congenital disorders Flashcards
When does myelination occur in CNS
Mainly after birth, and by 6 years it is nearly complete.
How to prevent neural tube defects
folic acid supplementation periconceptually from 4 weeks before pregnancy through first trimester. 0.4mg/day (or 4mg/day for women with history of prior pregnancy with NTD)
How are neural tube defects detected
AFP elevation in amniotic fluid (peaks 12-14GW), elevated maternal serum or amniotic fluid acetylcholinesterase
Period during development when neural tube defects occur
day 14-26 (week 3) prenatally
Period during development when holoprosencephaly occurs
week 5-6 prenatally
Period during development when disorders of neuronal proliferation occur
weeks 8-16 prenatally
Period during development when disorders of neuronal migration occur
weeks 12- 16 prenatally
Period of development when disorders of elaboration of neurons and glia occurs
from week 20 prenatally - 5 years post natally
Cranioraschisis totalis
The most severe form of neural tube defect, a complete failure of primary neurulation. The word stem raschis means “main axis” or “shaft. Least common
Anencephaly
failure of the rostral neuropore to close, around day 23-25. The forebrain neuroectoderm fails to separate from the cutaneous ectoderm, and a red area cerebrovasculosa is seen where the calvarium would have developed.
Encephalocele
Defect in the skull with protrusion of leptomeninges brain. Distinguished from anencephaly because they have an epidermal covering over the cranial neural tube closure defects
Myelomeningocele (spina bifida)
Results from failure of closure of the posterior neuropore, day 25-27. 80% in lumbar area (last area of neural tube to close). Consists of a neural placode without epidermal covering, with CSF leak. Can have lower extremity or urinary problems
Meningocele
a skin-covered, CSF-filled mass that is continuous with the CSF in the spinal canal
Lipomyelocele/lipomyelomeningocele
occurs when a lipoma extends from the
subcutaneous tissues to the dorsal aspect of the cord and tethering the cord inferiorly. This process reflects a premature separation of the cutaneous ectoderm during the process of neurulation that allows mesenchyme to enter the unclosed neural tube and differentiate into fat.occurs when a lipoma extends from the
subcutaneous tissues to the dorsal aspect of the cord and tethering the cord inferiorly. This process reflects a premature separation of the cutaneous ectoderm during the process of neurulation that allows mesenchyme to enter the unclosed neural tube and differentiate into fat.occurs when a lipoma extends from the
subcutaneous tissues to the dorsal aspect of the cord and tethering the cord inferiorly. This process reflects a premature separation of the cutaneous ectoderm during the process of neurulation that allows mesenchyme to enter the unclosed neural tube and differentiate into fat.
Dorsal dermal sinus tract
These are ectoderm-lined tracts that can transgress the dura and allow communication between the skin and the cerebrospinal fluid. The can also cause tethering of the spinal cord and can be associated with an intradural dermoid cyst or epidermoid.
Bony spina bifida occulta
At the L5-S1 level this is a common incidental finding on radiographs, both in children and adults, and it is usually not associated with symptoms or signs. Failure of bony laminar arch to completely envelop meningeal sac. Cutaneous abnormality often present, such as sacral dimple or hairy patch. If no signs are present, no further imaging workup is required
Sacrococcygeal teratoma
After primitive streak has regressed it forms pluripotent mass of cells called caudal eminence/end bud. These cells may give rise to a teratome
Where do most neural tube defects occur and what is the consequence of this
in lumbar region- In typical newborns, the conus medullaris is at L3 vertebral body , by 3 months its at L2 and by adulthood its at L1-L2. Lumbar NTD can tether the spinal cord, preventing its ascension over time and the tension on the cord may compromise blood supply and cause spinal cord dysfunction, pain and upper motor neuron signs (hyperreflexia and spasticity). Urinary incontinenc may occur.
Chiari type I malformation
Cerebellar tonsils are elongated and pushed down through the foramen magnum, blocking the normal flow of cerebrospinal fluid. CSF accumulates in central canal (hydromyelia), or a CSF-filled cyst breaks out of central canal and dissects into the cord (syringomyelia), or CSF accumulates in subarachnoid space (hydrocephalus). Myelopathy of spinal card can result. Likely mesodermal disorder, not NTD. usually discovered later in life and can affect urinary tract (spastic urinary bladders)
Chiari type II
complex malformation (elongated cerebellar vermis, breaking of midbrain tectal plate)- myelomeningocele, hydrocephalus, hindbrain, spine abnormalities, small posterior fossa with kinking of brainstem and herniation of cerebellum
Holoprosencephaly
when the single ventricle that exists in the early embryonic forebrain (ie., the prosencephalon) fails to form properly into the two lateral ventricles and one third ventricle. Partial failure of cerebral hemispheres to divide properly.
3 prosencephalic cleavages that occur during development
Horizontally to form paired optic vesicles, olfactory bulbs and tracts •Transversely to separate telencephalon from diencephalon (thalamus, hypothalamus) •Sagittally to form from the telencephalon the paired cerebral hemispheres, lateral ventricles
3 types of holoprosencephaly
Alobar: No division of cerebral cortex (single forebrain). Semilobar: Partial cleavage with cerebral hemispheres fused at frontal region only (horseshoe appearing central ventricle). Lobar: Cerebral hemispheres separated anteriorly and posterioly with some degree of fusion of structures.
Facial features in holoprosencephaly
Micocephaly, absent olfactory/optic nerves. Facial and ocular development is linked to the differentiation of the forebrain. May see cebocephaly (hypotelorism, single nostril), cyclopia (fused orbits with supra-orbital proboscis), ethmocephaly (hypotelorism, high midline proboscis), arhinia (no nose), coloboma of the iris and retina, microphthalmus, premaxillary agenesis (hypotelorism with absent nares and philtrum) and midline facial clefts.
Gene defect in holoprosencephaly
sonic hedgehog mutation- SHH is usually secreted ventrally creating a ventral-dorsal gradient When mutated, cleavage into telencephalic vesicles doesn’t occur
Holoprosencephaly prognosis
alobar are lethal within the first year of life. semilobar have a poor prognosis; however, some cases survive into infancy. Cases of lobar may have a normal life expectancy, but with severe
mental and physical impairmentalobar are lethal within the first year of life. semilobar have a poor prognosis; however, some cases survive into infancy. Cases of lobar may have a normal life expectancy, but with severe
mental and physical impairment
Describe Dandy Walker malformation
NOT a neural tube defect (not related to folate) a.) partial or complete absence of formation of the cerebellar vermis, b.) cystic dilatation of the fourth ventricle, and c.) upward displacement of the tentorium d.) hydrocephalus, which will require shunting of CSF. e.) enlarged posterior fossa
possible drug linked with Dandy Walker malformation
cis-retinoic acid medication
types of malformations of cortical development
- abnormal neural/glial proliferation. 2. abnormal cortical migration. 3. abnormal cortical organization (formation of gyri/sulci)
Forms of disturbed neuronal proliferation
microcephaly (5:1 ratio of cerebrum to cerebellum, opposed to 8:1 normal ratio, decreased cognition), macrocephaly. Normal full sized brain is about 1400g.
disorders of neuronal migration and gyral formation
Agyria (lissencephaly- smooth brain), polymicrogyra (excess gyri that are smaller than normal), heterotopias (double cortex, extra brain matter in brain)
Describe destructive events that can occur in late pregnancy
Large unilateral holes (porencephaly), bilateral symmetrical holes (schizencephaly), or destruction of the tissue of virtually one entire cerebral hemisphere (hydranencephaly) can occur when the fetal brain is injured in pregnancy. Vascular ischemic destructive events in late second or early third trimester of pregnancy are usually to blame.
Schizencephaly- location, causes and features
Gray matter lined clefts extending from the ependymal lining of the lateral ventricles to the pial covering of cortex •Both genetic and acquired causes •Gray matter lining the clefts is dysplastic
Causes of abnormal myelin or dendritic branching
Down syndrome, malnutrition and metabolic disorders
Principle cause of stroke in children 0-14 years plus type
Genetic malformations of heart or blood vessels. 55% is ischemic, 45% is hemorrhagic
Main cause of ischemic stroke in children. Hemorrhagic stroke?
ischemic: heart disease, unknown cause, moyamoya. Hemorrhagic: arteriovenous malformation, unknown, aneurysm
Stroke in perinatal period in term infants causes what?
Ulegyria (mushroom gyri) is result of perinatal watershed infarcts with subsequent growth of non-damaged parts of gyri
Stroke in perinatal period in preterm infants causes what? What are risk factors
In immature infants, blood supply is directed to deep structures so Germinal matrix hemorrhages (subependymal hemorrhages) are major causes of morbidity and mortality in preterm infants less than 32-34 weeks gestation. Risk factors include immaturity of lungs, hypercapnia, low birth weight, acidosis
Grading scale of subependymal hemorrhages
Grade I: confined to the germinal matrix. Grade II: spill into the ventricles but show no CSF blockage or hydrocephalus. Grade III: spill into the ventricles and produce hydrocephalus. Grade IV: show back dissection of the large hemorrhage into the surrounding cerebral white matter
subependymal hemorrhage survival rates
Infants with grade III and IV GMHs have lower survival as well as motor deficits and neurodevelopmental delay and learning difficulties. Infants with grade I and II GMHs have the same survival as infants without GMH but may or may not have subtle neurobehavioral and learning problems
