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General principles
   Tissue involvement
   Diagnostic testing
Neuromuscular Junction
   Cell body

Exceptions to the rules are listed in
   Neuropathy differential diagnosis
   Myopathy differential diagnosis
Physical Exam

Washington University Neuroscience

  • Clinical patterns:
    • General: The neuromuscular evaluation
      • Begins with: Evaluation & description of patterns of disease process
      • Gleaned from: History & physical examination
      • Unusual patterns
        • Especially important
        • Provide basis for listing most likely diagnoses
      • Summary of disease syndrome should include features from each descriptive category
    • Function patterns
      • General Most useful for differential diagnosis when selective involvement occurs
      • Motor
        • Weakness
        • Muscle size
        • Abnormal movements
      • Sensory
        • Loss: Large or Small fiber modalities
        • Discomfort
      • Autonomic
    • Anatomic patterns
      • Arms vs. Legs vs. Cranial
        • Most neuromuscular disorders: More prominent in legs early in disease course
        • Neuromuscular junction disorders: Cranial weakness early
      • Proximal vs Distal
      • Symmetric vs Asymmetric
        • Symmetric disorders are more common
        • Asymmetric neuropathies
          • Commonly treatable
          • Often related to immune disorders
          • Nerve biopsy often indicated
      • Selective regions involved in: Neuropathy or Myopathy
    • Temporal patterns
      • Course
        • Acute: Days to Weeks
        • Chronic: Months to Years
        • Episodic
        • Hereditary: By family history or examination of relatives
      • Fatigue: Over course of minutes to hours
      • Onset age
        • Pediatric
          • Neonatal
          • Childhood
        • Adult
          • 20 to 60 years
          • Geriatric
  • Tissue & Anatomic involvement
    Loci of NM Disease
    Tissue & Anatomic

  • Diagnostic (Molecular) testing: When a pattern of disease and its tissue localization are identified other laboratory testing can be employed to make a specific diagnosis, guide consultation of the patient, and direct treatment. Diagnostic tests include:
    • Muscle biopsy
      • Histochemistry: Diagnosis by specific morpholgic features
      • Immunohistochemistry: Absent or reduced staining for specific protein
      • Biochemistry: Absent or reduced enzyme function
      • Ultrastrucure: Rarely helpful
    • Nerve biopsy
    • Antibodies
      • Location: Serum or CSF
      • May define specific immune neuromuscular disorders
    • Genetic testing: May define specific hereditary disorders


Gowers' sign
Proximal weakness
Normal neuromuscular junction
  • Clinical patterns of disease
    • Weakness
      • Distribution
        • Proximal & Distal
        • Extraocular muscles & Face: Often involved
          • Cause: NMJs of extraocular muscles have
              different anatomy & physiology
      • Temporal changes: Variable through day; Fatigue
    • Sensory: Normal
    • Tendon reflexes: Normal
      • Cause: No involvement of sensory axons
  • Electrophysiology
    • Repetitive nerve stimulation
      • Normal: No change in amplitude of compound motor action potentials (CMAPs)
      • Neuromuscular junction disorders: Altered CMAP amplitude with repeated stimulation
        • Decrement
          • Anatomy: Post-synaptic disorders
          • Due to reduced safety factor at synapse
        • Increment
          • Anatomy: Pre-synaptic disorders
          • Due to altered release of vesicles from pre-synaptic terminal
    • EMG & Nerve conduction testing: Normal
  • Other laboratory tests

1890 illustration
of upper and lower
motor neurons by
Ramon y Cajal

Cell body
  • Clinical patterns of disease
    • Functional involvement
    • Distribution
      • Proximal & Distal
      • Arms: Involved early
      • Face & Bulbar: Common
      • Asymmetric
    • Time course
      • Onset frequently subacute: Weeks to months
      • Defect very persistent & poorly responsive to therapy
  • Electrodiagnostic
    • Selective loss of motor, sensory, or autonomic axons
    • Early involvement of proximal structures
      • Motor: Thoracic paraspinous muscles denervated
      • Sensory: Truncal sensory loss
      • Cause: Cell body pathology is not dependent on axon length
  • Other laboratory tests
    • Pathology: Loss of cell bodies
    • Antibodies: Immune disorders
    • Genetic evaluation: Often with positive family history
  • Clinical patterns of disease
    • Weakness: Proximal & Distal
    • Wasting: Not prominent unless concomitant axonal loss
    • Sensory loss
      • Mild
      • Symmetric
      • Distal > Proximal
    • Tendon reflex loss
      • Diffuse
      • Early in disease course
      • Causes: Demyelination
        • Occurs all along length of axons: No selective proximal or disat involvement
        • Produces asynchronous conduction of sensory stimuli to motor cell bodies
          • Depolarization of motor cell does not reach threshhold for generating action potential
  • Nerve conduction studies
    • Conduction velocity: Slow
      • Upper extremity velocities: < 32 M/s
      • Distal latencies & F-waves: Prolonged
    • Conduction block: Failure of impulse conduction along an anatomically intact axon
    • Cause of abnormalities: Disordered saltatory conduction of impulses along axons
  • Other laboratory tests
  • Clinical patterns of disease
    • Weakness
      • Distal
      • Legs > Arms
      • Muscle wasting: Early
        • Cause: Rapid muscle fiber atrophy after denervation or disuse
    • Sensory
      • Loss
        • Distal > Proximal
        • Legs > Arms
        • Modalities: Vibration loss > Proprioception loss; Pain & Temperature
      • Discomfort
        • Paresthesias & Pain
        • Distal > Proximal
        • Legs > Arms
        • Cause: Spontaneous action potentials from damaged small axons
    • Tendon reflex loss
  • Electrodiagnostic studies
    • EMG
      • Motor unit pathology
        • Pattern: High amplitude, Prolonged, Polyphasic, Rapid firing
        • Cause: Increased number of muscle fibers in each motor unit due to axonal sprouting
      • Spontaneous activity
      • Anatomic invlolvement
        • Distal > Proximal
        • Legs > Arms
        • Cause: Longer axons often more vulnerable to disease process
    • Nerve conduction studies
      • Small compound motor action potentials
      • Conduction velocities: Mildly slowed (Upper extremity > 35 M/s)
  • Other laboratory tests

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