Pathology Of Congenital Malformations And Brain Injuries Flashcards
Potential causes of CNS malformations
Prenatal/perinatal insults
Mutations in genes that regulate differentiation/maturation or intercellular communication
Chemicals or infectious agents (teratogens)
1-2% incidence globally
Rest syndrome
X-linked dominant disorder
Mutations affect genes associated with regulation of methyl CpG protein 2 (MECP2)
Causes issues with expression of genes that actually are there
ONLY seen in girls, since they have 2 X chromosomes and 1 can compensate the other if needed
- if a male gets it, 100% lethality in utero
Signs
- wringing hands
- walking on toes
- systolic feet
- spinal dysgenisis which causes severe scoliosis
What’s re the most frequent type of CNS defect?
Neural tube defects (NTDs)
- spina bifida
- myelomenignoceles
- anencephaly
- encephaloecles
- etc.
VERY common in folic acid/B9 deficiencies
Elevated a-feta protein levels = neural tube defects
- this allows NTDs to be caught earlier
Most common NTDs include what?
Spina bifida occulta and its various types
Posterior end of the neural tube has y far the highest rate for NTDs (anterior end is rare)
Myelomeningocele
Extension of CNS tissue through a defect in the vertebral column, usually in the lumbrosacral sacral region
- caused by a posterior NTD
Patients experience motor and sensory defects in the lower extremities as well as bowl and bladder incontinence.
Anencephaly
Absences of the forebrain CN top fo the skull caused by a defect in the closure of the anterior neural tube
- eyes will look bigger, but are actually not.
Still presents with normal posterior fossa structures
Encephalocele
A diverticulum of malformed CNS tissue extends through a defect in the cranium
- caused by an anterior NTD
Most often involves the occipital region and/or the posterior fossa
Microencephaly
A group of malformations that Causes decreased CNS tissue to be formed during gestation
- leads to an overall small head with a small skull
Some associations include the following
- fetal alcohol syndrome
- chromosome abnormalities
- HIV
- Zika virus
Two etiologies of microencephaly
1) Differentiation of CNS stimulation
- causes premature neuronal differentiation in the subependymal ventricular zone and prevents proliferation
2) severe reduction in overall numbers of neural progenitors
- progenitors experience too much cell cycle arrest and death
Holoprosencephaly
Disruption of normal midline patterning in a brain
- brain and head are normal size, but the neuronal tracts and nuclei are abnormally placed
Often disrupts olfactory build formation and nostril formation.
severe forms prevent brain division into 2 hemispheres, causes Cyclopia
Lissencephaly
Complete loss of gyri in the brain
Polymicrogyria
Over production of gyri in the brain
Posterior fossa anomalies
Usually refer to misplacement of absence of portions of the cerebellum
Includes the following
1) Arnold-chiari malformation (chiari type 2)
2) chiari type 1 malformation
3) dandy-walker malformation
Arnold-chiari malformation (type 2)
Misshapened midline cerebellum
- causes downward extension of the vermis through the foramen magnum
Also usually presents hydrocephalus and lumbar myelomeningocele
Severe type
Chiari type 1 malformations
Lower lying cerebellar tonsils that extend through the foramen magnum
Causes excess tissue in the foramen magnum which obstructs CSF flow and compresses the medulla
Results in headache or cranial nerve defects that manifest in adult life only (late blooming)
Milder type and can be reversed with surgery
