Embryology and Congenital Malformations

Question 1

what germ layer does the nervous system develop from?

Answer 1

Ectoderm-outer layer

Question 2

wen does the CNS appear?

Answer 2

beginning of the 3rd week

Question 3

what is the neural plate?

Answer 3

Thickening of ectoderm anterior to the primitive node

Question 4

what are neural folds?

Answer 4

Edges thicken and move upwards to form neural folds

Question 5

what is the neural tube?

Answer 5

Neural folds migrate towards each other and fuse at midline forming neural tube

Question 6

which ends of the neural tube initially remain open?

Answer 6

anterior and posterior ends

Question 7

when does the Anterior (cranial/rostral) neuropore close?

Answer 7

~25 days

Question 8

when does the Posterior (caudal) neuropore close?

Answer 8

~27 days

Question 9

describe the closure of the neural tube

Answer 9

Initiated at several points along A-P axis.
Proceeds in cranial and caudal directions.
Begins day 18
Completed by end of 4th week (~day 27).

Question 10

name some neural tube defects

Answer 10

Anencephaly
Encephalocoele
Spina bifida

Question 11

what is Anencephaly?

Answer 11

1:1500 births (~4x more common in females)
Failure of anterior neuropore to close.
Skull fails to form
Brain tissue degenerates.
Incompatible with life.

Question 12

what is Craniorachischisis?

Answer 12

failure of anterior neuropore and rostral neural tube to close

Question 13

what is Encephalocoele?

Answer 13

1:4000 births
Herniation of cerebral tissue through a defect in the skull.
Failure in closure of rostral neural tube.
Most frequent in occipital region.
Variable degree of neurological deficits.

Question 14

what is Spina Bifida?

Answer 14

Defective closure of the caudal neural tube.
Affects tissues overlying the spinal cord.
non-fusion of vertebral arches.
Neural tissue may or may not be affected.
Severity ranges from minor abnormalities to major clinical symptoms.

Question 15

what is Spina bifida occulta?

Answer 15

Most minor form.
Failure of embryonic halves of vertebral arch to grow normally and fuse.
Occurs in L5 and L6 vertebrae of 10% of otherwise healthy people.
Usually no clinical symptoms.
May result in dimple with small tuft of hair.

Question 16

what is Spina bifida cystica?

Answer 16

Protrusion of spinal cord and/or meninges through the defect in the vertebral arches.
1:1000 live births

Question 17

what is Spina bifida with meningocele

Answer 17

Rarest form
Protrusion of meninges and cerebrospinal fluid
easily removed with surgery

Question 18

what is Spina bifida with meningomyelocle?

Answer 18

Nerve roots and/or spinal cord included in the sac
Neurological deficits – loss of sensation and muscle paralysis
Area affected determined by level of lesion
Often associated with hydrocephalus

Question 19

what is Spina bifida with

myeloschisis

Answer 19

Most severe form
Spinal cord in affected area open due to failure of neural folds to fuse.
leads to degeneration of spinal cord

Question 20

what can prevent neural tube defects?

Answer 20

Folic acid supplements

50-70% decrease in risk

Question 21

describe the prenatal diagnosis of neural tube defects?

Answer 21

Maternal blood screening
Indicated by high levels α-fetoprotein (AFP) in maternal serum
Best detected 16 - 20 weeks Amniocentisis- high levels AFP in amniotic fluid
Ultrasound
(Anencephaly from 12 weeks, spina bifida from 16-20 weeks)

Question 22

what are the risk factors of neural tube defects?

Answer 22

Genetic predisposition
Nutritional (e.g. too little folate, too much vitamin A)
Environmental (e.g. hyperthermia; taking certain drugs – e.g. sodium valproate)

Question 23

when do the brain vesicles start to develop?

Answer 23

~25 days

Question 24

when and where does Cephalic flexure occur?

Answer 24

End of 3rd week.
Between midbrain (mesencephalon) and hindbrain (rhombencephalon).

Question 25

when and where does Cervical flexure occur?

Answer 25

End of 4th week. Between hindbrain and spinal cord.

Question 26

when and where does Pontine flexure occur?

Answer 26

5th week In hindbrain (between metencephalon and myelencephalon).

Question 27

when and how does the CSF begin to form?

Answer 27

during 5th week
Produced predominately by choroid plexus (in 3rd, 4th, lateral ventricles)
Drains into subarachnoid space via openings in roof of 4th ventricle
Absorbed into venous system

Question 28

what is Hydrocephalus?

Answer 28

Accumulation of cerebral spinal fluid
Results in enlarged brain and cranium
Frequently due to blocked aqueduct
Prevents CSF from lateral and 3rd ventricles passing into the 4th ventricle  can’t drain properly

Question 29

what is the initial cell layer of the neural tube?

Answer 29

neuroepithelial cells.

Pseudostratified epithelium.

Question 30

Neuroepithelium produces all cells of the CNS except?

Answer 30

microglia – mesenchymal cells migrate into CNS

Question 31

what forms the neurons and glia of CNS?

Answer 31

Neural tube

Question 32

what forms the neurons and glia of PNS (plus non-neuronal cells)?

Answer 32

Neural crest

Question 33

what forms the body and dorsal horn of the spinal cord?

Answer 33

Neural crest

Question 34

what forms the motor neurones of the spinal cord?

Answer 34

Neural tube

Question 35

what are the Positional changes of the spinal cord.?

Answer 35

3rd month – extends entire length of vertebral column.

Vertebral column and dura mater grow more rapidly  cord at progressively higher levels (newborn, ~L2 or L3; adult ~L1).

Question 36

what forms the Sympathetic and parasympathetic ganglia ?

Answer 36

Neural crest

Question 37

when are the sulk and gyro fully formed in development?

Answer 37

38 weeks

Question 38

what is Lissencephaly?

Answer 38

Rare brain disorder
Caused by defective neuronal migration.
Gyri and sulci fail to develop
Results in severe mental impairment, failure to thrive, seizures, and abnormal muscle tone.
Many affected children die before age 10.

Question 39

what is Polymicrogyria?

Answer 39

Excessive number of small gyri.

Variable degree of neurological problems (e.g. mental retardation, seizures, motor deficits etc)