Voltage-Gated Potassium Channel Antibody Disorders

  • Screening test for VGKC antibody receptor complex-associated autoantibodies
  • Reflexes to CASPR2 and LGI1 antibodies

Screening test for VGKC antibody receptor complex-associated autoantibodies

Screening test for VGKC antibody receptor complex-associated autoantibodies

Aids in diagnosis of LGI1 disorders​

Aids in diagnosis of LGI1 disorders

Aids in diagnosis of CASPR2 disorders

Aids in diagnosis of CASPR2 disorders

Aids in diagnosis of LGI1 and CASPR2 disorders​

  • Aid in the differential evaluation of encephalitis of unknown origin with subacute onset of seizures, confusion, memory loss, and/or behavioral change
  • For adults and patients with suspicion of cancer, additional evaluation of paraneoplastic autoantibodies is recommended; refer to Paraneoplastic Reflexive Panel (3002929)

See the Anti-NMDA Receptor (NR1) IgG Antibodies Test Fact Sheet for more information on the evaluation of NMDA antibodies in autoimmune encephalitis.

  • Acceptable reflexive panel for the differential diagnosis of acquired neuromuscular junction disorders
  • Panel includes acetylcholine receptor binding, blocking, and modulating antibodies; ganglionic acetylcholine receptor antibodies; P/Q-type and N-type voltage-gated calcium channels; voltage-gated potassium channels; titin antibody; striated muscle antibodies; leucine-rich glioma-inactivated protein 1 antibody; and contactin-associated protein-2 antibody IgG with reflex to titers.

Voltage-gated potassium channel antibody disorders include limbic encephalitis, faciobrachial dystonic seizures, and peripheral nerve hyperexcitability disorders that may occur following immunotherapy and/or plasmapheresis.

Disease Overview

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