Management of Neural Tube Defect: A Single-Center Experience

Objective: Neural tube defects are a heterogeneous and complex group of congenital central nervous system anomalies involving that involve the failed closure of the vertebral column. The spinal cord is frequently affected, and neural tube defects substantially increase the risk of disability and death within the first year of life. Neural malformations are often associated with abnormalities in other organ systems. This study presents our clinical experiences regarding the development and comorbidities of infants with neural tube defect and compares them with the literature. Materials and Methods: This retrospective study included 47 patients (24 females, 23 males) who underwent surgical treatment for neural tube defect in the neurosurgery department of Sivas Cumhuriyet University Faculty of Medicine Training and Research Hospital between 2000 and 2020. Results: Of the 47 patients, 34 (72.34%) had myelomeningocele and 13 (27.65%) had meningocele. Lesion location was thoracolumbar in 38 patients (80.85%), lumbar in 5 (10.63%), lumbosacral in 3 (6.38%), and cervical in 1 patient (2.12%). Twenty-seven patients (57.44%) underwent ventriculoperitoneal shunting due to hydrocephalus. Thirty patients (63.82%) had Chiari malformation type II, 13 (27.65%) had cranial anomalies, and 1 (2.12%) had Down syndrome. In 9 patients, the conus medullaris terminated at or below the L3 vertebral body (19.14%). Two patients (4.25%) died. Conclusion: Because of their multidimensional nature, neural tube defects have various effects on individuals, families, society, and the field of medicine. This study represents a small group of patients with neural tube defects. Cases should be included from other centers to compile more comprehensive data about patients with neural tube defects in Turkey.


acta medica ORIGINAL ARTICLE
A B S T R A C T Objective: Neural tube defects are a heterogeneous and complex group of congenital central nervous system anomalies involving that involve the failed closure of the vertebral column. The spinal cord is frequently affected, and neural tube defects substantially increase the risk of disability and death within the first year of life. Neural malformations are often associated with abnormalities in other organ systems. This study presents our clinical experiences regarding the development and comorbidities of infants with neural tube defect and compares them with the literature.

INTRODUCTION
Neural tube defect (NTD) is a congenital condition in which the vertebral column fails to close and frequently affects the spinal cord. NTD substantially increases the risk of disability and death within the first year of life [1][2][3]. Both genetic and environmental factors are involved in the development of NTD [4,5]. Moreover, its incidence can vary according based on the development status of the country, race, and sex of the child as well as the socioeconomic and education levels of the family [2,[5][6][7]. Different studies have reported the incidence of NTD as 0.72 to 6.2 per 1000 live births [1,2,5,[7][8][9]. Middle-and low-income countries have a higher incidence of NTD [1].
This study presents our clinical experiences regarding the development and comorbidities of infants with NTD and compares them with the literature.

MATERIALS and METHODS
This retrospective study was performed after obtaining ethical approval from the noninterventional clinical research ethics committee of Sivas Cumhuriyet University (2020-03/24, 18.03.2020). We retrospectively evaluated the medical records of 47 patients who underwent surgical treatment for NT in the neurosurgery department of Sivas Cumhuriyet University Faculty of Medicine Training and Research Hospital between 2000 and 2020. Of these, 24 patients (51.06%) were female, and 23 (48.93%) were male. Patients underwent surgical procedures between postnatal day 1 and day 10, as they became eligible for anesthesia. Postoperatively, the patients were monitored for hydrocephalus by examination of head circumference and fontanel bulging. Patients also underwent postoperative follow-up cranial and spinal magnetic resonance imaging (MRI) or cranial computed tomography if performing MRI was not possible.

DISCUSSION
NTD is a congenital abnormality that causes longterm disability and a significant burden on patients, their families, the health system, and society [16]. Half of all congenital anomalies cannot be linked to a specific cause. However, genetic factors and environmental teratogens are significant contributors to the development of congenital anomalies [5,4,16]. The incidence varies between populations, with reported rates per 1000 live births of 0.89-0.93 in European countries, 0.62-13.8 in Arab countries, 0.53 in the United States, 0. 19-6.6 in Southeast Asia, and 5.6-22.6 in Turkey [1,2,5]. Studies indicate that a daily supplement of 0.4 mg folic acid during pregnancy can reduce the risk of NTD [1,9,[16][17][18].
Among the 47 patients with NTD in our series, 27 (54.44%) underwent VP shunting due to hydrocephalus. McDowell et al suggested that 85% of patients with MMC who undergo surgical closure of the defect developed hydrocephalus postoperatively, and 80-90% of these patients require the placement of a VP shunt for treatment [18]. In their study, Gaitanis et al demonstrated that the prevalence of hydrocephalus was related to lesion level, with hydrocephalus occurring in more than 90% of patients with lumbar lesions [11]. In a study by North et al., hydrocephalus was observed in 91-92% of patients with MMC, whereas shunt placement was performed in 76-84% [13].
Chiari type II malformation is frequently associated with NTDs. We detected Chiari type II malformation in 30 (63.82%) of our patients. Turan et al [2] reported this rate to be 65%. Çelik et al determined this rate to be 71.4% and showed that 71% of patients with hydrocephalus with VP shunt were diagnosed with Chiari type II malformation [20,21]. In their study, Gaitanis et al reported that Chiari type II malformation was present in one-third of patients with MMC and caused severe morbidity and mortality. Chiari type II malformation is often detected in patients with a low pontomesencephalic junction [11]. In a study by Mitchell et al, although 75% of patients with MMC had radiological findings of Chiari type II malformation, only one-third of the patients were symptomatic [19]. According to the findings of Copp et al, 30% of patients are symptomatic. Chiari type II malformation is characterized by apnea, difficulty swallowing, and stridor in neonates, as well as headache, quadriparesis, scoliosis, and impaired balance/coordination in older children [3].
MMC is a complex CNS malformation that is frequently associated with other neural and extraneural anomalies. Malformation and hydrocephalus are exhibited in most Chiari type II patients. It is also associated with other anomalies of the CNS, including brainstem defects, dysgenesis of the corpus callosum, large massa intermedia, polymicrogyria, and low-lying tentorium. There are also anomalies observed in the cranial vault, vertebra, and ribs [14]. In our study, 13 (27.65%) patients had agenesis or dysgenesis of the corpus callosum. The level of conus medullaris termination was the L3 vertebra or lower in 9 patients (19.14%). Hannah et al reported various corpus callosum abnormalities in nearly all MMC patients in their study [22].
We observed a mortality rate of 4.25% in our study. One patient died at age 3 years, and the other at age 4 years. In a study of 40-year mortality among patients who underwent surgery for MMC in the United Kingdom between 1960 and 1970, the mortality rate was found to be associated with lesion level, with a 17% survival rate among patients with lesions above T11 and a 61% survival rate among those with lesions below L3 [23]. In patients with MMC, the mortality rate was 1% per year between the ages of 5 and 30 years, with a higher rate observed in patients with higher-level lesions [3].

CONCLUSION
Because of their multidimensional nature, NTDs have various impacts on individuals, families, society, and the field of medicine. This study represents a small group of patients with NTDs. To compile more comprehensive data about NTD patients in Turkey, cases from other centers should be included.

CONFLICTS of INTEREST
The authors declare that there is no conflict of interest.