Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.

BACKGROUND: Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism. METHODS: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios. RESULTS: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10-7), rs45580033 (ASB2, p = 4.2 × 10-10), and rs75426652 (LHPP, p = 7.2 × 10-14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants. CONCLUSIONS: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.

Association of spinal cord abnormalities with vertebral anomalies: an embryological perspective.

PURPOSE: To analyze the relationship between spinal cord and vertebral abnormalities from the point of view of embryology. METHODS: We analyzed the clinical and radiological data of 260 children with different types of spinal cord malformations in combination with vertebral abnormalities. RESULTS: Among 260 individuals, approximately 109 presented with open neural tube defects (ONTDs), 83 with split cord malformations (SCMs), and 83 with different types of spinal lipomas. Pathological spina bifida emerged as the most frequent vertebral anomaly, affecting 232 patients, with a higher prevalence in ONTD. Vertebral segmentation disorders, including unsegmented bars, butterfly vertebrae, and hemivertebrae, were present in 124 cases, with a higher prevalence in SCM. The third most common spinal anomaly group consisted of various forms of sacral agenesis (58 cases), notably associated with blunt conus medullaris, spinal lipomas, and sacral myelomeningocele. Segmental aplasia of the spinal cord had a typical association with segmental spinal absence (N = 17). CONCLUSION: The association between SCM and neuroenteric cyst/canal and vertebral segmentation disorders is strong. High ONTDs often coincide with pathological spina bifida posterior. Type 1 spinal lipomas and focal spinal nondisjunction also correlate with pathologic spina bifida. Segmental spinal absence or dysgenesis involves localized spinal and spinal cord aplasia, sometimes with secondary filar lipoma.

Challenges in the Management of Symptomatic Fallopian Canal Meningoceles: A Multicenter Case Series and Literature Review.

OBJECTIVE: To describe the presentations, the diagnosis, our treatment approaches, and the outcomes for 11 patients with fallopian canal meningocele (FCM). STUDY DESIGN MULTICENTER: Retrospective case series. SETTING: Tertiary referral centers. PATIENTS: Patients (N = 11) with radiographically or intraoperatively identified, symptomatic FCM. INTERVENTIONS: Surgical repair of cerebrospinal fluid (CSF) leak and meningocele versus observation. MAIN OUTCOME MEASURES: Presentation (including symptoms, radiographic imaging, and comorbidities), management (including surgical approach, technique for packing, use of lumbar drain), clinical outcomes (control of CSF leak, meningitis, facial nerve function), and revision surgery. RESULTS: Patients presented with spontaneous CSF leak (n = 7), conductive (N = 11) and sensorineural hearing loss (n = 3), nonpositional intermittent vertigo (n = 3), headaches (n = 4), and recurrent meningitis (n = 1). Risk factors in our series included obesity (n = 4), Chiari 1 malformation (n = 1), and head trauma (n = 2). Noncontrast computed tomography of the temporal bone and magnetic resonance imaging were positive for FCM in 10 patients. Eight patients were managed surgically via a transmastoid approach (n = 4), combined transmastoid and middle fossa (N = 3), or middle fossa alone (n = 1); three were managed conservatively with observation. Postoperative complications included worsened facial nerve palsy (n = 1), recurrent meningitis (n = 1), and persistent CSF leak that necessitated revision (n = 1). CONCLUSIONS: Facial nerve meningoceles are rare with variable presentation, often including CSF otorrhea. Management can be challenging and guided by symptomatology and comorbidities. Risk factors for FCM include obesity and head trauma, and Chiari 1 malformation may present with nonspecific otologic symptoms, in some cases, meningitis and facial palsy. Layered surgical repair leads to high rates of success; however, this may be complicated by worsening facial palsy.

Posterior median surgical approach to anterior sacral meningocele complicated by rectothecal fistula.

In this case report, we aimed to describe the clinical presentation, surgical approach, and follow-up of a patient with rare anterior meningocele associated with rectothecal fistula. An 17-year-old female patient was admitted to the emergency department with meningitis. On further examinations, an anterior sacral meningocele accompanied by rectothecal fistula was detected. Appropriate antibiotic treatment was arranged and surgical plan was made with the pediatric surgery clinic. The patient underwent meningocele repair via posterior approach and colostomy operation. The patient did not experience any neurological issues after the surgery. The colostomy was reversed 3 months later, and third-month follow-up MRI showed complete regression of the meningocele sac with no neurological complications. Anterior meningocele accompanied by a rectothecal fistula is a rare and complicated case. Only seven cases of coexisting ASM and RTF have been reported in literature. Although both anterior and posterior approaches have been used for the treatment of ASM, the choice of treatment is essentially based on the patient's clinical and imaging findings.

Posterior Surgical Ligation and Cyst Decompression -via Needle Puncture- of a Large Anterior Sacral Pelvic Meningocele Through Posterior Sacral Laminectomy.

The first documented description of an anterior sacral meningocele was Bryant's in 1823. Anterior sacral meningocele patients have constipation as a universal symptom; urinary incontinence is also common. All the symptoms are directly related to the pressure from a pelvic mass on adjacent structures. When the patient stands, a headache often develops because the spinal fluid pressure decreases as the meningocele sac fills. Finally, a scimitar-shaped sacrum on a neuroradiological anteroposterior plain assessment is pathognomonic. The coccyx may be absent, and the lower sacral laminae may be absent or incomplete. The surgical options for this rare clinical condition are still matter of debate.Anterior sacral meningocele is a pathology that lacks a current classification and neurosurgical therapeutic standards, even though a similar dynamic has been shown by the related traumatic pseudomeningocele. Anterior approaches (retro- and transperitoneal meningocele neck occlusion with internal cerebrospinal fluid (CSF) cyst drainage) and posterior approaches (posterior sacral laminectomy, dural sac ligation, and CSF cyst drainage) are the available surgical strategies.We now report the case of an adult patient for whom a posterior approach was suggested and performed and report her postoperative surgical follow-up. The surgical rationale is also discussed.

Determining the risk of spinal pathology progression in neurofibromatosis type 1 patients - a national tertiary neurofibromatosis type 1 centre study.

BACKGROUND: Neurofibromatosis type 1 (NF1) gives rise to a variety of spinal pathologies that include dural ectasia (DE), vertebral malalignments (VMA), spinal deformities (SD), syrinx, meningoceles, spinal nerve root tumours (SNRT), and spinal plexiform tumours (SPT). The relationship between these and the progression of these pathologies has not been explored before in detail and this paper aims to address this. METHODS: Data was retrospectively collected from adult NF1 multi-disciplinary team meetings from 2016 to 2022 involving a total of 593 patients with 20 distinct predictor variables. Data were analyzed utilizing; Chi-Square tests, binary logistic regression, and Kaplan-Meier analysis. RESULTS: SNRT (19.9%), SD (18.6%), and (17.7%) of VMA had the highest rates of progression. SD was significantly associated (p < 0.02) with the presence and progression of all spinal pathologies except for SPT. Statistically significant predictors of SD progression included the presence of DVA, VMA, syrinx, meningocele, and SNRT. Kaplan-Meier analysis revealed no statistically significant difference between the times to progression for SD (85 days), SNRT (1196 days), and VMA (2243 days). CONCLUSION: This paper explores for the first time in detail, the progression of various spinal pathologies in NF1. The presence and progression of SD is a key factor that correlated with the progression of different spinal pathologies. Early identification of SD may help support clinical decision-making and guide radiological follow-up protocols and treatment.

[A Surgical Case of Currarino Syndrome with Syringomyelia].

Currarino syndrome is characterized by a triad of anorectal malformations, sacral defects, and presacral masses. Although it is not extremely rare, this report presents a surgical case of Currarino syndrome with syringomyelia and discusses related literature. The patient is a girl, aged 2 years and 2 months, who presented with marked constipation, chronic cystitis, and lower limb weakness. After examining the patient through magnetic resonance imaging, we diagnosed her with rectal compression due to meningocele and syringomyelia. The base of the meningocele was detached, and the spinal cord was untethered. One week after surgery, her lower limb weakness and constipation improved. Following up on symptoms and performing imaging is essential to determine a treatment plan for Currarino syndrome. (Received 28 February, 2023; Accepted 22 March, 2023; Published 1 August, 2023).

Intrasacral meningoceles: Clinical presentation, surgical management, and postoperative outcome: The Giannina Gaslini Hospital's experience.

INTRODUCTION: Intrasacral meningoceles are cysts associated with herniating arachnoid with no nerve root within due to an area of weakness of the dura mater. They are thought to be congenital, but they are usually not symptomatic until adulthood. Surgical treatment is generally indicated in the presence of symptoms. METHODS: We selected cases belonging to the IB category of Nabors et al.'s classification who underwent surgery between 2008 and 2021 at Giannina Gaslini Hospital. Exclusion criteria were prior history of trauma, infections, or operations. Patients' clinical details, associated conditions, surgical techniques, peri- and postoperative complications, and outcomes were collected retrospectively from clinical charts. We compared our series to literature: keywords "intrasacral meningocele" were used on the search engine MEDLINE - Pubmed. RESULTS: We identified 23 cases: 5 of the 14 symptomatic patients had a complete resolution, and 5 had a substantial clinical improvement after surgery. Cyst recurrence and major postoperative complication occurred in none. Among 59 articles considered for evaluation, 50 were excluded and remaining 9 articles underwent full-text analysis. DISCUSSION AND CONCLUSION: The pathogenesis of instrasacral meningoceles is still not completely understood and the spectrum of symptoms is wide. A posterior surgical approach with sacral laminectomy is preferred, although in selected cases it is possible to perform a supplemental anterior approach (sometimes endoscopic). In our surgical series, the largest one published in the literature, a good clinical outcome was achieved in most patients with no cyst's recurrence, pointing out the importance of surgical interruption of communication between cyst and subdural space.

Prenatal and Neonatal Ultrasound and Magnetic Resonance Imaging Diagnosis of Sprengel's Deformity with Unusual Associations.

INTRODUCTION: Sprengel's deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and abnormal shoulder function. Nonsurgical management can be considered for mild cases. Surgical intervention is indicated in moderate to severe cases with the goal of improving cosmetic appearance and function. The best surgical results are obtained in children aged 3-8 years. Correct diagnosis is very important because Sprengel's deformity can be accompanied by additional abnormalities, even in mild cases, and lack of a diagnosis delays proper treatment of the child. The severity of the defect may progress, so it is important to correctly identify children with Sprengel's deformity, even those with a mild form of the defect. CASE PRESENTATION: We report a case of prenatal sonographic diagnosis of Sprengel's deformity with additional features, as yet undescribed and missed - although visible - on prenatal magnetic resonance imaging (MRI). Cesarean delivery was performed due to preterm rupture of membranes, and a postnatal MRI confirmed the unusual constellation of Sprengel's anomaly with lateral meningocele, vestigial posterior meningocele, and lipoma tethering of the cord to the dural sac at the cervical-thoracic junction. CONCLUSION: Diagnosis of Sprengel's deformity is possible with prenatal ultrasound. Asymmetry of the cervical spine, discontinuity of the vertebral arch and abnormal vertebral bodies, as well as the asymmetric position of the shoulder blades with the presence of an omovertebral bone are signs that can help diagnose the defect.

Amniotic band syndrome with CNS involvement: a pediatric neurosurgeon's dilemma-a case series and literature review.

BACKGROUND: Amniotic band syndrome (ABS) is a rare congenital disease characterized by a broad spectrum of congenital anomalies resulting from the strangulated developing organ(s) by the detached fibrous amniotic band. The prevalence of CNS involvement in ABS is rare, but the mortality rate in these cases is high, while morbidity among the surviving patients is inevitable. CASE REPORT: Three-month-old male, 9-month-old female, and newborn female babies were presented with head lump(s), severe facial cleft, syndactyly, and finger amputation. The patient's head imaging confirmed meningoencephalocele as the cause of the head lump in 2 patients; meanwhile, a porencephalic cyst was identified as the origin of head lumps in the other patient. VP shunt placement surgery was performed as the initial management in 2 patients, while one patient directly underwent meningoencephalocele resection surgery. Craniofacial and limb reconstructions were planned as the follow-up management in all cases. Unfortunately, one patient died of complications from suspected aspiration, while another never returned for follow-up treatment. CONCLUSION: Here, we report 3 ABS cases with CNS involvement. Despite the severe disfigurement and disability, the inexistence of fatal malformation might lead to long-term survival. The treatment of malformation(s) that might predispose to another fatal condition and surgery(-ies) to improve functional outcomes and patient's social acceptability should be prioritized in managing the surviving ABS patients.

A clinical clue toward recognition of split cord malformation type-I resembling meningocele in neonates.

This is a letter to share the clinical experience we had with neonates born with a specific feature of spina bifida. The lesion is like a meningocele containing skim amount of fluid, with a tiny dimple around the center of the cutaneous lesion which causes inward retraction of the dysplastic coverage. This feature is in favor of accompanied split cord malformation (SCM) type I, and the central nidus is in continuous with the dural sleeve around the bony septum of SCM. By recognition of this clinical clue, surgical repair can be planned to perform with appropriate provision, particularly foreseeing the amount of intraoperative bleeding and duration of anesthesia in the newborn patients.

Diagnóstico y tratamiento de pacientes con vejiga neurogénica en la Unidad Técnica de Cirugía Pediátrica / Diagnosis and treatment of patients with Neurogenic bladder in the Surgery Technical Unit Pediatric

El presente trabajo toma como base el documento: "Manejo Urológico del Mielomeningocele" de las Guías de Atención Pediátrica, del Hospital De Pediatría "Juan P. Garrahan" de la ciudad de Buenos Aires - Argentina; de los autores: Dra. Carol Burek y Dra. Liliana Campmany. En la Unidad Técnica de Cirugía Pediátrica del Hospital de Especialidades Carlos Andrade Marín, se atienden por mes unos 50 a 70 pacientes afectos de vejiga neurogénica desde el nacimiento hasta la adolescencia. Es una enfermedad crónica que requiere un diagnóstico correcto con estudios de imagen y función de la vía urinaria además de un posterior manejo diario por parte de los padres con la guía del médico especialista.

This work is based on the document: "Urological Management of Myelomeningocele" from the Pediatric Care Guidelines of the Hospital De Pediatría "Juan P. Garrahan" of the city of Buenos Aires - Argentina; by the authors: Dr. Carol Burek and Dr. Liliana Campmany. In the Pediatric Surgery Technical Unit of the Carlos Andrade Marín Specialties Hospital, 50 to 70 patients affected by neurogenic bladder from birth to adolescence are treated every month. It is a chronic disease that requires a correct diagnosis with imaging and urinary tract function studies, as well as subsequent daily management by the parents under the guidance of the specialist.

Allowing Standing and Assisted Steps in a Patient With Renshaw Type IV Sacral Agenesis: A Case Report of a Novel Surgical Approach.

CASE: A 6-year-old boy with a Renshaw type 4 sacral agenesis presented paraplegia and rigid, "Buddha-like" lower-limb contractures, including severe knee pterygia, which made crawling and sitting difficult. Staged surgical treatment involved bilateral knee disarticulation, soft tissue surgery, and bifocal femoral osteotomies for lower-limb reorientation. At 18 months postoperatively and after prosthetic fitting, the patient can stand and take steps with assistance. CONCLUSION: This effective surgical strategy achieves standing in a troublesome orthopaedic congenital condition. The intervention should be tailored to specific orthopaedic disorders and the wishes of patients and families, aiming to improve function.

Analysis of the Causes and Experience in the Diagnosis and Treatment of Meningocele Caused by Sternberg's Canal of the Sphenoid Sinus: Two Case Reports and a Review of the Literature.

OBJECTIVE: The present study aimed to improve the diagnosis and treatment outcome of cerebrospinal fluid (CSF) rhinorrhea caused by patent meningoencephalocele of Sternberg's canal of the sphenoid sinus by analyzing the clinical data and imaging features of two rare cases of this disease and by reviewing the relevant literature for possible etiology, diagnoses, and treatments. METHODS: Together with the relevant literature, we retrospectively studied the clinical and imaging data of two patients (mother and child) with CSF rhinorrhea caused by patent meningoencephalocele of Sternberg's canal of the sphenoid sinus, analyzed their diagnostic and treatment procedures, and proposed a potential, feasible treatment method. RESULTS: On the 2nd day after surgery, the expansive sponge and iodoform gauze in the nasal cavity were removed in both patients, and the lumbar subarachnoid drainage was removed 3 days after the operation, as no nasal discharge was observed. One week after the operation, head magnetic resonance imaging (MRI) showed that the abnormal tissue in the sphenoid sinus had disappeared, and no accumulation of the CSF was observed. Both patients were discharged after 2 weeks. At the time of discharge, both patients were without nasal drip, fever, headache, and other discomforts, and they had grade 5 muscle strength in their extremities, with normal muscle tension. CONCLUSION: CSF rhinorrhea is usually caused by secondary factors. Spontaneous CSF rhinorrhea caused by encephalocele of the skull base due to congenital dysplasia of the skull base is very rare and easily misdiagnosed. The presence of brain tissue or CSF signal in the sphenoid sinus on preoperative MR images is an important imaging feature of the disease. Conditional cisternography can be used to further detect CSF leaks. Endoscopic transnasal transsphenoidal repair of CSF leaks combined with short-term postoperative lumbar subarachnoid drainage is an effective treatment method. According to previous literature, the possible causes of meningoencephalocele with patent Sternberg's canal of the sphenoid sinus include abnormal development of the sphenoid sinus or the craniopharyngeal canal and bone defects of the skull base. There are no related reports on patent meningoencephalocele caused by Sternberg's canal in direct blood relatives, such as mother-son; therefore, the possibility of this disease having a genetic origin should be considered in future studies on its pathophysiological mechanisms.

Local conceptions of the role of folate in neural tube defects in Zambia.

OBJECTIVE: In sub-Saharan Africa, neural tube defects (NTDs) are the second most common birth defect, occurring eight times more frequently than in the US. The objective of this study was to assess baseline Zambian caregiver understanding of folate and NTDs and the effectiveness of an NTD prevention educational program. METHODS: This prospective survey-based study included Zambian caregivers of children born with NTDs who completed pre- and post-educational program surveys between January 2020 and January 2021. The verbal survey was administered in English or local Zambian dialects. The 1-hour educational program administered by local Zambian research nurses sought to facilitate understanding of the direct relationship between prenatal folate supplementation and NTDs. RESULTS: Sixty-one eligible caregivers with a median age of 20 (IQR 24-29) years completed the survey. Participants were predominantly from regions outside of Lusaka Province (68%, 41/60) rather than the capital city, Lusaka (32%, 19/60). Most had received prenatal care (91%, 57/61), and 80% (47/59) reported folate use in pregnancy. Of the mothers who took folate during pregnancy, 24% (11/45) reported use within the first 4 weeks after conception, while 76% (34/45) started thereafter. Myelomeningocele was the most common NTD (74%, 32/43), followed by meningocele (14%, 6/43). Prior to the educational program, 52% (29/56) of caregivers reported that NTDs were caused by a vitamin deficiency, which improved to 98% (55/56) after the program (p < 0.001). Furthermore, only 54% (33/61) of caregivers believed that folate should be taken before conception on the baseline survey evaluation, which improved to 95% (58/61, p < 0.001) after the program. All survey participants (58/58) found the educational session helpful. CONCLUSIONS: This study found that a high proportion of Zambian caregivers had received prenatal care and even had taken folate during pregnancy, but none had taken it prior to pregnancy. An educational program effectively improved understanding about the role and timing of perinatal folate administration in NTD prevention. This result also emphasizes the need for folate fortification and folate education for not only mothers but also primary care providers.

The Need for Emphasis on Intracranial Hypertension Management in Spontaneous Skull Base Meningoencephaloceles.

OBJECTIVE: To provide an analysis of patients with spontaneous skull base meningoencephaloceles (MECs) to determine whether definitive surgical treatment requires management of elevated intracranial pressure (ICP). METHODS: Data of 10 subjects with spontaneous MECs were collected and retrospectively evaluated. Measurement of ICP, prior interventions, treatment with acetazolamide, and characteristics of long-term elevated ICP, among others, were analyzed. Our own indications for cerebrospinal fluid (CSF) diversion and use of postoperative external lumbar drain were analyzed as well. RESULTS: The sphenoid region was the most common location of MECs. CSF leak was diagnosed in all subjects. The most common graphical signs of elevated ICP were empty sella and arachnoid pits, both of which were present in 90% of cases. Lumbar puncture with opening pressure measurement was performed in 7 patients. Ventriculoperitoneal shunt insertion was indicated in 4 cases before skull base repair and in 2 cases after skull base repair. Two postoperative CSF leaks were managed with external lumbar drain and subsequent shunt installation. CONCLUSIONS: Spontaneous MECs are often associated with CSF leak. ICP assessment should be a standard of care to ensure successful operative repair of MECs. Insertion of a CSF diversion device must be considered where direct or indirect signs of intracranial hypertension are present.

Untreated meningomyelocele and squamous cell carcinoma: a case report and literature review.

BACKGROUND: Early closure of the meningocele, meningomyelocele, is essential to prevent complications such as hypothermia, infection in the postnatal period. But for some reasons, it is not always possible to repair early. The possibility of malign transformation should be considered in long-term due to nonhealing ulcers and cerebrospinal fluid (CSF) fistula and frequent infections in an adult patient with meningomyelocele. The possibility of conversion to malignancy in the control of an untreated meningomyelocele patient with (CSF) drainage should be especially kept in mind. CASE DESCRIPTION: A case is described of a malignant transformation at the site of a myelomeningocele in a 22-year-old woman. The lumbosacral region was deformed by a large meningomyelocele 10 cm in diameter, with areas of scar and ulcer. For 7 years prior to this presentation, the lesion was a large fistula in the roof of the open myelomeningocele. She underwent continuous CSF draining. A biopsy was done which revealed it as squamous cell carcinoma. CONCLUSION: Early closure of meningocele, meningomyelocele is essential to prevent complications such as hypothermia, infection in the postnatal period. Also, especially if there is continuous CSF exposure, the possibility of malignant change should be kept in mind in neglected cases presenting in an adult.