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2 VD: definition Voiding dysfunction refers to daytime voiding disorders in children who do not have neurologic, anatomic, obstructive, or infectious abnormalities of the urinary tract These disorders result from functional disturbance of the normal micturition cycle

3 FUNCTIONAL OBSTRUCTION CAN PRODUCE REAL ANATOMIC DEFORMATION Thick Bladder Wall REFLUX SIMULATE ANATOMIC OBSTRUCTION

4 VD: Causes Causes of voiding dysfunction include the following: Uninhibited detrusor contractions: overactive bladder (most common) Dysfunction of the pelvic floor musculature: dysfunctional voiding (more severe form) Decreased force of detrusor contractions underactive bladder

5 VD: Pathophysiology Prolongation of infantile bladder behavior (OAB) Maturation delay especially of the cerebral control Abnormalities of the process of toilet training habits acquisition (overtraining for dysfunctional voiding) Significant constipation (dysfunctional voiding)

6 VD: Epidemiology 17% of 2856 students (mean age 7 years) reported any daytime urinary incontinence in the previous 6 months Sureshkumar P et al J Urol 2009 Prevalence of daytime wetting (at least once every 2 weeks): 10% at 5-6 years of age 5% at 6-12 years of age 4% at years of age Bloom DA et al J Urol to 5 times more common in girls Sureshkumar P et al J Urol 2009

7 VD: Complications Higher rate of parent reported psychological problems Joinson C et al Pediatrics 2006 In a study of 2000 children daytime wetting was almost as stressful as parental death and going blind Ollendick TH et al Behav Res Ther 1989 Association with VUR and recurrent UTIs in 16 to 60% of children Schulman SL et al Pediatricsl 1999 Hoebeke P et al BJU Int 2001 Renal damage up to the Hinman syndrome Cooper CS Medscape 2013

8 Clinical Case n 1 Barbara Barbara, 7 year old, had always been well, apart from recurrent cystitis the past 6 months. Normal prenatal US She presents with an acute cystitis: -symptoms : mild dysuria, increased diurnal voiding frequency, urinary incontinence. -Urinalysis (not on the first morning void) nitrites absent. -urine culture positive (E. Coli col/ml)

9 What do you believe is the most appropriate clinical approach? 1. Request a bladder ultrasound 2. Request a micturating cystogram 3. Obtain a voiding history 4. Obtain blood tests

10 What do you believe is the most appropriate clinical approach? 1. Request a bladder ultrasound 2. Request a micturating cystogram 3. Obtain a voiding history 4. Obtain blood tests

11 Voiding History: Frequency : 4 normale 8 Incontinence: incontrollable loss of urine Urgency : sudden need to micturate Hesitation: difficulty initiating micturition Effort: increased abdominal pressure Weak voiding Intermittent micturition: spraying Holding manoeuvers: postpone micturition Loss of urine after micturition Constipation 10

12 Typical position: Sitting on her heel to compress her urethra

13 Voiding History: Frequency : 4 normale 8 Incontinence: incontrollable loss of urine Urgency : sudden need to micturate Hesitation: difficulty initiating micturition Effort: increased abdominal pressure Weak voiding Intermittent micturition: spraying Holding manoeuvres: postpone micturition Loss of urine after micturition Constipation 10

14 Voiding History: Frequency : 4 normale 8 Incontinence: incontrollable loss of urine Urgency : sudden need to micturate Hesitation: difficulty initiating micturition Effort: increased Applicable abdominal pressure Weak voiding Intermittent micturition: spraying Holding maneuvers: postpone micturition Loss of urine after micturition Constipation After 5 years of age 10

15 PACCT Group Definition Chronic Constipation 2 of the following parameters in the past 8 weeks evacuations <3/week > 1 episode of fecal incontinence /week fecal masses palpable in the rectum or abdomen evacuation fecal masses of dimensions such that they obstruct water painful defecation J Pediatr Gastroenterol Nutr 2005

16 ICCS slide library v Measurement of rectal diameter (> 3 cm) A B Transducer Measurement of rectal diameter illustrated by Singh et al (2005, Fig 1).

17 Pelvic Ultrasound The bladder displaced by the intestine ICCS slide library v

18 Clinical Case n 1 Barbara Barbara s voiding history - frequent daytime wetting, with episodes of urgency - has always had bedwetting - compact feces, frequency daily What can help us now in the diagnosis?

19 DIARIO Voiding MINZIONALE Diary Orario Volume urinario(ml) Volume wet Mutandine bagnate Orario Liquidi drinking Tipo ingeriti , , , , , yes yes

20 -Voiding Diary (3 day) - volume max 130 ml (theoretically 240 ml) 30 + (age years x 30) normal % small bladder - micturates more than 8x daily (at night?) - often wets during day - at night she always bedwets - continuously voids

21 Clinical Case n 1 Barbara Barbara, 7 year old, recurrent cystitis. Overactive bladder. Are other imaging tests necessary? Is a urodynamic study necessary?

22 -Voiding Diary (3 day) - volume max 130 ml (theoretically 240 ml) 30 + (age years x 30) normal % Overactive bladder small bladder Oxibutinin (0.2 mg/kg x 2) - micturates more than 8x daily (at night?) Clinical amelioration - often wets during day - at night she always bedwets - continuously voids

23 Anticholinergic medications Increase the reservoir function and the compliance of the bladder inhibiting the detrusor muscle function Oxybutinin is a potent one, with significant side effects (withdrwal in 10%) Tolterodine is newer, less potent, but with lesser side effects To monitor post-void residuals, because of possible incomplete bladder emptying

24 Comparison of tolterodine with standard treatment in pediatric patients with nonneurogenic dysfunctional voiding/over active bladder: a systematic review. Medhi B et al 2013 A total of six randomized clinical trials and 11 other studies. The dose ranged from 0.5 to 8 mg/day. Tolterodine has comparable efficacy with better tolerability than oxybutynin in these studies. It can be considered as first line therapy for the treatment of urinary incontinence in children. Off-label!!!

25 Pharmacological therapy of the overactive bladder: practical indications Active principles Oxybutinin 2,5-5 mg twice daily Tolterodine 1-2 mg twice daily When to begin OAB without evidence of voiding dysfunction OAB with VUR or recurrent UTI Markedly reduced functional capacity of the bladder Before commencing Exclude or treat constipation Exclude or treat post micturition residual Clinical guideline Evaluate the response to therapy after 1-2 months Therapy is often necessary for > 6-12 months Reduce gradually Monitor the residual regularly Ensure good oral hygeine (inibitors of salivation)

26 Clinical case n 2 Marc - 8 years old - Hospitalisation for abdominal pain - US: left kidney dysplastic right kidney 75%ile in length massive bladder> crosses the umbilicus - Creatinine 1.2 mg/dl egfr 61 ml/min/ Micturition: voiding satisfactory in early years, now voiding interrupted, hesitant, with effort. At times daytime incontinence, dry at night. Always constipated. What is your diagnostic approach?

27 Clinical Case n 2 Marc - MAG 3 scan: left kidney18 %, right kidney 82% - MRI Lumbo-sacrum normal - Urodynamic study: detrusal hyperactivity non neurogenic, voiding residual 25-50%

28 Clinical Case n 2 Marc - MAG 3 scan: left kidney18 %, right kidney 82% - MRI Lumbo-sacrum normal - Urodynamic study: detrusal hyperactivity non neurogenic, voiding residual 25-50% -Diagnosis: dysfunctional bladder non-neurogenic -

29 - Programme: toilet training alpha-blocker (alfuzozine chloride) macrogol 4000 (osmotic laxative) hourly micturition Clinical Case n 2 Marc - MAG 3 scan: left kidney18 %, right kidney 82% - MRI Lumbo-sacrum normal - Urodynamic study: detrusal hyperactivity non neurogenic, voiding residual 25-50% -Diagnosis: dysfunctional bladder non-neurogenic

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33 Therapy for Dysfunctional Voiding Re-education of the pelvic floor relaxing the pelvic floor correct voiding position voiding at regular intervals alpha-blockers : when the re-education of the pelvic floor does not reduce the residual PM Other therapies botulinum A toxin biofeedback electrostimulation (TENS PTNS)

34 Clinical Case n 2 Marc At 10 years of age: - creatinine 0.75 mg/dl, egfr 106 ml/min/ US: no dilatation of the urinary tract voiding residual 12 ml - no constipation, normal urinary flow

35 Classification International Children s Continence Soc DYSFUNCTION IN THE REFILLING PHASE: BLADDER HYPERACTIVITY DYSFUNCTION IN THE EMTYING PHASE : DYSFUNCTIONAL VOIDING

36 Hyperactivity of the detrusor Hyperactivity of the sphincter Small Bladder Incomplete emptying +/- UTI + UTI

37 DYSFUNCTION IN THE REFILLING PHASE = BLADDER HYPERACTIVITY B CLINICAL --urgency voiding with autocontrol manouvers -urge incontinence -frequent voiding (>7/day) ULTRASOUND -increased bladder wall thickness -absence of residual urine post-micturition URODYNAMICS (detrusor hyperactive) -involuntary contractions during bladder refilling Close correlation between the clinical, ultrasound and urodynamic findings

38 Hyperactivity of the detrusor Hyperactivity of the sphincter Small Bladder Incomplete emptying +/- UTI + UTI

39 DYSFUNCTION IN THE EMTYING PHASE = DYSFUNCTIONAL VOIDING The child contracts the external urinary sphincter during voiding CLINICAL -voiding rare (<3/day), micturition postponed -weak and interrupted voiding -bladder capacity > for age -overdistension incontinence ULTRASOUND -post-micturition residual UROFLUXOMETRY -flow interrupted/staggered URODYNAMICS -activation of the internal sphincter and of the pelvic floor during micturition Usually it is not recognised by the family or the child. It is for secondary incontinence and UTIs that the child comes to attention

40 VOIDING DYSFUNCTION: Comorbidities - often association with constipation (BBD bladder bowel dysfunction) - association between bladder dysfunction, recurrent UTI and VUR (Sillen 2008 Yeung 2006 Sjostrom 2004 Koff 1998) - in children with bladder dysfunction and VUR, there is an increased risk of UTIs and renal damage (VUR necessary but not sufficient)

41 Secondary vesico-ureteric reflux Absent relaxation of the vesical sphincter Pressure Anatomic Urethral valves Ureterocele atresiastenosis Functional Neuropathic bladder Voiding dysfunction

42 SRT (J Urol 2010) : bladder dysfunction in 35% of children with dilating reflux Improvement of VUR in 22% of b. with in 56% of b without renal damage in 85% of b. with in 51% of b without Recurrence of febrile UTI in 33% of b. with In 20% of b without

43 UROTHERAPY : non pharmacological treatment is the cornerstone of therapy in both bladder hyperactivity and dysfunctional voiding Routine hydration Avoid dehydration Re-establish an elevated level of thirst Fluids from 200 ml 5-6 times daily according to age Avoid tea and caffeine Void at regular times

44 Adequate intake of water, dietary reference intake Institute of Medicine of the National Academies, Washington DC European Food Safety Authority. E. Jequier. European Journal of Clinical Nutrition 2010

45 THERAPY for bladder dysfunction a) Programme of voiding re-education training that acts on cerebral control of the bladder, teaching the children to recognise and utilise a conscious command on their lower urinary tract «Timed» micturition every 2-3 hours; increased intake of fluids; Position of legs separated Pelvic floor re-education b) pharmacologic treatment anticholinergics (oxybutinin, tolterodin) alphablockers c) advanced treatment biofeedback botox in the detrusor of the sphincter electrostimulation (TENS-PTNS)

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48 VD: Key points Voiding dysfunction is common in children Minimal invasive assessment Urotherapy with or without drugs represents the treatment of choice Therapy resistant patients need specialized centres Prognosis is good Can recur in adulthood