neural tube defects
Lecturette 2: Neural Tube Defects
Learning Objectives:
Describe the pathophysiology of anencephaly and spina bifida.
Describe the three major subtypes of spina bifida.
Explain common treatments and management approaches for spina bifida
Explain the public health management of an identified risk factor for spina bifida
Neural Tube Defects — Extremely Detailed Lecture Notes
Lecture introduction
Lecturer: Kay Double
Lecture topic: Neural tube defects
This lecture links to unit themes including:
Neural development
Vulnerable populations
Disease prevention
It is also linked to:
Wet anatomy lab class
The lecture also provides a chance to discuss:
Health at the population level
An Australian public health initiative
Definition of public health given in the lecture
Public health is:
“the art and science of preventing disease, prolonging life and promoting health through the organised efforts of society”
This definition was stated as being from the World Health Organization
Content warning
The lecturer warns that the lecture contains:
graphic medical images
Students with concerns are told to:
email the MEDS2001 coordination team
arrange a suitable replacement
Learning outcomes
By the end of the lecture, you should be able to:
Describe the pathophysiology of:
anencephaly
spina bifida
Describe the three major subtypes of:
spina bifida
Explain common treatments and management approaches for:
spina bifida
Explain a public health management approach for:
an identified risk factor for spina bifida
What are neural tube defects?
Definition
Neural tube defects are:
a group of disorders
caused by errors in the very early development of the neural tube
during the first month of life in utero
Prevalence
Global prevalence is about:
1 in 1000 births
Normal neural tube development
The lecture refers back to earlier lectures from Associate Professor Kathy Luu/Leamy on neural tube development.
The neural tube forms by:
closure of the tube
Closure begins:
in the middle of the neural tube
Then proceeds in both directions:
rostrally (towards the head)
caudally (towards the tail/lower end)
This normal closure process is critical because failure of closure at different ends causes different neural tube defects.
Failure of rostral neural tube closure: Anencephaly
What happens?
If the rostral neural tube fails to close properly:
a severe disorder called anencephaly results
Meaning
Anencephaly literally means:
“no brain”
Consequence
The brain does not develop properly
It is described as:
a fatal condition
Outcome
A fetus with anencephaly usually:
dies in utero
or in the first few days after birth
Failure of caudal neural tube closure (more common): Spina bifida
What happens?
If the caudal neural tube fails to close:
the condition is called spina bifida
Meaning of the term
Spina bifida comes from Latin and means:
“split spine”
This refers to:
a split down the spine
or failure of the neural tube/spinal structures to close properly
Spina bifida — overview
Definition
Spina bifida is a:
congenital disorder
Congenital means:
present from birth
Developmental basis
It arises when there is failure of development of:
the vertebral arches
during development of the vertebral column
as well as abnormal development of:
the spinal cord
associated nerves
associated muscles
Visible defect
A cyst-like sac may protrude from the spine
The spinal defect may be:
open to the environment
or closed, covered by skin
Worldwide burden
The lecturer states that about:
215,000 to 322,000 pregnancies worldwide
are affected by spina bifida
Major subtypes of spina bifida
The lecture describes three major subtypes:
Spina bifida occulta (mildest form)
Meningocele
Myelomeningocele
1. Spina bifida occulta
Severity
This is the mildest form of spina bifida
Structural defect
One or more vertebrae do not close properly
Usually around:
L5
S1
lower lumbar / sacral region
Key feature
There is no protrusion of the spinal cord through the vertebral column
External sign: cutaneous stigmata
Although the defect is internal, there may be visible skin signs over the lesion level:
called cutaneous stigmata
Typical appearance may include:
differently coloured skin
a small dimple
a patch of hair growth
These skin changes can indicate an underlying spinal lesion.
Internal associated abnormalities
Spina bifida occulta may be associated with abnormalities inside the vertebral canal, including:
Syringomyelia
A cyst in the spinal cord
This can:
place pressure on the developing spinal cord
damage spinal cord tissue
Tethered cord syndrome
The spinal cord is abnormally connected to the sides of the vertebral column
This can cause:
abnormal movement of the spinal cord
spinal cord damage
Symptoms and effects
These associated abnormalities can lead to a range of symptoms, including failure of normal development of associated systems.
Possible problems include:
anorectal problems
urogenital malformations
bowel dysfunction
bladder dysfunction
sexual dysfunction
Important point
In very mild cases, spina bifida occulta may be:
completely asymptomatic
Some people may not even know they have it
2. Meningocele
Severity
More serious than occulta
What protrudes?
A sac-like cyst of the meninges protrudes through the vertebral defect
Recall: meninges
The meninges are the membranes covering:
the brain
the spinal cord
They occur in three layers
Contents of the sac
The protruding meningeal sac contains:
cerebrospinal fluid (CSF)
Important distinction
Usually there is no spinal cord tissue in the cyst
It is mainly:
a meningeal protrusion filled with CSF
Associated problem
There are often spinal abnormalities at that lesion level
3. Myelomeningocele
Severity
This is the most severe
Also described as the most common form of spina bifida
What protrudes?
Both of the following protrude through the vertebral defect:
meninges
spinal cord tissue
Usual location
About 80% occur in:
the lower back
especially the lumbar and sacral regions
Why it is severe
The spinal cord itself is squeezed into the meningeal sac
Therefore there is direct involvement of:
neural tissue
This causes:
damage to spinal cord tissue
Associated symptoms
paralysis of limbs, especially:
lower limbs
paralysis/weakness of:
abdominal muscles
loss of sensation
loss of movement
incontinence
Management
If diagnosed in time:
surgery is usually required
Timing:
either before birth
or very soon after birth
Visual clue noted by lecturer
The lecturer notes the baby shown appears to have a very large head
This leads into discussion of complications such as hydrocephalus
Complications associated with myelomeningocele
A major complication discussed is:
Chiari II malformation
What happens?
Part of the lower brain:
cerebellum
brainstem
instead of remaining inside the skull,
protrudes through the:
foramen magnum
This is the large hole at the base of the skull
Direction of protrusion
These lower brain structures descend down toward:
what would be the vertebral column
Consequence
This protruding tissue may become:
compressed
damaged
Effects
This can cause a range of symptoms including:
sensory changes
motor symptoms
minor symptoms progressing to paralysis
brainstem damage
complications associated with brainstem dysfunction
Hydrocephalus (very serious)
Hydrocephalus
Meaning
Hydrocephalus means:
“water head”
Mechanism
Normally:
CSF flows through:
the ventricles of the brain
and down through the centre of the spinal cord
In hydrocephalus:
this flow becomes obstructed
Result
The ventricles enlarge due to accumulation of CSF
Increased fluid pressure causes:
compression of brain tissue against the hard skull
Effect on skull/head
In infants, the head enlarges
This produces the characteristic:
large head size
Why it is serious
It is a very serious condition
Outcomes depend on:
severity of pressure
extent of brain tissue compression
effectiveness of treatment
timing of treatment
Treatment
May require surgery
A shunt may be inserted to:
drain excess CSF from the ventricles
This may even be done:
while the child is in utero
Neurological outcome
Depends on:
how severe the hydrocephalus is
how effective treatment is
how early treatment occurs
Diagnosis of spina bifida
Prenatal diagnosis
In many cases, spina bifida is diagnosed:
in utero
Method 1: Ultrasound
First trimester ultrasound may show whether:
the neural tube is developing normally
the brain is developing normally
If something appears wrong:
further confirmation is often done by
second trimester ultrasound
when development is more advanced and clearer
Method 2: Maternal serum alpha-fetoprotein
A protein called alpha-fetoprotein (AFP) is mentioned
High levels in the mother’s serum during early pregnancy indicate:
increased risk of spina bifida
Therefore AFP can be used as:
a biomarker
Symptoms and functional outcomes of spina bifida
The lecture emphasizes that symptoms are very variable.
What determines severity?
Symptoms depend on:
level of the spinal cord lesion
severity of the lesion
Possible effects
paralysis
numbness
tingling
bladder dysfunction
bowel dysfunction
sexual dysfunction
cognitive dysfunction
Important point
Cognitive dysfunction is said to be:
very common in people with spina bifida
Treatment and long-term management
Cure?
There is no cure for spina bifida
Main aim of management
manage symptoms
maintain quality of life
Important principle
Management usually requires a:
multidisciplinary care team
This may include multiple:
medical specialists
allied health specialists
This is important because spina bifida is often:
a complex
long-term
lifelong
health condition
Prognosis / life expectancy / long-term outcomes
Quality of life
People with spina bifida can now often have:
a reasonable
even good
quality of life
especially if well managed
Survival
Mean survival is now around:
50 years
Common causes of death
Death usually occurs due to complications of:
CNS dysfunction
sepsis
cancer
Support needs
Because the condition is:
lifelong
complex
it is important to support:
the patient
and also the caregivers
The lecture stresses that caregivers need:
long-term support
Causes of spina bifida
General cause
Mostly:
sporadic
idiopathic
meaning the cause is not fully known in most cases
Genetic contribution
There is likely:
a genetic predisposition
Supported by:
increased prevalence in some populations in different parts of the world
Environmental and lifestyle contribution
The lecture says lifestyle and environmental factors also play a role.
Risk factors for spina bifida
Maternal health
diabetes
obesity
Drug exposure
especially valproate
Valproate
Used for:
epilepsy
bipolar disorder
prevention of migraines
Other substance exposure
abuse of other substances can increase risk
Environmental exposures
air pollution
Nutrition
poor nutrition
Alcohol and smoking
both are risk factors
Folate and neural tube development
Key nutrient
Folate = vitamin B9 (soluble)
Why it matters
Required for:
normal development of the brain and spinal cord
Particularly critical for:
normal closure of the neural tube
When is folate most important?
During weeks 3 to 6 of embryogenesis
This is very early pregnancy
Often:
before the mother even knows she is pregnant
So adequate folate must be available very early, not just later in pregnancy.
Dietary sources of folate
Foods mentioned as containing folate:
green leafy vegetables
liver
nuts
avocados
lentils
chickpeas
Practical issue
In some populations, these foods may be:
hard to obtain
expensive to obtain
Alternative: take a supplement
Folic acid supplementation
Difference between folate and folic acid
The supplement given is not folate itself
It is:
folic acid
Folic acid is described as:
a prodrug
It can be:
manufactured/synthesised
Then converted in the body to:
folate
Recommended dose
For women considering pregnancy:
recommended folic acid intake is about:
400–800 micrograms per day
taken:
before pregnancy
and during pregnancy
Public health intervention: United States
Historical development
In the 1990s, folate was discovered to be critical for neural tube closure
In 1998, the US Food and Drug Administration decided to:
fortify some grain and cereal products with folic acid
Purpose
To ensure the community/population received adequate folic acid
Outcome
Following fortification:
spina bifida rates in the US reduced by 23%
Importance
This showed that a:
community-wide public health initiative
could significantly reduce neural tube defects
Public health intervention: Australia
Policy
In 2009, the Australia New Zealand Food Standards Code mandated that:
commercial producers of bread
must use flour supplemented with folic acid
Amount added
Flour must contain:
2–3 mg folic acid per kg of flour
What this means nutritionally
About 100 g of bread (around 2 slices) gives about:
half the recommended daily intake of folate
The lecture says the daily intake is about:
0.2 mg/day
although the exact numbers were stated as not essential to remember.
Key point the lecturer wants remembered
You do not need to memorise the exact numbers.
What matters is:
In Australia, it is mandated by law
Commercial bakers must use flour with added folic acid
Australian evidence of effectiveness
2019 analysis
In 2019, researchers from SA Health analysed:
benefits versus costs
using Australian population data
Findings
They concluded the intervention was:
low cost
resulted in 32 fewer neural tube defect cases per year
saved about $1.5 million per year in the health system
Equity benefit
A very important conclusion was that it improved:
equity
Especially in vulnerable groups such as:
teenage mothers
Aboriginal and Torres Strait Islander mothers
Overall conclusion
This simple intervention:
adding small amounts of folic acid to commercial baker’s flour
produced a net benefit for society
in a:
low-cost
efficient
manner
Big-picture ideas from the lecture
1. Neural tube defects happen very early
They arise during the first month in utero
This is why prevention has to occur before or very early in pregnancy
2. Site of failed closure determines the defect
Rostral failure → anencephaly
Caudal failure → spina bifida
3. Spina bifida is not one single presentation
It ranges from:
very mild and asymptomatic
to severe disability with CNS complications
4. Symptoms depend on lesion level and severity
Functional outcomes vary greatly
5. There is no cure
Management focuses on:
symptom control
surgery where needed
preserving quality of life
multidisciplinary care
6. Folate is a major preventable risk factor
Adequate folate in early pregnancy is crucial
7. Public health policy can prevent disease
Food fortification with folic acid is a strong example of:
effective public health
disease prevention at the population level
improved equity in vulnerable groups
Quick exam-style summary
Neural tube defects
Group of disorders caused by failure of normal neural tube closure in early embryonic development.
Anencephaly
Due to failure of rostral neural tube closure.
Fatal because the brain does not develop properly.
Spina bifida
Due to failure of caudal neural tube closure.
Congenital defect involving abnormal vertebral arch/spinal cord development.
Three major subtypes
Occulta: vertebral defect only, no cord protrusion, may be asymptomatic
Meningocele: meninges + CSF protrude
Myelomeningocele: meninges + spinal cord tissue protrude; most severe/common
Important complications
Chiari malformation
Hydrocephalus
Motor, sensory, bladder, bowel, sexual, and cognitive dysfunction
Diagnosis
Prenatal ultrasound
Maternal serum alpha-fetoprotein
Treatment
No cure
Surgery in some cases
multidisciplinary long-term management
Risk factors
Genetic predisposition
maternal diabetes/obesity
valproate
alcohol
smoking
air pollution
poor nutrition
folate deficiency
Prevention
folic acid supplementation
folic acid fortification of flour/bread
proven public health benefit in US and Australia