Embryology and Congenital Malformations Flashcards
Describe granulation
Happens at week 3
Epiblast generates 3 germ layers
Hypoblast lines yolk sac
Primitive streak
Describe the 3 germ layers
Ectoderm - epidermis and nervous system
Mesoderm - bone, muscles and blood cells
Endoderm - gut, pharynx, and lungs
Describe the CNS beginning to appear at 3 weeks
Thickening of the ectoderm anterior to primitive node - neural plate
Edges thicken and move upwards to form the neural folds
Describe the neural tube
Neural folds migrate towards towards each other and fuse to form
Initially remains open at anterior and posterior ends
Anterior (cranial) neuropore close at 25days
Posterior (caudal) neuropore close around 27days
Describe the closure of the neural tube
Initiated at several points along the AP axis and proceeds in caudal to cranial direction
Begins at day 18 and completed at 4th week (27days)
Up to 5 closure sites
What are some neural tube defects caused by failure of tube to close properly?
Anencephaly
Encephalocele
Spina Bifda
What is Exencephaly/ Anencephaly?
Is failure of anterior neuropore to close - skull fails to form and brain tissue degenerates
Is incompatible with life
1:1500 births
What is craniorachischisis?
Failure of neural tube closure along entire neuroaxis
What is Encephalocele?
1:4000 births
Herniation of cerebral tissue through defect in the skull and failure in closure of rostral neural tube
Most frequent in occipital region
What is spinal bifta?
Defective closure of the caudal neural tube and affects the tissues overlying the spinal cord
Means there is non-fusion of vertebral arches
Neural tissue may or may not be affected
Describe spinal bifta occulta
Most minor and most common
Failure of embryonic halves of vertebral arched to grow normally and fuse
Occurs in L5 and 6 vertebrae f 10% of healthy individuals
How does spinal bifta occulta present?
Usually no clinical symptoms
May result in dimple with small tuft of hair
What is spinal bifta cystica?
Protrusion of spina cord and/or meninges through the defect in the vertebral arches
1:1000 live births
What is spinal bifta with meningocele?
Rarest form
Protrusion of meninges and CSF
No neural tissue damage so good outcome
What is spinal bifta with meningomyelocele?
Nerve roots and/or spinal cord included in the sac
Neurological defects so loss of sensation and muscle paralysis
Often associated with hydrocephalus
What is spinal bifta with myeloschisis?
Most severe form
Spinal cord in affected area open due to failure of neural folds to fuse
Neurological deficits
What is causing incidence decrease in UK of neural tube defects?
Folic acid supplements
Prenatal diagnosis - Maternal blood screening, amniocentesis and ultrasound
What are the risk factors of neural tube defects?
Genetic predisposition
Nutritional - little follate, too much vitamin A
Environmental - hyperthermia, certain drugs - sodium valproate
Describe maternal blood screening and amniocentesis
Maternal - Indicated by high levels alpha-fetoprotein (AFP) in serum as AFP from foetal liver leaks into amniotic fluid then maternal blood
Detected at 16-20 weeks
Amniocentesis - high levels AFP in amniotic fluid
What are the 3 primary vesicles in brain and spinal cord development?
Prosencephalon - forebrain
Mesencephalon - midbrain
Rhombencephalon - hindbrain
These appear at 27 days
What are the 5 secondary brain vesicles of brain and spinal cord development?
Prosencephalon - Telencephalon and Diencephalon
Mesencephalon
Rhombencephalon - metencephalon and myelencephalon
At 32 days
What are the olds of the CNS?
Cephalic flexure - 3rd week
Cervical flexure - 4th week
Pontine flexure - 5th week
Where is the cephalic flexure?
Between midbrain and hindbrain
Where is the cervical flexure?
Between hindbrain and spinal cord
What is the pontine flexure?
In hindbrain
What is the purpose of cortical folding?
Space saving as minimises brain volume
brings together parts of brain to optimise brain wiring and functional organisation
Describe lissencephaly
Rare
Caused by defective migration and gyri + sulci fail to develop
Results in seizers, abnormal muscle tone, severe mental impairment and failure to thrive
Describe polymicrogyria
Excessive number of small gyri
Variable degree of neurological problems - mental retardation, seizers and motor deficits
What forms the ventricular system?
Lumen of the neural tube
How is CSF formed?
Begins at 5th week
Produced predominantly by choroid plexus
Drains into subarachnoid space via opening at roof of 4th ventricle
Absorbed by venous system
Describe hydrocephalus
Accumulation of cerebral spinal fluid which results in large brain and cranium
Frequently due to blocked aqueduct
CSF from lateral and 3rd ventricles cant drain
What are some of the causes of hydrocephalus?
Genetic, prenatal viral infection or intraventricular haemorrhage, spinal bifta cystica
Describe cellular differentiation in the neural tube
Needs to make neuronal cells and connect cells together
Begins early embryogenesis, continues into postnatal period
Some regions add new cells through out life
What are the cells in the neural tube?
Initially a single layer of rapidly dividing neuroepithelial cells
Pseudostratified epithelium
Divide at ventricular surface
Neural tube produces most cells of the CNS except microglia
Describe the morphological differentiation of the spinal cord
At day 25 there is neuroepithelial cells
At 40 days there is neuroepithelial cells in ventricular zone and differentiated cells in mantle layer
What does the peripheral nervous system develop from?
Neural crest cells
What are some neural crest derivatives?
Sensory neurons, autonomic neurons, schwann cells, satelitte cells, aortic plexus, endocrine cells, ENS, pigment cells, teeth, non-neural head structures…
What do thoracic and lumbar crest cells form?
Sympathetic ganglia
What do cervical and sacral crest cells form?
Parasympathetic ganglia
Describe spinal nerve development
Dorsal root ganglia is the sensory component - neural crest
Extends 2 processes - peripheral is the body and central is dorsal horn
Motor component - motor neurons of spinal cord (neural tube)
When does spinal cord extend entire length of vertebrae column?
3rd month
Describe the positional change of the spinal cord
Vertebrae column and dura mater grow more rapidly
Initially spinal nerves found a level of origin but become elongated to form the cauda equina
Pia mater forms the terminal filum
What is microcephaly?
Due to genetics, drugs and infection (Zika)
Brain is smaller size and causes intellectual impairment, delayed motor, hyperactivity and seizers
What is aegenesis corpus callosum?
Corpus callosum is partially or completely not there
Effects range from subtle to severe
Cognitive and social difficulties
What is porencephaly?
CSF filled cysts or cavities
Usually from postnatal stroke or infection
Delayed growth and development, seizers, hypotonia, intellectual impairment
What is schizencephaly?
Large clefts or slits
Genetic, in utero stroke, infection
Paralysis, seizers, intellectual impairment and developmental delay
Describe disatematomyelia
Split cord malformation - split longitudinally into 2 parts
Bony or cartilage process fix cord in place
Scoliosis, weakness of lower extremity, hairy patch on lower back, foot deformities and loss of sensation
What are some causes of intellectual impairment?
Genetic, radiation, infectious agents, birth trauma, postnatal insults
Commonest - maternal alcohol abuse
