european journal of paediatric neurology 14 (2010) 400–409

Official Journal of the European Paediatric Neurology Society

Original article

Opsoclonus–myoclonus in children associated or

not with neuroblastoma

Pauline Krug a, Gudrun Schleiermacher a,*, Jean Michon a, Dominique Valteau-Couanet b,

Hervé Brisse c, Michel Peuchmaur d, Sabine Sarnacki e,f, Hélène Martelli g,
Isabelle Desguerre h, Marc Tardieu i,j
a
Pediatric Oncology, Institut Curie, 26 rue d’Ulm, 75248 Paris, France
b
Pediatric Oncology, Institut Gustave Roussy, Villejuif, France
c
Radiology, Institut Curie, Paris, France
d
Department of Pathology, Hôpital Robert Debré, Paris, France
e
Department of Surgery, Hôpital Necker-Enfants Malades, Paris, France
f
University Paris Descartes, France
g
Department of Surgery, Hôpital Kremlin-Bicêtre, Kremlin-Bicêtre, France
h
Neuropediatrics, Hôpital Necker-Enfants-Malades, Paris, France
i
Neuropediatrics, Hôpital Kremlin-Bicêtre, Kremlin-Bicêtre, France
j
University Paris Sud 11, France

article info abstract

Article history: Objective: To compare the clinical data at diagnosis, treatment and neurological outcome in
Received 16 June 2009 34 children with opsoclonus–myoclonus syndrome (OMS) associated with a detected
Received in revised form neuroblastoma or not.
7 December 2009 Study design: This is a multicentric retrospective study of 34 children presenting with OMS
Accepted 22 December 2009 from four pediatric centers diagnosed between 1988 and 2008.
Results: Twenty-two patients had OMS associated with a neuroblastoma. These patients all
Keywords: had neuroblastomas with favourable prognostic features; all underwent surgery, six
Opsoclonus–myoclonus syndrome received chemotherapy. Twelve children had OMS without a detected neuroblastoma. For
Dancing eye syndrome OMS, the main treatment in all children was corticotherapy (n ¼ 33), but immunoglobulins
Neuroblastoma (n ¼ 13), cyclophosphamide (n ¼ 4) and rituximab (n ¼ 4) were also given. In the 27 OMS
Developmental delay 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 ¼ 9), persistent ataxia (n ¼ 6) and moderate motor deficit
(n ¼ 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

* Corresponding author.
E-mail address: gudrun.schleiermacher@curie.net (G. Schleiermacher).
1090-3798/$ – see front matter ª 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejpn.2009.12.005
 european journal of paediatric neurology 14 (2010) 400–409 401

neurological sequelae. An international collaboration is required to improve the knowledge

about OMS, the treatment and the outcome in this rare disorder.
ª 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights
reserved.

1. Introduction with personality changes (such as irritability or sleeping

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 move-
ments), myoclonus, which can affect the trunk, the face and the
extremities, and ataxia.1,2 These symptoms are often associated
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 para-
infectious).4–9 Sometimes, no etiology is found: in these cases,

Fig. 1 – OMS evaluation criteria (adapted from Matthay et al.2).

402 european journal of paediatric neurology 14 (2010) 400–409

it seems possible that a small NB escaping detection or one catecholamine metabolites, and MYCN amplification), as well
which had already regressed may have occurred, suggesting as oncological treatment and outcome were recorded.
that OMS with or without a detected NB may be the same
entity. The mechanism leading to this condition is probably 2.2. Neurological data
autoimmune but the physiopathology remains poorly under-
stood.10–14 OMS is seen in 2–3% of children with NB10,15 and a NB For patients with OMS both with or without NB, the degree of
is found in 50–80% of children with OMS.2 Children with NB ataxia, opsoclonus, myoclonus and sleep or mood disturbance
presenting with this paraneoplastic syndrome have an excel- were evaluated at diagnosis, during treatment and during
lent oncological outcome. Most often, the oncological treat- follow up, and the scoring system was assessed a posteriori
ment consists of surgery only, and sometimes chemotherapy. based on the patients’ records. The grading scale used is rep-
However, the neurological outcome of pediatric patients resented in Fig. 1, adapted from that developed by Mitchell and
with OMS is more compromised: neurological sequelae have Pike.2 Infectious and immunological investigations were per-
been reported in 70–80% of patients, including motor, formed particularly when no NB was identified: viral serologies
language, praxic and cognitive deficits.2,13,15,16 Delayed iso- (adenovirus, enterovirus, coxsackie, EBV, HHV6, VZV, CMV,
lated cerebellar atrophy has been described on MRI during HSV, HTLV1 and 2, human Parvovirus), bacterial serologies
long-term follow up.17 In order to improve neurological (Mycoplasma pneumoniae, Chlamydia pneumoniae, Borrelia burg-
outcome, different treatment modalities for OMS including dorferi, syphilis), but were not performed in patients with an
steroids, cyclophosphamide, intravenous immunoglobulins identified NB. Study of the CSF consisted of cells count, protein
and more recently rituximab have been used, with many side electrophoresis, interferon dosage, as well as chromatography
effects and a variable efficacy.18–23 But to date, the treatment of of cerebral amino acids in some cases. Brain imaging (MRI or
OMS is not standardized. Thus, the hallmark of this syndrome tomodensitometry) was performed at diagnosis and two years
is on the one hand the frequent relapse of neurological symp- later for some of the children. Lastly, at the moment of the last
toms when immunosuppressive treatment is decreased, and neurological follow up, the neurological status was recorded.
on the other hand the threat of long-term cognitive sequelae.
The goal of this study was to compare the clinical presen- 2.3. Statistical analysis
tation, treatment and neurological outcome of OMS associ-
ated with NB versus OMS without NB. For comparison of continuous variables between the two
patients group, the Mann–Whitney test (MW) was used. For
comparison of categorical, the c2 test was used. The level of
2. Patients and methods significance for all statistical tests was p < 0.05. Statistical
analysis was performed using the medcalc software.
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 3. Results
Roussy), and two large pediatric neurology centers (Necker
hospital and Kremlin Bicêtre hospital), between 1988 and Clinical data of the whole population are summarized in
2008, in the Ile-de-France (Paris, France) region, with more Table 1.
referrals to these specialised centers occurring within more
recent years. The 34 children (12 males, 22 females) were
followed in a multidisciplinary setting. Eligible patients were Table 1 – Oncological and neurological characteristics of
those who had a diagnosis of OMS defined by the presence of the whole population (n [ 34).
at least three of the following criteria: opsoclonus, ataxia/ Whole NBþ NB#
myoclonus, behavior changes and NB. The medical records of population (n ¼ 22) (n ¼ 12)
these patients admitted for OMS were reviewed. All children (n ¼ 34)
were screened for a primary NB tumor by various imaging
Percentage of detected NB 64.7% – –
methods, including abdominal sonography, neck, chest and Median age (months) 20.8 18.1 26.2
abdomino-pelvic CT-scan or MRI and I123 metaiodo-benzyl- Median neurological score at 9.3 10.1 7.3
guanidine (MIBG) scintigraphy, as well as with urinary cate- diagnosis
cholamine metabolites detection. The detection methods
Treatment
were heterogeneous due to the large recruitement period and Corticosteroids alone 11 5 6
evolution of clinical practice. Corticosteroids and second 20 17 3
line treatment
2.1. Oncological data Unknown 3 – 3

Neurological outcome
For each child with OMS and NB, oncological data at diagnosis Recovery 38.2% 36.4% 41.7%
and during the follow up were collected. At diagnosis, the age (n ¼ 13) (n ¼ 8) (n ¼ 5)
of onset of symptoms, the symptoms that lead to the diag- Sequelae 52.9% 63.6% 33.3%
(n ¼ 18) (n ¼ 14) (n ¼ 4)
nosis of the tumor (OMS or not), the characteristics of the
Unknown 8.8% - 25%
tumor (histological features, fixation on MIBG scintigraphy,
(n ¼ 3) (n ¼ 3)
stage according to INSS classification, detection of urinary
 european journal of paediatric neurology 14 (2010) 400–409 403

Table 2 – Oncological characteristics of patients with OMS and detected neuroblastoma.

Patient Age at Gender Revelation Localization Primary tumor Treatment Oncological
diagnosis of NB of the NB condition
of OMS Stage Elevation of MYCN at the end of
(months) urinary amplification the treatment
catecholamines

1 18 F OMS Cervical 2b No No Surgery CR

2 22 F OMS Thoracic 1 U No Surgery CR
3 18 F OMS Abdominal 2a U No Surgery CR
4 21 M OMS Thoracic 1 No No Surgery CR
5 13 F OMS Abdominal 1 No No Surgery CR
6 12 F OMS Adrenal 2a No No Neo- and adjuvant CR
chemotherapy,
surgery
7 19 M OMS Adrenal 2b No U Adjuvant CR
chemotherapy,
surgery
8 30 F OMS Thoracic 1 No No Surgery CR
9 25 M OMS Thoracic 2b No No Surgery CR
10 15 M OMS Pelvis 2a No No Neoadjuvant CR
chemotherapy,
surgery
11 15 F OMS Adrenal 1 No No Surgery CR
12 17 F OMS Thoracic 2a Yes No Neoadjuvant RT
chemotherapy,
surgery
13 18 M OMS Adrenal 1 Yes No Surgery CR
14 14 M OMS Thoracic, 2b No No Surgery CR
associated
with adrenal
calcification
15 11 F OMS Adrenal 1 No No Surgery CR
16 29 F Abdominal Adrenal 3 Yes No Neo- and adjuvant CR
pain chemotherapy,
due to surgery
neuroblastoma
17 14 M OMS Thoracic 1 No No Surgery RT
18 33 F OMS Thoracic 1 NR No Surgery CR
19 25 F OMS Pelvis 1 No No Surgery CR
20 15 F OMS Pelvis 1 No No Surgery CR
21 17 F OMS Pelvis 1 No No Surgery RT
22 9 F OMS Abdominal 3 Yes No Neoadjuvant CR
chemotherapy,
surgery

Abbreviations: M: male, F: female, U: unknown, CR: complete remission, RT: residual tumor.

3.1. OMS associated with NB
3.1.1. Oncological data
In 22 patients, an OMS associated with a NB was observed. The
oncological data for these 22 patients are listed in Table 2.
Their age at diagnosis ranged from 9 to 33 months (median:
18.1 months). Follow up ranged from 12 months to 16 years
(median 72 months) (Table 3). OMS lead to diagnosis of NB in all
patients except one, in whom NB was discovered by abdominal
pain, and clinical signs of OMS appeared secondarily. The NB
of these children had mainly features of good prognosis (Table
2). Surgical resection was the only oncological treatment in 16
patients, and six others received chemotherapy associated
with surgery (neoadjuvant and/or adjuvant).
3.1.2. Neurological data
The degree of ataxia, myoclonus, opsoclonus and mood or
sleep disturbance were recorded at diagnosis and during the
follow up (Table 3). At diagnosis, all except one had severe
stance and gait abnormalities (score >2). All patients had
opsoclonus except one, 14 patients presented with mood
disturbance and all but one had ataxia. The neurological score
at diagnosis ranged from 2 to 15 (median 10.9).
Patient 11, 16 and 22 underwent a cerebral MRI after the
onset of OMS (range 18 months to 2 years), which was normal.
3.1.3. Treatment and follow up of OMS
All patients received corticotherapy during first line treatment
except one who recovered spontaneously just after the
surgical resection and two who received immunoglobulins
(Table 3). Oral corticotherapy was the main treatment: pred-
nisone (posology: 1–2 mg/kg/day) in 11 cases, either continu-
ously (n ¼ 10) or intermittently (n ¼ 1, patient 2), and
hydrocortisone (10–14 mg/kg/day) in 6 cases. Three patients
received IV methylprednisolone pulses and three received
dexamethasone pulses. The median duration of
 404
Table 3 – Neurological presentation, treatment and outcome on the patients with OMS and detected neuroblastoma.
Patient Neurologic initial presentation Chemotherapy Initial ttt Other ttt Administration Length of Follow Neurological
modalities of corticotherapy up outcome
Stance Gait Arm and Opsoclonus Mood/ Total/ corticotherapy
hand Behaviour 15
function

1 3 3 3 2 2 13 – Corticosteroid – Continuous oral 33 months 12 years Motor and praxis

prednisone sequelae
2 2 2 0 1 0 5 – Ig Corticosteroid MP pulses, 3 months 37 Dysmetria
oral prednisone months

european journal of paediatric neurology 14 (2010) 400–409

3 3 3 3 3 2 14 – Diazepam, – Continuous oral 5 years 16 years Language and
corticosteroid prednisone praxis sequelae
4 3 3 3 3 2 14 – Corticosteroid Ig MP pulses, 12 months 12 Persistent ataxia
oral prednisone months
5 3 3 3 3 2 14 – Corticosteroid – Continuous oral (14 months) 14 Recovery
HC months
6 3 3 0 2 0 8 2 VPC-CADO*, 1 Corticosteroid – Continuous oral 24 months 35 Recovery
VPC-CADO# prednisone months
7 2 2 3 0 0 7 2 VPC-CADO# Corticosteroid – Continuous oral 5 years 16 years Recovery
prednisone
8 2 2 2 2 0 8 – Corticosteroid Ig, cyclophosphamide Continuous oral (25 months) 25 Recovery
HC months
9 3 3 0 2 0 8 – Ig Corticosteroid Continuous oral 6 months 6 years Recovery
prednisone
10 3 3 1 1 0 8 2 CADO-PE* Corticosteroid – Continuous oral 4 years 16 years Motor and praxis
prednisone sequelae
11 3 3 3 3 2 14 – Corticosteroid Ig, RTX, DXM IV pulses, 15 months 24 Persistent ataxia,
cyclophosphamide, RTX months pyramidal
syndrome
12 3 3 3 3 0 12 2 VPC-CADO* Corticosteroid – Continuous oral 7 days 10 years Motor and praxis
prednisone sequelae
13 3 3 3 3 3 15 – Corticosteroid Risperidone Continuous oral (15 months) 15 Persistent ataxia
HC months
14 2 2 2 3 1 10 – Corticosteroid Ig Continuous oral 6 months 33 Persistent ataxia,
prednisone months developmental
delay
15 3 3 0 3 1 10 – No treatment – – – 12 years Recovery
16 3 3 3 3 2 14 2 VPC-CADO*, 1 Corticosteroid Ig, RTX DXM IV pulses U 24 Moderate motor
VPC-CADO# months sequelae
17 0 0 0 1 1 2 – Corticosteroid Ig, cyclophosphamide DXM IV pulses U 20 Persistent ataxia
months
18 3 3 2 3 2 13 – Corticosteroid Ig, RTX Continuous oral 15 months 31 Persistent ataxia,
prednisone months pyramidal
syndrome
19 3 3 0 2 0 8 – Corticosteroid – Continuous oral 12 months 38 Recovery
HC months

(continued on next page)

 european journal of paediatric neurology 14 (2010) 400–409 405

corticotherapy was 23.1 months (range 7 days to 8 years), with

8 years Persistent ataxia,

three patients still on corticosteroids at the time of last follow

4 years Persistent ataxia

Neurological

developmental
outcome
up. Ten patients received immunoglobulins (Ig): in two cases
Ig were given first without any success (posology: 1 gram per

7 years Recovery

Chemotherapy: VPC for VP16 and carboplatine, CADO for cyclophosphamide, doxorubicin and vincristine, PE for platinum and etoposide, *, neoajuvant, #, adjuvant, 2: number of cures.
kilo per day, during 2 days), whereas 8 other patients received

delay
Ig because OMS was corticoresistant or corticodependant.
Three patients received cyclophosphamide, and four had rit-
Follow

uximab. The evaluation of the efficacy of these treatments

modalities of corticotherapy up

was difficult. For example, for patient 11, symptoms persisted

in spite of 15 courses of dexamethasone, 13 courses of
Length of

immunoglobulin, 7 courses of cyclophosphamide, and one

3 months

4 years
8 years
course of rituximab. Only two patients (NB#) were treated for
relapse of OMS after complete recovery with steroids as first
line treatment, when steroids were totally stopped. 14
patients (9 NBþ and 5 NB#) were corticodependant, i.e. the
Administration

corticotherapy

Continuous oral

Continuous oral

Abbreviations: ttt: treatment, Ig: immunoglobulin/HC: hydrocortisone/MP: methylprednisolone/DXM: dexamethasone/RTX: rituximab/U: unknown.
relapses were observed when decreasing the corticotherapy.
HC MP pulses

In these 16 patients, seven received a second line treatment,

and 4 patients received a third line treatment. Other patients
were corticoresistant from the onset of the treatment.
HC
U

3.2. OMS non-associated with NB

corticosteroid, Ig
Other ttt

Twelve patients had OMS without NB (seven females, five

RTX, diazepam,

males). Median age of these patients at diagnosis was 26.2

months (range 11 months to 6 years). Follow up ranged from
24 months to 10 years (median 50.1 months).
CSF was normal and no oligoclonal band was identified in
–

all cases. In some rare cases, immunological and infectious

Corticosteroid,
Corticosteroid

Corticosteroid

investigations permitted to identify a possible infectious

clonazepam
Initial ttt

etiology. Patient 28 had a positive HHV6 serology, but only IgG

antibodies (IgM unknown). In patient 32, varicella preceeded
the onset of OMS. In patient 34, OMS was preceeded by fever
and diarrhea without any other infectious etiology found. In
patient 31, onset of OMS was observed following a fever linked
Chemotherapy

2 VPC-CADO*

to a routine vaccine (Table 4).

Neurological score at diagnosis ranged from 5 to 13
–

(median 7.3). All patients had severe gait and stance distur-
bance (score >2), and only one patient had no opsoclonus. All
these patients received a corticotherapy as first treatment
Total/
15

(intramuscular ACTH, oral prednisone or hydrocortisone but

8

8
10

no methylprednisolone pulse). The median duration of corti-

Behaviour

Length of corticotherapy: (12 months): still under treatment.

cotherapy was 17.8 months (range 12–24 months), and two

Mood/

patients still receive corticotherapy at the time of last follow

Neurologic initial presentation

1
2

up. Three patients additionally received intravenous Ig

because of high corticodependance, with no efficacy. Only one
Stance Gait Arm and Opsoclonus

patient (patient 32) received cyclophosphamide because of

high corticodependance, and this second line treatment lead
2

2
2

to a possibility of decrease of corticotherapy and neurological

0: None, 1: mild, 2: moderate, 3: severe.

recovery. Four patients showed complete neurological

recovery after corticotherapy as only treatment. In patient 23,
function
hand

a cerebral MRI was performed five years after the onset of the
1

1
0

OMS symptoms because of cognitive deficit and was normal

including for cerebellar volume.
Table 3 (continued )

2
3

3.3. Comparison of these two populations

2

2
3

3.3.1. Age at diagnosis

Patient

The median age for all patients at presentation was 20.8

months (range 9 months to 6 years), 18.1 months for patients
20

21
22

NB-positive, and 26.2 months for NB-negative. Although not

 406
Table 4 – Neurological presentation, treatment and outcome on the patients with OMS without detected neuroblastoma.
Patient Neurologic initial presentation Etiology Initial ttt Other ttt Administration Lenght of Follow Neurological
modalities corticotherapy up outcome
Stance Gait Arm and hand Opsoclonus Mood/ Total/ of corticotherapy

european journal of paediatric neurology 14 (2010) 400–409

function Behaviour 15

23 2 2 0 2 0 6 - Corticosteroid - Continuous oral 18 months 5 years Cognitive, praxic,

prednisone language
sequelae
24 2 2 0 2 0 6 - Corticosteroid - Continuous oral 19 months 24 Recovery
prednisone months
25 1 1 2 2 1 7 - Corticosteroid - Continuous oral HC 13 months 60 Recovery
months
26 2 2 0 2 0 6 - Corticosteroid Ig Continuous oral U 10 years Cognitive, praxic,
prednisone language
sequelae
27 3 3 2 3 2 13 - Corticosteroid U Continuous oral HC U U U
28 2 2 0 1 0 5 HHV6 IgGþ Corticosteroid - Continuous oral HC 15 months 25 Persistent ataxia,
months cerebellar
syndrom
29 U U U U U – - Corticosteroid U Continuous oral U U U
prednisone
30 3 3 0 0 2 8 - Corticosteroid - Continuous oral HC 24 months 26 Recovery
months
31 2 2 0 2 0 6 Fever just Corticosteroid U Continuous oral HC U U U
after
vaccination
32 U U U U U – Varicella Corticosteroid Ig, Continuous oral 24 months 32 Recovery
cyclophosphamide prednisone months
33 2 2 2 2 1 9 - Corticosteroid Ig IM ACTH 8 years 8 years Cognitive
sequelae
34 U U U U U – Fever, Corticosteroid - Continuous oral HC 12 months 26 Recovery
diarrhea months

0: None, 1: mild, 2: moderate, 3: severe.

Abbreviations: ttt: treatement/Ig: immunoglobulin/HC: hydrocortisone/U: unknown.
 european journal of paediatric neurology 14 (2010) 400–409 407

Table 5 – Treatment and outcome of the patients with OMS, associated or not with neuroblastoma.
Treatment Neurological outcome

Corticotherapy Ig Surgical Chemotherapy Other Recovery Cognitive/ Persistant Moderate Total

resection motor/ ataxia motor sequelae
language deficit
delay

Followed-up more than 2 years

NBþ 18 16 7 17 6 5 6 6 5 2 12
NB- 9 9 3 - - 1 5 3 1 1 4
Total 27 25 10 17 6 6 11 9 6 3 16

Followed-up less than 2 years

NBþ 4 4 2 4 0 2 1 0 3 0 3
NB- 0

Abbreviation: Ig: immunoglobulin.

statistically significant, there was a trend towards an older age
at diagnosis in the population of patients with OMS without
NB (Mann–Whitney test, p ¼ 0.07).
3.3.2. Neurological status at diagnosis
The NB-positive patients compared to the NB-negative OMS
patients had a statistically significant higher neurological
score at diagnosis: median 10.1 (range 2–15), versus median
7.3 (range 5–13), respectively (MW, p ¼ 0.01). In a next step, the
score of each symptom at diagnosis was compared between
the two groups. There was a significant difference between
the two groups considering stance (MW, p ¼ 0.03), gait (MW,
p ¼ 0.03) and the arm and hand function (MW, p ¼ 0.05). All
these symptoms’ scores were significantly higher in the NB-
positive patients. There was no significant difference in terms
of opsoclonus (MW, p ¼ 0.17) and mood and behavioral
changes (MW, p ¼ 0.35).
3.4. Neurological outcome
In Table 5, the neurological outcome of all the patients (with or
without a NB) whose follow up was greater than two years is
shown. Among 27 patients, 11 recovered completely (40.7%).
Sixteen (59.3%) had neurological deficit: nine had motor, praxic
and/or language sequelae, and six had persistent ataxia or
myoclonus. There is no significant difference in the neurolog-
ical outcome (presence of sequelae vs. recovery) between the
two groups of patients (with and without NB, c2 test p ¼ 0.27).
The neurological outcome was not different between the groups
of children who received oral or intravenous corticotherapy (c2
test, p ¼ 0.14), and between the groups of children who received
chemotherapy for treatment of the NB or not (c2 test, p ¼ 0.68).
4. 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 in the
oldest cases of this series. More recently, standardized imaging
strategies have been proposed to optimize neuroblastoma
diagnosis: MRI is the best modality to diagnose a primary tumor
and evaluate its local extension, except for abdominal tumors
for which CT remains the best modality. Metastatic extension
should be assessed with MIBG scan and liver sonography.25,26
Neurological features were reported according to a scaling
system, based a posteriori on the clinical description in the
medical files. In this study, patients with NB-positive OMS had
a higher neurological score at diagnosis. Due to the retro-
spective analysis of non standardized data, the results may be
difficult to interpret This underlines the importance of
a homogeneous scoring system and a multidisciplinary
approach in all future prospective studies.
Neurological treatment for OMS was heterogeneous,
especially because of the large period of this retrospective
study. Thirty-three in 34 patients received corticotherapy. The
different therapeutic modalities did not seem to have an
impact on outcome in this small series. However, it would be
interesting to compare the efficacy of these heterogeneous
modalities, in order to standardize the corticotherapy, and to
specify the indications of a second line treatment. A long-term
corticosteroid administration seems to be the most wide-
spread practice, even if it involves many side effects and an
unpredictable efficacy.27 Other immunomodulatory therapies,
like intravenous immunoglobulins, cyclophosphamide or rit-
uximab were tried, but it is difficult to determinate their effi-
cacy, as they often were tried after corticosteroids for
corticoresistant or corticodependant OMS, but also because of
the few patients who received them. These other treatments
were always given in addition to corticosteroids in our study,
and not as first line treatment, except immunoglogulins, given
as first line treatment in two patients who received cortico-
steroids as second line treatment. A 29 patients’ retrospective
analysis had found a significative association between
a treatment with chemotherapy and a good neurological
outcome.28 This observation had not been confirmed by other
studies1,15 and our study do not provide any conclusion
regarding the efficiency of the chemotherapy on the neuro-
logical outcome because of the very few patients who received
it (only six).
408 european journal of paediatric neurology 14 (2010) 400–409
Regarding neurological outcome, only one previous study
has already compared the neurological outcome of patients
with OMS with or without NB (8 with NB, 3 without), and the
authors concluded that OMS without NB had a better neuro-
logical outcome.24 These results were not confirmed in our
series, as among our patients, the frequency of neurological
sequelae was similar between OMS patients with and without
NB.
In order to evaluate the prevalence of neurological
sequelae in children with OMS and NB, we compared our
neurological results with the neurological data of the main
retrospective studies on the subject. In Russo’s series,28 20/29
children had persistent neurologic sequelae (speech delay,
cognitive deficits, motor delay, behavioral disturbances). The
nine children who recovered were not different from the
others of the group in term of age at diagnosis and duration of
symptoms. But 6/9 children with complete recovery received
chemotherapy. In Plantaz’s series,1 10/16 had persistent
neurological deficits, and there was no relation between
neurological outcome, age at diagnosis, duration of neuro-
logical symptoms or oncological treatment, especially
chemotherapy. In Rudnick’s study,15 14/19 children developed
neurological or behavioral sequelae. In Hayward’s study,17 9/
11 children had mild to severe neurological sequelae. Brain
MRI was performed in five children and showed cerebellar
atrophy in each of them. In Mitchell’s series,29 all of the 17
patients had neurological deficit. Pohl3 studied 54 patients
with OMS: leukemia was found in one case, NB only in three
cases. 91% had neurological deficit. Taken together, 70/99
patients (70.7%) had at long-term mild to severe neurological
deficit. In our patients whose follow up was greater than 2
years, 16/27 (59.3%) had a persistent mild to severe neurolog-
ical deficit, confirming the poor neurological outcome previ-
ously described in the litterature.
In conclusion, in NB-positive and NB-negative OMS,
although neurological features at the time of diagnosis seem
to be slightly worse in the NB-positive group, neurological
outcome is equally poor, justifying a homogeneous treatment
strategy. These results further support the hypothesis that
OMS with or without NB could be the same disease, a NB
having escaped detection in the latter group. Because of the
rarity of this disease, a multidisciplinary and international
collaboration to improve the knowledge about OMS is
required, in order to set up a standardized diagnostic proce-
dures and treatment, and to work towards improvement of
the neurological outcome. An international trial protocol in
order to evaluate prospectively the outcome of patients with
OMS would be interesting. This protocol should include brain
MRI to assess cerebellar abnormalities, videos and standard-
ized neuropsychological tests, performed by the same person
to make the interpretation easier.
references
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Chastagner P, Bergeron C, et al. [Opsoclonus–myoclonus
syndrome associated with non-metastatic neuroblastoma.
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