Neural Development

Question 1

What are the 4 phases of neuromuscular development?

Answer 1

1. Axonal growth
2. Myogenesis
3. Synaptogenesis (formation of NMJs)
4. Synapse elimination

Question 2

What happens during the axonal growth phase of neuromuscular development?

Answer 2

• Axons from motor neuron cell bodies grow out to innervate myotome region of somite
• Connections between muscles & nerves are specific

Question 3

When does neural outgrowth occur?

Answer 3

Before primitive muscle masses contain any muscle fibres

Question 4

What happens during the myogenesis phase of neuromuscular development?

Answer 4

• Muscle tissue develops from mesoderm when mesoblasts differentiate into myoblasts
• Skeletal muscles develop the length of the embryo fro small clusters of cells (somites)

Question 5

What is the number of muscle fibres determined by during myogenesis?

Answer 5

Number of foetal myoblasts

Question 6

What happens during the synpatogenesis phase of neuromuscular development (formation of NMJs)?

Answer 6

• ACh receptors sprout all over the surface of the muscle fibre
• As spinal nerves sprout & target individual myoblasts, motor end plates are formed
• Initially multiple synaptic connections form
• NMJ formation: electrical stimulation & stretch contributes to preventing further innervations

Question 7

What happens during the synapse elimination phase of neuromuscular development?

Answer 7

Extra synapses eliminated through neuronal death & axon retraction

Question 8

When does synapse elimination also occur?

Answer 8

After injury to a nerve or post BTX-A injections to treat spasticity

Question 9

When does distinction into slow & fast twitch muscle fibres occur?

Answer 9

18-20 weeks in utero

Question 10

In normal growth & development, what is increase in gross muscle size due to?

Answer 10

Hypertrophy (increase in muscle cell size), not hyperplasia (increase in cell number)

Question 11

What happens during postnatal growth of the brain?

Answer 11

• Increase in size of neurons
• Increase in number of supporting cells (glia)
• Continued development of neural processes & synapses
• Continued myelination

Question 12

When does maximum density of synapses occur?

Answer 12

• Rapid formation in first 12 months, max density at approx 6-12 months
• Natural pruning/attrition occurs after this (brain retains connections that are used most)

Question 13

What forms the basis of pathway/synapse retention?

Answer 13

• Stimulation & experience (movement & sensory) enhances function
• Lack of this may lead to loss of unused connections)

Question 14

Where does the greatest metabolic activity occur in the neonate, at 2-3 months and 6-12 months?

Answer 14

• Neonate: Sensory-motor cortex & brain stem
• 2-3 months: Visual & adjacent parietal cortex (development of visuospatial integrative function)
• 6-12 months: Frontal cortex (development of higher cortical function)

Question 15

When does myelination occur?

Answer 15

• Must occur before neurons with long axons become fully functional
• Begins in 4th fetal month, most sheaths completed by end of 3rd year of life
• Occurs at different rates in each system

Question 16

What is the consequence of myelination occurring at different rates in each system?

Answer 16

When neurons are damaged perinatally (time around birth), motor deficits may not be observed until the child is older (i.e. when the systems damaged would normally have become functional e.g. walking)

Question 17

What do typical developmental milestones reflect?

Answer 17

Maturation of the nervous system & progressive myelination

Question 18

How does motor control develop & what may it be impacted by?

Answer 18

• Head to toe
• Proximal to distal
• Gross to fine
• May be impacted by requirement of postural stability before the skill can be demonstrated
• E.g. newborns in supported seating show some aiming of arm movement towards slowly moving attractive object

Question 19

At what stages can disturbances to the developing brain occur?

Answer 19

• Prenatal
• Perinatal
• Postnatal

Question 20

What are the prenatal causes of brain injury?

Answer 20

• Genetics
• Fetal malformation during growth
• Maternal injection (rubella, CMV, herpes simplex)
• Toxins (alcohol, anti-epileptics, lead)
• Vascular problems, hypoxia, thrombotic episodes
• Metabolic (iodine deficiency, maternal thyroid disease)

Question 21

What are the perinatal causes of brain injury?

Answer 21

• Problems during labour & delivery (e.g. obstructed labour, antepartum haemorrhage, cord prolapse)
• Neonatal problems (e.g. severe hypoglycaemia, untreated jaundice, neonatal shock, infection, intracerebral haemorrhage, hypoxia ischaemic encephalopathy)

Question 22

What are the postnatal causes of brain injury?

Answer 22

• Infection e.g. meningitis
• Hypoxia e.g. drowning
• Trauma e.g. MVA, ABI, NAI

Question 23

What are the basic mechanisms supporting brain plasticity in children?

Answer 23

• Persistence of neurogenesis
• Elimination of neurons through programmed cell death
• Postnatal proliferation & pruning of synapses until 16 years (toddler has 2 x more synapses than adult)

Question 24

What happens following transient disruption of normal maturation processes in the developing brain?

Answer 24

• Intrinsic attempt to compensate for the injury
• Evidence for functional reorganisation available
• Exact mechanisms are poorly understood

Question 25

What are the key points regarding brain plasticity in children?

Answer 25

• Developing brain has enhanced plasticity
• Neural system retains connections that are used most
• Experience forms the basis of use & retention

Question 26

What is crucial in paediatric interventions?

Answer 26

Providing stimulation & experience (sensory & motor) as early as possible is crucial in paediatric interventions to maximise functional outcomes

Question 27

What is recovery from brain damage in children influenced by?

Answer 27

• Size of lesion
• Position of lesion
• Type of insult
• Timing of lesion
• Integrity of areas surrounding/contralateral to lesion (potential for compensation)
• Presence & duration of epilepsy

Question 28

How does the size of the lesion influence recovery?

Answer 28

• Not linear relationship
• Large lesion may cause shift from intra to inter-hemispheric compensation
• Larger lesions may include white & grey matter (visual/epilepsy/cognitive problems)

Question 29

How does the site of the lesion influence recovery?

Answer 29

• Different areas have different metabolic demands
• Some areas are less equipped to recover (e.g. poor blood supply)
• Cortical damage (unilateral = hemiplegia)
• Integrity of areas surrounding/contralateral to lesion (potential for compensation)

Question 30

How does the type of insult influence recovery?

Answer 30

• Post epileptic hemiplegia has less favourable outcome than vascular cause
• Presence & duration of epilepsy results in poorer outcomes

Question 31

How does the timing (age & developmental status) of the injury influence recovery in CP?

Answer 31

• <20 weeks: brain malformations due to disruptions of neuronal migration
• 26-30 weeks: white matter damage in periventricular areas
• Term babies: cortical & basal ganglia damage