Nerves conduction study, Axonal loss vs Demyelination
- 1. Nerves conduction study Part 2: Axonal loss vs Demyelination For post basic neurophysiology course Dr Ahmad Shahir Mawardi Neurology Departmert Hospital Kuala Lumpur 21 October 2015
- 2. Neuropathic lesions Single unit of neuron •Divided into Axonal loss and Demyelination Axonal loss Demyelination
- 3. • Causes: – Physical disruption of the nerve – toxic, metabolic, or genetic conditions Axonal loss Single unit of neuron
- 4. • Resulting from loss or dysfunction of the myelin sheath • Causes: – entrapment or compressive neuropathies (common) – genetic (e.g., Charcot-Marie-Tooth polyneuropathy), – toxic (e.g., diphtheria) – post immunologic attack on the myelin (e.g.GBS). Demyelination Single unit of neuron
- 5. Axonal loss
- 6. Axonal Loss • Most common pattern seen on NCSs. • Axons are lost--> amplitudes decrease • Reduced amplitude of the CMAP, SNAP, and MNAPs – reflect the number of underlying motor, sensory,and mixed nerve axons • How to assess axon loss? • To compare with: – previous baseline value – normal control value – contralateral (asymptomatic) side.
- 7. Axonal Loss • Conduction velocity and distal latency : Normal • Mild slowing of conduction velocity and distal latency may occur if the largest and fastest conducting axons are lost. • Marked slowing, does not occur.
- 8. Axonal Loss • While amplitude markedly decreases, the conduction velocity and distal latency remain normal, due to the preservation of the fastest fibers.
- 9. Axonal Loss • Axonal loss with abnormal CV only occur in 2 possible extremes: 1.severe loss of axons with only a few of the fastest fibers remaining 2.all axons are lost except for a few of the normal slowly conducting fibers (the amplitude also falls dramatically) • In general, axonal loss lesions result in a pattern between these two extremes.
- 10. Axonal Loss • However, conduction velocity can drop only as low as 35 m/s (~ 75% of the lower limit of normal). – normal myelinated fibers do not conduct anything slower than this. • Distal latencies generally do not exceed 130% of the upper limit of normaL
- 11. Axonal Loss • When there is random dropout of fibers, the amplitude falls, the conduction velocity slows slightly, and the distal latency mildy prolongs
- 12. Axonal Loss- Criteria 1) Amplitudes decrease 2) Conduction velocities are normal or slightly decreased but never below 75% of the lower limit of normal, and 3)Distal latencies are normal or slightly prolonged but never greater than 130% of the upper limit of normal. Normal Axonal loss
- 13. Axonal Loss • The only exception occurs in hyperacute axonal loss lesions e.g a nerve transection. • Day 3 to 4 : NCS normal (provided both stimulation and recording are done distal to the lesion). • Days 3 to 10, the process of Wallerian degeneration occurs: the nerve distal to the transection undergoes degeneration,resulting in a low amplitude both distally and proximally.
- 14. Axonal Loss • The process of wallerian degeneration for: – motor fibers (typically days 3-5) – sensory fibers (typically days 6-10). • At this point, the typical pattern of axonal loss will be seen on NCSs. – simulates conduction block – best termed pseudo-conduction block.
- 15. Demyelination
- 16. Demyelination • Myelin is essential for saltatory conduction. • Without myelin, nerve conduction velocity is either markedly slowed or blocked • Demyelination is associated with – marked slowing of conduction velocity (< than 75% of the lower limit of normal), – marked prolongation of distal latency (>130% of the upper limit of normal), or – both. • Conduction velocities and latencies slower than these cutoff values imply primary demyelination
- 17. Demyelination • All pain fibers not stimulated or recorded with routine NCS • Any motor, sensory, or mixed nerve conduction velocity that is slower than 35 m/s in the arms or 30 m/s in the legs signifies unequivocal demyelination. • Regenerating nerve fibers after a complete axonal injury (e.g., nerve transection) velocities can be this slow and not signify a primary demyelinating lesion (rare).
- 18. Demyelination • Boderline slowing--> refer to amplitude of the potential. – normal amplitude: demyelination – markedly reduced amplitude : severe axonal loss. • Example: demyelination severe axonal loss
- 19. Demyelination • In demyelination, amplitude changes are variable. • Reduced amplitudes not necessarily a marker of axonal loss • This is depends on two conditions: 1. whether sensory or motor studies are performed 2. whether or not conduction block is present. • Sensory amplitudes often are low in demyelinating lesions. – result from the temporal dispersion and phase cancellation. (normal processes) – Exaggerated by demyelinative slowing, which further lowers sensory amplitudes
- 20. Temporal dispersion & phase cancellation Sensory median nerve Distal stimulation (wrist) Proximal stimulation (elbow) •longer in duration •lower in amplitude and area *If the SNAP is small at the distal stimulation site, it may be difficult or impossible to obtain a potential with proximal stimulation.
- 21. Temporal dispersion & phase cancellation • present of fast and slow fiber • at proximal stimulation sites results in the negative phase of the slower fibers overlapping with the positive trailing phase of fastest fibers. • These superimposed positive and negative phases cancel each other out (phase cancellation) • resulting in a decrease in area and amplitude, beyond the decrease in amplitude and increase in duration from the effects of temporal dispersion alone.
- 22. Temporal dispersion & phase cancellation Temporal dispersion phase cancellation
- 23. Temporal dispersion & phase cancellation • less prominent for motor fibers
- 24. Conduction Block • Reduced amplitudes in demyelinating lesions are seen when conduction block is present Normal Conduction block stimulation stimulation
- 25. Conduction Block • If a conduction block is present in a demyelinating lesion, the CMAP amplitude depends on the site of stimulation and the location of the conduction block simulate an axonal loss lesion RecordingStimulation
- 26. Conduction Block • From studies of normal subjects – CMAP amplitude and area generally do not decrease by more than 20%, – CMAP duration generally does not increase by more than 15%, when recorded from the typical distal and proximal stimulation sites • However, in demyelinating lesions, temporal dispersion and phase cancellation become more prominent for motor fibers. Temporal dispersion without conduction block. Drop in amplitude in proximal is mainly due to abnormal temporal dispersion
- 27. Conduction Block • Using computer simulation models, electrophysiologic conduction block define as: Drop more than 50% drop in area between proximal and distal stimulation sites.
- 28. Demyelination : Clinical implication 1. Entrapment neuropathies – To detect exact localization by demonstrating focal demyelination, either by slowing or by conduction block. 1. Prognosis and the time of recovery – the relative degree of conduction block indicates how much weakness and sensory loss are due to demyelination rather than axonal loss. – e.g conduction block- demyelination axonal loss good prognosis after remyelination (weeks) less complete, longer recovery
- 29. Demyelination : Clinical implication 3. Presence of conduction block at nonentrapment sites often can be used to differentiate between acquired and inherited conditions. vs
- 30. • Inherited demyelinating polyneuropathies (e.g., Charcot-Marie-Tooth polyneuropathy), – uniform slowing of conduction velocity without conduction blocks. • Acquired demyelinating polyneuropathies (e.g., GBS, CIDP), – patchy and focal demyelination , resulting in conduction block on NCSs (Figure 3-21). Demyelination : Clinical implication CIDP Conduction block and temporal dispersion
- 32. Axonal Loss - time-related changes • Wallerian degeneration of the nerve does not occur until days 3 to 5 for motor fibers and days 6 to 10 for sensory fibers • After wallerian degeneration occurs, NCSs become abnormal -->axonal loss: – amplitudes decrease, – with relative preservation of (CVs) and (DLs).
- 33. Axonal Loss - time-related changes • After wallerian degeneration occurs: – Amplitudes for motor studies decline slightly earlier than sensory nerves – If the largest and fastest axons lost, there may be some slowing of CV and DL
- 34. Axonal Loss - needle EMG • Onset of the lesion : – ↓ recruitment of MUAP • Because some axons and their motor units have been lost, the only way to increase force is to fire the remaining available motor units faster – No spontaneous activity & normal MUAP • Next several weeks – Abnormal spontaneous activity (i.e denervating potentials-fibrillation potentials and PSWs) develops.
- 35. • Lesion of an L5-SI nerve root (i. e., the longest distance between a lesion and the muscle). • Fibrillation potentials and positive sharp waves take: 10 to 14 days to develop in the paraspinal muscles, 2 to 3 weeks in the proximal thigh, 3 to 4 weeks in the leg 5 to 6 weeks in the distal leg and foot. Axonal Loss - needle EMG • Lesion in the distal nerve or near the NMJ (i. e., the shortest distance between a lesion and the muscle, as occurs in botulism). • Fibrillation potentials develop in just a few days. The time it takes for denervating potentials to develop depends on 1. the length of nerve between the muscle being studied 2. the site of the lesion.
- 36. Axonal Loss - needle EMG • Chronic/Reinnervation : several months. – MUAPs become longer in duration, higher in amplitude, and polyphasic • If reinnervation is successful (months to years), – spontaneous activity disappears – leaving only reinnervated MUAPs with decreased recruitment on needle EMG. – Motor and sensory amplitudes may improve on NCSs after successful reinnervation.
- 37. Demyelinating lesions • The pattern of abnormalities is depends on the degree of demyelination. • Demyelination results in marked slowing of conduction velocity and if severe enough conduction block • Wallerian degeneration does not occur. • Motor: pure slowing therefore does not result in any fixed weakness. • Sensory: pure slowing may result in depressed or absent reflexes and a perception of altered sensation, but not in fixed numbness.
- 38. Demyelinating lesions • Nerve conduction parameters vary in demyelination, depending on the site(s) of demyelination. CV ↓ DL: prolonged F wave : prolonged Amplitud: ↓ CB : present CV : Normal DL: prolonged F wave : prolonged Amplitud: ↓ CB: absent CV Normal DL: Normal F wave : prolonged Amplitud: Normal CB: absent
- 39. Conduction block- implications 1.It implies that the clinical deficit (weakness, numbness) is secondary to demyelination that recovery can occur with remyelination. 2.Can be used to localize the lesion in entrapment neuropathies (e.g., radial neuropathy at the spiral groove, median neuropathy at the carpal tunnel) 3.Help to differentiates acquired from inherited demyelinating neuropathy conditions. – GBS (CB) vc CMT (uniform slowing)
- 40. Demyelinating lesions- Conduction block • When a demyelinating lesion results in CB, clinical numbness and weakness develop acutely. • Distal to the CB, the nerve continues to conduct normally – distal NCSs remain normal (acute axonal loss lesions) • Wallerian degeneration never occurs. • However, if the nerve is stimulated above the lesion, electrophysiologic evidence of focal demyelination (Le., marked CV slowing, conduction block, or both) will be seen.
- 41. Demyelinating lesions: Pseudo-conduction block • Conduction block may be seen in an axonal loss lesion ONLY in nerves transection If the studies are repeated after 1 week, the distal nerve will have degenerated and the apparent block will no longer be present.
- 42. Demyelinating lesions- EMG • Pure demyelinating lesion with conduction block : – reduced recruitment • Demyelination (results only in slowing), without conduction block, – Normal EMG Pure demyelinating lesions are uncommon. Most demyelinating lesions have some secondary axonal loss, whether they are inherited or acquired, with conduction block or with slowing alone
- 43. Axonal Loss
- 44. Axonal Loss
- 45. Demyelination
- 46. Demyelination
- 47. Demyelination
- 48. Thank you