Neural Tube Defects: Symptoms, Types, Causes and Treatment

Neural tube defects (NTDs) are among the most serious congenital malformations, impacting both newborns and their families with lifelong health challenges. These defects occur very early in pregnancy, often before a woman even knows she is expecting. Understanding their symptoms, types, causes, and treatment options is crucial not only for clinicians but also for anyone interested in maternal and infant health. In this article, we provide a comprehensive overview of NTDs, drawing on the latest research to inform and empower readers.

Symptoms of Neural Tube Defects

Neural tube defects can present with a wide variety of symptoms, from subtle physical findings to severe neurological impairment or even early death. Recognizing these symptoms is key for timely diagnosis and intervention, which can sometimes improve outcomes and quality of life.

Symptom	Description	Severity Range	Source(s)
Paralysis	Loss of movement, often below lesion site	Mild to severe	2 3 4 7
Loss of Sensation	Impaired or absent feeling below the defect	Mild to severe	2 3 4
Bladder/Bowel Issues	Incontinence or retention, frequent infections	Mild to severe	2 7
Visible Lesion	Open or closed defect on back or skull	Obvious to hidden	2 5 7
Hydrocephalus	Fluid buildup in the brain, enlarged head	Severe	7
Intellectual Impairment	Cognitive delays, learning difficulties	Mild to severe	3 7

Table 1: Key Symptoms of Neural Tube Defects

Understanding the Symptoms

Symptoms of neural tube defects can vary dramatically depending on the type and location of the defect. Some babies may be born with obvious physical abnormalities, while others might show only subtle signs that become apparent as they grow.

Visible and Neurological Signs

Many NTDs are detected at birth due to visible abnormalities. For example, open neural tube defects like myelomeningocele (a form of spina bifida) present as a sac-like protrusion on the back, often exposing the spinal cord and nerves. This exposure can lead to:

• Paralysis or weakness: Most often in the legs, which may be partial or complete depending on the level of the lesion.
• Loss of sensation: The child may not feel touch, pain, or temperature below the affected area 2 3 4.

Internal Complications

NTDs often affect more than just the nervous system. Many children suffer from:

• Bladder and bowel dysfunction: These problems can lead to chronic urinary tract infections or kidney damage if not managed properly.
• Hydrocephalus: Especially common in spina bifida, this condition involves the accumulation of fluid in the brain, requiring surgical intervention 7.

Cognitive and Developmental Impact

Although NTDs primarily affect the spinal cord and brain, some types—particularly those involving the brain—can result in:

• Intellectual disabilities
• Learning difficulties
• Problems with attention and memory 3 7

Asymptomatic Cases

Not every neural tube defect is immediately obvious. Closed NTDs, such as spina bifida occulta, can be asymptomatic or present only subtle skin changes like a tuft of hair or a small dimple over the spine 2 5. Sometimes, these are discovered incidentally during imaging for unrelated reasons.

Types of Neural Tube Defects

NTDs are not a single condition but a group of related disorders. Each type has distinct features, risks, and outcomes, making classification important for management and prognosis.

Type	Main Features	Severity	Source(s)
Anencephaly	Absence of large parts of brain/skull	Fatal	2 3 4 5
Spina Bifida (Myelomeningocele)	Open spinal cord, nerve protrusion	Severe	2 3 4 5 7
Spina Bifida Occulta	Hidden, skin-covered spinal defect	Mild	2 5
Encephalocele	Brain/meninges herniate through skull	Variable	2 9
Meningocele	Meninges protrude, no neural tissue involved	Mild to moderate	2
Craniorachischisis	Entire neural tube open along spine/brain	Fatal	2 6
Iniencephaly	Severe neck/spine malformation	Fatal	9

Table 2: Major Types of Neural Tube Defects

Open vs. Closed Defects

NTDs are generally divided into two main categories:

• Open NTDs: These occur when the brain or spinal cord is exposed at birth. Examples include anencephaly, myelomeningocele (open spina bifida), and craniorachischisis. These defects often result from primary neurulation failure and are usually severe or fatal 2 4 5.
• Closed NTDs: Here, the neural tissue is covered by skin. These defects may be mild and even asymptomatic, as seen in spina bifida occulta, or may cause neurological symptoms if nerves are tethered or compressed 2 5.

Common Types

Anencephaly

• Characterized by absence of a major portion of the brain, skull, and scalp.
• Infants are often stillborn or die shortly after birth 2 3 4.

Spina Bifida

• Myelomeningocele: The most severe form, with spinal cord and nerves protruding through an opening in the spine. Causes significant disability 2 4 5 7.
• Meningocele: The meninges (protective coverings of the spinal cord) protrude, but the spinal cord remains in place. Prognosis is generally better 2.
• Spina Bifida Occulta: A mild form, often with no symptoms, sometimes presenting with a patch of hair, birthmark, or dimple over the spine 2 5.

Encephalocele

• A sac-like protrusion of the brain and meninges through an opening in the skull. Severity depends on the size and location 2 9.

Craniorachischisis and Iniencephaly

• Craniorachischisis: The neural tube remains entirely open along the brain and spine, leading to early death 2 6.
• Iniencephaly: Marked by a severely malformed head and spine, usually fatal 9.

Causes of Neural Tube Defects

The causes of neural tube defects are multifactorial, involving complex interactions between genetic predispositions and environmental exposures. Despite extensive research, much remains to be learned about precisely why NTDs develop.

Cause	Description	Impact	Source(s)
Genetic Factors	Multiple genes involved, some identified in mice	Significant	1 3 6 7 8
Environmental	Folic acid deficiency, maternal diabetes, obesity	Modifiable	1 2 3 7
Medication	Certain drugs (e.g., antiepileptics, dolutegravir)	Increased risk	9 10
Gene-Environment	Interactions between genes and environment	Complex	6 7 8
Unknown Factors	Many cases remain unexplained	Unclear	7 8 11

Table 3: Causal Factors in Neural Tube Defects

Genetics: The Underlying Blueprint

Research in animal models has identified over 200 genes that can cause NTDs when mutated, especially in mice. In humans, the genetic basis is less clear, but evidence points to a polygenic or oligogenic inheritance pattern—meaning that several genes may work together, sometimes interacting with environmental factors, to influence risk 1 3 6 7 8.

Some key points:

• Mutations in genes involved in folate metabolism, such as MTHFR, have been linked to higher risk in some populations 8 11.
• Genes controlling cell signaling pathways like Sonic hedgehog and planar cell polarity (Wnt pathway) are implicated in neural tube closure 2 6.

Environmental Influences

Environmental factors that raise the risk of NTDs include:

• Folic acid deficiency: Low intake before and during early pregnancy is a well-established risk factor. Supplementation can substantially reduce the incidence of NTDs, though not all cases are prevented this way 1 2 3 7.
• Maternal diabetes and obesity: Both conditions increase NTD risk 2 7.
• Exposure to certain medications: Antiepileptic drugs (like valproic acid) and some antiretrovirals (e.g., dolutegravir) have been associated with increased NTD risk 9 10.

Gene-Environment Interactions

It's not just genes or environment alone—it's how they interplay:

• A woman with a genetic predisposition may only develop an affected pregnancy if she also encounters a specific environmental trigger, such as insufficient folic acid 1 6 7 8.
• This complexity explains why some NTDs occur even when mothers take recommended supplements.

Unknown and Emerging Factors

Despite advances, many NTDs have no clear cause. Ongoing research is exploring:

• Subtle genetic mutations
• Copy number variants
• Regulatory gene changes
• New environmental exposures 7 8

Treatment of Neural Tube Defects

Managing neural tube defects requires a combination of prevention, medical care, surgical intervention, and emerging therapies. Early diagnosis and a multidisciplinary approach are key to improving outcomes.

Treatment	Approach/Goal	Effectiveness	Source(s)
Folic Acid	Preconception/prenatal supplementation	Preventive (partial)	1 2 3 6 7 11
Inositol	Supplement for folic acid-resistant cases	Experimental	6 11
Surgery (Postnatal/In Utero)	Close defect, preserve function	Improves outcome	7 11 12
Multidisciplinary Care	Rehab, mobility, bladder/bowel management	Improves quality	7
Stem Cell Therapy	Experimental regeneration of neural tissue	Promising	12

Table 4: Treatments and Interventions for Neural Tube Defects

Prevention: The Power of Folic Acid

The single most effective prevention strategy is ensuring adequate maternal intake of folic acid before conception and during early pregnancy. This intervention can prevent up to 70% of NTDs, especially in populations with previously low folate intake 1 2 3 6 7 11.

• Public health initiatives: Many countries now fortify foods with folic acid, leading to a decline in NTD incidence 4 7.
• Limitations: Not all NTDs are folic acid-responsive, highlighting the need for additional preventive options 2 6.

Adjunct and Experimental Preventive Therapies

• Inositol supplementation: Has shown promise in animal models for preventing folic acid-resistant NTDs. Human trials are ongoing 6 11.

Surgical Interventions

Postnatal Surgery

• Traditional treatment involves surgical closure of the defect after birth to prevent infection and further nerve damage.
• This does not reverse existing neurological impairment but can reduce complications 7 11.

In Utero (Fetal) Surgery

• Advances now allow some NTDs (particularly myelomeningocele) to be repaired before birth.
• Early closure in the womb can reduce neurological damage and improve mobility and bladder function 7 11.

Experimental Regenerative Therapies

• Stem cell therapy: Recent animal studies show that injecting mesenchymal stem cells into the amniotic cavity can promote regeneration of neural tissue and improve functional outcomes. This approach is still experimental but offers hope for future treatment 12.

Multidisciplinary Long-Term Care

Children with NTDs often require:

• Physical therapy: To maximize mobility and independence
• Bladder and bowel management: To prevent infections and kidney damage
• Educational support: For learning difficulties and developmental delays
• Regular monitoring: For complications like hydrocephalus 7

Conclusion

Neural tube defects are complex, multifaceted conditions that continue to challenge clinicians, researchers, and families. While prevention through folic acid supplementation has made a significant impact, not all cases can be avoided. A combination of surgical advances, experimental therapies, and comprehensive care is providing new hope for affected children and their families.

Key Points:

• NTDs present with a wide range of symptoms, from subtle to life-threatening
• There are several major types, with varying severity and outcomes
• Causes are multifactorial, involving genetic, environmental, and gene-environment interactions
• Prevention with folic acid is highly effective, but not universal; new therapies are emerging
• Treatment includes surgery, experimental regenerative approaches, and lifelong supportive care

Continued research and public health action are essential to further reduce the burden of neural tube defects and improve outcomes for those affected.