Received: 30 January 2019 Revised: 19 March 2019 Accepted: 11 April 2019

DOI: 10.1002/pbc.27776 Pediatric

Blood &
The American Society of

RESEARCH ARTICLE
Cancer Pediatric Hematology/Oncology

An upfront immunomodulatory therapy protocol for pediatric

opsoclonus-myoclonus syndrome

Colin Wilbur1,2 Carmen Yea3 Christoph Licht4 Meredith S. Irwin5

E. Ann Yeh1,3

1 Division of Neurology, Department of

Pediatrics, The Hospital for Sick Children, Abstract

Toronto, Canada Background: Treatment of opsoclonus-myoclonus syndrome (OMS) has historically involved cor-
2 Division of Neurology, Department of
ticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6-12 months or longer. This
Pediatrics, Faculty of Medicine and Dentistry, study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab
Women and Children’s Health Research
Institute, University of Alberta, Edmonton,
reduces the duration of OMS therapy without adversely affecting OMS outcomes.
Canada
Procedure: Retrospective chart review was performed for consecutive children diagnosed with
3 Department of Neurosciences and Mental
OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada). Children treated
Health, SickKids Research Institute, Toronto,
Canada within 3 months of diagnosis with a treatment protocol involving pulse methylprednisolone (3-5
4 Division of Nephrology, Department of days, followed by an oral steroid taper), IVIG and/or plasma exchange, and rituximab (protocol
Pediatrics, The Hospital for Sick Children, group, n = 7) were compared to a historical group treated primarily with prednisone and IVIG
Toronto, Canada
(n = 8).
5 Division of Hematology-Oncology, Department

of Pediatrics, The Hospital for Sick Children,
Toronto, Canada
Correspondence
E. Ann Yeh, Division of Neurology, Department
of Pediatrics, The Hospital for Sick Children, 555
University Ave, Toronto, ON, Canada, M5G 1 X 8.
Email: ann.yeh@sickkids.ca
This work was presented as a poster at the Amer-
ican Academy of Neurology Annual Meeting
(April 2018). Abstract citation: Wilbur C, Yea
C, Licht C, Irwin MS, Yeh EA. Acute induction
immunotherapy plus rituximab for the treatment
of pediatric opsoclonus-myoclonus syndrome.
Neurology. 2018;90(Suppl 15):P2.311.
Results: The duration of corticosteroid treatment was shorter in the protocol (median 4.5 [range
3-12] months) compared to that in the historical group (median 21.5 [range 6-70] months,
P = .005), and subjects in the protocol group received fewer cycles of IVIG (median 1 [range 0-
7] cycle vs 7 [range 1-70] cycles, P = .01). The proportion of children with OMS relapse was similar
between the protocol and historic groups (2/6 vs 5/8, P = .59). OMS symptom rating scales at 12-
month follow-up were similar in the protocol group (median 2.5, range 0-3) compared to that in
the historical group (median 1, range 0-7; P = .66).
Conclusions: An upfront immunomodulatory therapy protocol with rituximab permits reduction
in the duration of corticosteroid and IVIG therapy without a detrimental effect on OMS outcomes.
Future studies with longer follow-up will have to determine whether neurocognitive and psy-
chosocial outcomes are improved by this approach.
KEYWORDS
neuroblastoma, opsoclonus-myoclonus syndrome, paraneoplastic, rituximab, therapeutic plasma
exchange

1 INTRODUCTION long-term neurologic outcomes; ongoing motor symptoms, speech

Opsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory
disorder, having an estimated incidence of 0.18 per million total pop-
ulation in the United Kingdom.1 OMS typically presents in early child-
hood and occurs as a paraneoplastic phenomenon in association with
neuroblastoma in approximately half of the pediatric cases.2 Chil-
dren with OMS experience a high rate of symptom relapse and poor
Abbreviations: CSF, cerebrospinal fluid; IV, intravenous; IVIG, intravenous immunoglobulin;
OMS, opsoclonus-myoclonus syndrome; TPE, therapeutic plasma exchange.
abnormalities, and/or cognitive deficits may be seen in more than
half of the affected children.3,4 Notably, the neuroblastoma tumors
detected in patients with OMS are usually biologically and clinically
favorable and often do not require adjuvant chemotherapy.5 Although
a single pathogenic autoantibody has not been identified in individu-
als with OMS,6 the presence of oligoclonal bands and expanded cere-
brospinal fluid (CSF) B-cell populations in untreated children support
an underlying autoimmune etiology and the importance of B cells in
OMS pathophysiology.7,8

Pediatr Blood Cancer. 2019;66:e27776. wileyonlinelibrary.com/journal/pbc 

c 2019 Wiley Periodicals, Inc. 1 of 7
https://doi.org/10.1002/pbc.27776
2 of 7
Based on the presumed immune basis of this disorder, corticos-
teroids alone or in combination with intravenous immunoglobulin
(IVIG) are frequently used for treatment, to which cyclophosphamide
or rituximab may be added. The treatment regimens are similar for
patients with or without neuroblastoma. Many treatment protocols
for pediatric OMS routinely continue with corticosteroids and regu-
lar IVIG for an initial duration of 6-12 months or longer.3,9–11 How-
ever, the optimal combination and duration of immunomodulatory
therapy remains unknown. Nonrandomized studies suggest improved
motor and developmental outcomes along with reductions in mark-
ers of CSF B-cell expansion following multimodal immunomodulatory
therapy.9,12–14 A recent phase 3 trial in children with OMS and neurob-
lastoma also demonstrated an improved OMS symptom response with
the addition of IVIG to prednisone and cyclophosphamide.11 While the
evidence for therapeutic plasma exchange (TPE) in pediatric OMS is
limited to case reports,15–17 studies of its use in other neuroinflamma-
tory conditions suggest efficacy in cases refractory to corticosteroid
treatment.18,19
Our aim was to evaluate the use of a brief upfront standardized
treatment protocol including high-dose corticosteroids, IVIG and/or
TPE, and rituximab in children with OMS in comparison to a historical
control group. We hypothesized that early aggressive therapy would
lead to reduced duration of corticosteroid treatment and fewer med-
ical visits related to immunomodulatory therapy administration, with-
out having a detrimental effect on OMS outcomes.
2 METHODS
2.1 Study population and design
This was a retrospective study of children diagnosed with OMS and
evaluated at The Hospital for Sick Children (Toronto, Canada) between
2006 and 2019. Children <18 years of age diagnosed with OMS during
the study period (with or without a diagnosis of neuroblastoma) were
identified through neuroblastoma and neuroinflammatory registries
maintained prospectively through the oncology and neurology clinics,
respectively. Additional cases were ascertained by screening the hos-
pital records of children having International Classification of Diseases
10th Revision diagnostic codes corresponding to ataxia (unspecified,
R27.0), myoclonus (G25.3), or nystagmus and other irregular eye move-
ments (H55). The diagnosis of OMS was considered confirmed retro-
spectively in all cases by documenting the presence of at least two
of the following three criteria: (1) opsoclonus, (2) myoclonus and/or
ataxia, and (3) neuroblastoma. Children were excluded if they had neu-
rological abnormalities due to a diagnosis other than OMS or if there
were insufficient data available to report OMS therapy and neurologi-
cal outcome. This study was approved by the SickKids Research Ethics
Board.
2.2 Clinical data and treatment groups
Clinical data were collected using standardized case report forms.
The duration of inpatient hospital days during admissions in which
WILBUR ET AL .
F I G U R E 1 Induction immunomodulatory therapy protocol; all
patients also had screening for neuroblastoma and treatment of
tumor, if found (surgical resection +/- chemotherapy). IVIG,
intravenous immunoglobulin
immunomodulatory therapy was administered and the number of out-
patient medical day unit visits attributable to immunomodulatory ther-
apy were counted. Potential adverse events related to OMS therapy
were identified in the protocol group and scored according to the
National Cancer Institute Common Terminology Criteria for Adverse
Events version 5.0.20 Adverse events of moderate severity or worse
(grades 2-5) were recorded.
A standardized protocol for the initial treatment of OMS was insti-
tuted in 2015 (Figure 1). Initial treatment consisted of pulse intra-
venous (IV) methylprednisolone (30 mg/kg/day for 3-5 days), followed
by a course of oral prednisone weaned over approximately 3-4 months
(extended for OMS relapse or poor treatment response). Children hav-
ing a poor clinical response to pulse steroid therapy, defined by a lack of
clinical improvement in ataxia and ongoing functional deficits, received
IVIG 2 g/kg, divided over 2 days, and/or TPE. TPE was administered
in children with severe symptoms despite pulse steroid therapy or
those with ongoing disabling symptoms following treatment with pulse
steroids and IVIG. TPE was administered through a double-lumen cen-
tral venous line and cycles consisted of either 1× or 1.5× plasma vol-
ume exchanges administered approximately daily or every other day,
with the number of cycles titrated to treatment response (5-10 cycles
total).
All children then received rituximab administered as two
500 mg/m2 doses 14 days apart, with the initial dose administered as
an inpatient, and the second dose administered through the outpatient
medical day unit. Due to the potential for TPE to increase rituximab
clearance if performed within 72 h of infusion21 —and the theoretical
risk of a resultant decrease in rituximab efficacy—the protocol dic-
tated rituximab be administered following the completion of acute
therapies. Standard premedication with acetaminophen, diphenhy-
dramine, and methylprednisolone was administered. Children whose
initial OMS therapy included IV pulse methylprednisolone and who
received rituximab within 6 months of diagnosis were analyzed as
the “protocol group.” Children first receiving any other therapy were
analyzed as the “historic group.”
WILBUR ET AL .
TA B L E 1 Participant demographic information
Protocol group (n = 7)
Female, n (%) 5 (71.4)
Age at diagnosis, median (range) 22 (13-57) months
Neuroblastoma, n (%) 4 (57.1)
Time to diagnosis, median (range) 19 (5-100) days
OMS severity score at onset, median (range) 10 (3-16)
Abbreviation: OMS, opsoclonus-myoclonus syndrome.
F I G U R E 2 Course of immunomodulatory therapy administered to children in the protocol group (N = 7) based on the time (months) from
diagnosis of OMS; IVIG, intravenous immunoglobulin; OMS, opsoclonus-myoclonus syndrome; TPE, therapeutic plasma exchange
2.3 Neurological outcomes
OMS symptoms at presentation, hospital discharge, and clinical follow-
up visits were scored retrospectively utilizing an OMS rating scale,12
which scores the following symptom domains on a scale from 0 (nor-
mal for age) to 3 (severe symptoms): stance, gait, arm/hand function,
opsoclonus, mood/behavior, and speech (maximum score = 18). Ambu-
lation status (classified as independent, ambulating with assistance,
or nonambulatory) was reported for the protocol group at the time
of protocol initiation and upon completion of acute therapy (ie, pulse
steroids, IVIG, and/or TPE). Long-term outcomes were then compared
between the protocol and historic groups at clinical follow-up closest
to 12 months following initiation of treatment and at last follow-up.
Relapses occurring >3 months after initiation of OMS therapy were
documented and defined as new or worsened OMS symptoms last-
ing >24 h and requiring an escalation in immunomodulatory therapy.
Children having clinical follow-up of less than 6 months’ duration from
the diagnosis of OMS were excluded from the analysis of long-term
outcomes.
2.4 Statistical analysis
Continuous variables were summarized as median (range), while cate-
gorical variables were categorized as frequency (%). Clinical variables
and outcomes were compared between the protocol group and historic
group using Mann-Whitney U-test or Fisher’s exact test, as appropri-
ate. Analysis was performed using R version 3.3.2 (R Core Team, 2016).
A P-value of <.05 was considered significant.
3 of 7
Historic group (n = 8) P-value
6 (75.0) >.9
21.5 (12-48) months >.9
6 (75.0) .61
29 (3-180) days .49
10 (5-13) .80
3 RESULTS
3.1 Study population
Fifteen children meeting study criteria were identified, seven of whom
entered the treatment protocol and were compared to eight children in
the historical cohort. Baseline clinical and demographic characteristics,
including initial OMS severity scores, were similar between the treat-
ment groups (Table 1). One child in the protocol group was followed for
less than 6 months from diagnosis and is only included in the analysis of
acute treatment.
The majority of children in our cohort were diagnosed with neu-
roblastoma, including 4/7 in the protocol group and 6/8 in the historic
group. All tumors were surgically resected within 4 weeks of diagnosis.
The majority (9/10) were categorized as low-risk neuroblastoma and
did not receive any additional neuroblastoma-directed therapy. One
patient in the historic group received seven cycles of chemotherapy
with vincristine, cyclophosphamide, and carboplatin for International
Neuroblastoma Staging System stage 3 intermediate-risk neuroblas-
toma. No recurrence of neuroblastoma was documented in any child.
3.2 Acute OMS treatment
Two children received immunomodulatory therapy prior to the diag-
nosis of OMS—one of whom received both pulse methylprednisolone
and IVIG and one who received pulse methylprednisolone alone
(Figure 2). In the acute phase after OMS diagnosis, all children in
the protocol group initially received pulse methylprednisolone for
3-7 days. Two received a second cycle of pulse methylprednisolone
4 of 7 WILBUR ET AL .

TA B L E 2 Clinical features, acute therapies, and response to acute therapy in the protocol group (N = 7)

Subject 1 2 3 4 5 6 7
Age at diagnosis 18/F 22/F 13/M 57/F 27/F 17/M 30/F
(months)/sex
Neuroblastoma No Yes Yes No No Yes Yes
OMS severity 14 8 14 7 15 16 3
score—initiation
of protocol
Ambulation With With Nonambulatory With Nonambulatory Nonambulatory Independent
status—initiation assistance assistance assistance
of protocol
Acute IVMP IVMP IVMP IVMP IVMP IVMP IVMP
immunomodulatory IVIG TPE IVIG IVIG TPE IVIG
therapies received TPE TPE TPE
Time from symptom 15 6 1 4 3 3 4
onset to initiation
of protocol (weeks)
Time from initiation of 2 1 2 2 2 N/A N/A
protocol to initiation
of TPE (weeks)
Volume per exchange 1.5× plasma 1.5× plasma 1× plasma 1× plasma 1.5× plasma volume N/A N/A
volume volume volume volume (3 exchanges),
then 1× plasma
volume (2
exchanges)
Number of exchanges 7 exchanges 7 exchanges 10 exchanges in 5 exchanges 5 exchanges in 8 N/A N/A
in 10 days in 24 days 21 days in 9 days days
OMS severity 11 4 15 5 9 13 3
score—end
of acute therapy
Ambulation With Independent Nonambulatory Independent With assistance Nonambulatory Independent
status—end of acute assistance
therapy
OMS severity 3 3 2 1 N/A 3 0
score—12-month
follow-up
Ambulation Independent Independent Independent Independent N/A Independent Independent
status—12-month
follow-up
Abbreviations: F, female; IVIG, intravenous immunoglobulin; IVMP, intravenous methylprednisolone; M, male; OMS, opsoclonus-myoclonus syndrome; TPE,
therapeutic plasma exchange.

(between 7 and 8 weeks after initiation of the protocol) due to persis- rituximab—one as part of initial therapy and two at a later point (12
tent or intercurrent worsening of OMS symptoms. Three subsequently months and 3 years following initial therapy).
received a single cycle of IVIG. Five children underwent TPE following
a lack of response to initial therapy (two of whom previously received 3.3 OMS relapses
IVIG as part of the protocol and one of whom received IVIG prior to
Two of six children in the protocol group relapsed after receiving ritux-
diagnosis), totaling 5-10 exchanges over 8-21 days. Four of five chil-
imab, at 14 and 17 weeks following initiation of therapy (each 6 weeks
dren undergoing TPE had an improved OMS severity score (range in
following completion of rituximab), in the context of weaning pred-
improvement of 2-6 points) at the completion of TPE compared to
nisone. Relapses in both children were treated with increased corti-
that at initiation of the protocol, including three who demonstrated
costeroid dosing, while one additionally received six cycles of monthly
improvement in ambulation status (Table 2). All children in the proto-
IVIG due to persistent OMS symptoms. Five of eight children in the his-
col group received rituximab within 2-9 weeks of OMS diagnosis. All
toric group relapsed, most commonly reported in the context of wean-
began a tapering course of oral prednisone following the last cycle of
ing prednisone or intercurrent illness, with the time to first relapse
methylprednisolone.
ranging from 17 weeks to 15 months following initial treatment.
All children in the historic group were initially treated with corti-
costeroids, seven of whom received oral prednisone (initial dose 1-
2 mg/kg/day) and one of whom received adrenocorticotropic hormone.
3.4 Treatment duration
All children in the historic group also received IVIG for a median of Excluding the one child in the protocol group with short duration
seven cycles (range 1-70 cycles). Three children in this group received follow-up, all children in both treatment groups had discontinued
WILBUR ET AL .
TA B L E 3 Clinical outcomes and duration of therapy in the treatment groups; only those children having follow-up at least 6 months from the
time of OMS diagnosis are included
Duration of follow-up, median (range)
Corticosteroid duration, median (range)
Cycles of IVIG, median (range)
Subjects having relapse, n (%)
OMS severity score at 12-month follow-up, median (range)
OMS severity score at last follow-up, median (range)
Inpatient hospital days (first year of treatment), median (range)
Outpatient medical day unit treatment days (first year of treatment), median (range)
Abbreviations: IVIG, intravenous immunoglobulin; OMS, opsoclonus-myoclonus syndrome.
immunomodulatory therapy at the time of last follow-up and those that
had received rituximab demonstrated evidence of B-cell reconstitution
(CD19 count >0). The median duration of corticosteroid exposure in
the protocol group (4.5 [range 3-12] months) was significantly shorter
than that in the historic group (21.5 [range 6-70] months, P = .005).
The protocol group also received fewer cycles of IVIG than the historic
group did (P = .01, Table 3).
The protocol group had a similar number of inpatient hospital days
in the first year of treatment compared to the historic group (Table 3).
However, the protocol group required fewer outpatient medical vis-
its related to immunomodulatory therapy administration in compari-
son to the historic group (median 3.5 [range 1-8] days vs 9 [range 4-14]
days, P = .03).
3.5 Neurologic outcomes
Follow-up data 12 months from treatment initiation (median 339
[range 238-429] days) were available for all participants except for
one child in each group. OMS symptom rating scores were similar at
this time point in the protocol group (median 2.5 [range 0-3]) and
the historic group (median 1 [range 0-7], P = .66; Table 3). Further-
more, the improvement in OMS symptom rating scores from base-
line to 12-month follow-up was similar between the protocol group
(median improvement 5 [range 3-13] points) and the historic group
(median improvement 7 [range 4-11] points, P = .83). OMS symptom
rating scores at last follow-up were also similar between the protocol
group (median 1.5 [range 0-3]) and the historic group (median 0 [range
0-6], P = .34). Expressive language was the domain most commonly
affected at last follow-up in both groups, with impairments noted in 4/6
children in the protocol group and 3/8 children in the historic group. Six
of eight children in the historic group underwent formal neuropsycho-
logical evaluation prior to the last follow-up, three of whom were clas-
sified as having intellectual disability or global developmental delay.
Given their young age, no children in the protocol group had formal
neuropsychological testing performed by the time of last follow-up.
3.6 Tolerability of treatment protocol
Overall, the treatment protocol was well tolerated, and all children
were able to complete the assigned treatment. Mild (grade 2) infusion
5 of 7
Protocol group (n = 6) Historical group (n = 8) P-value
15.5 (12-34) months 87 (13-120) months .04
4.5 (3-12) months 21.5 (6-70) months .005
1 (0-7) 7 (1-70) .01
2 (33.3) 5 (62.6) .59
2.5 (0-3) 1 (0-7) .66
1.5 (0-3) 0 (0-6) .34
19.5 (12-38) 23 (5-27) .39
3.5 (1-8) 9 (4-14) .03
reactions were seen in two children during each of rituximab and IVIG
infusions and in one child during TPE. Transient neutropenia during the
period of B-cell suppression was seen after rituximab in 4/6 children
(grade 3 in two children, grade 4 in one), while transient lymphope-
nia (grade 3) was also seen in one child. Two children receiving TPE
removed their central venous line, but this did not result in any further
complications or need for intervention.
4 DISCUSSION
In this study, we evaluated a brief upfront immunomodulatory ther-
apy protocol for the treatment of OMS, consisting of pulse methylpred-
nisolone followed by a short prednisone taper, IVIG and/or TPE, and rit-
uximab. The treatment was well tolerated and facilitated a significantly
shorter duration of corticosteroid exposure and fewer return out-
patient visits for immunomodulatory therapy (specifically IVIG) com-
pared to a historical cohort.
Long-term corticosteroid exposure is associated with adverse phys-
ical and behavioral effects and reduced quality of life in children.22,23
Many of the common toxicities, such as growth impairment, may be
of particular concern in patients with OMS who are usually diagnosed
as older infants or toddlers. Thus, the reduced exposure to corticos-
teroids, which was on average 1 year less in children who received this
upfront therapy protocol, may reduce the risk for these adverse events.
Similarly, increased hospital visits may disrupt child and family func-
tioning and impair quality of life.24,25 The reduction in outpatient vis-
its for immunomodulatory therapy—largely driven by reduced use of
IVIG in the protocol group—has the potential to reduce disruptions and
caregiver burden, although quality of life measures were not formally
assessed in the current study.
Despite the shorter duration of immunomodulatory therapy, only
one-third of children in the protocol group (2/6) experienced OMS
relapse, which is consistent with the relapse rate reported in previ-
ous studies of rituximab-containing OMS treatment protocols.10,13,26
While all the children included in the analysis of long-term outcomes
were followed for at least 12 months, the duration of follow-up
was shorter in the protocol group; therefore, the occurrence of late
relapses may not have been identified. However, the period of wean-
ing immunomodulatory therapy was associated with the majority of
6 of 7
relapses in both treatment groups and all children in the protocol group
included in this analysis had successfully discontinued immunomodu-
latory therapy at the time of last follow-up. This suggests that a shift
away from treatment strategies involving long-term corticosteroids
towards upfront, multimodal immunomodulatory therapy including
TPE may be achieved without a detrimental effect on relapse rate.
Due to the nature of the study, the effect of individual components
of the protocol cannot be evaluated. Previous nonrandomized studies
have demonstrated improvement in clinical outcomes and markers of
neuroinflammation with the use of rituximab-containing treatment
protocols.9,10,12,13,26 A recent randomized-controlled trial reported
improved OMS symptom response with the addition of IVIG—
administered monthly for the first 6 months and every 2 months for
months 6-12—to prednisone and cyclophosphamide in children with
associated neuroblastoma.11 However, the optimal number of IVIG
cycles has not been established and the role of IVIG within rituximab-
based protocols has not been similarly studied. Furthermore, although
TPE is used as a component of first- or second-line acute therapy for
various neuroinflammatory disorders, such as N-methyl D-aspartate
receptor encephalitis and severe demyelinating disease,27 only case
reports have described the benefit of TPE in the treatment of refrac-
tory OMS symptoms.15–17 However, its use as a component of a
standardized upfront OMS treatment protocol has not been reported
previously. TPE was well tolerated in the current study and associated
with a reduction in OMS symptom score in four of five children, with
ambulation specifically improved in three of five children following
the completion of TPE. Given that other immunomodulatory therapies
were administered both shortly prior to TPE and afterwards, conclu-
sions regarding the benefit from the addition of TPE specifically to
the early treatment of OMS cannot be drawn from this study. Further
research is required to determine whether the early use of TPE may
improve the rate of recovery in children with severe symptoms, alter
the need for additional therapies, or affect long-term OMS outcomes.
Neurological outcomes were similar between the study groups.
However, the small sample size limits the conclusions that can be
drawn. These results need to be replicated in larger cohorts. Compar-
ison to a historic group also limits the ability to compare the efficacy
of treatment approaches directly, as some differences—including pat-
terns of corticosteroid use—may relate to changes in clinical practice
or assessment over time. Additionally, the retrospective OMS symp-
tom scoring is only a limited measure of function and was not obtained
at standard time points during therapy and follow-up. More nuanced
differences in neurological outcomes or rate of improvement were
thus not captured in this study. Importantly, children in the protocol
group had not yet undergone formal neuropsychological assessment
and further follow-up will be required to determine whether long-term
cognitive outcomes are improved by this treatment approach.
While the evidence supporting multimodal immunomodulatory
therapy for pediatric OMS has mounted in recent years, more studies
are required to optimize treatment protocols to balance clinical effi-
cacy with exposure to potential adverse effects. This study demon-
strated that the majority of children with OMS have a less than optimal
clinical response after pulse steroid treatment and that OMS symptom
scores improve following treatment with TPE. A brief upfront treat-
WILBUR ET AL .
ment protocol for pediatric OMS that includes pulse steroids, with the
addition of IVIG and/or TPE in cases unresponsive to steroids, in com-
bination with rituximab was associated with a shorter duration of corti-
costeroid therapy and fewer total cycles of IVIG without a detrimental
effect on OMS symptom outcomes or relapse rate. Further studies are
needed to examine whether such a treatment protocol may improve
the rate of OMS symptom improvement, alter long-term neurocogni-
tive outcomes, or improve child and family quality of life.
CONFLICT OF INTEREST
The authors have no conflict of interest relevant to this article to dis-
close.
ORCID
Colin Wilbur https://orcid.org/0000-0003-4853-4047
Meredith S. Irwin https://orcid.org/0000-0002-2452-5181
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How to cite this article: Wilbur C, Yea C, Licht C, Irwin MS,
Yeh EA. An upfront immunomodulatory therapy protocol for
pediatric opsoclonus-myoclonus syndrome. Pediatr Blood Can-
cer. 2019;66:e27776. https://doi.org/10.1002/pbc.27776