CNS I Path - Congenital Malformations Flashcards
Malformations vs. Deformations
Malformations - Come from primary errors/disturbances of embryonic and fetal developmental programs
Generally GENETIC
Deformations –> from an insult superimposed on a NORMAL developmental program/secondary compromise of development due to problems like vascular interruption, necrosis due to infection, compression/mechanical trauma
Tough to distinguish between the two
Neural Tube Defects overview
Result as a failure of the neural folds to close during primary and secondary neurulation
These are the MOST COMMON MALFORMATIONS
CNS normally begins as a tube lined by ependymal and primitive cells, and the two ridges meet at the midline and close –> many genes involved, many steps where things can fuck up
FOLIC ACID and INOSITOL –> supplements with these compounds help to PREVENT NEURAL TUBE DEFECTS
Anencephaly
Most common congenital malformation in the human fetus!
INCOMPATIBLE with life, F > M, 10x higher in Wales and Ireland?!?! Very few women carry to term because they know the baby will die
If carried to term –> absent/hypoplastic skull vault, flat skull base, abnormal spheroid, shallow orbits, shallow sella, replacement of most of the brain by a RAGGED VASCULAR MASS – AREA CEREBROVASCULOSA
Myelomeningocele
Most SEVERE TYPE OF SPINAL NEURAL TUBE DEFECT
Both MENINGES and SPINAL CORD herniate through a large vertebral defect
Lesions above T12 show female predominance, others equal
Fluctuant mass filled with CSF, covered by skin or a think membrane; dilated central canal; posterior cord open and may blend with skin; nerve roots end blindly in the skin; flat, highly vascular cord at the area of defect –> AREA MEDULLOVASCULOSA
Associated with Chiari II malformations (95%) and hydrocephalus
SPINA BIFIDA - defect of tail bud development
OCCULT SPINA BIFIDA –> Small, bony defect that can cause some pain or trouble moving lower limbs, or could be asymptomatic
Tethered cord – a fixation of the FILUM TERMINALE - usually not fixed so SC can grow upward normally during growth –> condition fixes it due to lipoma, dermoid cyst or fibroid tissue –> may present as a dimple, thickening, or growth of hair in the sacral area; must be corrected surgically!
CHIARI MALFORMATIONS
Associated with cerebellar or neural tube defects
Involves ELONGATION of the INFERIOR CEREBELLAR VERMIS and DOWNWARD DISPLACEMENT of the brainstem into the cervical spinal canal
Associated with HYDROCEPHALUS, MYELOMENINGOCELE
Causes by insufficient growth of the posterior fossa mesodermal elements, causing the CNS to adapt and morph into the empty space
Often paralysis below the defect
HOLOPROSENCEPHALY
Disorder of forebrain induction/patterning; a spectrum of malformations characterized by INCOMPLETE SEPARATION of the cerebral hemispheres across the midline
Liveborn have facial dysmorphism, psychomotor retardation, spasticity, apnea, disturbed temp regulation
ALOBAR is most severe –> very small brain, holosphere undivided into hemispheres, absent olfactory bulbs, absent corpus callosum, fused basal ganglia, hippocampal formation rims ventricle, bizarre radiating gyral pattern
May survive a few hours, because brainstem and cerebellum are relatively normal; heart can beat; but still incompatible with life!
Other forms of holoprosencephaly
Semilobar and Lobar –> may be compatible with life; corpus callosum still absent
“Face predicts the brain” – same genes for facial formation used for brain formation, so we see defects of both –>
CYCLOPIA
PROBOSCIS(abnormal/abnormally located nose)
CEBECEPHALY (single nostril) HYPOTELORISM (close eyes)
Causes of Holoprosencephaly?
maternal diabetes, toxoplasmosis, syphillis, rubella
FAS
Genetics –> half have normal karyotype, other half have chromosomal or single gene abnormalities:
TRISOMY 13 MOST FREQUENT
SHH COMMONLY MUTATED
LISSENCEPHALY
“Smooth Brain” – Agyria, Pachygyria (less numbers of broadened gyri)
Brain is SMOOTH; different areas can be affected (other areas may be fine)
Normally, the cortex is composed of SIX layers of neurons with white matter below, but in lissencephaly, the cortex is COMPLETELY abnormal –> neurons all jumbled!
NEURONAL MIGRATION DISORDER
Causes of Lissencephaly - MILLER DIEKER
MILLER-DIEKER SYNDROME –> Caused by a deletion of the LIS-1 gene on chromosome 17 that codes for platelet activating factor (needed during migration)
The result is a SMOOTH and THICK cortex –> THICK gray matter –> less white matter on the hemispheres, and a rim of white matter between layers III and IV of cortex –> COMPATIBLE with life (mild facial abnormalities, microcephaly, profound mental/motor retardation, feeding problems, seizures
Causes of Lissencephaly
X-LINKED LISSENCEPHALY -> caused by a mutation in the DOUBLECORTIN gene on the X chromosome – Predominantly gets males!
Affected males have lissencephaly, while female carriers have “laminar heterotropia – double cortex”
Neuroblasts with normal X chromosomes migrate up to their proper place, while abnormal do not, resulting in t DOUBLE CORTEX (can see gray matter within white matter)
Can be asymptomatic or cause seizures later on
Normal layers
Normal brain has SIX LAYERS OF GRAY MATTER, followed by the white matter
Lissencephaly, all jumbled together, not distinct!
Polymicrogyria
Neuronal migration disorder like lissencephaly
Multiple, small, malformed convolutions
Gyri on gyri on gryi
Cobblestone look
Many distribution patterns and can be diffuse or localized to any cortical area
Dandy-Walker Syndrome
Most common CEREBELLAR malformation
Characterized by agenesis of the cerebellar vermis (middle divider of the cerebellum) and enlargement of the posterior fossa
May see a small remnant of the vermis, as well as a MASSIVE CYST around it
Usually presents with HYDROCEPHALUS and Prominent Occiput
Causes unknown, but may be due to atresia (blockage) of the FOURTH VENTRICLE FORAMINA
