Which nerve layer does the nervous system develop from?
The embryonic ectoderm
Also forms the epidermis
How is the neural plate formed?
Thickening of ectoderm anteroir to the primitive node
How are neural folds formed?
Edges thicken and move upwards to form neural folds
How is the neural tube formed?
Neural folds migrate towards each other and fuse at the midline
When do the anterior and posterior neural tube openings open/close?
•Anterior (cranial/rostral) neuropore closes 18 – 20 somite stage (~25 days)
•Posterior (caudal) neuropore closes ~ day 27.
At what point is the nervous system in open communication with the amniotic fluid?
When the neuropores are still open
What are the neural tube defects which happen as a result of failure of the neural tube to close properly?
(Some of the most common congenital abnormalities of the CNS)
What causes anencephaly?
Failure of the anterior neuropore to close
Skull fails to form
Brain tissue degenerates
What is craciorachischisis?
failure of neural tube closure along entire neuroaxis
What is the cause of encephalocele?
Failure in closure rostral neural
Results in herniation of cerebral tissue through a defect in the skull (most likely to be in the occipital region)
Variable degree of neurological defecits
What cause 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 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.
•Occurs in L5 and L6 vertebrae of 10% of otherwise healthy people.
What are the clinical features of spina bifida?
May result in a dimple with a small patch of hair
What causes spina bifida cystica?
Protrusion of spinal cord and or meninges through defect in vertebral arches
What causes spina bifida with meningocele (form of spina bifida cystica)
Protrusion of meninges and cerebrospial fluid
What causes Spina bifida with meningomyelocle (form of spina bifida cystica)
•Nerve roots and/or spinal cord included in the sac (that protrudes through the defect in the vertebral arches)
What are teh features of spina bifida with meningomyelocle?
•Neurological deficits – loss of sensation and muscle paralysis
•Area affected determined by level of lesion
•Often associated with hydrocephalus
What is the most severe form of spina bifida?
•Spinal cord in affected area open due to failure of neural folds to fuse.
How do we help to prevent spina bifida?
Folic acid supplements for pregnant women
How is prenatal diagnosis of spina bifida achieved?
Maternal blood screening for AFP (alpha fetoprotein) in serum
Best detected 16 - 20 weeks
Amniocentesis (high levels of AFP in amniotic fluid)
Ultrasound - anencephaly from 12 weeks and spina bifida from 16 - 20
What are the risk factors for spina bifida?
•Nutritional (e.g. too little folate, too much vitamin A)
Vitamin A is avoided by women – found in the liver. Vitamin A is converted into another compound in the body which is a teratogen
•Environmental (e.g. hyperthermia; taking certain drugs – e.g. sodium valproate)
When does development of brain vesicles begin?
With closure of anterior neuropore (around day 25)
What are the 3 primary brain vesicles and what are the 5 seconday brain vesicles that form from these?
Where do you find the cephalic flexure, the cervical flexure and the pontine flexure?
Cephalic flexure - Between midbrain (mesencephalon) and hindbrain (rhombencephalon)
Cervical flexure - between hindbrain and spinal cord
Pontine flexure - between metencephalon and myeloencephalon
When do the different flexures form?
Cephalic flexure - end of 3rd week
Cervical flexure - end of 4th week
Pontine flexure - 5th week
What forms from the diencephalon?
thalamus, hypothalamus, pituitary gland, pineal
What forms from the telencephalon?
What forms from the midbrain?
Superior and inferior colliculi
What forms from the metencephalon?
Cerebellum and pons
What forms from the myelencephalon?
What forms the ventricular system in the brain?
The lumen of the neural tube
Where is CSF produced?
Predominately by the choroid plexus in the 3rd and 4th ventricles
Where does CSF drain?
Drains into the subarachnoid space via openings in roof of 4th ventricle and absorbed into the venous system
What causes hydrocephalus?
Accumulation of CSF
Frequently due to blocked aqueduct - prevents CSF from lateral and 3rd ventricles passing into the 4th ventricle - can't drain properly
What are the causes of hydrocephalus?
Prenatal viral infection or intraventricular haemorrhage
Spina bifida cystica
What cell type makes up the initial neural tube?
Rapidly dividing neuroepithelial cells
What types of cells do neuroepithalial cells form in the CNS?
Forms all the cells in the CNS apart from microglia
(neurons, astrocytes, oligodendrocytes, ependymal cells)
Where do neural crest cells arise from?
They are part of the roof plate of the neural tube
What is the action of the neural crest cells?
Undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into varied cell types.
What cell types do neural crest cells form?
They give rise rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia
Neural crest cells form all the pigment in our body apart from the pigment in our eye
Each spinal nerve has a motor component and a sensory component, what is the embryological origin of both of these?
Sensory - cell bodies of dorsal root ganglia, arise from neural crest cells
Motor - Comes from motor neurones which are a neural tube derived cells - they line the ventral part of the neural tube, they extend their axons out via the ventral root where it meets the dorsal root to form the spinal nerve
What causes the spinal cord to ascend the vertebral column with age?
The vertebral column and the dura mater grow more rapidly
What forms the sympathetic and parasympathetic ganglia?
Neural crest cells
Where do you find sympathetic ganglia?
Chains along side the spinal cord (paravertebral)
Sympathetic organ plexuses (in heart, lungs GI tract)
Where do you find parasympathetic ganglia?
Near or within the organs they innervate
What causes the development of sulci and gyri in the brain?
The surface of cerebral hemispheres is initially smooth - rapid growth results in the development of sulci and gyri
The pattern becomes more complex as the brain enlarges
What is lissenceohaly?
Defective neuronal migration
Gyri and sulci fail to develop
What are the health implications of lissencephaly?
•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)
What are the causes of microcephaly?
What is the effect of microcephaly on the person?
•Intellectual impairment, delayed motor functions/speech, hyperactivity, seizures, balance/co-ordination problems etc.
What are the effects of agenesis of corpus callosum?
May come with ither cerebral abnormalities
•Effects range from subtle – severe
•Cognitive and social difficulties - intellectual impairment, seizures, hypotonia etc
What is porencephaly?
CSF filled cysts or cavities
What causes porencephaly?
Usually from postnatal stroke or infection
What is the result of porencephaly on the person?
•Delayed growth and development, seizures, hypotonia, intellectual impairment
What is schizencephaly characterised by?
Large clefts or slits
What causes schizencephaly?
In utero stroke
What is the effect of schizencephaly?
Paralysis, seizures, intellectual impairment, developmental delay
What is the name given to the condition resulting in split cord malformation?
Diastematomyelia - the chord is split longitudinally into 2 parts
What fixes the cord in one place in diastematomyelia?
Bony or cartilaginous process - fixes the cord in one place
What is the impact of diastematomyelia?
•Scoliosis, weakness of lower extremities, hairy patch over lower back, foot deformities, loss of sensation.
What are the causes of intellectual impairment?
COMMON CAUSES - Maternal alcohol abuse
What are the infectious agents that cause intellectual impairment?
What postnatal insults can result in intellectual impairment?