Opsoclonus-myoclonus in children associated or not with ... - sepeap

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
Article history:
Received 16 June 2009
Received in revised form
7 December 2009
Accepted 22 December 2009
Keywords:
Opsoclonus–myoclonus syndrome
Dancing eye syndrome
Neuroblastoma
Developmental delay
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 ¼ 33), but immunoglobulins
(n ¼ 13), cyclophosphamide (n ¼ 4) and rituximab (n ¼ 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 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
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).
4–9 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
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.
10–14 OMS is seen in 2–3% of children with NB 10,15 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. 18–23 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.
2. 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 multidisciplinary setting. Eligible patients were
those who had a diagnosis of OMS defined by the presence of
at least three of the following criteria: opsoclonus, ataxia/
myoclonus, behavior changes and NB. The medical records of
these patients admitted for OMS were reviewed. All children
were screened for a primary NB tumor by various imaging
methods, including abdominal sonography, neck, chest and
abdomino-pelvic CT-scan or MRI and I 123 metaiodo-benzylguanidine
(MIBG) scintigraphy, as well as with urinary catecholamine
metabolites detection. The detection methods
were heterogeneous due to the large recruitement period and
evolution of clinical practice.
2.1. Oncological data
catecholamine metabolites, and MYCN amplification), as well
as oncological treatment and outcome were recorded.
2.2. Neurological data
For patients with OMS both with or without NB, the degree of
ataxia, opsoclonus, myoclonus and sleep or mood disturbance
were evaluated at diagnosis, during treatment and during
follow up, and the scoring system was assessed a posteriori
based on the patients’ records. The grading scale used is represented
in Fig. 1, adapted from that developed by Mitchell and
Pike. 2 Infectious and immunological investigations were performed
particularly when no NB was identified: viral serologies
(adenovirus, enterovirus, coxsackie, EBV, HHV6, VZV, CMV,
HSV, HTLV1 and 2, human Parvovirus), bacterial serologies
(Mycoplasma pneumoniae, Chlamydia pneumoniae, Borrelia burgdorferi,
syphilis), but were not performed in patients with an
identified NB. Study of the CSF consisted of cells count, protein
electrophoresis, interferon dosage, as well as chromatography
of cerebral amino acids in some cases. Brain imaging (MRI or
tomodensitometry) was performed at diagnosis and two years
later for some of the children. Lastly, at the moment of the last
neurological follow up, the neurological status was recorded.
2.3. Statistical analysis
For comparison of continuous variables between the two
patients group, the Mann–Whitney test (MW) was used. For
comparison of categorical, the c 2 test was used. The level of
significance for all statistical tests was p < 0.05. Statistical
analysis was performed using the medcalc software.
3. Results
Clinical data of the whole population are summarized in
Table 1.
Table 1 – Oncological and neurological characteristics of
the whole population (n [ 34).
Whole
population
(n ¼ 34)
NBþ
(n ¼ 22)
NB
(n ¼ 12)
Percentage of detected NB 64.7% – –
Median age (months) 20.8 18.1 26.2
Median neurological score at
diagnosis
9.3 10.1 7.3
Treatment
Corticosteroids alone 11 5 6
Corticosteroids and second
20 17 3
line treatment
Unknown 3 – 3
For each child with OMS and NB, oncological data at diagnosis
and during the follow up were collected. At diagnosis, the age
of onset of symptoms, the symptoms that lead to the diagnosis
of the tumor (OMS or not), the characteristics of the
tumor (histological features, fixation on MIBG scintigraphy,
stage according to INSS classification, detection of urinary
Neurological outcome
Recovery 38.2%
(n ¼ 13)
Sequelae 52.9%
(n ¼ 18)
Unknown 8.8%
(n ¼ 3)
36.4%
(n ¼ 8)
63.6%
(n ¼ 14)
41.7%
(n ¼ 5)
33.3%
(n ¼ 4)
- 25%
(n ¼ 3)

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
pain
due to
neuroblastoma
Adrenal 3 Yes No Neo- and adjuvant
chemotherapy,
surgery
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
chemotherapy,
surgery
CR
Abbreviations: M: male, F: female, U: unknown, CR: complete remission, RT: residual tumor.
CR
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: prednisone
(posology: 1–2 mg/kg/day) in 11 cases, either continuously
(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

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
modalities of
corticotherapy
Stance Gait Arm and Opsoclonus
hand
function
Mood/
Behaviour
Total/
15
Length of Follow
corticotherapy up
Neurological
outcome
404
1 3 3 3 2 2 13 – Corticosteroid – Continuous oral
prednisone
2 2 2 0 1 0 5 – Ig Corticosteroid MP pulses,
oral prednisone
3 3 3 3 3 2 14 – Diazepam,
corticosteroid
– Continuous oral
prednisone
4 3 3 3 3 2 14 – Corticosteroid Ig MP pulses,
oral prednisone
5 3 3 3 3 2 14 – Corticosteroid – Continuous oral
HC
6 3 3 0 2 0 8 2 VPC-CADO*, 1
VPC-CADO#
Corticosteroid – Continuous oral
prednisone
7 2 2 3 0 0 7 2 VPC-CADO# Corticosteroid – Continuous oral
prednisone
8 2 2 2 2 0 8 – Corticosteroid Ig, cyclophosphamide Continuous oral
HC
9 3 3 0 2 0 8 – Ig Corticosteroid Continuous oral
prednisone
10 3 3 1 1 0 8 2 CADO-PE* Corticosteroid – Continuous oral
prednisone
11 3 3 3 3 2 14 – Corticosteroid Ig, RTX,
cyclophosphamide,
DXM IV pulses,
RTX
12 3 3 3 3 0 12 2 VPC-CADO* Corticosteroid – Continuous oral
prednisone
13 3 3 3 3 3 15 – Corticosteroid Risperidone Continuous oral
HC
14 2 2 2 3 1 10 – Corticosteroid Ig Continuous oral
prednisone
33 months 12 years Motor and praxis
sequelae
3 months 37 Dysmetria
months
5 years 16 years Language and
praxis sequelae
12 months 12 Persistent ataxia
months
(14 months) 14 Recovery
months
24 months 35 Recovery
months
5 years 16 years Recovery
(25 months) 25 Recovery
months
6 months 6 years Recovery
4 years 16 years Motor and praxis
sequelae
15 months 24 Persistent ataxia,
months pyramidal
syndrome
7 days 10 years Motor and praxis
sequelae
(15 months) 15 Persistent ataxia
months
6 months 33 Persistent ataxia,
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
VPC-CADO#
Corticosteroid Ig, RTX DXM IV pulses U 24 Moderate motor
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
prednisone
19 3 3 0 2 0 8 – Corticosteroid – Continuous oral
HC
15 months 31
months
Persistent ataxia,
pyramidal
syndrome
12 months 38 Recovery
months
(continued on next page)
european journal of paediatric neurology 14 (2010) 400–409

european journal of paediatric neurology 14 (2010) 400–409 405
Table 3 (continued)
Neurological
outcome
Follow
up
Length of
corticotherapy
Patient Neurologic initial presentation Chemotherapy Initial ttt Other ttt Administration
modalities of
corticotherapy
Total/
15
Opsoclonus Mood/
Behaviour
Stance Gait Arm and
hand
function
3 months 7 years Recovery
20 2 2 1 2 1 8 – Corticosteroid – Continuous oral
HC
21 2 2 1 2 1 8 – Corticosteroid – U 4 years 4 years Persistent ataxia
8 years 8 years Persistent ataxia,
developmental
delay
Continuous oral
HC MP pulses
RTX, diazepam,
corticosteroid, Ig
22 3 3 0 2 2 10 2 VPC-CADO* Corticosteroid,
clonazepam
0: None, 1: mild, 2: moderate, 3: severe.
Abbreviations: ttt: treatment, Ig: immunoglobulin/HC: hydrocortisone/MP: methylprednisolone/DXM: dexamethasone/RTX: rituximab/U: unknown.
Length of corticotherapy: (12 months): still under treatment.
Chemotherapy: VPC for VP16 and carboplatine, CADO for cyclophosphamide, doxorubicin and vincristine, PE for platinum and etoposide, *, neoajuvant, #, adjuvant, 2: number of cures.
corticotherapy was 23.1 months (range 7 days to 8 years), with
three patients still on corticosteroids at the time of last follow
up. Ten patients received immunoglobulins (Ig): in two cases
Ig were given first without any success (posology: 1 gram per
kilo per day, during 2 days), whereas 8 other patients received
Ig because OMS was corticoresistant or corticodependant.
Three patients received cyclophosphamide, and four had rituximab.
The evaluation of the efficacy of these treatments
was difficult. For example, for patient 11, symptoms persisted
in spite of 15 courses of dexamethasone, 13 courses of
immunoglobulin, 7 courses of cyclophosphamide, and one
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
relapses were observed when decreasing the corticotherapy.
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.
3.2. OMS non-associated with NB
Twelve patients had OMS without NB (seven females, five
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
investigations permitted to identify a possible infectious
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
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 disturbance
(score >2), and only one patient had no opsoclonus. All
these patients received a corticotherapy as first treatment
(intramuscular ACTH, oral prednisone or hydrocortisone but
no methylprednisolone pulse). The median duration of corticotherapy
was 17.8 months (range 12–24 months), and two
patients still receive corticotherapy at the time of last follow
up. Three patients additionally received intravenous Ig
because of high corticodependance, with no efficacy. Only one
patient (patient 32) received cyclophosphamide because of
high corticodependance, and this second line treatment lead
to a possibility of decrease of corticotherapy and neurological
recovery. Four patients showed complete neurological
recovery after corticotherapy as only treatment. In patient 23,
a cerebral MRI was performed five years after the onset of the
OMS symptoms because of cognitive deficit and was normal
including for cerebellar volume.
3.3. Comparison of these two populations
3.3.1. Age at diagnosis
The median age for all patients at presentation was 20.8
months (range 9 months to 6 years), 18.1 months for patients
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
modalities
Stance Gait
Opsoclonus
of corticotherapy
Arm and hand
function
Mood/
Behaviour
Total/
15
23 2 2 0 2 0 6 - Corticosteroid - Continuous oral
prednisone
24 2 2 0 2 0 6 - Corticosteroid - Continuous oral
prednisone
Lenght of
corticotherapy
Follow
up
Neurological
outcome
18 months 5 years Cognitive, praxic,
language
sequelae
19 months 24 Recovery
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
prednisone
U
10 years Cognitive, praxic,
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
months
Persistent ataxia,
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
after
vaccination
Corticosteroid U Continuous oral HC U U U
32 U U U U U – Varicella Corticosteroid Ig, Continuous oral
cyclophosphamide prednisone
24 months 32 Recovery
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,
diarrhea
Corticosteroid - Continuous oral HC 12 months 26 Recovery
months
european journal of paediatric neurology 14 (2010) 400–409
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
resection
Chemotherapy Other Recovery Cognitive/
motor/
language
delay
Persistant
ataxia
Moderate
motor
deficit
Total
sequelae
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 NBpositive
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 neurological
outcome (presence of sequelae vs. recovery) between the
two groups of patients (with and without NB, c 2 test p ¼ 0.27).
The neurological outcome was not different between the groups
of children who received oral or intravenous corticotherapy (c 2
test, p ¼ 0.14), and between the groups of children who received
chemotherapy for treatment of the NB or not (c 2 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 retrospective
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 widespread
practice, even if it involves many side effects and an
unpredictable efficacy. 27 Other immunomodulatory therapies,
like intravenous immunoglobulins, cyclophosphamide or rituximab
were tried, but it is difficult to determinate their efficacy,
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 corticosteroids
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
studies 1,15 and our study do not provide any conclusion
regarding the efficiency of the chemotherapy on the neurological
outcome because of the very few patients who received
it (only six).

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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 neurological
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 neurological
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. Pohl 3 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 neurological
deficit, confirming the poor neurological outcome previously
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 procedures
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 standardized
neuropsychological tests, performed by the same person
to make the interpretation easier.
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