Opsoclonus myoclonus syndrome: Difference between revisions

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*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]].
*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]].
*The syndrome was named as "myoclonic encephalopathy", but has also been called as "dancing eye syndrome".<ref name=":2">Blaes, Franz, and Backialakshmi Dharmalingam. "Childhood opsoclonus-myoclonus syndrome: diagnosis and treatment." ''Expert review of neurotherapeutics'' 16.6 (2016): 641-648.</ref> Recently it has been more often referred to as opsoclonus myoclonus syndrome.
*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.


== Classification==
== Classification==
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*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.
*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>Pranzatelli MR, Tate ED, McGee NR, Travelstead AL, Ranso- hoff RM, Ness JM, et al. Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS. J Neuroimmunol 2012;243:81–8.</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=":0">Pranzatelli, Michael R., and Elizabeth D. Tate. "Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome." ''Brain and Development'' 38.5 (2016): 439-448.</ref>
*[[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:
*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]].
**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>
**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=":0" />
*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" />
*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" />
*On microscopic histopathological analysis, [[gliosis]] and [[inflammation]] in the [[cerebellar vermis]] are characteristic findings of opsoclonus myoclonus syndrome.<ref name=":3" />


==Clinical Features ==
==Causes==


* Opsoclonus myoclonus syndrome (also often called: “dancing eyes-dancing feet” syndrome) is a rare syndrome of unknown etiology that presents with the following features:<ref name=":3" />
* 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.
**[[Opsoclonus]],
**[[Myoclonic jerk|Myoclonic]] jerks,
**[[Behavioral]] disturbances
**[[Ataxia]].
* The cause is not yet known but the accepted hypothesis is that it is an [[autoimmune]], [[inflammatory]] reaction which damages the [[central nervous system]]. It is theorized that I can be triggered by either a [[Paraneoplastic Syndromes|paraneoplastic]] (being associated with [[neuroblastoma]] in children) or an infectious etiology.<ref name=":3" />
* 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=":0" />
* 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=":0" />
* 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=":0" />
* 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=":2" />


== Differentiating Opsoclonus Myoclonus syndrome from other Diseases==
== Differentiating Opsoclonus Myoclonus syndrome from other Diseases==
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*There are no [[risk factors]] associated with the development of opsoclonus myoclonus syndrome.
*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==
==Natural History, Complications and Prognosis==


*The majority of patients with opsoclonus myoclonus syndrome present with a [[relapse]]-remitting form of the disease.
*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]].<ref name=":5">Matthay, Katherine K., et al. "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 letters'' 228.1-2 (2005): 275-282.</ref>
*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=":2" />
*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=":2" />
*[[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=":2" />
*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" />


==Diagnosis==
==Diagnosis==
=== Diagnostic Criteria===
===Diagnostic Study of Choice===


*The diagnosis of opsoclonus myoclonus syndrome is made when at least 3 of the following 4 diagnostic criteria are met:<ref name=":4" />
*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]].
**[[Neuroblastoma]]/
**Uncontrolled eye movement ([[opsoclonus]])/
**A movement disorder with sudden muscle contractions ([[myoclonus]]) and/or lack of coordination ([[ataxia]])/
**Behavioral and/or [[sleep disturbance]].


===Symptoms===
===History and Symptoms===


* Opsoclonus myoclonus syndrome presents in a relapse-remitting manner.  
*Opsoclonus myoclonus syndrome presents in a relapse-remitting manner.
* There are [[acute]] and [[chronic]] symptoms.
* There are [[acute]] and [[chronic]] symptoms.
* The classic symptoms are mostly seen in [[acute]] disease and they are:<ref name=":1" />
* The classic symptoms are mostly seen in [[acute]] disease and they are: [[myoclonus]], [[opsoclonus]], [[ataxia]].<ref name=":1" />
**[[Myoclonus]],
* 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" />
**[[Opsoclonus]],
*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" />
**[[Ataxia]].
* 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" />
* 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=":5" />
* 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===
===Physical Examination===


*Physical examination may be remarkable for:
*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 ataxias|cerebellar ataxia]] of childhood.<ref name=":5" />
**[[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" />
**[[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=":5" />
**[[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" />
**[[Myoclonus]]: ranges from polymyoclonia to coarse multifocal [[Jerking|jerks]], and may be persistent and exacerbated by emotional distress and movement.<ref name=":5" />
**[[Myoclonus]]: ranges from polymyoclonia to coarse multifocal [[Jerking|jerks]], and may be persistent and exacerbated by emotional distress and movement.<ref name="pmid15922508" />
**[[Behavioral]] changes: development regression and personality change may also be seen.<ref name=":5" />


===Laboratory Findings===
===Laboratory Findings===


*There are no specific laboratory markers associated with opsoclonus myoclonus syndrome.<ref>Pike M. Opsoclonus-myoclonus syndrome. Handb Clin Neurol 2013;112:1209–11.</ref>
*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>
*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>
*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>
*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" />
*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" />
*Atypical cases may warrant [[autoantibodies]] tests in some children, but this is not cost-effective.<ref name=":1" />


=== Imaging Findings===
===Electrocardiogram===
 
* There are no [[ECG]] findings associated with opsoclonus myoclonus syndrome.
 
===X-ray===


* 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=":5" />
* 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.<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>
* 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" />
* 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" />
*[[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" />
 
* On adults, the most associated [[neoplasms]] are [[small cell lung cancer]], [[breast carcinoma]], and [[ovarian teratoma]]<ref name=":7">Oh, Sun-Young, Ji-Soo Kim, and Marianne Dieterich. "Update on opsoclonus–myoclonus syndrome in adults." ''Journal of neurology'' 266.6 (2019): 1541-1548.</ref>, and [[Positron emission tomography|PET scans]] are done to evaluate for occult [[tumors]].<ref name=":1" />
===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===
===Other Diagnostic Studies===
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* 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" />
* 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" />
*[[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=":7" /> 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]].
*[[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]].
*[[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=":7" /> Most patients respond to such initial treatment.<ref>Rudnick, Emily, et al. "Opsoclonus‐myoclonus‐ataxia syndrome in neuroblastoma: Clinical outcome and antineuronal antibodies—a report from the children's cancer group study." ''Medical and Pediatric Oncology: The Official Journal of SIOP—International Society of Pediatric Oncology (Societé Internationale d'Oncologie Pédiatrique'' 36.6 (2001): 612-622.</ref>
*[[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>
*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=":7" />
*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" />
*[[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=":0" />
*[[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" />
*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=":0" />
*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" />
*[[Ofatumumab]] can be used in children [[allergic]] to [[rituximab]]. [[Rituximab]] should be avoided in the absence of [[B lymphocytes]] on the [[CSF]].<ref name=":0" />
*[[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=":7" />
*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=":7" />
*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=":0" />
*Patients should be assessed for treatment following the flowchart below as proposed by Pranzatelli:<ref name="pmid26786246" />


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*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]]).
*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]]).
*[[Surgery]] may be performed to treat such [[tumors]] along other methods of treatments such as [[chemotherapy]] and/or [[radiation]].
*[[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=":5" />
*[[Resection]] and treatment of the [[neuroblastoma]] improves the [[acute]] [[symptoms]], but only rarely prevents neurologic [[sequelae]].<ref name="pmid15922508" />
*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" />
*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" />
===Prevention===
*There are no primary preventive measures available for opsoclonus myoclonus syndrome.
==Overview==
==Historical Perspective==
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
==Classification==
There is no established system for the classification of [disease name].
OR
[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].
OR
[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
OR
Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
OR
If the staging system involves specific and characteristic findings and features:
According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].
OR
The staging of [malignancy name] is based on the [staging system].
OR
There is no established system for the staging of [malignancy name].
==Pathophysiology==
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
==Causes==
Disease name] may be caused by [cause1], [cause2], or [cause3].
OR
Common causes of [disease] include [cause1], [cause2], and [cause3].
OR
The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
OR
The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
==Differentiating ((Page 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], and [differential dx3].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.
OR
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
The majority of [disease name] cases are reported in [geographical region].
OR
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
==Risk Factors==
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
OR
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
OR
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
==Diagnosis==
===Diagnostic Study of Choice===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
OR
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
OR
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
OR
There are no established criteria for the diagnosis of [disease name].
===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.
OR
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
OR
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
OR
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].
===Electrocardiogram===
There are no ECG findings associated with [disease name].
OR
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
===X-ray===
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
OR
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===CT scan===
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===MRI===
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
==Treatment==
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR


Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
* There are no established measures for the primary prevention of opsoclonus myoclonus syndrome.
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].


* 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" />


==References==
==References==

Latest revision as of 14:34, 20 July 2020

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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

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

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

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

Laboratory Findings

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

MRI

Other Imaging Findings

Other Diagnostic Studies

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

Treatment

Medical Therapy


 
 
 
 
 
 
 
 
 
 
 
 
 
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

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. ↑ 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.
  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.
  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.
  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)
  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)
  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.
  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.
  9. ↑ "Genetic and Rare Diseases Information Center - Opsoclonus Myoclonus Syndrome". GARD. 07/04/2020. Check date values in: |date= (help)
  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.
  11. ↑ 11.0 11.1 11.2 11.3 "Radiopaedia - Neuroblastomas". Radiopaedia.org. 07/04/2020. Check date values in: |date= (help)
  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.
  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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