Ann Raes

One thousand video‐urodynamic studies in children with non‐neurogenic bladder sphincter dysfunction

Objective To ascertain the aetiology and epidemiology of non‐neurogenic bladder sphincter dysfunction (NNBSD) by assessing the results of prospective video‐urodynamic studies (VUD) in 1000 children.

TRANSCUTANEOUS NEUROMODULATION FOR THE URGE SYNDROME IN CHILDREN: A PILOT STUDY

PURPOSE Neuromodulation has been used to treat voiding dysfunction in adults. Due to its invasiveness it has rarely been used in children until now with the availability of transcutaneous neurostimulation. We evaluated clinical effects of transcutaneous neuromodulation on detrusor overactivity in children with the urge syndrome. MATERIALS AND METHODS Between May 1, 1998 and February 28, 1999, 15 girls (mean age 10.2 years) and 26 boys (mean age 10.7 years) with proved detrusor hyperactivity on videourodynamic study underwent neuromodulation. All children had been given anticholinergic therapy previously. Neurostimulation only was used in children in whom anticholinergics had no effect and those who had significant side effects. Anticholinergics were continued in children in whom they had a partial effect. Stimulation of 2 Hz. was applied for 2 hours every day. Surface electrodes were placed at the level of sacral root S3. After 1 month of trial stimulation those children who responded continued the treatment for 6 months, and were evaluated every 2 months. RESULTS Of the 41 children 15 boys and 13 girls responded after 1 month of trial therapy with an increase in bladder capacity, decrease in urgency, decrease in incontinence and/or better sensitivity. Of the 13 children who did not respond 9 lacked motivation and 4 had no clinical effect despite motivation. After 6 months of therapy a significant increase in bladder capacity, decrease in voiding frequency and decrease in incontinence periods were noted. Adverse effects were not observed. One year after therapy relapse was noted in 7 patients, leaving 21 of 41 children definitively cured. CONCLUSIONS Although preliminary, our results indicate that transcutaneous neuromodulation can improve symptoms of detrusor overactivity, as response to stimulation was noted in 76% of our patients and 56% were cured after 1 year. This therapeutic option is attractive for children because of its noninvasiveness and absence of adverse effects.

Desmopressin 30 Years in Clinical Use: A Safety Review

Desmopressin acetate is the synthetic analogue of the antidiuretic hormone arginine vasopressin. It has been employed clinically for >30 years in a range of formulations: intranasal solution (since 1972), injectable solution (since 1981), tablets (since 1987), and most recently, an oral lyophilisate (since 2005). The antidiuretic properties of desmopressin have led to its use in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. While a large body of clinical data is available for desmopressin, and despite its widespread use, comprehensive reviews of the safety of desmopressin are lacking (although some case series have attempted to correlate patient and/or dosing characteristics with the occurrence of adverse reactions). The purpose of this paper is to review the safety of desmopressin, based on analyses of both published data (MedLine) and of adverse reactions reported to Ferring Pharmaceuticals, the major manufacturer of desmopressin. Based on the findings, suggested strategies to reduce the risk of adverse reactions are proposed. Treatment with intranasal and oral formulations of desmopressin is generally well tolerated, and side effects are usually minor. The risk of hyponatraemia, although small, can be reduced by adhering to the indications, dosing recommendations and precautions when prescribing desmopressin.

Pelvic‐floor therapy and toilet training in young children with dysfunctional voiding and obstipation

Objective To analyse experience in treating young children (4–5 years old) with urodynamically confirmed voiding dysfunction, using a noninvasive training programme.

The effect of botulinum-A toxin in incontinent children with therapy resistant overactive detrusor.

PURPOSE We determined the effect of detrusor injection of botulinum-A toxin in a cohort of children with therapy resistant non-neurogenic detrusor overactivity. This prospective study included therapy resistant children with overactive bladder. MATERIAL AND METHODS During the study period of 19 months 10 boys and 11 girls were included. All patients showed decreased bladder capacity for age, urge and urge incontinence. Main treatment duration before inclusion was 45 months. A dose of 100 U botulinum-A toxin (Botox) was injected in the detrusor. RESULTS Side effects were evaluated in all 21 included patients. The side effects reported were 10-day temporary urinary retention in 1 girl and signs of vesicoureteral reflux with flank pain during voiding in 1 boy, which disappeared spontaneously after 2 weeks. No further examinations were done since the boy refused. Two girls experienced 1 episode each of symptomatic lower urinary tract infection. Eight girls and 7 boys with a minimum followup of 6 months represent the study group for long-term evaluation. In this study group after 1 injection 9 patients showed full response (no more urge and dry during the day) with a mean increase in bladder capacity from 167 to 271 ml (p <0.001). Three patients showed a partial response (50% decrease in urge and incontinence) and 3 remained unchanged. Eight of the 9 full responders were still cured after 12 months, while 1 of the initially successfully treated patients had relapse after 8 months. The 3 partial responders and the patient with relapse underwent a second injection with a full response in the former full responder and in 1 partial responder. CONCLUSIONS Botulinum-A toxin injection in children with non-neurogenic overactive detrusor is an excellent treatment adjunct, leading to long-term results in 70% after 1 injection.

Does monosymptomatic enuresis exist? A molecular genetic exploration of 32 families with enuresis/incontinence

Objectives  To confirm linkage to microsatellite markers on chromosome 8q, 12q, 13q and 22q in families with nocturnal enuresis/incontinence segregating with an autosomal dominant pattern, and to determine if there is an association between the clinical subtype and these linked loci.

Abnormal Sleep Architecture and Refractory Nocturnal Enuresis

PURPOSE The relation between sleep and nocturnal enuresis has been an area of discussion for many years. Children with enuresis are generally believed to have sleep that is too deep with decreased arousability. We investigated sleep characteristics in children with refractory nocturnal enuresis. MATERIALS AND METHODS Nine girls and 20 boys between 5 and 19 years old (mean +/- SD age 12.1 +/- 2.7) diagnosed with desmopressin dependent (14) and/or resistant (15) nocturnal enuresis and nocturnal polyuria underwent a standardized investigation protocol, including 1 night of polysomnography. Two age groups of 4 boys and 2 girls 5 to 9 years old, and 16 boys and 7 girls 10 to 19 years old were compared to previously defined controls, including 5 boys and 2 girls 5 to 9 years old and 7 boys and 2 girls 10 to 19 years old. Five to 9 and 10 to 19-year-old controls had a mean of 4.2 +/- 1.5 and 3.3 +/- 0.6 periodic limb movements per hour of sleep, respectively. The total number of arousal-awakenings during sleep was 21.6 +/- 8.1 at ages 5 to 9 years and 21.7 +/- 12.8 at ages 10 to 19. RESULTS All except 1 patient had greater than 5 periodic limb movements per sleep hour. The younger and older age groups had a mean of 18.6 +/- 5.7 and 18 +/- 7.8 periodic limb movements per sleep hour, respectively. Total arousal-awakenings were also increased at 86.7 +/- 58.1 and 73.8 +/- 34.8, respectively. Statistical differences were calculated with the Mann-Whitney U test in controls vs the study population for periodic limb movements and in the 2 age groups for arousal-awakening (p = 0.003 and <0.001, respectively). CONCLUSIONS Preliminary data indicate a high incidence of periodic limb movements in sleep at night in children with refractory nocturnal enuresis and increased cortical arousability, leading to awakening.

Disparities in Policies, Practices and Rates of Pediatric Kidney Transplantation in Europe

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA‐EDTA and ERA‐EDTA registries. Thirty‐two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0−13.5) per million children (pmc). A median proportion of 17% (interquartile range 2−29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10−52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

Desmopressin Resistant Nocturnal Polyuria Secondary to Increased Nocturnal Osmotic Excretion

PURPOSE We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. MATERIALS AND METHODS A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. RESULTS Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. CONCLUSIONS Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

The Role of Pelvic-Floor Therapy in the Treatment of Lower Urinary Tract Dysfunctions in Children

The pelvic-floor is under voluntary control and plays an important role in the pathophysiology of lower urinary tract (LUT) dysfunctions in children, especially of non-neuropathic bladder sphincter dysfunction. The following therapeutic measures can be applied to try to influence the activity of the pelvic-floor during voiding: proprioceptive exercises of the pelvic-floor (manual testing), visualization of the electromyographic registration of relaxation and contraction of the pelvic-floor by a curve on a display (relaxation biofeedback), observation of the flow curve during voiding (uroflow biofeedback), learning of an adequate toilet posture in order to reach an optimal relaxation of the pelvic-floor, an individually adapted voiding and drinking schedule to teach the child to deal consciously with the bladder and its function and a number of simple rules for application at home to increase the involvement and motivation of the child. In children however with persisting idiopathic detrusor instability additional therapeutic measures may be necessary to improve present urologic symptoms (incontinence problems, frequency, urge) and to increase bladder capacity. Intravesical biofeedback has been used to stretch the bladder and seems to be useful in case of sensory urge. Recently a less invasive technique, called transcutaneous electrical nerve stimulation (TENS), has been applied on level of S3 with promising results in children with urodynamicaly proven detrusor instability, in which previous therapies have failed.