patho peripheral nerve

• Components of a motor unit

  • motor neuron
  • peripheral axon
  • neuromuscular junctions
  • Skeletal muscle fibers
• Myelinated axons


  One Schwann cell makes and maintains exactly one myelin segment, or internode, along a single axon
• Peripheral nerves contain different types of axons
• Peripheral nerve diseases (neuropathies)

  Diseases related to the peripheral nervous system
• Causes of peripheral nerve diseases

  • Axonal neuropathy
  • Demyelinating neuropathy
  • Mixed
• Anatomical patterns of peripheral nerve diseases

  • Polyneuropathy
  • Mononeuritis multiplex
  • Mononeuropathy
• Specific peripheral nerve diseases

  • Guillain Barre syndrome
  • Chronic inflammatory demyelinating polyneuropathy
  • Diabetic peripheral neuropathy
  • Toxic, vasculitic peripheral neuropathy
  • Inherited peripheral neuropathy
• Axonal neuropathy


  Caused by insults that directly injure the axon, leading to distal axon degeneration and secondary loss of myelin (Wallerian degeneration)
• Axonal neuropathy


  • Decreased axon density
  • Traumatic neuroma formation if axon fails to find distal target
• Demyelinating neuropathies


  Damage to Schwann cells or myelin, resulting in abnormally slow nerve conduction velocities but preserved amplitude
• Demyelinating neuropathies


  • Segmental demyelination affecting individual internodes along the length of an axon in a random distribution
  • Normal axon density
  • Abnormally thin myelin sheaths and short internodes
• Polyneuropathy


  Symmetric, length-dependent axonal loss typically more pronounced in distal segments of longest nerves, resulting in a "stocking-and-glove" distribution of sensory changes
• Mononeuritis multiplex


  A disease process that damages individual nerves in a haphazard fashion, often due to vasculitis
• Mononeuropathy


  Only one nerve is affected, often due to traumatic injury, nerve compression, or infections
• Guillain Barre syndrome


  A rapidly progressive, acute, demyelinating, autoimmune disease that affects motor axons, often preceded by an acute, influenza-like illness
• Guillain Barre syndrome


  • Peripheral nerve inflammation with lymphocytic infiltration, segmental demyelination, and axonal damage
  • Ascending paralysis that can be fatal when respiratory muscles are involved
• Chronic inflammatory demyelinating polyneuropathy (CIDP)


  The most common chronic acquired inflammatory peripheral neuropathy, characterized by a symmetric mixed sensorimotor polyneuropathy that persists for at least 2 months
• Chronic inflammatory demyelinating polyneuropathy (CIDP)


  • Nerve sections contain areas of myelination and demyelination
  • Regenerating Schwann cells lead to "onion skin" appearance in long-term cases
• Diabetic peripheral neuropathy


  The most common cause of peripheral neuropathy, seen in long-term diabetes, with autonomic, lumbosacral radiculopathy, and distal symmetrical sensorimotor polyneuropathy as common forms
• Diabetic peripheral neuropathy


  • Distal symmetrical sensorimotor polyneuropathy is the most common form, with sensory fibers more affected than motor fibers, leading to sensory loss
• Toxic/vasculitic peripheral neuropathy


  Caused by drugs, environmental toxins, metabolic causes, connective tissue diseases, and infections, often presenting as a painful, asymmetric sensory and motor neuropathy with patchy involvement
• Inherited peripheral neuropathy


  May have demyelinating or axonal neuropathy, progressing slowly in adults, often due to mutations in genes encoding myelin-related proteins
• Neuromuscular junction


  The interface of motor nerve axons and skeletal muscle, where acetylcholine is released to initiate muscle contraction
• Neuromuscular junction diseases


  • Myasthenia Gravis
  • Lambert-Eaton Syndrome
• Myasthenia Gravis


  An autoimmune disease with autoantibodies against postsynaptic acetylcholine receptors, leading to receptor depletion and decreased function, causing fluctuating weakness that worsens with exertion
• Lambert-Eaton Syndrome


  Caused by antibodies that block acetylcholine release by inhibiting presynaptic calcium channels, leading to improvement of weakness with repetitive stimuli, often associated with small cell lung cancer
• Other neuromuscular junction diseases include congenital myasthenic syndrome and diseases caused by Clostridium tetani and Clostridium botulinum toxins
• Motor unit


  Composed of one lower motor neuron, its axon, neuromuscular junctions, and the associated skeletal muscle fibers it innervates
• Skeletal muscle fiber types

  • Type I (slow twitch)
  • Type II (fast twitch)
• Normally, skeletal muscle fibers of different types are distributed in a checkerboard-like pattern
• Neuropathic changes in skeletal muscle

  Loss of innervation causes atrophy of myofibers, with grouped atrophy and fiber-type grouping as the main morphologic hallmarks
• Reinnervation of myofibers leads to a switch in fiber type and segregation of fibers of like type, often with an increase in motor unit size
• Fibers of different types


  • Distributed in checkerboard patterns
• Four normal motor units

  • Show a normal checkerboard-type admixture of light- and dark-stained fibers (Type I and Type II)
• Primary muscle diseases or myopathies

  Must be distinguished from secondary neuropathic changes caused by disorders that disrupt muscle innervation
• Neuropathic changes


  Loss of innervation causes atrophy of myofibers
• Two main morphologic hallmarks of neurogenic changes

  • Grouped atrophy
  • Fiber-type grouping
• Four normal motor units

  1. Checkerboard-type admixture of light- and dark-stained fibers of opposite type

  2. Damage to innervating axons >>> loss of trophic input >>> atrophy of myofibers

  3. Reinnervation of myofibers >>> a switch in fiber type >>> segregation of fibers of like type

  4. Reinnervation is also often associated with an increase in motor unit size, with more myofibers innervated by an individual axon
• Normal muscle has a checkerboard-type distribution of type I (light) and type II (dark) fibers on this adenosine triphosphatase reaction (pH 9.4)
• Clustered flattened, "angulated" atrophic fibers (group atrophy)


  • A typical finding associated with disrupted innervation