Peds Neuro - Embryogenesis Flashcards
What is the rhombencephalon?
Metencephalon: Pons, Cerebellum
Myelencephalon: medulla
What is the most common cause of mental retardation? What is it associated with?
Fetal Alcohol Syndrome
Associated with microcephaly, congenital heart disease, most severe form = holoprosencephaly
What are examples of neuralation failure? (4)
Anencephaly (failure of anterior neural tube closure)
Encephalocele (herniation of brain tissue into open space typically occipital, restricted failure of anterior neural tube closure)
Spina Bifida
Chairi Malformation
What kind of receptors are Meisnner’s Corpsule? Pacinian Corpuscles?
Meisnner’s: Touch
Pacinian: Vibration
Define the difference between Chairi Types 1-4
Chiari Type I: Displacement of cerebellar tonsils through foramen magnum >5mm; Syringomyelia
Chiari Type 2: Displacement of medulla, 4th ventricle and vermis through foremen magnum, associated with peaked tectum and lumbar myelomeningocele, +Hydrocephalus from cerebral aqueduct stenosis
Chiari Type 3: Similar to Chiari Type w/ occipital encephalocele, hydrocephalus
Chiari Type IV: Cerbellar hypoplasia (now called primary cerebellar agenesis)
What are the 3 areas of the brain that contain no BBB?
Subfornical Organ
Area Postrema
Neurohypophysis
Describe holoprosencephaly: appearance, mutation
Failure of the prosencephalon development (forebrain) resulting in failure to divide into two hemispheres.
Mutation: Sonic HedgeHog
Describe the 3 subtypes of Holoprosencephaly?
- Alobar: Severe, hemispheres fail to separate resulting in cyclopia
- Semilobar: Incomplete separation
- Lobar: Inter-hemispheric fissure is complete, thalami separated, frontal horns of lateral ventricles are fused, septum pellucidum is absent
Why can a tethered spinal cord occur? What diseases is it associated with?
Stretching of spinal cord from strong film terminals or lipoma causing ischemia
Associated with Chiari Type 1, Trisomy 13/18, DiGeorge Syndrome
What is the difference between porencephaly vs schizencephaly?
Porencephaly: cleft or cyst in cerebral hemisphere, NOT lined with grey matter; Likely from in utereo injury, Can cause hydrocephalus
Schizencephaly: cleft lined with grey matter connecting the ventricle to the plural surface of the brain
Describe the difference between schizencephaly: open vs closed lip?
Open lip: cleft walls are separated and filled with CSF
Closed lip: cleft walls are in apposition (no separation)
What disease is associated with semilobar prosencephaly?
Septo-optic Dysplasia (mutation: HESX-1>Sonic Hedgehog)
- Hypothalamic hamartomas leading to panhypopituitarism
- Agenesis of cerebellar vermis
- Absence of septum pullicidum
- Optic nerve hypoplasia
- Fusion of the dentate (ataxia)
What is the difference between simple vs complex craniosynostosis?
Simple : early closure of one or more skull sutures but do not cause hydrocephalus or symptoms
Complex: Several syndromes (Crouzon, Alpert = most high yield)
What are the examples of neuronal migration? (4)
- Schizencephaly
- Lissencephaly
- Polymicrogyria
- Neuronal heterotopia
What are examples of neuronal proliferation (3rd month of gestation)?
Microcephaly
- Syndromic (trisomy 13/18, TORCH, metabolic-toxic)
- Familial genetic (fragile x, tuberous sclerosis)
What is the pathophysiology of caudal regression syndrome/sacral agenesis?
- Degeneration of the coccyx and sacral vertebrae/spinal cord secondary to decreased sonic hedgehog expression at the caudal end of the neural tube
- Atrophy of lower extremities & malformations of rectum/GU system
What is the main embryonal layer forming the CNS?
Ectoderm
Define acquired causes for non-communicating vs communicating acquired pediatric hydrocephalus?
Non-communicating: aqueduct stenosis caused by intrauterine infection, hemorrhage, trauma, tumor
Communicating: SAH, Meningitis
What 3 syndromes does sonic hedgehog mutation cause?
Holoprosencephaly
VACTERL Syndrome: vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal abnormalities, limb abnormalities
Caudal Regression/Sacral agenesis
What is derived from the prosencephalon?
Telencephalon: cortex, amygdala, caudate, putamen
Diencephalon: thalamus, hypothalamus, globus pallidus
How does the diagnosis of pediatric hydrocephalus differ from adults?
The diagnosis requires a head circumference >2 SD for gestational age or inc in head circumference >2SD during first year of life
Elevated ICP is not usually seen until after cranial sutures close
What kind of developmental failure leads to agenesis of corpus callosum? Associated with what disease?
Midline Prosencephalic Cleavage failure
Associated with Aicardi Syndrome (IDD, Myoclonic Epilepsy, Chorioretinal abnormalities, vertebral abnormalities, Agenesis of Corpus Callosum, Polymicrogyria)
What are examples of prosencephalic development failure? (3)
- Holoprosencephaly
- Septo-optic dysplasia
- Agenesis of corpus callosum
What are the chromosomes associated with neural tube defects? Teratogens?
Trisomy 13/18
Valproate, Phenytopin, thalidomide
Answer the following high yield points for myelination:
- When does myelination begin?
- Does the PNS or CNS myelinate first?
- What are the earliest structures to be myelinated
- What is the most rapid myelination period?
- 4 month of gestation
- PNS myelinates first
- Earliest structures at 14 weeks: MLF, dorsal roots, cranial nerves (except II, VIII, V)
- Rapid myelination: birth - 2 years
Describe the neural tube formation process
Notocord -> Formation of neural plate (from ectoderm) —> Neural tube formation vita neurulation (3-6wk)
Neural tube gives rise to Neural Crest Cells, Anterior Neuropore (Defects: Ancephaly, Encephalocele), Posterior neuropore (Spina bifida, myelomeningocele)
Neural crest cells derived from the neural tube gives rise to PNS, adrenal medulla, chromatin tissue, melanocytes
What are the two x-linked hydrocephalus syndromes? Mutation?
Mutation: L1CAM (cell adhesion)
- MASA Disorder: M-MR, A-Aphasia, S-Shuffling gait, A- Adducted thumbs
- X-linked aqueduct stenosis: Adducted thumbs, agenesis of corpus callosum, brain stem malformation, hypoplastic corticospinal tracts
What syndrome is this?
- Brahycephaly (short head)
- Soft tissue syndactyly
- Short upper extremities
- Intellectual Disability (IDD)
Alpert Syndrome
When does the neural tube close? Anterior neuropore? Posterior neuropore? Secondary neurulation (caudal neural tube formation)
- Closure of neural tube: Day 22
- Anterior closure: Day 25
- Posterior closure: Day 27
- Secondary neurulation forms sacral/coccygeal/filum terminals/ventricular terminalis: Days 28-32
Describe hydranecephaly? Causes?
Cerebral hemispheres are absent and replaced by CSF
- Caused by destructive process (microcephaly) or hydrocephalus (macrocephaly)
What type of developmental failure causes spina bifida?
Neuralation during the closure of vertebral arches
What disorder is Polymicrogyria common in?
Zellweger Syndrome
What are three kinds of heterotopia (and associated gene)?
- Focal Cortical Dysplasia
- Periventricular Heterotopia (Filamin Gene)
- Laminar (Band) Heterotopia (DCX/Doublecortin gene - Females only)
What syndrome is this?
- Brachyencephaly results in shortened depth of anterior cranial fossa leads to multiple CN lesions (conductive hearing loss)
Crouzon Syndrome
What is derived from mesencephalon?
Midbrain
Define Dandy-Walker Malformation? Associations?
Most severe form:
- Absence of cerebellar vermis
- Large posterior fossa
- Cystic dilation of 4th ventricle
Name all 6 layers of cerebral cortex. When are they present in gestation?
27 weeks
- Molecular layer
- External granular layer
- External pyramidal layer
- Internal granular layer
- Internal pyramidal layer
- Multiform layer
Define the difference in presentation for the vein of Galen malformations (caused by direct arterial connections):
Neonatal, Infantile, Childhood, Adult
- Neonatal: shunt involves sig proportion of cardiac output; presents as high-output CHF
- Infantile: Hydrocephalus from obstruction of aqueduct of Sylvia season by enlarged veins of Galen
- Childhood: Presents as IDD, Seizures
- Adult: Hemorrhagic infarction
Name these malformations:
- Few gyri that are broad and thick
- Numerous small gyri
- Pachygyri
2. Polymicrogyri
What are the 4 subtypes of spina bifida? Describe the differences
- Spina bifida occulta: incidental defect in dorsal bony vertebrae, cord remains in canal with no external sac
- Meningocele: meningeal outpouching that does not contain neural tissues & covered by skin, minimal association with brain malformation
- Myelomeningocele: failure of posterior neuropore closure; meningeal outpouching includes neural tissue; associated with Chiari Type II —> Hydrocephalus from the cerebral aqueduct stenosis
- Myeloschisis: neural elements uncovered, v bad prognosis = stillborn babies
What syndrome is this:
- Congenital Muscular Dystrophy
- Lissencephaly
- Cerebellar malformation
- Retinal malformation
- Macrocephaly
Walker-Warburg Syndrome
Describe the difference between Lissencephaly Type I vs Type II? (appearance, gene, failure of developmental process, associated diseases)
Type 1: Smooth Brain, Few to no gyro, LIS1 gene (Miller-Decker) or DCX gene in Males (X-linked)
Type 2: Failure of neurons to terminate radial migration in cerebral cortex, Cobblestone, Fukuyama Muscle Dystrophy, Walker-Warburg Syndrome)
