Original article
Opsoclonus–myoclonus in children associated or not with neuroblastoma

https://doi.org/10.1016/j.ejpn.2009.12.005Get rights and content

Abstract

Objective

To compare the clinical data at diagnosis, treatment and neurological outcome in 34 children with opsoclonus–myoclonus syndrome (OMS) associated with a detected neuroblastoma or not.

Study design

This is a multicentric retrospective study of 34 children presenting with OMS from four pediatric centers diagnosed between 1988 and 2008.

Results

Twenty-two patients had OMS associated with a neuroblastoma. These patients all had neuroblastomas with favourable prognostic features; all underwent surgery, six received chemotherapy. Twelve children had OMS without a detected neuroblastoma. For OMS, the main treatment in all children was corticotherapy (n = 33), but immunoglobulins (n = 13), cyclophosphamide (n = 4) and rituximab (n = 4) were also given. In the 27 OMS patients with or without neuroblastoma whose follow up was greater than two years, the neurological outcome was evaluated: 59.3% had neurological sequelae, including motor, praxic and/or language sequelae (n = 9), persistent ataxia (n = 6) and moderate motor deficit (n = 3). No significant difference in neurological outcome was noted between the two patient groups.

Conclusion

Our retrospective study provides further evidence that OMS with or without a detected neuroblastoma is the same disease, whose major challenges are the neurological sequelae. An international collaboration is required to improve the knowledge about OMS, the treatment and the outcome in this rare disorder.

Introduction

Ospoclonus–myoclonus syndrome (OMS), also called “dancing eyes syndrome” or “Kinsbourne syndrome”, is a rare entity, characterized by three main symptoms: opsoclonus (i.e. conjugate, non-phasic fast and multidirectionnal eyes movements), myoclonus, which can affect the trunk, the face and the extremities, and ataxia.1, 2 These symptoms are often associated with personality changes (such as irritability or sleeping disturbances) and developmental regression. This syndrome is more frequently reported in adults than in children.

In children, OMS is most frequently paraneoplastic, found in association with neuroblastoma (NB), or much more rarely with other cancers.3 Apart from the paraneoplastic association with NB other etiologies include infection (post or parainfectious).4, 5, 6, 7, 8, 9 Sometimes, no etiology is found: in these cases, it seems possible that a small NB escaping detection or one which had already regressed may have occurred, suggesting that OMS with or without a detected NB may be the same entity. The mechanism leading to this condition is probably autoimmune but the physiopathology remains poorly understood.10, 11, 12, 13, 14 OMS is seen in 2–3% of children with NB10, 15 and a NB is found in 50–80% of children with OMS.2 Children with NB presenting with this paraneoplastic syndrome have an excellent oncological outcome. Most often, the oncological treatment consists of surgery only, and sometimes chemotherapy.

However, the neurological outcome of pediatric patients with OMS is more compromised: neurological sequelae have been reported in 70–80% of patients, including motor, language, praxic and cognitive deficits.2, 13, 15, 16 Delayed isolated cerebellar atrophy has been described on MRI during long-term follow up.17 In order to improve neurological outcome, different treatment modalities for OMS including steroids, cyclophosphamide, intravenous immunoglobulins and more recently rituximab have been used, with many side effects and a variable efficacy.18, 19, 20, 21, 22, 23 But to date, the treatment of OMS is not standardized. Thus, the hallmark of this syndrome is on the one hand the frequent relapse of neurological symptoms when immunosuppressive treatment is decreased, and on the other hand the threat of long-term cognitive sequelae.

The goal of this study was to compare the clinical presentation, treatment and neurological outcome of OMS associated with NB versus OMS without NB.

Section snippets

Patients and methods

This retrospective study comprised pediatric patients who were treated for OMS with or without a NB, from two large pediatric oncology centers (Institut Curie and Institut Gustave Roussy), and two large pediatric neurology centers (Necker hospital and Kremlin Bicêtre hospital), between 1988 and 2008, in the Ile-de-France (Paris, France) region, with more referrals to these specialised centers occurring within more recent years. The 34 children (12 males, 22 females) were followed in a

Results

Clinical data of the whole population are summarized in Table 1.

Discussion

This study is a retrospective analysis of the neurological features of 34 patients with OMS.

In 22 cases, OMS was associated with a NB of favourable prognosis. Among 12 NB-negative OMS patients, in only 4 could an infectious etiology be suspected. However, despite multiple investigations having been performed, the search for an infectious etiology was not standardized. Furthermore, as the sensitivity of all imaging methods increased during the study period, small NB tumors could have been missed

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