Rituximab (anti-CD20) adjunctive therapy for opsoclonus-myoclonus syndrome.
OBJECTIVE
To determine if rituximab, an anti-CD20 monoclonal antibody, reduces cerebrospinal fluid (CSF) B-cell expansion in opsoclonus-myoclonus syndrome (OMS) and results in clinical improvement.


METHODS
Sixteen children with OMS and increased % CD20 B-cells in CSF received 4 rituximab infusions (375 mg/m IV) as add-on therapy to corticotropin (ACTH), intravenous immunoglobulins, or both, and were reevaluated 6 months later. Outcome measures were clinical (motor function, behavior, sleep) and immunologic (CSF and blood immunophenotype and Ig levels). Controls were 16 age-matched and sex-matched children, who did not have OMS.


RESULTS
After rituximab, 81% of OMS had a lower motor severity score, and 44% improved one severity category. Mean total score decreased by 44% (P = 0.0005). Rituximab reduced rage score, nighttime awakenings, and the number of children with opsoclonus, action myoclonus, drooling, gait ataxia, and rage. Despite a 51% reduction in ACTH dose, 9 of 11 children on ACTH did not relapse. The percentage of CSF CD19 (and CD20) B-cells was lowered in all children (undetectable in 6), with a 90% reduction in the group mean (P = 0.00003). CSF B-cells were no longer expanded compared with controls. In blood, CD19 B-cells decreased (-90%, P = 0.0003), as did the CSF:blood CD19 B-cell ratio (P = 0.00003). Serum IgM fell by 69% (below reference range), with no statistically significant change in IgG or IgA.


CONCLUSIONS
Rituximab seems efficacious and safe as adjunctive therapy for OMS. Selective targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy for centrally mediated paraneoplastic disorders.
Pranzatelli
Michael R
MR
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, IL, USA. mpranzatelli@siumed.edu
Tate
Elizabeth D
ED
Travelstead
Anna L
AL
Barbosa
Jerry
J
Bergamini
Robert A
RA
Civitello
Lucy
L
Franz
David N
DN
Greffe
Brian S
BS
Hanson
Robin D
RD
Hurwitz
Craig A
CA
Kalinyak
Karen A
KA
Kelfer
Howard
H
Khakoo
Yasmin
Y
Mantovani
John F
JF
Nicholson
Stacy H
SH
Sanders
Joann M
JM
Wegner
Stephen
S
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects; D001519:Behavior / Q000187:drug effects; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy; D007223:Infant; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009447:Neuroblastoma / Q000150:complications / Q000188:drug therapy; D020361:Paraneoplastic Syndromes, Nervous System / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D000069283:Rituximab; D012890:Sleep / Q000187:drug effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab