Embryology and Congenital Malformations Flashcards
Nervous system develpos form the embryonic __________
ectoderm
CNS appears at the beginning of the _____ week
3rd
Thickening of ectoderm anterior to the primitive node leads to the formation of what?
neural plate
edges of the neural plate thicken and move upwards to form what?
neural folds
Neural folds migrate towards each other and fuse at midline forming the _________
neural tube
Where does the neural tube originally remain open at?
anterior and posterior ends
When do the anterior and posterior ends close?
Anterior (cranial/rostral) neuropore closes 18 – 20 somite stage (~25 days)
Posterior (caudal) neuropore closes ~ day 27
(neuropore - either of the openings to the exterior at the anterior and posterior ends of the neural tube of a vertebrate embryo)
The neural plate goes on to form what?
neural tube
What is closure of the neural tube essential for?
normal development and function
What is the process of the neural tube closing?
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)
Up to 5 closure sites in humans
Failure of neural tube to close properly results in neural tube defects (NTDs), what are some examples?
- Anencephaly
- Encephalocoele
- Spina bifida
What is Anencephaly?
Failure of anterior neuropore to close
Skull fails to form
Brain tissue degenerates
Incompatible with life
How common is Anencephaly?
1:1500 births (~4x more common in females)
What is Craniorachischisis?
failure of neural tube closure along entire neuroaxis
What is Encephalocoele?
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
How common is Encephalocoele?
1:4000 births
What is Spina Bifida?
Defective closure of the caudal neural tube
Affects tissues overlying the spinal cord
Spina bifida = non-fusion of vertebral arches
Neural tissue may or may not be affected
Severity ranges from minor abnormalities to major clinical symptoms
What is spina bifida occulta?
Most minor form of spina bifida
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
What is spina bifida cystica?
Protrusion of spinal cord and/or meninges through the defect in the vertebral arches
1:1000 live births
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 (a condition in which excess cerebrospinal fluid (CSF) builds up within the ventricles)
Most severe form is myeloschisis. Spinal cord in affected area open due to failure of neural folds to fuse
How are neural tube defects prevented?
Folic acid supplements (400 µg/day - 50-70% decrease in risk)
How is a prenatal diagnosis made of neural tube defects?
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 are the risk factors for neural tube defects?
Genetic predisposition
Nutritional (e.g. too little folate, too much vitamin A)
Environmental (e.g. hyperthermia; taking certain drugs - e.g. sodium valproate)
What is A?
Prosencephalon
What is B?
Mesencephalon
What is C?
Rhombencephalon
A?
Telencephalon
B?
Diencephalon
C?
Metencephalon
D?
Myelencephalon
How many primary and how many secondary brain vesicles are there?
3 primary and 5 secondary
What are the 3 flextures seen in the developing embryo, when do they develop and where are they?
Cephalic flexure - End of 3rd week. Between midbrain (mesencephalon) and hindbrain (rhombencephalon)
Cervical flexure - End of 4th week. Between hindbrain and spinal cord
Pontine flexure - 5th week. In hindbrain (between metencephalon and myelencephalon)
A?
Prosencephalon
B?
Diencephalon
C?
telencephalon
D?
Mesencephalon
E?
Rhombencephalon
F?
metencephalon
G?
myelencephalon
What does the telencephalon form
cerebral hemispheres, hippocampus, basal ganglia
What does the Diencephalon form?
thalamus, hypothalamus, pituitary gland, pineal
What does the Mesencephalon form?
superior and inferior colliculi
What does the metencephalon form?
cerebellum, pons
What does the myelencephalon form?
medulla
The lumen of the neural tube forms the ventricular system, what does the Telencephalon form
lateral ventricles
The lumen of the neural tube forms the ventricular system, what does the Diencephalon form
3rd ventricle
The lumen of the neural tube forms the ventricular system, what does the Mesencephalon form
cerebral aqueduct
The lumen of the neural tube forms the ventricular system, what does the Metencephalon and Myelencephalon form
4th ventricle
When is CSF formed, what is it made by, and where does it drain?
Begins to form 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
What is an accumulation of cerebral spinal fluid called?
Hydrocephalus
What does hydrocephalus, reason for it happening and its causes
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
Causes: genetic, prenatal viral infection or intraventricular haemorrhage, spina bifida cystica
Cellular differentiation happens in the neural tube, itially what is formed?
Initially a single layer of rapidly dividing neuroepithelial cells
Pseudostratified epithelium
Divide at ventricular surface
What produces most cells of the CNS?
neuroepithelium
What cells do neuroepithelial cells make?
Microglia are the exception as they are not made by the neuroepithelium, what makes microglia?
What are neural crest cells?
Cells of PNS, Autonomic nervous system (neurons and glia)
Non-neuronal cells: e.g. melanocytes, adrenal medulla, meninges, facial bones/cartilage
Located at the dorsal tip of the neural tube and migrate off the neural tube and give rise to a whole host of structures in the embryo
What are some neural crest 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
Neural crest forms ___ neurons and ____
Neural crest forms PNS neurons and glia
The dorsal root ganglia (DRG; spinal ganglia) – sensory component, is formed form what?
neural crest
The motor component - motor neurons of spinal cord is formed by what?
the neural tube
What do the elongated spinal nerves form?
cauda equina
What does the piat mater form at the end of the spinal cord?
terminal filum
Surface of cerebral hemispheres is initially ______ then you develop ______ (grooves) and ____ (elevations)
smooth
sulci
gyri
What is the reason for the sulci and gyri developing?
space saving - minimises brain volume
Brings together brain regions that would otherwise be far apart – optimises brain wiring and functional organisation
What is Lissencephaly?
also known as “smooth brain”
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
What is Polymicrogyria?
Excessive number of small gyri
Variable degree of neurological problems (e.g. mental retardation, seizures, motor deficits etc)
Other congenital abnormalities (all very rare):
What is Microcephaly?
Genetic, drugs, infection (e.g. Zika virus)
Intellectual impairment, delayed motor functions/speech, hyperactivity, seizures, balance/co-ordination problems etc
smaller head than normal
Other congenital abnormalities (all very rare):
What is Aegenesis corpus callosum?
a complete or partial absence of the corpus callosum
Alone or with other cerebral abnormalities
Effects range from subtle – severe
Cognitive and social difficulties - intellectual impairment, seizures, hypotonia etc
Other congenital abnormalities (all very rare):
What is Porencephaly?
Other congenital abnormalities (all very rare):
What is Schizencephaly?
characterized by abnormal slits or clefts in the cerebral hemispheres of the brain
What is diastematomyelia (split cord malformation)?
a congenital disorder in which a part of the spinal cord is split (sagittal), usually at the level of the upper lumbar vertebra
Spinal cord split longitudinally into 2 parts
Usually associated with vertebral anomalies
Bony or cartilaginous process “fixes” cord in place
Scoliosis, weakness of lower extremities, hairy patch over lower back, foot deformities, loss of sensation
What are causes of intellectual impairment?
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)
Common cause – maternal alcohol abuse
in intellectual impairment there is often ________ gross brain defects
no obvious
Development of the nervous system begins in week _
3
Neural tube develops from ______________
embryonic ectoderm
Neural tube closed by end of _th week. Defects in closure result in ____ (e.g. spina bifida
4th
NTDs
Neural tube forms _______ and ____ of CNS
neurons and glia of CNS
•Neural crest cells form neurons and glia of _____ (plus non-neuronal cells)
PNS
Expansion and bending of neural tube forms _ primary and _ secondary brain vesicles.
3
5
Lumen of neural tube forms ____________
ventricular system
