Congenital Neuropathology

Question 1

Pathological processes that can occur during embryonic development

Answer 1

• From earliest to latest:
• Neural Tube Defects
• Prosencephalic Development
• Cerebellar Development
• Malformations of Cortical Development
• Destructive Lesions
• Disordered formation of dendrites, synapses, axons, myelination

Question 2

Neural tube defects

Answer 2

• **failure of neural tube closure ==> neural tissue contiguous with the ectoderm
• Craniorachischisis totalis
• • Anencephaly
• • Encephalocele
• Tethering of spinal cord
  
  • Myelomeningocele/Chiari malformation
  • • Lipomyelomeningocele
  • • Dermal Sinus Tract
• • Spina Bifida Occulta

Question 3

Anencephaly/Cranioraschisis totalis cause/timing

Answer 3

• failure of closure of skull and skin ==> any formed brain degrades in utero
• totalis = complete lack of closure
• anencephaly = failure of closure of anterior neuropore
  
  • day 23-25

Question 4

Encephaloceles characteristics

Answer 4

• defect in skull w/protrusion of leptomeninges +/- brain
• epidermal covering over cranial neural tube closure defects

Question 5

Meningocele vs. Meningoencephalocoele vs. Meningohyrdoencephalocele

Answer 5

• meningocele = skin-covered, CSF-filled mass that is continuous w/the CSF in the spinal canal

Question 6

Myelomeningocele

Answer 6

• failure of closure of posterior neuropore
• Day 25-27
• cord at the level of closure failure and below is also malformed

Question 7

Spinal lipoma characteristic

Answer 7

• fat deposits w/in pouch created by closure failure

Question 8

Chiari malformations

Answer 8

• Chiari I: caudal cerebellar tonsillar ectopia, below the foramen magnum; association of chronic tonsillar herniation with syringomyelia
• Chiari II: complex malformation - myelomeningocele, hydrocephalus, hindbrain, spine abnormalities

Question 9

Type II Chiari malformation

Answer 9

• Elongation of cerebellar vermis pushed through foramen magnum
  
  • can blosk CSF flow
• type of myelomeningocele
• z-kinkink of brainstem @ medulla and “herniation” of cerebellum
• hydrocephalus due to blocking of aqueduct
• abnormalities of dural venous sinus

Question 10

Chiari I malformation characteristics

Answer 10

• protrusion/chronic herniation of cerebellar tonsils (vs. vermis in Chiari II)
• not typically discovered until after birth (vs. Chiari II present at birth)
• problem w/bony development (vs. Chiari II = neural tube defect); not associated w/myelomeningocele

Question 11

Symptoms of Chiari I malformation

Answer 11

• tussive headache when pressure increases due to trapping of CSF by herniated tonsils
• syringomyelia = cystic collection @ spinal cord
  
  • early syrinx formation ==> cape-pattern of loss of pain, temp sensation along back due to cyst @ spinal cord
  • urinary symptoms or bowel problems

Question 12

General sequence/timing of CNS development

Answer 12

• neural tube develops @ surface of embryo @ 14 days
  
  • neural tube closes between 18-26 days
  • neural crest cells form as neural tube closes
• primitive cerebral hemispheres @ ~7 weeks
• developing neurons & glia migrate from the germinal matrix ==> form cerebral cortex, basal ganglia, etc. ==> general structures formed @ 20 weeks
• second half of gestation = formation of gyri and sulci + neuronal differentiation
  
  • • formation of cerebellum

Question 13

Main general cause of neural tube defects

Answer 13

• failure of neurectoderm to forma complete, closed tube during primary neurulation
• OR disordered differentiation of the caudal cell mass into the conus medullaris and filum terminale during secondary neurulation

Question 14

Lipomyelocele/lipomyelomeningocele

Answer 14

• occurs when lipoma extends from subcutaneous tissues to dorsal aspect of cord ==> tethers cord inferiorly

Question 15

Dorsal dermal sinus tract

Answer 15

• = ectoderm-lined tract that trsngress dura and cause a communication between the skin and CSF
• can also cause tethering of the spinal cord

Question 16

Bony spina bifida occulta

Answer 16

• @ L5-S1
• = common incidental finding, often w/out symptoms

Question 17

Causes and impacts of tethered spinal cord

Answer 17

• @ birth: conus medullaris @ L3 level ==> L1-L2 in adult
• NTDs can “tether” spinal cord ==> prevent ascension of vonus over time
• physical tension ==> compromise of blood supply ==> spinal cord dysfxn

Question 18

Hydromyelia definition

Answer 18

• accumulation of CSF w/in central canal
• can occur w/obstruction of exit of central canal into subarachnoid space
• can occur w/Chiari Type I malformation

Question 19

myelopathy definition

Answer 19

• dysfunction of spinal cord
• can occur in Chiari Type I

Question 20

syringomyelia definition

Answer 20

• formation of CSF-filled cyst that breaks out of the central canal and dissects into cord
• can occur in Type I Chiari malformation

Question 21

Holoprosencephaly: stage of development

Answer 21

• occurs during the telencephalic development
• single ventricle (prosencephalon) fails to form properly into the two lateral ventricles and one third ventricle
• @ 5th week of fetal life

Question 22

Holoprosencephaly characteristics

Answer 22

• failure of ventricular formation from prosencephalon
• some degree of failure of two cerebral hemispheres to divide properly
• three types:
  
  • alobar holoprosencephaly
  • semilobar holoprosencephaly
  • lobar holoprosencephaly
• typically w/deformities of face and eyes
  
  • cyclopia, probiscus (long, deformed nose), midline facial clefts
• ==> microcephaly, absent olfactory/optic nerves, midline facial defects

Question 23

Alobar holoprosencephaly

Answer 23

• no evidence of division of cerebral cortex
• single forebrain w/single ventricle

Question 24

Semilobar holoprosencephaly

Answer 24

• only partial cleabage w/cerebral hemispheres fused @ the frontal region

Question 25

Lobar holoprosencephaly

Answer 25

• cerebral hemispheres are separated anteriorly and posteriorly w/some degree of fusion of other structure (e.g. thalami, corpus callosum)

Question 26

Important morphogen in prosencephalic (+ other CNS structures) development

Answer 26

• sonic hedgehog
• secreted from ventral sites ==> gradient that is lower dorsally ==> differential gene expression

Question 27

Dandy-Walker malformation

Answer 27

• cerebellar malformation
• partial or complete absence of formation of cerebellar vermis
• custic dilation of fourth ventricle
• upward displacement of the tentorium
• NOT a neural-tube defect or related to folate
• sx:
  
  • hydrocephalus
  • assoc/ w/other cerebral/visceral abnormalities

Question 28

Perinatal stroke characteristics (general)

Answer 28

• commonly due to other childhood conditions: vascular/heart malformations, clotting problems, sickle cells, etc.
• ischemic strokes = generally unidentifiable cause; hemorrhagic = usually definable etiology

Question 29

Cerebral palsy

Answer 29

• birth trauma and/or other perinatal stroke
• some regrowth after ischemic event ==> mushroom-shaped gyri ==> cerebral palsy
• motor-sensory cerebral disorders

Question 30

Stroke in preterm infants

Answer 30

• most focus of development on periventricular, subependymal germinal matrix
• preterm infants less than 32-34 weeks: vascular complications ==> hemorrhage into germinal matrix = SEH (subependymal hemorrhages)