Malformations & Developmental Diseases Part 2 Flashcards Preview

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Flashcards in Malformations & Developmental Diseases Part 2 Deck (50):
1

What are the 3 main categories of Forebrain Anomalies?

  • Disorders of migration & sulcation
    • Polymicrogyria
    • Agyria & Pachygyria
  • Disorders of cleavage of forebrain
    • Arrhinencephaly
    • Holoprosencephaly
    • Olfactory aplasia
  • Agenesis of corpus callosum 

2

What is the general pathogenesis of disorders of migration & sulcation?

  • Disturbance of process of neuronal migration from germinal matrix to cortex
  • Sulcation is induced by presence of normally migrated neuronal population 

3

Polymicrogyria 

Definition

Focal vs. Diffuse

  • Too many irregular small fused gyri
    • Disordered organization of the neurons in the cortex at the time of migration
    • Neurite extension, synaptogenesis & maturation 
  • Focal or Diffuse 
    • Clinical findings range from minimal cognitive impairment to severe mental retardation 

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4

What is the etiology of Polymicrogyria?

  • Intrauterine ischemia
    • Polymicrogyria associated w/ in utero infarcts
  • Twinning
  • Intrauterine infection (CMV, toxo, VZV, syphilis)
  • Familial syndromes (mutations identified)

5

How does Polymicrogyria present grossly?

  • Many small gyri fused together
  • Cortical ribbon is thin & excessively folded & fused
  • 2 or 4 cortical layers 

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6

What is this?

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Polymicrogyria 

  • Stains myelin blue 
  • 6 layered cortex very patchy
  • Gray matter thickened & wavy
  • Abnormal sulcation 

7

What is the difference between Agyria & Pachygyria?

  • Agyria (lissencephaly) = absence of gyri
  • Pachygyria = decreased numbers of broad coursed gyri
  • Brain is small

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8

What is the pathogenesis of Agyria & Pachygyria?

What is Miller Dieker syndrome?

  • Neurons migrate only part way to cortex
  • Gyri don’t form correctly (or at all)
  • 4th month of gestation
  • Several genetic types (mutated chr 17 or X chromosome)
    • Miller Dieker Syndrome
      • Seizures, mental retardation, lissencephaly
      • Deletion in LIS1 gene (chr 17)

9

What are the symptoms of Agyria & Pachygyria?

  • Failure to thrive
  • Microcephaly
  • Marked developmental delay
  • Severe seizure disorder
  • Hypoplasia of the optic nerve
  • Microphthalmia 

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10

What are the symptoms of Miller-Dieker syndrome?

  • Prominent forehead, bitemporal hallowing, anteverted nostrils, prominent upper lip, micrognathia
  • 90% w/ chr deletions of 17p13.3 (lissencephaly I gene) 

11

Sometimes the pattern of agyria allows prediction of the _______ _____. 

Females with _____ mutation have imaging abnormalities distinct from other agyrias. 

Causative gene

DCX

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12

How does Pachygyria present grossly?

Thickened cortical ribbon (4 layers)

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13

What is this?

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Pachygyria 

  • Ribbon formation
  • Sulci missing

14

What is Schizencephaly?

  • Unilateral or bilateral clefts w/i the cerebral hemispheres
  • Abnormality of morphogenesis
  • Cleft may be fused or unfused
  • Usually surrounded by abnormal brain, microgyria 

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15

How does Schizencephaly present when the clefts are bilateral?

  • Severe MR
  • Intractable Szs
  • Microcephaly
  • Spastic quadriplegia 

16

What is Arrhinencephaly?

“Disorders of cleavage of forebrain”

  • Term applied to this category of malformations
  • Absence of olfactory tract/bulbs
  • Holoprosencephaly & olfactory aplasia 

17

Arrhinencephaly 

Severity of craniofacial defect __________ severity of underlying brain abnormality. 

mirrors 

  • “The face predicts the brain”
  • Cyclopia – most severe
  • Hypotelorism – minimal change 

18

How does Arrhinencephaly present clinically?

  • Clinical findings vary with severity of malformation
  • Severe mental retardation, stillbirth, lack of olfaction 

19

What is the pathogenesis of Arrhinencephaly?

  • Attributed to absent cleavage of forebrain
    • 4th-6th wk of gestation
  • Usually sporadic
  • Autosomal dominant form (SHH on 7q26)
  • Associated w/ Trisomies
  • Association w/ EtOH, Accutane (retinoic acid) during pregnancy & DM

20

What is the definition of Holoprosencephaly?

What are the 3 types?

Incomplete separation of hemispheres 

  • Alobar holoprosencephaly
  • Semilobar holoprosencephaly
  • Lobar holoprosencephaly 

21

What is Alobar holoprosencephaly?

  • Small brain
  • Cerebral hemispheres fused into single mass w/ no interhemispheric fissure: single large ventricle
  • Hypoplasia of cortex 

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22

What is Semilobar holoprosencephaly?

Partial formation of interhemispheric fissure 

23

What is Lobar holoprosencephaly?

  • Midline continuity of cortex at frontal pole
  • Almost normal brain size – often associated w/ craniofacial anomalies 

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24

What is this?

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Holoprosencephaly

  • Lots of mature cells
  • Clumps, no layers

25

What are the symptoms of Holoprosencephaly?

  • Profound MR, seizures, rigidity, apnea, temp imbalance
  • HCP w/ aqueductal obstruction
  • Endocrine disorders w/ hypothalamic or pituitary malformations
  • Facial abnormalities
    • Cyclopia
    • Cebocephaly
    • Premaxillary agenesis 

26

How is Holoprosencephaly diagnosed?

  • Facial X-ray – deformed anterior craniobasal bones
  • Cytogenetics
  • MRI
  • EEG, VER, ABR generally abnormal 

27

What is Olfactory Aplasia?

Absence of olfactory bulbs, tracts, trigone & anterior perforated area 

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28

What is this?

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Holoprosencephaly

29

Agenesis of the Corpus Callosum 

Definition

Probst bundles

Etiology 

  • Results from an insult to the commissural plate during embryogenesis
  • No corpus callosum or cingulate gyrus
  • Gyri extending perpendicular to 3rd ventricle roof
    • Corpus callosum forms first
    • Cingulate gyrus forms in response
    • So if you have a cingulate gyrus, that means you MUST have a corpus callosum
  • Probst bundles – stumps of white matter at edge of cortex
  • No specific etiology or timing 

30

What are symptoms of Agenesis of the Corpus Callosum?

 

  • Isolated: asymptomatic (except in close perception/language tests)
  • Associated migration defects (heterotopia, microgyria, pachygyria) may present w/ MR, microcephaly, hemiparesis, diplegia & seizures
  • Frequently found in association w/ other malformations
    • Aicardi Syndrome – X-linked, chorioretinal defects, seizures

31

How does Agenesis of the Corpus Callosum present on CT/MRI?

  • Widely separated frontal horns
  • Abnormally high position of the 3rd ventricle 

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32

What is this?

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Agenesis of the Corpus Callosum 

  • Corpus callosum & cingulate gyrus missing
  • Cortex plowing straight into the ventricle 

33

Aicardi Syndrome 

Males vs. Females 

Characterizations

EEG

  • Patients almost all females (lethal in males)
  • Characterized by:
    • Severe MR
    • Intractable seizures
    • Onset btwn birth & 4 mo
    • Chorioretinal lacunae
    • Hemivertebrae & costovertebral anomalies
  • EEG – independent activity from both hemispheres (absence of CC)

34

Type 1 Chiari Malformation 

Definition

Associations

Genetics 

  • Chronic tonsillar herniation
  • Associated with:
    • Hydrocephalus
    • Sudden death
    • Neurologic signs/symptoms
      • Cranial nerve palsies
      • Ataxia
      • Long tract signs
    • May be asymptomatic
  • 90% also have syringomyelia
  • No known genetic or associated risk factors at present 

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35

Type 2 Chiari Malformation

Definition

Associations 

“Arnold-Chiari malformation”

  • Herniated cerebellar tissue through foramen magnum w/ displacement of dorsal medulla 
    • Hump or Z-shape in brainstem/spinal cord
  • Associated w/ lumbar Myelomeningocele (Chiari 2 in 95% of children w/ MMC)

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36

Type 2 Chiari Malformation

Clinical Findings 

  • Lower CN defects (swallowing, respiration)
  • Arm weakness, spasticity
  • S/S referable to hydrocephalus 

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37

Type 2 Chiari Malformation

Etiology 

Pathogenesis 

  • Vit A deficiency (maternal) associated w/ Chiari II & Myelomeningocele
  • No genetic associations yet found
  • Pathogenesis (hypothesis)
    • Disproportion btwn growth of posterior fossa & its contents (posterior fossa too small)
    • Kinking or medullar & “squashing” of cerebellum into spinal canal 

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38

Dandy Walker Malformation

Definition

Associations 

Risk Factors

  • Agenesis of vermis
    • Cystic dilatation of 4th ventricle
    • Enlargement of posterior fossa
    • Hydrocephalus frequently present
  • Associated w/ motor retardation, spasticity, respiratory failure
  • Risk factors: Isotretinoin use during pregnancy 

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39

Dandy Walker Malformation

Etiology

Pathogenesis 

  • Etiology
    • Most cases sporadic
    • Associated w/ Trisomies
  • Pathogenesis
    • Not understood
    • Believed to occur before 3rd month gestation 

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40

Syringomeylia (syrinx)

Definition

Associations 

  • Fluid-filled cleft-like cavity in spinal cord
    • Cavity extends transversely cross cord crossing behind central canal
    • Largest in cervical regions
  • Associated w/ Chiari type 1 malformation (90%)
  • Also seen post trauma & in association w/ spinal cord tumors 

41

Syringomyelia (syrinx)

Clinical Presentation

  • Loss of pain/temperature
  • Retention of position & vibration senses & motor function
  • Onset of symptoms in 2nd/3rd decades (progressive)

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42

What are the 2 types of Perinatal Hypoxic/Ischemic Lesions?

What is the main Perinatal Hemorrhagic lesion?

  • Hypoxia/Ischemia
    • White matter
      • White matter necrosis (periventricular leukomalacia)
    • Gray + white matter
      • Multicystic encephalopathy
  • Hemorrhagic Lesions
    • Subependymal germinal plate/matrix hemorrhage 

43

How do perinatal insults present clinically?

Cerebral Palsy

  • Non-progressive neurologic motor defect
    • Spasticity, dystonia, ataxia/athetosis, paresis
  • Attributed to insults occuring in the fetal & perinatal periods
  • Wide range of Neuropathologic findings
    • Often hypoxic/ischemic or hemorrhagic events 

44

White Matter Necrosis: Periventricular Leukomalacia

Definition

Population

  • Sharply defined foci of necrosis in WM
    • Gross discrete chalky yellow plaques
    • May eventually cavitated
  • Common in premature infants w/ ischemia/hypoxia
  • Also occurs in full-term infants w/ cardiac or pulmonary disease

45

Periventricular Leukomalacia

Pathogenesis

  • Impaired perfusion of boundary zone
  • Poor cerebral vascular autoregulation
  • Selectively vulnerable oligodendrocytes 

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46

What is this?

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Periventricular Leukomalacia

  • Central zone of necrosis
  • Surrounding mineralization axons 

47

Multicystic Encephalopathy

Definition

Clinical 

  • Destruction of both gray & white matter in 3rd trimester
  • Sponge-like glial lined cysts remain
  • Attributed to extensive hypoxia/ischemia 

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48

Subependymal Germinal Matrix Hemorrhage

Location

Onset 

  • Originate in periventricular germinal matrix
    • Most frequently in germinal zone overlying head of caudate & thalamus
    • Frequently break through into ventricular system or underlying parenchyma
  • Onset related to extreme physical distress (context of prematurity)
    • Perinatal occurrence
    • Hemodynamic instability
    • Mechanical ventilation
    • Hyaline membrane disease 

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49

Subependymal Germinal Matrix Hemorrhages 

  • Grade 1
  • Grade 2
  • Grade 3
  • Grade 4

  • Grade 1
    • confined to germinal matrix 
  • Grade 2
    • germinal matrix & lateral ventricle
    • no ventricular dilatation
  • Grade 3
    • germinal matrix & lateral ventricle
    • acute ventricular distention
  • Grade 4
    • as above w/ extension into adjacent brain parenchyma 

50

What is this?

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Subependymal Germinal Matrix Hemorrhage