Peds Neuro - Embryogenesis

Question 1

What is the rhombencephalon?

Answer 1

Metencephalon: Pons, Cerebellum
Myelencephalon: medulla

Question 2

What is the most common cause of mental retardation? What is it associated with?

Answer 2

Fetal Alcohol Syndrome

Associated with microcephaly, congenital heart disease, most severe form = holoprosencephaly

Question 3

What are examples of neuralation failure? (4)

Answer 3

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

Question 4

What kind of receptors are Meisnner’s Corpsule? Pacinian Corpuscles?

Answer 4

Meisnner’s: Touch

Pacinian: Vibration

Question 5

Define the difference between Chairi Types 1-4

Answer 5

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)

Question 6

What are the 3 areas of the brain that contain no BBB?

Answer 6

Subfornical Organ
Area Postrema
Neurohypophysis

Question 7

Describe holoprosencephaly: appearance, mutation

Answer 7

Failure of the prosencephalon development (forebrain) resulting in failure to divide into two hemispheres.

Mutation: Sonic HedgeHog

Question 8

Describe the 3 subtypes of Holoprosencephaly?

Answer 8

1. Alobar: Severe, hemispheres fail to separate resulting in cyclopia
2. Semilobar: Incomplete separation
3. Lobar: Inter-hemispheric fissure is complete, thalami separated, frontal horns of lateral ventricles are fused, septum pellucidum is absent

Question 9

Why can a tethered spinal cord occur? What diseases is it associated with?

Answer 9

Stretching of spinal cord from strong film terminals or lipoma causing ischemia

Associated with Chiari Type 1, Trisomy 13/18, DiGeorge Syndrome

Question 10

What is the difference between porencephaly vs schizencephaly?

Answer 10

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

Question 11

Describe the difference between schizencephaly: open vs closed lip?

Answer 11

Open lip: cleft walls are separated and filled with CSF

Closed lip: cleft walls are in apposition (no separation)

Question 12

What disease is associated with semilobar prosencephaly?

Answer 12

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)

Question 13

What is the difference between simple vs complex craniosynostosis?

Answer 13

Simple : early closure of one or more skull sutures but do not cause hydrocephalus or symptoms

Complex: Several syndromes (Crouzon, Alpert = most high yield)

Question 14

What are the examples of neuronal migration? (4)

Answer 14

• Schizencephaly
• Lissencephaly
• Polymicrogyria
• Neuronal heterotopia

Question 15

What are examples of neuronal proliferation (3rd month of gestation)?

Answer 15

Microcephaly

• Syndromic (trisomy 13/18, TORCH, metabolic-toxic)
• Familial genetic (fragile x, tuberous sclerosis)

Question 16

What is the pathophysiology of caudal regression syndrome/sacral agenesis?

Answer 16

• 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

Question 17

What is the main embryonal layer forming the CNS?

Answer 17

Ectoderm

Question 18

Define acquired causes for non-communicating vs communicating acquired pediatric hydrocephalus?

Answer 18

Non-communicating: aqueduct stenosis caused by intrauterine infection, hemorrhage, trauma, tumor

Communicating: SAH, Meningitis

Question 19

What 3 syndromes does sonic hedgehog mutation cause?

Answer 19

Holoprosencephaly
VACTERL Syndrome: vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal abnormalities, limb abnormalities
Caudal Regression/Sacral agenesis

Question 20

What is derived from the prosencephalon?

Answer 20

Telencephalon: cortex, amygdala, caudate, putamen
Diencephalon: thalamus, hypothalamus, globus pallidus

Question 21

How does the diagnosis of pediatric hydrocephalus differ from adults?

Answer 21

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

Question 22

What kind of developmental failure leads to agenesis of corpus callosum? Associated with what disease?

Answer 22

Midline Prosencephalic Cleavage failure

Associated with Aicardi Syndrome (IDD, Myoclonic Epilepsy, Chorioretinal abnormalities, vertebral abnormalities, Agenesis of Corpus Callosum, Polymicrogyria)

Question 23

What are examples of prosencephalic development failure? (3)

Answer 23

1. Holoprosencephaly
2. Septo-optic dysplasia
3. Agenesis of corpus callosum

Question 24

What are the chromosomes associated with neural tube defects? Teratogens?

Answer 24

Trisomy 13/18

Valproate, Phenytopin, thalidomide

Question 25

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?

Answer 25

- 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

Question 26

Describe the neural tube formation process

Answer 26

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

Question 27

What are the two x-linked hydrocephalus syndromes? Mutation?

Answer 27

Mutation: L1CAM (cell adhesion) 1. MASA Disorder: M-MR, A-Aphasia, S-Shuffling gait, A- Adducted thumbs 2. X-linked aqueduct stenosis: Adducted thumbs, agenesis of corpus callosum, brain stem malformation, hypoplastic corticospinal tracts

Question 28

What syndrome is this? - Brahycephaly (short head) - Soft tissue syndactyly - Short upper extremities - Intellectual Disability (IDD)

Answer 28

Alpert Syndrome

Question 29

When does the neural tube close? Anterior neuropore? Posterior neuropore? Secondary neurulation (caudal neural tube formation)

Answer 29

- 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

Question 30

Describe hydranecephaly? Causes?

Answer 30

Cerebral hemispheres are absent and replaced by CSF | - Caused by destructive process (microcephaly) or hydrocephalus (macrocephaly)

Question 31

What type of developmental failure causes spina bifida?

Answer 31

Neuralation during the closure of vertebral arches

Question 32

What disorder is Polymicrogyria common in?

Answer 32

Zellweger Syndrome

Question 33

What are three kinds of heterotopia (and associated gene)?

Answer 33

- Focal Cortical Dysplasia - Periventricular Heterotopia (Filamin Gene) - Laminar (Band) Heterotopia (DCX/Doublecortin gene - Females only)

Question 34

What syndrome is this? - Brachyencephaly results in shortened depth of anterior cranial fossa leads to multiple CN lesions (conductive hearing loss)

Answer 34

Crouzon Syndrome

Question 35

What is derived from mesencephalon?

Answer 35

Midbrain

Question 36

Define Dandy-Walker Malformation? Associations?

Answer 36

Most severe form: - Absence of cerebellar vermis - Large posterior fossa - Cystic dilation of 4th ventricle

Question 37

Name all 6 layers of cerebral cortex. When are they present in gestation?

Answer 37

27 weeks 1. Molecular layer 2. External granular layer 3. External pyramidal layer 4. Internal granular layer 5. Internal pyramidal layer 6. Multiform layer

Question 38

# Define the difference in presentation for the vein of Galen malformations (caused by direct arterial connections): Neonatal, Infantile, Childhood, Adult

Answer 38

1. Neonatal: shunt involves sig proportion of cardiac output; presents as high-output CHF 2. Infantile: Hydrocephalus from obstruction of aqueduct of Sylvia season by enlarged veins of Galen 3. Childhood: Presents as IDD, Seizures 4. Adult: Hemorrhagic infarction

Question 39

Name these malformations: 1. Few gyri that are broad and thick 2. Numerous small gyri

Answer 39

1. Pachygyri | 2. Polymicrogyri

Question 40

What are the 4 subtypes of spina bifida? Describe the differences

Answer 40

1. Spina bifida occulta: incidental defect in dorsal bony vertebrae, cord remains in canal with no external sac 2. Meningocele: meningeal outpouching that does not contain neural tissues & covered by skin, minimal association with brain malformation 3. Myelomeningocele: failure of posterior neuropore closure; meningeal outpouching includes neural tissue; associated with Chiari Type II —> Hydrocephalus from the cerebral aqueduct stenosis 4. Myeloschisis: neural elements uncovered, v bad prognosis = stillborn babies

Question 41

What syndrome is this: - Congenital Muscular Dystrophy - Lissencephaly - Cerebellar malformation - Retinal malformation - Macrocephaly

Answer 41

Walker-Warburg Syndrome

Question 42

Describe the difference between Lissencephaly Type I vs Type II? (appearance, gene, failure of developmental process, associated diseases)

Answer 42

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)