disorders of neural tube closure and migration

1. Disorders of neural tube
closure,
diverticulation,cleavage and
cellular migration

2.  Over view of embryology
 Disorders of neural tube closure
 Disorders of diverticulation, cleavage
and cellular migration

3. CNS Embryology

5. Flexures

6. Spinal cord

8. Medulla oblongata

9. Pons

10. Mid brain

11. Ventricles

13. Cortex

14. Diencephalon

15. Basal ganglia

17. Commisures

18. Neural tube closure disorders
 Disorders of closure of rostral neural
pore
 Disorders of closureof caudal neural
pore

19. Cranial defects
 Meningocele, meningoencephalocele, and
meningohydroencephalocele are all caused
by an ossification defect in the bones of the
skull. The most frequently affected bone is
the squamous part of the occipital
bone, which may be partially or totally
lacking. If the opening of the occipital bone
is small, only meninges bulge through it
(meningocele), but if the defect is
large, part of the brain and even part of the
ventricle may penetrate through the
opening into the meningeal sac

20.  The latter two malformations are
known as meningoencephalocele and
meningohydroencephalocele

22. Anencephaly
 Exencephaly is characterized by failure of the
cephalic part of the neural tube to close. As a
result, the vault of the skull does not
form, leaving the malformed brain exposed.
Later this tissue degenerates, leaving a mass
of necrotic tissue. This defect is called
anencephaly, although the brainstem remains
intact. Since the fetus lacks the mechanism
for swallowing, the last 2 months of
pregnancy are characterized by hydramnios.
The abnormality can be recognized on a
radiograph, since the vault of the skull is
absent.

24. Defects of caudal neuropore
 Neural tube defects (NTDs), may
involve the
meninges, vertebrae, muscles, and
skin.
 Spina bifida is a general term for
NTDs affecting the spinal region. It
consists of a splitting of the vertebral
arches and may or may not involve
underlying neural tissue. Two different
types of spina bifida occur:

25. ◦ Spina bifida occulta is a defect in the
vertebral arches that is covered by skin
and usually does not involve underlying
neural tissue. It occurs in the lumbosacral
region (L4 to S1) and is usually marked by
a patch of hair overlying the affected
region.
◦ Spina bifida cystica is a severe NTD in
which neural tissue and/or meninges
protrude through a defect in the vertebral
arches and skin to form a cyst like sac.

26.  Occasionally the neural folds do not
elevate but remain as a flattened
mass of neural tissue (spina bifida
with myeloschisis or rachischisis).

31. Cerebral cleavage and neural
migration defects
 Child with delayed devolopment and
seizures
 Especially when child is dysmorphic
 MRI is the investigaton of choice
 After the imaging we have to see the MR
in a orderly fashion
◦ Midline structures
◦ Cerebral cortex and cortico white matter
junctions
◦ White matter
◦ Basal ganglia and ventricular system and
posterior fossa structures

32. Midline structures
 Cerebral commisures are the most
common anomolies
 Hypothalamus and pituatary
 Midline leptomeninges
 Large csf spaces in posterior fossa

33. Cerebral cortex
 Is 2-3mm thick
 Too thick polymicrogyria and
pachygyria
 Greywhite matter junction irregular
polymicrogyria or cobble stone cortex
 Abnormally thin perinatal or ishaemic
injury

34. White matter
 Myelination appropriate or not
 Diffuse layer of hypomyelination or
amyelination associated heterotopia or
polymicrogyria suggestive of CMV
 Absent myelination may be localised
to a gyrus or may extend towards the
ependymal layer transmantle sign
characteristic of FCD

35. Posterior fossa
 Brain stem and cerebellum
 4 th V and vermis
 Size of the pons with cerebellum

38. Callosal dysgenesis
 Partial or complete absence corpus
callosum and hippocampal
commisures
 Atrium or occipital horn dilatation
colpocephaly
 Probst bundles
 Vertical or posterior course ACAs
 Most common presentation seizures
devolopmental delay and cranial
deformity and hypertelorism

41. Dandy-Walker malformation
 Classic Dandy Walker malformation
 HVR
 BPC
 MCM

42. Classic DWM
 Cystic dilatation of
4thV
 Torcular lambdoid
inv
 HVR

43.  HVR
◦ Variable vermian
hypoplasia
 BPC
◦ Open 4th V
communicates with
cyst
 MCM
◦ Enlarged
pericerebellar cisterns
communicate with sub
arachnoidspace
◦ Vermis and 4 th V
normal

44. Rhombencephalosynapsis
 Etiology
◦ Unknown: 2 major theories
 Failure of vermian differentiation
 Vermian agenesis allowing hemisphere
continuity
 Features
◦ Congenital continuity (lack of division) of
cerebellar hemispheres
◦ Usually with fusion of dentate nuclei and
superior cerebellar peduncles

45. ◦ Small, single hemisphere cerebellum with
continuous white matter (WM) tracts crossing
midline
◦ Diamond or keyhole-shaped 4th ventricle
◦ Absent primary fissure
 Clinical features
◦ Variable neurological signs
◦ Ataxia, gait abnormalities, seizures
◦ Developmental delay
◦ RES discovered in near-normal patients at
autopsy

47. Molar Tooth Malformations
(Joubert)
 Hindbrain anomaly characterized by
dysmorphic vermis, lack of
decussation of superior cerebellar
peduncle, central pontine
tracts, corticospinal tracts
 "Molar tooth" appearance of midbrain
on axial images
 Etiology
◦ result from mutations of
ciliary/centrosomal proteins that can affect
cell migration, axonal pathway

48.  Clinical features
◦ Most common signs/symptoms:
Ataxia, developmental delay, oculomotor
and respiratory abnormalities

51. Holoprosencephaly
 Features
◦ Failure to delineate normal
prosencephalic midline with
absent/incomplete hemispheric and basal
cleavage
◦ Single ventricle
◦ Azygous ACA
◦ associated facial defects

52.  Clinical features
 Most common signs/symptoms
◦ Facial malformation (hypotelorism +++)
◦ Seizures and developmental delays
◦ Hypothalamic/pituitary malfunction
(75%, mostly diabetes insipidus), poor
body temperature regulation
◦ Dystonia and hypotonia: Severity
correlates with degree of BG
nonseparation

55. Heterotopic Gray Matter
 Arrested/disrupted migration of groups
of neurons from periventricular
germinal zone (GZ) to cortex
 Ectopic nodule or ribbon, isointense
with gray matter (GM) on every MR
sequence
 Periventricular, subcortical/transcerebr
al, molecular layer
 Band heterotopia

58. Lissencephaly
 Features
◦ Disorders of cortical formation caused by
arrested neuronal migration, resulting in thick
4-layer cortex and smooth brain surface
◦ "Hourglass" or "figure eight" shape of
cerebral hemispheres
◦ 3 layers
 Outer cellular layer → may be relatively
thin, smooth
 Intervening cell-sparse layer
 Deeper thick layer of arrested neurons mimicking
band heterotopia

60. Schizencephaly
 Features
◦ Transmantle gray matter lining clefts
◦ Ca++ when associated with CMV
 Pathology
◦ Can be result of acquired in utero insult
affecting neuronal migration
◦ Infection (CMV), vascular insult, maternal
trauma, toxin
 Types
◦ Closed lip
◦ Open lip

62. Hemimegalencephaly
 Features
◦ Hamartomatous overgrowth of part/all of
hemisphere
◦ Abnormal proliferation, migration, and
differentiation of neurons
◦ Embryology
 Insult to developing brain causes development of
too many synapses, persistence of supernumerary
axons, and potential for white matter overgrowth
 Localized epidermal growth factor (EGF) in cortical
neurons and glial cells may lead to excessive
proliferation

63. ◦ Large cerebral hemisphere, hemicranium
◦ Posterior falx and occipital pole "swing" to
contralateral side
◦ Lateral ventricle is large with abnormally
shaped frontal horn

65. Polymicrogyria
 Features
◦ Malformation due to abnormality in late
neuronal migration and cortical
organization
◦ Result is cortex containing multiple small
sulci that often appear fused on gross
pathology and imaging
◦ Neurons reach cortex but distribute
abnormally forming multiple small
undulating gyri