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

Sean J. Pittock, Joseph E. Parisi, Andrew McKeon, Shanu F. Roemer, Claudia F. Lucchinetti, K. Meng Tan, B. Mark Keegan, Samuel F. Hunter, Paul R. Duncan, Joachim M. Baehring, Joseph Y. Matsumoto, Vanda A. Lennon

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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 OutcomeMethods: 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 brain-stem 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 brain-stem reticular formation) is the proximal cause of this syndrome. Early and aggressive therapy offers the prospect of neurologic improvement or stabilization.

Original languageEnglish (US)
Pages (from-to)1109-1115
Number of pages7
JournalArchives of neurology
Issue number9
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


Dive into the research topics of 'Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri)'. Together they form a unique fingerprint.

Cite this