B113 Congenital malformations of the nervous system

Question 1

What are the major classes of congenital CNS malformations?

Answer 1

Neural Tube defects

Forebrain Malformations

Posterior Fossa Abnormalitites

Spinal Cord Malformations.

Question 2

What are the neural tube defects? (list)

Answer 2

Spina Bifida Oculta

Meningocele

Myelominigocele

Rachischisis

Anencephaly

Encephalocele

Question 3

Describe:

Spina bifida occulta

Meningocele

Myelomeningocele

Rachischisis

Answer 3

All are neural tube defects caused by abnormal closure of the neural folds in the 3rd and 4th weeks of embryonal development. Are the most frequent type of CNS malformation. Occurence of one of these indicates a risk of 5% in subsequent pregnancies.

Maternal Folate deficiencies increase risk by unclear mechanism. Folate should be taken during pregnancy.

Increased alpha feto protein in maternal serum indicates a neural tube defect.

Spina bifida oculta: Incomplete closure of the vertebrae and an open vertebral canal. This is asymptomatic and has a hairy patch over the affected area. Presents possibility for damage.

Meningocele: vertebrae don’t close, and the fluid filled meningeal arachnoid and dura layers extend outward from the infants back.

Meningomyelocele: As meningocele, but the spinal cord itself is also herniated out into the expansion.

Rachischisis: The neural tube never closes at all, and instead of a spinal cord at that segment there is only a flat disorganized mass of neural tissue with no overlying meninges or skin.

70% of these form in the lumbosacral region.

They cause motor and sensory deficits in the lower limbs, and often bowel and bladder incontenince. Also expose the CNS to infections.

Severe Rachischisis is often fatal to the developing fetus.

Question 4

Describe

Anencephaly

Encephalocele

Answer 4

Anencephaly:

Malformation of the anterior neural tube. Results in absence of the brain and cranium.

Encephalocele:

Diverticulum of malformed CNS tissue protruding outward through a defect in the cranium.

Typically occurs in the occipital region or the posterior cranial fossa

Can occur in the anterior fossa allowing CNS tissue to extend into the sinuses.

The formation of brain tissue in the encephalocele also results in less brain growth in the cranium, so the rest of the brain and skull is smaller than normal.

Question 5

List the forebrain malformations

Answer 5

Microencephaly

Megalencephaly

Polymicrogyria

Pachgyria

Lissencephaly

Holoprosencephaly

Question 6

Describe the presentation and causes of microencephaly and megalencephaly

Answer 6

Microcephaly

• much more common
• small brain and small head (microcephaly), and decreased neuron counts
• Causes:
  
  • Fetal alchol syndrome
  • Chromosome abnormalities
  • Fetal HIV infeciton.
• Unifying feature is decreased generation of neurons from the subependymal zone progenitors.

Megalencephaly:

• Unknown cause most of the time.
• A mutation in the PI3K-AKT pathway is believed to be the primary cause of these two disorders
  
  • megalencephaly-capillary malformation (MCAP)
  • megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH).

Question 7

Describe Lissencephaly and Pachygyria

Answer 7

Lissencephaly, aka agyria

Lack of cerebral gyri formation, smooth brain surface. Pachygyria is also called ‘incomplete lissencephaly’, with only a few very large, wide gyri.

The cortex is abnormally thick and contains four layers. (normally 6: molecular, external granular, pyramidal, inner granular, ganglionic, multiform)

Cause is unknown, but some single-gene defects have been seen in specific cases of lissencephaly

Symptoms:

• mental and motor retardation
• failure to thrive
• seizures, and
• muscle spasticity
• muscle hypotonia

The severity of symptoms vary greatly from child to child depending on the degree of brain malformation and seizure control.

Life expectancy can be shortened, generally due to respiratory problems

Question 8

Describe polymicrogyria

Answer 8

Polymicrogyria - excessive numbers of abnormally small gyri, brain looks like cauliflower/cobblestone surface.

The polymicrogyria changes can be focal or widespread.

Question 9

Describe Holoprosencephaly

Answer 9

Disrupted midline patterning, with no hemisphere formation of the prosencephalon.

The telencephalon and prosencephalon is composed of a single sheet of tissue, with some mild gyration and a huge dilated cavity underneath it.

In most cases it is associated with severe midline malformations of the face as well, and is lethal embryonically.

Very mild cases jsut present with normal brain development and midline facial deformities like cleft lip, palate, jaw.

Again cause is unkown, but some single gene defects in the Shh pathway have been observed in cases.

Question 10

List the posterior fossa abnormalities

Answer 10

Cerebellar malformations of agenesis of portions of the cerebellum.

Chiari type 1 malformation

Chiari type II malformation, Arnold-Chiari malformation

Dandy-Walker malformation

Joubert syndrome

Question 11

Chiari type I and type II malformations

Answer 11

Chiari type 1

Due to development of an abnormally small posterior cranial fossa, cerebellar tonsils herniate down through the foramen magnum over the cervical spine. Causes secondary hydrocephalus due to obstruciton of the Magendie (median aperture) and Lateral foramina of Lushka

Chiari type 2 malformation

More severe form, with a both a small posterior fossa and a malformed cerebellar vermis. The vermis herniates through the foramen magnum, and causes malformations of the medulla as well. Cause secondary hydrocephalus from foramen compression, and usually co-presents with lumbar meningomyelocele and syringomyelia or syrinx formation.

Question 12

List and describe the spinal cord malformations.

What else can cause them?

Answer 12

Hydromyelia - dilation of the central canal.

Syringomyelia or Syrinx - A fluid filled longitudinal shaped cyst in the parenchyma of the cord. May or may not communicate with the central canal.

• Both types of lesions invovle atrophy and destruction of the adjacent gray and white matter, and are surrounded by reactive gliosis and scarring.
• Most often occur in the cervical spinal cord, and congeintally are most associated with Chiari type 2 syndrome.
• Can be acquired due to spinal cord damage from:
  
  • trauma
  • meningitis
  • hemorrhage
  • tumor

Question 13

Describe Dandy-Walker malformation

Answer 13

An enlarged posterior fossa, and egenesis of the vermis of the cerebellum.

The vermis is replaced by a midline cyst, lined by normal leptomeninges.

Lack of the vermis causes the fourth ventricle to lack a roof and directly open into the surrouidning CNS.