SCIENTIFIC LETTER

Rituximab for Opsoclonus Myoclonus Ataxia SyndromeAssociated with Neuroblastoma

Shalini Sinha & Yogesh Kumar Sarin

Received: 17 December 2012 /Accepted: 5 April 2013# Dr. K C Chaudhuri Foundation 2013

To the Editor: A 1½-y-old girl presented with features ofOpsoclonus-Myoclonus Ataxia (OMA) syndrome and py-rexia of unknown origin of 6 mo duration. Detailed neuro-logical workup was negative. Further evaluation revealed a5.2×2.3 cm solid mass in the right para-spinal region abut-ting the D10-L1 vertebral bodies. Despite a delay in seekingtreatment, the tumor size remained unchanged for 4 mo.Urinary VMA and metastatic workup were negative. Trucutbiopsy of the lesion showed a malignant blue round celltumor. Trans-diaphragmatic R1 resection was done. His-topathology confirmed Stage 2A low risk (COG) neuro-blastoma (NB). She received 4 cycles of chemotherapy(cyclophosphamide, doxorubicin and vincristine) withoutany reversal of OMA syndrome. We also tried oralprednisolone (2 mg/kg/d) for 1 mo and intravenousimmunoglobulin (IVIG) (1 g/kg) once a month for2 mo without any response. Finally, intravenous rituximabtherapy (375 mg/m2 weekly for 4 wk) was given afterpremedication (acetaminophen and diphenhydramine). Therewere no side effects and a dramatic sustained improvementwas observed within a month. She has been followed upthereafter for 2.5 y without any NB recurrence or relapse ofOMA syndrome. Her gait and speech are normal; she isattending a regular school.

OMA syndrome is a rare neurobehavioral syndromeaffecting 2–3 % of children with NB [1]. Though ma-jority of these patients have slow growing, stage I/IItumors with favorable biology and excellent overallsurvival rates [1], they have long-term neurologic,

cognitive, behavioral, developmental, and academic im-pairment [2].

The underlying etiology of OMA syndrome is thought tobe autoimmune. Immunosuppressive therapies like cyclo-phosphamide based chemotherapy, corticosteroids, IVIG,Corticotropin (ACTH) and plasmapheresis have been foundto ameliorate the acute symptoms of OMA syndrome butnone have shown long-term results with reported relapserates as high as 68 % [3, 4].

Rituximab is a genetically engineered monoclonalanti B-cell antibody, which was initially approved bythe US Food and Drug Administration to treat B-cellnon-Hodgkin’s lymphomas [5]. It has been ever sinceused for the treatment of several autoimmune disordersincluding OMA syndrome [4]. It is a safe drug withonly mild to moderate adverse effects, the commonbeing infusion-related reactions that can be managedwith premedication, supportive care, and adjusted infu-sion rates [5]. An exhaustive literature review howeverdid not reveal its use for OMA syndrome from theIndian subcontinent hitherto. We add evidence thatrituximab is safe therapy for OMA syndrome in chil-dren with NB that gives promising long-term results.

References

1. Rudnick E, Khakoo Y, Antunes NL, Seeger RC, Brodeur GM,Shimada H, et al. Opsoclonus-myoclonus-ataxia syndrome in neu-roblastoma: Clinical outcome and antineuronal antibodies-A reportfrom the Children’s Cancer Group Study. Med Pediatr Oncol.2001;36:612–22.

2. Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, MitchellWG, et al. Opsoclonus myoclonus syndrome in neuroblastoma areport from a workshop on the dancing eyes syndrome at the

S. Sinha :Y. K. Sarin (*)Department of Pediatric Surgery, Maulana Azad Medical College,New Delhi 110002, Indiae-mail: yksarin@hotmail.com

Indian J PediatrDOI 10.1007/s12098-013-1042-7

advances in neuroblastoma meeting in Genoa, Italy, 2004. CancerLett. 2005;228:275–82.

3. Mitchell WG, Davalos-Gonzalez Y, Brumm VL, Aller SK,Burger E, Turkel SB, et al. Opsoclonus-ataxia caused by child-hood neuroblastoma: Developmental and neurologic sequelae.Pediatrics. 2002;109:86–98. Erratum in: Pediatrics 2002;110:853–4.

4. Pranzatelli MR, Tate ED, Travelstead AL, Longee D. Immunologicand clinical responses to rituximab in a child with opsoclonus-myoclonus syndrome. Pediatrics. 2005;115:e115–9.

5. Grillo-López AJ, White CA, Varns C, Shen D, Wei A, McClure A,et al. Overview of the clinical development of rituximab: Firstmonoclonal antibody approved for the treatment of lymphoma.Semin Oncol. 1999;26:66–73.

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