Peripheral nerve injury

Question 1

Epineurium

Answer 1

surrounds entire nerve

Question 2

Perineurium

Answer 2

around bundles of axons (fascicles)

Question 3

Endoneurium

Answer 3

contained within the perineurium, consists of axons

Question 4

BBB

Answer 4

between inner perineurium and endothelial cells of microvasculature within endoneurium

Question 5

Group A axons

Answer 5

fastest conduction velocity
large diameter
myelinated
subdivided into alpha, beta, delta, gamma - typically used for motor neurons (drop A)

Question 6

Group B axons

Answer 6

smaller

still myelinated

Question 7

Group C axons

Answer 7

smallest
unmyelinated
slowest conduction velocity

Question 8

Sensory axon categorizations

Answer 8

by diameter
I: fastest
I, II, III: myelinated
IV: unmyelinated ( = type C)
subdivided into a, b

Question 9

Soma in neurons

Answer 9

contains organelles and cellular machinery required to produce empty vesicles
Vesicles transported (with energy) to axon terminals
ACh synthesized in axon terminals and then stored in vesicles
Soma absolutely required for neuron health
death of the soma = denervation

Question 10

Peripheral nerve axons

Answer 10

require cytoplasmic continuity between soma and axons for viability
2 types of Schwann cells associated: myelinating and ensheathing
Ensheathing Schwann cells ensheath the full length of axons
Basal lamina surrounding individual axon and myelin for continuity

Question 11

Demyelination of peripheral nerve axons

Answer 11

mildest form of nerve damage = segmental demyelination (Grade I injury; neuropraxia)
Schwann cells compromised

Question 12

Remyelination

Answer 12

Requires trophic factors and cytokines release by damaged Schwann cells and affected axons
Reciprocal signalling –> triggers proliferation of undifferentiated Schwann cells
Process takes time

Question 13

EMG/NCS

Answer 13

nerve conduction studies
Stimulate peripheral nerves with external stimulator, then record from skin surface above a skeletal muscle (e.g. thenar muscle)

Question 14

M-wave

Answer 14

Compound Muscle Action Potential (CMAP)

evoked by peripheral nerve stimulation of alpha motor neurons generated during muscle contraction

Question 15

Segmental demyelination

Answer 15

Reduced myelin thickness
AP travels more slowly
Prolonged M-wave latency
If several adjacent segments lost –> blockade, reduction in M-wave amplitude

Question 16

Peripheral nerve axon degeneration

Answer 16

Grade II (axonotmesis) or III (neurotmesis) nerve injury
Transected distal axon stump is not viable
Axonal and Schwann cell factors contribute to degeneration
Distal stump initiates Wallerian degeneration within minutes of injury

Question 17

Axonal loss in peripheral nerve

Answer 17

degeneration of alpha motor neuron –> denervation of motor units
fewer motor units fire AP within a skeletal muscle
decreased M-wave amplitude

Question 18

Wallerian degeneration

Answer 18

axonal factors:

• Ca influx at injury site: protein synthesis, growth cone formation
• Axon fragments into small pieces
• Growth factors released –> initiates Schwann cells dedifferentiation and proliferation

Schwann cell involvement

• myelin sheath breaks down into droplets
• Proliferation of undifferentiated Schwann cells –> phagocytose myelin droplets
• Increased differentiation of ensheathing Schwann cells
• -> forms Schwann cell tube around basal lamina of degenerating stump

Immune involvement

• breakdown of BBB
• Macrophage infiltration to engulf debris from degenerating axons

Question 19

Axon regeneration

Answer 19

Axons initiate growth

• transected proximal stump almost immediately initiates regeneration
• multiple growth cones form
• each has several filopodia expressing cellular adhesion molecules

Basal lamina required:
- Laminin and fibronectin interact with growth cone adhesion molecules to guide axon sprouts

Schwann cells:

• ensheathing Schwann cells encapsulate basal lamina/sprouting axons forming Schwann cell tube/column, which guides growth cone towards innervation target
• Secrete growth factors and guidance molecules within tube
• myelinating Schwann cells remyelinate each axonal outgrowth as it sprouts

Question 20

Nerve regeneration flaws

Answer 20

not perfect
some do not find innervation targets –> persistent deficits
Myelination not as extensive
Rate of regeneration is 1-4 mm/day

Question 21

Nerve laceration tx

Answer 21

Trim and repair

if not trimmed - higher likelihood of neuroma formation

Question 22

Small laceration gap repair

Answer 22

Conduit tubes for fibers to reattach

Question 23

Large laceration gap repair

Answer 23

Neuroma can form (esp without trimming)
best to connect it to distal end
if too wide to reconnect, can use graft (e.g. sural nerve)

Question 24

Time limit for re-innervation

Answer 24

Muscle: rough 12 month rule before irreversible change

Sensory end organs - can re-innervate after a long time lapse

Question 25

Nerve compression pathophys

Answer 25

Ischemia: O2-dependent ion channel dysfunction

• axoplasmic transport disrupted
• prolonged - death to support cells

Mechanical deformation

• myelin separation near nodes
• demyelination
• axon tears

Question 26

Effects of nerve compression

Answer 26

Depends on duration and pressure

Longer –> demyelination, fibrotic scar, axon disruromeption

Question 27

Carpal tunnel syndrome

Answer 27

Median nerve at base of hand
Numbness, tingling in lateral 3.5 fingers
Tx: splint and activity modification to provide largest volume for carpal tunnel

Question 28

Cubital tunnel syndrome

Answer 28

ulnar nerve behind elbow
Management: padding and avoid prolonged elbow flexion/leaning until improved
small towel or pillow wrapped around elbow when sleeping