Anomaly

Anomaly in
in
CNS
CNS and
and Endocrine
Endocrine
Development
Development

Phases of Prenatal Development

Ovum + sperm
zygote

Once zygote
implants in
uterus
embryo

Week 8 until
birth
fetus

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

EVENTS OF IMPORTANCE

TIME OF
OCCURRENCE
1-4 WEEKS: NTD 2 - 8 weeks
4-8 WEEKS: Holo
2 5 months

EVENT
Organ induction

Neural
Proliferation
6 mo prenatally Glial cell
to
Proliferation
6 mo
postantally
2nd mo
Myelination
prenatally up to
3rd decade
5 mo prenatally Synaptogenesis

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

The University of South Wales, Dr. Mark Hill

Phases of brain development

Neural plate induction
Neural proliferation
Migration & Aggregation
Axon growth & Synapse formation
Cell death & Synapse
rearrangement

EMBRYOLOGY
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
Nelson.

EMBRYOLOGY
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
Nelson.

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

Neural plate at forehead

1st occipital
somite

12

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 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.

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.

Cavitation

16

Rostral end:
forebrain, mid
and hindbrain
=

central vesicle
ventricular
system

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

POSITIONAL CHANGES OF THE

CORD
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.

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

Disorders of
Neuralization
(1-4 w gestation)

 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).

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

Open Neural Tube Defects

ETIOLOGY:

ONTDs 95%
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

 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.

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

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

Spina Bifida Occulta

Very mild
form.

&

common

Level - L5 & S1.

Asymptomatic
which
can only detected by xray or investigating a
back injury.
May be associated with
tethered cord/ recurrent
meningitis
(
dermal
sinus )

28

 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

29

Dimple

30

Tuft of hair
31

Dimple with nauves port wine

32

Meningocele
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.

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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

Tethered cord
The spinal cord could
be caught against the
vertebrae
Normal cord ends
lower end of L 1

at

Motor
weakness
lower limbs

of

Sphincteric
problems
such
as
inefficient
bladder control.

35

Autopsy of Infant with tethered cord

36

Myelomeningocele
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.

37

 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.

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 +

Myelomeningocele

40

Spina bifida

Intact Mylomeningocele

Thin transparent membrane

42

Intact Mylomeningocele
covered by thin membrane
surrounded by hyper pigmentation

43

ARNOLD CHIARI SY ARNOLD

CHIARI SYNDROME
NDROAME

ARNOLD CHIARI
SYNDROME

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Prenatal detection of NTD

47

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

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

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Ultrasound

Detect

In

90-95 % of cases of spina bifida

100% cases of anencephaly

cases of elevated AFP diffrentiate NTD

fron non-neurological causes of elevated AFP
e.g. omphalocele

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Amniocentesis

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

Is prophylaxis feasible?

Factors
Associated
With
Factors
Associated
With
52
Increased
Increased Risk
Risk of
of NTDs.
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

53

The only most significant

risk factor associated with
NTDs is folic acid deficiency

Folic
Folic Acid
Acid For
For Women
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

54

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.

What is the proper management?

Nursing Care

57

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).

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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

Post-operative

59

E
R
U
T
U
F
E
H
T
R
FO

Fetal Treatment
61

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

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

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

Prenatal Diagnosis

U/S

Maternal alpha-fetoprotein AFP increased

amniocentesis - a test
performed to determine
chromosomal and genetic
disorders and certain birth
defects.

Encephalo-meningocele

.Various types of brain herniation

due to abnormal ossification of the
skull.

Cephalocele

a defect in the skull and dura

with extracranial herniation of
intracranial structures

They can occur in isolation or

with various syndromes.

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

ENCEPHALOCELE
Contains sac + cerebral cortex + cerebellum + brain
stem

Site:
mainly: OCCIPITAL region,
less : in frontal or nasofrontal

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Investigation
MRI

Cephaloceles Classification
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.

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

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

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.

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.

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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

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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

 93% midline facial defects , single nare

, hypertelorism , midline cleft palate &
cleft lip e single median eye
Others have normal face .
CP +: severe , MR , seizures ,
hydrocephalus , endocrine dysfunction

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Thank You