Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri).
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.
Pittock
Sean J
SJ
Mayo Medical School College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. pittock.sean@mayo.edu
Parisi
Joseph E
JE
McKeon
Andrew
A
Roemer
Shanu F
SF
Lucchinetti
Claudia F
CF
Tan
K Meng
KM
Keegan
B Mark
BM
Hunter
Samuel F
SF
Duncan
Paul R
PR
Baehring
Joachim M
JM
Matsumoto
Joseph Y
JY
Lennon
Vanda A
VA
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
D000974:Antibodies, Antinuclear; D000912:Antibodies, Neoplasm; C487483:ANNA-2 antibody