Embryology of congenital malformations

Question 1

what are the three germ layers of the epiblast embryologically

Answer 1

ectoderm
mesoderm
endoderm

Question 2

what do each of the three germ layers go on to form

Answer 2

ectoderm

• epidermis
• nervous system

mesoderm

• bone
• muscle
• blood cells, etc

endoderm

• gut
• pharynx
• lungs

Question 3

when does the CNS start to appear embryonically and what occurs at this time

Answer 3

beginning of the third week

Question 4

how does the neural tube develop

Answer 4

thickening of the ectoderm anterior to primitive node = NEURAL PLATE

edges thicken and move up to form NEURAL FOLDS

neural folds migrate towards each other and fuse at midline = NEURAL TUBE

Question 5

when do the anterior and posterior ends of the neural tube close

Answer 5

anterior (cranial/rostral) neuropore - 25 days

posterior (caudal) neuropore - 27 days

Question 6

what does failure of the neural tube to close properly cause

Answer 6

neural tube defects

Question 7

give 3 examples of neural tube defects

Answer 7

anencephaly
encephalocoele
spina bifida

Question 8

what causes anencephaly

Answer 8

failure of the anterior neuropore to close

Question 9

what are the consequences of anencephaly

Answer 9

skull fails to form
brain tissue degenerates
incompatible with life

Question 10

what causes encephalocoele

Answer 10

failure of the rostral neural tube to close

Question 11

what are the consequences of encephalocoele

Answer 11

herniation of cerebral tissue through a defect in the skull

most frequent in the occipital region

causes variable degrees of neurological deficits

Question 12

what causes spina bifida

Answer 12

defective closure of the caudal neural tube

Question 13

what are the consequences of spina bifida

Answer 13

affects the tissues overlying the spinal cord

causes non-fusion of the vertebral arches

neural tissue may or may not be affected

severity ranges from minor abnormalities to major clinical symptoms

Question 14

what is the most minor form of spina bifida

Answer 14

spina bifida occulta

Question 15

what occurs in spina bifida occulta

Answer 15

failure of embryonic halves of vertebral arch to grow and fuse

occurs in L5 and L6 vertebrae

usually no clinical symptoms

may result in dimple with small tuft of hair

Question 16

what is spina bifida cystica

Answer 16

protrusion of the spinal cord and or/meninges through the defeat in the vertebral arches

Question 17

what are the three types of spina bifida cystica

Answer 17

spina bifida with meningocele

spina bifida with meningomyelocele

myeloschisis

Question 18

what occurs in meningocele

Answer 18

protrusion of meninges and cerebrospinal fluid

Question 19

what occurs in meningomyelocle

Answer 19

nerve roots and/or spinal cord included in the protruding sac

neurological deficits - loss of sensation and muscle paralysis

Question 20

what determines the area affected in meningomyelocle

Answer 20

the level of the lesion

Question 21

what is meningomyelocle associated with

Answer 21

hydrocephalus

Question 22

what occurs in myeloschisis

Answer 22

most severe form

spinal cord in affected area open due to failure of neural folds to fuse

Question 23

what can decrease the risk of spina bifida during pregnancy

Answer 23

folic acid supplements

Question 24

what types of prenatal diagnosis techniques are used for neural tube disorders

Answer 24

maternal blood screening
- high a-fetoprotein (AFP) in serum - leaks from foetal liver

amniocentesis
- high levels AFP in amniotic fluid

ultrasound

• anencephaly from 12 weeks
• spina bifida from 16-20 weeks

Question 25

what are risk factors for neural tube disorders

Answer 25

genetic predisposition nutrition - too like folate, too much vit A environmental - hyperthermia drugs - sodium valproate

Question 26

when do the brain vesicles begin to form

Answer 26

begin with the closure of he anterior neuropore - 25 days

Question 27

when do the 3 primary and 5 secondary vesicles form

Answer 27

primary - week 4 secondary week 5

Question 28

name the 3 primary vesicles

Answer 28

prosencephalon mesencephalon rhombencephalon

Question 29

name the 5 secondary vesicles

Answer 29

``` telencephalon diencephalon mesencephalon metencephalon myelencephalon ```

Question 30

what are the three flexures (bends) of the embryological brain and when do they occur

Answer 30

cephalic - end week 3 cervical - end week 4 pontine - week 5

Question 31

where do the brain flexures occur

Answer 31

cephalic - between midbrain and hindbrain cervical - between hindbrain and spinal cord pontine - in hindbrain between metencephalon and myelencephalon

Question 32

what does the telencephalon go on to form

Answer 32

cerebral hemispheres, hippocampus, basal ganglia

Question 33

what does the diencephalon go on to form

Answer 33

thalamus, hypothalamus, pituitary gland, pineal

Question 34

what does the mesencephalon go on to form

Answer 34

midbrain, superior and inferior | colliculi

Question 35

what does the metencephalon go on to form

Answer 35

cerebellum, pons

Question 36

what does the myelencephalon go on to form

Answer 36

medulla

Question 37

what does the caudal neural tube go on to form

Answer 37

spinal cord

Question 38

what do the lumen of the neural tube go on to form

Answer 38

the ventricular system

Question 39

what parts of the neural tube lumen do the different ventricles form from

Answer 39

lateral - telencephalon interventricular foramen - telencephalon 3rd - diencephalon cerebral aqueduct - mesencephalon 4th - metencephalon, myelencephalon central canal - caudal end of neural tube

Question 40

when does CSF begin to form and where does it go

Answer 40

week 5 produced by choroid plexus drains into subarachnoid space absorbed into the venous system

Question 41

what is hydrocephalus

Answer 41

accumulation of cerebral spinal fluid results in an enlarged brain and cranium

Question 42

what is the pathology of hydrocephalus

Answer 42

frequently due to blocked cerebral aqueduct prevents CSF from lateral and 3rd passing into 4th can't drain properly

Question 43

what are the causes of hydrocephalus

Answer 43

genetic prenatal viral infection prenatal intraventricular haemorrhage spina bifida cystica

Question 44

what occurs during cellular differentiation in the neural tube and when does it occur

Answer 44

neuronal cells made - neurons and glia cells connected together starts in embryogenesis and continues postnatal

Question 45

what occurs at the cells of the neural tube

Answer 45

begin as a single layer of rapidly dividing neuroepithelial cells pseudo stratified epithelium divide at ventricular surface

Question 46

what CNS cells do neuroepithelial cells produce

Answer 46

neruons astrocytes oligodendrocytes become ependymal cells once cell division finished

Question 47

what CNS cells are not produced by the neuroepithelial cells

Answer 47

microglia = mesenchymal cells that migrate to the CNS

Question 48

what do neural crest cells form

Answer 48

the cells of the PNS, autonomic nervous system neurons and glia

Question 49

where does the sensory component of the nervous system grow from

Answer 49

grows from the neural crest extend two processes - peripheral - body - central - dorsal horn of spinal cord

Question 50

where does the motor component of the nervous system grow from

Answer 50

grows from the neural tube motor neruons

Question 51

how does the spinal cord position change throughout development

Answer 51

S1 at 3 months - extends entire length of vertebral column L2/3 in newborns L1 in adults

Question 52

what do the elongated spinal nerves from below the end of the spinal cord form

Answer 52

the caudal equina

Question 53

why does the position of the spinal cord change during development

Answer 53

the vertebral column and dura mater grow more rapidly than the spinal cord

Question 54

what forms the terminal filum

Answer 54

pia mater

Question 55

what forms the sympathetic and parasympathic ganglia and where do they end up

Answer 55

neural crest cells sympathetic - chains along spinal cord parasympathetic - near or within the nerves they innervate

Question 56

what is the surface of the cerebral hemispheres initially like

Answer 56

initially smooth

Question 57

what does rapid growth of the cerebral hemispheres result in

Answer 57

formation of sulk and gyro pattern becomes more complex as the brain enlarges

Question 58

what is lissencephaly

Answer 58

"smooth brain" rare brain disorder gyri and sulci fail to develop

Question 59

what causes lissencephaly

Answer 59

caused by defective neuronal migration

Question 60

what does lissencephaly result in

Answer 60

severe mental impairment failure to thrive seizures abnormal muscle tone many affected children die before 10

Question 61

what is polymicrogyria and what can it cause

Answer 61

excessive number of small gyri variable degree of neurological problems (e.g. mental retardation, seizures, motor defects, etc)

Question 62

what are some other congenital abnormalities

Answer 62

microcephaly - abnormally small head aegenesi corpus callosum - complete/partial absence of the corpus callosum porencephaly - CSF filed cysts and cavities in cerebrum schizencephaly - large clefts or slits in cerebrum diastematomyelia - split cord malformation

Question 63

what can cause microcephaly and what are the impairments

Answer 63

genetic, drugs, infection (e.g. pika virus) Intellectual impairment, delayed motor functions/speech, hyperactivity, seizures, balance/co-ordination problems

Question 64

what can cause porencephaly and what are the impairments

Answer 64

postnatal stroke or infection Delayed growth and development, seizures, hypotonia, intellectual impairment

Question 65

what can cause schizencephaly and what are the impairments

Answer 65

genetic, in utero stroke, infection paralysis, seizures, intellectual impairment, developmental delay

Question 66

what is diastematomyelia and what are the impairments

Answer 66

spinal cord splits longitudinally into two parts - usually associated with vertebral anomalies Scoliosis, weakness of lower extremities, hairy patch over lower back, foot deformities, loss of sensation

Question 67

what can cause intellectual impairment

Answer 67

often no gross brain defects - genetic - downs syndrome - radiation - infection agents - rubella, toxoplasmosis, CMV - birth trauma - postnatal insults - head injury, infection (meningitis) maternal alcohol abuse - foetal alcohol syndrome