Pathology

• Neuropraxia


  A disorder of the PNS in which there is a temporary loss of motor and sensory function due to blockage of nerve conduction, usually lasting an average of six to eight weeks before full recovery
• Axonotmesis


  An injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory functions distal to the point of injury are completely lost over time leading to Wallerian degeneration due to ischemia, or loss of blood supply
• Neurotmesis


  An injury in which the nerve is completely divided, resulting in complete paralysis, atrophy of muscles innervated by the nerve, and total anesthesia of the nerve's cutaneous distribution
• Physical examination may reveal a tender mass, a neuroma, at the distal stump of the amputated nerve. Clinicians should assume that a neurological dysfunction referable to a nerve injury resulting from a laceration is a neurotmetic injury, unless there is evidence to the contrary
• Spontaneous recovery does not occur after neurotmesis. If a surgical repair is performed, some degree of recovery may be observed, but it will not be complete. Complete recovery is not possible because of degenerative changes that affect the target muscles and end organs and because of disordered axonal regrowth at the site of the anastomosis. Recovery starts at the proximal towards the distal segment
• The PNS


  • It is composed of 31 pairs of spinal nerves attached to the spinal cord and 10 pairs of cranial nerves attach to the brainstem
  • The optic and olfactory nerves are attached to the cerebrum and considered part of the CNS
  • It serves to link the CNS to muscles for movement, and provides information back to the CNS about both internal and external conditions
  • Cell bodies of ANS neurons reside in the brainstem and spinal cord, and within ganglia that lie outside the CNS
• Peripheral nerves


  • They have two main components involved in impulse transmission: axons and myelin sheaths made by Schwann cells
  • Injuries to either component may result in a peripheral neuropathy
• Structure of myelinated peripheral nerve fibers

  1. Axons are myelinated in segments (internodes) separated by nodes of Ranvier, unmyelinated gaps, which are uniformly spaced along the axon

  2. A single Schwann cell supplies myelin sheath for each internode

  3. Specialized proteins are essential for assembly and function of myelin

  4. Segments of several unmyelinated axons are surrounded by cytoplasm of one Schwann cell

  5. Most peripheral nerves carry out both motor and sensory functions and contains axons of variable diameter and myelin thickness
• Introduction

  • Specific sensations and motor signals are conveyed by axons distinguished based on their diameter
  • Axonal diameter correlates with myelin sheath thickness and conduction speeds
  • Thin unmyelinated fibers mediate autonomic functions, pain and temp., sensation, slowest conduction speed

  
• Covering (sheaths) of the peripheral nerve

  • Epineurium - covers the nerve trunks
  • Perineurium - covers the nerve bundles
  • Endoneurium - covers the individual nerve fiber

  
• Circulation to the peripheral nerve is provided by an artery which penetrates the epineurium; arterioles penetrate the perineurium; and capillaries penetrate the endoneurium
• Lower motor neuron


  • Cell bodies located either in the anterior horn of the spinal cord or the cranial nerve nuclei of the brainstem
  • Axons travel through the ventral root to the intended target as a spinal or cranial nerve
  • Damage results in paresis or paralysis of muscles distal to the lesion; decreased to absent DTR, atrophy, contracture formation, deformity and edema

  
• Sensory neurons


  • Lesions may occur in the dorsal root ganglion or in the nerve root proximal to the ganglia
  • Loss of sensation will follow a peripheral nerve distribution if that is the anatomic region involved, or it will follow a dermatomal pattern when the spinal nerve or dorsal root ganglia or cell body has been affected

  
• Changes in the PNS with aging

  • Perineurium and epineurium thicken
  • Endoneurium becomes fibrosed with increased collagen
  • Cross-sectional area decreases
  • Atherosclerosis and occlusion of blood vessels leads to loss of nerve fibers
  • Decreased neurotransmitters (β-endorphin, GABA synthesis, and GABA and serotonin receptors)
  • ANS dysfunction due to loss of cell bodies
  • Altered axonal myelination leads to slowed conduction
  • Loss of fibers decreases amplitude of potential and affects movement, safety and quality of life

  
• Factors behind aging neuropathy

  • Loss of both motor and sensory cell bodies
  • A dying-back condition, suggesting neurons can metabolically support a limited number of fibers or receptors
  • Chronic compression of the peripheral nerves or repetitive trauma over a lifetime

  
• Electromyography (needle EMG)


  Involves the recording of electrical activity within muscles by way of a needle electrode similar to having an electrical microphone at the tip of the needle

  
• Nerve conduction study


  Involves placing two electrodes along the length of a nerve. One electrode stimulates the peripheral nerve greater than the threshold values required to cause firing. The second electrode records the characteristics of the generated action potential at a different point than the stimulation

  
• Information obtained from nerve conduction studies

  • Conduction velocity, wave forms, and amplitude
  • Conduction at distal site slowed at the NMJ (distal latency)
  • Useful for diagnosis of compression neuropathies since thick fibers are most vulnerable to compression injury
  • Can localize the injury and identify LMN vs UMN lesions and degree of damage

  
• Neurapraxia


  Temporary failure of nerve conduction in the absence of structural changes, typically due to blunt injury, compression or ischemia; axon remains intact, no muscle atrophy; due to segmental demyelination which slows or blocks local conduction of action potential; paresis without degeneration; slow and full recovery of function
• Axonotmesis


  Axon has been damaged, but the connective tissue coverings that support and protect the nerve remain intact; can be due to prolonged compression producing an area of infarction and necrosis; in the presence of disease, Wallerian degeneration occurs
• Neurotmesis


  Most severe axonal loss; with complete severance of the axon plus disruption of the connective tissue coverings at site of injury; can be caused by gunshot wounds or avulsion injuries that disrupt a section or entire nerve; when axonal continuity is lost, axons degenerate distal to the lesion
• Wallerian degeneration


  1. Begins immediately and completed in few weeks

  2. Nerve cells swell and undergo chromatolysis

  3. Distal axon degenerates, myelin fragments within 12 hrs

  4. Macrophages phagocytise cell debris

  5. Cell body synthesizes cytoplasm and transported down the axon

  6. Regeneration begins as sprouting of growth cones

  7. Release proteases that dissolve material and permit the axon to enter the tissue easily
• Neuroma


  A tender mass that forms at the distal stump of an amputated nerve
• Clinical manifestations of peripheral nerve injury

  • Flaccid paralysis in muscles distal to the lesion with atrophy due to loss of trophic influences of the innervating nerve
  • Sensory function is likewise lost below the level of the lesion
• Diagnosis of peripheral nerve injury

  1. Based on history and clinical examination to diagnose neurotmesis

  2. Electrophysiologic studies including EMG which will show presence of fibrillation potentials and positive sharp waves indicating denervation

  
• Treatment of peripheral nerve injury

  Surgical treatment (cable and interfascicular grafts); epineurial repair; symptomatic treatment e.g. splinting
• Prognosis for recovery is poor in neurotmesis, even with surgical intervention
• Mononeuropathy


  Single peripheral nerve affected, usually due to trauma
• Polyneuropathy


  Involvement of several peripheral nerves

  
• Radiculoneuropathy


  Involvement of nerve root as it emerges from the spinal cord
• Polyradiculitis


  Involvement of several nerve roots, occurs when infection results in an inflammatory response
• Neuropathic diseases affecting the axon or cell body

  • Cause axonal degeneration, typically affecting the longest nerve fibers first with symptoms beginning distally and spreading proximally as the disease progresses
• Neuropathic diseases affecting only the myelin

  • Cause segmental demyelination of both sensory and motor fibers, disrupting conduction of action potentials from proprioceptors and mechanoreceptors, leading to sensory changes

  
• Early symptoms of neuropathy


  • Often sensory in nature, e.g. tingling, pricking, burning, or band-like dysesthesias and paresthesias in the feet
  • When more than one nerve is involved, sensory loss follows a glove-and-stocking distribution due to dying-back of the longest fibers in all nerves from distal to proximal
• Motor neuropathy


  • Most commonly manifests as distal weakness, hypotonia or flaccidity, and muscle tenderness or cramping
  • Motor loss in myopathy is opposite that of a neuropathy, with weakness tending to be proximal

  
• Compressive neuropathies


  Occur due to the proximity of peripheral nerves to bony, muscular and vascular structures

  
• Mechanical injury to nerves

  Occurs once tension exceeds 10-20% of the axon resting length and the available slack is taken up, resulting in damage
• Carpal tunnel syndrome (CTS)


  • Results from compression of the median nerve in the wrist, marked by pain, paresthesia, numbness, and weakness in the distribution of the median nerve
  • Most commonly associated with performance of repetitive tasks determined by position of the hand and degree of load, causing neurapraxia of the median nerve
  • Acute CTS less common and directly associated with fractures, dislocation, and vascular disorders of the wrist
• Incidence of CTS is 2.8 per 1000 in studies using nerve conduction study to confirm the diagnosis

  
• Prevalence of CTS is 1 to 10% among the general population, 14.5% among specific occupational groups