targets: medical students and postgraduate

1. CNS DEVELOPMENT AND
congenital anomalies
HUSSEIN ABDELDAYEM, MD.
Professor OF Pediatric Neurology
Chief of Ped Neurology Unit,
Department of Pediatrics.
Alex University, Egypt

2. Phases of Development
• Certain elements of the nervous system are
quite mature at FT, other continue their
development throughout infancy and
childhood
2

3. EVENTS OF IMPORTANCE
TIME OF
OCCURRENCE
EVENT
1-4 WEEKS: NTD
4-8 WEEKS: Holo
2 ½ - 8 weeks
Organ induction
2 – 5 months
Neural Proliferation
6 mo prenatally to
6 mo postantally
Glial cell
Proliferation
2nd mo prenatally
up to 3rd decade
Myelination
5 mo prenatally
Through learning all
life
Synaptogenesis
3

4. Organ Induction
• 16th day: embryo is 3 layers (ectod, mesod,
endo)
• 18th day: notochord mesod induces ectod
thickening in the central portion to form he
neural plate
• 28th day: complete neural tube
4

5. EMBRYOLOGY
Nelson.
A single sheet of cells – midline ectoderm
Ectodermal plate enlarges
Neural folds become elevated and fuse forming
Neural tube
Fusion occurs in cervical region and proceed
both caudally and cephalic, by secondary
neuralization
Cephalic completed by 23rd day
Caudally completed by 28th day
Thus neural tube formation completed by 4th
week

6. Neural Tube
Development
Normal embryological
development

Neural plate
development -16th day

Cranial closure 24th
day (upper spine)

Caudal closure 28th
day (lower spine)
6

7. •
7
Neural plate at forehead
1st occipital
somite

8. 8

9.  The central nervous system
(CNS) appears at the beginning
of the third week as a slipper-
shaped plate of thickened
ectoderm, the neural plate, in
the middorsal region in front of
the primitive node.
Its lateral edges soon elevate to
form the neural folds.

10. Central Nervous System
 The cephalic end of the neural tube shows
three dilations, the primary brain vesicles:
1. The prosencephalon, or forebrain;
2. The mesencephalon,or midbrain;
3. The rhombencephalon, or hindbrain.
 Simultaneously it forms two flexures:
A. The cervical flexure at the junction of the
hindbrain and the spinal cord.
B. The cephalic flexure in the midbrain region.
 When the embryo is 5 weeks old, the
prosencephalon consists of two parts:
i. The telencephalon, formed by a midportion
and two lateral outpocketings, the primitive
cerebral hemispheres,
ii. The diencephalon, characterized by
outgrowth of the optic vesicles.

11. Cavitation
Rostral end:
forebrain, mid
and hindbrain
= central vesicle 
ventricular system
11

12. 12

13. Spinal cord
• Develops from caudal
cylindrical part of neural
tube
• Cavity of the tube
bounded by thick lateral
wall, thin roof and floor

14. POSITIONAL CHANGES OF THE CORD
• In the third month of development the spinal
cord extends the entire length of the embryo,
and spinal nerves pass through the
intervertebral foramina at their level of origin.
• With increasing age, the vertebral column
and dura lengthen more rapidly than the
neural tube, and the terminal end of the
spinal cord gradually shifts to a higher level.
• At birth, this end is at the level of the third
lumbar vertebra.
• As a result of this disproportionate growth,
spinal nerves run obliquely from their
segment of origin in the spinal cord to the
corresponding level of the vertebral column.

15. POSITIONAL CHANGES OF THE CORD
• The dura remains attached to the vertebral
column at the coccygeal level.
• In the adult, the spinal cord terminates at the
level of L2 to L3,
• The dural sac and subarachnoid space extend
to S2.
• Below L2 to L3, a threadlike extension of the
pia mater forms the filum terminale, which is
attached to the periosteum of the first
coccygeal vertebra and which marks the tract
of regression of the spinal cord.
• Nerve fibers below the terminal end of the
cord collectively constitute the cauda equina.
• `

16. Disorders of Neuralization
(1-4 w gestation)

17. • During pregnancy, the human brain and spine
begin as a flat plate of cells, which rolls into a
tube, called the neural tube. If all or part of
the neural tube fails to close, leaving an
opening, this is known as an open neural tube
defect, or ONTD. This opening may be left
exposed (80 percent of the time), or covered
with bone or skin (20 percent of the time).

18. Disorders of closure of Neural tubes
• 1- Anencephaly
• 2- Neural tube defect (spinal defect)
• 3- encephalocele

19. • ONTDs →95% -ve FH
• ONTDs result from a combination of genes
inherited from both parents, coupled with
environmental factors. For this reason, ONTDs
are considered multifactorial traits, meaning
"many factors," both genetic and
environmental, contribute to their occurrence
Open Neural Tube Defects
ETIOLOGY:

20. Folic acid deficiency:
Drugs antagonizing folic acid:
Valproic acid, CBZ, phenytoin, phenoba., alcohol,
thalidomide, irradiation, maternal diabetes
Syndromal disorders: trisomy 18, 13,
Malnutrition – zinc , folate def.

21. TYPES OF ONTDs
PRIMARY
-95% of all NTD
Primary failure of closure/disruption of NT
btw 18-28 days.
Eg. -Myelomeningocele
Encephalocele
Anencephaly

22. TYPES OF NTD
SECONDARY
-5% of all NTD.
Abnormal development of lower sacral
segment during secondary neuralization
• Skin is usually intact
• Involves lumbo-sacral region
Eg. Spina Bifida Occulta
Meningocele

23. Spina Bifida Occulta
• Very mild & common form.
• Level - L5 & S1.
• Asymptomatic which can only
detected by x-ray or
investigating a back injury.
• May be associated with
tethered cord/ recurrent
meningitis ( dermal sinus )
23

24. • Usually associated with skin visible signs on the back.
– Dimple
– Dermal Sinus
– lipoma / Pad of subcutaneous fat
– small hair growth
– Nevus flaminous (red spot) or port wine
24

25. Dimple 25

26. Tuft of hair 26

27. Dimple with nauves port wine
27

28. Meningocele
• Least common form
• Sac contains meninges and
cerebro-spinal fluid. And covered
with skin
• Cerebro-spinal fluid protects the
brain and spinal cord.
• The nerves are not badly damaged
and able to function normally.
• Small sac which increases on crying
• Limited disability is present.
28

29. Meningocele
Investigation:-
• MRI HEAD – exclude hydrocephalus/ dysgenesis
• MRI SPINE – exclude
(i)Diastematomyelia – division of spinal cord into two
halves by projection of fibrocartilagenous or bony septum
from post vertebral body
(ii) Tethered cord – slender threadlike filum terminale
attached to coccyx conus here is below L2 instead L 1
Treatment –
• Skin intact – surgery in infancy
• Skin lacerated – urgent treatment
• Look for recto vaginal fistula

30. Tethered cord
• The spinal cord could be
caught against the
vertebrae
• Normal cord ends at lower
end of L 1
• Motor weakness of lower
limbs
• Sphincteric problems such
as inefficient bladder
control. 30

31. Autopsy of Infant with tethered cord
31

32. Myelomeningocele
• Most serious and common
• The cyst not only contains
meninges and CSF but also the
nerves and spinal cord.
• The spinal cord is damaged or
not properly developed resulting
in motor and sensory deficit.
• Majority have bowel and
bladder problems.
32

33. • Myelomeningocele, is the most severe and
occurs when the spinal cord is exposed
through the opening in the spine, resulting in
partial or complete paralysis. and may have
urinary and bowel dysfunction.

34. Meningomyelocele
Sac + CSF + neural element +
discontinuous skin +
hydrocephalus(80%).
TYPE – 94% of all NTD - Lumbo sacral
- Area of well developed skin at
periphery With thin apex covered by
glistening arachnoid membrane
- Usually CSF oozing +

35. Myelomeningocele
35

36. Spina bifida

37. Intact Mylomeningocele
37
Thin transparent membrane

38. Intact Mylomeningocele
covered by thin membrane
surrounded by hyper pigmentation
38

40. ARNOLD CHIARI SY ARNOLD CHIARI
SYNDROME NDROAME
ARNOLD CHIARI
SYNDROME

41. 41

42. Prenatal detection of NTD
Serum alpha-fetoprotein (AFP)
• Normal fetal glycoprotein (MW= 70,000)
• Present normally in amniotic fluid and mother
serum start 12 week increase steadily till 32
week
• High maternal serum AFP > 2 multiples of
median for appropriate week of gestation is
diagnostic
• 91% sensitivity in spina bifida
42

43. Alpha-fetoprotein screening
• Measures the level of AFP in mothers' blood
during pregnancy.
• Abnormal levels of AFP -
Open neural tube defects (ONTD)
Down syndrome
Other chromosomal abnormalities
Defects in the abdominal wall of the fetus
Twins - more than one fetus is making the
protein

44. Ultrasound
44
 Detect 90-95 % of cases of spina bifida
100% cases of anencephaly
 In cases of elevated AFP diffrentiate NTD
fron non-neurological causes of elevated AFP
e.g. omphalocele

45. Amniocentesis
45
Indication:
Pregnancies subsequent to NTD
Elevated AFP with normal US
 Show elevated AFP between 12-15 week
earlier than serum AFP
 Carries 6% risk of abortion and fetal loss

46. Is prophylaxis feasible?

47. Factors Associated With
Increased Risk of NTDs. . .
• Family history of NTD
• A previous pregnancy affected with NTD
• Maternal insulin-dependent diabetes
• Maternal obesity
• Anti-epileptic drugs (Valporic Acid, Carbamazapine)
• Lower socioeconomic/educational level, dietry
deficiency specially folic acid
47

48. The only most significant risk factor
associated with NTDs is folic acid
deficiency
48

49. Folic Acid For Women
• As NTD occur before diagnosis
of pregnancy.
• All women of childbearing age
should receive 400 micrograms
(0.4 mg) of folic acid daily.
• Women who have had a
previous child with NTD should
receive 4000 micrograms (4 mg)
of folic acid daily. 2 months
before pregnancy
49

50. Neural tube defects – prevention
Folic acid deficiency:
If previous history of NTD in family :
4mg – 1 – 2 month before pregnancy To 3 months
thereafter
Else for every other women of child bearing age :
0.4mg – 1 month before conception till 12 weeks
gestation.

51. What is the proper management?

52. Nursing Care
Like any other neonate with congenital anomalies
efforts should be towards careful examination and
investigations to rule out other anomalies.
Nursed in Trendlenburg position aiming to reduce
pressure and keep it away from cystic lesion.
Much care not to disturb intact membrane (high
incidence of infection and urgent surgery).
52

53. • Cover lesion with Gauze ring soaked with normal
saline or Ringer solution to prevent dryness
• Avoid antiseptics e.g betadine as it is Neurotoxic
affecting functioning roots in placode
• Avoid mechanical trauma to placode
• no need for ultra frequent dressing
53

54. General assessment (Multi-team)
1- Ped Surgery:
• Assess whether lesion is ruptured or unruptured
– Ruptured lesions start prophylactic antibiotic
– Urgent surgery
• Measure size and site of defect for proper planing for
closure
2- Neonatologist :
– Other anomalies (average 2-2.5% additional anomalies)
– Condition oppose with surgery e.g lung immaturity
3- Ped Nephrologist/ Ped Urologist:
– Start with on regular urinary catheterization
– Urological Follow-up
4-Orthopedic consultation:
- severe kyphotic or scoliotic deformities
- hip, knee and foot deformities
5- Pediatric Neurologist: ‫الكل‬
‫فى‬
‫الكل‬
54

55. Neurological Preop. Assessment
• Watch for spontaneous movement of lower limbs which
associated with better outcome.
• Check for reflexes, muscle power of LL. Check for SPHINTER
and ANAL reflexes
• Assess lowest level of neurological function
– Response to painful stimuli
– Differentiate between voluntary movement from reflex movement
which is stereotyped and not persist after stimulus
• Evaluate other neurological associations
– Hydrocephalus------ Arnold Chiari Syndrome
• Anterior fontanel
• Head circumference
• Brain U/S, Brain MRI
– Chiari II
• Check for inspiratory stridor and apneic episodes
55

56. LOBERS CRITERIA 1972 - FOR
SELECTIVE SURGERY
SURGERY NOT DONE IF –
• Severe praplegia below L3 with bladder
paralysis
• Gross Hydrocephalus
• ASSOCIATED LIFE THREATENING GROSS CONG.
MALFORMATION.

57. LOBERS CRITERIA 1972 - FOR
SELECTIVE SURGERY
SURGERY NOT DONE IF –
• Kyphosis
• Associated gross congenital anomalies
• Very large lesions
• Infection of sac ormeningitis

58. Post-operative
58

60. Fetal Treatment
60

61. • Anencephaly is a type of ONTDs
• Anencephaly and spina bifida are
the most common ONTDs
ANENCEPHALY

62. ANENCEPHALY
• Failure of closure of rostral neuropore.
• Large defect of calvarium, meninges, scalp
associated with rudimentary brain.
• Cerebral hemisphere and cerebellum
usually absent
• Die at birth or few days
• Etiology – genetic, environmental toxins,
nutrition

63. Symptoms
• In pregnancy :polyhydroamnios
At Birth:
• absence of bony covering over
the back of the head
• missing bones around the front
and sides of the head
• folding of the ears
• Associated anomalies-
- cleft palate
- congenital heart defects
• some basic reflexes, but
without the cerebrum, there
can be no consciousness and
the baby cannot survive

64. Prenatal Diagnosis
• U/S
• Maternal alpha-
fetoprotein - AFP
increased
• amniocentesis - a test
performed to
determine
chromosomal and
genetic disorders and
certain birth defects.

65. Encephalo-meningocele

66. .Various types of brain herniation
due to abnormal ossification of the
skull.

67. Cephalocele
• a defect in the skull and dura
with extracranial herniation
of intracranial structures
• They can occur in isolation or
with various syndromes.

68. Cephalocele
The swelling is:
• soft to firm in consistency,
• non pulsatile
• no impulse on crying.
• no discharge or leak from the swelling.
• the lesion remained static in size over
these years.
• Developmental milestones were normal

69. ENCEPHALOCELE
• Contains sac + cerebral cortex +
cerebellum + brain stem
• Site:
mainly: OCCIPITAL region,
less : in frontal or nasofrontal

71. 71

72. 72

73. 73

74. Investigation
MRI

76. • Based on its contents:
meningoencephaloceles, meningocele, atretic
cephaloceles & glioceles.
• Based on the bone defects : occipitocervical,
occipital, parietal, frontal, temporal,
frontoethmoidal, sphenomaxillary,
sphenoorbital, nasopharyngeal and lateral.
Occipital cephaloceles originate between the
foramen magnum and the lambda They
contain dysplatic and gliotic brain tissue
within.
Cephaloceles Classification

77. Associated anomalies/disorders
• absent corpus callosum,
• orofacial clefting,
• craniostenosis,
• Dandy-Walker defect,
• Arnold-Chiari defect
• Microcephaly,
• Epilepsy , MR , motor impairment ,cortical
blindness in occipital encephaloceles

78. R/
• In small lesions :surgical excision and closure of small
defects
• R/ of seizures & hydrocephalus

79. 79

80. Midline malformation of the fetal brain
(4-8ws gestation)
Holoprosencephaly :
• is a disorder caused by the failure of
the prosencephalon (the embryonic
forebrain) to sufficiently divide into
the double lobes of the cerebral
hemispheres resulting in a single-
lobed brain structure and severe
skull and facial defects.
•

81. Midline malformation of the fetal brain
(4-8ws gestation)
Holoprosencephaly :
In most cases of holoprosencephaly, the
malformations are so severe that babies die before
birth.
• In less severe cases, babies are born with normal or
near-normal brain development and facial
deformities that may affect the eyes, nose, and
upper lip.

82. Case presentation
• 20 mo boy with : GDD ( 2-3 mo mental age)
and CP mixed ( spastic and dyskinetic-
dystonia) with myoclonic seizures . No
consanguinity. Normal Pre and perinatal
History
82

83. 83

84. 84

85. 85

86. 86

87. 87

88. Three classifications of
holoprosencephaly
• Alobar, in which the brain has not divided at all, is usually
associated with severe facial deformities.
• Semilobar, in which the brain's hemispheres have somewhat
divided, causes an intermediate form of the disorder.
• Lobar, in which there is considerable evidence of separate
brain hemispheres, is the least severe form. In some cases of
lobar holoprosencephaly the baby's brain may be nearly
normal.
• Middle interhemispheric variant :hypoplasia of the middle
part of the corpus callosum & associated sts of medial side of ‘
hemisphere

89. • 93% midline facial defects , single nare ,
hypertelorism , midline cleft palate & cleft lip
e’ single median eye
• Others have normal face .
• CP +: severe GDD , MR , seizures ,
hydrocephalus , endocrine dysfunction

90. 90