Voltage-Gated Potassium Channel Antibody Disorders

Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Method: Quantitative Radioimmunoassay/Semi-Quantitative Indirect Fluorescent Antibody
  • 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

Aid in diagnosis of LGI1 disorders​

Contactin-Associated Protein-2 Antibody, IgG with Reflex to Titer 2009452
Method: Semi-Quantitative Indirect Fluorescent Antibody

Aid in diagnosis of CASPR2 disorders

Aid in diagnosis of LGI1 and CASPR2 disorders​

Autoimmune Encephalitis Reflexive Panel 2013601
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Radioimmunoassay
  • Differential evaluation of encephalitis of unknown origin with subacute onset of seizures, confusion, memory loss, and/or behavioral change
  • Panel includes NMDA receptor antibody, VGKC antibody, GAD65 antibody, AQP4 antibody, and LGI1 and CASPR2 antibodies.
  • For adults and patients with suspicion of cancer, additional evaluation of paraneoplastic autoantibodies is recommended
  • Individual tests in panel may also be ordered separately
Autoimmune Encephalitis Extended Panel 3001431
Method: Semi-Quantitative Indirect Fluorescent Antibody/Quantitative Radioimmunoassay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
  • Differential evaluation of encephalitis of unknown origin with subacute onset of seizures, confusion, memory loss, and/or behavioral change
  • Testing for LGI1 and CASPR2 antibodies always performed.
  • Panel includes NMDA receptor antibody, VGKC antibody, GAD65 antibody, AQP4 antibody.
  • For adults and patients with suspicion of cancer, additional evaluation of paraneoplastic autoantibodies is recommended
  • Individual tests in panel may also be ordered separately
Autoimmune Neuromuscular Junction Reflexive Panel 2005640
Method: Quantitative Radioimmunoassay/Qualitative Radiobinding Assay/Semi-Quantitative Flow Cytometry/Semi-Quantitative Indirect Fluorescent Antibody
  • Acceptable reflexive panel for the differential diagnosis of acquired neuromuscular junction disorders
  • Panel includes acetylcholine receptor binding, blocking, and modulating antibodies; VGKC antibody; VGCC antibody; titin antibody; striated muscle antibody; and LGI1 and CASPR2 antibodies

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

  • 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
    • Important to diagnose these illnesses due to therapeutic responsiveness

Physiology

  • VGKC autoantibodies
    • Directed against a protein that is complexed with potassium channels in both 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 RIA test 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

Last Update: August 2019