Blake A. Wynia, MD, MPH
Ellen Shapiro, MD, FACS
BASICS
DESCRIPTION
• Myelodysplasia (spinal dysraphism, neural tube defect) is a very broad term encompassing a large heterogeneous group of congenital vertebral column defects that result from defects that occur during neural tube closure.
• Group of developmental abnormalities that can be open (meningocele, myelomeningocele, lipomyelomeningocele) or closed (spinal bifida occulta, posterior meningoceles, lipomyelomeningocele, and myelocystocele).
• Primary functional deficits can be lower limb paralysis and sensory loss, bladder and bowel dysfunction, and cognitive dysfunction.
• Affected children often have varying degrees of neurogenic bladder dysfunction.
ALERT
Patients with myelodysplasia have a high incidence of latex allergy. From birth, parents need to be educated in latex precautions.
EPIDEMIOLOGY
Incidence
• Spinal dysraphism:
– 1 per 1,000 births in USA previously
– 2.5 times more common in Caucasians than blacks
– Incidence decreasing over past 20 yr due to prenatal diagnosis and use of folic acid
Prevalence
• Open spinal dysraphism: 60,000 cases estimated in USA
• Spina bifida occulta: 5–10% of the general population; most cases are found incidentally
RISK FACTORS
• Maternal folate deficiency during pregnancy
• Family history: Incidence for mother with one affected child is 20–50/1,000 live births; also 2nd and 3rd degree affected relative
• Prepregnancy obesity or diabetes
• Exposure to high temperatures in early pregnancy (fever or hot tub)
• Intrauterine exposure to valproate or carbamazepine
• Low vitamin B-12 levels
• Chromosome trisomies 13 and 18, triploidy, and single-gene mutations.
Genetics
Genes involved in folate-homocysteine metabolism and transport (see Risk Factors)
PATHOPHYSIOLOGY
• Increased maternal blood AFP (α-feto protein) at 16 wk can indicate the presence of an NTD (neural tube defect).
• Spinal cord begins normal development on day 18 of gestation:
– The canal closes in a cephalocaudal direction; complete closure day 35 of gestation
– Exact mechanism of dysraphism undefined
• Myelodysplastic states can be subdivided:
– Spina bifida occulta: The mildest form. No overt signs of spinal abnormality; may be associated with tethering of the spinal cord and often associated with a low-lying conus (below L2–L3); usually detected by plain x-ray, demonstrating open vertebral bodies
– Posterior meningoceles, myelocystocele, and lipomyelomeningocele are closed defects associated with a skin-covered back mass
– Meningocele: The meninges or dural sac, but no neural elements, extend beyond the vertebral canal. Mostly normal lower extremity
– Myelomeningocele: The nerves and spinal cord are exposed through an opening in the spinal column, meninges, and skin. Significant neurologic defects (paralysis, urinary incontinence) are usually associated.
– Lipomyelomeningocele: Fatty tissue along with cord structures extend with protruding sac.
• Myelomeningocele account for >90% of spinal dysraphism:
– Arnold–Chiari malformation in 85% of children with myelomeningocele:
Cerebellar tonsils herniated through foramen magnum
The 4th ventricle is obstructed leading to hydrocephalus if shunting is not performed
ASSOCIATED CONDITIONS
• Cloacal anomalies/Cloacal exstrophy
• Hydrocephalus/Arnold–Chiari malformation
• Imperforate anus
• Latex allergy
• Sacral agenesis
• VACTERL syndrome (Vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities)
GENERAL PREVENTION
• Folic acid 0.4 mg/d in all women of childbearing age; 4.0 mg/d in women with previous NTD-affected pregnancy
– Begin 2 mo before planned conception
• Prenatal surgery for meningomyelocele at special centers by 26 wk gestation.
– Outcomes encouraging with shunt placement in only 68% vs. 98% who underwent postnatal repair; also results in improved mental development and motor function at 30 mo of age
– Has not been shown to impact on urologic outcomes
DIAGNOSIS
HISTORY
• Review medical and developmental history
• Most patients now diagnosed prenatally
• Older patients commonly present with urinary and bowel incontinence:
• Change in bowel habits or gait, onset of leg or back pain, presence of seizures or other neurologic symptoms may suggest subsequent spinal cord tethering
PHYSICAL EXAM
• Assess general appearance, body habitus, gait, dexterity, muscular, and neurologic development
• Genitalia: Presence or absence of hypospadias, cryptorchidism, labiovulvar abnormalities
• Rectal exam: Perianal sensation, rectal tone, fecal impaction
• Back exam for open (obvious exposed neural tissues) or closed defects. Stigmata that may be associated with occult spinal dysraphism include:
– Dimples or sinuses, subcutaneous mass, skin tags, hemangiomas, abnormal hair patches, pigmentation, or abnormal gluteal cleft.
• Neurologic exam:
– Gait, balance, muscular development/tone
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Urinalysis, urine culture, basic metabolic panel with high-grade reflux or hydronephrosis
Imaging
• 15–20% of neonates have abnormality of upper tract when 1st studied
• Plain abdominal x-rays:
– May show structural vertebral anomalies or evaluate for partial or complete sacral agenesis
– May visualize stones or fecal impaction
• Renal US (ultrasound):
– Determine baseline of urinary tract; should be performed shortly after birth; important to repeat after back closure prior to discharge
– Assess for hydronephrosis, hydroureter, and PVR (postvoid residual) if patient voids spontaneously
• Voiding cystourethrogram (VCUG):
– Assess for vesicoureteral reflux, bladder wall appearance, bladder capacity, PVR
• Dimercaptosuccinic acid (DMSA) renal scan in select cases including: High-grade reflux, renal scarring, and solitary functioning kidney
• Magnetic resonance imaging (MRI):
– Assess spinal cord and vertebral anomalies in patients with suspected occult spinal dysraphism or a “closed” lesion. Spinal sonogram useful in children <3 mo of age prior to boney ossification.
Diagnostic Procedures/Surgery
• Urodynamic studies (UDS): Fill rate based on average bladder capacity in milliliters: (24.5 × age + 62) divided by 10 is the rate of filling the bladder with warm saline
– Often with video (video urodynamic studies or VUDS)
– Performed 2–3 mo after back closure or at time of diagnosis of occult spinal dysraphism
– Assess bladder capacity, volume, and pressure at abdominal and detrusor leak points (compliance), pressure when reflux, if present, is observed, detrusor overactivity, detrusor sphincter dyssynergia (DSD)
– Findings: Synergic (26%), dyssynergic with or without poor detrusor compliance (37%) and complete denervation (36%)
Pathologic Findings
See Pathophysiology
DIFFERENTIAL DIAGNOSIS
• Other causes of neurogenic bladder (see Chapter on Neurogenic Bladder, general)
• Tethered cord syndrome
TREATMENT
GENERAL MEASURES (1,2,3)
• Urgent neurosurgical intervention is critical for open defects which may lead to hydrocephalus.
• Upper tract preservation is the primary goal with the achievement of continence at an appropriate age.
• Incomplete bladder emptying or significant upper tract hydronephrosis/high-grade reflux before and after repair of the back defect
• Clean intermittent catheterization (CIC) for detrusor filling pressures of >30–40 cm H2O. May often require the addition of anticholinergic therapy (see Medication)
• Cutaneous vesicostomy or urethral dilation to lower emptying pressures not usually performed
MEDICATION
First Line
• Anticholinergics: Decrease detrusor overactivity, increases bladder compliance and functional capacity
– Oxybutynin 0.2 mg/kg BID-TID; should be initiated early in life when indicated to prevent upper tract deterioration secondary to poor detrusor compliance and DSD
– Tolterodine 0.01 mg/kg BID to a maximum of 0.4 mg/kg BID; long-acting forms when older
– Almost always used in conjunction with CIC
– Side effects: Headaches, dry mouth, flushing of skin, abdominal discomfort, blurred vision
• Prophylactic antibiotics considered for reflux
Second Line
• α-sympathomimetic, α-sympatholytic, β-sympatholytic, smooth muscle relaxants
• Imipramine 0.7 mg/kg BID with maximum dosing of 1.2 mg/kg TID; consider pretreatment EKG
SURGERY/OTHER PROCEDURES
• When pharmacotherapy and CIC do not result in favorable bladder dynamics and/or continence in older patients, consider:
– Cystoscopy and botulinum-A toxin injection
– Bladder augmentation usually with creation of continent catheterizable stoma since many of the children are wheelchair bound; wait until the child is 4–5 yr old for continence if upper tracts not deteriorating and bladder is not hostile
– Anti-reflux procedure for high-grade reflux
– Bladder neck reconstructions: Young-Dees-Leadbetter, Kropp, Pippi–Salle modification, bladder neck closure
– Fascial sling or artificial urinary sphincters
• Bowel incontinence:
– If oral laxatives, enemas/irrigation, and rectal suppositories do not result in social bowel continence consider MACE procedure selectively
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
• Neuromodulation of the bladder via intravesical electrical stimulation, sacral nerve stimulation, transcutaneous stimulation, and biofeedback; all of unproven efficacy
• Tissue-engineered bladder augmentation (experimental)
• Artificial somatic-autonomic reflex pathway procedure (experimental)
ONGOING CARE
PROGNOSIS
• Self-performance of CIC is likely in school-aged children with supervision.
• Regular monitoring for silent upper tract deterioration including renal sonogram and VUDs
• Erectile and ejaculatory dysfunction
• Delivery concerns especially at the end of gestation in myelodysplasia patients with bladder/bladder neck reconstruction
COMPLICATIONS
• Incontinence with resulting skin ulceration due to ammonia burns; consider delaying circumcision until continence program instituted since the prepuce provides protection for the glans
• Renal insufficiency
• Symptomatic UTIs
• Shunt failure or infections
• Seizure disorders
• Musculoskelet al problems (scoliosis, club foot, others)
FOLLOW-UP
Patient Monitoring
Close follow-up with pediatric urology and neurology from infancy and throughout childhood is required to avoid upper tract deterioration and achieve urinary and bowel continence. Annual US and VUD when continent with stable upper tracts.
Patient Resources
Spina Bifida Association http://www.spinabifidaassociation.org
REFERENCES
1. Bauer SB, Austin PF, Rawashdeh YF, et al. International Children’s Continence Society’s recommendations for initial diagnostic evaluation and follow-up in congenital neuropathic bladder and bowel dysfunction in children. Neurourol Urodyn. 2012;31:610–614.
2. Rawashdeh YF, Austin P, Siggaard C, et al. International Children’s Continence Society’s recommendations for therapeutic intervention in congenital neuropathic bladder and bowel dysfunction in children. Neurourol Urodyn. 2012;31:615–620.
3. de Kort LM, Bower WF, Swithinbank LV, et al. The management of adolescents with neurogenic urinary tract and bowel dysfunction. Neurourol Urodyn. 2012;31:1170–1174.
ADDITIONAL READING
• Biencowe H, et al. Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol. 2010;Suppl 1:110–121.
• De Jong T, Chrzan R, Klijn AJ, et al. Treatment of the neurogenic bladder in spina bifida. Pediatr Nephrol. 2008;23:889–896.
• Hopps C, Kropp K. Preservation of renal function in children with myelomeningocele managed with basic newborn evaluation and close followup. J Urol. 2003;169:305–308.
• Kochakarn W, Ratana-Olarn K, Lertsithichai P, et al. Follow-up for long-term treatment with clean intermittent catheterization for neurogenic bladder in children. Asian J Surg. 2004;27:134–136.
• Tarcan T, Bauer S, Olmedo E, et al. Long-term followup of newborns with myelodysplasia and normal urodynamic findings: Is followup necessary? J Urol. 2001;165(2):564–567.
See Also (Topic, Algorithm, Media)
• Latex allergy, Urologic Considerations
• Myelodysplasia (Spinal Dysraphism), Urologic Considerations Image 
• Neurogenic Bladder, General Considerations
• Tethered Cord Syndrome
CODES
ICD9
• 238.75 Myelodysplastic syndrome, unspecified
• 596.54 Neurogenic bladder NOS
• 788.30 Urinary incontinence, unspecified
ICD10
• D46.Z Other myelodysplastic syndromes
• N31.9 Neuromuscular dysfunction of bladder, unspecified
• R32 Unspecified urinary incontinence
CLINICAL/SURGICAL PEARLS
• Affected children often have varying degrees of neurogenic bladder and bowel dysfunction.
• 1st-line treatment consists of CIC for elevated PVR and anticholinergics when VUD testing suggests poor detrusor compliance and/or detrusor overactivity with or without upper tract deterioration. Botulinum-A toxin injections, bladder augmentation, antireflux procedures and /or bladder neck procedures performed to protect upper tracts and achieve urinary continence.