CONGENITAL ANOMALI

OF THE CNS

Rina Gustuti
 Noted :
• Dorsal induction refers to
events of notochordal
process  neural plate
neural tube spinal
cord and brain
• Ventral induction refers
to events occurring
ventrally in the rostral
end of the embryo
face and brain

AJNR:9, March/April 1988

AJNR:9, March/April 1988
“23 Carnegie stages”
 NEURAL TUBE DEFECTS
 Normal embryology :
• The development of the human  NTDs embryology :
nervous system commences with the • The failure of any step of
development of the notochordal differentiation from the initial
processprimitive knot to the cranial step of primary neural
end of the embryo. induction to the end of neural
• The notochordal process neural tube closure result NTD
plate neural tube complete • The relative timing of the
cranial and caudal neuophore closure different zones of
 gives rise to the brain and spinal differentiation critically
cord made between primary and important to development.
secondary neurulation.
• There are separate genes
• Primary neurulation  generates the expressed at each closure site
entire neural tube rostral to the during neurulation
caudal neurophore / anterior part of
neural tube 3rd and 4th weeks of • “ multiple site of neural tube
gestation fussion” NTD
• Secondary neurulation  form • The earlier the failure of
posterior part of neural tube / lumbo differentiation the more
sacral area severe the NTD
Type of NTDs relate to stage of closure
TYPES OF NTDs
• Exencephaly failure of cranial neural tube closures the brain neural folds remain open and exposed to the
environment continued growth and differentiation  neuroepithelium characteristic appears to protrude
from the developing brain.
• Anencephaly failure of cranial neural tub closures both cerebral hemispheres are absent  theskull vault
does’nt form over the open region absence of cranial vault and structures derived from forebrain and skull
• Myelomeningeocele  in normal embryo the vertebral arches develop from the sclerotomal component of the
axial mesoderm, which migrates dorsally to surround the closed neural tube before undergoing cartilaginous
and bonny differentiation  when neural folds remain open the sclerotome is unable the cover the
neuroepithelium
• Craniorachischisis entire neural tube remains open from midbrain to low spine disruption of the
embryonic process of convergent extension signalling PCP pathway
• Closed spinal lesion
 defect skeletal development
 absent neural arches or midline bony spur  abnormality of spinal cord  over distension of the central
canal  hydromyelia, longitudinal duplication or splitting  diplomyelia , tethering of the cord’s lower end which
are often associatyed with lipoma  lipomyelomeningocele.
• Encephalocele and meningocele  defect of cranial mesoderm development  a persistent opening in the
skull , at occipital, parietal or frontoethmoidal location  allows meninges to herniate creating an extra cranial
mass
Risk fc of NTDs
Relation of folic acid and neural tube defects
Polyunsaturated fatty acid (PUFA) synthesis
may contribute to NTDs
• SAM provide phosphoetanolamin
methyltransferase (PEMT) enzyme 
create PUFA in embryonic neural tissue 
high demand neural lipid during early
development
• PEMT  methylated 3 components of the
cytoskeleton (actin, alfa and ß tubulin,
neurofilamentr L)  cell contraction and
movement if reduced methylation of
cytoskeletal elements  caused NTDs
 Molecular Mechanism underlying Neural Tube closure

1. Shaping of the neural plate  convergent extension is Required to initiate

Closure
2. Planar Cell polarity (PCP signalling) prevent convergent extension
3. Bending of the Neural Fold  Regulation by Shh and BMP Signaling
4. Cranial neurulation disruption of the actin cytoskeleton prevent closure in the
cranial
5. Adhesion and fusion of the neural fold
6. Regulation of cell proliferation and Cell death
 Key signalling pathways in neurulation and NTDs
1. PCP signalling
 at the onset of neurulation  lengthening and narrowing of the initially dish shaped neural plate 
termed convergent extension  closure initiation of the neural fold
2. SHH signalling
 initiates an intracellular signalling pathway  processed as transcriptional activators
3. BMP signalling
 members of the TGFß superfamily of proteins that signal to regulate transcription via Smad proteins in
canonical pathway and via tyrosine kionase in non canonical signalling
4. GRHL genes
 regulate  growth imbalance between the slowly proliferating hindgut and the normally proliferating
neural plate  enhances curvature of the caudal region which mechanically opposes neural fold
elevation and fussion
5. Retinoid signalling
 any disturbance in the balance between production and turnover of retinoid can adversely effect
developmental events including neural tube closure
CONCLUSSION

Identification of the mechanism by which folate status

affects neural tube closure will assist in developing
more efficacious and better targeted preventative
measures.
TERIMAKASIH