Malformations & Developmental Diseases Part 2 Flashcards
(50 cards)
1
Q
What are the 3 main categories of Forebrain Anomalies?
A
-
Disorders of migration & sulcation
- Polymicrogyria
- Agyria & Pachygyria
-
Disorders of cleavage of forebrain
- Arrhinencephaly
- Holoprosencephaly
- Olfactory aplasia
- **Agenesis of corpus callosum **
2
Q
What is the general pathogenesis of disorders of migration & sulcation?
A
- Disturbance of process of neuronal migration from germinal matrix to cortex
- Sulcation is induced by presence of normally migrated neuronal population
3
Q
Polymicrogyria
Definition
Focal vs. Diffuse
A
-
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
4
Q
What is the etiology of Polymicrogyria?
A
- Intrauterine ischemia
- Polymicrogyria associated w/ in utero infarcts
- Twinning
- Intrauterine infection (CMV, toxo, VZV, syphilis)
- Familial syndromes (mutations identified)
5
Q
How does Polymicrogyria present grossly?
A
- Many small gyri fused together
- Cortical ribbon is thin & excessively folded & fused
- 2 or 4 cortical layers
6
Q
What is this?
A
Polymicrogyria
- Stains myelin blue
- 6 layered cortex very patchy
- Gray matter thickened & wavy
- Abnormal sulcation
7
Q
What is the difference between Agyria & Pachygyria?
A
- Agyria (lissencephaly) = absence of gyri
- Pachygyria = decreased numbers of broad coursed gyri
- Brain is small
8
Q
What is the pathogenesis of Agyria & Pachygyria?
What is Miller Dieker syndrome?
A
- 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
9
Q
What are the symptoms of Agyria & Pachygyria?
A
- Failure to thrive
- Microcephaly
- Marked developmental delay
- Severe seizure disorder
- Hypoplasia of the optic nerve
- Microphthalmia
10
Q
What are the symptoms of Miller-Dieker syndrome?
A
- Prominent forehead, bitemporal hallowing, anteverted nostrils, prominent upper lip, micrognathia
- 90% w/ chr deletions of 17p13.3 (lissencephaly I gene)
11
Q
Sometimes the pattern of agyria allows prediction of the _______ _____.
Females with _____ mutation have imaging abnormalities distinct from other agyrias.
A
Causative gene
DCX
12
Q
How does Pachygyria present grossly?
A
Thickened cortical ribbon (4 layers)
13
Q
What is this?
A
Pachygyria
- Ribbon formation
- Sulci missing
14
Q
What is Schizencephaly?
A
- Unilateral or bilateral clefts w/i the cerebral hemispheres
- Abnormality of morphogenesis
- Cleft may be fused or unfused
- Usually surrounded by abnormal brain, microgyria
15
Q
How does Schizencephaly present when the clefts are bilateral?
A
- Severe MR
- Intractable Szs
- Microcephaly
- Spastic quadriplegia
16
Q
What is Arrhinencephaly?
A
“Disorders of cleavage of forebrain”
- Term applied to this category of malformations
- Absence of olfactory tract/bulbs
- Holoprosencephaly & olfactory aplasia
17
Q
Arrhinencephaly
Severity of craniofacial defect __________ severity of underlying brain abnormality.
A
mirrors
- “The face predicts the brain”
- Cyclopia – most severe
- Hypotelorism – minimal change
18
Q
How does Arrhinencephaly present clinically?
A
- Clinical findings vary with severity of malformation
- Severe mental retardation, stillbirth, lack of olfaction
19
Q
What is the pathogenesis of Arrhinencephaly?
A
-
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
Q
What is the definition of Holoprosencephaly?
What are the 3 types?
A
**Incomplete separation of hemispheres **
- Alobar holoprosencephaly
- Semilobar holoprosencephaly
- Lobar holoprosencephaly
21
Q
What is Alobar holoprosencephaly?
A
- Small brain
- Cerebral hemispheres fused into single mass w/ no interhemispheric fissure: single large ventricle
- Hypoplasia of cortex
22
Q
What is Semilobar holoprosencephaly?
A
Partial formation of interhemispheric fissure
23
Q
What is Lobar holoprosencephaly?
A
- Midline continuity of cortex at frontal pole
- Almost normal brain size – often associated w/ craniofacial anomalies
24
Q
What is this?
A
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
28
What is this?
**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
32
What is this?
**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
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)
36
**Type 2 Chiari Malformation**
Clinical Findings
* Lower CN defects (swallowing, respiration)
* Arm weakness, spasticity
* S/S referable to hydrocephalus
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
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
39
**Dandy Walker Malformation**
Etiology
Pathogenesis
* Etiology
* **Most cases sporadic**
* Associated w/ Trisomies
* Pathogenesis
* Not understood
* Believed to occur before _3rd month gestation_
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)
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**
46
What is this?
**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
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
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?
Subependymal Germinal Matrix Hemorrhage
