Refractory Monosymptomatic Nocturnal Enuresis Treatment

Refractory Monosymptomatic zero(prenominal)turnal Enuresis TreatmentRole of Posterior Tibial Nerve Stimulation in the Treatment ofRefractory Monosymptomatic Nocturnal Enuresis A Pilot StudyAli Abdel Raheem,* Yasser Farahat, Osama El-Gamal, Maged Ragab,Mohamed Radwan, Abdel Hamid El-Bahnasy, Abdel Naser El-Gamasyand Mohamed RasheedPurpose We evaluated the betimes clinical and urodynamic results of posterior tibial eye stimulation in unhurrieds with refractory monosymptomatic nocturnal enuresis.Materials and Methods We randomly assigned 28 patients with refractorymonosymptomatic nocturnal enuresis to 2 equal pigeonholings. Group 1 received ahebdomadary session of posterior tibial nerve stimulation for 12 weeks and radical 2 wasthe placebo classify. Evaluation was performed in each group at baseline and after(prenominal)(prenominal)posterior tibial nerve stimulation to compare clinical and urodynamic findings.Another clinical assessment was done 3 months after the first followup. Results The 2 groups were similar in baseline clinical and urodynamic data.Over altogether, 13 patients (46.4%) had detrusor overactivity and 14 (50%) had change magnituded vesica capacity. After treatment 11 group 1 patients (78.6%) had a softenial or full(a) solution to posterior tibial nerve stimulation but only 2 (14.3%) in group 2 had a uncomplete chemical reaction (p 0.002). Also, the honest number of wet nights in group 1 wasimportantly lower than at baseline (p 0.002). all in all urodynamic parameters cruciallyimproved in group 1. In contrast, the number of wet nights and urodynamicparameters did not change importantly in group 2. At 3-month followup the numberof patients with a partial or full reaction in group 1 had decreased from 11 (78.6%)to 6 (42.9%). No change was evident in group 2.Conclusions Posterior tibial nerve stimulation can be a viable treatment optionin some patients with refractory monosymptomatic nocturnal enuresis. However,deterioration in some res ponders with period suggests the wish for concernprotocols.Key Words urinary vesica, nocturnal enuresis, transcutaneous electricnerve stimulation, urodynamics, treatment outcomeNOCTURNAL enuresis is usually associatedwith skanky psychological and socialdistress to children and their families.1 In recent years several treatmentmodalities emerged to treat NE, suchas behavioral therapy,2 alarm treatment,3 medical therapy with desmopressin,oxybutynin and imipramine,and combination therapy.46 However,none has been completely successful andthe relapse rate of all of them is significant.79 Therefore, there is a great needto find other treatments that could bemore effective and durable than currenttherapy.The pathogenesis of refractory NEwas discussed in many studies and attributedto decreased bladder capacityand/or PTNS was introduced with earlypromising results as neuromodulativetherapy for diseases that involve thelower urinary tract and for refractory conditions inadults and childr en.1519 These beneficial effectuate ofPTNS for controlling various bladder disorders ledus to try it in patients with refractory primary MNE.MATERIALS AND METHODSA total of 28 patients were included in this prospective,randomized, placebo controlled, single blind study fromJanuary 2010 to environ 2012 at the urology department atTanta University Hospital. The study protocol was reviewedand approved by the Tanta University institutionalreview board. Informed consent was obtained fromall participants or from parents if the patient was youngerthan 18 years.We recruited patients with severe (3 or more wet nightsper week) primary MNE at least 6 months in duration inwhom available conventional and combination therapieshad failed, including desmopressin, anticholinergics andan alarm. We excluded those with secondary NE, nonMNE,nocturnal polyuria and any neurological abnormality.All patients provided a detailed history and underwentcomplete physical examination, urinalysis, x-ray of thel umbo-sacral spine and ultrasound of the urinary system.All patients were asked to keep a nocturnal enuresis diaryfor 2 weeks, which included the time of sleep and arousal,and whether they had a dry or wet cope in the morning.Nocturnal urinary production was measured as the total urinevolume collected in the diaper after misdirecting during the furthestnight (assessed by weighing the diaper in the morning)plus the first morning urine volume. Nocturnal polyuriawas defined as nocturnal urine output 130% or greater of EBC for age.20The Arabic version of a 2-day frequency-volume chart(adapted from the Pan Arab Continence Society, www.pacs mangleice.com) was obtained from all patients to confirmthat the problem was MNE. Daytime functional bladdercapacity was considered the recorded MVV. EBC for agewas calculated by the formula, 30 _ (age in years _ 30).Children with MVV less than 65% of EBC for age wereconsidered to have a small bladder.20All patients as well as underwent urodynamic tests, as performedby the same urodynamicist using a Delphis-KTdevice (Laborie, Toronto, Ontario, Canada), including1) uroflowmetry with PVR estimation by ultrasound for atleast 2 voids and 2) cystometrogram, including 1 plectroncycle using an 8Fr double lumen urethral catheter withthe patient supine and a slow filling rate of 10 ml perminute. unhurrieds were randomly carve up into 2 equal groups bymethod. Randomization was done blindly by having anindependent nurse randomly take a card from an envelopecontaining 14 cards for group 1 and 14 for group 2. Group1 received active PTNS treatment sessions using theUrgent PC Neuromodulation System, while group 2 underwenta sham procedure.Treatment ProtocolWe applied the technique described by Stoller.21 The patientlay supine with the soles of the feet together, and theknees abducted and flexed (frog position). A 34 sensneedle was inserted percutaneously approximately 2inches (5 cm) cephalad to the medial malleolus and 1 cmfrom the poste rior margin of the tibia at an angle of 60degrees from the skin surface and the engineer wire attachedto it. The surface electrode was placed on the same legnear the arch of the foot over the calcaneus bone. Thedevice was turned on and amplitude was slowly increaseduntil the largest toe of the patient began to curl, the digitsfanned or the entire foot extended, indicating proximity tothe nerve bundle (see figure). If this answer was notachieved or pain occurred near the insertion site, thedevice was turned off and the procedure was repeated.When the needle was inserted in the correct position, thecurrent was set at a resistant level (pain threshold) andthe session continued for 30 minutes.For the sham procedure we tested only the foot solutionto the electrical impulse and then turned off theapparatus during the whole session. To avoid patientidentification of the grammatical case of procedure all participantswere informed that they may or may not feel a sensorystimulus in the l ower extremities during the treatmentsessions.Groups 1 and 2 underwent 12 weekly outpatient treatmentsessions. All participants were advised to stop allmedical treatment for NE at least 1 month sooner startingPTNS but to continue behavioral therapy, including fluidA, neuromodulation system. B, system in utilisation with flexion of left largest toe.restriction at night, complete bladder emptying beforesleep and awakening 2 hours after sleep to void.Patient appraisalThe first patient evaluation was done in the first 2 weeksafter the last session. This evaluation involved repeatingthe clinical and urodynamic assessments. The clinical partincluded a nocturnal enuresis diary for 2 weeks in whichthe number of wet nights/week was reported as well as a2-day frequency-volume chart.The clinical response to treatment was assessed asoutlined by the International Childrens Continence Society,including no responseless than a 50% decrease inthe total number of wet nights, partial response50% to8 9% decrease, response90% or greater decrease and fullresponse100% decrease.20 Urodynamic assessment includeduroflowmetry, PVR measurement and cystometry.The second evaluation was done 3 months after the lastsession. It involved clinical evaluation using nocturnaland voiding diaries only.Statistical AnalysisAll statistical analysis was performed using SPSS 17.Data are shown as the sozzled SD unless otherwise specified.The Student t and polar sample t tests were usedfor comparison between groups and in the same group,respectively. Nonparametric data were compared by theWilcoxon signed ranks or Mann-Whitney U test. Statistical importation was considered at p 0.05.RESULTSRecruited for this study were 28 patients with refractoryNE who met inclusion criteria. Initial assessmentand baseline characteristics of each groupshowed no significant remnant in clinical and urodynamicparameters (table 1). Overall, in the 2groups DO was present in 13 patients (46.4%) and14 (50%) had decreased blad der capacity.The procedure was performed easily with no uncomelyeffects in all cases. No patient discontinuedthe planned sessions.At the end of the PTNS sessions clinical assessmentrevealed significant good in the average numberof wet nights per week in group 1 (decrease from4.7 to 2.6, p 0.002, table 2). Compared to the placebogroup, the number of wet nights after treatment wassignificantly lower in group 1 (p 0.041, table 2). Atthat time 4 group 1 patients (28.6%) had a completeresponse to PTNS, 7 (50%) had a partial response and3 were nonresponders. However, in group 2 there were2 patients (14.3%) with a partial response, while theremainder did not respond. When we compared the 2groups, the difference in this response rate was statisticallysignificant (p 0.002, table 2).At first evaluation after the end of treatment, theactive group showed significant improvement in allurodynamic parameters compared to baseline, includingfirst and strong desire to void, and MCC(p 0.002, 0.01 an d 0.000, respectively, table 2). Ingroup 2 these parameters did not significantly differcompared to baseline (table 2). Also, DO disappearedin 2 of 7 group 1 patients but this improvement wasnot noted in the sham treated group (table 2). Statisticalanalysis revealed that the difference be-Table 1. Patient characteristicsActive Placebo p ValueNo. boys/girls 8/6 9/5 1Mean SD age (yrs) 13.7 2.8 14 2.8 0.8Mean SD body mint candy index(kg/m2)24.95 4.40 26.27 4.23 0.43Mean SD max urine flow(ml/sec)26.85 6.74 23.28 5.49 0.13Mean SD PVR (ml) 6.21 7.11 5.86 5.48 0.9Mean SD daytime frequency 3.9 0.67 4.29 0.64 0.07Mean SD MVV (ml) 266.57 82 288.93 106.29 0.27Mean SD No. wet nights/wk 4.7 1.3 5.1 1.4 0.42No. detrusor overactivityPresent 7 6 1Absent 7 8 Mean SD void desire (ml)1st 148.46 25.89 153.50 21.65 0.59Strong 260.43 84.18 271.79 75.43 0.71Mean SD MCC (ml) 291.21 86.82 322.21 76.04 0.32Table 2. inner and intergroup comparisons of clinical and urodynamic findings after PTNS at first eva luationActive PlaceboBaseline After Treatment p Value Baseline After Treatment p Value Posttreatment p ValueMean SD void desire (ml)1st 148.46 25.89 177.71 35.48 0.002 153.50 21.65 154.14 20.71 0.59 0.041Strong 260.43 84.18 283.64 72.03 0.01 271.79 75.43 271.6 72.8 0.94 0.67Mean SD MCC (ml) 291.21 86.82 322.5 65.89 0.000 322.21 76.04 323.57 77.44 0.57 0.97No. detrusor overactivityPresent 7 5 0.44 6 6 1 0.7Absent 7 9 8 8Mean SD MVV (ml) 266.57 82 280.14 71.81 0.022 288.93 106.29 291.07 96.84 0.73 0.6Mean SD No. wet nights/wk 4.7 1.3 2.6 2.2 0.002 5.1 1.4 4.7 2.1 0.08 0.041No. response Full 4 0 0.002Partial 7 2None 3 121516 POSTERIOR TIBIAL NERVE STIMULATION FOR REFRACTORY NOCTURNAL ENURESIStween the 2 groups in this regard was not statisticallysignificant (p 0.7, table 2). Furthermore, inthis evaluation urodynamic parameters showed thatbladder volume at first desire to void was significantlyhigher in group 1 than in group 2 (p 0.041).On the other hand, bladder volume at strong des ireto void and MCC did not significantly differ betweenthe groups (p 0.67 and 0.97, respectively, table 2).Five of the 8 group 1 patients with decreased EBCshowed improved capacity. MVV also significantlyincreased after treatment from a mean of 266.5782 to 280.14 71.81 cc (p 0.022, table 2).When we studied the relationship between the responseto PTNS and initial urodynamic findings, wenoted that all 10 group 1 patients with small bladdercapacity and/or DO showed a good response to treatment,including 4 and 6 with a full and partial response,respectively. However, when we compared the type ofresponse in those with normal vs abnormal urodynamicresults, the 4 patients with normal urodynamic findingsin this group had a poor response to the sessions, including3 with no response and 1 with only a partial response.This difference was significant (p 0.007).Clinical results at 3 months after the last sessionshowed some deterioration in early results in theactive group. In this group the numb er of patients ith a full response decreased from 4 to 2 and thenumber of those with a partial response decreasedfrom 7 to 4. No change was detected in the othergroup. However, when we compared the responserate in the 2 groups at this time, we detected nosignificant difference (p 0.13). In addition, theaverage number of wet nights per week at that timewas 2.9 in group 1 and 4.2 in group 2, which did notsignificantly differ (p 0.07).DISCUSSIONThis study demonstrates that PTNS could be of valuein some patients with primaryMNEin whom previousconventional therapies failed. To our knowledge thistreatment modality has not been tried before in suchcases but it has been successfully used for overactivebladder syndrome,22,23 lower urinary tract dysfunctionin adults and children,15,18 refractory overactive bladder,16 refractory vesical dysfunction19 and refractorynonneurogenic bladder sphincter dysfunction.17Absent daytime lower urinary tract symptoms inpatients with NE does not necessarily m ean that thebladder functions well because DO and/or decreasedbladder capacity was previously reported in suchpatients.10,11 The clinical response to desmopressintherapy is less acceptable when NE is associatedwith decreased bladder capacity and/or DO.1214 Inour study we detected DO and decreased bladdercapacity in 46.4% and 50% of patients, respectively,although patients with MNE only were included inanalysis. These values agree with previous reportsshowing bladder overactivity24 and small bladdercapacity25 in 49% and 50% of children with MNE,respectively. These findings may partly explainthe mechanism of resistance to the previous treatmenttrials in our patients.Our results and those of others reveal that PTNScan be applied easily and safely in children.18,19After the 12 PTNS sessions in our series, patientsshowed a significant increase in MVV and urodynamicparameters, including first and strong desireto void, and MCC, compared to the placebo group.These results agree with those in previous reportsdemonstrating that PTNS increased cystometric capacityfrom 197 to 252 cc26 and from 243 to 340 cc,27and increased MVV by 39 cc, which was statisticallysignificant.23However, at 3-month followup we detected somedeterioration in the response rate compared to earlyresults. The overall number of full and partial respondersdecreased from 11 (78.6%) to 6 (42.9%) ingroup 1. This deterioration during followup suggeststhat PTNS may have temporary efficacy and its effectdecreases gradually with time. This finding was alsonoted in patients with overactive bladder treated withPTNS. van der Pal reported that 7 of 11 patients withan initially good response had evidence of indispensableand objective deterioration after PTNS.28 They suggestedthe need for maintenance treatment.The early promising results of this study encouragedus to suggest that PTNS might be effectivein patients with refractory primary MNE inwhom nocturnal polyuria is not an etiological factorbut in whom the ma in underlying pathologicalcondition is decreased bladder capacity and/or DO.However, the exact mechanism that could explainthe mode of action of this treatment modality isstill unknown. PTNS may induce some inhibitoryeffects on DO. The existence of this functionalabnormality in the bladder implies that the detrusoris not completely relaxed between voids.Therefore, the capacity of the overactive bladder isusually smaller than that of the bladder with anormal detrusor. Consequently, the clinical responseusually occurs when bladder capacity increasesand DO improves after PTNS. This explanationmay be supported by the improvement inbladder capacity (functional and cystometric) andthe disappearance of DO in patients who respondedto PTNS in our study.The main limitations of this study are the smallsample size and the short 3-month followup. Inaddition, we did not repeat urodynamic tests atthe second followup at 3 months to avoid patientdiscomfort but depended only on the patient clinicalre sponse. However, this information could be important for assessing the cause of the deterioration in PTNS efficacy after treatment wasstopped.CONCLUSIONSPTNS appears to be a viable treatment option insome patients with refractory primary MNE. However,deterioration in the response rate with timeraises important questions about the long-termefficacy of this therapy and the need for furthermaintenance sessions. More studies are needed tosupport our findings and select patients whowould be good candidates for this therapy.