Clinical-pathologic correlations in voltage-gated Kv1 potassium channel complex-subtyped autoimmune painful polyneuropathy

Muscle Nerve. 2017 Apr;55(4):520-525. doi: 10.1002/mus.25371. Epub 2017 Feb 13.

Abstract

Introduction: Voltage-gated Kv1 potassium channel complex (VGKC) autoantibodies subtyped for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated-proteinlike 2 (CASPR2), and Kv IgGs have a spectrum of neurological presentations. Painful polyneuropathy is seen in some patients, but nerve pathology descriptions are lacking.

Methods: Clinicopathologic features were studied in subtyped VGKC-autoantibody-seropositive patients who had undergone nerve biopsies.

Results: Five patients were identified, 1 LGI1 IgG positive and 1 CASPR2 IgG positive, but all negative for Kv1.1-, 1.2-, 1.6-subtyped IgG autoantibodies. Median symptom duration was 17 months. Pain was the predominant symptom; 3 had mild sensory loss and/or weakness. Histopathological abnormalities were limited to axonal loss in 3. None had mononuclear cellular infiltrates. Electron micrographs revealed no interstitial abnormalities. Three patients reported marked improvement in pain with immunotherapy.

Conclusions: The nerve biopsy histopathology of patients subtyped for LGI1 and CASPR2 IgGs within the VGKC-complex spectrum disorders shows either normal density or axonal fiber loss without inflammatory infiltrates. A reversible neural hyperexcitable mechanism is considered to be the cause of this painful polyneuropathy. Muscle Nerve 55: 520-525, 2017.

Keywords: channelopathy; immunotherapy; nerve biopsy; pain; voltage-gated potassium antibody.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Female
  • Guillain-Barre Syndrome / blood*
  • Guillain-Barre Syndrome / complications*
  • Guillain-Barre Syndrome / pathology
  • Guillain-Barre Syndrome / therapy
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Intracellular Signaling Peptides and Proteins
  • KCNQ1 Potassium Channel / immunology*
  • Male
  • Membrane Proteins / immunology
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Nerve Tissue Proteins / immunology
  • Neural Conduction / physiology
  • Pain / blood
  • Pain / drug therapy
  • Pain / etiology*
  • Pain / pathology
  • Proteins / immunology
  • Severity of Illness Index
  • Sural Nerve / pathology
  • Sural Nerve / ultrastructure

Substances

  • Autoantibodies
  • CNTNAP2 protein, human
  • Immunoglobulins, Intravenous
  • Intracellular Signaling Peptides and Proteins
  • KCNQ1 Potassium Channel
  • LGI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins