STUDY DESIGN: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. PURPOSE: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. OVERVIEW OF LITERATURE: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. METHODS: Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. RESULTS: We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. CONCLUSIONS: We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.
Cells, Cultured ; Ethics ; Fibroblasts ; Humans ; Induced Pluripotent Stem Cells* ; Infant, Newborn* ; Meningomyelocele ; Plasmids ; Pluripotent Stem Cells ; Regenerative Medicine ; Skin ; Spina Bifida Cystica* ; Spinal Cord ; Spinal Dysraphism* ; Stem Cell Transplantation ; Stem Cells

OBJECTIVE: To examine the effect of meningomyelocele sac size on prognosis by retrospective review of 64 cases operated for meningomyelocele between January 2009 and December 2012. METHODS: We evaluated newborn babies operated for meningomyelocele by retrospectively reviewing their files for head circumference, location and with of the defect, accompanying anomalies, treatments administered, drugs that mother used during pregnancy. Based on the defect size, 3 patient groups were created as 0–24 cm² (group I), 25–39 cm² (group II), and 40 cm² and above (group III). RESULTS: Throughout the study, 64 babies were evaluated. Mean head circumference was 37.4 cm (range, 30.7–50 cm). Based on their location, 49 of the defects (76.5%) were lumbar, 7 (10.9%) were thoracolumbar, 4 (6.2%) were thoracic, 3 (3.1%) were sacral, 1 (1.5%) was cervical. Mean size of the meningomyelocele sac was 4.7 cm×5.8 cm (range, 1 cm×1 cm—10 cm×8 cm), 13 of the babies (20.3%) had skin defect requiring flap. According to accompanying anomalies, 47 of the babies (73.4%) had hydrocephalus, 7 (10.9%) had club foot, 1 (1.5%) had diastematomyelia, 1 (1.5%) had tethered cord. Thirty-nine of the babies (60.9%) had paraplegia, 10 (15.6%) had paraparesis, 8 (12.5%) had monoplegia; neurological examination in the remaining 7 babies was normal. CONCLUSION: In our study, increased diameter of meningomyelocele sac was associated with greater amount of neural tissue within the sac, which worsens the prognosis. Sac localization was not changing prognosis but infection rates, hospitalization duration were increased in babies with bigger diameter of sacs.
Foot ; Head ; Hemiplegia ; Hospitalization ; Humans ; Hydrocephalus ; Infant, Newborn ; Meningomyelocele* ; Mothers ; Neural Tube Defects ; Neurologic Examination ; Paraparesis ; Paraplegia ; Pregnancy ; Prognosis* ; Retrospective Studies ; Skin

PURPOSE: Augmentation enterocystoplasty (AE) has been shown to improve clinical symptoms in patients with end-stage bladder disease (ESBD). Herein, we report the long-term outcomes of a series of patients with different etiologies of ESBD who received AE. METHODS: We retrospectively reviewed 102 patients with ESBD who received AE at the Hualien Tzu Chi General Hospital from 1992 to 2014. ESBD in this study was defined as including neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) or myelomeningocele, inflammatory bladder disease (IBD), ESBD occurring after pelvic cancer surgery, and other etiologies. Complications including active lower urinary tract problems and urinary tract infection (UTI), as well as patients’ self-reported satisfaction with the procedure, were evaluated. RESULTS: A total of 102 patients were included in the study. A majority of patients received AE for NLUTD (n=43), followed by IBD (n=38), ESBD after pelvic cancer surgery (n=15), and the other etiologies (n=6). Patients had a mean age of 39.4±18.7 years and were followed for a mean of 78 months. All patients had significantly increased cystometric bladder capacity and compliance at the time of follow-up. Fifty-four patients (52.9%) reported moderate to excellent satisfaction with the outcome, and there were no significant differences among the groups (P=0.430). The most common reason for dissatisfaction was the need for clean intermittent catheterization (CIC; 41.7%), followed by urinary incontinence (25.0%) and recurrent UTI (16.7%). CONCLUSIONS: AE is a safe and effective procedure for patients with ESBD. Postoperative urinary incontinence and UTI as well as the need for CIC may affect quality of life and decrease patient satisfaction.
Compliance ; Cystitis ; Follow-Up Studies ; Hospitals, General ; Humans ; Intermittent Urethral Catheterization ; Lower Urinary Tract Symptoms ; Meningomyelocele ; Patient Satisfaction ; Pelvic Neoplasms ; Quality of Life ; Retrospective Studies ; Spinal Cord Injuries ; Urinary Bladder Diseases* ; Urinary Bladder* ; Urinary Bladder, Neurogenic ; Urinary Incontinence ; Urinary Tract ; Urinary Tract Infections

No abstract available.
Adult ; Biopsy ; Carcinoma, Squamous Cell/complications/*diagnostic imaging/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Meningomyelocele/*complications/diagnosis ; *Positron Emission Tomography Computed Tomography ; Predictive Value of Tests ; *Radiopharmaceuticals ; Spinal Neoplasms/complications/*diagnostic imaging/pathology

STUDY DESIGN: Fifty patients surgically treated for tethered cord syndrome (TCS) were retrospectively studied at Liaquat National Hospital, Karachi from 2010 until 2014. PURPOSE: To assess the common presentations of TCS in our part of the world and the surgical outcome of the different presentations. OVERVIEW OF LITERATURE: TCS is a stretch-induced functional disorder of the spinal cord with its caudal part anchored by an inelastic structure, which results in characteristic symptoms and signs. Due to the variety of lesions and clinical presentations and the absence of high-quality clinical outcome data, the decision regarding treatment is difficult. METHODS: Fifty consecutive patients with TCS were reviewed retrospectively with a follow-up period of 12–48 months. The majority of the patients were 0-15 years of age with the mean age of 4 years. The presenting complaints and the associated pathologies were documented, and the patients were assessed using the new Karachi TCS severity scale for clinical assessment. RESULTS: Eighty five percent of the patients with thickened filum terminale improved. Sixty six percent of the patients with diastematomyelia, 60% with lipoma and only 46% with myelomeningocele showed clinical improvement postoperatively. Sixty two percent of the patients who presented with paraperesis improved following surgery while 37% remained stable and only one patient deteriorated. Back and leg pain improved in 93% of patients and 50% of patients with urinary impairment improved. CONCLUSIONS: Outcome of patients with TCS varies according to pathology and severity of symptoms. Diastematomyelia and thickened filum had the best outcome. The Karachi TCS severity scale is a valid tool for future studies.
Cauda Equina ; Follow-Up Studies ; Humans ; Leg ; Lipoma ; Meningomyelocele ; Neural Tube Defects* ; Pathology ; Retrospective Studies ; Spinal Cord ; Spine

BACKGROUND: The global prevalence of myelomeningocele has been reported to be 0.8-1 per 1,000 live births. Early closure of the defect is considered to be the standard of care. Various surgical methods have been reported, such as primary skin closure, local skin flaps, musculocutaneous flaps, and skin grafts. The aim of this study was to describe the clinical characteristics of myelomeningocele defects and present the surgical outcomes of recent cases of myelomeningocele at our institution. METHODS: Patients who underwent surgical closure of myelomeningocele at our institution from January 2004 to December 2013 were included in this study. A retrospective chart review of their medical records was performed, and comorbidities, defect size, location, surgical procedures, complications, and the final results were analyzed. RESULTS: A total of 14 patients underwent surgical closure for myelomeningocele defects. Twelve cases were closed with direct skin repair, while two cases required local skin flaps to cover the skin defects. Three cases of infection occurred, requiring incision and either drainage or removal of allogenic materials. One case of partial flap necrosis occurred, requiring secondary revision using a rotational flap and a full-thickness skin graft. Despite these complications, all wounds eventually healed completely. CONCLUSIONS: Most myelomeningocele defects can be managed by direct skin repair alone. In cases of large defects, in which direct repair is not possible, local flaps may be used to cover the defect. Complications such as wound dehiscence and partial flap necrosis occurred in this study; however, all such complications were successfully managed with simple ancillary procedures.
Comorbidity ; Drainage ; Humans ; Live Birth ; Medical Records ; Meningomyelocele* ; Myocutaneous Flap ; Necrosis ; Prevalence ; Retrospective Studies ; Skin ; Standard of Care ; Surgical Flaps ; Transplants ; Wound Closure Techniques ; Wounds and Injuries

OBJECTIVE: Neurogenic bladder dysfunction (NBD) in myelomeningocele (MMC) remains a major cause of renal decline. We evaluate the initial presentation, ultrasonographic, urodynamic and VCUG findings in search of indicators that can guide in early decisions in treatment to avoid poor long-term outcomes.

MATERIALS AND METHODS: From 1989 to 2013, 178 patients with neurogenic bladder due to MMC had records accessible for review. The median follow up was 10.4 years (0.9 - 25.0). Parameters reviewed were: patients' initial presentation; Ultrasonography: hydronephrosis grade and bilaterality, bladder wall thickness, and kidney size; Urodynamics: compliance, Detrusor Leak Point Pressure (DLPP), bladder activity and sphincter synergy; VCUG: grade of reflux, bladder pattern, and bladder neck appearance. Endpoints to which all parameters were compared were: 1. need for surgery, 2. continence 3. renal status, and 4. follow-up urodynamics

RESULTS: Recurrent UTI at presentation was associated with 3.1 times [OR = 3.1 (95% CI: 1.3 - 8.5)] need for surgery and incontinence at presentation was 11 times [OR=11.0 (95% CI: 3.8 - 33.4)] more likely to be incontinent in the long term. Hydronephrosis was associated with 4.4 times [OR= 4.4 (95% CI: 1.3 - 19.0)] risk for renal deterioration and 6 times [OR = 6.3, (95% CI: 3.8- 14.7)] need for surgery. Those with thickened bladder were 6 times [0R=6.0 (95% CI: 2.9 - 12.5)] more likely to have needed surgery. Patients with urodynamic findings of low compliance are 2.7 times [OR 2.7(95% CI: 1.2 - 6.3)] more likely to have needed surgery and high DLLP on initial consultation are 5.6 times [OR=5.6 (95% CI: 1.2 - 51.6)] more likely to have renal deterioration and 2.1 times [OR 2.1(95% CI: 1.1 - 4.4)] more likely needing surgery. On VCUG, those with "Christmas tree" pattern of bladder have 90% [0R=0.9 (95% CI: 0.01 - 0.70)] more risk for renal deterioration, 5 [0R=5 (95% CI: 2.5 - 10.2)] times more likely to need surgery and 70% [0R=0.7 (95% CI: 0.1 - 0.9)] more likely to have urodynamic deterioration. Finally, reflux, specifically bilateral, was associated with 4 times [OR = 4.0 (95% CI: 1.2 - 14.3)] risk renal deterioration as compared to those with no reflux findings and 9.6 times [OR=9.6 (95% CI: 4.1 - 23.8)] more likely to need surgery, while high-grade reflux had 90% more risk [OR = 0.9 (95% CI: 0.1 - 0.8)] to have urodynamic deterioration.

CONCLUSIONS: Prognostication early in the course of NBD in MMC is possible. It is recommended that patients with risk factors for deterioration be provided a more intensive regimen of treatment and follow-up to prevent further morbidity.

Human ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Child ; Child Preschool ; Infant ; Urinary Bladder, Neurogenic ; Meningomyelocele

PURPOSE: This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. MATERIALS AND METHODS: The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. RESULTS: Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. CONCLUSIONS: Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.
Anesthesia, General ; Catheterization ; Catheters ; Child* ; Compliance ; Humans ; Meningomyelocele ; Muscarinic Antagonists ; Myelodysplastic Syndromes ; Prospective Studies ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urinary Bladder, Overactive ; Urinary Incontinence* ; Urodynamics

Vertebral, anal, cardiac, tracheo-esophageal, renal, and limb(VACTERL) association is defined as the presence of at least three of the above-mentioned six manifestations. An estimated incidence of the VACTERL association is 1 in 20,000 to 35,000 live births although the diagnostic criteria vary. The VACTERL association is highly heterogeneous in clinical presentation. It may represent a spectrum from the less severely affected to the more severely affected. Diagnosis is difficult because of the number of disorders that have overlapping features with trisomy 13 syndrome, trisomy 18 syndrome, trisomy 21 syndrome, Feingold syndrome, and so on. The incidence of trisomy 18 syndrome, a type of a chromosomal disorder, is estimated to be 1 in 6,000-8,000 live births. It includes characteristic craniofacial anomalies, clenched hand with overlapping of index finger over third, fifth finger over fourth, underdeveloped thumbs, short sternum, cardiac anomalies such as ventricular septal defect, and renal anomalies such as horseshoe kidney. Approximately over 50% of infants with trisomy 18 syndrome live less than one week. In 1983, Khoury et al. reported VACTERL association combined with trisomy 18 syndrome. Here, we report a case of a low birth weight female infant with VACTERL association, whose second diagnosis is Edward syndrome, and that she also has another combined anomaly, meningomyelocele. To the best of our knowledge, this is the first reported case of VACTERL association with meningomyelocele combined with trisomy 18 syndrome in Korea.
Chromosome Disorders ; Diagnosis ; Down Syndrome ; Female ; Fingers ; Hand ; Heart Septal Defects, Ventricular ; Humans ; Incidence ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Kidney ; Korea ; Live Birth ; Meningomyelocele* ; Sternum ; Thumb ; Trisomy*

Neural tube defects are the major targets of prenatal diagnoses, along with Down syndrome. Prenatal diagnosis of spina bifida is possible at second trimester of gestation through alpha-fetoprotein and acetylcholinesterase biochemistry assays and ultrasound. In particular, the discovery of characteristic intracranial signs on ultrasound leads to a very high diagnosis rate. However, it is rare for spina bifida to present without intracranial signs while also showing normal values of maternal serum alpha-fetoprotein, amniotic fluid alpha-fetoprotein, and acetylcholinesterase. In our hospital, a fetus with spina bifida was delivered at 37+5 weeks' gestation by cesarean section, and was continually followed up over 2 years to date.
Acetylcholinesterase* ; alpha-Fetoproteins* ; Amniotic Fluid* ; Biochemistry ; Cesarean Section ; Diagnosis ; Down Syndrome ; Female ; Fetus ; Humans ; Meningocele ; Meningomyelocele* ; Neural Tube Defects ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; Reference Values ; Spinal Dysraphism ; Ultrasonography*