CNS DEVELOPMENT ANDcongenital anomalies

CNS DEVELOPMENT ANDcongenital anomalies

HUSSEIN ABDELDAYEM, MD.

Professor OF Pediatric NeurologyChief of Ped Neurology Unit,Department of Pediatrics.

Alex University, Egypt

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Phases of Development

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

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EVENTS OF IMPORTANCETIME OF

OCCURRENCEEVENT

1-4 WEEKS: NTD4-8 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

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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

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 dayCaudally completed by 28th day

Thus neural tube formation completed by 4th week

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Neural Tube Development

Normal embryological development

ÞNeural plate development -16th day

ÞCranial closure 24th day (upper spine)

ÞCaudal closure 28th day (lower spine)

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•

Neural plate at forehead

1st occipital

somite

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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.

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Cavitation

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• 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.

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.

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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

• 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:

Folic acid deficiency:Drugs antagonizing folic acid:Valproic acid, CBZ, phenytoin, phenoba., alcohol,

thalidomide, irradiation, maternal diabetesSyndromal 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 NTDSECONDARY

-5% of all NTD. Abnormal development of lower sacral

segment during secondary neuralization• Skin is usually intact• Involves lumbo-sacral regionEg. Spina Bifida Occulta Meningocele

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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 )

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• 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

25Dimple

26Tuft of hair

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Dimple with nauves port wine

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MeningoceleMeningocele• 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.

MeningoceleInvestigation:-• 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

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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.

31Autopsy of Infant with tethered cord

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MyelomeningoceleMyelomeningocele• 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.

• 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 +

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Myelomeningocele

Spina bifida

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Intact Mylomeningocele

Thin transparent membrane

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Intact Mylomeningocelecovered by thin membrane

surrounded by hyper pigmentation

ARNOLD CHIARI SY ARNOLD CHIARI SYNDROME NDROAME

ARNOLD CHIARI SYNDROME

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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

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 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

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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?

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Factors Associated With Increased Risk of NTDs. . .

Factors Associated WithIncreased 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

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

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Folic Acid For WomenFolic 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

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?

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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).

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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

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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 closure2- 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 deformities5- Pediatric Neurologist: الكل فى الكل

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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

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.

LOBERS CRITERIA 1972 - FOR SELECTIVE SURGERY

SURGERY NOT DONE IF – • Kyphosis• Associated gross congenital anomalies• Very large lesions• Infection of sac ormeningitis

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Post-operative

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Fetal Treatment

• Anencephaly is a type of ONTDs• Anencephaly and spina bifida are

the most common ONTDs

ANENCEPHALY

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 :polyhydroamniosAt 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

• 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

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

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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.

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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 GDD , MR , seizures ,

hydrocephalus , endocrine dysfunction

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