Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri)

Arch Neurol. 2010 Sep;67(9):1109-15. doi: 10.1001/archneurol.2010.209.


Background: Opsoclonus-myoclonus syndrome and breast carcinoma were initially described as neurologic and oncologic accompaniments of antineuronal nuclear autoantibody type 2 (ANNA-2, also known as anti-Ri). However, the neurologic spectrum of ANNA-2 autoimmunity is broader, includes a syndrome of jaw dystonia and laryngospasm, and can be accompanied by lung carcinoma.

Objective: To describe clinically (with a video) ANNA-2-associated jaw dystonia and laryngospasm, its pathologic correlates, and therapeutic outcomes.

Design: Retrospective case series with prospective clinical follow-up.

Setting: Mayo Clinic's Neuroimmunology Laboratory, Rochester, Minnesota.

Patients: Consecutive patients with ANNA-2 seropositivity identified since January 1, 1990.

Main outcome methods: Clinical (in 9 patients) and neuropathologic (in 2 patients) findings were reviewed.

Results: Of 48 patients with ANNA-2 seropositivity, 9 (19%) had multifocal neurologic manifestations that included jaw dystonia and laryngospasm. Among 6 patients with jaw dystonia, 5 had severely impaired nutrition, causing profound weight loss. Five patients had documented laryngospasm, which contributed to 1 patient's death. Neuropathologic examination revealed diffuse infiltration by CD8(+) T lymphocytes, with axonal loss and gliosis in brainstem and descending spinal cord tracts. Some patients improved symptomatically after immunosuppressant or cytotoxic therapies; 1 patient improved after treatment with botulinum toxin. One patient who underwent tracheostomy because of recurrent laryngospasm was alive and well longer than 3 years after symptom onset.

Conclusions: Jaw dystonia and laryngospasm are common accompaniments of ANNA-2 autoimmunity and are associated with significant morbidity. We propose that selective damage to antigen-containing inhibitory fibers innervating bulbar motor nuclei by CD8(+) T lymphocytes (histopathologically observed infiltrating brainstem reticular formation) is the proximal cause of this syndrome. Early and aggressive therapy offers the prospect of neurologic improvement or stabilization.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / immunology
  • Antibodies, Neoplasm / immunology*
  • Brain / immunology
  • Brain / pathology*
  • Dystonic Disorders / immunology*
  • Dystonic Disorders / pathology
  • Dystonic Disorders / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Jaw / immunology*
  • Jaw / pathology
  • Jaw / physiopathology
  • Laryngismus / immunology*
  • Laryngismus / pathology
  • Laryngismus / physiopathology
  • Male
  • Middle Aged
  • Paraneoplastic Syndromes / immunology*
  • Paraneoplastic Syndromes / pathology
  • Paraneoplastic Syndromes / physiopathology
  • Retrospective Studies


  • ANNA-2 antibody, human
  • Antibodies, Antinuclear
  • Antibodies, Neoplasm