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
Anatomy of Peripheral
Nerves
• Each axon is surrounded by a
connective tissue layer called the
endoneurium
Anatomy of Peripheral
Nerves
• Axons are grouped together into fascicles,
and each fascicle is surrounded by another
connective tissue layer, the perineurium
Anatomy of Peripheral
Nerves
• Fascicles are grouped together, covered by
an outer connective tissue layer, the
epineurium, to form a peripheral nerve
Anatomy of Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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.
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• Neurapraxia
– Characteristics more associated with
ischemia include:
• Acute pain
• paraesthesias - particularly those of
intermittent character
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• Axonotmesis
– Nerve injury
characterized by:
• Disruption of the
axon and myelin
sheath distal to crush
• Preservation of the
endoneurium,
perineurium &
epineurium
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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.
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• Wallerian Degeneration
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Damage to Peripheral
Nerves
• 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
Normal
Neuron
Neuron with
Transected Axon
Damage to Peripheral
Nerves
• 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
Normal
Neuron
Neuron with
Transected Axon
(chromatolysis)
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
Radiculopathy
• Anatomy of the
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
Radiculopathy
• Anatomy of the
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
Radiculopathy
• Anatomy of the
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. Sympathetic
2. Intervertebral foramen
Ganglion
3. Pedicle
4. Superior articular facet
5. Transverse process
6. Spinous process
7. Ligament of the transverse process
8. Dorsal ramus of spinal nerve
9. Ventral ramus of spinal nerve
10. Vertebral body
11. Intervertebral Disc
Radiculopathy
• Anatomy of the
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. Sympathetic
2. Intervertebral foramen
Ganglion
3. Pedicle
4. Superior articular facet
5. Transverse process
6. Spinous process
7. Ligament of the transverse process
8. Dorsal ramus of spinal nerve
9. Ventral ramus of spinal nerve
10. Vertebral body
11. Intervertebral Disc
Radiculopathy
• Contents of intervertebral 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
2. Ventral root
3. Pia mater
4. Arachnoid
5. Dura mater
6. Dorsal root
7. Subarachnoid space
8. Gray matter
9. White matter
10. Spinal Nerve
Radiculopathy
• Contents of intervertebral 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
2. Ventral root
3. Pia mater
4. Arachnoid
5. Dura mater
6. Dorsal root
7. Subarachnoid space
8. Gray matter
9. White matter
10. Spinal Nerve
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 ganglion
2. Ventral root
3. Pia mater
4. Arachnoid
5. Dura mater
6. Dorsal root
7. Subarachnoid space
8. Gray matter
9. White matter
10. 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 ganglion
2. Ventral root
3. Pia mater
4. Arachnoid
5. Dura mater
6. Dorsal root
7. Subarachnoid space
8. Gray matter
9. White matter
10. 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
Extension
– Most pronounced in the
Flexion
cervical spine
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 Events
COMPRESSION  edema  fibroblast invasion

INJURY TO THE NERVE

 risk of
traction injuries 
to the nerve

 fibrotic tissues

 adhesion of
the nerve which
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
Radiculopathy
• Classic Signs and Symptoms
– 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
Radiculopathy
• Classic Signs and Symptoms
–  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
Radiculopathy
• Classic Signs and Symptoms
– 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
Radiculopathy
• Diagnosis
– 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
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized
by:
• Prolonged or enhanced "insertional" activity
Radiculopathy
• Diagnosis
– Abnormal EMG activity is
characterized by:
• 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
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized by:
• Spontaneous sharp positive waves and
fibrillation potentials when normally not seen
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized by:
• Spontaneous fasciculation potentials when
normally not seen
Radiculopathy
• Diagnosis
– Abnormal EMG activity
is characterized by:
• 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)
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized by:
• Altered morphology of motor unit action
potentials from normal biphasic to polyphasic
Abnormal polyphasic MUAPs
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized by:
• Poor recruitment of MUAPs seen as decreased
maximal activity (interference pattern) when
maximal voluntary contraction
Normal
Reduced
Radiculopathy
• Diagnosis
– Abnormal EMG activity is characterized by:
• If dorsal root disorder, normal MUAPs but slowed
or blocked H-wave evoked reflex
Normal H-reflex
Slowed H-wave
Blocked H-reflex
Radiculopathy
• What is an H-reflex?
– Electrical stretch reflex
– Stretch reflex - stretched muscle reflexively
contracts
Radiculopathy
• What is an H-reflex?
– 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
Radiculopathy
• What is an H-reflex?
– 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
Radiculopathy
• What is an H-reflex?
– 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
Radiculopathy
• What is an H-reflex?
– 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)
M-wave
Stimulus
Radiculopathy
• What is an Hreflex?
– Motor  M-wave
M-wave
H-wave
Stimulus
• Short distance
• Short latency (time
from stimulus to
recorded potential)
– Sensory  H-wave
• Long distance
• Long latency
Radiculopathy
• If damage is along
the dorsal root
X
M-wave
X
Site of
Damage
Stimulus
H-wave
– There should be no
effect on the motor
response (M-wave)
– However the
sensory response
(H-wave) should be
blocked
Radiculopathy
• Loss of only H-wave
is seen with damage
along the dorsal root
Before Damage intact
M-wave & H-wave
Site of Damage X
X
After Damage loss of
only H-wave
Radiculopathy
• What is an H-reflex?
– 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)