1b.) Development of Nervous System Flashcards
Why is the nervous system most susceptible to insult during the pre-natal period?
It is the most complex body system and is also:
- One of the first to develop
- One of last to complete development
- … long length of time to develop increases susceptibility
During what week does the neural tube form?
Week 4
When is the notochord formed?
Gastrulation produces the notochord in week 3
What is the notochord?
A solid rod of cells running the midline of mesoderm which releases signalling molecules with directs the differentiation of overlying ectoderm into neuorectoderm
Describe the formation of the neural tube
- Gastrulation produces notochord in week 3
- Notochord releases signalling molecules to cause overlying ectoderm to differentiate into neuroectoderm- forms the neural plate
- Neural plate thickens at lateral edges to form neural folds
- Neural folds elevate and start to turn towards each other
- Depressed mid region is called the neural groove
- Neural folds gradually approch each other in midline and fuse to from tube
What is the neural groove?
Depression in mid region of the neural plate
By what day is the neural tube completely closed?
28-32 days (whole process takes ~10 days)
Why is it important to know the approximate time of closure of the neural tube when considering fetal abnormalities with the CNS?
Closes at 28-32 days; hence, woman may not know she is pregnant and may still therefore be unknowingly having teratogenic things e.g. alcohol etc…
What is the name given to the opening at each end of the neural tube?
When does each one close?
- Cranial end= anterior neuropore (closes middle 4th week)
- Caudal end= posterior neuropore (closes end 4th week)
Where does fusion of neural tube start?
Fusion starts in the middle of tubes. Fusion then occurs along length of neural tube with cranial end closing just before caudal end
State consequence of failure of closure of neural tube at:
- Cranial end
- Caudal end
- Cranial: anencephaly
- Caudal: spina bifida
What is anencephaly?
What is the prognosis?
- Baby is born without parts of brain, skull and scalp
- Very poor; most do not survive birth and those that do only survive a few hours or days
Spina bifida, caused by failure of closure of caudal end of neural tube can occur anywhere along length but where is it most common?
Lumbosacral region
State and descibe the 4 different types of spina bifida
- Spina bifida occulta: divided vertebral arch but no other abnormality
- Spina bifida cystica: coverings of neurla tissue +/- neura tube tissues protrude through vertebral arches adn skin to form cyst like sac (has two subtypes)
- Meningocoele: neural tube in normal position. Protruding subarachnoid space forms cyst
- Meningomyelocoele/myelomeningocoele: neural tubes lies within the cystic space
- Rachischisis: neural folds don’t round up and remain as folds continous with surface of ectoderm. Neural tissue is exposed.
Order the 4 types of spina bifida in terms of seriousness; starting with least serious
- Spina bifida occulta
- Meningocele
- Meningomyelocoele/myelomeningocele
- Rachischisis
Is rachischisis compatible with life?
No???
CHECK
Do neurologial deficits occur with spina bifida?
- Spina bifida occulta: no neurological defects malformation is not usually detected at birth and doesn’t cause disability
- Meningocele: neurological deficits as development of spinal cord may be affected but less severe than below
- Myelomeningocele: neurological deficits (fluid in womb damages spinal exposed spinal cord)
What occurs in 80-90% of children born with severe NTDs (such as meningocele and myelomeningocele)?
Hydrocephalus (excess CSF in ventricular system). **NOTE: hydrocephalus can lead to seconary neurological deficits
Is spina bifida associated with cognitive delay?
NO, some types are just associated with neurological deficits
Briefly explain why most children born with severe NTDs have hydrocephalus
Presence of Arnold-Chiari malformation (herniation of part of cerebellum into foramen magnum). This happens as the spinal cord is tethered to the vertebral column (due to its abnormal development) and hence as column lengthens it pulls cerebellum inot foramen magnum and cuts off flow of CSF
How do we treat hydrocephalus in children with severe NTDs?
Ventriculoperitoneal shunt (drains CSF from one of ventricles into peritoneal cavity)
State two ways in which NTDs can be diagnosed
- Raised maternal serum alpha-fetoprotein
- Ultrasound (12 weeks)
What may we offer women who are pregnant with a child with a NTD?
Perform surgery in utero as early as 22 weeks. Fetus is exposed by incision in womb and defect repaired and then fetus placed back in uterus
NTDs have multifactorial aetiology but what can reduce incidence by 70%?
Folic acid pre-conceptually (ideally 3 months) and for the duration of first trimester
Summarise how we make a nervous system
*Think of Mongan’s diagram
Explain why we have a cauda equina
- At 3rd month spinal cord length= vertebral column length
- Thereafter, vertebral column grows faster
- Spinal roots must therefore elongate to still exit at their intervertebral foramen- this forms cauda equina
During the 4th weekthree dilations develop at the cranial end of the tube; state these 3 dilations
- Prosencephalon (forebrain)
- Mesencephalon (midbrain)
- Rhombencephalon (hindbrain)
Describe how the primary brain vesicles are formed
After neural tube closes in 4th week, the three dilations (prosencephalon, mesencephalon, rhombencephalon) become the 3 primary brain vesicles (forebrain, midbrain and hindbrain)
During the 5th week the 3 primary brain vesicles develop into 5 secondary brain vesicles; state which secondary brain vesicle each of the primary brain vesicles gives rise to
State the mature derivatives of each of the secondary brain vesicles:
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
This image is a nice summary of brain vesicle development
The neural tube has to bend at the cranial end as it’s growth and development exceeds the available space linearly; state the two flexures formed and where each one is
- Cervical flexure: between rhombencephalon (hindbrain) and spinal cord
- Cephalic flexure: in mesencephalon (midbrain) region
*Hence, neuroaxis does not remain straight
What is the ventricular system in the brain?
Set of communication cavities in brain that produce, transport and and remove CSF which bathes CNS
State 3 roles of CSF
- Protection
- Buoyancy (reduces net weight of brain to prevent excess pressure on base of brain)
- Chemical stabillity (helps produce an enviroment that brain can function in)
Where is the ventricular system derived from embryologically?
Lumen of neural tube
Describe which part of ventricular system each of the following primary vesicles gives rise to:
- Forebrain
- Midbrain
- Hinbrain
- Forebrain: lateral ventricles & 3rd ventricle
- Midbrain: cerebral aqueduct
- Hindbrain: 4th ventricle
The spinal cord initially develops as three layers; state these three layers
- Neuroepithelial lyer
- Intermediate/mantle layer
- Marginal layer
Describe what each of the following three layers of teh neural tube gives rise to:
- Neuroepithelial layer
- Intermediate/mantle layer
- Marginal layer
- Neuroepithelial layer: becomes ependymal layer (thin layer of glial cells lining ventricular system of brain and central canal of spinal cord)
-
Mantle layer:
- Forms the neuroblasts that will become neurons of the grey matter
- Differentiation of neuroblasts forming thickenings in dorsal and ventral regions of the cord alar and basal plates
-
Marginal layer:
- Contains axons leaving and entering the mantle zone. After myelination this layer looks white-ish and constitutes to white matter of spinal cord.
What region does each of the following become:
- Alar plate
- Basal plate
- Alar plate (dorsal): sensory
- Basal plate (ventral): motor
Describe where neural crest cells develop and what happens to them
- Develop on edges of the neural folds (entire length)
- Become displaced and enter mesoderm
- Undergo epithelial to mesenhymal transition
- Go on to form many structures in body
State some structures that are neural crest cell derivatives
Neural crest cell migration is complex and hence neural crest cells are extremely vulnerable to enviromental insult especially….?
Alcohol
Abnormalities in neural crest cell migration can cause defects in one component or multiple components (resulting in recognisable syndromes); give an example of each
- One component: Hirschsprung’s disease (aganglionic megacolon- nerves that control passing bowel movement absent in section of bowel)
- Multiple component: DiGeorge syndrome (thymus hypoplasia, parathyroid dysfunction, cardiac abnormalities, facial defects)
