The clinical spectrum of Caspr2 antibody-associated disease

Neurology. 2016 Aug 2;87(5):521-8. doi: 10.1212/WNL.0000000000002917. Epub 2016 Jul 1.

Abstract

Objective: To report a large cohort of patients with antibodies against contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder.

Methods: Serum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent.

Results: Median age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy-seven percent of the patients had ≥3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses.

Conclusions: Caspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / cerebrospinal fluid
  • Autoantibodies / immunology*
  • Disease / psychology*
  • Female
  • Humans
  • Limbic Encephalitis / complications
  • Limbic Encephalitis / diagnosis
  • Limbic Encephalitis / immunology
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / cerebrospinal fluid
  • Membrane Proteins / immunology*
  • Middle Aged
  • Myokymia / complications
  • Myokymia / diagnosis
  • Myokymia / immunology
  • Nerve Tissue Proteins / blood
  • Nerve Tissue Proteins / cerebrospinal fluid
  • Nerve Tissue Proteins / immunology*
  • Syndrome

Substances

  • Autoantibodies
  • CNTNAP2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins