Neurodevelopment

Question 1

Critical events in neurodevelopment and timeline

Answer 1

1. Neurulation: done by 4 wks
2. Segmentation and cleavage: done by 8 wks
3. Proliferation and migration: 8 weeks-birth

Question 2

Three major events occur in neurulation:

Answer 2

1. Differentiation: neuroectoderm and neural crest
2. Establish axes of symmetry: cephalic to caudal, ventral to dorsal
3. Signal molecule gradients

Question 3

Closure of the neural tube results in formation of which axis?

Answer 3

Dorsoventral

Question 4

What three segments form? And what do they split into?

Answer 4

1. Prosencephalon (forebrain)
   
   • Telencephalon (basal ganglia, cortex)
   • Diencephalon (thalamus, hypothalamus)
2. Mesencephalon (midbrain)
3. Rhombencephalon (hindbrain)
   
   • Metencephalon (pons, cerebellum)
   • Myelencephalon (medulla)

Question 5

Three major events in proliferation & migration

Answer 5

1. Evolution of computational capacity
2. Neuroectodermal precursors
3. Migration

Question 6

Which neural tube defects are involved with the anterior neuropore?

Answer 6

• Anencephaly (most severe)

- Encephalocoele

Question 7

Which neural tube defects are involved with the posterior neuropore?

Answer 7

• Meningomyelocoele
• Meningocoele
• Spina bifida occulta (least severe)

Question 8

Which neural tube defect involves both anterior and posterior neuropore?

Answer 8

Arnold chiari malformation

Question 9

How can neural tube defects be detected in utero? Which neural tube defect cannot be detected in utero?

Answer 9

Measure maternal serum alpha fetaprotein (AFP) with confirmation of dysraphia by US

Spina bifida occulta

Question 10

What are well-documented risk factors for neural tube defects

Answer 10

• Folate deficiency
• Retinoic acid administration for acne
• Valoproate for seizures

Question 11

What is a Dandy Walker malformation

Answer 11

Segmentation/cleavage problem - Sites where CSF flow out of ventricle get blocked, blows hole in midline of cerebellum

Question 12

What is Holoprosencephaly? What chromosomal defect is it associated with?

Answer 12

Spectrum of defects of segmentation between prosencephalon into telencephalic hemispheres

Trisomy 13 Patau’s and trisomy 18

Question 13

What is most minimal lesion of holoprosencephaly

Answer 13

Arrhinencephaly - “no nose brain”

Question 14

What is most severe lesion of holoprosencephaly

Answer 14

Alobar holoprosencephaly with cyclopia and other midfacial defects

Question 15

What three types of defects of proliferation and migration are there?

Answer 15

1. Axonal migration - agenesis of corpus callosum
2. Gyral pattern formation
   
   • Lissencephaly - smooth brain - intellectual disability assoc. with seizures (defect of migration)
   • Polymicrogyria - “many small gyri” - only two layers (molecular and neuronal)
3. Cortical organization - Band heterotopia: double cortex, Focal cortical neuronal heterotopia