Non-syndromic urogenital tract malformation

Non-syndromic urogenital tract malformation does not characterise a specific disease but a group of rare pathologies of the nervous system resulting in a severe bladder dysfunction called neurogenic bladder (NB). Why are neurological pathologies, as spinal dysraphism with lipoma, or spina bifida,  described in a group of urogenital disease? Because a severe bladder dysfunction is common to observe as a result in a lesion at any level in the nervous system, mainly in the lumbar sacral area.

Neurological rare causes of non-syndromic urogenital disease are

  • Spina bifida (ORPHA 823)
  • Neural tube closure defect (ORPHA:268357)
  • Lipoma associated with neurospinal dysraphism (ORPHA:268832)
  • Lipomyelomeningocele (ORPHA:268835)

Spina bifida is the most common of a group of birth defects called neural tube defects, and in this disease is most common to find a neurogenic bladder. Open spina bifida affects the backbone and spinal cord, defining the dorsal malclosure of vertebrae, associated with various degrees of spinal defects, containing meninges (meningocele) or spinal cord and meninges (myelomeningocele). Prevalence is 1:2000. The disorder is most often located in the lumbar or sacral area of the spine. Consequences can include paraplegia (paralysed lower limbs), hydrocephaly, urinary and faecal dysfunction. Open Spina Bifida, myelomeningocele, can be easily detected prenatally by ultrasound examination of the fetal spine. Myelomeningocele surgery is performed at birth, ventriculo-peritoneal derivation can be added if hydrocephaly is present. The disabilities vary greatly with the level and extent of the lesion.

In Lipoma and other forms of closed spina bifida, bladder sphincter dysfunction is poorly correlated with the type and spinal level of the neurological lesion. Surgery, detethering, is often performed after diagnosis. Surgery permits to avoid a worsening of symptoms but rarely fully recover, and NB dysfunctions are commonly observed life-long. Surgery indications in patients with anorectal malformation is debated and required in selected cases.

What is the result of NB?
The bladder has the role to collect urine and empty in a continuous cycle in the 24 hours, a complete emptying, without urine residual and with a low-pressure mechanism, without strengthening. A defect in innervations of the bladder muscle, called detrusor, and of the outlet mechanism, called sphincter, results in an incomplete emptying or in a continuous urine leak, because of incoordinate actions of the 2 muscles. This is described as dyssinergia. Another common finding is the overactivity of the bladder/detrusor muscle, fighting against a not relaxed sphincter for emptying the bladder. The urine leak is most affecting the quality of life, for the incontinence, while the incomplete emptying is more dangerous for the individual, due to the risk of urinary infections and renal damage. For this reason, a bladder management is commonly requested after the diagnosis, that for spina bifida is at the birth, Management of NB is complex for older patients, with changing pattern after puberty and requires lifelong follow-up.

In some patients a secondary tethering may occur and redo surgery is required. The urological interest for these pathologies is related to the fact that all these conditions cause various forms, more or less severe, of lower urinary tract dysfunction, which may lead to incontinence, urinary tract infections, vesico ureteral reflux, and renal damage. If not properly managed NB can potentially cause renal failure, requiring dialysis or transplantation. In the past urological problems was the most common cause of death in spina bifida patients. The management of NB presented major changes over the past 20 years, becoming more conservative. Clean intermittent catheterization (CIC) has revolutionized the management. CIC is a therapeutic and rehabilitation technique that consists in the insertion of a catheter in the bladder, through the natural orifice, urethra, for completely empty the bladder, avoiding a stressful condition for the urinary tract.

What are the risks for the child?
At birth, the majority of patients have normal upper urinary tracts, but nearly 60% of them develop upper tract deterioration due to infections, bladder changes and reflux. In these patients, the main goals of treatment are the prevention of urinary tract deterioration and achievement of continence. For these reasons a promptly start with CIC is recommended in all, where the first line treatment is based on CIC and drugs, in order to reduce the pressure inside the bladder. This permits to avoid surgery in the majority. Botulinum toxin use permitted a more conservative approach in the past 15 years avoiding or delaying major surgery in others. For this reason today, major surgery is required in few cases if CIC is started and followed during time and without delay in diagnosis of occult spinal dysraphism.

Indications for surgery must be carefully evaluated either for timing either for kind of reconstruction: augmentation (enlargement of the bladder) associated or not to a derivation (an alternative way for bladder emptying) called Mitrofanoff, and surgery for continence (partial closure of the bladder neck in order to maintain people dry). Surgery must be performed in a selected centre after a careful called urodynamics. This permits to define exactly the function of the bladder, capacity, compliance, emptying attitude, considering the fact that increasing continence there is a risk for upper urinary tract damage and secondary reflux if the reservoir is not adequate or emptying is difficult to obtain. Also, bowel management is important to increase the quality of life, continence, and reducing urinary tract infection. The introduction of an advanced procedure for transanal irrigation reduced the indications of surgical treatment, as Malone. Of course, a complete bladder and bowel management is suggested.

Other causes of NB are Traumatic or neoplastic spinal cord lesion, less frequent in children respect to adult, representing anyway an increasing population due to more effective treatment and increasing survival rate in neoplastic pathologies and trauma.

In some adolescents is possible to observe other forms of NDSD, being Hinman syndrome (ORPHA 84085) or non-neurogenic neurogenic bladder or occult neurogenic bladder. Hinman syndrome is a severe voiding dysfunction of unknown origin, maybe on neuropsychological basis that is characterized by functional bladder outlet obstruction in the absence of neurologic deficits. Prevalence is not known. The syndrome occurs mainly in late childhood but some adult cases have been observed. It typically manifests at some point after toilet training with bladder dysfunction mimicking neurologic disease.

Diagnosis is based on the presence of the clinical and instrumental manifestations of NB in the absence of an underlying neurogenic abnormality. The severity of dysfunction is sometimes missed and severe impairment of bladder and renal function can be observed, including end stage renal disease.