Embryology and Congenital Malformations Flashcards
What does the nervous system develop from?
Embryonic ectoderm
When does the CNS begin to appear?
Beginning of the 3rd week
Neural plate
Thickening of ectoderm anterior to the primitive node
How do the neural folds form?
Edges of the neural plate thicken and move upwards to form the neural folds
How is the neural tube formed?
Neural folds migrate towards each other and fuse at the midline forming the neural tube
Where does the neural tube initially remain open?
Anterior and posterior ends
When does the anterior (cranial/rostral)neurpore close?
Closes 18-20 somite stage (~25 days)
When does the posterior (caudal) neuropore close?
~day 27
What is essential for normal development and function?
Closure of the neural tube
Where is neural tube closure initiated?
At several points along A-P axis
What direction does neural tube closure proceed in?
Cranial and caudal directions
When does neural tube closure begin?
Day 18
When is neural tube closure complete?
Completed by end of 4th week (~day 27)
How many closure sites is there in the neural tube?
Up to 5 closure sites in humans
What does failure of the neural tube to close properly lead to?
Neural tube defects (NTDs)
- Anencephaly
- Encephalocele
- Spina bifida
Who is affected by exencephaly/ anencephaly (meroencephaly)
- 1:1500 births
- ~4x more common in females
What occurs in exencephaly/ anencephaly (meroencephaly)?
- Failure of anterior neuropore to close leads to failure of skull formation and brain tissue degeneration
- It is incompatible with life
Craniorachischisis
Failure of neural tuve closure along entire neuroaxis
How many people are affected by encephalocoele?
1:4000 births
What occurs in encephalocoele?
- Herniation of cerebral tissue through a defect in the skull due to failure of the rostral neural tube to close
- Results in variable degree of neurological deficits
What is the most frequent region involved in encephalpocoele?
Occipital region
What is spina bifida?
- A condition where there is defective closure of the caudal neural tube which affects the tissues overlying the spinal cord
- Neural tissue may or may not be affected and severity ranges from minor abnormalities to major clinical symptoms
What causes spina bifida?
Non-fusion of vertebral arches
What is the most minor form of spina bifida?
Spina bifida occulta
What causes spina bifida occulta?
Failure of embryonic halves of vertebral arch to grow normally and fuse
Where does spina bifida occulta usually occur?
Occurs in L5 and L6 vertebrae of 10% of otherwise healthy people
How does spina bifida occulta usually present?
- 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.
What is spina bifida with meningocele?
Protrusion of meninges and cerebrospinal fluid
What is spina bifida with meningomyelocle?
Nerve roots and/or spinal cord included in the protruding sac
What is spinal bifida with myeloschisis?
Spinal cord in affected area open due to failure of neural folds to fuse
How many people are affected by spina bifida cystica?
1:1000 live births
What is the rarest form of spina bifida cystica?
Spina bifida with meningocele
What is the most severe form of spina bifida cystica?
Spina bifida with myeloschisis
What neurological deficits accompany spina bifida with meningomyelocle?
Loss of sensation and muscle paralysis
What is the area affected by spina bifida with meningomyelocle determines by?
Level of lesion
What is spina bifida with meningomyelocle often associated with?
Hydrocephalus
Why is incidence of congenital abnormalities decreasing in the UK?
- Folic acid supplements
- Prenatal diagnosis
How effective are folic acid supplements?
400 µg/day can produce a 50-70% decrease in risk
What forms of prenatal diagnosis are there?
- Maternal blood screening
- Amniocentesis
- Ultrasound
What abnormalities can be detected on ultrasound?
- Anencephaly from 12 weeks
- Spina bifida from 16-20 weeks
What can be detected by amniocentesis?
High levels AFP in amniotic fluid
What can be detected by 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.
What are the risk factors for congenital abnormalities?
- 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 the development of the brain vesicles start with?
Begins with closure of anterior neuropore (~day 25; 18 – 20 somite stage)
What are the 3 primary brain vesicles called?
- Prosencephalon
- Mesencephalon
- Rhombencephalon
What are the 5 secondary brain vesicles called?
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
Where is the cephalic flexure found?
Between midbrain (mesencephalon) and hindbrain (rhombencephalon
When does the cephalic flexure develop?
End of 3rd week
When does the cervical flexure develop?
End of 4th week
Where is the cervical flexure found?
Between hindbrain and spinal corrd
When does the pontine flexure develop?
5th week
Where is the pontine flexure found?
In hindbrain (between metencephalon and myelencephalon
What does the caudal neural tube develop into?
Spinal cord
What does the telencephalon develop into?
- Cerebral hemispheres
- Hippocampus
- Basal ganglia
What does the diencephalon develop into?
- Thalamus
- Hypothalamus
- Pituitary gland
- Pineal
What does the mesencephalon develop into?
- Midbrain
- Superior and inferior colliculi
What does the metencephalon develop into?
- Cerebellum
- Pons
What does the myelencephalon develop into?
Medulla
What does the lumen of the neural tube develop into?
Ventricular system
What connects the lateral and III ventricle?
Foramina of Munro
When does the CSF begin to form?
During 5th week
What is the CSF produced by predominantly?
Choroid plexus (in III and IV, lateral ventricles)
What does the CSF drain into?
Drains into subarachnoid space via openings in roof of 4th ventricle
What is the CSF absorbed into?
Venous system
What is hydrocephalus?
Accumulation of cerebral spinal fluid which results in enlarged brain and cranium
What is hydrocephalus frequently due to?
Frequently due to blocked aqueduct which prevents CSF from lateral and 3rd ventricles passing into the 4th ventricle meaning it can’t drain properly.
What can cause hydrocephalus?
- Genetic
- Prenatal viral infection
- Intraventricular haemorrhage
- Spina bifida cystica
When does cellular differentiation in the neural tube take place?
Begins early embryogenesis, continues into postnatal period
Give an example of a region which adds new cells throughout life?
Olfactory epithelium
What is the neural tube initially?
Initially a single layer of rapidly dividing neuroepithelial cells
What epithelium is found in the neural tube?
Pseudo stratified epithelium
Where does the epithelium of the neural tube divide?
Ventricular surface
What produces most cells of the CNS?
Neuroepithelium
What are microglia?
Mesenchymal cells that migrate into CNS
What can neuroepithelial cells form?
- Ependymal cells
- Neurons
- Astrocytes
- Ogliodendrocytes
What is the sensory component of the spinal cord?
Dorsal root ganglia
How does the position of the spinal cord change?
- 3rd month – extends entire length of vertebral column.
- Vertebral column and dura mater grow more rapidly leading to a cord at progressively higher levels (newborn, ~L2 or L3; adult ~L1).
Where are the spinal nerves initially found?
Level of origin
How is the cauda equine formed?
Spinal nerves become elongated
What forms the terminal filum?
Pia mater
What are the sympathetic and parasympathetic ganglia formed by?
Neural crest cells
Ganglia
Collection of neuronal cell bodies
Where are the parasympathetic ganglia found?
Near or within organs they innervate
Where are the sympathetic ganglia found?
-Chains along side of spinal cord.
-Preaortic ganglia
-Sympathetic organ plexuses
(in e.g. heart, lungs, GI tract).
How do sulci and gyri develop?
- Surface of cerebral hemispheres initially smooth.
- Rapid growth results in the development of sulci (grooves) and gyri (elevations).
- Pattern becomes more complex as brain enlarges.
What is lissencephaly?
Rare brain disorder where the gyri and sulci fail to develop
What is lissencephaly caused by?
Defective neuronal migration
How does lissencephaly present?
- Severe mental impairment
- Failure to thrive
- Seizures
- Abnormal muscle tone
What is the prognosis of lissencephaly?
Many affected children die before age 10
What is polymicrogyria?
Excessive number of small gyri
How does polymicrohyria present?
Variable degree of neurological problems (e.g. mental retardation, seizures, motor deficits etc)
What can cause microcephaly?
- Genetic
- Drugs
- Infection (Zika virus)
How does microcephaly present?
- Intellectual impairment
- Delayed motor -Functions/speech,
- Hyperactivity
- Seizures
- Balance/co-ordination problems
How does agenesis corpus callosum present?
- Alone or with other cerebral abnormalities
- Effects range from subtle – severe
- Cognitive and social difficulties to intellectual impairment, seizures, hypotonia etc
What is porencephaly usually caused by?
- Postnatal stroke
- Infection
How does porencephaly present?
- Delayed growth and development
- Seizures
- Hypotonia
- Intellectual impairment
What can cause schizencephaly?
- Genetic
- In utero stroke
- Infection
How does schizencephaly present?
- Paralysis
- Seizures
- Intellectual impairment
- Developmental delay
What is diastematomyelia?
Split cord malformation where the cord splits into 2 parts longitudinally
What is diastematomyelia usually associated with?
Vertebral abnormalities
How doe diastematomyelia present?
- Scoliosis
- Weakness of lower extremities
- Hairy patch over lower back
- Foot deformities
- Loss of sensation
What is often absent in intellectual impairment?
Gross brain defects
What can cause 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)
What is most common cause of intellectual impairment?
Maternal alcohol abuse
What is the incidence of foetal alcohol syndrome?
- Foetal alcohol syndrome 1:1000
- Estimated up to 1:100 some degree of intellectual impairment
What is porencephaly?
CSF filled cysts or cavities in the brain
What is schizencephaly?
Large clefts or silts in the brain
