E-ISSN : 2757-7163
Materials and Methods: Patients completed the PTNS treatment with tapering protocols applied for 6, 9, 12, and 24 months. After 12 weeks of therapy, PTNS was applied at 14 day intervals for 3, at 21 day intervals for 3, and at 28 day intervals for 3 months. The patients completed a 3-day voiding diary at the 3rd, 6th, 9th, 12th, and 24th months. The patients were requested to complete validated questionnaires (ICIQ-SF, OAB-V8, OAB-q SF) within 3-month intervals thereafter during their enrolment in the study.
Results: The mean age of 57 patients who completed the PTNS treatment protocol and were included in the study was 42.6 ± 8.2 (23-64) years. Fifteen (26.3%) patients were male and 42 (73.6%) were female. The improvements for all voiding diary parameters were significant at 3rd, 6th, 9th, 12th, and 24th months when compared with the baseline. After 24 months, the daily frequencies of voiding decreased by 6.7 (p<0.001), urge urinary incontinence by 4.2 (p<0.001), urge by 8.4 (p<0.001), nocturia by 2.2 (p<0.001), and the mean voiding volume increased by 85.8 cc (p<0.001). No treatment-related side effects were reported in the patients for 24 months.
Conclusion: This study showed that the symptoms of the patients with NOAB due to MS improved after 24 months of PTNS treatment.
There are many medical and surgical treatment options for DO, but their therapeutic success is controversial. The firstline treatment of DO includes bladder training, pelvic floor muscle training, and anticholinergics. Since side effects of anticholinergic drugs which are among effective treatment options for DO such as dry mouth and constipation are common, only 20% of patients continue to take these drugs after 6 months [3,4]. Treatment options such as neuromodulation, intravesical botulinum toxin injection, bladder augmentation, detrusor myomectomy and urinary diversion are available for patients who discontinue the treatment due to its side effects, do not want to use drugs, or do not benefit from medical treatment.
Percutaneous tibial nerve stimulation (PTNS) can be preferred as a safe and effective treatment option for the patients with DO symptoms who have not benefited from conservative and medical therapy or did not respond to treatment with at least two oral anticholinergic drugs [2,5-8]. It has been reported that neuromodulation of the sacral nerve plexus (S2-4 roots) can be achieved by stimulating the posterior tibial nerve (PTN). The PTN contains mixed motorsensory fibers that originate from L5 through S3 in the spinal cord. It modulates the innervation to the bladder, urinary sphincter, and pelvic floor. The mechanism of PTNS in attenuating lower urinary tract symptoms (LUTS), however, is not yet fully understood [2,5,8].
The effectiveness of PTNS for LUTS in overactive bladder (OAB) has been demonstrated in several studies [9]. It has been also reported that interruption of PTNS treatment may result in the reappearance of OAB symptoms [10]. Therefore, the introduction of maintenance therapy for PTNS is important for the treatment plan. Our study aims to reveal the changes in LUTS after 24 months of maintenance PTNS therapy in MS patients.
Inclusion Criteria
The volunteer MS-linked NOAB patients aged 18-65 years
with neurogenic LUTS for more than 3 months, and did not
receive medical treatment including antimuscarinic drug(s) for
more than two weeks or tried useless conservative treatment
modalities without obtaining any therapeutic benefit were
included in the study.
Exclusion Criteria
Patients with DSD, peripheral nerve lesions, serious secondary
metabolic disease, prostate enlargement and/or bladder stone,
diabetes mellitus, severe cardiopulmonary complaints, urinary
system or vaginal infection, bladder malignancy or high-grade
dysplasia. Patients who had undergone continence surgery,
neuromodulation therapy applied from a different site or PTNS
treatment, botulinum toxin injection therapy for neurogenic
OAB in the last year or those using a pacemaker or implantable
defibrillator, pregnants or those planning to become pregnant
were not included in the study.
Urinalysis was performed at the start of the therapy and at each visit to exclude the possibility of urinary tract infection from all patients. The expanded disability status scale (EDSS) was used to assess disability due to MS. Patients with a higher EDSS score (>7) were excluded from the study. Overactive Bladder Questionnaire Short Form (OAB-q SF), Overactive Bladder Questionnaire (OAB-V8), and International Continence Interrogation Questionnaire Short Form (ICIQ-SF) were used to determine the levels of discomfort before, and after treatment of NOAB.
PTNS Technique
PTNS was performed with a 26G or 34G concentric needle
(Medtronic, Denmark) inserted into the posterior side of the
medial malleolus. The PTN is most easily accessible from the
posterior side of the medial malleolus. Following the finding of
the correct point reaching the nerve via the percutaneous route,
electrical stimuli are delivered by observing action potential
traces on the screen or the rhythmic digital plantar flexion in
the toe. Electrical stimulation is delivered for a duration of 200
μs and at a frequency of 10-20 Hz, 1.5 times the amplitude of
the motor response or at the level that the patient can withstand
(average 0.5-9.0 mA). The electrical excitation generator
can be supplied with portable devices or via an EMG device.
EMG device was used in our study (Medtronic Key Point Net,
Denmark).
Application Protocol
The treatment was initially administered once a week for 30
minutes for 12 weeks. In this study, the treatment protocol was
extended up to 24 months from the beginning with longer intervals
between PTNS sessions. This protocol is based on previous studies
of PTNS on the treatment of idiopathic OAB [11].
PTNS was administered at the beginning of treatment every 7 days for 12 weeks, every 14 days for the next 3 months, every 21 days for the next 3 months and then every 28 days for 24 months. Patients were evaluated using a 3-day voiding diary, ICIQ-SF, OAB-V8, and OAB-q SF questionnaires at baseline and at the 3rd, 6th, 9th, 12th, and 24th months. Neurological and urological evaluations were performed at each session to determine any side effects, emergency medical conditions, or diagnoses.
Statistical analysis
The results were evaluated in Statistical Package for Social
Sciences (SPSS) 22.0 (SPSS Inc, Chicago, IL, USA) program.
Descriptive statistical methods (number, percentage, mean,
standard deviation) were used in the analysis of the data. In the
comparison of quantitative data between two groups, t-test was
used for independent groups and paired t-test for dependent
variables. The repeated measurement ANOVA test was used
to compare the treatment success rates of the groups. Results
were considered statistically significant at p<0.05 within a 95%
confidence interval.
According to the voiding diary parameters, the improvement in neurogenic overactive bladder symptoms including the frequency of voiding, nocturia, urgency, urinary incontinence, and voiding volume was statistically significant at the third month of treatment in patients receiving PTNS. Improvements in all voiding diary parameters first started to be observed at the 3rd month and the recovery was statistically significant at the 3rd, 6th, 9th, 12th, and 24th months compared to baseline. However, there was no significant difference between the 3rd month and the subsequent visits in terms of these parameters (p>0.001). At the end of the 24th month, daily frequencies of voiding (6.7) (p<0.001), urinary incontinence (4.2) (p<0.001), urgency (8.4) (p<0.001) and nocturia (2.2) (p<0.001) were as indicated and voiding volume increased by an average of 85.8 cc (p<0.001) (Table 1), (Figure 1-4). According to the OAB-V8 questionnaire, there was a statistically significant improvement in symptom severity at the 3rd, 6th, 9th, 12th and 24th months compared to baseline (p<0.001) (Table 2), (Figure 5). According to the OAB-q questionnaire, there was a statistically significant improvement in symptom severity and health-related quality of life (HRQOL) at the 3rd, 6th, 9th, 12th, and 24th months compared to baseline (p<0.001) (Table 2), (Figure 6). The ICIQSF questionnaire showed a significant improvement in the severity of symptoms at 3rd, 6th, 9th, 12th, and 24th months compared to baseline (p<0.001) (Table 2), (Figure 7). No side effects related to treatment were reported for 24 months. Five patients (8.7%) had mild to moderate pain at the needle insertion site, cramps and tingling in the legs of unknown association with PTNS.
Figure 1. Change of urinary incontinence according to months before and after PTNS treatment
Figure 2. Change in the complaints of urgency before and after PTNS treatment according to months
Figure 3. Variation of voiding volume by months before and after PTNS treatment
Figure 4. Changes of nocturia complaints before and after PTNS treatment according to months
Figure 5. Change in OAB-V8 months before and after PTNS treatment
Figure 6. Variation of OAB-q months before and after PTNS treatment
Neuromodulation can be applied in many different ways including direct bladder stimulation, intravesical electrical stimulation, pelvic nerve stimulation, sacral spinal stimulation, pudendal nerve stimulation, electrical stimulation of thigh muscles, transcutaneous or percutaneous stimulation of PTN [13,14]. Among these techniques, PTNS is a minimally invasive technique with greater treatment efficacy than other techniques. It is an alternative treatment for patients with OAB [3,4].
PTNS was first described by McGuire et al. who placed the transcutaneous electrode on PTN and grounding electrode on the corresponding contralateral side for the treatment of incontinence. [15]. In another study, Stoller et al., performed this method by placing a percutaneous needle electrode on the ipsilateral side [16]. Since then, there have been many studies investigating the efficacy of intermittent PTNS treatment of OAB.
Although many studies have been conducted in NOAB, the effective mechanism of action of PTNS is still unclear. Danisman et al. showed that after PTNS, the number of mast cells in the bladder of female rats decreased [17]. Finazzi-Agro et al. demonstrated a significant increase in the amplitude of delayed somatosensory evoked potentials for 24 hours at the end of a 12-session PTNS treatment and indicated that it exerts its effect on supraspinal centers [5]. This finding may lead to a change in our understanding of mechanism of sensory stimuli, suggesting a possible reorganization of cortical stimulation after PTNS treatment [18].
Vandoninck et al. demonstrated the effects of PTNS in a study involving 35 women with refractory idiopathic DO. They reported that 71% of patients responded to PTNS treatment and there was a greater than 50% reduction in the frequency of urge incontinence in the patient group compared to placebo (p<0.001) [19]. A multicenter study of 53 female patients with refractory idiopathic OAB has shown that 71% of the patients had significant improvement in their complaints, with 35% improvement in urinary incontinence, 20% in QoL, and 30% reduction in pain [20]. In their study, MacDiarmid et al., reported its therapeutic effectiveness in patients with idiopathic OAB who completed a 12-week session consecutively and the persistent PTNS treatment for 1 year. They showed that after 12 weeks of treatment, it was an effective treatment in decreasing symptoms of voiding frequency, nocturia, urgency, and urinary incontinence, and increasing voiding volume with resultant persistent improvement of symptoms during 12 months of prolonged treatment [21]. In another study, patients receiving PTNS and PTNS + lowdose oxybutynin were compared and their response rates were reported as 61.6% and 83.2%, respectively [22]. In another study conducted with MS patients with refractory LUTS, the symptoms of 89% of the patients who received PTNS treatment had improved at a rate of 70% with a significant improvement in their QoLs [7]. De Seze et al. published 3-month results of TTNS administered transcutaneously to 70 MS patients and showed that more than 80% of patients had congestive urinary incontinence and clinical improvement in urinary frequency [23]. TTNS was also shown to be effective in the review by Tu et al. [24]. Similarly, in our study, we have seen an improvement in all of these parameters thanks to PTNS treatment starting from the 3rd month compared to the baseline.
Kabay et al. investigated the acute urodynamic effects of PTNS in MS and Parkinson"s disease patients [3,4]. These studies showed an increase in voluntary detrusor contractions and cystometric capacity. Another study demonstrated the efficacy of 12-week PTNS treatment in clinical and urodynamic parameters in MS patients with LUTS. This study also reported that 12-month treatment of PTNS in MS patients with NOAB was effective and safe [25].
The improvement achieved as a result of the first 12 weeks of treatment was maintained for patients who received this treatment for 12 months. It has been reported that the frequency of voiding, voided urine volume, nocturia, urinary incontinence, and urgency symptoms improved significantly compared to baseline and this improvement lasted for 12 months during treatment. Consistent with voiding diary results, ICIQ-SF, OAB-q, and OAB-V8 scores confirmed sustained improvement over 12 months, reflecting the clinical significance of symptomatic improvement in patients [25,26]. In our study, we observed an improvement in ICIQ-SF, OAB-V8, and OAB-q scores starting from the 3rd month compared to the baseline, and this improvement continued similarly during the treatment.
In our study, in accordance with the literature, a significant improvement was observed in all parameters of the voiding diary starting from 3 months, and extending up to 24 months. This improvement continued until 24 months with maintenance therapy. However, there was no statistically significant change in the effectiveness of symptomatic treatment after 3 months. In our study, we observed an improvement in ICIQ-SF, OAB-V8, and OAB-q scores starting from the 3rd month compared to the baseline, and this improvement was maintained during the 24-month treatment. We think that this improvement, which was observed starting from the 3rd month of the treatment did not show any significant change during the ongoing controls which indicates limited effectiveness of PTNS. However, it also signifies that long-term effectiveness of PTNS has not regressed and continues to be effective thanks to this treatment protocol.
The limitation of this study is that it was conducted with a small number of patients. In addition, urodynamic examination was not performed during the follow-up of the patients after the diagnosis of NOAB was made. The reason why we could not perform urodynamic examination during follow-up in our study was that most of the patients did not accept urodynamic examination. In this case, we thought that the decrease in the number of patients we followed and included in the study would make it impossible to carry out the study further.
Ethics Committee Approval:The study was approved by the Clinical Research Ethics Committee of Canakkkale Onsekiz Mart University with the decision dated 05.08.2015 and numbered 2015-13.
Informed Consent: Written informed consent was obtained from patients who participated in this study.
Publication: The results of the study were not published in full or in part in form of abstracts.
Peer-review: Externally and internally peer-reviewed.
Authorship Contributions: Any contribution was not made by any individual not listed as an author. Concept – M.S., S.K., S.C.K.; Design – M.S., B.A., S.K., S.C.K.; Supervision – S.C.K., S.K., B.A.; Resources – M.S., S.K., B.A.; Materials – M.S., S.C.K., S.K.; Data Collection and/or Processing – M.S., S.K., B.A.; Analysis and/or Interpretation – M.S., B.A., S.K., S.C.K.; Literature Search – M.S., B.A.; Writing Manuscript – M.S., B.A., S.K., S.C.K.; Critical Review – M.S., S.K., B.A., S.C.K.
Conflict of Interest: The authors declare that they have no conflict of interest.
Financial Disclosure: The authors declare that this study received no financial support.
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