Central nervous system (CNS) malformations are amongst the most common of the major congenital abnormalities and are an important cause of childhood chronic impairment. One of the major causes of child morbidity and mortality and foetal death may be known to be CNS congenital malformations. Congenital Malformations of the central nervous system are extremely common, affecting 1 to 10:1,000 live births1, can be isolated or appear as part of a hereditary condition or a complex congenital malformations.

A major risk factor for the growth of CNS malformations is maternal diabetes mellitus. Substantial risk factors for the development of CNS malformations are maternal alcoholism, maternal age above 35 years, multiple pregnancy, oligohydramnios, hydramnios, maternal hyperthermia, valproate use by epileptic women during pregnancy. Also, at high risk are fetuses that are small for gestation age. Compared to the population of infants of acceptable size for their gestational age, the incidence of malformations (any type) in the population of babies who are small for the gestation term is 3.3 percent.2,3

The mechanism producing these congenital CNS abnormalities are still highly speculative and seem to be very complicated. Occasionally, classical mendelian inheritance is found. The pattern of incidence is most often associated with polygenic mechanisms, environmental material exposure, or a combination of the two. The teratogenic effect interrupts the complex sequence of steps that are interrelated. Interference with normal development at any level will adversely affect all subsequent developmental programmes, so, as a general rule, the more extensive and extreme the malformation, the sooner the insult in embryonic development. Normally, such a well-defined, time-limited occurrence will not create a simple anomaly, but will adversely affect the whole subsequent developmental progress chain. A number of conceptual frameworks have been developed for the underlying mechanisms of teratogenesis, such as the one suggested by Zwilling4, which includes abnormal initial stimulus (absent, deficient or excessive), abnormal reaction of reacting tissues (absent, deficient or excessive), abnormal stimulus and response, abnormal differentiation, abnormal structure development, degenerative pro- response, abnormality of both stimulus and response, abnormal differentiation, abnormal structure development, CNS anomalies can be divided into developmental malformations and disturbances (5). Brain developmental abnormalities result from developmental malformations. This may be caused by chromosomal anomalies and mutations of single genes or by imbalances of factors that regulate the expression of genes during the development of the brain. Gene defects may be in the germline or may, by spontaneous somatic mutation, evolve after conception or be connected to physical or chemical agents acting as teratogens. Multifactorial aetiology in relation to various genetic and environmental influences induces certain malformations. Disruptions are caused by environmental or intrinsic causes, such as foetal infection, exposure of the foetus to toxic chemicals, radiation, and foetal hypoxia, resulting from the disruption of a normally developing brain. Unless the exposure recurs or persists, disturbances do not recur. Exposure during pregnancy to established teratogens and viral infections can occur. For all malformations and disturbances, the timing of exposure is important. The earlier the exposure, the more serious the CNS vulnerability is. Fetal cytomegalovirus (CMV) infection, for instance, may be responsible for microcephaly and polymicrogyria before midgestation. Encephalitis is caused by CMV infection in the third trimester, close to postnatal CMV encephalitis caused by other diseases, such as deafness.6,7 The third to eighth week of gestation, during which the brain and most organs mature, is the most important time for malformations and disturbances.5

The aim of the present study was to assess the various types of congenital CNS malformations in relation to their neuroimaging findings.

This was a single centric, observational, cross sectional, descriptive study conducted in Department of pediatrics of a tertiary care hospital. The study was conducted for a period of 24 month from 1st January 2019 to 31st December 2020. All patients in the age group of 0 to 12 years, presented to our hospital with CNS malformation. The sample size calculated was 100.

Ethical considerations

The study was initiated after obtaining approval from the institutional ethics committee and department of pediatrics. A written informed consent was taken from the mothers after the babies were stable and ready for enrolment into the study.

Selection criteria

Participants were selected based from the following selection criteria

Inclusion criteria

• Patients of age group of 0 to 12 years admitted in tertiary care center with diagnosed CNS malformation and confirmed on neuroimaging studies
• Patients whose parents or legal guardian are ready to give written informed consent
• Patients whose parents or legal guardian are willing to be part of the study

Exclusion criteria

• Still born with CNS malformation.
• Patient with CNS malformation above 12 years of age.
• Patients whose parents or legal guardian are not ready to give written informed consent
• Patients whose parents or legal guardian are not willing to be part of the study

Study procedure

The study was an observational, descriptive design carried among patients in the age group of 0 to 12 years, presented to our hospital with CNS malformation. The study was conducted after IEC clearance for a period of 24 months from 1st January 2019 to 31st December 2020. All the patients in this study were admitted either through out-patient department or through emergency department of the hospital. All the relevant data was entered in pre tested case record form.

After obtaining approval from the Institutional Ethics Committee, patients fulfilling the inclusion and exclusion criteria and whose parents or legal guardian willing to give informed consent were included in the study. The detailed history of the patient was taken from parents or legal guardian regarding personal data history, mode and type of delivery, chief complaints and other relevant findings. Full CNS clinical examination of patients was done to assess the general condition of the patient. Neuroimaging done includes USG skull, CT brain and spine, MRI brain and spine.

Statistical analysis

Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD and median. Normality of data was tested by Kolmogorov-Smirnov test. A p value of <0.05 was be considered statistically significant. The data was entered in MS EXCEL spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 26.0.

Table 1: Baseline characteristics

The average age of enrolled patients in our study was 84.64 ± 336.07 days (̴3months). Majority of patients diagnosed at an age of < 7 days (76%).  Gender wise distribution showed relative prevalence of female patient (55%) in the study.

Table 3: Weight wise distribution and mode of delivery

The average birth weight among our study participants were 3.64 ± 3.42 kg. 50 % of children had birth weight ≤ 2.8 kg. Majority of patients enrolled had vaginal delivery. 26% patients underwent LSCS.

Table 3: Term wise distribution

Full term delivery was seen in majority of patients (93%) enrolled in study. 2% patients were born extremely preterm.

Table 4: Presenting complain

Large head was the most common (75%) presentation seen in our patients. 29% patients presented with large head and mass at the back. The other common presentation seen were seizure and mass at the nape of neck.

Table 5: Type of seizure

Majority of patients presented with no seizure (75%). GTCS was the most common type of seizure among those who presented with seizure.

Table 6: Associated congenital anomaly

Majority of patients presented with no associated anomaly. CTEV was the most common associated anomaly followed by presence of tetralogy of fallot and PDA. Other common anomalies were Right ventricular dilation, Lumbar kyphoscoliosis and horseshoe kidney, Kyphoscoliosis.

Table 7: Limb weakness and Muscle tone among patients

Limb weakness was absent in majority of patients (88%). 12 % presented with limb weakness. Majority of patients presented with normal muscle tone (87%). Hypotonia was seen in 9% patients. Hypertonia was seen in 4% patients.

Table 8: Diagnosis

Hydrocephalous was the most common (75%) type of neural tube defect among patients enrolled in our study followed by those presenting with meningomyelocele (29%) and Arnold Chiari malformation (13%). The other common NTD were Dandy walker syndrome, Spina bifida occulata and Occipital encephalocele.

Central nervous system malformations are an important problem of child neurology. The term malformation means any morphological abnormality of the CNS that dates to the embryonic or foetal period, regardless of the mechanism of its origin. Neural tube defects (NTDs) account for the most congenital anomalies of the central nervous system (CNS) and result from failure of the neural tube to close spontaneously between the 3rd and 4th week of embryonic development. Major neural tube defects include spina bifida occulta, meningocele, myelomeningocele and encephalocele. Spina bifida occulta consists of a midline defect of vertebral bodies without protrusion of the spinal cord or meninges. Most individuals are asymptomatic and lack neurological signs. In some cases patches of hair, lipoma, discoloration of the skin or a dermal sinus in the midline of the lower back suggests a significant malformation of the spinal cord. Meningocele occurs when the meninges herniate through the defect in the posterior vertebral arches.

Myelomeningocele represents the most severe form of dysraphism that involves vertebral column and occurs with an incidence of 1/ 4000 live births. Myelomeningocele may be located anywhere along the neuraxis, however, lumbosacral region accounts for at least 75% of the cases. Hydrocephalus develops in at least 80% of patients with myelomeningocele. Ventricular enlargement may be slow growing or may be rapid.8-10

The average age of enrolled patients in our study was 84.64 ± 336.07 days (̴3months) with majority of patients diagnosed at an age of < 7 days. With recent advances in the diagnosing modality, majority of the CNS malformation are Diagnosed prenatally, during pregnancy, through laboratory or imaging tests and those without prenatal evaluation are diagnosed immediately after birth. Gender wise distribution showed relative prevalence of male patient (55%) in the study, with male to female ratio of 1.2:1. There is increasing evidence that gender of the child influences risk for developing an NTD. Historically, neural tube defects have predominated in female infants but the reasons remain unclear.11 Animal studies have highlighted female embryos tend to be developmentally delayed compared with their male littermates at neurulation stages, leading to the hypothesis that the longer duration of cranial neural tube closure would lead to greater susceptibility to NTD- causing insult. However, going against this hypothesis, the delay in development may occur prior to neural tube closure, with female and male embryos taking the same time to complete cranial neurulation.12 Other suggested mechanisms include sex differences in genetic risk, epigenetic factors, a differential rate of fetal loss and susceptibility to environmental influences.13 Study conducted by Turhan AH14 also reported female prevalence in the study. But similar to our study, male predominance was seen in study conducted by AbouEl-Ella.15 The average birth weight among our study participants were 3.64 ± 3.42 kg, which was almost similar in study conducted by Emine Aydın16 where the average birth weight was 3060±647.5 g. Retrospective study by Turhan AH14 also reported similar median birth weight of 3150 g.

Hydrocephalous was the most common (75%) type of neural tube defect among patients enrolled in our study followed by those presenting with meningomyelocele (29%) and Arnold Chiari malformation (13%). The mechanisms producing these anomalies are still largely speculative and appear to be quite complex. Classical Mendelian inheritance is occasionally found. More frequently, the pattern of occurrence is consistent with polygenic mechanisms, exposure to environmental substances, or a combination of the two. The etiology of CNS malformations remains obscure in most cases. The timing of an insult to the foetus is more important than the nature of the insult in determining the type of resulting malformations. The most frequent CNS malformations in study conducted by Hadzagić-Catibusić F3 were neural tube defects (38.6%), hydrocephalus was seen in (26.8%), microcephaly in (18.9%), agenesis of corpus callosum in (7.9%), Dandy Walker malformation in (4.7%). Study conducted in Brazil by Guardiola A17 reported the most frequent neurological malformations as congenital clubfoot, hydrocephalus and meningomyelocele, other malformations included microcephaly (3.2%), craniosynostosis with neurologic alterations (2.1%), holoprosencephaly (2.1%), macrocephaly (2.1%), Arnold Chiari syndrome (2.1%), ocular hypertelorism (1.1%), Moebius syndrome (1.1%), agenesis of the corpus callosum (1.1%) and squizencephaly (1.1%). In the study conducted in united states 18, anencephaly and spina bifid are the most commonly described CNS malformations, affecting 1:1000 gestations, and more than 300,000 patients worldwide. Both spina bifid and anencephaly are significant causes of infant and fetal deaths.19 Children with anencephaly usually die at birth or with a few hours of life. Children with spina bifida that do survive are at increased risk for permanent incapacities and psychosocial difficulties.20 Clinical problems such as paralysis, hydrocephalus Arnold-Chiari type II, syringobulbia, syringomyelia and endocrine dysfunction may result from the defect itself or from its repair.20 Ethopian study reported the commonest type of neural tube defects among newborn is anencephaly, which accounts for 48.1% of total cases. The second and the third common types of NTDs are spinal bifida and encephalocele that account for 36.2% and 11.8% of total cases, respectively.21

Large head was the most common (75%) presentation seen in our patients, 29% patients presented with large head and mass at the back. The other common presentation seen in our study were seizure and mass at the nape of neck. GTCS was the most common type of seizure among neonates. Studies presented in past have highlighted the most common presentation of a closed NTD is an obvious abnormality along the spine such as a fluid-filled cystic mass, area of hypopigmentation or hyperpigmentation, cutis aplasia, congenital dermal sinus, capillary telangiectasia/haemangioma, hairy patch (hypertrichosis), skin appendages, or asymmetrical gluteal cleft.22

Among   patients   associated   congenital   anomaly,   congenital   talipes equinovarus (CTEV) was the most common associated anomaly followed by presence of tetralogy of fallot and Patent ductus arteriosus (PDA). Infants with neural tube defects (NTDs) may have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. In our study associated malformation was seen in 15% patients. Emine Aydın (100) in his study highlighting 10-year experience of among childrens presenting with congenital CNS malformation reported common associated anomalies such as VSD, TOF, TGA and bilateral foot defect. Stoll C et al23 in his study highlighted of the 360 infants with NTDs born during this period, 20.5 % had associated malformations. Malformations in the face (oral clefts), in the musculoskeletal system, in the renal system, and in the cardiovascular system were the most common other anomalies. Study conducted in northern India, where the prevalence of NTD is reported to be the highest in India, reported about 36.84% of total cases had associated malformations such as paraplegia, Arnold–Chiari malformation, and talipesequinovarus.24 Presence of such anomalies not only  increases the morbidity in the post neonatal life but also increases mortality among patients.25,26

Hydrocephalous as the most common type of neural tube defect among patients enrolled in our study followed by those presenting with meningomyelocele and Arnold Chiari malformation. The other common NTD were Dandy walker syndrome, Spina bifida occulata and Occipital encephalocele. CTEV was the most common associated anomaly followed by presence of tetralogy of fallot and PDA. Majority of patients diagnosed at an age of < 7 days. Majority of patients enrolled had vaginal delivery. Full term delivery was seen in majority of patients.

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