title: Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri).
abstract: 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.
  
  
  METHODS
  Retrospective case series with prospective clinical follow-up.
  
  
  METHODS
  Mayo Clinic's Neuroimmunology Laboratory, Rochester, Minnesota.
  
  
  METHODS
  Consecutive patients with ANNA-2 seropositivity identified since January 1, 1990.
  
  
  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.
authors.affiliation: Mayo Medical School College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. pittock.sean@mayo.edu
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
authors.forename: Shanu F
authors.initials: SF
authors.lastname: Roemer
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: K Meng
authors.initials: KM
authors.lastname: Tan
authors.forename: B Mark
authors.initials: BM
authors.lastname: Keegan
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Hunter
authors.forename: Paul R
authors.initials: PR
authors.lastname: Duncan
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Baehring
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Matsumoto
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology*; D020821:Dystonic Disorders / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007568:Jaw / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007826:Laryngismus / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies
chemical_list: D000974:Antibodies, Antinuclear; D000912:Antibodies, Neoplasm; C487483:ANNA-2 antibody