Knowledge of developmental anomaly and physiology is fundamental to understanding some pediatric neurological disorders
Whole of the nervous system is derived from ectoderm except blood vessels and neuroglial elements
The relative position is altered by number of flexuresCervical flexureMesencephalic flexurePontine flexureTelencephalic flexure
The relative position is altered by number of flexuresCervical flexureMesencephalic flexurePontine flexureTelencephalic flexure
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).
cns embryology and anomalies
CNS DEVELOPMENT AND congenital anomalies HUSSEIN ABDELDAYEM, MD. Professor OF Pediatric Neurology Chief of Ped Neurology Unit, Department of Pediatrics. Alex University, Egypt
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 EVENT TIME OF OCCURRENCEOrgan induction 2 ½ - 8 weeks 1-4 WEEKS: NTD 4-8 WEEKS: HoloNeural Proliferation 2 – 5 monthsGlial cell 6 mo prenatally toProliferation 6 mo postantallyMyelination 2nd mo prenatally up to 3rd decadeSynaptogenesis 5 mo prenatally Through learning all life
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 A single sheet of cells – midline ectoderm Ectodermal plate enlargesNeural 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 platedevelopment -16th day Cranial closure 24th day (upper spine) Caudal closure 28th day (lower spine)
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.
CavitationRostral end:forebrain, midand hindbrain= central vesicle ventricular system
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.• `
• 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% -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
TYPES OF ONTDsPRIMARY -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
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 )
• 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
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.
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 1Treatment –• 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 at lower end of L 1• Motor weakness of lower limbs• Sphincteric problems such as inefficient bladder control.
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.
• 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 +
Prenatal detection of NTDSerum 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 syndromeOther chromosomal abnormalitiesDefects in the abdominal wall of the fetusTwins - more than one fetus is making the protein
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
AmniocentesisIndication: 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
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
The only most significant risk factorassociated with NTDs is folic aciddeficiency
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
Neural tube defects – preventionFolic acid deficiency:If previous history of NTD in family :4mg – 1 – 2 month before pregnancy To 3 months thereafterElse for every other women of child bearing age :0.4mg – 1 month before conception till 12 weeks gestation.
Nursing CareLike any other neonate with congenital anomaliesefforts should be towards careful examination andinvestigations to rule out other anomalies.Nursed in Trendlenburg position aiming to reducepressure and keep it away from cystic lesion.Much care not to disturb intact membrane (highincidence of infection and urgent surgery).
• 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
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 immaturity3- Ped Nephrologist/ Ped Urologist: – Start with on regular urinary catheterization – Urological Follow-up4-Orthopedic consultation: - severe kyphotic or scoliotic deformities - hip, knee and foot deformities5- Pediatric Neurologist:
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 SURGERYSURGERY NOT DONE IF –• Severe praplegia below L3 with bladder paralysis• Gross Hydrocephalus• ASSOCIATED LIFE THREATENING GROSS CONG. MALFORMATION.
LOBERS CRITERIA 1972 - FOR SELECTIVE SURGERYSURGERY NOT DONE IF –• Kyphosis• Associated gross congenital anomalies• Very large lesions• Infection of sac ormeningitis
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 :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.
.Various types of brain herniationdue 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.
CephaloceleThe 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
Cephaloceles Classification• Based on its contents: meningoencephaloceles, meningocele, atretic cephaloceles & glioceles.• Based on the bone defects : occipitocervical, occipital, parietal, frontal, te mporal, frontoethmoidal, sphenomaxillary, sp henoorbital, 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.
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
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 brains 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 babys 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