Five Years Follow-up of Opsoclonus–Myoclonus–Ataxia Syndrome-Associated Neurogenic Tumors in Children

Abstract

Aim Opsoclonus–myoclonus–ataxia syndrome (OMAS) is a rare autoimmune disorder. Approximately half of the cases are associated with neuroblastoma in children. This study's aim is to review management of our cases with OMAS-associated neuroblastoma for treatment approach as well as long-term follow-up.

Methods Age at onset of symptoms and tumor diagnosis, tumor location, histopathology, stage, chemotherapy, OMAS protocol, surgery, and follow-up period were evaluated retrospectively in six patients between 2007 and 2022.

Results Mean age of onset of OMAS findings was 13.5 months and mean age at tumor diagnosis was 15.1 months. Tumor was located at thorax in three patients and surrenal in others. Four patients underwent primary surgery. Histopathological diagnosis was ganglioneuroblastoma in three, neuroblastoma in two, and undifferentiated neuroblastoma in one. One patient was considered as stage 1 and rest of them as stage 2. Chemotherapy was provided in five cases. The OMAS protocol was applied to five patients. Our protocol is intravenous immunoglobulin (IVIG) 1 g/kg/d for 2 consecutive days once a month and dexamethasone for 5 days (20 mg/m²/d for 1–2 days, 10 mg/m²/d for 3–4 days, and 5 mg/m²/d for the fifth day) once a month, alternatively by 2-week intervals. Patients were followed up for a mean of 8.1 years. Neuropsychiatric sequelae were detected in two patients.

Conclusion In tumor-related cases, alternating use of corticosteroid and IVIG for suppression of autoimmunity as the OMAS protocol, total excision of the tumor as soon as possible, and chemotherapeutics in selected patients seem to be related to resolution of acute problems, long-term sequelae, and severity.

Keywords

opsoclonus–myoclonus–ataxia syndrome - neuroblastoma - immunosuppression - tumor - surgery - sequelae

Authors' Contribution

E.H.A., N.Y., and İ.E. designed the study; E.H.A., H.Ö.G., and N.Y. collected the data; E.H.A., N.Y., İ.E., and F.S. performed the analysis and interpretation of results; E.H.A., N.Y., İ.E., A.E., and F.S. contributed to draft manuscript preparation.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Publication History

Received: 20 December 2022

Accepted: 08 March 2023

Article published online:
05 April 2023

• References

• 1 Bhatia P, Heim J, Cornejo P, Kane L, Santiago J, Kruer MC. Opsoclonus-myoclonus-ataxia syndrome in children. J Neurol 2022; 269 (02) 750-757
• 2 Klein A, Schmitt B, Boltshauser E. Long-term outcome of ten children with opsoclonus-myoclonus syndrome. Eur J Pediatr 2007; 166 (04) 359-363
• 3 Wilbur C, Yea C, Licht C, Irwin MS, Yeh EA. An upfront immunomodulatory therapy protocol for pediatric opsoclonus-myoclonus syndrome. Pediatr Blood Cancer 2019; 66 (08) e27776
• 4 Yamamoto K, Ohta S, Ito E. et al. Marginal decrease in mortality and marked increase in incidence as a result of neuroblastoma screening at 6 months of age: cohort study in seven prefectures in Japan. J Clin Oncol 2002; 20 (05) 1209-1214
• 5 Rudnick E, Khakoo Y, Antunes NL. et al. Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies-a report from the Children's Cancer Group Study. Med Pediatr Oncol 2001; 36 (06) 612-622
• 6 Brunklaus A, Pohl K, Zuberi SM, de Sousa C. Outcome and prognostic features in opsoclonus-myoclonus syndrome from infancy to adult life. Pediatrics 2011; 128 (02) e388-e394
• 7 Mizia-Malarz A, Stolpa W, Sobol-Milejska G. The treatment of opsoclonus-myoclonus syndrome secondary to neuroblastic tumors-single centre experience and literature review. Medicina (Kaunas) 2020; 56 (08) 412
• 8 de Alarcon PA, Matthay KK, London WB. et al. Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial. Lancet Child Adolesc Health 2018; 2 (01) 25-34
• 9 Matthay KK, Blaes F, Hero B. et al. Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004. Cancer Lett 2005; 228 (1-2): 275-282
• 10 Pranzatelli MR, Tate ED. Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome. Brain Dev 2016; 38 (05) 439-448
• 11 Pranzatelli MR, McGee NR, Tate ED. Relation of intrathecal oligoclonal band production to inflammatory mediator and immunotherapy response in 208 children with OMS. J Neuroimmunol 2018; 321: 150-156
• 12 Takama Y, Yoneda A, Nakamura T. et al. Early detection and treatment of neuroblastic tumor with opsoclonus-myoclonus syndrome improve neurological outcome: a review of five cases at a single institution in Japan. Eur J Pediatr Surg 2016; 26 (01) 54-59
• 13 Rossor T, Yeh EA, Khakoo Y. et al; OMS Study Group. Diagnosis and management of opsoclonus-myoclonus-ataxia syndrome in children. Neurol Neuroimmunol Neuroinflamm 2022; 9 (03) e1153
• 14 Meena JP, Seth R, Chakrabarty B, Gulati S, Agrawala S, Naranje P. Neuroblastoma presenting as opsoclonus-myoclonus: a series of six cases and review of literature. J Pediatr Neurosci 2016; 11 (04) 373-377
• 15 Mitchell WG, Wooten AA, O'Neil SH, Rodriguez JG, Cruz RE, Wittern R. Effect of increased immunosupression on developmental outcome of opsoclonus myoclonus syndrome. J Child Neurol 2015; 30 (08) 976-982
• 16 Johnston WR, Hwang R, Mattei P. Surgical considerations for neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome: a series of 14 patients from a single institution. Pediatr Surg Int 2022; 38 (02) 249-255
• 17 Kuyama H, Nii A, Takehara H, Inoue N, Watanabe H, Sakaki M. Ganglioneuroblastoma, intermixed with opsoclonus-myoclonus syndrome. Pediatr Int 2012; 54 (03) e26-e28
• 18 Aydin GB, Kutluk MT, Buyukpamukcu M, Akyuz C, Yalcin B, Varan A. Neurological complications of neuroblastic tumors: experience of a single center. Childs Nerv Syst 2010; 26 (03) 359-365
• 19 Anand S, Agarwala S, Jain V. et al. Neuroblastoma with opsoclonus-myoclonus-ataxia syndrome: role of chemotherapy in the management: experience from a tertiary care center in a resource-limited setting. J Pediatr Hematol Oncol 2021; 43 (07) e924-e929
• 20 Sahu JK, Prasad K. The opsoclonus–myoclonus syndrome. Pract Neurol 2011; 11 (03) 160-166
• 21 Sun Q, Wang Y, Xie Y, Wu P, Li S, Zhao W. Long-term neurological outcomes of children with neuroblastoma with opsoclonus-myoclonus syndrome. Transl Pediatr 2022; 11 (03) 368-374
• 22 Yıldırım M, Öncel İ, Bektaş Ö. et al. Clinical features and outcomes of opsoclonus myoclonus ataxia syndrome. Eur J Paediatr Neurol 2022; 41: 19-26