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1. Congenital Malformations of the Brain
By:-Dr.Abduljelil .MD,RRII
June ,5, 2020 GC

2. OUTLINE
• Normal brain development
• Approach to Congenital Malformations
• Disorders of neurulation
• Disorders of Regionalization
• Disorders of Cortico-genesis

3. Normal brain development
• Basic events in normal brain development includes four stages
1. Dorsal Induction: Formation and closure of the neural tube
• Occurs at 3-5 weeks
2. Ventral Induction: Formation of the brain segments and face
• Occurs at 5-10 weeks of gestation
3. Migration and Histogenesis
• Occurs at 2-5 months of gestation
4. Myelination
• Begins at 5 months of gestation; matures by 2 years

4. NEURULATION
vNeural tube forms the brain and spinal cord, whereas the neural crest gives
rise to peripheral nerves, roots, and ganglia of the autonomic nervous system
vAs the neural tube closes, the neuroectoderm (which will form the CNS)
separates from the cutaneous ectoderm in a process known as disjunction

5. •Fusion begins in the cervical region and proceeds in cephalic
and caudal directions
•cranial neuropore occurs at 25th day; closure of the caudal
neuropore occurs approximately 2 days later

6. •The cephalic end of the neural tube shows three dilations, the
primary brain vesicles
•When the embryo is 5 weeks old, the prosencephalon(tel n di)
and rhombencephalon(met n my) consists of two parts each

7. NEURONAL PROLIFERATION
• As the cerebral vesicles develop and expand, layers of
stem cells arise around the primitive ventricular
ependyma, forming the germinal matrix.
• These neural stem cells (NSCs) are multipotent cells that
generate the main CNS phenotypes, i.e.,neurons,
astrocytes, and oligodendrocytes

8. NEURONAL MIGRATION
•Migration of newly proliferated neurons occurs along scaffolding provided by
the RGCs(radial glial cells)- span the entire hemisphere
•Peak neuronal migration occurs between 11-15 fetal weeks although
migration continues up to 35 weeks.
•Organizaton into the normal six-layered laminaton of the cortex

9. MYELINATION
• Begins during the fifth fetal month and is largely complete by 18-24
postnatal months
• In general, myelination proceeds from inferior to superior, from back
to front, and from central to peripheral
Eg
• brainstem > peripheral cerebellar hemispheres
• posterior limbs of the IC > the anterior limbs
• deep periventricular white matter (WM) > subcortical U-fiber
• exception of the parietooccipital association tracts

11. • Two method
a) Categorizes lesions according to developmental and genetic
considerations
b) Malformations are grouped according to imaging findings -
– more traditional morphologic-based approach
– simplest for radiologists to follow
Approach to Congenital Malformations

13. Disorders of neurulation (Neural Tube Closure Defects)
1.Anencephaly (most common anomaly)
2.Cephalocele
3.Chiari Malformations

14. Anencephaly
• Cephalic end of the neural tube fails to close
• Absence of forebrain cortical tissue as well as absence of the cranial vault
– although brainstem and cerebellum may be variably present
• The most severe form of cranial NTD
• Pregnancy termination is offered at any gestational age
• Incidence :-1:1000 , more in females , F:M = 4:1

15. Radiographic Features (Antenatal Ultrasound & Fetal MRI)
• No tissue above the orbits + absent calvarium
• Less than expected value for CRL
• Frog eye or Mickey mouse appearance (coronal)
– due to absent cranial bone / brain and bulging orbits
• Polyhydramnios due to impaired swallowing

16. Cephaloceles
• Herniation of intracranial contents through a congenital defect in the dura and
skull
• Usually located at the midline.
• More in females
• Location :Occipital, 75%
Fronto-ethmoidal 10-15%
Parietal, 5-10%
• Occipital encephaloceles may be associated with Chiari or Dandy-Walker
malformations and callosal or migrational anomalies,
• Frontoethmoidal lesions are not typically associated with these types of
anomalies

19. Fronto-ethmoidal cephaloceles
3 subtype:
• Nasofrontal (40-60%)
• Nasoethmoidal (30%) - patent foramen
cecum in front of the crista galli
• Nasoorbital (10%) - medial wall of orbit
between maxilla and lacrimal/ethmoid
bone

20. Atretic Parietal cephalocele
• subgaleal soft tissue mass with an intracranial extension
• via a sharply demarcated calvarial defect (cranium bifidum)
• CSF tract and vertical falcine vein point to the subcutaneous scalp mass
• persistent falcine sinus frequently split the SSS
• Poor prognosis; Increased incidence of intracranial anomalies
– The prognosis of atretic cephaloceles is generally good

22. Atretic Occipital cephalocele
• Small defect containing just dura, fibrous and dysplastic brain
tissue
• Good prognosis; low associated brain anomaly
• Small mass just above external occipital protuberance

23. Chiari Malformations
• Hans Chiari first described three subtypes(1891).
• Chiari I and Chiari II are the most commonly encountered
• Chiari Variants - Chiari 0, 1.5, and IV.

24. Chiari I Malformation
• Most common
v Cxd by cerebellar tonsillar protrusion below the
foramen magnum in the absence of an open spinal
dysraphism or intracranial mass effect.
• Incidental (14% vs 50 % asymptomatic)
• Classic c/f -occipital headache induced or exacerbated by
a Valsalva maneuver.
– brainstem compression, syringomyelia, or scoliosis.

25. Imaging features
• Elongated, peg-shaped (abnormal pointed) cerebellar
tonsils
• Tonsillar descent ≥5 mm below McRae line
• Crowded foramen magnum
• Normal vermis, 4th ventricle and medulla

26. Associated conditions
• Hydrocephalus in 10% (up to 30 %) of cases
• Syringomyelia (40-80% of symptomatic)

27. Associated conditions
• Skeletal anomalies ~35%:
v Basilar invagination ( tip of the odontoid process
projects above the foramen magnum ) , 30%
v syndromic associations
• Klippel-Feil syndrome : fusion of 2 or more cervical
vertebrae(10%)
• Posterior fossa decompression ( suboccipital
craniectomy and C1 laminectomy)

28. Ddx-Chiari I Malformation
• Normal variants － "low-lying" tonsils
(rounded)
• Acquired tonsillar herniation (Increased ICP)
• Signs of descending transtentorial
herniation
• downward midbrain displacement
• Chiari 1.5
v Brainstem descent + tonsillar ectopia
v posteriorly angled odontoid
v cervicomedullary "kink"

29. Chiari II Malformation
v Dx
• Displacement of the medulla, fourth ventricle and cerebellum
• Myelomeningocele is universally present, typically lumbar

30. Imaging features-Antenatal Ultrasound
• Bifrontal concavity of the calvarium (“lemon” sign)
– indentation of the frontal bone
• Flattened cerebellum wrapping around the
brainstem (“banana sign”)
• Fetal ventriculomegaly
• Myelomeningocele
• Associated malformations (e.g. corpus callosal
dysgenesis)

31. Imaging features -Infratentorial
• Small posterior fossa+downward sloping tentorium
• Inferiorly displaced medulla, vermis
• Tectal beaking.
• “Straw shaped” fourth ventricle
• Hypogenesis of the corpus callosum
• Prominent massa intermedia
• Heart shaped cerebellum

32. Imaging features-Supratentorial
• Hydrocephalus almost always present before shunting
• Fenestrated Falx(marked by interdigitating hemispheric sulci)
• Stenogyria ( numerous and small gyri) 50%
• Subependymal gray matter heterotopia

33. Imaging features cont..
vSpinal Cord
• Myelomeningocele
• Cervicomedullary kink (pressure effect), 70%
• Syringohydromyelia and diastematomyelia,50%
vOsseous Abnormalities
• Scalloped clivus and petrous ridge (pressure effect)
• Enlarged foramen magnum

34. Ddx-Chiari II Malformation
• Chiari 1
A.Tonsils (not the vermis) that are herniated inferiorly.
B. Myelomeningocele is absent
C. Posterior fossa and its contents appear relatively normal.
• Chiari 3
– CM2 plus a low occipital or high cervical cephalocele
• Chiari 1.5
– posteriorly angled odontoid, brainstem descent, and tonsillar
ectopia without myelodysplasia

35. Chiari III Malformation
• The rarest of the Chiari malformations
v Features similar to Chiari II but with an occipital
and / or high cervical encephalocele
ü Small posterior fossa
ü Caudally displaced brainstem
ü Low occipital or upper cervical bony defect
Ddx: Isolated occipital cephalocele

36. Chiari Variants
A) Chiari 0 Malformation
• Hydrosyringomyelia and FM "crowding."
• Cerebellar tonsils are normally positioned
• Chiari 0 patients are typically symptomatic (usually
because of the syrinx)
• Sagittal T2 scans show thoracic syrinx ſt. The cerebellar tonsil is rounded
and in normal position, but the FM appears "crowded" posteriorly

37. Chiari Variants cont..
B) Chiari 1.5 Malformation
• Cerebellar tonsillar herniation is + (e.g., caudally displaced
brainstem and fourth ventricle and/or cervicomedullary
"kink").
• Syringomyelia in 50% of cases
• spina bifida and myelodysplasia are absent
• shows retroflexed odontoid st, tonsillar herniation ſt,
crowded FM, and low-lying nucleus gracilis .

38. Chiari Variants cont..
C) Chiari 4 Malformation
• The terms "primary cerebellar agenesis" or "severe cerebellar hypoplasia"
should be used instead
• Posterior fossa is normal in size and mostly filled with CSF.
• Pons appears small and flat.
• No myelomeningocele

39. Disorders of Regionalization
• Holoprosencephaly
• Septo-optic Dysplasia
• Dysgenesis of the Corpus Callosum
• Dandy Walker Malformation

40. Holoprosencephaly
v Abnormal communication of gray and/or
white matter across midline.
• Failure of normal midline prosencephalic
cleavage at 5th wks
• 50% of patients have trisomy 13
• Materal DM, rubella, toxoplasmosis,
syphillis, fetal alcohol syndrome
• Associated with azygos ACA
• Facial dysmorphism ( 80%)

41. Holoprosencephaly:Clinical Picture
• Facial abnormalities usually correlate with severity of
brain abnormalities but not vice versa
v "the face predicts the brain"
• Hypotelorism (eyes too close together)
• Cleft lip &/or palate
• Cyclopia (single eye)
• Craniofacial anomaly absent or mild - lobar type

42. Two major classes
1) Classic HPE
A. Alobar
B. Semilobar
C. Lobar
2) HPE variant
– Middle interhemispheric variant
of HPE-Syntelencephaly
v Presence of a septum pellucidum
excludes the diagnosis of HPE

43. Holoprosencephaly:Alobar
• No cleavage into two hemispheres : flat
("pancake") to cup- or ball-shaped brain
• Single U-shaped monoventricle almost always
communicates with a large dorsal cyst
• Absent third ventricle

44. Holoprosencephaly:Alobar
• Absent falx,sagittal sinus , corpus callosum , fornix
, olfactory bulbs and tracts
• Fused thalami and basal ganglia
• optic nerves can be normal, fused, or absent
• Brainstem and cerebellum are structurally normal

45. Ddx:Alobar Holoprosencephaly
• Hydranencephaly
– Not associated with midline facial abnormalities
– Normal or large head with fluid-filled cranial
vault ("water bag" brain)
– Falx is present and BG/thalami are separated
– No cortex present or sometimes small islands
of tissue
– Normal posterior fossa.

46. • Severe "open lip" schizencephaly
– Falx and tentorium are normal

47. Holoprosencephaly:Semilobar
• Partial cleavage into hemispheres (posterior cerebral hemispheres)
, partially fused anteriorly
• Partial occipital and temporal horns
• If a rudimentary third ventricle is present, the thalami may be
partially separated.
• Basal ganglia and hypothalami are still largely fused

48. Holoprosencephaly:Semilobar cont..
• Septi pellucidi are absent.
• Dorsal cyst 1/3 of the case.
• Corpus callosum splenium is present, but
the body and genu are absent(Barkovich)

49. Holoprosencephaly:Lobar
• Complete cleavage into two hemispheres
– except for fusion in the most rostral aspect of the frontal
neocortex
• well-developed occipital horns and third ventricle
• Frontal horns almost always appear
dysmorphic(squared).
• Hippocampi often more vertically oriented
• Splenium and most of the body of CC identified

50. Ddx:Lobar Holoprosencephaly
• Septooptic dysplasia
– Frontal horns are well formed
– Fusion of the frontal lobes and of
the fornices is not a feature

51. Middle interhemispheric variant of HPE
(syntelencephaly)
ü CC genu and splenium are formed; however, the body is missing
ü Upward extension of an anomalous sylvian fissure across the midline
ü Midportions of the hemispheres appear fused across the midline

52. Septo-optic Dysplasia( de Morsier
syndrome)
• Mild form of lobar holoprosencephaly
• Optic nerve and chiasm hypoplasia
• Absence of septum pellucidum
• Hypoplastic pituitary stalk ( 2/3 of cases)
• Associated anomalies:Schizencephaly (50 % ),callosal dysgenesis- SOD plus
• Optic nerve hypoplasia is more reliably diagnosed on ophthalmologic examination
• Only 50% of affected patients have appreciable optic nerve hypoplasia on MRI.

53. Imaging findings -SOD
• Hypoplastic optic chiasm and absent septi
pellucidi
• Box-like or "squared-off" appearance of the
frontal horns
• Inferior pointing of both frontal horns
• Empty-appearing lateral ventricle with low-
lying fornix

54. Dysgenesis of the Corpus Callosum
• Development: Genu → body → splenium →
rostrum(last)
• The part formed later will absent(except in destructive
causes and holoprosecencephaly)
• Splenium should be at least as thick as the genu by 1
year of age
Types
• Complete CC Agenesis
• CC Hypogenesis

55. Complete CC Agenesis-
Sagittal
• Anterior commissure (AC) often present
• Hippocampal commissure (HC) absent
• Cingulate gyrus absent
– with radiating "spoke-wheel" gyral
pattern extending perpendicularly to the
roof of the third ventricle

56. Coronal
• “Viking helmet” or “moose head” appearance-
frontal horns small & pointed
• “High-riding” third ventricle-which appears
continuous with the interhemispheric fissure
• Probst bundles
• Heterotopic GM

57. Axial
• Parallel and widely separated Ventricles- racing car sign
• Colpocephaly (dilatation of the trigones and occipital
horns)-teardrop configuration

58. CC Dysgenesis-Association and Clinical Picture
• Associated CNS anomalies occur in 60%
1. Chiari II-most common
2. Interhemispheric cysts or lipomas (calcified in
10%)
3. Underrotation of the hippocampi
4.DW malformation
5. Encephalocele
6. Migration anomalies
• The most common clinical manifestations-
refractile seizures &/or developmental delay

59. Associated CNS anomalies cont..

60. Dandy–Walker Continuum
• Spectrum of anomalies that includes DWM, VH,
BPC, and MCM
• Tegmento-vermian angle (normally < 18°)
• Fastigium-declive ~50% of the vermis should lie
below this line

61. Dandy-Walker malformation (DWM)
• Consists of:-
A. Large posterior fossa (PF)
B. Cyst extending posteriorly from fourth ventricle
C. Vermian agenesis or hypogenesis
○ Seriously increased tegmento-vermian angle ( > 45°)
D. Torcular-lambdoid inversion (sinus confluence and
tentorial apex are elevated above the lambdoid suture)
• The fourth ventricle choroid plexus is absent.

62. DWM cont..
• Generalized obstructive hydrocephalus is common
complication >80% at birth

63. Vermian hypoplasia (VH)
• Old term = Dandy-Walker variant
• Reduced vermian tissue below fastigium-
declive line
• Superior rotation of vermis
– Increased tegmento-vermian angle (18-45°)
• PF normal size
• More common than DWM
• Hydrocephalus -25 %
• "keyhole" appearance of the fourth
ventricle

64. Blake pouch cyst (BPC)
• Ependyma-lined protrusion from fourth ventricle
through the foramen of Magendie
• Normal size and morphology of vermis
• Elevated vermis
– Increased tegmento-vermian angle (18-45°)
• Tetraventricular Hydrocephalus
• delayed or incomplete perforation foramen of
Magendie and foramina of Luschka

65. Mega cisterna magna (MCM)
• Enlarged retrocerebellar CSF collection (> 10 mm).
• No mass effect on the cerebellar hemispheres or vermis.
• Vermis is normal with tegmento-vermian angle (< 18°)
• Fluid crossed by veins, falx cerebelli
• No hydrocephalus
• Accounting 54% of cystlike posterior fossa
malformation
• May scallop, remodel occiput**
** All categories in DWC may "scallop" inner occipital bone

67. Ddx:Dandy-Walker Continuum
Arachnoid Cyst
• Cerebellopontine angle > retrovermian
• No communication with 4th ventricle
• No crossing veins or falx cerebelli
• Causes mass effect

68. Miscellaneous Malformations
• Joubert Syndrome and Related Disorders
(JSRD)
v classic findings:-
A. vermian hypoplasia
B. “Molar tooth sign” - thickening and
elongation of the superior cerebellar
peduncles
C. Bat wing 4th ventricle

69. Rhombencephalosynapsis
• Incomplete separation of the cerebellar
hemispheres
– transversely oriented continuous folia
• Partial or complete absence of the vermis
– flattened fastigial recess
• Aqueductal stenosis in 65% cases

70. Disorders of Cortico-genesis
• Brain malformations as a result disturbances:-
1. Glial/Neuronal Proliferation or Apoptosis
2. Neuronal migration, and/or
3. Cortical organization(Postmigration development)

72. Microcephaly
• Head circumference more than three standard deviations
below the mean for age and sex
• Marked decrease in cranial-to-facial proportions
• Slanted frontal bones
•
v Primary- genetic
• Three types of primary microcephaly (gyral patterns,
cortical thickness)
v Secondary –Infection. Ischemia, Maternal DM, Trauma

73. Types of primary microcephaly
1) Microcephaly with simplified gyral pattern
(MSG)
– gyri reduced in number with shallow
sulci(hallmark)
– cortex is normal or thinned, not thickened.

74. Types of primary microcephaly cont..
2) Microlissencephaly
– The most severe manifestation of decreased cellular
proliferation
– Brain is extremely small
– Sulcation pattern appears greatly simplified or almost
completely smooth
– Cortex is thickened, usually measuring > 3 mm
3) Microcephaly with extensive polymicrogyria
– Polymicrogyria is the predominant gyral pattern

75. Ddx: primary microcephaly
• Secondary microcephaly
– Calcifications, cysts, gliosis, and
– Encephalomalacia

76. Hemimegalencephaly
• Cxd by hamartomatous overgrowth all or a part of a
cerebral hemisphere
• < 5% of MCDs
Imaging findings
• Large, dysplastic-appearing hemisphere
• Ipsilateral ventricle large and malformed
• Falx inserts off midline
• Thick cortex + focal subcortical masses of dysplastic
GM

77. Imaging findings cont..
Fig:
• CT-enlarged right hemisphere, lateral
ventricle with right hemispheric WM
appears less hypodense than the left
• Off midline insertion of the falx ( Initial
diagnosis was left MCA stroke)
• MR-extensive cortical thickening
• Closely evaluate the contralateral
hemisphere to exclude additional
abnormalities-hemispherotomy

79. Lissencephaly-pachygyria Spectrum
• spectrum of diseases that cause relative
smoothness of the brain surface
• Types
• Type I (classic) lissencephaly
– usually associated with band heterotopia.
A. Complete—Agyria (uncommon)
B. Incomplete—Pachygyria-agyria
• Type II (cobblestone) lissencephaly

80. Complete Type I (classic) lissencephaly
• Agyria (uncommon)
ü complete absence of gyri/sulci
ü “hour-glass” or “figure-of-8” appearance
• due to broad and shallow sylvian fissures
ü Thick inner band GM
ü Cell sparse WM zone ↓T1↑T2
ü Thin outer layer GM
• Associated with CC/SP agenesis/hypoplasia

81. Incomplete Type I (classic) lissencephaly
• Incomplete—Pachygyria-agyria
– Parietooccipital agyria with areas of broad, flat gyri ("pachygyria") and
shallow sulci along the inferior frontal and temporal lobes

82. Ddx: Type I (classic) lissencephaly
• Premature brain (up to 26 wks)

83. Type II (cobblestone complex) lissencephaly
• Unlike type I lissencephaly ,type II is due to
overmigration
• Microlobulated (bumpy or pebbly) cortical
surface
• Band heterotopia is not evident and the cortex
is thinner
• Associated with muscular dystrophy
syndromes

84. Ddx:Type II lissencephaly
• Lissencephaly type I
– cortex is thicker and smoother
• Polymicrogyria
– only affects a part of the brain
– often associated with schizencephaly

86. Schizencephaly
• Gray-matter lined cleft that extends from the
ventricular ependyma to the pial surface of the
cortex
• Lined by dysplastic gray matter
• Sometimes bilateral
• Two morphological types:
• closed lip (type I)
– the cleft walls are in apposition
– most common form in unilateral cases
– MR:nipple-like out-pouching at the ependymal
surface

87. Two morphological types cont..
• open lip (type II)
– the cleft walls are separated and filled with CSF
– most common form in bilateral cases
– Lined by dysplastic gray matter

88. Schizencephaly cont..
• Frequently associated (50-90%) with other cerebral
anomalies:
I. septo-optic dysplasia
II. grey matter heterotopia
III. absent septum pellucidum
IV. dysgenesis of the corpus callosum

89. Ddx:Schizencephaly
• Porencephaly
– Zone of encephalomalacia that extends from the
cortical surface to the ventricular surface
– Lined by gliotic white matter, not grey matter

90. Reference
• Osborns : BRAIN IMAGING,PATHOLOGY, AND ANATOMY, 2ed ©
2018
• BRANT : Fundamentals of Diagnostic Radiology, 5th ed © 2019
• Congenital brain abnormalities: Pictorial essay Eastern Journal of
Medicine (2015)
• Classification of Congenital Abnormalities of the CNS,AJNR,1987
• Radiopaedia.org, 2020

91. THANK YOU