Malformations & Developmental Diseases Part 2 Flashcards
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 **
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
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
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)
How does Polymicrogyria present grossly?
- Many small gyri fused together
- Cortical ribbon is thin & excessively folded & fused
- 2 or 4 cortical layers
What is this?
Polymicrogyria
- Stains myelin blue
- 6 layered cortex very patchy
- Gray matter thickened & wavy
- Abnormal sulcation
What is the difference between Agyria & Pachygyria?
- Agyria (lissencephaly) = absence of gyri
- Pachygyria = decreased numbers of broad coursed gyri
- Brain is small
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)
-
Miller Dieker Syndrome
What are the symptoms of Agyria & Pachygyria?
- Failure to thrive
- Microcephaly
- Marked developmental delay
- Severe seizure disorder
- Hypoplasia of the optic nerve
- Microphthalmia
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)
Sometimes the pattern of agyria allows prediction of the _______ _____.
Females with _____ mutation have imaging abnormalities distinct from other agyrias.
Causative gene
DCX
How does Pachygyria present grossly?
Thickened cortical ribbon (4 layers)
What is this?
Pachygyria
- Ribbon formation
- Sulci missing
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
How does Schizencephaly present when the clefts are bilateral?
- Severe MR
- Intractable Szs
- Microcephaly
- Spastic quadriplegia
What is Arrhinencephaly?
“Disorders of cleavage of forebrain”
- Term applied to this category of malformations
- Absence of olfactory tract/bulbs
- Holoprosencephaly & olfactory aplasia
Arrhinencephaly
Severity of craniofacial defect __________ severity of underlying brain abnormality.
mirrors
- “The face predicts the brain”
- Cyclopia – most severe
- Hypotelorism – minimal change
How does Arrhinencephaly present clinically?
- Clinical findings vary with severity of malformation
- Severe mental retardation, stillbirth, lack of olfaction
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
What is the definition of Holoprosencephaly?
What are the 3 types?
**Incomplete separation of hemispheres **
- Alobar holoprosencephaly
- Semilobar holoprosencephaly
- Lobar holoprosencephaly
What is Alobar holoprosencephaly?
- Small brain
- Cerebral hemispheres fused into single mass w/ no interhemispheric fissure: single large ventricle
- Hypoplasia of cortex
What is Semilobar holoprosencephaly?
Partial formation of interhemispheric fissure
What is Lobar holoprosencephaly?
- Midline continuity of cortex at frontal pole
- Almost normal brain size – often associated w/ craniofacial anomalies
What is this?
Holoprosencephaly
- Lots of mature cells
- Clumps, no layers
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
How is Holoprosencephaly diagnosed?
- Facial X-ray – deformed anterior craniobasal bones
- Cytogenetics
- MRI
- EEG, VER, ABR generally abnormal
What is Olfactory Aplasia?
Absence of olfactory bulbs, tracts, trigone & anterior perforated area
What is this?
Holoprosencephaly
**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
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
How does Agenesis of the Corpus Callosum present on CT/MRI?
- Widely separated frontal horns
- Abnormally high position of the 3rd ventricle
What is this?
Agenesis of the Corpus Callosum
- Corpus callosum & cingulate gyrus missing
- Cortex plowing straight into the ventricle
**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)
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
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)
Type 2 Chiari Malformation
Clinical Findings
- Lower CN defects (swallowing, respiration)
- Arm weakness, spasticity
- S/S referable to hydrocephalus
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
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
Dandy Walker Malformation
Etiology
Pathogenesis
- Etiology
- Most cases sporadic
- Associated w/ Trisomies
- Pathogenesis
- Not understood
- Believed to occur before 3rd month gestation
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
Syringomyelia (syrinx)
Clinical Presentation
- Loss of pain/temperature
- Retention of position & vibration senses & motor function
- Onset of symptoms in 2nd/3rd decades (progressive)
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
- White matter
-
Hemorrhagic Lesions
- Subependymal germinal plate/matrix hemorrhage
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
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
Periventricular Leukomalacia
Pathogenesis
- Impaired perfusion of boundary zone
- Poor cerebral vascular autoregulation
- Selectively vulnerable oligodendrocytes
What is this?
Periventricular Leukomalacia
- Central zone of necrosis
- Surrounding mineralization axons
Multicystic Encephalopathy
Definition
Clinical
- Destruction of both gray & white matter in 3rd trimester
- Sponge-like glial lined cysts remain
- Attributed to extensive hypoxia/ischemia
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
**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
What is this?
Subependymal Germinal Matrix Hemorrhage
