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Latest revision as of 14:34, 20 July 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]

Synonyms and keywords:dancing eyes-dancing feet, dancing eye syndrome, Kinsbourne syndrome, myoclonic encephalopathy (Kinsbourne type), OMAS (opsoclonus-myoclonus-ataxia syndrome), OMS (opsoclonus myoclonus syndrome), opsoclonic encephalopathy

Overview

Opsoclonus myoclonus syndrome (OMS) is a rare neurological disorder, which can be very heterogenous, presenting itself with many different symptoms such as opsoclonus and/or myoclonus - which name the syndrome, but also ataxia, behavioral and/or sleep disturbances. It is believed to be caused by an immune system dysfunction, either induced by infection or paraneoplastic etiologies.

Historical Perspective

Opsoclonus myoclonus syndrome was first described in 1962 by M. Kinsbourne, who presented a series of six cases of children with ataxia, myoclonus and opsoclonus.
The syndrome was named as "myoclonic encephalopathy", but has also been called as "dancing eye syndrome".^[1] Recently it has been more often referred to as opsoclonus myoclonus syndrome.

Classification

There is no established system for the classification of opsoclonus myoclonus syndrome.

Pathophysiology

The pathogenesis of opsoclonus myoclonus syndrome is characterized by neuroinflammation involving dysregulated B cells. It is believed that loss of tolerance and autoantibody production causes the neurological damage seen in the disease.
Cerebrospinal fluid studies have shown B cell recruitment to the brain via CXCL13/CXCR5 and CXCL10/ CXCR3 ligand/receptor pairs^[2]^[3]. The B cell activating factor plays a role increasing B cell survivability and there may be seen intrathecal production of oligoclonal bands.^[3]
There are two theories about the cause of the disease:
- Dysfunction of the Purkinje cells in the cerebellar vermis leading to disinhibition of the oculomotor neurons of the fastigial nucleus of the cerebellum.
- Disinhibition of burst neurons, which are mostly under inhibition from omnipause cells, causing saccadic eye movements.^[4]
It is not known if the triggers that causes opsoclonus myoclonus syndrome and those that causes relapses of the disease are the same or if they affect the same region of the brain.^[3]
There is no obvious gene/mutation associated with the development of opsoclonus myoclonus syndrome.^[4]
On microscopic histopathological analysis, gliosis and inflammation in the cerebellar vermis are characteristic findings of opsoclonus myoclonus syndrome.^[4]

Causes

Opsoclonus myoclonus syndrome is caused by neuroinflammation, though its mechanism is yet unknown. There is evidence supporting the neuroinflammatory theory due to the increase of oligoclonal bands on CSF. This theorized pathophysiology is discussed on its own section.

Differentiating Opsoclonus Myoclonus syndrome from other Diseases

Opsoclonus myoclonus syndrome must be differentiated from acute inflammatory cerebellar ataxia, which can be differentiated by the type of eye movement, rapid recovery without treatment and absence of irritability.^[5]

Epidemiology and Demographics

The prevalence of opsoclonus myoclonus syndrome is approximately 1 per 1,000,000 individuals worldwide.

Age

Opsoclonus myoclonus syndrome is more commonly observed among patients aged 18 months old and may occur up to 5-6 years old.^[6]
Relapses of the disease may affect adults.

Gender

Girls are slightly more affected with opsoclonus myoclonus syndrome than boys.^[6]

Race

There is no racial predilection for opsoclonus myoclonus syndrome.^[4]

Risk Factors

There are no risk factors associated with the development of opsoclonus myoclonus syndrome.

Screening

There is insufficient evidence to recommend routine screening for opsoclonus myoclonus syndrome as it is a very rare disease.

Natural History, Complications and Prognosis

The majority of patients with opsoclonus myoclonus syndrome present with a relapse-remitting form of the disease.
Early clinical features begin mostly at 18 months of age, and include myoclonus, opsoclonus, irritability and ataxia.^[7]
If left untreated, the neurological deficits of patients with opsoclonus myoclonus syndrome may remain more severe and affect neurological development through childhood and teenage years.^[1]
Prognosis is generally poor, as the patients with opsoclonus myoclonus syndrome usually remain with developmental delays and severe learning difficulties.^[1]
Adult opsoclonus myoclonus syndrome can occur as a paraneoplastic syndrome in association with small cell lung cancer or breast cancer, half of the cases being idiopathic and parainfectious.^[1]

Diagnosis

Diagnostic Study of Choice

The diagnosis of opsoclonus myoclonus syndrome is made when at least 3 of the following 4 diagnostic criteria are met:^[4] neuroblastoma; uncontrolled eye movement (opsoclonus); movement disorder with sudden muscle contractions (myoclonus) and/or lack of coordination (ataxia); behavioral and/or sleep disturbance.

History and Symptoms

Opsoclonus myoclonus syndrome presents in a relapse-remitting manner.
There are acute and chronic symptoms.
The classic symptoms are mostly seen in acute disease and they are: myoclonus, opsoclonus, ataxia.^[6]
The symptoms presenting in the chronic disease may be a residual opsoclonus and abnormalities of eye movement which may be elicited by re-fixating from near to far or squeezing the eyelids shut. Hypometric saccades and smooth eye pursuit movements can remain abnormal for years. Children may also remain not as coordinated as their peers. Expressive language is generally more affected than receptive language, and cognitive deficits may become more evident in teenagers.^[7]
In children it is associated neuroblastoma in approximately half of cases.^[4] In this age group it also presents with gait ataxia, dysarthria, drooling, irritability, vomiting, and insomnia.^[3]
It has a relapse-remitting course. Symptoms may vary in duration during relapses and the remission period is also variable, but usually the relapses last at least 48-72h.^[3]
Children affected by the disease may not be fully asymptomatic between the episodes of the disease, persisting with significant speech and language deficits, sleep and some behavioral changes.^[3]
Most patients have no detectable antibody, but a few patients presenting with neuroblastoma do have anti-neuronal and anti-Purkinje cell antibodies.^[4]
Children with neuroblastoma and opsoclonus myoclonus syndrome usually have a better prognosis for their neuroblastomas as they are in more differentiated stages.^[1]

Physical Examination

Physical examination may be remarkable for:
- Ataxia: children present with an acute or subacute form of ataxia, losing the ability to walk and/or sit over a period ranging from one day to a few weeks, accompanied by severe irritability and myoclonus, being the first diagnosis proposed for most children often post-infectious acute cerebellar ataxia of childhood.^[7]
- Opsoclonus: must be differentiated from nystagmus, which is present in most acute cerebellar ataxias. Opsoclonus is multidirectional, conjugate, non-phasic and fast in contrast with nystagmus, which is phasic, may be conjugated, unidirectional.^[7]
- Myoclonus: ranges from polymyoclonia to coarse multifocal jerks, and may be persistent and exacerbated by emotional distress and movement.^[7]

Laboratory Findings

There are no specific laboratory markers associated with opsoclonus myoclonus syndrome.^[8]
In adults with opsoclonus myoclonus syndrome, a blood exam may show Hu anti-neuronal nuclear antibodies (anti-Hu) but not in children.^[9]
In some patients cerebrospinal fluid evaluation is necessary to detect neuroinflammation. These studies should include oligoclonal bands (with paired serum sample), aiming to detect antibodies in the CSF and flow cytometry of the lymphocytes using immunophenotyping, which may find an increased frequency of CSF CD19+ B cells, which is a biomarker of opsoclonus myoclonus disease activity.^[6]
Atypical cases may warrant autoantibodies tests in some children, but this is not cost-effective.^[6]

Electrocardiogram

There are no ECG findings associated with opsoclonus myoclonus syndrome.

X-ray

There are no specific x-ray findings associated with opsoclonus myoclonus syndrome.

Echocardiography or Ultrasound

There are no specific echocardiography/ultrasound findings associated with opsoclonus myoclonus syndrome.

CT scan

Opsoclonus myoclonus syndrome may present with neuroblastoma in half of the cases (one author reported 80% of the cases), though only 2-3% of neuroblastoma present with opsoclonus myoclonus syndrome.^[10]^[7]
In the evaluation of a child with opsoclonus myoclonus syndrome, it is usually performed either a CT scan with contrast or MRI with gadolinium of the neck, chest, abdomen, and pelvis^[6] as neuroblastomas can arise from sympathetic nervous system, being most frequent in the abdomen (2/3 of the cases) and thorax (20% of the cases)^[11]
On CT scans, the neuroblastoma is heterogeneous with calcifications being commonly seen. Usually the tumor insinuates itself beneath the aorta and lifting it off the vertebral column.^[11]

MRI

In the evaluation of a child with opsoclonus myoclonus syndrome, it is usually performed either a CT scan with contrast or MRI with gadolinium of the neck, chest, abdomen, and pelvis^[6] as neuroblastomas can arise from sympathetic nervous system, being most frequent in the abdomen (2/3 of the cases) and thorax (20% of the cases)^[11]
MRIs are superior to all other exams on detecting neuroblastomas and shows the tumor being heterogenous and iso to hypo intense on T1, and hyper intense on T2, with cystic/necrotic areas being easily identifiable.^[6]. Usually the tumor insinuates itself beneath the aorta and lifting it off the vertebral column.^[11]

Other Imaging Findings

On adults, the most associated neoplasms are small cell lung cancer, breast carcinoma, and ovarian teratoma^[12], and PET scans are done to evaluate for occult tumors.^[6]

Other Diagnostic Studies

There are no other diagnostic studies that may be used to diagnose opsoclonus myoclonus syndrome.

Treatment

Medical Therapy

The mainstay of therapy for opsoclonus myoclonus syndrome is rule it out as a paraneoplastic syndrome and then early and aggressive immunotherapy to obtain a durable and complete neurological remission.^[6]
Corticosteroids (prednisolone at 2mg/kg/day and tapered slowly or dexamethasone 20mg/m2/day for 3 days) and ACTH are the gold standard^[12] and they act by binding to intracellular receptors which then act to modulate gene transcription in target tissues, decreasing the production of pro-inflammatory cytokines.
IVIG (1gr/kg for 12 cycles) may also be used alone or in combination with corticosteroids, and recent studies suggests that the combination is indeed more effective.^[12] Most patients respond to such initial treatment.^[13]
There have been reports of dexamethasone being used with cyclophosphamide, rituximab (chimeric anti-CD20 monoclonal antibody that depletes circulating B cells) in moderately severe opsoclonus myoclonus syndrome, but such associations as also plasma exchange should be reserved for severe cases or cases refractory to IVIG, corticosteroids or a combination of both.^[12]
Corticosteroids and IVIG alone are insufficient to prevent relapse or disease progression, and multimodal combination immunotherapy with disease modifying agents significantly improve long-term outcome when given early.^[3]
Some studies show that combining imunotherapy with rituximab, ACTH and IVIG, adhering to a more aggressive approach can significantly reduce the cognitive impairment and morbidity on opsoclonus myoclonus syndrome.^[3]
Ofatumumab can be used in children allergic to rituximab. Rituximab should be avoided in the absence of B lymphocytes on the CSF.^[3]
There are reports that intensive immunosuppression can be associated with improved long-term neurological outcome.^[12]
Most children will have relapses with corticosteroid dose tapering.^[12]
Patients should be assessed for treatment following the flowchart below as proposed by Pranzatelli:^[3]

TREATMENT

Mitigate Trigger

Treat/Retreat Neuroinflammation

Reassess for high risk

Treat Infections with antimicrobials

Escalate or restart steroids or ACTH

Retest for neuroinflammation as needed

Review previous drug responses

Add or change modifying disease drugs

Formal IQ testing

Treat comorbid neuropsychiatric problems

Avoid potential pitfalls

Give IVIG as needed

Select tapering method

Multimodal combination immunotherapy

Intensify speech therapy, PT, OT

Surgery

If opsoclonus myoclonus syndrome is due to a paraneoplastic etiology, then surgical resection of the tumor is needed (in children, neuroblastoma is the most common, in adults there are many such as small cell lung cancer and breast cancer).
Surgery may be performed to treat such tumors along other methods of treatments such as chemotherapy and/or radiation.
Resection and treatment of the neuroblastoma improves the acute symptoms, but only rarely prevents neurologic sequelae.^[7]
Most children with paraneoplastic opsoclonus myoclonus syndrome have localized disease which makes surgical resection more feasible. They also are likely to have tumors with favorable cytogenetic and histopathologic traits, with a better prognosis of their oncologic disease.^[4]

Primary Prevention

There are no established measures for the primary prevention of opsoclonus myoclonus syndrome.

Secondary Prevention

Effective measures for the secondary prevention of opsoclonus myoclonus syndrome are not yet established, but chronic immunotherapy with disease modifying agents is being studied with positive results.^[3]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 Blaes F, Dharmalingam B (2016). "Childhood opsoclonus-myoclonus syndrome: diagnosis and treatment". Expert Rev Neurother. 16 (6): 641–8. doi:10.1080/14737175.2016.1176914. PMID 27095464.
↑ Pranzatelli MR, Tate ED, McGee NR, Travelstead AL, Ransohoff RM, Ness JM; et al. (2012). "Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS". J Neuroimmunol. 243 (1–2): 81–8. doi:10.1016/j.jneuroim.2011.12.014. PMID 22264765.
↑ ^3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 Pranzatelli MR, Tate ED (2016). "Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome". Brain Dev. 38 (5): 439–48. doi:10.1016/j.braindev.2015.11.007. PMID 26786246.
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 "American Academy of Ophthalmology - Opsoclonus Myoclonus Syndrome". American Academy of Ophthalmology. 07/04/2020. Check date values in: |date= (help)
↑ "ORPHANET - Opsoclonus-Myoclonus Syndrome". ORPHANET. 07/04/2020. Check date values in: |date= (help)
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 ^6.9 "NORD - National Organization for Rare Diseases - Opsoclonus-Myoclonus Syndrome". NORD. 07/04/2020. Check date values in: |date= (help)
↑ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG; et al. (2005). "Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004". Cancer Lett. 228 (1–2): 275–82. doi:10.1016/j.canlet.2005.01.051. PMID 15922508.
↑ Pike M (2013). "Opsoclonus-myoclonus syndrome". Handb Clin Neurol. 112: 1209–11. doi:10.1016/B978-0-444-52910-7.00042-8. PMID 23622330.
↑ "Genetic and Rare Diseases Information Center - Opsoclonus Myoclonus Syndrome". GARD. 07/04/2020. Check date values in: |date= (help)
↑ Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG; et al. (2005). "Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004". Cancer Lett. 228 (1–2): 275–82. doi:10.1016/j.canlet.2005.01.051. PMID 15922508.
↑ ^11.0 ^11.1 ^11.2 ^11.3 "Radiopaedia - Neuroblastomas". Radiopaedia.org. 07/04/2020. Check date values in: |date= (help)
↑ ^12.0 ^12.1 ^12.2 ^12.3 ^12.4 ^12.5 Oh SY, Kim JS, Dieterich M (2019). "Update on opsoclonus-myoclonus syndrome in adults". J Neurol. 266 (6): 1541–1548. doi:10.1007/s00415-018-9138-7. PMID 30483882.
↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1038/nrdp.2016.78 Check |pmid= value (help).

Template:WikiDoc Sources

[pmid27095464-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 Blaes F, Dharmalingam B (2016). "Childhood opsoclonus-myoclonus syndrome: diagnosis and treatment". Expert Rev Neurother. 16 (6): 641–8. doi:10.1080/14737175.2016.1176914. PMID 27095464.

[pmid22264765-2] Pranzatelli MR, Tate ED, McGee NR, Travelstead AL, Ransohoff RM, Ness JM; et al. (2012). "Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS". J Neuroimmunol. 243 (1–2): 81–8. doi:10.1016/j.jneuroim.2011.12.014. PMID 22264765.

[pmid26786246-3] 3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 Pranzatelli MR, Tate ED (2016). "Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome". Brain Dev. 38 (5): 439–48. doi:10.1016/j.braindev.2015.11.007. PMID 26786246.

[:3-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 "American Academy of Ophthalmology - Opsoclonus Myoclonus Syndrome". American Academy of Ophthalmology. 07/04/2020. Check date values in: |date= (help)

[5] "ORPHANET - Opsoclonus-Myoclonus Syndrome". ORPHANET. 07/04/2020. Check date values in: |date= (help)

[:1-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 ^6.9 "NORD - National Organization for Rare Diseases - Opsoclonus-Myoclonus Syndrome". NORD. 07/04/2020. Check date values in: |date= (help)

[pmid15922508-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG; et al. (2005). "Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004". Cancer Lett. 228 (1–2): 275–82. doi:10.1016/j.canlet.2005.01.051. PMID 15922508.

[pmid23622330-8] Pike M (2013). "Opsoclonus-myoclonus syndrome". Handb Clin Neurol. 112: 1209–11. doi:10.1016/B978-0-444-52910-7.00042-8. PMID 23622330.

[:4-9] "Genetic and Rare Diseases Information Center - Opsoclonus Myoclonus Syndrome". GARD. 07/04/2020. Check date values in: |date= (help)

[pmid159225082-10] Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG; et al. (2005). "Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004". Cancer Lett. 228 (1–2): 275–82. doi:10.1016/j.canlet.2005.01.051. PMID 15922508.

[:6-11] 11.0 ^11.1 ^11.2 ^11.3 "Radiopaedia - Neuroblastomas". Radiopaedia.org. 07/04/2020. Check date values in: |date= (help)

[pmid30483882-12] 12.0 ^12.1 ^12.2 ^12.3 ^12.4 ^12.5 Oh SY, Kim JS, Dieterich M (2019). "Update on opsoclonus-myoclonus syndrome in adults". J Neurol. 266 (6): 1541–1548. doi:10.1007/s00415-018-9138-7. PMID 30483882.

[pmidhttps://doi.org/10.1038/nrdp.2016.78-13] Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1038/nrdp.2016.78 Check |pmid= value (help).

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@@ Line 3: / Line 3: @@
 {{CMG}} {{AE}} {{Jose}}
-{{SK}}
+{{SK}}dancing eyes-dancing feet, dancing eye syndrome, Kinsbourne syndrome, myoclonic encephalopathy (Kinsbourne type), OMAS (opsoclonus-myoclonus-ataxia syndrome), OMS (opsoclonus myoclonus syndrome), opsoclonic encephalopathy
 ==Overview==
-'''Opsoclonus myoclonus syndrome''' ('''OMS''') is a rare [[neurological]] [[disease|disorder]] of unknown causes which appears to be the result of an [[autoimmune]] process involving the [[nervous system]]. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people per year. It affects 2 to 3% of [[child]]ren with [[neuroblastoma]].
+'''Opsoclonus myoclonus syndrome''' ('''OMS''') is a rare [[neurological]] [[disease|disorder]], which can be very heterogenous, presenting itself with many different [[symptoms]] such as [[opsoclonus]] and/or [[myoclonus]] - which name the [[syndrome]], but also ataxia, [[behavioral]] and/or [[sleep disturbances]]. It is believed to be caused by an [[Immune systems|immune system]] dysfunction, either induced by [[infection]] or [[Paraneoplastic Syndromes|paraneoplastic]] etiologies.
 ==Historical Perspective==
-OMS was first described by Dr. M. Kinsbourne in [[1962]] (The term 'Opsoclonus' was coined by Orezechowski in [[1913]], but it was classically described and associated with neuroblastoma by Kinsbourne). Other names for OMS include:
-*Opsoclonus-Myoclonus-Ataxia (OMA)
-*Paraneoplastic Opsoclonus-Myoclonus Ataxia (POMA)
-*Kinsbourne syndrome
-*Myoclonic Encephalopathy of Infants
-*Dancing Eyes-Dancing Feet syndrome
-*Dancing Eyes syndrome
-==Signs and symptoms==
+*Opsoclonus myoclonus syndrome was first described in 1962 by M. [[Kinsbourne Syndrome|Kinsbourne]], who presented a series of six cases of children with [[ataxia]], [[myoclonus]] and [[opsoclonus]].
-[[Symptoms]] include:
+*The syndrome was named as "myoclonic encephalopathy", but has also been called as "dancing eye syndrome".<ref name="pmid27095464">{{cite journal| author=Blaes F, Dharmalingam B| title=Childhood opsoclonus-myoclonus syndrome: diagnosis and treatment. | journal=Expert Rev Neurother | year= 2016 | volume= 16 | issue= 6 | pages= 641-8 | pmid=27095464 | doi=10.1080/14737175.2016.1176914 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27095464  }}</ref> Recently it has been more often referred to as opsoclonus myoclonus syndrome.
-*[[opsoclonus]] (rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without intersaccadic [quick rotation of the eyes] intervals)
-*[[myoclonus]] (brief, involuntary twitching of a muscle or a group of muscles)
-*[[ataxia|cerebellar ataxia]], both truncal and appendicular
-*[[dysphasia]] (a language disorder in which there is an impairment of speech and of comprehension of speech, caused by brain damage)
-*[[mutism]] (a social anxiety disorder, in which a person who is normally capable of speech is unable to speak in given situations)
-*[[lethargy]]
-*[[Irritation|irritability]] or [[malaise]]
-*[[drooling]]
-*[[strabismus]] (a condition in which the eyes are not properly aligned with each other)
-*[[vomiting]]
-*sleep disturbances
-About half of all OMS cases occur in association with [[neuroblastoma]] (a cancer of the sympathetic nervous system usually occurring in infants and children).
+== Classification==
+* There is no established system for the classification of opsoclonus myoclonus syndrome.
+== Pathophysiology ==
+*The pathogenesis of opsoclonus myoclonus syndrome is characterized by neuroinflammation involving dysregulated [[B cells]]. It is believed that loss of tolerance and [[autoantibody]] production causes the neurological damage seen in the disease.
+*[[Cerebrospinal fluid]] studies have shown [[B cell]] recruitment to the brain via [[CXCL13]]/[[CXCR5]] and [[CXCL10]]/ [[CXCR3]] ligand/receptor pairs<ref name="pmid22264765">{{cite journal| author=Pranzatelli MR, Tate ED, McGee NR, Travelstead AL, Ransohoff RM, Ness JM | display-authors=etal| title=Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS. | journal=J Neuroimmunol | year= 2012 | volume= 243 | issue= 1-2 | pages= 81-8 | pmid=22264765 | doi=10.1016/j.jneuroim.2011.12.014 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22264765  }}</ref><ref name="pmid26786246">{{cite journal| author=Pranzatelli MR, Tate ED| title=Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome. | journal=Brain Dev | year= 2016 | volume= 38 | issue= 5 | pages= 439-48 | pmid=26786246 | doi=10.1016/j.braindev.2015.11.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26786246  }}</ref>. The [[B cell activating factor]] plays a role increasing [[B cell]] survivability and there may be seen [[intrathecal]] production of [[oligoclonal bands]].<ref name="pmid26786246" />
+*There are two theories about the cause of the disease:
+**Dysfunction of the [[Purkinje cells]] in the [[cerebellar vermis]] leading to disinhibition of the [[oculomotor]] [[neurons]] of the [[fastigial nucleus]] of the [[cerebellum]].
+**Disinhibition of burst [[Neuron|neurons]], which are mostly under inhibition from omnipause cells, causing [[Saccadic movement|saccadic]] eye movements.<ref name=":3">{{Cite web|url=https://www.aao.org/disease-review/opsoclonus-myoclonus-syndrome|title=American Academy of Ophthalmology - Opsoclonus Myoclonus Syndrome|last=|first=|date=07/04/2020|website=American Academy of Ophthalmology|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
+*It is not known if the triggers that causes opsoclonus myoclonus syndrome and those that causes relapses of the disease are the same or if they affect the same region of the [[brain]].<ref name="pmid26786246" />
+*There is no obvious gene/mutation associated with the development of opsoclonus myoclonus syndrome.<ref name=":3" />
+*On microscopic histopathological analysis, [[gliosis]] and [[inflammation]] in the [[cerebellar vermis]] are characteristic findings of opsoclonus myoclonus syndrome.<ref name=":3" />
-==Classification==
-*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
-:*[group1]
-:*[group2]
-:*[group3]
-*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].
-==Pathophysiology==
-*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
-*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
-*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
-*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 ==Causes==
-* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
-* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
-* There are no established causes for [disease name].
-About half of all cases are associated with neuroblastoma and most of the others are suspected to be associated with a low-grade neuroblastoma that spontaneously regressed before detection. It is one of the few paraneoplastic (meaning indirectly caused by cancer') syndromes that occurs in both children and adults, although the mechanism of immune dysfunction underlying the adult syndrome is probably quite different.
-It is hypothesized that a [[virus|viral]] infection (perhaps St. Louis encephalitis, Epstein-Barr, Coxsackie B, or enterovirus) causes the remaining cases, though a direct connection has not been proven.
+* Opsoclonus myoclonus syndrome is caused by neuroinflammation, though its mechanism is yet unknown. There is evidence supporting the neuroinflammatory theory due to the increase of [[oligoclonal bands]] on [[CSF]]. This theorized pathophysiology is discussed on its own section.
+== Differentiating Opsoclonus Myoclonus syndrome from other Diseases==
+*Opsoclonus myoclonus syndrome must be differentiated from [[acute]] [[inflammatory]] [[Cerebellar ataxias|cerebellar ataxia]], which can be differentiated by the type of eye movement, rapid recovery without treatment and absence of [[irritability]].<ref>{{Cite web|url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1183|title=ORPHANET - Opsoclonus-Myoclonus Syndrome|last=|first=|date=07/04/2020|website=ORPHANET|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
+== Epidemiology and Demographics==
-Certainly OMS is not an [[infectious]] [[disease]]. OMS is not passed on genetically.
+*The [[prevalence]] of opsoclonus myoclonus syndrome is approximately 1 per 1,000,000 individuals worldwide.
-==Differentiating [disease name] from other Diseases==
-*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
-:*[Differential dx1]
-:*[Differential dx2]
-:*[Differential dx3]
-==Epidemiology and Demographics==
-* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
-* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
 ===Age===
-*Patients of all age groups may develop [disease name].
+*Opsoclonus myoclonus syndrome is more commonly observed among patients aged 18 months old and may occur up to 5-6 years old.<ref name=":1">{{Cite web|url=https://rarediseases.org/rare-diseases/opsoclonus-myoclonus-syndrome/|title=NORD - National Organization for Rare Diseases - Opsoclonus-Myoclonus Syndrome|last=|first=|date=07/04/2020|website=NORD|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
-*[Disease name] is more commonly observed among patients aged [age range] years old.
+*[[Relapse|Relapses]] of the disease may affect adults.
-*[Disease name] is more commonly observed among [elderly patients/young patients/children].
 ===Gender===
-*[Disease name] affects men and women equally.
+*Girls are slightly more affected with opsoclonus myoclonus syndrome than boys.<ref name=":1" />
-*[Gender 1] are more commonly affected with [disease name] than [gender 2].
-* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
+=== Race===
-===Race===
+* There is no racial predilection for opsoclonus myoclonus syndrome.<ref name=":3" />
-*There is no racial predilection for [disease name].
-*[Disease name] usually affects individuals of the [race 1] race.
-*[Race 2] individuals are less likely to develop [disease name].
 ==Risk Factors==
-*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
-== Natural History, Complications and Prognosis==
-*The majority of patients with [disease name] remain asymptomatic for [duration/years].
-*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
-*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
-*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
-*Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
-===Natural History===
+*There are no [[risk factors]] associated with the development of opsoclonus myoclonus syndrome.
-In most cases OMS starts with an acute flare-up of physical symptoms within days or weeks, but some less obvious symptoms such as irritability and [[malaise]] may begin weeks or months earlier.
-===Complications===
-===Prognosis===
+==Screening==
-Currently there are no clinically established laboratory investigations available to predict prognosis or therapeutic response.
-Tumors in children who develop OMA tend to be more mature, showing favorable histology and absence of n-myc oncogene amplification than similar tumors in children without symptoms of OMA (Cooper et al., 2003). Involvement of local lymph nodes is common, but these children rarely have distant metastases and their prognosis, in terms of direct morbidity and mortality effects from the tumor, is excellent (Gesundheit et al., 2004). The three-year survival rate for children with non-metastatic neuroblastoma and OMA was 100% according to Children’s Cancer Group data (gathered from 675 patients diagnosed between 1980 to 1994); three-year survival in comparable patients with OMA was 77% (Rudnick et al., 2001). Although the symptoms of OMA are typically steroid-responsive and recovery from acute symptoms of OMA can be quite good, children often suffer lifelong neurologic sequelae that impair motor, cognitive, language, and behavioral development (Dale, 2003; Mezey and Harris, 2002).
+* There is insufficient evidence to recommend routine screening for opsoclonus myoclonus syndrome as it is a very rare disease.
-Most children will experience a relapsing form of OMA, though a minority will have a monophasic course and may be more likely to recover without residual deficits (Mitchell et al., 2005). Viral infection may play a role in the reactivation of disease in some patients who had previously experienced remission, possibly by expanding the memory B cell population (Armstrong et al., 2005). Studies have generally asserted that 70-80% of children with OMA will have long-term neurologic, cognitive, behavioral, developmental, and academic impairment. Since neurologic and developmental difficulties have not been reported as a consequence of neuroblastoma or its treatment, it is thought that these are exclusively due to the immune mechanism underlying OMA (Hayward et al., 2001).
+==Natural History, Complications and Prognosis==
-One study (Medical and Pediatric Oncology 36:612-622,2001, see below) came to the conclusion that:
+*The majority of patients with opsoclonus myoclonus syndrome present with a [[relapse]]-remitting form of the disease.
-''Patients with OMA and neuroblastoma have excellent survival but a high risk of neurologic sequelae.   Favourable disease stage correlates with a higher risk for development of neurologic sequelae.   The role of anti-neuronal antibodies in late sequelae of OMS needs further clarification.''
+*Early clinical features begin mostly at 18 months of age, and include [[myoclonus]], [[opsoclonus]], [[irritability]] and [[ataxia]].<ref name="pmid15922508">{{cite journal| author=Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG | display-authors=etal| title=Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004. | journal=Cancer Lett | year= 2005 | volume= 228 | issue= 1-2 | pages= 275-82 | pmid=15922508 | doi=10.1016/j.canlet.2005.01.051 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15922508  }}</ref>
+*If left untreated, the neurological deficits of patients with opsoclonus myoclonus syndrome may remain more severe and affect [[neurological]] [[development]] through childhood and teenage years.<ref name="pmid27095464" />
+*[[Prognosis]] is generally poor, as the patients with opsoclonus myoclonus syndrome usually remain with [[developmental delays]] and severe [[learning difficulties]].<ref name="pmid27095464" />
+*Adult opsoclonus myoclonus syndrome can occur as a [[paraneoplastic syndrome]] in association with [[small cell lung cancer]] or [[breast cancer]], half of the cases being [[idiopathic]] and parainfectious.<ref name="pmid27095464" />
-Another study ([http://www.omsusa.org/Neuroepidemiologic.pdf Neuroepidemiologic Trends in 105 US Cases of Pediatric Opsoclonus-Myoclonus Elizabeth D. Tate, Michael R. Pranzatelli, Tyler Allison, Steven Verhurst, Springfield, IL] states that:
+==Diagnosis==
-''Residual behavioral, language, and cognitive problems occurred in the majority''.
+===Diagnostic Study of Choice===
-==Diagnosis==
+*The diagnosis of opsoclonus myoclonus syndrome is made when at least 3 of the following 4 diagnostic criteria are met:<ref name=":3" /> [[neuroblastoma]]; uncontrolled eye movement ([[opsoclonus]]); movement disorder with sudden muscle contractions ([[myoclonus]]) and/or lack of coordination ([[ataxia]]); behavioral and/or [[sleep disturbance]].
-Because OMS is so rare and occurs at an average age of 19 months (6 to 36 months), a [[diagnosis]] can be slow. Some cases have been misdiagnosed as having been caused by a [[virus]]. After a diagnosis of OMS is made, an associated neuroblastoma is discovered in half of cases, with median delay of 3 months.
+===History and Symptoms===
+*Opsoclonus myoclonus syndrome presents in a relapse-remitting manner.
+* There are [[acute]] and [[chronic]] symptoms.
+* The classic symptoms are mostly seen in [[acute]] disease and they are: [[myoclonus]], [[opsoclonus]], [[ataxia]].<ref name=":1" />
+* The symptoms presenting in the [[chronic]] disease may be a residual opsoclonus and abnormalities of eye movement which may be elicited by re-fixating from near to far or squeezing the [[eyelids]] shut. Hypometric [[saccades]] and smooth eye pursuit movements can remain abnormal for years. Children may also remain not as coordinated as their peers. [[Expressive language disorder|Expressive language]] is generally more affected than receptive language, and cognitive deficits may become more evident in teenagers.<ref name="pmid15922508" />
+*In children it is associated [[neuroblastoma]] in approximately half of cases.<ref name=":3" /> In this age group it also presents with [[gait ataxia]], [[dysarthria]], [[drooling]], [[irritability]], [[vomiting]], and [[Insomnia Disorder|insomnia]].<ref name="pmid26786246" />
+* It has a [[relapse]]-remitting course. Symptoms may vary in duration during [[relapses]] and the remission period is also variable, but usually the relapses last at least 48-72h.<ref name="pmid26786246" />
+* Children affected by the disease may not be fully asymptomatic between the episodes of the disease, persisting with significant [[Speech and language pathology|speech]] and language deficits, [[sleep]] and some [[behavioral]] changes.<ref name="pmid26786246" />
+* Most patients have no detectable [[antibody]], but a few patients presenting with [[neuroblastoma]] do have anti-neuronal and anti-Purkinje cell antibodies.<ref name=":3" />
+* Children with [[neuroblastoma]] and opsoclonus myoclonus syndrome usually have a better [[prognosis]] for their [[neuroblastomas]] as they are in more differentiated stages.<ref name="pmid27095464" />
+===Physical Examination===
-=== Symptoms ===
-*[Disease name] is usually asymptomatic.
-*Symptoms of [disease name] may include the following:
-:*[symptom 1]
-:*[symptom 2]
-:*[symptom 3]
-:*[symptom 4]
-:*[symptom 5]
-:*[symptom 6]
-=== Physical Examination ===
-*Patients with [disease name] usually appear [general appearance].
 *Physical examination may be remarkable for:
-:*[finding 1]
+**[[Ataxia]]: children present with an [[acute]] or [[subacute]] form of [[ataxia]], losing the ability to walk and/or sit over a period ranging from one day to a few weeks, accompanied by severe [[irritability]] and [[myoclonus]], being the first diagnosis proposed for most children often post-infectious [[acute]] [[Cerebellar ataxias|cerebellar ataxia]] of childhood.<ref name="pmid15922508" />
-:*[finding 2]
+**[[Opsoclonus]]: must be differentiated from [[nystagmus]], which is present in most [[acute]] [[cerebellar ataxias]]. [[Opsoclonus]] is multidirectional, [[Conjugate gaze|conjugate]], non-phasic and fast in contrast with [[nystagmus]], which is phasic, may be [[Conjugate gaze|conjugated]], unidirectional.<ref name="pmid15922508" />
-:*[finding 3]
+**[[Myoclonus]]: ranges from polymyoclonia to coarse multifocal [[Jerking|jerks]], and may be persistent and exacerbated by emotional distress and movement.<ref name="pmid15922508" />
-:*[finding 4]
-:*[finding 5]
+===Laboratory Findings===
-:*[finding 6]
-=== Laboratory Findings ===
-*There are no specific laboratory findings associated with [disease name].
-*A  [positive/negative] [test name] is diagnostic of [disease name].
+*There are no specific laboratory markers associated with opsoclonus myoclonus syndrome.<ref name="pmid23622330">{{cite journal| author=Pike M| title=Opsoclonus-myoclonus syndrome. | journal=Handb Clin Neurol | year= 2013 | volume= 112 | issue=  | pages= 1209-11 | pmid=23622330 | doi=10.1016/B978-0-444-52910-7.00042-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23622330  }}</ref>
-*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
+*In adults with opsoclonus myoclonus syndrome, a blood exam may show Hu anti-neuronal nuclear [[antibodies]] ([[anti-Hu]]) but not in children.<ref name=":4">{{Cite web|url=https://rarediseases.info.nih.gov/diseases/10009/opsoclonus-myoclonus-syndrome/cases/24932#ref_7345|title=Genetic and Rare Diseases Information Center - Opsoclonus Myoclonus Syndrome|last=|first=|date=07/04/2020|website=GARD|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
-*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
+*In some patients [[cerebrospinal fluid]] evaluation is necessary to detect neuroinflammation. These studies should include [[oligoclonal bands]] (with paired [[serum]] sample), aiming to detect [[antibodies]] in the [[CSF]] and [[flow cytometry]] of the [[lymphocytes]] using [[immunophenotyping]], which may find an increased frequency of [[CSF]] [[CD19|CD19+]] [[B cells]], which is a [[biomarker]] of opsoclonus myoclonus disease activity.<ref name=":1" />
+*Atypical cases may warrant [[autoantibodies]] tests in some children, but this is not cost-effective.<ref name=":1" />
-===Imaging Findings===
-*There are no [imaging study] findings associated with [disease name].
+===Electrocardiogram===
-*[Imaging study 1] is the imaging modality of choice for [disease name].
+* There are no [[ECG]] findings associated with opsoclonus myoclonus syndrome.
-*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
-*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
+===X-ray===
-=== Other Diagnostic Studies ===
+* There are no specific [[x-ray]] findings associated with opsoclonus myoclonus syndrome.
-*[Disease name] may also be diagnosed using [diagnostic study name].
-*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
+===Echocardiography or Ultrasound===
+* There are no specific echocardiography/ultrasound  findings associated with opsoclonus myoclonus syndrome.
+===CT scan===
+*Opsoclonus myoclonus syndrome may present with [[neuroblastoma]] in half of the cases (one author reported 80% of the cases), though only 2-3% of [[neuroblastoma]] present with opsoclonus myoclonus syndrome.<ref name="pmid159225082">{{cite journal| author=Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG | display-authors=etal| title=Opsoclonus myoclonus syndrome in neuroblastoma a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004. | journal=Cancer Lett | year= 2005 | volume= 228 | issue= 1-2 | pages= 275-82 | pmid=15922508 | doi=10.1016/j.canlet.2005.01.051 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15922508  }}</ref><ref name="pmid15922508" />
+* In the evaluation of a child with opsoclonus myoclonus syndrome, it is usually performed either a [[CT scan]] with contrast or [[MRI]] with [[gadolinium]] of the [[neck]], [[chest]], [[abdomen]], and [[pelvis]]<ref name=":1" /> as [[neuroblastomas]] can arise from [[sympathetic nervous system]], being most frequent in the [[abdomen]] (2/3 of the cases) and [[thorax]] (20% of the cases)<ref name=":6">{{Cite web|url=https://radiopaedia.org/articles/neuroblastoma?lang=us|title=Radiopaedia - Neuroblastomas|last=|first=|date=07/04/2020|website=Radiopaedia.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
+* On [[CT scans]], the [[neuroblastoma]] is [[heterogeneous]] with [[calcifications]] being commonly seen. Usually the [[tumor]] insinuates itself beneath the [[aorta]] and lifting it off the [[vertebral column]].<ref name=":6" />
+===MRI===
+* In the evaluation of a child with opsoclonus myoclonus syndrome, it is usually performed either a [[CT scan]] with contrast or [[MRI]] with [[gadolinium]] of the [[neck]], [[chest]], [[abdomen]], and [[pelvis]]<ref name=":1" /> as [[neuroblastomas]] can arise from [[sympathetic nervous system]], being most frequent in the [[abdomen]] (2/3 of the cases) and [[thorax]] (20% of the cases)<ref name=":6" />
+*[[Magnetic resonance imaging|MRIs]] are superior to all other exams on detecting [[neuroblastomas]] and shows the tumor being heterogenous and iso to hypo intense on T1, and hyper intense on T2, with [[cystic]]/[[necrotic]] areas being easily identifiable.<ref name=":1" />. Usually the [[tumor]] insinuates itself beneath the [[aorta]] and lifting it off the [[vertebral column]].<ref name=":6" />
+===Other Imaging Findings===
+* On adults, the most associated [[neoplasms]] are [[small cell lung cancer]], [[breast carcinoma]], and [[ovarian teratoma]]<ref name="pmid30483882">{{cite journal| author=Oh SY, Kim JS, Dieterich M| title=Update on opsoclonus-myoclonus syndrome in adults. | journal=J Neurol | year= 2019 | volume= 266 | issue= 6 | pages= 1541-1548 | pmid=30483882 | doi=10.1007/s00415-018-9138-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30483882  }}</ref>, and [[Positron emission tomography|PET scans]] are done to evaluate for occult [[tumors]].<ref name=":1" />
+===Other Diagnostic Studies===
+*There are no other diagnostic studies that may be used to diagnose opsoclonus myoclonus syndrome.
 ==Treatment==
-There is no known definitive cure for OMS. However, several drugs have proven to be effective in its treatment.
+===Medical Therapy===
-Some of medication used to treat the symptoms are:
+* The mainstay of therapy for opsoclonus myoclonus syndrome is rule it out as a [[paraneoplastic syndrome]] and then early and aggressive [[immunotherapy]] to obtain a durable and complete neurological [[Remission (medicine)|remission]].<ref name=":1" />
-* [[corticotropin|ACTH]] has shown improvements in symptoms but can result in an incomplete recovery with residual deficits.
+*[[Corticosteroids]] ([[prednisolone]] at 2mg/kg/day and tapered slowly or [[dexamethasone]] 20mg/m2/day for 3 days) and [[ACTH]] are the gold standard<ref name="pmid30483882" /> and they act by [[binding]] to [[intracellular]] [[receptors]] which then act to modulate [[gene transcription]] in target tissues, decreasing the production of pro-[[inflammatory]] [[cytokines]].
-*[[Corticosteroid]]s (such as ''[[prednisone]]'' or ''[[methylprednisolone]]'') used at high dosages (500 mg - 2 g per day [[intravenous]]ly for a course of 3 to 5 days) can accelerate regression of symptoms. Subsequent very gradual tapering with pills generally follows. Most patients require high doses for months to years before tapering.
+*[[Intravenous immunoglobulin|IVIG]] (1gr/kg for 12 cycles) may also be used alone or in combination with [[corticosteroids]], and recent studies suggests that the combination is indeed more effective.<ref name="pmid30483882" /> Most patients respond to such initial treatment.<ref name="pmidhttps://doi.org/10.1038/nrdp.2016.78">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.1038/nrdp.2016.78 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }}</ref>
-*[[Intravenous Immunoglobulin]]s (IVIg) are often used with varying results.
+*There have been reports of [[dexamethasone]] being used with [[cyclophosphamide]], [[rituximab]] ([[Chimeric protein|chimeric]] anti-[[CD20]] [[monoclonal antibody]] that depletes circulating [[B cells]]) in moderately severe opsoclonus myoclonus syndrome, but such associations as also plasma exchange should be reserved for severe cases or cases refractory to [[IVIG]], [[corticosteroids]] or a combination of both.<ref name="pmid30483882" />
-*Several other immunosuppressive drugs, such as [[cyclophosphamide]] and [[azathioprine]], may be helpful in some cases.
+*[[Corticosteroid|Corticosteroids]] and [[IVIG]] alone are insufficient to prevent [[relapse]] or disease progression, and multimodal combination [[immunotherapy]] with disease modifying agents significantly improve long-term outcome when given early.<ref name="pmid26786246" />
-*Chemotherapy for [[neuroblastoma]] may be effective, although data is contradictory and unconvincing at this point in time.
+*Some studies show that combining imunotherapy with [[rituximab]], [[ACTH]] and [[IVIG]], adhering to a more aggressive approach can significantly reduce the [[cognitive impairment]] and [[morbidity]] on opsoclonus myoclonus syndrome.<ref name="pmid26786246" />
-*[[Rituximab]] has been used with encouraging results.  See  [http://pediatrics.aappublications.org/cgi/content/full/115/1/e115 Immunologic and Clinical Responses to Rituximab in a Child With Opsoclonus-Myoclonus Syndrome Michael R. Pranzatelli, MD, Elizabeth D. Tate, FNP-C, MN, Anna L. Travelstead, BS, MT(ASCP)§ and Darryl Longee,MD]
+*[[Ofatumumab]] can be used in children [[allergic]] to [[rituximab]]. [[Rituximab]] should be avoided in the absence of [[B lymphocytes]] on the [[CSF]].<ref name="pmid26786246" />
+*There are reports that intensive [[immunosuppression]] can be associated with improved long-term neurological outcome.<ref name="pmid30483882" />
+*Most children will have relapses with [[Corticosteroids|corticosteroid]] dose tapering.<ref name="pmid30483882" />
+*Patients should be assessed for treatment following the flowchart below as proposed by Pranzatelli:<ref name="pmid26786246" />
-*Other medications are used to treat symptoms without influencing the nature of the disease (symptomatic treatment):
+<br />{{familytree/start}}
-**[[Trazodone]] can be useful against irritability and sleep problems
+{{familytree | | | | | | | | | | | | | | A01 | | |A01=TREATMENT}}
-*Additional treatment options include [[plasmapheresis]] ("washing the blood", showing similarities to [[dialysis]]) for severe, steroid-unresponsive [[relapse|relapses]].
+{{familytree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | | | | }}
-A more detailed summary of current treatment options can be found at http://www.omsusa.org/pranzatelli-medications.htm.
+{{familytree | | | |,|-|-|-|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|-|-|-|-|.| | | | | | | | | | | | | | }}
+{{familytree | | | B01 | | | | | | | | | B02 | | | | | | | | | | B03 | | | |B01=Mitigate Trigger|B02=Treat/Retreat Neuroinflammation|B03=Reassess for high risk}}
+{{familytree | | | |!| | | | | | | | | | |!| | | | | | | | | | | |!| | | | | | | | | | | | | | }}
+{{familytree | |,|-|^|-|.| | | |,|-|-|-|-|+|-|-|-|.| | | |,|-|-|-|+|-|-|-|.| }}
+{{familytree | |!| | | |!| | | |!| | | | |!| | | |!| | | |!| | | |!| | | |!| }}
+{{familytree | C01 | | C02 | | C03 | | | C04 | | C05 | | C06 | | C07 | | C08| |C01=Treat Infections with antimicrobials|C02=Escalate or restart steroids or ACTH|C03=Retest for neuroinflammation as needed|C04=Review previous drug responses|C05=Add or change modifying disease drugs|C06=Formal IQ testing|C07=Treat comorbid neuropsychiatric problems|C08= Avoid potential pitfalls}}
+{{familytree | |!| | | | | | | | | | | | | | |,|-|^|-|.| | | | | |!| | | | | | | }}
+{{familytree | D01 | | | | | | | | | | | |  D02 | | | D03 | | | | D04 | | | | | | | |D01=Give IVIG as needed|D02=Select tapering method|D03=Multimodal combination immunotherapy|D04=Intensify speech therapy, PT, OT}}
+{{familytree/end}}
+<br />
-The following medications should probably be avoided:
+===Surgery===
-* [[Midazolam]] - Can cause irritability.
-* [[Melatonin]] - Is known to stimulate the immune system.
-* Also, see [http://www.omsusa.org/pranzatelli-abstracts.htm An Innovative Approach to the Problem of Sedating Children with Opsoclonus-Myoclonus Syndrome (<i>Annals of Neurology. 1994;36(3):543-544</i>)] for more details
-=== Medical Therapy ===
+*If opsoclonus myoclonus syndrome is due to a [[Paraneoplastic syndrome|paraneoplastic]] etiology, then [[surgical resection]] of the [[tumor]] is needed (in children, [[neuroblastoma]] is the most common, in adults there are many such as [[small cell lung cancer]] and [[breast cancer]]).
-*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
+*[[Surgery]] may be performed to treat such [[tumors]] along other methods of treatments such as [[chemotherapy]] and/or [[radiation]].
+*[[Resection]] and treatment of the [[neuroblastoma]] improves the [[acute]] [[symptoms]], but only rarely prevents neurologic [[sequelae]].<ref name="pmid15922508" />
-*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
+*Most children with [[Paraneoplastic Syndromes|paraneoplastic]] opsoclonus myoclonus syndrome have localized disease which makes [[surgical resection]] more feasible. They also are likely to have tumors with favorable [[cytogenetic]] and [[histopathologic]] traits, with a better [[prognosis]] of their oncologic disease.<ref name=":3" />
-*[Medical therapy 1] acts by [mechanism of action 1].
-*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
-=== Surgery ===
-*Surgery is the mainstay of therapy for [disease name].
-*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
-*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
-=== Prevention ===
-*There are no primary preventive measures available for [disease name].
-*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
-*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
+===Primary Prevention===
-==References==
+* There are no established measures for the primary prevention of opsoclonus myoclonus syndrome.
-{{Reflist|2}}
-*Armstrong MB. Robertson PL. Castle VP. Delayed, recurrent opsoclonus-myoclonus syndrome responding to plasmapheresis. Pediatric Neurology. 33(5): 365-7, 2005 Nov.
+===Secondary Prevention===
-* Cooper R. Khakoo Y. Matthay KK. Lukens JN. Seeger RC. Stram DO. Gerbing RB. Nakagawa A. Shimada H. Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: histopathologic features-a report from the Children's Cancer Group. Medical & Pediatric Oncology. 36(6): 623-9, 2001 Jun.
-*Dale RC. Childhood opsoclonus myoclonus. Lancet Neurology. 2(5): 270, 2003 May.
-* Gesundheit B. Smith CR. Gerstle JT. Weitzman SS. Chan HS. Ataxia and secretory diarrhea: two unusual paraneoplastic syndromes occurring concurrently in the same patient with ganglioneuroblastoma. Journal of Pediatric Hematology/Oncology. 26(9): 549-52, 2004 Sep.
-*Hayward K. Jeremy RJ. Jenkins S. Barkovich AJ. Gultekin SH. Kramer J. Crittenden M. Matthay KK. Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus-myoclonus-ataxia syndrome: relationship to MRI findings and anti-neuronal antibodies. Journal of Pediatrics. 139(4): 552-9, 2001 Oct.
-* Kinsbourne M. Myoclonic enecphalopathy of infants. ''Journal of Neurology, Neurosurgery, Psychiatry'' 25:271-276, 1962.
-* Mezey LE. Harris CM. Adaptive control of saccades in children with dancing eye syndrome. Annals of the New York Academy of Sciences. 956: 449-52, 2002 Apr.
-*Mitchell WG. Davalos-Gonzalez Y. Brumm VL. Aller SK. Burger E. Turkel SB. Borchert MS. Hollar S. Padilla S. Opsoclonus-ataxia caused by childhood neuroblastoma: developmental and neurologic sequelae. Pediatrics. 109(1): 86-98, 2002 Jan.
-* [http://www.neurology.org/cgi/content/abstract/62/9/1526 Pranzatelli, M. R., Travelstead, A. L., Tate, E. D., Allison, T. J.,Moticka, E. J., Franz, D. N., Nigro, M. A., Parke, J. T., Stumpf, D. A., Verhulst, S. J. (2004). B- and T-cell markers in opsoclonus-myoclonus syndrome: Immunophenotyping of CSF lymphocytes. ''Neurology'' 62: 1526-1532]
-* Rudnick E. Khakoo Y. Antunes NL. Seeger RC. Brodeur GM. Shimada H. Gerbing RB. Stram DO. Matthay KK. Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies-a report from the Children's Cancer Group Study. Medical & Pediatric Oncology. 36(6): 612-22, 2001 Jun.
-* Longitudinal Neurodevelopmental Evaluation of Children With Opsoclonus-Ataxia. ''PEDIATRICS Vol. 116 No. 4 October 2005, pp. 901-907 (doi:10.1542/peds.2004-2377)''
+* Effective measures for the secondary prevention of opsoclonus myoclonus syndrome are not yet established, but chronic [[immunotherapy]] with disease modifying agents is being studied with positive results.<ref name="pmid26786246" />
-== External links ==
+==References==
-* [http://groups.yahoo.com/group/OMSFamilies/ An active OMS Support forum]
+{{Reflist|2}}
-* [http://www.ninds.nih.gov/health_and_medical/disorders/opsomyo_doc.htm short description of OMS]
-* [http://www.geocities.com/HotSprings/Spa/2190/ OMS Support Network]
-* [http://www.omsusa.org/ The National Pediatric Myoclonus Center (US)]
-* [http://www.dancingeyes.org.uk/ Dancing eyes syndrome (UK name for OMS)]
-* [http://www.peacehealth.org/kbase/nord/nord679.htm National Organization for Rare Disorders, Inc.]
-* [http://jameskara.blogspot.com/ A blog about Amelia, an OMS patient diagnosed at 4.5 years (stage I neuroblastoma)]
-* [http://www.geocities.com/HotSprings/Spa/2190/Diebold.html The experience of a man who had OMS at age 32]
-* [http://www.chaseawayoms.org/       Chase Away OMS Foundation: A non-profit foundation dedicated to funding research to improve the diagnosis, treatment and ultimately find a cure for OMS]
-*[http://www.ii.bham.ac.uk/clinicalimmunology/Neuroimmunology/Ri.htm Antibody information related to opsocponus]
 [[Category:Rheumatology]]
 [[Category:Neurology]]
-[[de:Opsoklonus-Myoklonus-Syndrom]]
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