Voltage-Gated Potassium Channel Antibody Disorders

Incidence

Unknown

Symptoms

• Limbic encephalitis (mainly LGI1 antibodies):
  • Amnesia
  • Seizures
  • Disorientation
  • Psychiatric disturbance
  • Peripheral nerve hyperexcitability
  • Neuromyotonia
  • CSF usually normal
• Morvan syndrome (mainly CASPR2 antibodies):
  • Limbic encephalitis
  • Neuromyotonia
  • Confusion
  • Amnesia
  • Insomnia
  • Pain
  • Autonomic dysfunction: hyperhidrosis, constipation, urinary incontinence

Diagnostic Issues

Antibody testing may aid in diagnosis.

• Testing should be performed only when neuromuscular and/or neurological symptoms are present.
• Anti-VGKC disorders are rare and present with symptoms similar to those of other encephalitic disorders.
• Antibody testing should not be used for screening.
• Antibodies may be associated with paraneoplastic (autoimmune) or nonparaneoplastic neurological disorders.
• Not all neurological disorders or antibodies are associated with tumors.
  • In most antibody-mediated, non-neoplastic-associated diseases, individuals improve substantially with immunotherapy.
  • It is important to diagnose these illnesses due to therapeutic responsiveness.

Physiology

• VGKC autoantibodies:
  • Directed against a protein that is complexed with potassium channels in both the peripheral nervous system and CNS
    • CASPR2:
      • Present in ~50% of individuals with neuromyotonia
      • CASPR2 antibodies are common in individuals with thymic malignancies.
    • LGI1:
      • Not directed against the potassium channels
      • Associated with limbic encephalitis, faciobrachial dystonic seizures, hyponatremia, and myoclonic movements
      • Disorders are rarely associated with tumors
• VGKC radioimmunoassay (RIA) tests can be used as a general screen for VGKC-complex antibodies directed against:
  • LGI1
  • CASPR2
  • Other unidentified targets

Test Interpretation

Results

VGKC Antibody, Serum

• Positive: >88 pmol/L
  • Suggests VGKC antibody-related disease
• Indeterminant: 32-87 pmol/L
  • Retest in 2-4 weeks
• Negative: 0-31 pmol/L
  • Likelihood of VGKC antibody-related disease is reduced but not necessarily eliminated

VGKC Antibody, CSF

• Positive: >1.1 pmol/L
  • Suggests VGKC antibody-related disease
• Negative: 0.0-1.1 pmol/L
  • Likelihood of VGKC antibody-related disease is reduced but not necessarily eliminated

LGI1 Antibody, Serum

• Positive: ≥1:10
  • Suggests LGI1 antibody-related disease
• Negative: <1:10
  • Does not rule out disorders associated with VGKC complex antibodies

CASPR2 Antibody, Serum

• Positive: ≥1:10
  • Suggests CASPR2 antibody-related disease
• Negative: <1:10
  • Does not rule out disorders associated with VGKC complex antibodies

Limitations

VGKC Antibody

• Presence of VGKC antibodies should be used in conjunction with clinical manifestations for:
  •  Neuromyotonia spectrum of disorders
  •  VGKC antibody-associated limbic encephalitis
• Should not be used as the sole criterion for diagnosis
• VGKC receptor-complex proteins may be coprecipitated by anti-VGKC antibodies, including:
  • LGI1
  • CASPR2
  • Other unidentified targets