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 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 matter 2. Ventral root 9. White matter 3. Pia mater 10. Spinal Nerve 4. Arachnoid 5. Dura mater 6. Dorsal root 7. Subarachnoid space

Radiculopathy Contents of inter-vertebral foramen: Radicular artery Veins vertebral foramen 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 matter 2. Ventral root 9. White matter 3. Pia mater 10. Spinal Nerve 4. Arachnoid 5. Dura mater 6. Dorsal root 7. 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 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 Most pronounced in the cervical spine Extension Flexion

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  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

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

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

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 H-reflex? Motor  M-wave Sensory  H-wave Short distance Short latency (time from stimulus to recorded potential) Sensory  H-wave Long distance Long latency M-wave H-wave Stimulus

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 X M-wave Site of Damage X H-wave Stimulus

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 After Damage loss of only H-wave X

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)