Malformations & Developmental Diseases Part 1 Flashcards
The anatomic pattern of malformation reflects ________ ____ ___________ at time of injury.
______ or ______ insults may cause failure of development and/or tissue destruction.
_______ & _______ are contributing factors to malformations.
Stage of brain formation
Prenatal, perinatal
Genetics, environment
Definitions
- Malformation
- Deformation
- Disruption
- Malformation – intrinsic abnormality
- Deformation – extrinsic force
- Disruption – destructive force
What is the deformation sequence of renal agenesis?
What are the steps to normal development of the CNS? (5)
- Induction
- Neural tube formation
- Regionalization & specification
- Proliferation & migration
- Connection & selection
Major Events in Human Brain Development
*fill in the blanks*
What stages are pictures A, B & C?
A. Late presomite & early neural plate stage
B. Early somite & neural groove stage
C. Eight-somite & early neural tube stage
Gestation
When/where does neural tube closure occur?
What happens with failure of closure?
- Neural tube closure occurs early in gestation
- 28 days
- Closure occurs at several sites along neuraxis
- Failure of closure at these sites results in defects (anencephaly, spina bifida)
Sulcation of the Brain
*how many months?*
- Major fissures
- Secondary sulci
- Tertiary sulci
- Major fissures – 5 months
- Secondary sulci – 7 months
- Tertiary sulci – 9 months
What is the pattern of cerebral myelination?
What is this?
Cytoarchitecture of the Cerebral Cortex
What is the definition of a neural tube defect?
- Most common category of CNS malformations
- Disturbance of formation of neuroectodermal and/or overlying mesodermal structures
What is the etiology of neural tube defects?
-
Genetics
- Trisomy 13, 18
-
“Environment” during pregnancy
- Folic acid deficiency
- Maternal DM
- Hyperthermia
- Alcohol
- Valproic acid (anti-seizure drug)
What is the pathogenesis of neural tube defects?
-
Failure of closure of neural tube
- Primary failure of neuroectoderm or mesoderm
- **Reopening or secondary rupture of closed tube **
What are the 3 main categories of neural tube defects?
- Spina bifida
- Anencephaly
- Encephalocele
Neural Tube Defects
Detection
Diagnosis
Prevention
- Failure of closure of the neural tube allows excretion of fetal substances (AFP, acetylcholinesterase) into the amniotic fluid
- Diagnosable by ultrasound and/or prenatal screening of maternal serum for AFP at 16-18 week GA
- Maternal periconceptional use of folic acid supplementation reduces the incidence of NT defects by at least 50%
Spina Bifida
Definition
Types
- Combined malformations of vertebral column & spinal cord
- Types
- Spina bifida occulta (least severe form)
- Spina bifida cystica (80-90% lumbosacral)
- Meningocele (less common – 10-20%)
- Myelomeningocele (more common – 80-90%)
Spina Bifida Occulta
Definition
Clinical Presentation
- Non-closed vertebral arches w/o visible lesion (externally)
- Most often lumbosacral
- Often asymptomatic
- May be foot & gait abnormalities
- Patches of hair, lipoma, discoloration of skin or dermal sinus
How is spina bifida occulta diagnosed?
- Spine X-ray
- Defect in closure of the posterior vertebral arches & laminae (usually L5 & S1)
- May be associated w/ syringomyelia, diastematomyelia & tethered cord
- Recurrent meningitis of occult origin should prompt careful exam for dermal sinus tract
What is the definition of a meningocele?
- Cyst lined w/ meninges & dura (but no spinal cord)
- Herniated through vertebral defect
- Spinal cord may be normal, or may present w/ tethering, syringomyelia, or diastematomyelia
- Most are lumbosacral
What are the symptoms of a Meningocele?
- Little or no neurological defect
- Anterior Meningocele may project into the pelvis through a defect in the sacrum causing symptoms of constipation & bladder dysfunction
- Female patients may have associated anomalies of the genital tract (rectovaginal fistula, vaginal septa)
Meningocele
Diagnosis
Treatment
-
Diagnostic testing
- Plain X-ray
- MRI (spine)
- CT of head to rule out HCP
-
Treatment approaches
- Asymptomatic children w/ no neuro findings & full-thickness skin may have surgery delayed
- Patients w/ leaking CSF or thin skin covering should undergo immediate repair to prevent meningitis
Myelomeningocele
Definition
Cord abnormalities
Location
- Both meninges & spinal cord herniated through vertebral defect
- Usually broad-based
- Cyst (“cele”) often ruptures & skin covering absent
-
Variable cord abnormalities
- Complete disorganization & flattening
- Slight midline opening
- Most (75%) are lumbosacral
- *exposure of neurons to amniotic fluid damaging
What are the risk factors for a Myelomeningocele?
- ~1/4,000 live births
- Risk of recurrence after 1 affected child increases to 3-4% & increases to 10% w/ 2 previous abnormal pregnancies
- Certain drugs that antagonize folic acid (TMP, AEDs: CBZ, PHY, Pb, Primidone) increase the risk of Myelomeningocele
- Valproic acid causes NT defects in ~1-2% of pregnancies
What are the symptoms of a Myelomeningocele?
Complications?
- Extent & degree of neuro deficit depend on location
- CM
- Flaccid paralysis
- Absent DTRs
- Sensory deficit below the affected level
- Postural abn of the LE (clubfeet, subluxation of the hips)
- Constant urinary dribbling & relaxed anal sphincter
- Weakness or flaccid paralysis, sensory loss, bowel/bladder dysfunction
- Complications: meningitis, hydrocephalus, pneumonia
What are the complications of a Myelomeningocele?
What is a Chiari crisis?
- HCP in associated w/ type II Chiari defect (80%)
- Infants w/ HCP & Chiari II: symptoms of hindbrain dysfunction
- Difficulty feeding
- Choking, stridor, apnea
- VC paralysis
- Pooling of secretions
- Spasticity of UEs
-
Chiari crisis
- Downward herniation of the medullar & cerebellar tonsils
How is a Myelomeningocele treated?
- Multidisciplinary approach: surgeon, therapist, pediatrician
- Surgery: repair & shunting, orthopedic procedure, urologic evaluation
- GUT: regular catheterization to prevent UTI & reflux (PN & hydronephrosis), urine cult, serum elec, creatinine, renal scan, IV pyelogram, Utz
- Rehab: functional ambulation (sacral or LS lesion)
What is the prognosis for a Myelomeningocele?
- MR: 10-15%
- Most deaths occur before 4 YO
- 70% normal intelligence
- Learning problems & seizures common
- History of meningitis or ventriculitis adversely affect the ultimate IQ
Anencephaly
Definition
Diagnosis
Prognosis
- Large defect of the calvarium, meninges & scalp associated w/ a rudimentary brain (failure of closure of the rostral neuropore)
- Diagnosis: increased AFP in amniotic fluid
- Primitive brain: connective tissue + vessels + neuroglia
- Cerebral & cerebellar hemispheres usually absent
- Only residue of brainstem identified (eyes & CNs V-XIII intact)
- Die w/i several days of birth
- 1/1000 live births
- Recurrence risk: 4% –> 10% w/ 2 previously affected pregnancies
What is this?
Anencephaly
Encephalocele
Definition
Location
- Broad-based pedunculated masses of cerebral tissue & dura protruding through cranial defect, covered by skin
- Occipital region most common site
- Frontal/nasal locations more common in some countries
- Tissue mass attached by pedicle
- Ethmoidal location: “nasal glioma”
- Disorganization of remaining brain in cranial cavity
How is Encephalocele diagnosed?
- Plain X-ray of the skull & cervical spine
- Cranial utz
- In utero: AFP, biparietal diameter
What is the prognosis of an Encephalocele?
- Encephalocoele: at risk for visual problems, microcephaly, MR, seizures
- Meckel-Gruber syndrome: AR condition, occipital encephalocoele, cleft lip or palate, microcephaly, microphthalmia, abnormal genitalia, polycystic kidneys, polydactyly
What is this?
Encephalocele
wavy cortical architecture
