Intraoperative neuromonitoring potentials and evidence of preserved neuronal circuitry below the anatomical and functional level in patients with complex spinal dysraphism undergoing detethering reoperations.

OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.

Regional activity and functional connectivity in brain networks associated with urinary bladder filling in patients with tethered cord syndrome.

PURPOSE: Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging using analyses of regional activity and functional connectivity of brain networks. This study was designed to demonstrate functional network alterations in patients with detrusor overactivity. MATERIALS AND METHODS: In this study, we recruited 36 patients with tethered cord syndrome who had detrusor overactivity and 34 normal controls. We used regional homogeneity and seed-based functional connectivity computational methods to reveal resting-state brain activity features associated with patients. RESULTS: Compared with normal controls, patients with tethered cord syndrome showed regional abnormalities, mainly in the bilateral frontal cortex, anterior and midcingulate cortex, and temporal lobes. When these regions were defined as seeds, we demonstrated widespread modification in brain networks. The brain-bladder network was not positively connected with the cognitive control network. Both altered regional activity and changed functional connectivity were found in the brain-bladder network. CONCLUSION: Patients with NDO, activated areas in the frontal lobe and anterior cingulate gyrus decreased significantly and have fewer brain activation areas in the caudate nucleus and hypothalamus (limbic system). In functional connectivity work, we found a small positive correlation in different regions of frontal lobe. This study helped us better to understand the characteristics of neural network modifications in patients with tethered cord syndrome.

Impact of the cystic neural tube defects on fetal motor function in prenatal myelomeningocele repairs: A retrospective cohort study.

OBJECTIVE: To determine the impact of the lesion type (cystic [myelomeningocele] or flat [myeloschisis]) on the fetal motor function (MF) in cases candidates for prenatal open neural tube defect (ONTD) repair. METHODS: Retrospective cohort study of patients with ONTD who underwent prenatal repair at a single institution between 2011 and 2019. The lesion type and the measurements of the length and width of the lesions to calculate the surface of the ellipsoid lesion were performed using MR scans. Prenatal MF of the lower extremities was evaluated by ultrasound following a metameric distribution at the time of referral. Intact MF was defined as the observation of plantar flexion of the ankle. Logistic regression was performed to determine the predictive value of the type of lesion for having an intact MF at the time of referral. RESULTS: 103 patients were included at 22.9 (19-25.4) weeks; 65% had cystic and 35% had flat lesions. At the time of referral, there was a higher proportion of cases with an intact MF in the presence of flat lesions (34/36; 94.4%) as compared to cystic lesion (48/67; 71.6%, p < 0.01). When adjusting for gestational age and anatomical level of the lesion, flat ONTD were 3.1 times more likely to be associated by intact motor function (CI%95 [2.1-4.6], p < 0.01) at the time of referral. CONCLUSION: Cystic ONTD are more likely to be associated with impaired MF at mid-gestation in candidates for prenatal ONTD repair.

Association between rare variants in specific functional pathways and human neural tube defects multiple subphenotypes.

BACKGROUND: Neural tube defects (NTDs) are failure of neural tube closure, which includes multiple central nervous system phenotypes. More than 300 mouse mutant strains exhibits NTDs phenotypes and give us some clues to establish association between biological functions and subphenotypes. However, the knowledge about association in human remains still very poor. METHODS: High throughput targeted genome DNA sequencing were performed on 280 neural tube closure-related genes in 355 NTDs cases and 225 ethnicity matched controls, RESULTS: We explored that potential damaging rare variants in genes functioning in chromatin modification, apoptosis, retinoid metabolism and lipid metabolism are associated with human NTDs. Importantly, our data indicate that except for planar cell polarity pathway, craniorachischisis is also genetically related with chromatin modification and retinoid metabolism. Furthermore, single phenotype in cranial or spinal regions displays significant association with specific biological function, such as anencephaly is associated with potentially damaging rare variants in genes functioning in chromatin modification, encephalocele is associated with apoptosis, retinoid metabolism and one carbon metabolism, spina bifida aperta and spina bifida cystica are associated with apoptosis; lumbar sacral spina bifida aperta and spina bifida occulta are associated with lipid metabolism. By contrast, complex phenotypes in both cranial and spinal regions display association with various biological functions given the different phenotypes. CONCLUSIONS: Our study links genetic variant to subphenotypes of human NTDs and provides a preliminary but direct clue to investigate pathogenic mechanism for human NTDs.

Tethered Cord Syndrome Caused by Duplicated Filum Terminale in an Adult with Split Cord Malformation.

BACKGROUND: Tethered cord syndrome (TCS) is a clinical diagnosis of progressive neurologic aggravation of the lower spinal cord due to a traction on the conus medullaris. Untethering surgery is effective for most TCS; however, when anatomic variations of spinal cord and filum terminale (FT) exist, regular untethering may lead to a failed outcome. CASE DESCRIPTION: The authors present the case of a 45-year-old patient with TCS caused by duplicated FT with split cord malformation (SCM). Lumbosacral magnetic resonance imaging revealed a type II SCM with a significant low-lying conus medullaris. Laminectomy was performed. Neurophysiologic monitoring was used for nerve root identification and 2 thickened fila, which failed to respond on stimulation, were found during the surgery. Both fila were sectioned, and the diagnosis was finally confirmed by pathologic examination. Postoperatively, the patient's symptoms disappeared immediately and no neurologic sequela was found after surgery. CONCLUSIONS: This is the first documented adult of duplicated FT with preoperative radiologic evidence and reported in association with SCM as a cause of TCS. When SCM exists, a careful observation for duplicated FT is warranted on preoperative magnetic resonance imaging and during surgery. Complete transection of the double FT under intraoperative neurophysiologic monitoring is the best treatment for this anomaly.

Surgical Treatment of Tethered Cord Syndrome in Adults: A Systematic Review and Meta-Analysis.

OBJECTIVE: In the healthy spine, the spinal cord moves unimpeded with spinal fluid pulsation in the rostral and caudal directions. When a portion of the spinal cord becomes attached to lesions within the spinal column, excess strain can cause signs and symptoms such as pain, motor deficits, sensory deficits, bladder dysfunction, and bowel dysfunction. This condition is termed tethered cord syndrome. There are no clear guidelines for offering surgical intervention, although there is a general consensus that worsening signs and symptoms increase the likelihood that patients will need surgery. METHODS: In this article, we conduct a systematic review and meta-analysis for all available literature within the Ovid (MEDLINE), PubMed, and Google Scholar databases to evaluate common symptoms among patients with tethered cord and to examine how surgery affects symptoms. RESULTS: Within the cohort of 730 patients, 708 (97%) were treated surgically by a detethering procedure. The most common preoperative sign or symptom was pain (81%), followed by motor deficits (63%), sensory deficits (61%), bladder dysfunction (56%), and bowel dysfunction (15%). One percent of patients had no deficit or symptom. Pain was the symptom that was most responsive to surgery, with 81% of patients reporting that their pain improved after detethering. CONCLUSIONS: Tethered cord syndrome should be included in the differential diagnosis in patients presenting with back or leg pain, somatosensory symptoms of the lower extremities, muscular weakness, urodynamic dysfunction, or bowel dysfunction. After a definitive diagnosis is made, patients should be counseled about surgical detethering as an option.

Urological presentations of adult primary tethered cord syndrome.

AIMS: To investigate the urological presentations of patients initially diagnosed with closed spinal dysraphism in adulthood: adult primary tethered cord syndrome (ApTCS). METHODS: Patients with ApTCS who underwent subsequent untethering were studied. Urological presentations were evaluated grouped by symptom onset period of either after (group 1) or before (group 2) the completion of physical growth. RESULTS: Of the 43 patients, median age at diagnosis and initial untethering was 35.5 (18.4-67.2) years. At diagnosis, 90.7% (39/43) had urological symptoms and 18.6% (8/43) initially consulted a urologist without noticeable neurological symptoms. Enuresis was observed in 16.3% (7/43) and common among patients without significant neurological symptoms (62.5%, 5/8). Urgency urinary incontinence and frequency prevailed in group 1. Stress urinary incontinence and straining to void prevailed in group 2. Among 26 patients with pre- and post-operative urodynamics, detrusor overactivity predominated in group 1 and acontractile detrusor predominated in group 2. Glomerular filtration rate ≥90 mL/min/1.73m2 was noted in 86.0% (37/43) and 84.9% (73/86) of renal units were morphometrically intact. More patients in group 2 (93.3%) relied on assisted emptying than in group 1 (53.6%). CONCLUSIONS: In ApTCS, enuresis was prevalent among patients without noticeable neurological symptoms. Over 80% in both groups had favorable renal function. Bladder conditions were different based on symptom onset period. Significantly more patients whose symptoms developed before completion of growth relied on assisted emptying. Proper discerning might be crucial in ApTCS which has a potential of misdiagnosis even in the modern developed era.

Low Prevalence of Folic Acid Supplementation during Pregnancy: A Multicenter Study in Vietnam.

Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects (NTDs), but little information is known about its use in Vietnam. It is important that FA supplements start to be taken when planning a pregnancy and continued through the first trimester to prevent NTDs, as the neural tube closes in the first month of pregnancy. However, FA supplementation in Vietnam is usually recommended to commence from the first antenatal visit, which is usually at 16 weeks, and very few women take FA before their first visit. This multicenter study aimed to determine the prevalence of FA supplement use and associated maternal characteristics in Vietnam. FA supplementation was assessed in 2030 singleton pregnant women between 2015 and 2016. In total, 654 (32.2%) women reported taking either supplements containing FA alone or multivitamins containing FA, and 505 (24.9%) reported correctly taking supplements containing FA alone. Women who were aged 30 years or over, had low education levels, had formal employment, and whose current pregnancy was first or unplanned were less likely to supplement with FA. Education programs are needed to encourage FA supplementation when contemplating pregnancy.

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

OBJECTIVE: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. METHODS: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. RESULTS: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53-10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05). CONCLUSION: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

Transradial approach in the treatment of a sacral dural arteriovenous fistula: a technical note.

Sacral dural arteriovenous fistulas (SDAVFs) are rare, constituting no more than 10% of all spinal dural fistulas. They are most commonly fed by the lateral sacral artery (LSA), a branch of the internal iliac artery (IIA). Catheterization of this vessel requires either a crossover at the aortic bifurcation in cases of right femoral access or retrograde catheterization from the ipsilateral common femoral artery. We present the case of a 79-year-old man with tethered cord syndrome and a symptomatic SDAVF fed by two feeders from the left LSA. Spinal diagnostic angiography was made exceptionally challenging by an aorto-bi-iliac endograft, and selective catheterization of the left IIA was not possible. The patient could not undergo surgery due to multiple comorbidities, therefore embolization was considered the best approach. The procedure was carried out through a transradial access (TRA) with Onyx and n-butyl cyanoacrylate. The SDAVF was successfully treated and the patient made a full neurological recovery.

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway.

BACKGROUND: Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. METHODS: We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. RESULTS: There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308). CONCLUSION: Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.

Excision and short segment fusion of a double ipsilateral lumbar hemivertebrae associated with a diastematomyelia and fixed pelvic obliquity.

We report the surgical treatment course of a 4-year-old girl with congenital scoliosis, diastematomyelia and double adjacent hemivertebrae. She had a lumbar curve with an apparent pelvic obliquity. Simultaneous excision of double segmented sequential hemivertebra at the L3-L4 level and fusion with short-segment instrumentation was performed via a posterior approach. Intraoperative radiographs revealed satisfactory curve correction and 0° pelvic obliquity. Following the excision of double adjacent hemivertebrae, three adjacent nerve roots were placed in one intervertebral foramen bilaterally. Nevertheless, no neurological deficit was developed, and the patient was able to ambulate with a brace at day one. Pelvic balance and deformity correction were maintained with no implant failure at the fifth year follow-up. Excision of two ipsilateral adjacent hemivertebra and short-segment posterior fusion performed via posterior-only approach simultaneously is an effective, safe, and less invasive technique for the treatment of the described case.

Short-term results of patients with neural tube defects followed-up in the Konya region, Turkey.

BACKGROUND: Additional congenital anomalies have often been found in patients with neural tube defect (NTD). We aimed to find out the clinical features, short term prognosis, treatment approaches, and systemic anomalies of NTD patients in the Konya region. METHOD: A total of 186 newborn babies with NTD were retrospectively included in the study and all were assessed in detail for congenital anomalies and clinical features. RESULTS: When the application month of the patients was examined, it was seen that the most frequent month was July. Of 186 babies, 101(54.3%) had meningomyelocele, 53 (28.5%) had meningocele, 13 (7.0%) had encephalocele, 16 (8.6%) had spina bifida occulta, and 4 (2.1%) had anencephaly. Of these patients, 97 (52.2%) were male and 89 (47.8%) were female. Hydrocephalus was an almost constant finding and was found in 140 (75.3%) patients. 51 (27.4%) patients had congenital heart disease (CHD). The most common CHD was atrial septal defect 22.3%. Orthopedic anomaly was detected in 51 (27.4%) patients, nephrological anomaly was found in 47 (25.3%) of the cases, congenital hypothyroidism was diagnosed in 14 (7.5%) patients with NTD. The mortality rate of patients diagnosed with NTD was 7.5%. The rates of premature delivery and consanguinity between parents were higher in patients with NTD. CONCLUSIONS: Our results indicate that at least one congenital anomaly is also present in about two-thirds of newborn babies with NTD, and these anomalies significantly increase their morbidity and mortality. All newborn babies with NTD should be screened for additional congenital anomalies and evaluated with more organized, multidisciplinary methods.

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.

BACKGROUND: Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE: The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN: A retrospective cohort study. SETTING: Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION: Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS: Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. CONCLUSION: Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.

[Tethered cord syndrome in children: about a case]. / Syndrome de la moelle attachée chez l'enfant: à propos d'un cas.

Tethered cord syndrome is a spectrum of neurological symptoms due to a constant or intermittent axial traction of the terminal cone of the spinal cord, fixed in abnormal caudal position. It is a rare congenital lesion whose symptoms can be observed only in adulthood. We report the case of a 10-year-old boy with tethered cord syndrome discovered due to bladder and anal incontinence and confirmed by lumbosacral magnetic resonance imaging. He underwent neurosurgical release of the terminal cone by posterior approach. Evolution was marked by improvement of sphincteric disorders. This case study has been followed by a literature review on this subject. This case study highlights the role of magnetic resonance imaging (MRI) in the diagnosis of this disorder.

The folic acid metabolism gene mel-32/Shmt is required for normal cell cycle lengths in Caenorhabditis elegans.

Neural tube defects are common and serious birth defects in which the brain and/or spinal cord are exposed outside the body. Supplementation of foods with folic acid, an essential vitamin, is linked to a lower risk of neural tube defects; however, the mechanisms by which folic acid influence neural tube defect risk are unclear. Our research seeks to identify the basic cellular roles of known folic acid metabolism genes during morphogenesis using the roundworm Caenorhabditis elegans (C. elegans) as a simple model system. Here, we used live imaging to characterize defects in embryonic development when mel-32 is depleted. mel-32 is an essential folic acid metabolism gene in C. elegans and a homolog to the mammalian enzyme serine hydroxymethyltransferase (Shmt). Disruption of mel-32 resulted in a doubling or tripling of cell cycle lengths and a lack of directed cell movement during embryogenesis. However, the order of cell divisions, as determined by lineage analysis, is unchanged compared to wild type embryos. These results suggest that mel-32/Shmt is required for normal cell cycle lengths in C. elegans.

Mutated zinc finger protein of the cerebellum 1 leads to microcephaly, cortical malformation, callosal agenesis, cerebellar dysplasia, tethered cord and scoliosis.

Heterozygous gain of function mutations in the ZIC1 gene have been described with syndromic craniosynostosis, variable cerebral or cerebellar abnormalities and mild to moderate developmental delay. Deletion of chromosome 3q25.1 including both adjacent ZIC1 and ZIC4 genes have been described as a cause of variable cerebellar abnormalities including Dandy-Walker malformation. We report two siblings presenting with neonatal microcephaly, agenesis of the corpus callosum, brachycephaly with reduced volume of the posterior fossa, cerebellar and pons hypoplasia, scoliosis and tethered cord (closed neural tube defect). One of the siblings had apparent partial rhombencephalosynapsis. Trio analysis of exome sequencing data revealed a novel heterozygous frameshift mutation in ZIC1 at the end of exon 3 in one sibling and was confirmed by Sanger sequencing in both children. The mutation was not detected in DNA of both parents, which suggests parental gonadal mosaicism. We show that expression of the mutant allele leads to synthesis of a stable abnormal transcript in patient cells, without evidence for nonsense-mediated decay. Craniosynostosis was not present at birth, which explains why ZIC1 mutations were not initially considered. This severe brain malformation indicates that premature closure of sutures can be independent of the abnormal brain development in subjects with pathogenic variants in ZIC1.

High burden of neural tube defects in Tigray, Northern Ethiopia: Hospital-based study.

INTRODUCTION: Neural tube defects are the major causes of fetal loss and considerable disabilities in infants. Currently, there is no significant research on the incidence of Neural tube defects in the Tigray region of Ethiopia. OBJECTIVE: To determine the incidence and clinical pattern of the Neural Tube Defects. METHODS: A hospital-based cross-sectional study was conducted from October 2016 to June 2017. All pregnancy outcomes were examined for any externally visible birth defects and neurological integrity by trained midwives under the supervision of senior obstetrics and gynecology and a neurosurgeon. Data were collected using a survey tool to collect maternal and newborn demographic data and a checklist developed to capture newborns with Neural Tube Defects. Data were analyzed using SPSS version 20. The prevalence of NTDs was calculated per 10,000 births. RESULT: Out of the 14,903 births during the study period, a total of 195 infants were born afflicted with Neural Tube Defects. The burden of infants with anencephaly and spina bifida was 66.4 and 64.4 per 10, 000 births, respectively. The overall incidence rate of NTDs in this study was 131 per 10, 000 births of which 23% were liveborn and 77% were stillborn. The highest burden of Neural Tube Defects was observed in Adigrat Hospital from Eastern Zone of Tigray (174 per 10,000 births) and Lemlem Karl Hospital from Southern Zone of Tigray (304 per 10,000 births) compared to Kahsay Abera Hospital from Western Zone (72.8 per 10,000 births) and Sihul Hospital from North Western Zone of Tigray (69.8 per 10,000 births). CONCLUSION AND RECOMMENDATION: Assuming that the non folic acid preventable rate should be 5 per 10,000 births, our prevalence rate is 131 per 10,000 births, and then we have a rate or an epidemic that is 26 times what it should be. This just emphasizes the urgency to implement effective programs to get all women of reproductive age to have adequate folic acid to prevent all of folic acid-preventable spina bifida and anencephaly, which would prevent 96% (125/130) of spina bifida and anencephaly in the Tigray Provence.