Urology reports (St. - Petersburg)Urology reports (St. - Petersburg)2225-90742687-1416Eco-Vector1789910.17816/uroved10125-32Research ArticleClinical effectiveness of intradetrusor injections of botulinum toxin type a in dose 100 units in multiple sclerosis patients with neurogenic detrusor overactivityFilippovaЕkaterina S.<p>Candidate of Medical Sciences, Associate Professor of the Department of Urology; Urologist</p>filippova.cat@yandex.ruhttps://orcid.org/0000-0003-3065-3953BazhenovIgor V.<p>Doctor of Medical Sciences, Professor of the Department of Urology; Head of the Urological Unit</p>biv@okb1.ruhttps://orcid.org/0000-0003-1745-700XZyrjanovAleksandr V.<p>Doctor of Medical Sciences, Professor. Chairman of the Department of Urology; Head of the Regional Urological Center of the Sverdlovsk Regional Clinical Hospital No. 1</p>zav1965@mail.ruhttps://orcid.org/0000-0001-8105-7233ZhuravlevVladimir N.<p>Doctor of Medical Sciences, Professor</p>zhuravlev@okb1.ruBorzunovIgor V.<p>Doctor of Medical Sciences, Professor of the Department of Urology</p>ivborzunov@e1.ruhttps://orcid.org/0000-0002-9827-8451UstinovGennadiy S.<p>Student</p>GennadiyUstinov@mail.ruhttps://orcid.org/0000-0002-4263-4568Urals State Medical University of the Ministry of Healthcare of the Russian FederationSverdlovsk Regional Clinical Hospital No. 11505202010125322611201922032020Copyright © 2020, Filippova Е.S., Bazhenov I.V., Zyrjanov A.V., Zhuravlev V.N., Borzunov I.V., Ustinov G.S.2020<p>Intravesical injections of botunulinum toxin type A (BTA) demonstrate good results in treatment of detrusor overactivity symptoms in patients with neurogenic low urinary tract dysfunction (NLUTD) when use in recommended doses of 200 and 300 Units. In clinical practice a government insurance dose not cover the price for the 200 BTA Units and only 100 Units may be injected in patients with neurogenic and nonneurogenic detrusor overactivity.</p>
<p><strong>The aim</strong> was to evaluate the efficiency of intradetrusor injections of BTA in patients with NLUTD.</p>
<p><strong>Materials and methods.</strong> The study included 28 MS patients with resistant to medical treatment neurogenic detrusor overactivity. All patients received intradetrusor injections of 100 BTA Units. The results were assessed after 1, 3 and 6 months after procedure.</p>
<p><strong>Results.</strong> Clinical improvement had been achieved in all 28 patients. According to the urodynamic studies three months after BTA injections maximal cystometric capacity increased by 119.9 37.6% (<em>p</em> 0,05), volume at first detrusor involuntary contraction increased by 74.8 21.4% (<em>p</em> 0,05), maximal detrusor pressure at involuntary contraction decreased by 53.5 29.7% (<em>p</em> 0,05). The NBSS total score decreased from 38.04 14.27 to 29.06 14.46 (<em>p</em> = 0,000), mainly because of questions about incontinence and urgency. SF-Qualiveen total score turned from 2.32 0.70 to 1.61 0.85 (<em>p</em> = 0.000). Before procedure 2 patients performed intermittent catheterization, 4 patients catheterized after BTA injections.</p>
<p><strong>Conclusion.</strong> Intradetrusor injection of 100 BTA Units in MS patients with NLUTD resulted in improvement of urodynamic parameters followed by reduction of clinical symptoms and life quality improvement for 6 months of observation. Using of BTA low dose didnt provide a total abortion of neurogenic detrusor overactivity symptoms but led to the starting of IC only in 2 patients.</p>neurogenic bladderdetrusor overactivitybotulinum toxinнейрогенный мочевой пузырьгиперактивность детрузоработулотоксин神经源性膀胱逼尿肌过度活跃肉毒杆菌毒素<h2>INTRODUCTION</h2>
<p>Intradetrusor injections of botulinum toxinA (BTX-A)<em></em>decreases detrusor overactivity in patients with neurogenic lower urinarytract dysfunction (NLUTD). This procedure decreases urinary frequency, reducesurge urinary incontinence, improves urodynamic variables, and the quality oflife of the patients[1]. The main mechanism ofaction of botulinum toxin is the inhibition of presynaptic acetylcholine release in neuro-muscular synapses[2, 3]. The direct specific effect of the agent ona bladder urothelium has also been described [4].</p>
<p>In 2004,А. Reitz et al. [5] reported data on the first treatment experience using onabotulinumtoxin A in 200 patients with neurogenic detrusor overactivity(NDO) in Europe. The patients received intradetrusor injections of BTX-A at a dose of 300 U. The authors observed significant improvements inthe urodynamic parameters at weeks 12 and 36 after treatment. Since 2011, results of studies have emerged, providing ahigh-level evidence for BTX-A in the treatment of NDO. Resultsof the multicenter, randomized, double-blind, placebo-controlled study knownas DIGNITY (Double-Blind Investigation of Purified Neurotoxin Complex in NeurogenicDetrusor Overactivity) were published [6]. This study had 63 participating centers inEurope, North and South America, South Africa, and Asia. It involved 275patients with urinary incontinence due to NDO: 154 with multiple sclerosisand 121 after spinal cord injury. Patients were randomly dividedin three groups: 92 patients received intravesical injections of BTX-A at a dose of 200 U,91 patients at a dose of 300 U, and 92patients received a placebo [6]. The program DIGNITY also conducted a second investigation, which included 85 centers worldwide. The results of these investigations which provided ahigh level of evidence for BTX-A efficacy in the treatment of NDO were published byD.Ginsberg et al. in 2012. [7]. This large studyprogram involved 416 patients with NDO (227with multiple sclerosis and 189 with spinal cord injury). In2016,T.Cheng et al. [8] conducted a meta-analysis to assess the efficacyand safety of onabotulinumtoxinA in patients with NDO and theirresults confirmed the efficacy and safety of the botulinum toxin therapy for NDO.</p>
<p>Accordingto A. Apostolidis [9], in patients with NDO after spinalcord injury, BTX-A at a dose of 200 U wasassociated with the highest effect and longest duration of actioncomparing with BTX-A at a dose of 50 and 100U. However, several researchers have shown that there is nosignificant difference in terms of urologic efficacy and improvement ofthe quality of life between 200 U and 300 Uof the drug [10]. According to A.S. Arkchireev et al.[11], a high dose of BTX-A did not guarantee amore longstanding improvement of the bladder function and 200 Uhad an equal efficiency compared with higher doses of thedrug. Authors recommend 200 U injections for patients with NDOand 100 U for idiopathic detrusor overactivity.</p>
<p>In an effort toreduce the risk of urinary retention after botulinum toxin injection, U. Mehnert et al. [12] attempted to reduce its dose to 100 Udiluted in 10 ml of 0.9% saline in patients withNDO associated with multiple sclerosis. The study showed that injecting the drug at sucha dose improved the urodynamic parameters and reduced urgency<em></em>for 12weeks.</p>
<p>In Russian clinical recommendations for NLUTD in adults, BTX-A ata dose of not less than 200 U is recommendedfor the treatment of NDO. However, the tariffs existing inthe system of obligatory health insurance do not cover thecost of intradetrusor injections of 200 U of the drugand often force clinicians to use a lower dosage (100U) in patients with both idiopathic and neurogenic detrusor overactivity.</p>
<p>Therefore,<em>the aim</em>of this study was to investigate the efficacy of intradetrusor injections of 100 Uof BTX-A in patients with NDO associated with multiple sclerosis.</p>
<h2>MATERIALSAND METHODS</h2>
<p>The study was performed at<em></em>the Sverdlovsk regional urologiccenter of Sverdlovsk regional clinical hospital #1 in 20172019.The study included 28 patients with NDO associated with multiple sclerosis(64.3% were women and 35.7% were men) aged 1870years (mean age, 38.7612.43 years). Primary progressivemultiple sclerosis was found in 7% of patients, secondary progressive in 37%, andrelapsing-remitting in 56%. The average EDSS (Expanded Disability Status Scale) score was 3.94 2.10. In allthe patients, a previous medical therapy with muscarinic antagonists had no clinical effect.</p>
<p>The patientsunderwent standard examination, including taking of the medical history andcomplaints, physical examination, general laboratory tests (urinalysis, urine cultureand sensitivity analysis, biochemical blood test), ultrasonography of the bladder and upper urinary tract, keeping amicturition diary or self-catheterization for 3 days, filling the validated Russian versions of questionnaires (SF-Qualiveen,a short questionnaire that measures the urinary-specific quality of life; NBSS, a neurogenic bladder symptom score), uroflowmetry with measurement of themaximum flow rate (<em>Q</em><sub>max</sub>, ml/sec), voided volume and postvoid residual urine volume, urodynamic study using the Triton measurement system (Laborie Medical Technologies, Canada) with 25 ml/sec rate of bladder filling to determine the maximal cystometric capacity (MCC, ml), maximumdetrusor pressure during involuntary detrusor contraction (Pdet<sub>max</sub>IDC, cm H<sub>2</sub>O), and the volume infused at the onset of the first involuntary detrusor contraction (V<sub>1</sub>IDC, ml).</p>
<p>The study design included several stages: comprehensive examination of the patients prior to BTX-A injection (visit1); BTX-A therapy at the urology department (visit 2); fillingof questionnaires 1, 3, and 6 months after BTX-A therapy(visits 3, 4, 5); repeated uroflowmetry and urodynamic study 3months after therapy (visit 4); and assessment of the finaloutcome of the BTX-A therapy (visit 6).</p>
<p>Regarding the BTX-A injectionprocedure, urethrocystoscopy was performed under intravenous anesthesia, after which anendoscopic needle was passed through the working channel of theurethrocystoscope, and 100 U of the onabotulinumtoxin A (Botox) wasinjected through the needle into 20 detrusor sites with thedepth of 235 mm, depending on the thickness of itswall.</p>
<p>All the patients gave a voluntary informed consent with regardsto the invasive manipulations, blood and urinary collection for investigation.The study design was approved by the local ethics committeeof Sverdlovsk regional clinical hospital #1.</p>
<p>Statistical data analysis was performedusing the SPSS v23.0 software package for Windows. Students t-testwas used to evaluate difference between means.</p>
<h2>RESULTS</h2>
<p>The enrolled patients complainedof frequent urination (88%), micturition urgency (100%), urge urinary incontinence(85%), difficult urination (61%). According to the micturition diaries, themean number of daytime voids varied from 5 2.3to 17 3.6 (mean value, 9,5 3,6) andnighttime voids from 0 to 7 1.2 (mean value,2,4 1.8), while the mean volume of urine voidedduring a single micturition (mean voided volume of each micturition)was in the limits of 66.5 51.4 to 339.3 147.9 ml (mean value, 160.8 73.4 ml). TotalNBSS score was 38.08 17.27; for domain Incontinence14.11 8.18, Storage and Voiding 13.46 4.05,and Consequences 7.24 4.28. All the patients reporteda significant impact of urinary disorders on the quality oflife. In the study group, the mean score in SF-Qualiveenwas 2.20 0.95. More than 75% of patients reportedthat bladder problems graded as quite a bit or extremelycomplicate their life; 70% of those with quite a bitor extremely bladder problems, are worried that it will worsen,while 83% feel more or less embarrassed because of theseproblems.</p>
<p>During filling cystometry a detrusor overactivity was confirmed inall patients. The maximum cystometric capacity was reduced to 158.3 72.2 ml. In some patients, a spontaneous involuntary bladder contraction was already observed when filled up to 20 ml(Fig.1). A mean volume infused at the onsetof the first involuntary detrusor contraction was 155.0 47.6ml and the maximum detrusor pressure during involuntary detrusor contraction was 17.57 11.3 cm H<sub>2</sub>O. When urodynamic study was repeated 3 months after the intradetrusor botulinum toxin injections (Fig.2), a significant difference in terms of positive dynamics in allthe urodynamic parameters was registered. Maximum cystometric capacity, mean volumeinfused at the onset of the first involuntary detrusor contraction(Fig. 3) and maximum detrusor pressure during involuntary detrusor contraction (Fig. 4) were increased by119.9 37.6% (<em>p</em>0.05), 74.8 21.4% (<em>p</em>0.05)and by 53.5 29.7% (<em>p</em>0.05), respectively.</p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 1.Cystometry of patient F., 64 years old, suffering from multiple sclerosis with neurogenic detrusor overactivity. Urodynamic signs of detrusor hyperactivity. First involuntary detrusor contraction is accompanied byurge urinary incontinence.V1IDC=19.7 ml, PdetmaxIDC=63.5 cm H2O" href="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63533-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63533-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 1.Cystometry of patient F., 64 years old, suffering from multiple sclerosis with neurogenic detrusor overactivity. Urodynamic signs of detrusor hyperactivity. First involuntary detrusor contraction is accompanied byurge urinary incontinence.V<sub>1</sub>IDC=19.7 ml, Pdet<sub>max</sub>IDC=63.5 cm H<sub>2</sub>O</strong></p>
<p><strong>Рис. 1.Цистометрия пациентки Ф., 64 года, страдающей нейрогенной дисфункцией нижних мочевыводящих путей на фоне рассеянного склероза. Уродинамические признаки гиперактивности детрузора. Первое непроизвольное сокращение детрузора сопровождается ургентным недержанием мочи. V<sub>1</sub>IDC = 19,7 мл, Pdet<sub>max</sub>IDC = 63,5см Н<sub>2</sub>О</strong></p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 2.Cystometry of patient F., 64 years old, suffering from multiple sclerosis with neurogenic detrusor overactivity in 3 months after botulinum therapy. The volume of filling at the first involuntary detrusor contraction is 264 ml, urge urinary incontinence is absent" href="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63534-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63534-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 2.Cystometry of patient F., 64 years old, suffering from multiple sclerosis with neurogenic detrusor overactivity in 3 months after botulinum therapy. The volume of filling at the first involuntary detrusor contraction is 264 ml, urge urinary incontinence is absent</strong></p>
<p><strong>Рис. 2.Цистометрияпациентки Ф., 64 года, страдающей нейрогенной дисфункцией нижних мочевыводящих путей на фоне рассеянного склероза, через 3 мес. после ботулинотерапии. Объем наполнения при первом непроизвольном сокращении детрузора 264 мл, ургентное недержание мочи отсутствует</strong></p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 3.Changein the urodynamic parameters of patients with neurogenic detrusor hyperactivity in 3 months after botulinum therapy at a dose of 100Units,n=28 (MCC maximal cystometric capacity; V1IDC volume at first involuntary detrusor contraction; *p0.05with avalue before treatment)" href="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63535-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63535-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 3.Changein the urodynamic parameters of patients with neurogenic detrusor hyperactivity in 3 months after botulinum therapy at a dose of 100Units,n=28 (MCC maximal cystometric capacity; V1IDC volume at first involuntary detrusor contraction; *p0.05with avalue before treatment)</strong></p>
<p><strong>Рис. 3.Изменение уродинамических параметров пациентов с нейрогенной детрузорной гиперактивностью через 3 мес. после внутридетрузорного введения ботулинического токсина типа А (БТА) в дозе 100 ЕД,n= 28 (MCC максимальная цистометрическая емкость, Vp<sub>max</sub>IDC объем мочевого пузыря при первом непроизвольном сокращении детрузора; *<em>p</em> 0,05достоверно со значением до лечения)</strong></p>
<p><strong></strong></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 4.Changein the maximum detrusor pressure at first involuntary contraction of patients with neurogenic detrusor hyperactivity 3 months after botulinum therapy at a dose of 100 Units,n= 28; *p0.05with avalue before treatment" href="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63536-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63536-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 4.Changein the maximum detrusor pressure at first involuntary contraction of patients with neurogenic detrusor hyperactivity 3 months after botulinum therapy at a dose of 100 Units,n= 28; *p0.05with avalue before treatment</strong></p>
<p><strong>Рис. 4.Изменение максимального детрузорного давления при первом непроизвольном сокращении детрузора у пациентов с нейрогенной детрузорной гиперактивностью через 3 мес. после внутридетрузорного введения ботулинического токсина типа А (БТА) в дозе 100 ЕД,n= 28;*<em>p</em> 0,05достоверно со значением до лечения</strong></p>
<p></p>
<p>Figures 1 and 2clearly illustrate a positive dynamic in urodynamic results. Despite thepositive changes according to cystometry, statistical analysis of the micturitiondiary parameters showed no significant differences in the urination frequencybefore and after botulinum toxin therapy (Table 1). Nevertheless, allthe patients reported an improvement, which was reflected in theresults of the questionnaire survey.</p>
<p></p>
<table>
<tbody>
<tr>
<td colspan="5">
<p><em>Table 1/ </em><em>Таблица</em><em> 1</em></p>
<p><strong>Patient micturition diary analysis results before and after botulinum therapy (<em>n</em>=28)</strong></p>
<p><strong>Результаты анализа дневников мочеиспускания пациентов до и после ботулинотерапии (<em>n</em>= 28)</strong></p>
</td>
</tr>
<tr>
<td>
<p>Parameter</p>
</td>
<td>
<p>Before BTX-A</p>
</td>
<td>
<p>1 month after BTX-A</p>
</td>
<td>
<p>3 months after BTX-A</p>
</td>
<td>
<p>6 months after BTX-A</p>
</td>
</tr>
<tr>
<td>
<p>Number of daytime voids, n</p>
</td>
<td>
<p>9.52 3.59</p>
</td>
<td>
<p>8.22 3.73</p>
<p>(<em>р</em>= 0.290)</p>
</td>
<td>
<p>7.95 3.21</p>
<p>(<em>р</em>= 0.755)</p>
</td>
<td>
<p>8.45 3.61</p>
<p>(<em>р</em>= 0.344)</p>
</td>
</tr>
<tr>
<td>
<p>Number of night‐time voids, n</p>
</td>
<td>
<p>2.45 2.17</p>
</td>
<td>
<p>2.18 1.84</p>
<p>(<em>р</em>= 0.722)</p>
</td>
<td>
<p>2.27 1.68</p>
<p>(<em>р</em>= 0.560)</p>
</td>
<td>
<p>2.36 1.52</p>
<p>(<em>р</em>= 0.540)</p>
</td>
</tr>
<tr>
<td>
<p>Minimum voided volume, ml</p>
</td>
<td>
<p>69.44 56.70</p>
</td>
<td>
<p>77.77 38.00</p>
<p>(<em>р</em>= 0.652)</p>
</td>
<td>
<p>43.33 15.55</p>
<p>(<em>р</em>= 0.058)</p>
</td>
<td>
<p>58.72 22.15</p>
<p>(<em>р</em>= 0.256)</p>
</td>
</tr>
<tr>
<td>
<p>Maximum voided volume, ml</p>
</td>
<td>
<p>368.88 178.28</p>
</td>
<td>
<p>315.55 148.92</p>
<p>(<em>р</em>= 0.477)</p>
</td>
<td>
<p>368.33 63.11</p>
<p>(<em>р</em>= 0.145)</p>
</td>
<td>
<p>345.21 98.6</p>
<p>(<em>р</em>= 0.350)</p>
</td>
</tr>
<tr>
<td>
<p>Mean voided volume, ml</p>
</td>
<td>
<p>160.82 73.41</p>
</td>
<td>
<p>170.27 88.44</p>
<p>(<em>р</em>= 0.058)</p>
</td>
<td>
<p>162.1 68.64</p>
<p>(<em>р</em>= 0.355)</p>
</td>
<td>
<p>170.27 88.44</p>
<p>(<em>р</em>= 0.098)</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>The total NBSS score decreasedfrom 38.04 14.27 to 29.06 14.46 (<em>р</em>= 0.001), predominantly due to questions about urinary incontinence and urgency (Fig.5). The proportion of patients with urge urinary incontinence reduced from 84.6% to 62.5%, in addition, the number of patientswho used 2 and more) pads per day decreased from50% to 18%, and the percentage of patients whonoticed large loss of urine and needed 3 and more pads reduced from 19% to 6%.</p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 5.The values of the indicators Neurogenic Bladder Symptom Score (NBSS) in patients with neurogenic detrusor overactivity before and after1,3and 6 months after intradetrusor injection of BTA, points (n=28)" href="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63537-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="https://journals.eco-vector.com/files/journals/11/articles/17899/supp/17899-63537-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 5.The values of the indicators Neurogenic Bladder Symptom Score (NBSS) in patients with neurogenic detrusor overactivity before and after1,3and 6 months after intradetrusor injection of BTA, points (n=28)</strong></p>
<p><strong>Рис. 5.Значения показателей шкалы симптомов нейрогенного мочевого пузыря (NBSS) пациентов с нейрогенной детрузорной гиперактивностью до и через 1, 3 и 6 мес. после внутридетрузорных инъекций БТА, баллы (n= 28)</strong></p>
<p></p>
<p>Accordingto SF-Qualiveen, the clinical effect of botulinum toxin therapy for NOD was associated with significant (<em>p</em> 0.001) improvement in the quality of life of the patients that had beenlasting for the entire 6 months follow-up (Table 2). Only21% of patients responded that bladder problems quite a bitcomplicated their life, in addition, none of the patients chose extremely.</p>
<p></p>
<table>
<tbody>
<tr>
<td colspan="5">
<p><em>Table 2/ </em><em>Таблица</em><em> 2</em></p>
<p><strong>Changes in the quality of life associated with micturition disorders in patients with neurogenic detrusor overoctivity after botulinum therapy according to the SF-Qualiveen questionnaire(<em>n</em>= 28)</strong></p>
<p><strong>Изменения в качестве жизни, связанном с нарушениями микции, у пациентов с нейрогенной детрузорной гиперактивность после ботулинотерапии по данным опросника SF-Qualiveen (<em>n</em>= 28)</strong></p>
</td>
</tr>
<tr>
<td>
<p>SF-Qualiveen</p>
</td>
<td>
<p>Before BTX-A</p>
</td>
<td>
<p>1 month after BTX-A</p>
</td>
<td>
<p>3 months after BTX-A</p>
</td>
<td>
<p>6 months after BTX-A</p>
</td>
</tr>
<tr>
<td>
<p>Total score</p>
</td>
<td>
<p>2.32 0.70</p>
</td>
<td>
<p>1.61 0.85***</p>
</td>
<td>
<p>1.51 0.91</p>
</td>
<td>
<p>1.590.73</p>
</td>
</tr>
<tr>
<td>
<p>Domain Bother with limitations</p>
</td>
<td>
<p>2.43 0.75</p>
</td>
<td>
<p>1.53 0.94***</p>
</td>
<td>
<p>1.27 0.95</p>
</td>
<td>
<p>1.38 0.93</p>
</td>
</tr>
<tr>
<td>
<p>Domain Fears</p>
</td>
<td>
<p>1.93 0.89</p>
</td>
<td>
<p>1.50 1.12*</p>
</td>
<td>
<p>1.36 1.07</p>
</td>
<td>
<p>1.42 1.04</p>
</td>
</tr>
<tr>
<td>
<p>Domain Feeling</p>
</td>
<td>
<p>2.43 1.17</p>
</td>
<td>
<p>1.68 1.11*</p>
</td>
<td>
<p>1.45 1.31</p>
</td>
<td>
<p>1.55 1.28</p>
</td>
</tr>
<tr>
<td>
<p>Domain Frequency of limitations</p>
</td>
<td>
<p>2.50 0.81</p>
</td>
<td>
<p>1.71 0.97**</p>
</td>
<td>
<p>1.95 1.08</p>
</td>
<td>
<p>1.65 0.89</p>
</td>
</tr>
<tr>
<td colspan="5">
<p><em>Note.</em>*<em>p</em> 0.05, **<em>p</em> 0.01, ***<em>p</em> 0.001 comparing with baseline before treatment.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>Despite the fact that therewas a statistically significant correlation between NBSS and SF-Qualiveen beforeand after botulinum toxin therapy (from 0.618 to 0.844 atp 0.001), there was no significant relationship between thedegree of change in symptoms according to the NBSS andquality of life, which may be explained by patients subjectiveperception of the dynamics of their condition.</p>
<p>Relapse of symptoms andthe return of NBSS scores to baseline were considered asthe end of effect of botulinum toxin therapy. The durationof the clinical effects of BTX-A at a dose of100 U was 411 months (mean duration, 8.4 2.1months). There was no correlation between baseline urodynamic parameters anddegree and duration of the clinical effect. There were alsono association between changes in NBSS under botulinum toxin therapyand estimates of the patients according to EDSS.</p>
<p>Complications of botulinumtoxin therapy were observed, including mild hematuria on day 1(5.1%), increase in postvoid residual urine volume requiring the useof intermittent self-catheterisation (ISC) in 2 patients (7.14%). The qualityof life in patients that were required to use ISCwas similar compared to that of other patients.</p>
<h2>DISCUSSION</h2>
<p>The positiveeffect of botulinum toxin therapy at a dose of 200U and 300 U on the quality of life of patientswith NLUTD associated with multiple sclerosis was confirmed in randomizedplacebo-controlled trials [9, 13]. The assessment of the effectof botulinum toxin therapy on the quality of life ofpatients with neurogenic bladder was the aim of several studies. For example,V. Kalsi et al. [14, 15] evaluated the quality oflife after intradetrusor injection of onabotulinumtoxin A in twostudies. The first one involved 48 patients with NDO (including 24patients with multiple sclerosis) and 16 patients with idiopathic detrusor overactivity [14]. Patients with neurogenicbladder received 300 U of botulinum toxin and the dosefor idiopathic overactivity was 200 U. Despite the need for ISC in 29patients with NDO and in 2 patients with idiopathic detrusor overactivity aftertherapy, the quality of life was improved significantly in bothgroups on weeks 4 and 16. Another study showed similarresults in 43 patients with multiple sclerosis [15]. Authors proved thatthe need for ISC after botulinum toxin injection impaired the quality oflife less than frequent urination and urge urinary incontinence.</p>
<p>As Table 2 shows,injection of 100 U of botulinum toxin into the detrusoralso led to an improvement in the quality of lifeof the patients over the 6 months of follow-up, includingthose who were required to use ISC after the botulinumtoxin therapy.</p>
<p>ISC was required in 7.4% of observed patients. Accordingto different authors, the necessity for ISC after chemical denervationwith botulinum toxin is variable. A. Kalsi et al. [14]noted that 88% of patients with NDO needed ISC afterbotulinum toxin injection. The study included only patients withmultiple sclerosis and 65% of patients had been performing ISCbefore injection of botulinum toxin. After the procedure, allthe 43 patients except one required ISC. Similar data published by S. Khanet al. [16] showed that 65% of patients with multiplesclerosis required ISC before botulinum toxin therapy and 95% after therapy.D. Ginsberg et al. [7] showed that of the 60% of patients who didnot perform ISC before botulinum toxin injection, ISC after the procedurewas required in 42% of patients who received a dose of 300 U, 35% of patients who recieved a dose of 200 U, and 10%of patients in the placebo group.</p>
<p>Low-dose botulinum toxin seems to result in a reductionof the probability of urinary retention in patients with multiple sclerosis, as was shownpreviously by U. Mehnert et al. [12].</p>
<p>Despite significant positivedynamics in symptoms according to the NBSS, a detrusor overactivity remained in allpatients during filling cystometry. More than a half of patientsstill had an urge urinary incontinence, however, the severity of incontinence reduced. The subjective positive evaluation of BTX-A therapy outcomes bythe patients corresponded with the changes in the urodynamic parameters, although not in all the patients. Micturitiondiaries and repeated urodynamic study allowed for objective assessment ofthe efficacy of the botulinum toxin therapy, which is especially relevantin patients with high risk of upper urinary tract disorders. M. Koschorke et al. [17] analyzed records of 148 patients with NDO who hadreceived botulinum toxin injections and concluded that urodynamic studies wereessential both before and after the botulinum toxin therapy. Highbaseline detrusor pressure is a predictor for poorer urodynamic parameters after injection of botulinum toxin. High intravesicular pressure before treatment provides a more accurate evaluation of proceduresefficiency than clinical absence of urinary incontinence.</p>
<h2>CONCLUSION</h2>
<p>Intradetrusor injection of 100 U of BTX-A in patients with neurogenic bladder improves urodynamic parametersfollowed by significant reduction in clinical symptoms and quality oflife improvement. Low-dose BTX-A does not lead to a totalreduction of NDO symptoms, but reduces the probability of urinaryretention after botulinum toxin therapy in patients with multiple sclerosis.</p>[Linsenmeyer TA. Use of botulinum toxin in individuals with neurogenic detrusor overactivity: state of the art review. J Spinal Cord Med. 2013;36(5):402-419. https://doi.org/10.1179/2045772313Y.0000000116.][Montecucco C, Rossetto O, Caccin P, et al. Different mechanisms of inhibition of nerve terminals by botulinum and snake presynaptic neurotoxins. Toxicon. 2009;54(5):561-564. https://doi.org/10.1016/j.toxicon.2008.12.012.][Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000;80(2):718-750. https://doi.org/10.1152/physrev.2000.80.2.717.][Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;49(4):644-650. https://doi.org/10.1016/j.eururo.2005.12.010.][Reitz A, Stohrer M, Kramer G, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur Urol. 2004;45(4):510-515. https://doi.org/10.1016/j.eururo.2003.12.004.][Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742-750. https://doi.org/10.1016/j.eururo.2011.07.002.][Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6): 2131-2139. https://doi.org/10.1016/j.juro.2012.01.125.][Cheng T, Shuang WB, Jia DD, et al. Efficacy and Safety of Onabotulinumtoxin A in patients with neurogenic detrusor overactivity: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2016;11(7): e0159307. https://doi.org/10.1371/journal.pone.0159307.][Apostolidis A, Thompson C, Yan X, Mourad S. An exploratory, placebo-controlled, dose-response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity. World J Urol. 2013;31(6):1469-1474. https://doi.org/10.1007/s00345-012-0984-0.][Schurch B, de Seze M, Denys P, et al. Botulinum toxin type A is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo-controlled 6-month study. J Urol. 2005;174(1):196-200. https://doi.org/10.1097/01.ju.0000162035.73977.1c.][Архиреев А.С., Ромих В.В., Пантелеев В.В., и др. Эффективность лечения больных нейрогенной и идиопатической детрузорной гиперактивностью в зависимости от дозы ботулинического токсина типа А // Экспериментальная и клиническая урология. – 2017. – № 3. – С. 98–103. [Arhireev AS, Romih VV, Panteleev VV, et al. The efficacy of therapy in patients with neurogenic and idiopathic detrusor hyperactivity depending on the dose of botulinum toxin type A. Experimental and clinical urology. 2017;(3):98-113. (In Russ.)]][Mehnert U, Birzele J, Reuter K, Schurch B. The effect of botulinum toxin type A on overactive bladder symptoms in patients with multiple sclerosis: a pilot study. J Urol. 2010;184(3):1011-1016. https://doi.org/10.1016/j.juro.2010.05.035.][Schurch B, de Seze M, Denys P, et al. Botulinum toxin type A is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo-controlled 6-month study. J Urol. 2005;174(1):196-200. https://doi.org/10.1097/01.ju.0000162035.73977.1c.][Kalsi V, Popat RB, Apostolidis A, et al. Cost-consequence analysis evaluating the use of botulinum neurotoxin-A in patients with detrusor overactivity based on clinical outcomes observed at a single UK centre. Eur Urol. 2006;49(3):519-527. https://doi.org/10.1016/j.eururo.2005.11.006.][Kalsi V, Gonzales G, Popat R, et al. Botulinum injections for the treatment of bladder symptoms of multiple sclerosis. Ann Neurol. 2007;62(2):452-457. https://doi.org/10.1002/ana.21209.][Khan S, Game X, Kalsi V, et al. Long-term effect on quality of life of repeat detrusor injections of botulinum neurotoxin-A for detrusor overactivity in patients with multiple sclerosis. J Urol. 2011;185(4): 1344-1349. https://doi.org/10.1016/j.juro.2010.12.002.][Koschorke M, Leitner L, Sadri H, et al. Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: do we need urodynamic investigation for outcome assessment? BJU Int. 2017;120(6):848-854. https://doi.org/10.1111/bju.13976.]