Pathophysiology of Peripheral Nerve Lesions David A. Lake, PT, PhD Department of Physical Therapy Armstrong Atlantic State University Savannah, GA

Pathophysiology of Peripheral Nerve Lesions

David A. Lake, PT, PhD

Department of Physical Therapy

Armstrong Atlantic State University

Savannah, GA

Anatomy of Peripheral Nerves

• Peripheral nerves are composed of many nerve fibers (axons) bundled together by connective tissues


• Each axon is surrounded by a connective tissue layer called the endoneurium


• Axons are grouped together into fascicles, and each fascicle is surrounded by another connective tissue layer, the perineurium


• Fascicles are grouped together, covered by an outer connective tissue layer, the epineurium, to form a peripheral nerve


• These connective tissue layers protect the nerve axons from injury

Damage to Peripheral Nerves

• Nerve injury is classified by the extent of the injury to the nerve into one of 3 classification– Neurapraxia– Axonotmesis– Neurotmesis


• Neurapraxia• Defined as failure of

conduction in a nerve in the absence of structural changes, due to compression or ischemia

• Lack of conduction through the area of compression but conduction above and below the compression

• Return of function normally ensues.


• Neurapraxia– Histological

analysis shows enlargement at the site of entrapment secondary to in thickness & amount of perineurial and endoneurial connective tissues.

Normal Nerve

Compressed Nerve


• Neurapraxia– Occasionally compression can result in

only slowed conduction through the region due to widened nodal regions (formerly referred to as axonostenosis)

– Sites of slowing often just distal & proximal to the site of compression

– Symptoms of compression (pain, numbness & paraesthesias) are more common and more intense when compression is combined with peripheral ischemia


• Neurapraxia– Characteristics more associated with

the degree of compression include:

• Amount of Action Potential slowing

• Decrease in sensory evoked potentials and sensory NCV.

• Numbness

• Amount of muscle denervation

• Muscle weakness & wasting


• Neurapraxia– Characteristics more associated with

ischemia include:

• Acute pain

• paraesthesias - particularly those of intermittent character


• Neurapraxia– Pain may be the result of direct irritation

of the abnormal spectrum of surviving nerve fibers (small > survival than large)

– Paraesthesias may result from spontaneous activity in the entrapped fibers resulting from ischemia


• Neurapraxia - Levels of Severity– Pre-symptomatic - in perineural and

endoneural microvasculature– Minimal - perineurial and epineurial

fibrosis without changes in the nerve fibers

– Moderate - thinning of myelin in large myelinated fibers

– Severe - change in distribution of fiber sizes with dramatic in large myelinated fibers and proportional in small unmyelinated fibers


• Axonotmesis– Nerve injury

characterized by: • Disruption of the

axon and myelin sheath distal to crush

• Preservation of the endoneurium, perineurium & epineurium


• Axonotmesis– Conduction block occurs immediately

across the site of injury

– Followed by irreversible loss of excitability of the nerve impulse beginning at the neuromuscular junction and then spreads proximally over the length of the distal segment

– Little change in the proximal segment at least initially


• Axonotmesis– Initially, conduction testing proximal to

injury cannot distinguish between neuropraxia & axonotmesis

– Once Wallerian degeneration completes its process, proximal nerve conduction velocity can be expected to be decreased by 30-40% of normal.


• Axonotmesis– Wallerian degeneration results and

takes 3-5 days– Degeneration lasts for several days

prior to any regenerative activity in the distal ends of the damaged nerve

– Regeneration occurs at a rate of 1 mm/day on average assuming normal oxygen tissue tensions

– Generally the prognosis for recovery is good


• Wallerian Degeneration - characterized by:

• Axonal enlargement into an amorphorous mass

• Breakdown of the axons, and schwann cell

• Ingestion of fragmented myelin to provide clean endoneural tubes for advancement of regenerating axons


• Wallerian Degeneration


• Wallerian Degeneration - characterized by:– Cell body increases in

size and nucleus migrates to the cell periphery

– Proximal nerve segment degeneration extends proximally to the next node of Ranvier and is proportional to the severity of injury


• Wallerian Degeneration - characterized by:– Distal nerve segment has:

• Schwann cell proliferation • Collapse of endoneurium• Entire axonal material is

phagocytosed from the site of injury to the endplates


• Wallerian Degeneration - Regeneration– Within 96 hours of the

injury, the proximal end of the nerve fiber sends out sprouts towards distal connective tissue tubes

– The sprouts are attracted by growth factors produced by Schwann cells in the tubes


• Neurotmesis – Partial or complete

severance of a nerve– Disruption of the axon and

its myelin sheath and the connective tissue elements

– Regeneration may occur if peripheral distruption is incomplete but often the pattern and rate of regeneration in those cases amy be abnormal


• Neurotmesis – With complete

severance of a nerve regeneration does not occur

– If regeneration does not occur often the nerve endings bundle up to form a neuroma


• Cell Body Changes – Large neurons have

abundant rough endoplasmic reticulum (RER) which forms aggregates, the Nissl granules

– If the axon is transected, the RER disaggregates and neuronal cell body swells

Neuron with Transected Axon

Normal Neuron


• Cell Body Changes – Cytoplasm becomes

smooth and the nucleus is displaced toward the periphery

– This appearance is called retrograde or central chromatolysis

– Neurons can die if damage is substantial

Neuron with Transected Axon (chromatolysis)

Normal Neuron

Radiculopathy• Damage along a peripheral nerve is

often secondary to entrapment• Entrapment can occur at particular

places along a peripheral nerve where the nerve is in a confined space where pressure can be applied

• This begins with the nerve roots and trauma to the nerve roots is called radiculopathy

Radiculopathy• Anatomy of the

Spinal Nerves– Dorsal and ventral

roots leave the spinal cord and merge to form the spinal nerve

– 31 pairs:• 8 cervical• 12 thoracic• 5 lumbar• 5 sacral • 1 coccygeal


Spinal Nerves– Spinal nerves pass

out through the intervertebral foramina (IVF)

– Cervical nerves exit above their similarly numbered vertebra

– C8 nerve exits below C7 vertebra


Spinal Nerves– Thoracic & lumbar

nerves exit below their similarly numbered vertebra

– Sacral nerves exit through the sacral foramina

– Coccygeal nerves exit just lateral to the coccyx bone

Radiculopathy• Anatomy of the Spinal

Nerves– In cervical & thoracic

spinal segments the spinal roots and nerves exit the IVF almost immediately upon arising from the spinal cord

– However the spinal cord ends between L1 and L2 vertebrae

Radiculopathy• Anatomy of the Spinal

Nerves– At that point spinal

nerves must descend in the spinal canal to their level of exit

– The descending spinal nerves form the cauda equina (horse tail)

– Spinal nerve length from spinal cord to foramen varies widely


Spinal Nerve– As it exits the IVF the

spinal nerve bifurcates into dorsal and ventral rami

– Dorsal ramus passes dorsal to ligament of the transverse process to innervate the muscles and skin of the back

1. Spinal Nerve 12. Sympathetic2. Intervertebral foramen Ganglion3. Pedicle 4. Superior articular facet5. Transverse process6. Spinous process7. Ligament of the transverse process8. Dorsal ramus of spinal nerve9. Ventral ramus of spinal nerve10. Vertebral body11. Intervertebral Disc


Spinal Nerve– Ventral ramus runs

ventral to ligament of the transverse process to innervate the muscles and skin anterior trunk and extremities

1. Spinal Nerve 12. Sympathetic2. Intervertebral foramen Ganglion3. Pedicle 4. Superior articular facet5. Transverse process6. Spinous process7. Ligament of the transverse process8. Dorsal ramus of spinal nerve9. Ventral ramus of spinal nerve10. Vertebral body11. Intervertebral Disc

Radiculopathy• Contents of inter-

vertebral foramen (area of picture where 1 & 2 are):– Spinal nerve– Dorsal root ganglion

when more laterally located

– Connective tissue - dural sleeve & loose areolar connective tissue

– Fat

1. Dorsal root ganglion 8. Gray matter2. Ventral root 9. White

matter3. Pia mater 10. Spinal Nerve4. Arachnoid5. Dura mater6. Dorsal root7. Subarachnoid space

Radiculopathy• Contents of inter-

vertebral foramen:– Radicular artery– Veins vertebral

foramen– Radicular artery– Veins communi -

cating between internal and external venous plexuses

– 2-4 recurrent meningeal nerve branches

Not labeled are the radicular artery & communicating veins which are the large red and smaller blue objects respectively just below 1) Dorsal root ganglion and 2) the ventral root.

Not shown are the recurrent meningeal nerves branches

Radiculopathy• Meningeal

Coverings– Dural sleeve (dura &

arachnoid) and pia mater with CSF in subarachnoid space extend most of the length of the spinal nerve as it passes through the IVF

– Dural sleeve ends and is contiguous with epineurium of spinal nerve

1. Dorsal root ganglion 8. Gray matter2. Ventral root 9. White

matter3. Pia mater 10. Spinal Nerve4. Arachnoid5. Dura mater6. Dorsal root7. Subarachnoid space

Radiculopathy• Dorsal Root Ganglion

– Variable positioning within IVF

– Most sensitive to injury if medially located from osteophytes & posterolateral disc herneation

– Highly vascularize so exposured to mediators of inflammation

1. Dorsal root ganglion2. Ventral root3. Pia mater 4. Arachnoid5. Dura mater6. Dorsal root7. Subarachnoid space8. Gray matter9. White matter10. Spinal Nerve

Radiculopathy• Dorsal Root Ganglion

– Peripheral nerve fibers of different sizes are mixed within the nerve

– As peripheral nerve approaches DRG

• Large caliber fibers are more dorsomedial

• Small caliber fibers are more anterolateral

1. Dorsal root ganglion2. Ventral root3. Pia mater 4. Arachnoid5. Dura mater6. Dorsal root7. Subarachnoid space8. Gray matter9. White matter10. Spinal Nerve

Radiculopathy• Primary causes of

compression include:– Protruding discs– Osteophytes of

uncovertebral region– Posterior narrowing– Superior articular

process– Ligamentum flavum– Periradicular fibrous

tissues

Radiculopathy• Factors that contribute to pain with disc

herniation:– protrusion of disc material– Distention secondary to water-polyglycan content– Inflammatory interface between fragment and the

nerve root

Radiculopathy• Compression of spinal

nerve influenced by head & trunk posture– IVF volumes with flexion– IVF volumes with

extension– Most pronounced in the

cervical spine

ExtensionFlexion

Radiculopathy• Compression of

spinal nerve influenced by head & trunk posture– Cervical rotation

further IVF volume ipsilateral to the rotation direction

IVF volume contralateral to the rotation direction

Radiculopathy• Compression of

spinal nerve influenced by head & trunk posture– Spurling's test for

radiculopathy is a reproduction of pain with rotation and extension of the neck

Radiculopathy• Compression of spinal nerve

influenced by head & trunk posture– Extension of the cervical spine relaxes

the spinal nerve root• Relaxing the nerve its diameter• The nerve dural sleeve is relaxed and thicker

so fills more of the IVF compression is applied to the spinal nerve

– Flexion stretches, straightens and thins nerve and the sheath and thus spinal nerve compression

Radiculopathy• Inflammation similar to seen

elsewhere: phospholipid A activity which

produces PGE2 & leukotrienes

Nitric oxide Cytokine release - such as

interleukins, TNF-– Macrophage invasion into inflamed site

Radiculopathy

Sequence of EventsCOMPRESSION edema fibroblast invasion

INJURY TO THE NERVE fibrotic tissues

risk of adhesion of

traction injuries the nerve which

to the nerve immobilizes it

Radiculopathy• Classic Signs and Symptoms

– Sensory Abnormalities• Pain• Paresthesia• hypesthesia & numbness• hypesthesia and numbness often follow

dermatomal patterns• pain & paresthesia may of may not

follow dermatomal patterns depending upon if there is paraspinal muscle involvement


– Sensory Abnormalities• Progression from neuropraxia to

axonotmesis from conduction block to discontinuity of the axons

• There may be regeneration if axonotmesis, but if spouting occurs locally without regeneration can form neuromas which may be the cause of "electric pain" sensations

nerve irritability - hypersensitivity of the nerve to compression and stretch


DTRs - muscle stretch reflexes– Paresis - muscle weakness– Muscle atrophy

– Dysautonomia & trophic changes (pilomotor, sweating, skin changes) are most associated with peripheral nerve damage but can also occur with radiculopathy


– Complex pain patterns – Can be myotomal or sclerotomal as

well as dermotomal patterns incidence of peripheral pain

syndromes such as complex regional pain syndrome - CRPS (previously called reflex sympathetic dystrophy - RSD)

Radiculopathy• Diagnosis

– Most commonly diagnosed using needle EMG


– Only useful in diagnosis of motor nerve disturbances - not seen with dorsal root lesions (sensory only)

– Seen as abnormal EMG activity in two or more muscles along same spinal nerve distribution (segmental innervation)

– Abnormal EMG activity in the paraspinals


– Abnormal EMG activity is characterized by:

• Prolonged or enhanced "insertional" activity



• Spontaneous sharp positive waves and fibrillation of fasciculation potentials

• Altered morphology of motor unit action potentials

• Poor recruitment of MUAPs• If dorsal root disorder, normal MUAPs but

slowed or blocked H-wave evoked reflex or diminished somatosensory evoked potentials


– Abnormal EMG activity is characterized by:• Spontaneous sharp positive waves and

fibrillation potentials when normally not seen


– Abnormal EMG activity is characterized by:• Spontaneous fasciculation potentials when

normally not seen



• Altered morphology of motor unit action potentials from normal biphasic to polyphasic potentials

Normal biphasic motor unit action potentials (MUAP) superimposed upon motor endplate potentials (MEPP)


– Abnormal EMG activity is characterized by:• Altered morphology of motor unit action

potentials from normal biphasic to polyphasic

Abnormal polyphasic MUAPs


– Abnormal EMG activity is characterized by:• Poor recruitment of MUAPs seen as decreased

maximal activity (interference pattern) when maximal voluntary contraction

Reduced

Normal


– Abnormal EMG activity is characterized by:• If dorsal root disorder, normal MUAPs but slowed

or blocked H-wave evoked reflex

Normal H-reflex

Blocked H-reflex

Slowed H-wave

Radiculopathy• What is an H-reflex?

– Electrical stretch reflex– Stretch reflex - stretched muscle reflexively

contracts


– Electrically stimulate nerve to muscle so stimulate both sensory afferent (Ia) and motor efferent

– Record from muscle

Stimulate nerve to muscle which includes both motor & sensory fibers

Record electrical activity in the muscle


– When stimulate motor fibers there is a short distance traveled

– A short distance traveled will produce a short latency potential recorded from muscle

Stimulate motor fibers

Record electrical activity in the

muscle


– When stimulate sensory fibers there is a long distance traveled

– A long distance traveled will produce a long latency potential recorded from muscle

Stimulate sensory fibers

Record electrical activity in the

muscle


– So when you stimulate the nerve from a muscle, stimulation of the motor fibers will produce a short latency potential recorded in muscle (M-wave)

Stimulus

M-wave

Radiculopathy• What is an H-

reflex?– Motor M-wave

• Short distance• Short latency (time

from stimulus to recorded potential)

– Sensory H-wave• Long distance• Long latencyStimulus

M-wave

H-wave

Radiculopathy• If damage is along

the dorsal root– There should be no

effect on the motor response (M-wave)

– However the sensory response (H-wave) should be blocked

Stimulus

M-wave

H-wave

X

XSite of Damage

Radiculopathy

• Loss of only H-wave is seen with damage along the dorsal root

X

XSite of Damage

Before Damage intact M-wave & H-wave

After Damage loss of only H-wave


– So when you stimulate the nerve from a muscle, stimulation of the motor fibers will produce a short latency potential recorded in muscle (M-wave)

Documents

Pathophysiology of Peripheral Nerve Lesions David A. Lake, PT, PhD Department of Physical Therapy Armstrong Atlantic State University Savannah, GA