Overview of CNS Embryo

Question 1

When does brain development begin?

Answer 1

Brain development begins in the 3rd week of gestation with the formation of the neural tube and crest cells.

•The embryo has 3 layers: the endoderm that forms the internal organs, the mesoderm that forms the muscles and skeleton, and the ectoderm that forms the skin and nervous system. Think of the brain as just fancy skin.

Question 2

Question 3

• The left upper figure presents fetal development at approximately 4 weeks with the 3 vesicle brain and it’s location within the fetus. The right upper figure shows the brain’s further progression to a 5 vesicle brain at 5 weeks gestation.
• By five weeks the telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon are identifiable; these structures have corollaries in the adult brain as shown in the lower figure.

Question 4

This slide demonstrates the remarkable speed of fetal growth. The smaller yellow rhomboid box shows fetal development in the first month and the large orange irregular shaped figure shows fetal growth at the end of the second month.

Answer 4

During this period, CNS development proceeds rapidly with approximately 250,000 future CNS cells being produced per minute.

Question 5

In week 3, the _____ forms.

Answer 5

Neural plate

Question 6

In week 4, the _____ has formed and the anterior and posterior pores close at 25 and 27 days respectively.

Answer 6

Neural tube

The 3 primary brain vesicles have also appeared constituting the Prosencephalon, Mesencephalon and Rhombencephalon.

Question 7

In week 5, the 3 vesicles become what 5 primary brain vesicles?

Answer 7

Telencephalon, Diencephalon, Mesencephalon, Metencephalon and Myelencephalon as shown on the previous slide.

In week 8, the cerebral hemispheres are enlarged.

Question 8

What is histogenesis?

Answer 8

The differentiation of cells into specialized types in the central nervous system.

Question 9

The lower figure is the neural tube. A slice of the neural tube is blown up and shown above. The ventricular zone neuroepithelial cells differentiate into what?

Answer 9

neuroblasts and glioblasts.

Question 10

What do neuroblats form?

Answer 10

all of the neurons within the central nervous system.

Question 11

What do glioblasts form?

Answer 11

The glioblasts form radial glial cells, astrocytes, oligodendrocytes, ependymocytes, tanycytes, and choroid plexus cells.

Most other glial cells are formed after neuroblast formation is complete.

Question 12

How do microglia form?

Answer 12

Microglia arise from monocytes in the circulation and invade the CNS during the third week with the formation of cerebral blood vessels

Question 13

Most radial glial cells are formed before neuroblasts differentiate into neurons. What do they do?

Answer 13

• Radial glial cells (blue) serve as guide wires for the migration of neurons (red). Migrating neurons attach to and travel along the radial glial cells to their final destination.

Question 14

This slide presents slices through the embryo neural tube, shown on the left and labelled A, and the adult spinal cord shown on the right and labelled B.

Follow the migration of sensory neurons, shown in blue, and the motor neurons, shown in red, from the neural tube into the adult spinal cord.

Question 15

The alar plate of the embryo neural tube is separated from the basal plate by the what?

Answer 15

the sulcus limitans.

Question 16

What does the sulcus limitans do in the adult brain?

Answer 16

Remains a useful anatomical marker in the adult brain where it separates the sensory brain stem nuclei from the motor brain stem nuclei.

Question 17

Neurogenesis in the alar plate forms what?

Answer 17

the sensory neurons and nuclei of the spinal cord and the brain stem. The dorsal root ganglia neurons are also derived from the alar plate via the neural crest formation.

Question 18

Neurogenesis in the basal plate forms what?

Answer 18

the motor neurons and nuclei of the spinal cord and also the brain stem

Question 19

This slide presents the neural tube labelled A on the left and two slices through the adult brainstem labelled B and C. Note that the sulcus limitans, present in both the neural tube and the adult brainstem, separates the brain stem sensory neurons from the motor neurons.

Question 20

Here you can see the formation of the neural crest from the fusion of the neural tube followed by its separation from the neural tube. Neural crest cells produce the dorsal root ganglia and various autonomic and enteric ganglia

Question 21

The spinal column and spinal cord grow at different rates. Which grows faster?

Answer 21

The spinal column elongates faster than the spinal cord so that there is a rostral migration of the conus medullaris, that is the end of the spinal cord, during fetal development and after birth until the adult position of the conus medullaris is reached at L1-2

Question 22

Stages of spinal cord growth in embryo

Answer 22

In the 3 month fetus the conus medullaris terminates at the end of the spinal column

In the 6 month fetus the spinal column begins to outgrow the cord and the conus ends at vertebrae S1

In the 9 month fetus the spinal cord ends at vertebrae L3

Question 23

In the adult the spinal cord ends where?

Answer 23

L1-2

Question 24

What is the filum terminale?

Answer 24

A strand of fibrous tissue originating from pia mater, about 20 cm long in the adult, that connects the conus medullaris to the coccygeal ligament.

Question 25

What happens if the connection between the conus medullaris and the coccygeal ligament is too tight?

Answer 25

the normally loose spinal cord is stretched during growth. The resulting damage produces a tethered spinal cord syndrome.

Question 26

How does tethered spinal cord syndrome present?

Answer 26

Children present with back pain, leg pain, leg weakness, scoliosis and loss of bowel and bladder control.

Question 27

Congenital Malformations/Neural Tube Related Birth Defects to be aware of:

Answer 27

• Anencephaly
• Encephaloceles
• Spinal Dysraphism (Spina Bifida)
• Meningoceles
• Myelomeningoceles
• Arnold-Chiari Malformations

Question 28

This slide shows the neural tube at 3 weeks with the anterior and posterior pores still open. Failure to properly close the anterior pore may cause what?

Answer 28

anencephaly and/or an encephalocele.

Question 29

Failure to properly close the posterior pore may cause what?

Answer 29

spina bifida, a spinal meningocele, or a spinal myelomeningocele.

Question 30

Neural tube closure defects are closely associated with what?

Answer 30

folic acid deficiency in the mother.

Folic acid supplements taken early in pregnancy, especially during the first few weeks of gestation significantly reduce the incidence of neural tube closure defects.

Question 31

How can neural tube defects be tested for?

Answer 31

Failure of neural tube closure allows alpha-fetal protein to leak out into the amniotic fluid and into the blood stream of the mother. Testing for elevated alpha-fetal protein levels in mother’s blood or via amniocentesis can reveal neural tube defects.

Question 32

What is this?

Answer 32

an encephalocele.

Question 33

What is the difference between spina bifida occulta, abbreviated SBO on the left and spina bifida aperta, abbreviated SBA on the right?

Answer 33

The difference between the two is a matter of degree and of associated neurologic symptoms.

SBO involves failure of mesodermal cells to form the bony dorsal vertebrae that surrounds the spinal cord. Such individuals rarely develop neurologic symptoms. The meninges and spinal cord/filum terminale are not involved in the SBO defect. SBO may be clinically evident by a tuft of hair over the lumbar-sacral area or a sinus tract in the region as shown below.

In SBA with meningocele, the meninges extend into the outpouching and in myelomeningocele the spinal cord/filum terminale and the meninges extend into the outpouching as shown on the lower right. SBA commonly causes neurologic symptoms which may be severe.

Note: spina bifida occulta and aperta may develop at other levels of the spinal column; the drawings shown here are only of the lumbar-sacral column.

Question 34

This is a photograph of a baby with spina bifida aperta with a myelomeningocele.

Question 35

What is an Arnold Chiari Malfornation?

Answer 35

Displacement of the cerebellar tonsils below the foramen magnum that is very common and can obstruct the foramen magnum and cause hydrocephalus as CSF flow is blocked (can cause lower brain herniation). CSF backup then has be offset by increasing the MAP, causing HTN

NOTE: In recent years, the term Arnold Chiari has been replaced with the simpler Chiari and we will adopt that convention.

Question 36

In the drawing on the left, the arrow indicates the tonsillar herniation below the foramen magnum.

The MRI on the right presents a real life Chiari Malformation. The drawing and MRI show a severe Chiari Type I malformation.

Question 37

How does a Chiari malformation present?

Answer 37

The outflow of cerebral spinal fluid into the spinal canal may become obstructed to raise intracranial pressure and produce headache. More often, the tonsilar herniation is mild and asymptomatic.

Question 38

What is a Chiari Type II Malformation?

Answer 38

has the herniated cerebellar tonsils plus an associated cervical or occipital encephalocele.

Question 39

Blood flow needs to decrease 50% before neural tissue is impacted