NS Development

Question 1

Why is the nervous system the most susceptible to injury during the pre-natal period compared to other systems?

Answer 1

It’s one of the first systems to develop and one of the last to complete development

It’s the most complex body system

Question 2

What begins to form in week 3 of neural tube development and what does this trigger? What has it become by week 4?

Answer 2

Primitive streak - starts gastrulation (creates 3 germ layers)

By end of week four have a neural tube with more complex structures e.g. somites

Question 3

Describe the formation of the neural tube

Answer 3

Gastrulation->
notochord->
induces neurulation (induction of neural plate) day 18 ->
elevation of lateral edges of plate -> depressed mid-region = neural groove day 19
-> neural folds gradually approach each other in midline and fuse -> neural tube (day 21-23)

By day 28-32 neural tube completely closed (early when mothers may not realise pregnant)

Question 4

What is the notochord and what does it do?

Answer 4

Solid rod of cells running in the midline with important signalling role

Directs conversion of overlying ectoderm to neuroectoderm

Question 5

How does the neural tube fuse together and what does this create initially?

How could mistakes in this process lead to serious common birth defects of the nervous system?

Answer 5

Neural tube fuses along its length starting dentally

Creates an anterior neuropore and posterior neuropore

Defects in closure of neuropores

Question 6

What do cranial failures of the neural tube to close result in? What about at the caudal end?

Answer 6

Cranial defect -> anencephaly (no head or brain)

Caudal defect -> spina bifida

Question 7

What are the 4 types of spina bifida and how serious is each one?

Answer 7

Occulta - mildest (1+ vertebrae malformed)

Closed neural tube defect - some of bones spinal cord don’t completely form -> bulges of tissue

Meningocele - a cyst with meninges and and CSF but spinal cord not in cyst so less risk of neurological deficit

Myelomeningocele - most serious, spinal cord and nervous tissue in cyst -> commonly causes neurological deficits

Question 8

Where does spina bifida occur, what does it cause? How can you treat that?

Answer 8

Can occur anywhere along length of Spinal column - most common in lumbosacral region

Neurological deficits occur although not associated with cognitive delay

Hydrocephalus (accumulation CSF in the ventricular system) nearly always occurs and can lead to secondary cognitive impairment if untreated ✅ ventricular peritoneal shunt

Question 9

What is Rachischisis?

Answer 9

Failure of neural fold elevation -> just end up with primitive nervous tissue along posterior surface of foetus - incompatible with life

Question 10

How are neural tube defects screened for, diagnosed and prevented ?

Answer 10

Screened - raised maternal serum alpha-fetoprotein

Diagnosed - USS

Multifactorial aetiology but folic acid pre-conceptually (3months) and for first trimester reduces incidence by 70%

Question 11

What are the anatomical divisions of the adult CNS?

Answer 11

• cerebral hemispheres

Midbrain

Thalamus

Pins

Cerebellum

Medulla oblongata

Spinal cord

Question 12

Explain how the hollow neuroectoderm tube develops into different structures?

Answer 12

Lumen -> ventricular system

Cranially 3 dilations-> cranially 5 dilations -> 5 anatomical divisions of brain (then patterning and organisation)

Caudally -> spinal cord (then patterning and organisation)

Bends -> flexures

Migration-> neural crest

Question 13

Explain why the cauda equina forms?

Answer 13

Most of the length of neural tube -> spinal cord

3rd month - spinal cord same length as vertebral column. Then vertebral column grows faster as trunk expands

Spinal roots must elongate as they still exit at their intervertebral foramen -> cauda equina

Question 14

Describe the formation of primary and secondary brain vesicles. What do the secondary vesicles eventually become?

Answer 14

During neural folding three primary brain regions develop:

1. Forebrain/ prosencephalon
2. Midbrain/ mesencephalon
3. Hindbrain/ rhombencephalon

After neural tube closure (4th week) dilations become three primary brain vesicles

At 5 weeks of development the primary Brian vesicles become 5 secondary vesicles:

Forebrain-> telencephalon + diencephalon (cerebral hemispheres + thalamus)

Midbrain -> mesencephalon (midbrain)

Hindbrain -> metencephalon + myelencephalon (pons/ cerebellum + medulla oblongata)

Question 15

What are the two cranial neural tube flexures that form? Why do they need to form?

Answer 15

Exceeds available space linearly

Cervical flexure (spinal cord- hindbrain junction)

Cephalic flexure (midbrain region)

Neuraxis no longer straight

Question 16

What is the ventricular system in adults and what is it’s function?

Answer 16

Tubular structure of interconnected reservoirs of CSF produced by cells of ventricular lining

Cushions Brian and Spinal cord

Question 17

What is hydrocephalus, how is it treated?

Answer 17

Ventricular system abnormality - any blockage e.g. tumour/ infection -> accumulation CSF

Most common newborns with spina bifida

Readily treated by shunt

Question 18

Describe the early organisation of the neural tube

Answer 18

Inside out: 
Neuroepithelial layer (cells that produce CSF) 

Intermediate mantle layer with neuroblasts

Marginal layer with processes

Roof and floor plates

Alar and basal plates

Sulcus limitans (boundary of dorsal and ventral halves)

Question 19

What is the function of the roof and floor plates?

Answer 19

Determine what different ion happens to the dorsal and ventral halves of tube

Question 20

What is the function of the alar and basal plates?

Answer 20

Alar - sensory (superior)

Basal - motor (inferior)

Question 21

What are neural crest cells, where do they migrate to, what do they become?

Answer 21

Cells of lateral border of neuroectoderm tube become displaced and enter mesoderm - Epithelial -> mesenchymal transition

As neural tube folds neural crest cells leave and spread throughout body ->

Peripheral ganglia (dorsal root G/ sympathetic G), chromatic cells of adrenal medulla, Skelton of face, melanocytes, Schwann cells, dermis, conotruncal septum of heart etc.

Question 22

Why are neural crest cells so vulnerable to environment insult especially alcohol?

Answer 22

Migrate extensively and contribute to wide range of structures - complex migratory pattern

Defects can affect single component or multiple resulting in syndromes

Question 23

Give an example of a neural crest defect affect one and then multiple structures

Answer 23

Defects in migration or morphogenesis

One structure - Hirschsprung’s disease (aganglionic megacolon)

Multiple structures - DiGeorge syndrome (thyroid deficiency, immunodeficiency secondary thymus defect, cardiac defects, abnormal facial structures)