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NEUROMUSCULAR DISEASE: TYPICAL PATTERNS

General principles
   Clinical
   Tissue involvement
   Diagnostic testing
Muscle
Neuromuscular Junction
Nerve
   Cell body
   Axon
   Myelin

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

Washington University Neuroscience


GENERAL PRINCIPLES
  • Clinical patterns: The neuromuscular evaluation begins with an evaluation and description of patterns of the disease process that are gleaned from the history and physical examination. Unusual patterns are especially important to define as they often provide a basis for listing the most likely diagnoses in a differential diagnosis. A summary of the patient's disease syndrome should include features from each descriptive category: Functional, Anatomical & Temporal.
    • Functional disorders: Especially useful for differential diagnosis when selective involvement occurs
      • Motor
        • Weakness
        • Muscle size
        • Abnormal movements
      • Sensory
        • Loss: Large or Small fiber modalities
        • Discomfort
      • Autonomic
    • Anatomical patterns
      • Arms vs. Legs vs. Cranial
        • Most neuromuscular disorders are more prominent in the 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 features
      • 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 involvement
    Anatomical loci of neuromuscular disease include: The anatomical locus of disease in the sensory system or motor unit may be inferred from the clinical examination. The locus of tissue involvement is usually confirmed by electrodiagnostic testing using electromyography, repetitive nerve stimulation, and nerve conduction testing. Muscle biopsy and serum creatine kinase (CK) may also be useful, but nerve biopsy is not generally employed for this purpose.    
    Anatomic loci of
    neuromuscular disease

  • 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

MUSCLE

Gowers' sign
Proximal weakness
NEUROMUSCULAR JUNCTION
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
NERVE

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
Myelin
  • 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
Axon
  • 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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7/15/2009