Spina Bifida Research Articles

Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

A national postgraduate nurse practitioner and physician assistant fellowship in cystic fibrosis: An innovative approach to the provider shortage in complex and rare disease.

Cystic fibrosis (CF) is a complex life-limiting genetic condition that affects the respiratory, digestive, reproductive system, and sweat glands. Advances in treatment have led to improved survival and quality of life. Today, most persons with CF live to adulthood but require highly specialized care at accredited CF Care Centers. The growing and aging CF population combined with the provider workforce shortage have increased the demand for qualified CF providers. Nurse practitioners (NPs) and physician assistants (PAs) have been providing CF care for decades, but most learned on the job. The Leadership and Education for Advanced Practice Provider (LEAPP) fellowship in CF care aims to address the provider gap, ease transition to practice, and ensure access to specialized care. Unlike other institutional based joint NP/PA fellowships, LEAPP was designed to train providers at various locations across the national CF care center network. The program is innovative in several ways: (1) LEAPP employs a flipped classroom that pairs an online curriculum with case-based virtual discussion with content experts from the CF care network; (2) fellows receive mentored clinical training at their home CF center; (3) LEAPP partnered with a university-based team to ensure best practices and evaluation for adult learners; and (4) LEAPP promotes organizational enculturation through program components of professional mentoring, quality improvement, and leadership. This innovative approach may be suitable for other complex conditions that require highly specialized care, such as sickle cell disease, spina bifida, and solid organ transplant.

“Crafting a ‘TransitionOmeter’: A Proposed Framework for Developing and Honing Capabilities of Young People Transitioning to Adult Healthcare Services.”

ABSTRACT This paper focuses on an innovative approach to preparing children and young people, with Spina Bifida, to move from child-centered to adult-oriented healthcare systems. Reflecting on our role in delivering a national nurse led service, we set to identify and critique international transition tools in use for this population. Specifically, we aimed to identify the core capabilities and indicators of progression to successful transition, so that holistic interventions could be planned to match the needs of individuals and their carers. There were two phases to the study, initially focusing on a systematic literature review on transition tools and the specific items that these tools captured, including skills, abilities and behaviors. Phase two culminated in the articulation of a segmented and incremental “road map”, aligned with facets deemed essential for a successful healthcare transition. The reporting of the literature review (phase one) followed the PRISMA guidelines and shaped the qualitative element of the study (phase two) through the use of semi-structured interviews and thematic analysis. The search strategy yielded 11 studies, which were then manually searched for other relevant literature, adding a further 14 articles. The review analyzed 7 specific tools for spina bifida and 8 generic tools, which were deemed appropriate for this group of patients. A comprehensive list of core capabilities was then articulated and framed to fit a progression timeline. Specific interventions were formulated to explore ways to co-produce resources that could enhance and support a planned transition to adult-focused services. Our proposed mapping of capabilities and progression could shape other transition programs, where nurses work collaboratively with young people, carers and other members of a team. More work is needed to further explore and embed the framework that, as we did, could be digitized and shared with all stakeholders involved in the transition process.

Long-Term Quality of Life for Patients with Spina Bifida

Abstract Purpose of Review This review explores the literature that currently exists regarding quality of life for patients with spina bifida and assesses screening tools available for practitioners to assess these outcomes. Domains addressed include health related quality of life, relationships, bowel and bladder dysfunction, sexuality, pain, and mood. Recent Findings Several recent papers have assessed available questionnaires and reviewed findings of key quality of life domains, with varying results. Summary Historically, the literature has focused on surgical outcomes for patients with spina bifida. Though some authors have begun to explore quality of life for this patient population, particularly in the short-term, a paucity of quality, long-term studies exist that describe quality of life domains or offer potential targets for improvements in outcomes.

Quality of Life and Bladder Symptoms in Adolescents and Young Adults With Spina Bifida Who Catheterize via Urethra Versus Catheterizable Channel.

To assess associations between health-related quality of life (HRQOL), bladder-related QOL, bladder symptoms, and bladder catheterization route among adolescents and young adults (AYA) with spina bifida (SB). Clinical questionnaires administered to individuals ≥ 12-years-old requiring catheterization between June 2019-March 2020 in a SB center were retrospectively analyzed. Questionnaires were completed in English or Spanish independently or with caregiver assistance. Medical records were reviewed for demographic and clinical characteristics. Primary exposure was catheterization route (urethra or channel). Primary outcome was HRQOL, measured by Patient Reported Outcome Measure Information System Pediatric Global Health 7 (PGH-7). Secondary outcomes were bladder-related QOL and bladder symptoms, measured by Neurogenic Bladder Symptom Score (NBSS). Nested, multivariable linear regression models assessed associations between catheterization route and questionnaire scores. Of 162 patients requiring catheterization, 146 completed both the PGH-7 and NBSS and were included. Seventy-three percent catheterized via urethra and 27% via channel. Median age was 17.5 years (range 12-31), 58% of patients were female, and 80% had myelomeningocele. Urinary incontinence was more common among those who catheterized via urethra (60%) compared to channel (33%). On adjusted analyses, catheterization route was not significantly associated with PGH-7 or NBSS bladder-related QOL scores. More bladder symptoms were associated with worse bladder-related QOL. Patients who catheterized via channel had fewer bladder symptoms than those who catheterized via urethra. Catheterization route was not significantly associated with QOL. Though catheterization via channel was associated with fewer bladder symptoms, only degree of current bladder symptoms was significantly associated with bladder-related QOL.

Risk of meningomyelocele mediated by the common 22q11.2 deletion.

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Antibiotic Overtreatment of Presumed Urinary Tract Infection among Children with Spina Bifida

To identify factors associated with overtreatment of presumed urinary tract infection (UTI) among children with spina bifida using such criteria. A retrospective review of children with spina bifida (age < 21 years) evaluated in the Emergency Department (ED) at a single institution was performed. Patients with a urinalysis (UA) performed who were reliant on assisted bladder emptying were included. The primary outcome was overtreatment, defined as receiving antibiotics for presumed UTI but ultimately not meeting spina bifida UTI criteria (≥ 2 urologic symptoms plus pyuria and urine culture growing >100k CFU/mL). The primary exposure was whether the components of the criteria available at the time of the ED visit (≥ 2 urologic symptoms plus pyuria) were met when antibiotics were initiated. Among 236 ED encounters, overtreatment occurred in 80% of cases in which antibiotics were initiated (47% of the entire cohort). Pyuria with <2 urologic symptoms was the most important factor associated with overtreatment (OR 9.6). Non-Hispanic White race was associated with decreased odds of overtreatment (OR 0.3). Overtreatment of presumed UTI among patients with spina bifida was common. Pyuria, which is not specific to UTI in this population, was the main driver of overtreatment. Symptoms are a cornerstone of UTI diagnosis among children with spina bifida, should be collected in a standardized manner, and considered in a decision to treat.

6290914 14 year review of the anaesthetic management of the parturient with spina bifida

6290914 14 year review of the anaesthetic management of the parturient with spina bifida

A case of dumbbell-shaped accessory scrotum with concomitant lipoma

BackgroundAccessory scrotum is a congenital scrotal anomaly that is usually located anterior to the anus and frequently presents with a lipoma in a bead-like shape. Herein, we present an unusual case of an accessory scrotum with a lipoma connected by a narrow stalk and located posterior to the anus.Case presentationA 1-month-old boy was referred to our hospital for a perineal mass present at birth. He was born at 37 weeks and 2 days, with a birth weight of 2962 g. No abnormalities occurred during the perinatal period, and the birth was uneventful. The mass had an unusual shape, comprising two masses connected by a narrow stalk. The base of the mass was posterior to the anus and was connected to the rectal mucosa. The proximal mass was elastic and soft without skinfolds, whereas the distal mass was elastic and soft with a scrotum-like skinfolds. Magnetic resonance imaging showed no spina bifida. High-intensity adipose tissues in both masses and low-intensity vessels or fibrous stroma in cord-like structures between the two masses were found on T2-weighted images. At 3 months of age, the patient underwent resection in the prone jackknife position. No tumorous lesions were connected to the mass on the rectal and coccyx sides, and the mass was completely removed, preserving the anal sphincter. Histologically, the distal mass had characteristics of a scrotum, whereas the proximal mass was exclusively a lipoma. The connecting stalk had normal skin structures and a blood vessel with parallel-running nerve bundles. The postoperative course was uneventful, and the patient was discharged on postoperative day 6.ConclusionsThis case of accessory scrotum was unusual in its location and the presence of a stalk connecting the accessory scrotum and lipoma. The mechanism underlying accessory scrotum development remains unclear, and our report may impact the discourse regarding the embryological development of the accessory scrotum.

Raman spectroscopy analysis of human amniotic fluid cells from fetuses with myelomeningocele

Prenatal surgery for the treatment of spina bifida (myelomeningocele, MMC) significantly enhances the neurological prognosis of the patient. To ensure better protection of the spinal cord by large defects, the application of skin grafts produced with cells gained from the amniotic fluid is presently studied. In order to determine the most appropriate cells for this purpose, we tried to shed light on the extremely complex amniotic fluid cellular composition in healthy and MMC pregnancies. We exploited the potential of micro-Raman spectroscopy to analyse and characterize human amniotic fluid cells in total and putative (cKit/CD117-positive) stem cells of fetuses with MMC in comparison with amniotic fluid cells from healthy individuals, human fetal dermal fibroblasts and adult adipose derived stem cells. We found that (i) the differences between healthy and MMC amniocytes can be attributed to specific spectral regions involving collagen, lipids, sugars, tryptophan, aspartate, glutamate, and carotenoids, (ii) MMC amniotic fluid contains two particular cell populations which are absent or reduced in normal pregnancies, (iii) the cKit-negative healthy amniocyte subpopulation shares molecular features with human fetal fibroblasts. On the one hand we demonstrate a different amniotic fluid cellular composition in healthy and MMC pregnancies, on the other our work confirms micro-Raman spectroscopy to be a valuable tool for discriminating cell populations in unknown mixtures of cells.

A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2022.

Mandatory fortification of staple foods with folic acid is an effective public health strategy to prevent folic acid-preventable spina bifida and anencephaly (FAP SBA). We estimated the global proportion of FAP SBA prevented through mandatory folic acid fortification of cereal grains (i.e., wheat flour, maize flour, and rice). We used year 2022 data from the Food Fortification Initiative to identify countries (n = 69) with mandatory fortification of grains that includes folic acid. Sixty-eight countries were eligible for analysis with complete data. Proportion of FAP SBA prevention was modeled assuming >150 mcg/day of folic acid fortification protects against FAP SBA, reducing post-fortification prevalence to a lowest achievable level of 0.5 cases per 1000 births. Our analysis found that a total of 63,520 cases of FAP SBA were prevented in the year 2022 in 68 countries implementing mandatory folic acid fortification of grains with folic acid. This translated to a 23.7% prevention of all possible FAP SBA prevention globally. An excess of 204,430 cases of FAPSBA still occurred in over 100 countries where mandatory staple food fortification with folic acid is not implemented. Our study showed that only a quarter of all FAP SBA cases were averted through mandatory folic acid fortification in the year 2022; many countries are not implementing the policy, resulting in a large proportion of FAP SBA cases that can be prevented. Fortification will help countries with achieving 2030 Sustainable Development Goals on neonatal- and under-five mortality, disability, stillbirths, and elective terminations prevention, from FAP SBA.

The Pittsburgh Impairment Testing Tool (PITT) for Spina Bifida Can Predict Ambulation and Transfer Ability in Adults with Spina Bifida.

The aim of this study was to evaluate the predictive accuracy of the Pittsburgh Impairment Testing Tool (PITT). It was hypothesized that PITT would have a good overall accuracy (>80%) for predicting both ambulation and transfer ability and that overall accuracy of PITT would be higher than that of other scales. A retrospective chart review was used to classify 409 adults with spina bifida according to seven neurological scales. A Naïve Bayes classifier was used to obtain accuracy estimates for predicting both ambulation and transfer ability as a function of each scale. PITT was the only scale demonstrating >80% overall accuracy for predicting both ambulation and transfer ability. While several scales demonstrated >80% overall accuracy in predicting transfer ability, none were useful in predicting inability to transfer. Inability to transfer was difficult for all tools to predict. PITT demonstrated good overall accuracy for predicting both ambulation and transfer ability. Sensory and anatomic levels were less useful than motor level in predicting functional ability.

Pathological Alterations Induced by Nickel Oxide Nanoparticles in Pregnant Mice and Their Embryos

The purpose of this study was to investigate the effects of nickel oxide nanoparticles on pregnant mice and fetal development. Nickel oxide nanoparticles (&lt;50 nm) were injected intraperitoneally (1, 10, 20 mg/kg) in pregnant mice daily from the 7th -18th gestation day. At the 18th gestation day, the mice were euthanized, necropsied, and pathological examination of the mice and their embryos was done. Exposure to the nickel nanoparticles induced an increase (low and medium doses) and a decrease (high dose) in the activity of the mice. Abortion was recorded at the rates 10%, 20%, and 30% in groups treated with doses of 1, 10, and 20 mg/kg, respectively. Fetal malformations were noted at rates of 60%, 70%, and 75%, for the doses 1, 10, and 20 mg/kg, respectively. They included arrested growth, absence of the extremities, C-shaped fetuses, anencephalon, myelocele, exophthalmia, spina bifida, absence of facial details, absence or deformities of the tail, micromelia, cyanotic skin, abdominal hemorrhages, and meningocele. Microscopically, degenerative, necrotic, circulatory, and inflammatory lesions in the kidneys, liver, lungs, brain, and heart were noted in pregnant mice. In the embryos, there was incomplete growth of the renal, nervous, and pulmonary tissues. Additionally, there were degenerative, necrotic, and circulatory changes in the kidneys, liver, brain, lungs and heart. It was concluded that exposure to intraperitoneally administered nickel oxide nanoparticles (&lt;50 nm) induces abortion and toxic lesions in the kidneys, liver, brain, lungs and heart of pregnant mice; and fetal malformations and pathological lesions in the embryos.

Closing the gaps in self-management for young adults with spina bifida: Sociodemographic, condition-specific, and neuropsychological factors.

Closing the gaps in self-management for young adults with spina bifida: Sociodemographic, condition-specific, and neuropsychological factors.

Prenatal diagnosis of meningomyelocele resolves as a mature cystic teratoma in the thoracolumbar region.

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region. She presented prenatally with a preliminary diagnosis of meningomyelocele, diastematomyelia, and Chiari II malformation and a possible teratoma. However, a mass containing solid glandular tissues and bony calcifications approximately 3 × 4cm in size was observed in the thoracolumbar region upon birth. During surgical resection, no nerve roots were found in the associated meningocele. The patient retained full lower body function postoperatively following surgical excision of the thecal sac and teratoma.

Utilizing an Environmental Framework to Explore the Acceptability of a Health Promotion Program for Youth with Disabilities

ABSTRACT This study explored the acceptability of Children and Teens in Charge of their Health (CATCH), a program for children with spina bifida or cerebral palsy to enhance their physical activity and diet. Qualitative interviews were conducted with children (n = 6) and their parents (n = 6) who participated in CATCH. Analysis used an environmental systems framework. Microsystem factors impacting acceptability of the program were: Children’s motivations for change, their age, and their physical health. Mesosystem factors were: Use of virtual coaching and the relationship between coach and child. Macrosystem factors (e.g. Covid-19), did not impact acceptability, but affected some goal attainment strategies. CATCH was broadly acceptable to children and parents and shows promise as a health promotion program tailored to children with disabilities. An environmental systems framework can potentially help other health promotion programs enhance their acceptability and success.

A Pathophysiological Approach to Spontaneous Orbital Meningoceles: Case Report and Systematic Review

Background: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. Methods: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. Results: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. Conclusions: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount.

Decisional regret and impacts on quality of life following genitourinary reconstruction for neurogenic bladder: A comparison between acquired and congenital spinal cord injury.

Patient expectations and baseline health are important drivers of outcomes following major genitourinary reconstructive surgery for neurogenic bladder (NGB). Differences in expectations and quality of life (QoL) improvements among different populations with NGB remain insufficiently explored in the literature. To compare decisional regret (DR) and urinary-related QoL (UrQoL) in patients undergoing urinary diversion for NGB arising from spinal cord injury of acquired (A-SCI) and congenital (C-SCI) etiologies. We hypothesize that patients with A-SCI have higher expectations of improvement in QoL following surgery when compared with C-SCI, which may lead to higher DR and decreased UrQoL, postoperatively. In this cross-sectional survey study, we compared A-SCI to C-SCI in terms of DR, UrQoL, and postoperative changes in self-reported physical health, mental health, and pain using validated patient-reported outcome measures. Participants were enrolled from a quaternary care institution via mail and MyChart. The A-SCI group consistied of 17 patients with traumatic spinal cord injury the C-SCI group was composed of 20 patients with spina bifida. Not applicable. The Decisional Regret Scale, Short form- Qualiveen (SF-Qualiveen), and Patient-reported outcomes measurement Information system-10 (PROMIS-10) Global Health surveys. The A-SCI group displayed poorer preoperative physical health than the C-SCI cohort, but absolute postoperative changes in this score, along with mental health score and pain level, were not significant after adjusting for baseline scores and follow-up time. SF-Qualiveen scores revealed significantly worse impact of NGB in UrQoL for A-SCI than for C-SCI when adjusted for other factors. No differences in DR were seen between the groups. Patients with A-SCI demonstrate lower self-reported baseline physical health compared with patients with C-SCI, which may have implications in setting patient expectations when undergoing urinary diversion. In this small cohort, we found a milder self-reported postoperative impact of NGB in UrQoL in patients with C-SCI.

Sleep-related breathing disorders in infants with spina bifida repaired prenatally and postnatally.

Advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. We performed a retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t-test and Chi-square Test were used to analyze results. 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01). Patients with SB who've undergone closure of neural tube defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.

Socioeconomic profile of families with spina bifida children in Turkey

BackgroundSpina bifida’s prevalence and incidence vary across geographical regions with sociodemographic characteristics and socioeconomic status of the populations having a significate influence over its epidemiology. This study aimed to outline the socioeconomic profile of families with spina bifida children, based on sociodemographic characteristics.MethodsBetween August and December 2022, 86 surveys completed by parents of children that underwent spina bifida repair in our institution were included in this analysis. The first part of the survey included questions based on sociodemographic characteristics. The second part of the survey was based on care provided by the families, regular follow-ups, participation in rehabilitation programs, and type of burdens perceived by the caregivers.ResultsA close look at the highest level of parent education showed that more than half of them were only middle school graduates. Occupational status in the perioconceptional period revealed that 77% of mothers were housewives/unemployed. 23% had a history of induced or spontaneous abortion. A high number of consanguine marriages were registered with 58% of the subjects being biologically related. 53% of the spina bifida children came from families with low household income. Only 15% of the spina bifida children had access to physiotherapy and 18% to rehabilitation programs.ConclusionsChildren with spinal dysraphism were more likely to come from families resulted from consanguineous marriages, with at least two children, low level of parent education and household income. Emotional and financial burden perceived by caregivers should be addressed in order to diminish the numerous challenges that this group of families encounter.