Insights on chronic-relapsing opsoclonus-myoclonus from a pilot study of mycophenolate mofetil.
Opsoclonus-myoclonus syndrome is characterized by abnormal lymphocyte trafficking into brain. The authors hypothesized that mycophenolate mofetil, a lymphocyte proliferation inhibitor, might be therapeutic. The cerebrospinal fluid and blood immunophenotypes of 15 children with predominantly chronic-relapsing opsoclonus-myoclonus syndrome were compared before and after treatment by flow cytometry. Mycophenolate mofetil reduced the cerebrospinal fluid expansion of HLA-DR+ activated T cells (-40%); the frequency of other T-cell or natural killer cell subsets remained unchanged, but cerebrospinal fluid B cells increased significantly. Adrenocorticotropic hormone dose was lowered by 64% over an average of 1.5 years, yet 73% eventually relapsed despite therapeutic drug levels. Prior treatment with rituximab prevented relapse-associated increase in cerebrospinal fluid B cells, without hindering mycophenolate mofetil-induced reduction in T-cell activation. These data demonstrate resistant immunologic problems in chronic-relapsing opsoclonus-myoclonus syndrome. Mycophenolate mofetil did not prevent relapse. The novel effect of mycophenolate mofetil on chronically activated T cells may contribute to its efficacy in T-cell mediated neurological disorders.
Pranzatelli
Michael R
MR
National Pediatric Myoclonus Center and Department of Neurology, SouthernIllinois University School of Medicine, Springfield, Illinois, USA. mpranzatelli@siumed.edu
Tate
Elizabeth D
ED
Travelstead
Anna L
AL
Baumgardner
Christine A
CA
Gowda
Narayana V
NV
Halthore
Sri N
SN
Kerstan
Peter
P
Kossak
Brian D
BD
Mitchell
Wendy G
WG
Taub
Jeffrey W
JW
D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053578:Opsoclonus-Myoclonus Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology; D010641:Phenotype; D010865:Pilot Projects; D012008:Recurrence; D000069283:Rituximab; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D000324:Adrenocorticotropic Hormone; D009173:Mycophenolic Acid