Embryology Congenital malformations Flashcards
what does the nervous system develop from?
embryonic ectoderm
when does the CNS first appear?
beginning of week 3
label the stages of gastrulation?
label the different germ layers?
what is contained within the ectoderm?
epidermis and nervous system
what is contained within the mesdoderm?
bone, muscle, blood cells etc
what is contained within the endoderm?
gut, pharynx, lungs
label the CNS at 18 and 20 days?
what forms the neural plate?
Thickening of ectoderm anterior to the primitive node
what forms the neural folds?
Edges thicken and move upwards
What are the steps of neuralisation?
Neural plate forms from thickening of the ectoderm anterior to the primitive node
Neural folds form from the edges thickening and moving upwards
Neural folds migrate towards each other and fuse at midline forming neural tube, which remains open at anterior and posterior ends
Neural tube closure
what forms the neural tube?
Neural folds migrate towards each other and fuse at midline
where does the neural tube initially remain open?
anterior and posterior ends
when does Anterior (cranial/rostral) neuropore close?
closes 18 – 20 somite stage (~25 days)
when does posterior (caudal) neuropore close?
day 27
label the neural tube at day 22/23?
what does this image show? 1
neural plate
second arrow - ectoderm
what does this image show? 2
neural folds
neural groove
ectoderm
what does this image show? 3
further folding of neural folds
ectoderm
what does this image show?
neural tube
ectoderm
Describe the process of neural tube closure?
Initiated at several points along A-P axis
Proceeds in cranial and caudal directions
Begins on day 18 and is completed by end of 4th week (about day 27)
What does failure of the neural tube to close correctly lead to?
Failure to close properly leads to neural tube defects (NTDs):
Anencephaly
Encephalocoele
Spina bifida
The are some of the most common congenital abnormalities of the CNS
How many closure sites of the neural tube are there in humans?
Up to 5
Describe the epidemiology of exencephaly/ancenephaly?
(incidence, sex)
1:1500 births (4x more common in females)
Describe the pathology of exencephaly/anencephaly?
Failure of anterior neuropore to close
Skull fails to form
Describe the prognosis of exencephaly/anencephaly?
Brain tissue degenerates, is incompatible with life
What is craniorachischisis?
Craniorachischisis = failure of neural tube closure along entire neuroaxis
Describe the epidemiology of encephalocoele?
(incidence)
1:4000 births
Describe the pathology of encephalocoele?
Herniation of cerebral tissue through a defect in the skull
Failure in closure of rostral neural tube
Most frequently in occipital region
Describe the prognosis of encephalocoele?
Variable degree of neurological deficits
Describe the pathology of spina bifida?
Defective closure of the caudal neural tube
Affects tissues overlying the spinal cord
Neural tissue may or may not be affected
What is spinda bifida?
Spina bifida = non-fusion of vertebral arches
Describe the prognosis of spina bifida?
Severity ranges from minor abnormalities to major clinical symptoms
What are the different kinds of spina bifida?
Spina bifida occulta
Most minor form
Failure of embryonic halves of vertebral arch to grow normally and fuse
Occurs in L5 and L6 vertebrae
Usually no clinical symptom
May result in dimple with small tuft of hair
Spina bifida cystica
Protrusion of spinal cord and/or meninges through the defects in vertebral arches
1:1000 births
Different kinds
Spina bifida with meningocele
Rarest form
Protrusion of meninges and CSF
Spina bifida with meningomyelocle
Nerve roots and/or spinal cord included in the sac
Neurological deficits such as loss of sensation and muscle paralysis
Area affected determined by level of lesion
Often associated with hydrocephalus
Myeloschisis
Most severe form
Spinal cord in affected area open due to failure of neural folds to fuse
Spina bififa occulta - pathology
Most minor form
Failure of embryonic halves of vertebral arch to grow normally and fuse
Occurs in L5 and L6 vertebrae
Spina bifida occulta - presentation
Usually no clinical symptom
May result in dimple with small tuft of hair
Spina bifida cystica - pathology
Protrusion of spinal cord and/or meninges through the defects in vertebral arches
Spina bifida cystica - epidemiology (incidence)
1:1000 births
Spina bifida cystica - different kinds
Spina bifida with meningocele
Rarest form
Protrusion of meninges and CSF#
Spina bifida with meningomyelocle
Nerve roots and/or spinal cord included in the sac
Neurological deficits such as loss of sensation and muscle paralysis
Area affected determined by level of lesion
Often associated with hydrocephalus
Myeloschisis
Most severe form
Spinal cord in affected area open due to failure of neural folds to fuse
what is spina bifida with meningocele?
Rarest form
Protrusion of meninges and cerebrospinal fluid
what is spina bifida with meningomyelocle?
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
what is myeloschisis?
Most severe form myeloschisis
Spinal cord in affected area open due to failure of neural folds to fuse.
Is incidence of neurological congenital malformations increasing or decreasing? Why?
Incidence is decreasing in the UK due to:
Folic acid supplements (400ug/day)
Prenatal diagnosis
Maternal blood screening
Indicated by high levels of α-fetoprotein (AFP) in serum – AFP from foetal liver leaks into amniotic fluid then into maternal blood.
Best detected 16-20 weeks
Amniocentesis
High levels of AFP in amniotic fluid
Ultrasound
Anencephaly from 12 weeks, spina bifida from 16-20 weeks
what are different types of prenatal diagnosis?
Maternal blood screening
Indicated by high levels α-fetoprotein (AFP) in serum – AFP from foetal liver leaks into amniotic fluid then into maternal blood.
Best detected 16 - 20 weeks.
- Amniocentesis (high levels AFP in amniotic fluid) - Ultrasound (Anencephaly from 12 weeks, spina bifida from 16-20 weeks)
what does maternal blood screening test for?
Indicated by high levels α-fetoprotein (AFP) in serum – AFP from foetal liver leaks into amniotic fluid then into maternal blood.
Best detected 16 - 20 weeks.
what does amniocentesis test for?
(high levels AFP in amniotic fluid)
what does ultrasound test for?
(Anencephaly from 12 weeks, spina bifida from 16-20 weeks)
What are risk factors for neurological congenital malformations?
Genetic predisposition
Nutritional (such as too little folate, too much vitamin A)
Environmental (such as hyperthermia, taking certain drugs)
what are risk factors for spina bifida?
Genetic predisposition
Nutritional (e.g. too little folate, too much vitamin A)
Environmental (e.g. hyperthermia; taking certain drugs – e.g. sodium valproate)
What does development of brain vesicles begin with?
Begins with closure of anterior neuropore (about day 25, 18-20 somite stage)
label parts of the brain and spinal cord at 22 days?
label the 3 primary brain vesicles in week 4?
label the 5 secondary brain vesciles?
What bends in the neural tube occur?
Cephalic flexure
End of 3rd week
Between midbrain (mesencephalon) and hindbrain (rhomboencephalon)
Cervical flexure
End of 4th week
Between hindbrain and spinal cord
Pontine flexure
5th week
In hindbrain (between metencephalon and myelencephalon)
when does the cephalic flexure develop?
End of 3rd week.
Between midbrain (mesencephalon) and hindbrain (rhombencephalon).
when does the cervical flexure develop?
End of 4th week.
Between hindbrain and spinal cord.
when does the pontine flexure develop?
5th week.
In hindbrain
(between metencephalon and myelencephalon).
Where do the following bends occur:
cephalic flexure
cervical flexure
pontine flexure
Cephalic flexure
Between midbrain (mesencephalon) and hindbrain (rhomboencephalon)
Cervical flexure
Between hindbrain and spinal cord
Pontine flexure
Between metencephalon and myelencephalon)
What forms the ventricular system?
Lumen of neural tube
What are the 3 primary brain vesicles?
Prosencephalon (forebrain)
Mesencephalon (midbrain)
Rhombencephalon (hindbrain)
What is the forebrain formed from?
Prosencephalon
What is the midbrain formed from?
Mesencephalon
What is the hindbrain formed from?
Rhomboencephalon
What are the 5 secondary brain vesicles?
Telencephalon
Diencephalon
Mesencephalon
Metencephalon
Myelencephalon
What do the following develop from:
telencephalon
diencephalon
mesencephalon
metencephalon
myelencephalon
Prosencephalon
Telencephlon
Diencephalon
Mesencephalon remains the same, is a primary and secondary brain vesicle
Rhombencephalon
Metencephalon
Myelencephalon
What do the following develop from:
lateral ventricle
III ventricle
Cerebral aqueduct
IV ventricle
Lateral ventricle
Telencephalon
III ventricle
Telencephalon/diencephalon
Cerebral aqueduct
Mesencephalon
IV ventricle
Metencephalon/myelencephalon
what structures are formed from telencephalon?
proscenceophalon(forebrain)
what structures are formed from diencephalon?
proscenceophalon(forebrain)
what structures are formed from mesencephalon?
proscenceophalon(forebrain)
what structures are formed from metencephalon?
rhombencephalon (hindbrain)
what structures are formed from myelencephalon?
rhombencephalon (hindbrain)
what is the process of cortical folding?
Surface of cerebral hemispheres initially smooth.
Develop sulci (grooves) and gyri (elevations).
Pattern becomes more complex as development proceeds
what is the function of cortical folding?
Space saving – minimises brain volume
Brings together brain regions that would otherwise be far apart – optimises brain wiring and functional organisation
pathology of lissencephaly?
Rare brain disorder
Caused by defective neuronal migration.
Gyri and sulci fail to develop
who does lissencephaly affect most commonly?
Many affected children die before age 10.
what does lissencephaly result in?
Results in severe mental impairment, failure to thrive, seizures, and abnormal muscle tone.
what does polymicrogyria result in?
Excessive number of small gyri.
Variable degree of neurological problems (e.g. mental retardation, seizures, motor deficits etc)
When does CSF production begin?
Begins for form during 5th week
What is CSF originally produced and drained by?
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
What is an example of congenital malformation to do with CSF?
Hydrocephalus
Hydrocephalus - pathology
Accumulation of cerebrospinal fluid
Results in enlarged brain and cranium
Frequently due to blocked aquaduct
Prevents CSF from lateral and 3rd ventricles passing into the 4th ventricle, so cant drain properly
Hydrocephalus - aetiology
Frequently due to blocked aquaduct
Genetic
Prenatal viral infection or intraventricular haemorrhage
Spina bifida cystic
hydrocephalus aetiology?
Causes: genetic, prenatal viral infection or intraventricular haemorrhage, spina bifida cystica
When does cellular differentiation in the neural tube begin and end?
Need to make neuronal cells (glia and neurons) and connect cells together
Begins in early embryogenesis, continues into postnatal period
Some regions (such as olfactory epithelium) add new cells throughout life
What cells does the neuroepithelium produce?
Most cells of CNS
Exception is microglia, which is formed by mesenchmal cells that migrate to CNS
what is the cells are the the neural tube made from initially?
Initially a single layer of rapidly dividing neuroepithelial cells.
Pseudostratified epithelium.
Divide at ventricular surface.
What does microglia form from?
Formed by mesenchymal cells and migrates to CNS
What do neural crest cells go onto form?
Cells of PNS, autonomic nervous system (neurons and glia)
Also forms non-neuronal cells such as:
Melanocytes
Adrenal medulla
Meninges
Facial bones/cartilage
What are meninges formed from?
neural crest cells
What are examples of neural crest cell derivatives?
Sensory neurons
Autonomic neurons (sympathetic and parasympathetic ganglia)
Schwann cells + satellite cells of ganglia
Aortic plexuses (nerves surrounding the aorta)
Endocrine cells (chromaffin cells of adrenal medulla; calcitonin producing cells of carotid body; parafollicular cells of thyroid).
Enteric nervous system
Pigment cells (melanocytes) – all pigment except RPE
Leptomeninges of anterior brain (prosencephalon and part of mesencephalon)
Non-neural head structures (including bone, cartilage and connective tissue).
Teeth (dental papilla; odontoblasts)
Iris muscle and pigment; ciliary muscles
Corneal stroma
Inner ear development
Regions of the heart + walls of large arteries
What are PNS neurons formed from?
Migrating neural crest cells
What is glia formed from?
migrating neural crest cells
Decribe spinal nerve development?
Dorsal root ganglion (DRG, spinal ganglia) is a sensory component
Formed from neural crest
Extend two processes
Peripheral process forms body
Central process forms dorsal horn of spinal cord (via dorsal roots)
Motor component is motor neurons of spinal cord (formed from neural tube)
what are thoracic and lumbar crest cells form?
sympathetic ganglia
what do cervical and sacral crest cells form?
parasympathetic ganglia
label the cadaveric image?
What are the following formed from:
dorsal root ganglion
motor neuron of spinal cord
Dorsal route ganglion
Neural crest
Motor neuron of spinal cord
Neural tube
what are the positional changes of the spine in the third month?
extends entire length of vertebral column.
what does the spine look like at 6 months and at birth?
What positional changes occur in the spinal cord?
3rd month extends entire length of vertebral column
Vertebral column and dura mater grow more rapidly, cord at progressively higher levels (newborn is about L2 or L3, adult is about L1)
Initially spinal nerves found at level of origin
Become elongated forming cauda equina
Pia mater forms terminal filum (long fibrous thread)
What are some examples of neurological congenital abnormalities?
Lissencephaly
Polymicrogyria
Microecephaly
Aegenesis corpus collosum
Porencephaly
Schizencephaly
Diastermatomyelia
Intellectual impairment
microcephaly pathology?
Genetic, drugs, infection (e.g. Zika virus)
microcephaly effect?
Intellectual impairment, delayed motor functions/speech, hyperactivity, seizures, balance/co-ordination problems etc.
Aegenesis corpus callosum pathology?
Alone or with other cerebral abnormalities
Effects range from subtle – severe
Aegenesis corpus callosum effect?
Cognitive and social difficulties 🡺 intellectual impairment, seizures, hypotonia etc
porencephaly pathology?
Usually from postnatal stroke or infection
porencephaly effect?
Delayed growth and development, seizures, hypotonia, intellectual impairment
Schizencephaly pathology?
Genetic, in utero stroke, infection
schizencephaly effect?
Paralysis, seizures, intellectual impairment, developmental delay.
Diastematomyelia - pathology
Diastematomyelia (split cord malformation):
Spinal cord split longitudinally into 2 parts
Usually associated with vertebral anomalies
Bony or cartilaginous process “fixes” cord into place
Diastematomyelia - complications
Scoliosis, weakness of lower extremities, hairy patch over lower back, foot deformities, loss of sensation
Intellectual impairment - aetiology
genetic (e.g. Down’s syndrome)
Radiation
Infectious agents (e.g. rubella, toxoplasmosis, cytomegalovirus)
Birth trauma
postnatal insults (e.g. head injury, infections (e.g. meningitis), lead exposure)
what is the most common cause of intelectual impairment?
maternal alcohol abuse
Foetal alcohol syndrome 1:1000
Estimated up to 1:100 some degree of intellectual impairment
