Case 1 summary
General ILOs:
- To demonstrate knowledge of the structure and development of the CNS and
associated connective tissues
Gastrulation results in invagination, forming three cell layers: ectoderm, mesoderm,
endoderm.
Notochord is an aggregation of the mesoderm which extends across the primitive pit
(precedent to primitive streak). Morphogens released by the notochord to the overlying
ectoderm result in the formation of the neural plate (neurulation, day 22).
Upregulation of FGF and downregulation of BMP stimulates the formation of the neural
plate, an aggregation of cells in the ectoderm. The neural plate folds inwards, creating a
neural crest, beginning in the cranial/cephalic region and travelling to the caudal end
(finishing day 25/27).
Two partitioning rounds follow initial brain formation (controlled by HOX-genes):
Spinal cord development:
1
MBChB Y2 – Guillaume Antem
, Neuroepithelium within the neural tube convert to neuroblasts, forming mantle layer
(grey matter).
In the outermost layer (marginal layer), nerve fibres form neuroblasts (white matter).
Neural tube thickens, forming sulcus limitans within inner lateral wall dividing tube
into basal (ventral, primarily motor) and alar (dorsal, primarily sensory) plates.
Neurons between those two areas form the intermediate horn (present at T1-T12 and
L2/L3).
Neural differentiation is determined by concentration gradients of morphogens. This process
occurs in the dorsoventral (BMP & SHH) and anteroposterior aspects (retinoic acid & FGF).
Retinoic acid is released by somites.
Note: anteroposterior is referred to as cephalic/caudal in the diagram
Neuron and glia differentiation:
Precursor cells are found in the ventricular zone of the neural tube lumen. They form via
symmetrical division of neuroectodermal cells. Neuroblasts divide asymmetrically, resulting
in one daughter becoming a postmitotic neuroblast (the other remains a neuroblast).
Postmitotic cells migrate from the ventricular zone and differentiate according to morphogen
patterning. PNS neural cells migrate and differentiate based on protein gradients (antero-
posterior patterning).
Glia support neurons by:
Maintaining ionic milieu
Modulating nerve signal propagation
Controlling neurotransmitter uptake
Aiding neural injury recovery
2
MBChB Y2 – Guillaume Antem
, Glial cell types:
Astrocytes: found in brain and spinal cord. Maintain chemical environment for
neuronal signalling.
Oligodendrocytes: found in CNS. Lay myelin around axons. Equivalent in PNS are
Schwann cells.
Microglial cells: remove cellular debris, involved in immune system (cytokine
release).
- To demonstrate basic knowledge about neural tube defects including pathology,
epidemiology, investigation, prevention and treatment
In general, neural tube defects (NDTs) result from failure of the neural tube to close at the
anterior/cranial (day 25) or posterior/caudal (day 27/28) pores:
Anterior pore fails to close – anencephaly.
Posterior pore fails to close – spina bifida
Cranial dysraphism:
Anencephaly (detectable at 12wks; absence of cerebral hemispheres, incompatible
with life)
Cephaloceles are herniations of cranial contents, several types exist:
o Cranial meningocele contains only meninges
o Encephalocele contains brain tissue
o Ventriculocele contains part of the ventricle
Holoprosencephaly, failure of prosencephalon segmentation and cleavage.
Incompatible with life.
Spinal dysraphism:
Spina bifida is detectable at 16-20wks and can be divided into two types:
Occulta (no external lesion),
o Benign in majority of cases.
o Naevus forms at site of defect.
o MRI to assess impact.
o If attachment of the spinal cord in found, neurosurgical intervention to free it
from its tethering may be indicated.
Cystica (cystic lesion present on back) can be further considered as being:
o Meningocele: no neural tissue contained in protrusion, found in 5% of spina
bifida cystica cases.
o Myelomeningocele: spinal cord protrusion found in 90% of children with
spina bifida cystica (associated with Chiari II malformation), lumbosacral in
80% of cases.
o Always causes bladder/bowel disfunction
3
MBChB Y2 – Guillaume Antem
General ILOs:
- To demonstrate knowledge of the structure and development of the CNS and
associated connective tissues
Gastrulation results in invagination, forming three cell layers: ectoderm, mesoderm,
endoderm.
Notochord is an aggregation of the mesoderm which extends across the primitive pit
(precedent to primitive streak). Morphogens released by the notochord to the overlying
ectoderm result in the formation of the neural plate (neurulation, day 22).
Upregulation of FGF and downregulation of BMP stimulates the formation of the neural
plate, an aggregation of cells in the ectoderm. The neural plate folds inwards, creating a
neural crest, beginning in the cranial/cephalic region and travelling to the caudal end
(finishing day 25/27).
Two partitioning rounds follow initial brain formation (controlled by HOX-genes):
Spinal cord development:
1
MBChB Y2 – Guillaume Antem
, Neuroepithelium within the neural tube convert to neuroblasts, forming mantle layer
(grey matter).
In the outermost layer (marginal layer), nerve fibres form neuroblasts (white matter).
Neural tube thickens, forming sulcus limitans within inner lateral wall dividing tube
into basal (ventral, primarily motor) and alar (dorsal, primarily sensory) plates.
Neurons between those two areas form the intermediate horn (present at T1-T12 and
L2/L3).
Neural differentiation is determined by concentration gradients of morphogens. This process
occurs in the dorsoventral (BMP & SHH) and anteroposterior aspects (retinoic acid & FGF).
Retinoic acid is released by somites.
Note: anteroposterior is referred to as cephalic/caudal in the diagram
Neuron and glia differentiation:
Precursor cells are found in the ventricular zone of the neural tube lumen. They form via
symmetrical division of neuroectodermal cells. Neuroblasts divide asymmetrically, resulting
in one daughter becoming a postmitotic neuroblast (the other remains a neuroblast).
Postmitotic cells migrate from the ventricular zone and differentiate according to morphogen
patterning. PNS neural cells migrate and differentiate based on protein gradients (antero-
posterior patterning).
Glia support neurons by:
Maintaining ionic milieu
Modulating nerve signal propagation
Controlling neurotransmitter uptake
Aiding neural injury recovery
2
MBChB Y2 – Guillaume Antem
, Glial cell types:
Astrocytes: found in brain and spinal cord. Maintain chemical environment for
neuronal signalling.
Oligodendrocytes: found in CNS. Lay myelin around axons. Equivalent in PNS are
Schwann cells.
Microglial cells: remove cellular debris, involved in immune system (cytokine
release).
- To demonstrate basic knowledge about neural tube defects including pathology,
epidemiology, investigation, prevention and treatment
In general, neural tube defects (NDTs) result from failure of the neural tube to close at the
anterior/cranial (day 25) or posterior/caudal (day 27/28) pores:
Anterior pore fails to close – anencephaly.
Posterior pore fails to close – spina bifida
Cranial dysraphism:
Anencephaly (detectable at 12wks; absence of cerebral hemispheres, incompatible
with life)
Cephaloceles are herniations of cranial contents, several types exist:
o Cranial meningocele contains only meninges
o Encephalocele contains brain tissue
o Ventriculocele contains part of the ventricle
Holoprosencephaly, failure of prosencephalon segmentation and cleavage.
Incompatible with life.
Spinal dysraphism:
Spina bifida is detectable at 16-20wks and can be divided into two types:
Occulta (no external lesion),
o Benign in majority of cases.
o Naevus forms at site of defect.
o MRI to assess impact.
o If attachment of the spinal cord in found, neurosurgical intervention to free it
from its tethering may be indicated.
Cystica (cystic lesion present on back) can be further considered as being:
o Meningocele: no neural tissue contained in protrusion, found in 5% of spina
bifida cystica cases.
o Myelomeningocele: spinal cord protrusion found in 90% of children with
spina bifida cystica (associated with Chiari II malformation), lumbosacral in
80% of cases.
o Always causes bladder/bowel disfunction
3
MBChB Y2 – Guillaume Antem
