Malformations and Developmental Diseases - Basel & Lawlor Flashcards Preview

M2 Neuro/Psych > Malformations and Developmental Diseases - Basel & Lawlor > Flashcards

Flashcards in Malformations and Developmental Diseases - Basel & Lawlor Deck (43):

Speaking in terms of the pathogenic mechanisms behind congenital defects, what might we call a defect due to:

  • Intrinsic abnormality?
  • Extrinsic force?
  • Destructive force?

  • Malformation
  • Deformation
  • Disruption


Give the development timeframe of the each of the following:

  • Neurulation (formation of the neural tube)
  • Prosencephalic stage (formation of hemispheres, large structures of the brain)
  • Neuronal proliferation (full complement of neurons in the brain)
  • Neuronal migration (transition from 4-layered cortex to 6-layered cortex)
  • Organization (synaptogenesis and apopotosis)
  • Myelination

  • 3-4 wks
  • 2-3 mos
  • 3-4 mos
  • 3-5 mos
  • 5 mos to postnatal years
  • Birth to postnatal years


When does neural tube closure occur?

Name a major result of failure of the anterior neuropore to close?

Name a major result of failure of the posterior neuropore to close?

28 days


Spina bifida


Describe the process of sulcation of the brain and the approximate gestiational timeline for this process

Major fissures form at ~5 mos

Secondary sulci form at ~7 mos

Tertiary sulci form at ~9 mos


Describe the pattern of cerebral myelination during development (which parts myelinate first, last?)

Myelination starts around birth and completes around the end of the second year

Posterior frontal lobes, parietal lobes, and parts of the occipital lobe myelinate first

Followed by frontal lobes and temporal lobes

The rest of the cerebrum finishes myelination by the end of the 2nd year


What is (probably) the most common environmental factor in neural tube defect development?

Name some others

What genetic conditions are also associated with neural tube defects?

Folic acid deficiency

Also: maternal diabetes, hyperthermia, alcohol, and valproic acid

Genetic: Trisomies 13 and 18


Give the two general pathogenic processes behind neural tube defects

  • Primary: failure of closure of the neural tube
  • Secondary: reopening or rupture of closed tube


Among 'neural tube defects', name the conditions associated with the following

  • primary neural tube closure defects
  • primary axial mesodermal defects with herniation of neural tissue
  • primary axial mesodermal defects (closed)
  • Tail bud defects

  • anencephaly, craniorachischisis, myelomeningocele
  • Encephalocele, meningocele
  • split cord (high)
  • spina bifida occulta, split cord (low), hydromyelia


What two substances might be detected in the amniotic fluid that are indicative of neural tube defects?

AFP and acetylcholinesterase


Spina bifida

  • Most common location?
  • Least severe form?
  • Most common (diagnosed) subtype?

  • lumbosacral (80-90%)
  • spina bifida occulta (usually asymptomatic)
  • myelomeningocele (80-90%)


What external findings might be associated with spina bifida occulta?

Patches of hair, lipomas, skin dimpling/discoloration over the site of the defect (usually L5 or S1)

Possible foot and/or gait abnormalities

may be associated with syringomyelia, diastematomyelia, and tethered cord

often completely asymptomatic


Contrast meningocele and myelomeningocele


  • cyst lined with meninges and dura
  • no spinal cord herniation present
  • Not usually associated with neurological defect
  • May be associated with GU and rectal issues


  • Both meninges and spinal cord herniated through vertebral defect
  • Cyst may often rupture open
  • Flaccid paralysis, sensory deficit, absent DTRs, GU issues, postural abnormalities of lower extremities
  • Often complicated by meningitis, hydrocephalus, and pneumonia


Describe the diagnosis and treatment of meningocele

  • Dx
    • imaging: x-ray, MRI, CT of head (r/o hydrocephalus)
  • Rx
    • asymptomatic w/ full-thickness skin: surgery may be delayed
    • Thin skin, symptoms, or leaking CSF: immediate surgical repair


What is a Chiari Crisis?

Downward herniation of the medullar and cerebellar tonsils

Complication associated with myelomeningocele


80% of patients with myelomeningocele develop what life-threatening complication?

Describe the symptoms of this process

Hydrocephalus with Type II Chiari Defect

Symptoms of hindbrain dysfunction (difficulty feeding, choking, stridor, apnea, VC paralysis, spasticity, pooling of secretions)


Describe the treatment of myelomeningocele

What is the prognosis?

Surgery: repair and shunting, ortho to correct anatomic abnormalities

Medical: urologic evaluation, regular catheterization, metabolic/blood/renal monitoring

Rehab goal: functional ambulation (sacral or LS lesion)

MR 10-15%. Most deaths occur before age 4. 70% have normal intelligence, but learning problems and seizure disorders are common. Meningitis and ventriculitis complications may adversely affect IQ.


What is the prognosis of anencephaly?

Describe grossly

Death within several days of birth

Large defect of the calvarium with associated failure of the cerebral and cerebellar hemispheres to form. Primitive brain consists of partial brainstem, eyes, and CN 5-12


What neural tube defect is commonly grossly described as 'frog facies'?



What is an encephalocele?

What is the most common site?

What is a 'nasal glioma'?

When during development does this defect arise?

Broad-based pedunculated masses of cerebral tissue and dura protruding through a cranial defect (covered by skin) with disorganization of the remaining cranial brain tissue.

Most common site: occipital

Nasal glioma = ethmoidal encephalocele

Occurs during the neurulation period (<4wks)


How in encephalocele diagnosied in utero?

Biparietal diameter on U/S

AFP in amniotic fluid


What is Meckel-Gruber syndrome?

Autosomal recessive condition featuring:

  • occipital encephalocele
  • cleft lip/palate
  • microcephaly
  • microphthalmia
  • abnormal genitalia
  • polycystic kidneys
  • polydactyly


Generally, what is the pathogenesis behind:

  • polymicrogyria, agyria, and pachgyria?
  • holoprosencephaly and olfactory aplasia?

  • Disorders of migration and sulcation during brain development
  • Disorders of cleavage of the forebrain during brain development


Sulcation of the brain is more or less driven by what process?

Neuronal migration from the germinal matrix to the cortex



  • Define
  • Describe the etiology

  • Too many irregular small/fused gyri resulting from disordered organization of the neurons in the cortex at the time of migration
    • may be focal or diffuse
    • Two or four cortical layers may be noted
  • Etiolgies
    • intrauterine ischemia
    • twinning
    • intrauterine infection
    • familial syndromes


Contrast agyria  and pachygyria

Discuss the pathogensis of these disorders

Agyria: absence of gyri

Pachgyria: decreased numbers of broad, coarse gyri


  • Partial/incomplete migration of neurons to the cortex
  • Gyri don't form


What is Miller-Dieker Syndrome?

Seizures, mental retardation, and lissencephaly (agyria)

Prominent forehead, bitemporal hollowing, anteverted nostils, prominent upper lip, micrognathia

Due to deletion of LIS1 gene on chromosome 17 (17p13.3)


Describe several symptoms of agyria and pachygyria

  • failure to thrive
  • microcephaly
  • marked developmental delay
  • severe seizure disorder
  • hypoplasia of the optic nerve
  • microphthalmia


What is the significance of an agyric female with a DCX gene mutation?

(supposedly) distinctive agyric pattern vs. agyric males with same genetic defect



What is schizencephaly?


What problems can it cause?


clefted cerebral hemispheres.  This is typically caused by a problem in neuron migration during development.


Epilepsy, Retardation, spastic quadriplegia



What is arrhinencephaly?



What developmental problems are seen?




Arrhinencephaly is failure of the olfactory bulb and tract formation. 


retardation and lack of olfaction.  It is closely associated with holoprosencephaly.  



What can cause arrhinencephaly?


Autosomal dominant mutation of sonic hedgehog 7q26


Various Trisomies


Exposure to alchocol, accutane, diabetes during pregnancy



What is holoprosencephaly?


What are the 3 holoprosencephaly classifications?


Failure of forebrain cleavage to produce two separate hemispheres.  


From most severe to most mild

  1. Alobar holoprosencephaly
    • No hemisphere formation at all, brain is small, with cortex hypoplasia, one large ventricle
  2. Semilobar holoprosencephaly
    • partial formation of the interhemispheric fissure
  3. Lobar holoprosencephaly
    • complete hemisphere formation, grossly normal looking brain
    • usually associated with craniofacial defects



What facial abnormalities can present with holoprosencephaly?


What medical symptoms can present?


cyclopia (one eye), cebocephaly (nose w/ one nostril) or premaxillary agenesis


retardation, seizures, rigidity, apnea and temperature imbalance. 

Endocrine/pituitary/ventricle problems can also arise because of malformations. 



What causes agenesis of the corpus callosum?


What additional structures are seen or are missing? 


Problems with the commissural plate during embryogenesis. (The commissural plate is what the neurons follow to form the corpus callosum)


Without the commissural plate, white matter that would have formed the callosum become "probst bundles".  Additionally, the cingulate gyrus is also not formed.



What symptoms does corpus callosum agenesis present with?


What syndrome is it associated with?



Largely asymptomatic, but minor differences can be observed on language tests



Aicardi syndrome



What symptoms does aicardi syndrome have?


Who does it affect?


severe retardation, seizures, chorioretinal lacunae.  Hemivertabrae and costovertebral anomalies are common.


Affects females (it is X-linked and believed to be lethal for males)



What are chiari malformations?


What "types" are there?


Cerebellar herniation resulting from an underdeveloped posterior fossa


Type 1- cerebellar herniation

Type 2- cerebellar herniation with medulla displacement



What symptoms are seen in chiari malformations?



Lower cranial nerve defects

syringomyelia (cyst in the spinal cord- type 1)

myelomeningocele (failure of spine to fuse- type 2)



What is an Dandy-Walker malformation?


What symptoms does it have?


What can cause it? 


A Dandy-Walker formation is a failure of the cerebellar vermis to form; the fourth ventricle usually dilates to take up the space


motor retardation, spasticity, hydrocephalus, and respiratory failure


Can be caused by trisomies, or isoretinoin use during pregnancy, though most cases are sporadic



What syndrome is syringomyelia associated with?


What symptoms can it cause?


Associated with Chiari type 1 malformations


Progressive loss of pain and temperature starting in the 2nd to 3rd decade



What three pathologies result from perinatal hypoxia/hemorrhage?


What disease can be caused by all  of them?


  1. Periventricular Leukomalacia
    • results from ischemia to area around the ventricles around birth
    • hits white matter, particularly oligodendrocytes
  2. Multicystic Encephalopathy
    • results from ischemia during 3rd trimester
    • hits both white and grey matter, but spares glial cells
  3. Subependymal germinal hemorrhage
    • results from hemorrhage due to extreme perinatal distress


Cerebral palsy can be caused by all of these. 



What is seen on histology in the following diseases:


periventricular leukomalacia

multicystic encephalopathy



periventricular leukomalacia

area of necrosis surrounded by mineralization 


multicystic encephalopathy

large cysts surrounded by "spongy" parenchyma



What are the different grades of subependymal hemorrhages?


Grade 1- Confined to the germinal nucleus

Grade 2- Confined to germinal nucleus and lateral ventricle, but does not dilate the ventricle 

Grade 3- Confined to germinal nucleus and lateral ventricle, with ventricular dilation

Grade 4- Germinal nucleus, lateral ventricle, and surrounding parenchyma, with ventricular dilation