Nerve and Skeletal Muscle

Nerve and Skeletal Muscle

Nerve Objectives

• Key Differences to Understand:

  • Axonal degeneration vs. Wallerian degeneration.

  • Most common cause of acute peripheral neuropathy.

  • Characteristic histopathologic findings in CMT I disease.

  • Clinical features of Guillain-Barre syndrome.

  • Formation of traumatic neuroma.

  • Treatment options for diabetic neuropathy.

Pre-lecture Questions

• Neuropathy Presentation: Organophosphates, pesticides, and industrial solvents have a common clinical presentation referred to as neuropathy.

• Common Cause of Acute Peripheral Neuropathy: Identify the most common cause.

• Nerve Conduction Studies: Useful for distinguishing between demyelinating neuropathy and axonal neuropathy.

• Axon Composition: True or false: a single axon contains both myelinated and unmyelinated fibers.

• Myelin Production: Myelin is produced by Schwann cells in the peripheral nervous system.

• Diabetic Neuropathy Treatment: Best treatment options need to be identified.

• Muscular Dystrophy Characteristic: Identify which muscular dystrophy is characterized by the inability to “let go” of a handshake.

• Duchenne Muscular Dystrophy: Absent structural protein needs to be pinpointed.

• Corticosteroid Response: Inclusion body myositis response to corticosteroids needs verification (True/False).

• Staining for Muscle Fibers: Identify the histochemical stain used to distinguish between slow (Type I) and fast (Type II) twitch muscle fibers.

• Myasthenia Gravis Diagnosis: Name the test used for diagnosing Myasthenia Gravis.

Peripheral Nerves

Normal Structure

• Normal peripheral nerves consist of bundles of axons, including both myelinated and unmyelinated fibers.

• Myelin Production: Produced by Schwann cells.

Neuron Cell Components

• Parts of a neuron:

  • Neuron cell body

  • Dendrites

  • Myelin sheath

  • Nodes of Ranvier

  • Neuron nucleus

  • Schwann cell

  • Axon
    

    

Motor Units

• Types of motor units:

  • Normal

  • Segmental demyelination

  • Axonal degeneration

  • Reinnervation

  • Myopathy

Tests for Neuropathies

• Nerve Conduction Studies:

  • Distinguish between demyelinating neuropathy (DN) characterized by slowing of conduction velocity or conduction block, versus axonal neuropathy (AN) which is associated with low-action potential amplitudes.

• Other Tests:

  • CSF analysis, EMG (Distinguishes between denervation atrophy vs. primary muscle disease), Muscle or Nerve biopsy.

Segmental Demyelination

Characteristics

• The axon remains intact, the neuron cell body remains, but myelin is lost (can sometimes be recovered).

• Results in conduction block.

• Clinical Examples:

  • Acute: Guillain-Barre syndrome

  • Chronic: Charcot-Marie-Tooth disease.

Guillain-Barre Syndrome

• Epidemiology:

  • Most common acute peripheral neuropathy.

  • Leading cause for acute flaccid paralysis.

  • Primarily affects motor pathways; variants can be motor and sensory.

  • Involves nerve roots and peripheral nerves.

• Preceding Illness:

  • Approximately 2/3 of cases are preceded by an influenza-like illness.

• Pathogenesis:

  • An autoimmune demyelination syndrome is suspected to be the cause,

  • Characterized by inflammation of the peripheral nerve with perivenular and endoneurial infiltration of lymphocytes, macrophages, and few plasma cells.

  • Causes included infections from Mycoplasma pneumoniae, Campylobacter jejuni, and viral infections (HIV, EBV, CMV, influenza).

• Symptoms:

  • Rapidly progressive ascending paralysis beginning with proximal muscles and can spread, leading to respiratory muscle paralysis and potential death.

  • May experience decreased or absent deep tendon reflexes.

Laboratory Testing in Guillain-Barre Syndrome

• Findings:

  • Oligoclonal bands on high-resolution electrophoresis.

  • CSF indicates elevated protein, normal glucose, and little or no pleocytosis.

• Mortality and Recovery:

  • Improvements in mortality due to better supportive measures including mechanical ventilation and treatments like IV immunoglobulin or plasmapheresis.

  • 95% survival with most patients experiencing no lasting defects. Continuance of symptoms three weeks post onset correlates with lower chances of complete recovery.

Charcot-Marie-Tooth Disease

• Description:

  • Most common hereditary neuropathy, incidence ~1 in 2500.

  • Inheritance pattern: Autosomal dominant; typically affects young adults.

• Pathology and Clinical Features:

  • Peroneal nerve neuropathy leading to weakness and atrophy of calf muscles, presenting with an “inverted champagne bottle” appearance in the lower legs.

  • Other findings include abnormal gait and hammer toes.

  • Treatment: Supportive including orthotics and physical therapy.

• Pathologic Findings:

  • Degeneration of the posterior column, demyelination, remyelination(Presenting as thin myelin sheaths), axonal loss, onion bulb formation.

Wallerian Degeneration

• Mechanism:

  • Occurs when the axon connection to the neuronal cell body is lost, typically due to trauma or degeneration.

• Clinical Examples:

  • Often seen in traumatic scenarios.

  • Sequence of Events:

  • Image illustrating biology of Wallerian degeneration demonstrates axon degeneration, repair processes by Schwann cells, and associated debris clearance.

• End Results:

  • We observe axonal sprouts among the Schwann cells undergoing mitosis, with growth cones directed toward regeneration.

Traumatic Neuroma

• Occurs post injury either from:

  • Poor approximation and repair of the injury resulting in a tangled mass of regenerating nerve fibers that fail to connect with the distal end.

  • Presents as a painful mass.

• Pathologic Features:

  • Characterized by a disordered mix of nerve fibers (axons), fibroblasts, Schwann cells, and scar tissue.

Distal Axonopathy

• Definition: A condition where degeneration affects the distal part of the axon and its myelin first,

• Results in a characteristic distal