing performance bias, and with the exception of one, none of the studies employed a blinded investigator in the data collection and analysis, leading with the detection bias.

Furthermore, the methodologies implemented in some studies, involving combined treatments, do not allow us to determine the isolated effectiveness of specific strategies. Small sample sizes resulted in poor statistical power in most of the trials.

Additionally, there was some lack of consistency in outcome measures between studies, and most studies lacked long-term follow-up data.

Finally, some of the studies did not report the reasons for dropouts, increasing the attrition bias.

Consequently, further high-quality RCTs are essential to explore the effects of physiotherapy in treating MNE in children. Future studies should incorporate larger sample sizes, longer follow-up periods, placebo controls, and standardization of outcome measures and treatment protocols.

In addition to the limitations of the included studies, the present systematic review, despite efforts to minimize biases, has its own limitations.

Despite the time interval between the initiation and the publication of this review, it was updated twice to ensure the inclusion of all relevant RCTs that met the inclusion criteria, thereby minimizing the risk of selection bias.

The fact that the sample in the majority of the studies was selected from a single hospital renders this sample non-representative of the population, increasing the risk of selection bias and consequently contributing to the selection bias in the present systematic review.

Another aspect that also increases the selection bias is the fact that this review included only studies written in English.

In addition, since the quality of the majority of the included studies is moderate, and in some cases, low, means that the methods used misrepresent the true values of the variables being studied, increasing the measurement bias.

Given that there is generally greater acceptance and publication of studies with positive results, there is a possibility that studies with negative or less positive results may have been conducted but not published. Thus, a systematic review always carries a risk of publication bias.

Conclusions

Physiotherapy treatment modalities can be used in clinical practice, as they were well tolerated, and provided a safe and efficacious contribution to second line treatment options for children and adolescents with refractory MNE to first line treatments.

The different types of ES generally showed significant results, especially when used in association with BT. The combination of ES with BT act on the different pathophysiological mechanisms of MNE. ES promotes neural reconditioning while BT endorses the children´s and family’s empowerment in the adoption of healthier lifestyles towards EN. BF, PMFT and MGT also showed interesting preliminary results, however, without the same evidence and impact as ES and BT. In this context, alongside the effectiveness of the identified physiotherapy strategies, the utilization of non-invasive methods can also provide added value in terms of treatment compliance.

Supplementary Digital Material 1

Supplementary Table I

Effects of Physiotherapy on children and adolescents with MNE: characteristics of each study selected.3-5, 9, 11-13, 18-20