Multidisciplinary management of people with spina bifida across the lifespan.

The average worldwide prevalence of neural tube defects (NTDs) is 1.0 per 1000 births. Its development is multifactorial due to genetic and non-genetic factors. Spina bifida (SB) is one of main representatives of NTD. The spinal cord lesion level is the main determinant of the level of paralysis, numbness, and difficulties with bladder/bowel functions. Myelomeningocele prenatal repair reduces hydrocephalus and hindbrain herniation and improves motor function. The severity of hydrocephalus is associated with poorer neurodevelopmental outcomes whether operated on prenatally or after birth. People with SB tend to have a lower IQ and cognitive difficulties. Early diagnosis, proactivity, and lifelong multidisciplinary follow-up are key protective issues. Invasive urological interventions should be considered in selected patients after failure of conservative treatment. Transition to adult care should be well planned as it is challenging. Health literacy is directly associated with success at transition. Sexuality and fertility should be addressed before/during puberty. Overall, the rates of fecal and urinary continence and skin breakdown increase with age, whereas the ability to ambulate declines with age. Bowel and urinary incontinence are independent predictors of lower health-related quality of life (HRQoL) in adults with SB. Bowel incontinence has negative impact on HRQoL regardless of frequency or amount. Long-term caregiver support should be offered at diagnosis. Survival at a mean of 50 years is poor, at 32%, due to central nervous system deaths, cancer, urological disease, and sepsis. Challenges to implementation of recommended practices exist, especially in low and middle-income countries.

Importance of Regular Examination and Follow-up in Pediatric Patients with Neurogenic Bladder: 24-Month Follow-up Study Using a Japanese Health Insurance Database.

INTRODUCTION: Data on the long-term management of neurogenic bladder (NGB) are scarce. We evaluated the current status of NGB management in Japanese children over 24-month follow-up using the JMDC database. METHODS: In this descriptive, observational, retrospective cohort study, patients (≤ 17 years) with NGB were included. Patient characteristics and their management status were investigated. A multivariate analysis evaluating the potential risk factors for the development of urinary tract infection (UTI) was performed. The diagnosis of spina bifida, demographics, baseline comorbidities, and early use of clean intermittent catheterization (CIC) and/or overactive bladder (OAB) drugs were used as independent variables. RESULTS: Of 883 eligible children, 39.3% had spina bifida. Over 12/24-month post-index periods, renal urinary tract ultrasound and urinalysis were performed at least once in > 35%/> 45% patients, respectively, while specific tests (urodynamics, cystourethrography, scintigraphy) were performed in substantially fewer (< 11%/< 13%) patients. Over 24 months, 21.5% patients used OAB medications (mostly anticholinergics) and 10.8% underwent CIC, alone or with medications; 1.2% patients underwent surgery. Lower UTI (23.3%), urinary incontinence (9.7%), and hydronephrosis (7.0%) were the most common incident complications. Multivariate analysis evaluating risk factors for UTI showed significantly higher odds ratios with point estimates of ≥ 2 for CIC (5.70), presence of spina bifida (2.86), and constipation (2.07). Overall, urodynamic assessments were inadequately performed. CONCLUSION: Patients with use of CIC and/or having spina bifida and constipation had a higher risk of UTI, suggesting the need for careful follow-up. More guideline-compliant and diligent patient management is necessary in Japanese children with NGB.

Improving Bowel Management in Children With Spina Bifida.

OBJECTIVES: In individuals with spina bifida (SB), bowel incontinence is associated with lower quality of life and lower likelihood of employment. In an effort to maximize bowel continence in children and adolescents, we created a bowel management assessment and follow-up protocol in a multidisciplinary clinic. Here we report the results of this protocol using quality-improvement methodology. METHODS: Continence was defined as no unplanned bowel movements. Our protocol involved: (1) a standardized 4-item questionnaire about bowel continence and consistency; (2) if the patient was not achieving continence, an intervention starting with oral medication (stimulant and/or osmotic laxatives), and/or suppositories (glycerin or bisacodyl) followed by an escalation to trans-anal irrigation, or continence surgery; and (3) follow-up phone calls at regular intervals to monitor progress and make changes as needed. Results are summarized with descriptive statistics. RESULTS: We screened 178 eligible patients in the SB clinic. Eighty-eight agreed to participate in the bowel management program. Of those who did not participate, the majority (68/90, 76%) were already achieving continence with their bowel regimen. Of children in the program, most (68/88, 77%) had a diagnosis of meningomyelocoele. At 1 year, the proportion of patients who were bowel accident free improved to 46% (vs 22% initially, P = 0.0007). CONCLUSIONS: A standardized bowel management protocol, primarily the use of suppositories and trans-anal irrigation to achieve social continence, as well as frequent telephone follow-up, can reduce bowel incontinence in children and adolescents with SB.

Multi-Institutional Review From the Pediatric Colorectal and Pelvic Learning Consortium of Minor Spinal Cord Dysraphism in the Setting of Anorectal Malformations: Diagnosis, Treatment, and Outcomes.

BACKGROUND/RATIONALE: Anorectal malformations (ARM) are associated with congenital anomalies of the spine, but the impact of a minor spinal cord dysraphism (mSCD) on fecal continence in the setting of ARM remains unclear. MATERIALS/METHODS: A retrospective review was performed utilizing data from the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry. The patient cohort was reviewed for ARM type, mSCD screening/incidence/neurosurgical intervention and age-based BMP utilization. RESULTS: 987 patients with ARM were categorized into mild (38%), moderate (32%) or complex (19%). 694 (70%) had normal spinal (NS) status. 271 (27.5%) patients had mSCD. MRI alone (49%) was the most common screening test for mSCD. US screening had a positive predictive value of 86.3% and a negative predictive value of 67.1%. Surgical intervention rates for mSCD ranged between 13% and 77% at a median age of 0.6-5.2 years. 726 (73.6%) patients were prescribed BMP (74.4% NS, 77.5% mSCD). Laxatives were most utilized BMP in all groups <5yo. ≥5yo, enema utilization increased with ARM complexity independent of spine status (with or without neurosurgical intervention). Neurosurgical intervention did not affect BMP utilization at any age or with any ARM when mSCD was identified. CONCLUSIONS: MSCD influence on bowel function in the setting ARM remains unclear. No significant impact of mSCD was noted on ARM patient bowel management program utilization. Variability exists within PCPLC site with screening and intervention for mSCD in patients with ARM. Future studies with standardized care may be needed to elucidate the true impact of mSCD on long term patient outcomes in ARM patients. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: III.

Transitioning care for adolescents with spina bifida in the US: challenges for management.

Open spina bifida (OSB) is a common neural tube defect. Medical and surgical care involves addressing the baseline orthopedic, urologic, and neurological dysfunction as well as the changes or declines that may occur as the patient ages. Given the complexity of this disease, coordinated, multidisciplinary care involving specialists in neurosurgery, orthopedics, urology, rehabilitation and physical medicine, pediatrics, and psychology is necessary to establish and optimize baseline function. Traditionally in the US, pediatric multispecialty spina bifida clinics have provided the patient with a coordinated medical support system. Unfortunately, this coordinated, medical home has been difficult to establish during the transition from pediatric to adult care. Medical professionals must have a strong understanding of OSB to properly manage the disease and detect and prevent associated complications. In this manuscript, we (1) describe the changing needs and challenges of people living with OSB over a lifespan, (2) delineate current practices in the transition of care for people with OSB from childhood to adulthood, and (3) provide recommendations for best practices in navigating the transition process for clinicians who provide care for those afflicted with this most complex congenital abnormality of the nervous system compatible with long term survival.

Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida.

BACKGROUND: To evaluate the safety and efficacy of autologous bone marrow mononuclear cell (BMMNC) infusion in the management of neurological sequelae in children with spina bifida (SB). METHODS: BMMNCs were harvested from bilateral anterior iliac crests. Two intrathecal BMMNC administrations were performed with an interval of 6 months. The measurements of outcomes included clinical assessments, cystomanometry and rectomanometry. RESULTS: Eleven children with SB underwent autologous BMMNC infusions from 2016 to 2020. There were no severe adverse events during the study period. The number of patients requiring assistance to expel stools decreased from 11 before cell infusion to 3 after the second cell infusion. The number of patients who had urine leakage decreased from 9 patients at baseline to 3 patients after the second BMMNC infusion. The mean bladder capacity increased from 127.7 ± 59.2 ml at baseline to 136.3 ± 54.8 ml at six months and to 158.3 ± 56.2 ml at 12 months after BMMNC infusions. Detrusor pressure (pdet) decreased from 32.4 ± 22.0 cm H2O at baseline to 21.9 ± 11.8 cm H2O after 12 months of follow-up. At baseline, six patients could walk independently. After the 2nd infusion, eight patients could walk independently. CONCLUSION: Intrathecal infusions of autologous bone marrow mononuclear cells are safe and may improve bowel, bladder, and motor function in children with SB. TRIAL REGISTRATION: NCT, NCT05472428. Registered July 25, 2022- Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05472428 .

Combining Bone Collagen Material with hUC-MSCs for Applicationto Spina Bifida in a Rabbit Model.

Spina bifida is one of the neural tube defects, with a high incidence in human birth defects, which seriously affects the health and quality of life of patients. In the treatment of bone defects, the source of autologous bone is limited and will cause secondary damage to the patient. At the same time, since the bone tissue in animals needs to play a variety of biological functions, its complex structure cannot be replaced by a single material. The combination of mechanical materials and biological materials has become a common choice. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have the advantages of easy access, rapid proliferation, low immunogenicity, and no ethical issues. It is often used in the clinical research of tissue regeneration and repair. Therefore, in this study, we established a spina bifida model using Japanese white rabbits. This model was used to screen the best regenerative repair products for congenital spina bifida, and to evaluate the safety of regenerative repair products. The results showed that the combination of hUC-MSCs with collagen material had better regeneration effect than collagen material alone, and had no negative impact on the health of animals. This study provides a new idea for the clinical treatment of spina bifida, and also helps to speed up the research progress of regenerative repair products.

From autism to zoom®: Spina bifida advocacy, care, education, and research in a changing word.

Whereas legislation mandates for folic acid fortification have been implemented throughout many nations, divergent neural tube defects (NTDs) prevalence rates still remain among the world's populations. In North America, the prevalence estimate is 39 infants per 100,000 live births. Open spina bifida (SB), also known as myelomeningocele, remains the most complex congenital abnormality of the central nervous system compatible with long term survival; this recognized complexity gives rise to emerging comorbidities and interventions. For example, increasing autism spectrum disorder rates have been reported among individuals with SB utilizing a 31,220 subject population-based birth cohort. Along with new clinical observations, telecommunication platforms such as Zoom® have evolved as clinical and investigational tools. Historically, society meetings, research conferences, and journals have provided opportunities for professional development and dissemination of up-to-date materials. The Journal of Pediatric Rehabilitation Medicine (JPRM) has arisen as an open-access global platform for the dissemination of SB-related inquiry. The journal has also highlighted the research presented at the Spina Bifida Association's previous Spina Bifida World Congresses. At the last congress, which was held in 2017, twenty-three countries were represented; this number is expected to grow by the next convocation in 2023. This congress will provide an opportunity for health care professionals from around the globe to present a broad array of research topics and build collaborations. Concurrently, the JPRM will continue as an open-access platform for SB advocacy, care, education, and investigation, across our fast changing world for the international SB community well into the future.

Investigating the landscape and trajectory of spina bifida research in Asia: a bibliometric analysis.

BACKGROUND: Spina bifida is a type of a neural tube defect which affects 243.14 per 100,000 babies in Asia. Research articles on spina bifida have increased in the recent years. However, no study has focused on the research trends in this field in Asia. METHODS: A systematic review of literature on spina bifida in Asia was performed using the Scopus database from inception to 2020. All published studies on spina bifida conducted in or published by authors from Asia were included in our analysis. Bibliometric information was obtained from Scopus and bibliometrics diagrams were created using VOSviewer software. RESULTS: A total of 652 articles were obtained in this study. The number of publications showed an upward trend starting 2000s. The country with the greatest number of publications was Japan while All India Institute of Medical Sciences was the most productive institution in spina bifida research in Asia. The current focus of this field in Asia was prevalence of spina bifida, prenatal diagnosis, folic acid supplementation, and complications of spina bifida. Future areas of research in spina bifida include the genetic basis of neural tube defects and the use of stem cell technology as therapies for spina bifida. CONCLUSION: This is the first bibliometric analysis on spina bifida in Asia. It showed the trend and future areas of research on spina bifida in Asia. Despite the increase in scientific literature on spina bifida research, more research outputs and collaborations are needed especially in developing countries in Asia.

[Chronic sacral neuromodulation for pelvic floor dysfunction in children with spina bifida]. / Lechenie narusheniya funktsii tazovykh organov u detei s mielodisplaziei metodom khronicheskoi sakral'noi neirostimulyatsii.

OBJECTIVE: To estimate the effectiveness of chronic sacral neurostimulation for neurogenic lower urinary tract dysfunction in children with spina bifida. MATERIAL AND METHODS: Eight patients with spina bifida and neurogenic lower urinary tract dysfunction underwent surgical treatment. Three patients had detrusor-sphincter dyssynergia and urinary incontinence. Five patients had detrusor overactivity and urine retention. Conservative treatment was failed in all cases. We implanted quadripolar test electrode on the S3 root through Tuohy needle under fluoroscopic control. Test stimulation was ineffective in three children with detrusor overactivity. Five patients with positive response to stimulation underwent implantation of chronic neurostimulation system. We estimated the efficacy of neurostimulation considering symptoms of neurogenic lower urinary tract dysfunction, urinary diary, PAD test and complex urodynamic examination data. RESULTS: Positive clinical effects were observed in 3 patients with detrusor-sphincter dyssynergia and 2 patients with detrusor overactivity. Clinical effect included improvement in urine leakage and higher bladder volume. In patients with urinary retention, we revealed voluntary urination and less number of daily catheterization procedures. In one patient, clinical effect of chronic stimulation regressed within 3 month after surgery. CONCLUSION: Preliminary results of chronic sacral neuromodulation confirmed its advisability in children with neurogenic lower urinary tract dysfunction. Patients with detrusor-sphincter dyssynergia had better results compared to those with detrusor overactivity.

Amniotic fluid-derived stem cell potential for therapeutic and surgical use: A review of the literature.

OBJECTIVE: Spina bifida is a debilitating neutral tube defect affecting many infants. The impact and severity of spina bifida depends on whether the patient exhibits a closed defect, spina bifida occulta, or an open defect, spina bifida aperta. Patients with spina bifida have physical and mental disabilities which merit further research into less invasive, more successful treatments. In addition to serving as protection for the growing fetus and facilitating nutrient exchange, amniotic fluid (AF) is a rich source of a mixed population of stem cells. As such, in vitro culture of AF-derived stem cells has shown promise among therapeutic and surgical applications. We present a critical evaluation of the current preclinical efforts, amniotic fluid-derived stem cell (AFSC) culture process, and the subsequent therapeutic application, with a focus on improvements for spina bifida outcomes in the pediatric patient population. METHOD: An evidence - based literature review to investigate the current literature surrounding AFSC culture and use, with an emphasis on the benefits for spina bifida treatment. RESULTS: 47 literature sources from PubMed and three studies from ClinicalTrials.gov. CONCLUSION: This review synthesizes the current literature, which shows promising data on AFSC pluripotency, as well as successful in utero coverage from AFSC - supported environments in a multitude of animal models.

Prenatal Neural Tube Anomalies: A Decade of Intrauterine Stem Cell Transplantation Using Advanced Tissue Engineering Methods.

Neural tube defects (NTDs) are among the most common congenital defects during neurulation. Spina bifida is a type of NTD that can occur in different forms. Since myelomeningocele (MMC) is the most severe form of spina bifida, finding a satisfactory treatment for MMC is a gold standard for the treatment of spina bifida. The Management of Myelomeningocele Study (MOMS) demonstrated that intrauterine treatment of spina bifida could ameliorate the complications associated with spina bifida and would also reduce the placement of ventriculoperitoneal (VP) shunt by 50%. Recently developed tissue engineering (TE) approaches using scaffolds, stem cells, and growth factors allow treatment of the fetus with minimally invasive methods and promising outcomes. The application of novel patches with appropriate stem cells and growth factors leads to better coverage of the defect with fewer complications. These approaches with less invasive surgical procedures, even in animal models with similar characteristics as the human MMC defect, paves the way for the modern application of less invasive surgical methods. Significantly, the early detection of these problems and applying these approaches can increase the potential efficacy of MMC treatment with fewer complications. However, further studies should be conducted to find the most suitable scaffolds and stem cells, and their application should be evaluated in animal models. This review intends to discuss advanced TE methods for treating MMC and recent successes in increasing the efficacy of the treatment.

The importance of dedicated colorectal team participation in the management of spina bifida and spinal cord injury patients.

PURPOSE: In September 2020, the colorectal team of the International Center for Colorectal and Urogenital Care joined the spina bifida and spinal cord injury multidisciplinary clinic at Children's Hospital Colorado. Many important lessons were learned. METHODS: A retrospective review of patients seen in the spina bifida and spinal cord injury multidisciplinary clinic from September 2020 to May 2021 was conducted. Data collected included demographics, diagnosis, pre or post-natal repair for those with myelomeningocele, whether the patient was previously seen by the colorectal team, wheelchair usage, voluntary bowel control vs. fecal incontinence, urinary control vs. clean intermittent catheterization, characteristics of contrast enema, and our proposed intervention. RESULTS: Overall, 189 children were seen during the study period, ranging from 3 months to 20 years of age (average = 9.5 years). One hundred and two were males and 87 were females. Diagnosis included myelomeningocele (n = 153), spinal cord injury (n = 18), transverse myelitis (n = 7), sacral agenesis (n = 5), diastematomyelia (n = 2), spinal stenosis (n = 2), and tethered cord with lipoma (n = 2). Fifteen patients with myelomeningocele were repaired in-utero. One hundred and sixty patients were new to the colorectal team. Eighty-one patients were wheelchair users. One hundred and twenty-three patients suffered from fecal incontinence and needed enemas to be artificially clean for stool and thirty-eight patients had voluntary bowel movements and were clean with laxatives, suppository, or rectal stimulations. Twenty-eight patients were younger than three years of age and still in diapers. Despite a non-dilated colon on contrast enema, this population has a hypomotile colon. One hundred and twenty-eight patients required clean intermittent catheterization. CONCLUSION: Joining the spina bifida and spinal cord injury multidisciplinary clinic allowed us to better serve this population and gave us enormous satisfaction to contribute to improve the quality of life of the patients and their parents. LEVEL OF EVIDENCE: III.

The impact of constant antibiotic prophylaxis in children affected by spinal dysraphism performing clean intermittent catheterization: a 2-year monocentric retrospective analysis.

INTRODUCTION: Spinal dysraphism (SD) is a general term used to refer to developmental abnormalities of the spine that involves many clinical conditions including myelomeningocele (MMC). In these patients, neurogenic bladder (NB) is a common and predisposing factor for renal damage; the most frequently used approach to manage this situation is based on clean intermittent catheterization (CIC) and anticholinergic drugs. Urinary tract infections (UTIs) are a significant concern for these patients, and antibiotic prophylaxis is frequently used even if it is still a debated topic of literature. The purpose of this paper is to investigate the role and the real effectiveness of antibiotic prophylaxis in the reduction of incidence of UTIs in patients with spina bifida performing CIC. METHODS: We collected data of all patients performing CIC, who did their last follow-up visit in the period between January 2019 and January 2021, followed at the children multidisciplinary Spina Bifida Center of A. Gemelli Hospital in Rome. Data collected included age at referral, gender, type of SD lesion, serum creatinine and cystatin C levels, the use of anticholinergic medications, antibiotic prophylaxis and type of prophylaxis (oral/endovesical), age of starting prophylaxis with its duration/adherence, number of CIC/day and its duration, episodes of UTIs in the 2 years prior to the last follow-up, and presence and grade of vesical-ureteric reflux (VUR) on cystourethrogram. RESULTS: A total of 121 patients with SD performing CIC was included in the study; 66 (54%) presented ≥ 1 episode of UTIs in the last two years and 55 (46%) none. During the study period, 85 (70%) patients received antibiotic prophylaxis (ABP group) and 36 (30%) did not (NABP group): no statistically significative difference in terms of UTI development was observed between the two groups (p = 0.17). We also evaluated compliance to the therapy; 71 patients (59%) took antibiotic prophylaxis constantly (CABP group) and 50 (41%) did not do antibiotic prophylaxis constantly or did not do antibiotic prophylaxis at all (NCABP group): we observed a statistically significative difference in terms of UTIs with a 2.2 times higher risk of development at least one episode of UTIs in NCABP group. CONCLUSION: In conclusion, antibiotic prophylaxis performed constantly, without interruption, is associated with a lower risk of developing urinary tract infections and consequently to develop renal failure in adulthood.

[Expert consensus on diagnosis and treatment of spina bifida].

Spina bifida and tethered spinal cord are congenital diseases that can lead to severe disability. At present, most doctors in relevant specialties in China still have insufficient understanding of spina bifida, resulting in high incidence and aggravation of its complications. To provide guidance for the diagnosis and treatment of spina bifida and tethered spinal cord in China, experts from neurosurgery, urology, orthopedics, spine surgery, and rehabilitation departments who have experiences in the diagnosis and treatment of spina bifida discussed and summarized their experiences, and referred to the relevant literature on the diagnosis and treatment of spina bifida at home and abroad. Expert consensus was formed in the following aspects: concept, classification, and pathological changes of spina bifida; diagnosis; treatment process and operation timing; principles and methods of treatment; rehabilitation; and follow up. This expert consensus can provide reference for relevant care providers of spina bifida in China.

[Effectiveness and safety of sacral neuromodulation on neurogenic bladder and bowel dysfunction in patients with spina bifida].

OBJECTIVE: To evaluate the effectiveness and safety of sacral neuromodulation (SNM) in the treatment of neurogenic bladder and bowel dysfunction in patients with spina bifida. METHODS: The clinical data of 33 patients with neurogenic bladder and bowel dysfunction caused by spina bifida treated with SNM between July 2012 and May 2021 were retrospectively analyzed. There were 19 males and 14 females, with an average age of 26.0 years (range, 18.5-36.5 years). The disease duration ranged from 12 to 456 months, with an average of 195.8 months. The types of spina bifida included 8 cases of occult spina bifida and 25 cases of meningocele/myelomeningocele. Clinical symptoms included 19 cases of urgency-frequent urination, 18 cases of urinary incontinence, 27 cases of chronic urinary retention, and 29 cases of bowel dysfunction. Image urodynamics showed that 4 patients had detrusor overactivity (DO) and 29 patients had detrusor underactivity (DU). Vesicoureteral reflux (VUR) was found in 5 ureters (4 patients). SNM procedure was divided into experiential treatment and permanent implantation. Patients who were evaluated as successful or willing to be permanently implanted after experiential treatment would implant the permanent pulse generator. RESULTS: The duration of experiential treatment was 14-28 days, with an average of 19.2 days; there was no complication during this period, and the overall success rate was 69.69% (23/33). At the end of experiential treatment, the urination frequency in 24 hours, urine volume per time, urinary urgency score, and urine leakage of patients were significantly improved when compared with those before experiential treatment ( P<0.05); there was no significant difference in postvoid residual volume between before and after experiential treatment ( t=1.383, P=0.179). The success rate of patients with chronic urinary retention after experiential treatment (25.93%) was significantly lower than that of urgency-frequent urination (63.16%) and urinary incontinence (61.11%) ( χ 2=7.260, P=0.064). Compared with those before experiential treatment, the maximum cystometric capacity and compliance increased and the maximum detrusor pressure during filling decreased significantly ( P<0.05). Among the 4 patients with DO before experiential treatment, DO disappeared in 2 cases; 27 patients with DU before experiential treatment did not recover the normal contraction of detrusor during micturition. Among the 5 ureters with VUR before experiential treatment, 2 VUR disappeared at the end of experiential treatment, and the VUR grade or the bladder volume before VUR of the other 3 ureters were improved. At the end of experiential treatment, the neurogenic bowel dysfunction (NBD) score and the grade of bowel dysfunction significantly improved ( P<0.05). A total of 19 patients received permanent implantation, of which 11 patients needed to empty the bladder in combination with intermittent catheterization. CONCLUSION: SNM is effective for neurogenic bladder and bowel dysfunction in patients with spina bifida. At the same time, it can significantly improve the urodynamic parameters during urine storage and avoid upper urinary tract damage.

Pediatric Spinal Cord Diseases.

Spinal cord diseases in pediatric patients are highly variable in terms of presentation, pathology, and prognosis. Not only do they differ with respect to each other but so too with their adult equivalents. Some of the most common diseases are autoimmune (ie, multiple sclerosis, acute disseminated encephalomyelitis, and acute transverse myelitis), congenital (ie, dysraphism with spina bifida, split cord malformation, and tethered cord syndrome), tumor (ie, juvenile pilocytic astrocytoma, ependymoma, and hem-angioblastoma), and vascular (ie, cavernous malformations, arteriovenous malformations, and dural arteriovenous fistulas) in nature. These each require their own niche treatment paradigm and prognosis. Furthermore, presentation of different spinal cord diseases in children can be difficult to discern without epidemiologic and imaging data. Interpretation of these data is crucial to facilitating a timely and accurate diagnosis. Correspondingly, the aim of this review was to highlight the most pertinent features of the most common spinal cord diseases in the pediatric population.

Enhancement of transamniotic stem cell therapy for spina bifida by genetic engineering of donor mesenchymal stem cells with an Fgf2 transgene.

BACKGROUND/PURPOSE: We examined whether engineered overexpression of fibroblast growth factor-2 (Fgf2) in donor mesenchymal stem cells (MSCs) could enhance spina bifida coverage induced by transamniotic stem cell therapy (TRASCET). METHODS: Pregnant Sprague-Dawley dams (n = 24) exposed to retinoic acid for induction of fetal spina bifida were divided in three groups. An untreated group had no further manipulations. Two groups received volume-matched intra-amniotic injections into all fetuses (n = 157) of either amniotic fluid-derived MSCs (afMSC; n = 85) or afMSCs transduced with an Fgf2 transgene (Fgf2-afMSC; n = 72) on gestational day 17 (term=21-22 days). Defect coverage was categorized at term by histology and pan-cytokeratin immunohistochemistry. Statistical coverage comparisons were by logistic regression. RESULTS: Among 84 survivors with isolated spina bifida, 71 had definitive histology. Defect coverage rates in both the afMSC (38.5%) and Fgf2-afMSC (73.3%) groups were statistically significantly higher than in the untreated group (10%; p<0.001 for both). There was a significantly higher coverage rate in the Fgf2-afMSC group compared with the afMSC group (p = 0.025). CONCLUSIONS: Fgf2 overexpression in donor mesenchymal stem cells increases defect coverage rates in a rodent model of transamniotic stem cell therapy for spina bifida. Genetic engineering of donor cells is a promising strategy for the enhancement of this emerging therapy.

Trends in Procedures to Initiate Renal Replacement Therapy among People Living with Spina Bifida.

PURPOSE: Given the increasing prevalence of chronic kidney disease in people with spina bifida, we sought to determine if this is associated with an increase in end stage kidney disease. We examined population based data to measure the frequency of procedures to establish renal replacement therapy-a marker for end stage kidney disease-among patients with spina bifida. MATERIALS AND METHODS: We used the Healthcare Cost and Utilization Project State Inpatient Database and State Ambulatory Surgery and Services Database from Florida, Kentucky, Maryland and New York (2000 to 2014), which include encounter level data. With a diagnosis code based algorithm we identified all procedural encounters made by patients with spina bifida. We determined the percentage of these encounters that were for facilitating renal replacement therapy (ie arteriovenous anastomosis, renal transplantation). We assessed for changes over time in this percentage with the Cochran-Armitage trend test. Bivariate analysis was performed using chi-square test. RESULTS: Of all procedures performed on patients with spina bifida over this time the proportion of procedures performed to establish renal replacement therapy significantly decreased in both the inpatient and outpatient settings (p=0.042 and p <0.001, respectively). People with spina bifida undergoing procedures to establish renal replacement therapy were, on average, young adults (mean age 34.5 and 36.0 years) with a high prevalence hypertension (75.8% of inpatients, 68.6% of outpatients). CONCLUSIONS: The frequency of surgeries to initiate renal replacement therapy among people with spina bifida undergoing procedures is low and is not increasing. This highlights the importance of consistent care throughout adolescence and young adulthood, and hypertension screening.