Congenital Disorders I-III

Question 1

2. Describe the following prototypical congenital malformations, including the period during embryogenesis and development when they occur: Neural tube defects, holoprosencephaly, disorders of neuronal proliferation, disorders of neuronal migration, and disorders of elaboration of neurons and glia.
3. Discuss the principal causes and consequences of stroke in the perinatal period.
4. Describe the association between Chiari I malformation and syringomyelia, and the association between Chiari II malformation and myelomeningocele.
5. Recognize symptoms that result when a process such as syringomyelia or tethering affects the spinal cord.

Answer 1

x

Question 2

1. Level of conus at birth, 3 m/o, adult. State consequences/presentation of tethering.

Answer 2

Newborn: L3 vertebral level
3 months: Conus at least level with L2 vertebral body
Adult: L1-L2 vertebral bodies

Tethering can cause pain, as well as UMN symptoms (hyperreflexia, spasticity)

Question 3

During what week(s) of embryonic development will NTD occur? What are examples of NTD-linked defects?

Answer 3

During week 3 - NTD are occurring before women even know they are pregnant (hence the importance of prenatal folate supplements)

**NT closure between 18-26 days

Tethered Spinal cord
Chiari II malformation
Neuroschisis (meningocele, anencephaly)

Question 4

During what week(s) of embryogenic development will prosencephalic malformations occur (holoprosencephaly)?

Answer 4

Weeks 5-6

Question 5

During what week(s) of embryogenic development will disorders of neuron proliferation occur (macrencephaly/micrencephaly)?

Answer 5

Weeks 8-20

Question 6

During what week(s) of embryonic development will disorders of neuronal migration occur (Lissencephaly, polymicrogyria)?

Answer 6

Weeks 10-20

Question 7

During what timeframe will destructive lesions occur in the fetus/child?

Answer 7

14 weeks gestation until 2.5 years.

**Mentioned in class that the greatest risk is in premature babies, due to difficulties regulating acid/base balance, etc. in premature infants. Most dangerous 22-32 week old preemies.

Question 8

During what timeframe are children vulnerable to disorders of elaboration of neurons and glia (axonal growth, myelination, malnutrition, metabolic disorders)?

Answer 8

20 weeks gestation to 5 years

Question 9

Describe anencephaly.

Answer 9

The back is completely intact, there is often nothing wrong with the body cavity. Fetus can survive to term. Brainstem is usually intact, so if the pregnancy isn’t terminated these babies can sometimes survive for several days. Bulbous eyes. Foramen magnum and spinal cord are often completely intact. At 8-10 weeks the head is really small (as opposed to normal where the head is disproportionately large

Question 10

What differentiates anencephaly from encephaloceles or craniomeningoceles?

Answer 10

Epidermal covering over the cranial neural tube closure defect. Encephalocele may contain +/- brain tissue.

Question 11

What is a myelomeningocele?

Answer 11

Results from failure of the caudal neural tube closure. (lumbar/sacral area open to the outside). Closure of the pore is necessary to prevent ascending infection, but not sufficient.

Question 12

What is spina bifida oculta?

Answer 12

Failure of the vertebral arch to seal posteriorly. Will be more vulnerable to trauma.

Question 13

What is a lipomyelomeningocele?

Answer 13

“Fat trapped in the meningocele” This needs to be femoved by surgeons. Stuck neural tube is not going to ascend with the conus medullaris in normal fashion because the lipoma is attached/anchored to the skin, which leads to tethering (stretching) of the spinal cord. One of the main goals of surgery is to allow the spinal cord to float freely to prevent tethering.

Question 14

For what would a pediatrician be looking in the lumbar/sacral area of a newborn?

Answer 14

Sacral dimple/dermal sinus tract.

**Interesting BONUS info: 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. Several cutaneous abnormalities indicative of underlying spinal dysraphism are situated in or near the midline, usually in the lumbosacral region. These can include a dermal dimple, a hairy patch of skin, a lipoma or other midline visible mass, a dermal sinus, or capillary hemangioma

Question 15

What is a teratoma? From what cells does it arise?

Answer 15

A teratoma is a huge mass on the caudal end of the fetus/infant. It is a jumble of different cell and tissue types, and results from inappropriate continued growth of the cells of the primitive streak.

Teratomas can be removed surgically and often have an excellent outcome.

Question 16

What is the clinical recommendation for folic acid supplementation in women who hope to become pregnant?

Answer 16

0.4mg/day beginning 4 weeks prior to conception through the first trimester prevents 50% of NTD.

**If a woman has a previous miscarriage due to NTD, 10x the dose (4mg)

Question 17

Which of the Chiari malformations involves a NTD?

Answer 17

Chiari II (Arnold-chiari)

Question 18

What are the defining characteristics of a Chiari II malformation?

Answer 18

1) Myelomeningocele
2) Hydrocephalus (occluded/stenotic aqueduct)
3) Small posterior fossa with “z-shaped kinking” of the brainstem
4) herniation of the vermis of the cerebellum (ie cerebellum “unrolled” into the foramen magnum).

Question 19

What differentiates a meningocele from a myelomeningocele?

Answer 19

**Skin vs no skin, respectively

Myelomeningocele - Results from failure of closure of the posterior neuropore. 80% in lumbar area (last area of neural tube to close). Consists of a neural placode without epidermal covering, with CSF leak.

Meningocele-a skin-covered, CSF-filled mass that is continuous with the CSF in the spinal canal.

Question 20

Summarize Type I Chiari.

Answer 20

Caused by cerebellar “tonsils” that protrude into the foramen magnum and impede CSF out of the central canal into the subarachnoid space. This leads to hydromyelia - accumulation of fluid in the central canal of SYRINGOMYELIA, a condition where a CSF cyst dissects out of the central canal into the matter of the spinal cord. This causes myelopathy (spinal cord dysfunction). Hydrocephalus can also be seen due to impeded flow through the aqueduct.

**This is a mesodermal disorder, and is not associatd with a NTD.

Question 21

What is the mechanism that causes the phenotype in Chiari II?

Answer 21

CSF leakage from the myelomeningocele causes loss of turgor pressure in the spinal column. The brain sags and drops into the foramen magnum, disrupting CSF flow into the subarachnoid and causing the hydrocele.

Text [Leakage of CSF from the primitive ventricular system leads to a failure of the ventricles to increase in size and volume, due to both downward and upward herniation of the small cerebellum. In addition, the posterior fossa does not develop to its full size, and the neuroblasts do not migrate outward at a normal rate from the ventricles into the cortex. Therefore, the entire posterior fossa anomalies are related to a single initial inciting event.]

Question 22

What clinical signs might result from spingomyelia?

Answer 22

Classic presentation: “cape-like” loss of pain/temp sensation due to disruption of the anterior commisure at C6 level

Depending on the location of the spinal lesion, can see many manifestations

Question 23

What is the peak period of prosencephalic generation?

Answer 23

2-3 months gestation

**The face is involved, and dysmorphic facial features often indicate impaired brain development.

Question 24

What are the three categories of holoprosencephaly? What is the most severe outward manifestation?

Answer 24

Alobarholoprosencephaly - one big lobe (cyclopia would be the most severe outward manifestation)
Semilobar - frontal lobes fused (horseshoe)
Lobar - some fusion (dispersed)

Question 25

To what might a holoprosencephalic malformation be due?

Answer 25

Shh mutation.

Question 26

Describe the Danny-Walker Malformation

Answer 26

Essentially a dilated, cystic 4th ventricle causes and enlargment in the posterior fossa, resulting in a raised tentorium cerebelli, agenesis of the vermis, and hydrocephalus.

[NOT related to folate deficiency or NTD]

Question 27

What is the term for the type of stroke suffered by preterm infants that can lead to long term disability (“cerebral palsy”) if severe?

Answer 27

Germinal Matrix Hemorrhages (GMH) or Subependymal Hemorrhage (SEH).

[In immature infants the majority of the blood supply to the brain during gestation is directed to deep structures. Much of the metabolic demand is directed to the formative periventricular, subependymal germinal matrix which serves as a “growth plate” for neurons and glia. The germinal matrix is highly vascular, highly cellular, and possesses little structural support during early fetal life. By the age of 32-34 weeks gestation, all of the neuronal groups and most of the glia have migrated from the germinal matrix and it undergoes involution. Risk factors associated with the development of GMHs include immature gestational age, immature fetal lungs resulting in hyaline membrane disease, hypercapnia, low birth weight under 1500 gm, acidosis, and coagulation defects.]

Question 28

Define each term:

Porencehpaly, hydranencephaly, schizencephaly

Answer 28

Large unilateral holes (porencephaly),
destruction of the tissue of virtually one entire cerebral hemisphere (hydranencephaly)
bilateral symmetrical holes (schizencephaly)

Question 29

What does dystonia mean? (sidebar, often seen in Cerebral Palsy)

Answer 29

a simultaneous co-contraction of normally opposing muscles that results in fixed, often painful postures