Opsoclonus myoclonus syndrome
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Opsoclonus myoclonus syndrome (OMS), also known as opsoclonus-myoclonus-ataxia (OMA), is a rare
neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
disorder Disorder may refer to randomness, non-order, or no intelligible pattern. Disorder may also refer to: Healthcare * Disorder (medicine), a functional abnormality or disturbance * Mental disorder or psychological disorder, a psychological pattern a ...
of unknown cause which appears to be the result of an
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
process involving the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people per year. It affects 2 to 3% of children with
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
and has been reported to occur with
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...
and diseases of neurologic and autonomic dysfunction.


Signs and symptoms

Symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an disease, illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormali ...
include: *
opsoclonus Opsoclonus refers to uncontrolled, irregular, and nonrhythmic eye movement. Opsoclonus consists of rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without inter- saccadic intervals. It is a ...
(rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without inter
saccadic A saccade ( , French for ''jerk'') is a quick, simultaneous movement of both eyes between two or more phases of fixation in the same direction.Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishi ...
uick rotation of the eyesintervals) *
myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
(brief, involuntary twitching of a muscle or a group of muscles) *
cerebellar ataxia Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...
, both truncal and appendicular *
aphasia Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine but aphasia due to stroke is estimated to be 0.1–0.4% in th ...
(a language disorder in which there is an impairment of speech and of comprehension of speech, caused by brain damage) *
mutism Muteness or mutism () is defined as an absence of speech while conserving or maintaining the ability to hear the speech of others. Mutism is typically understood as a person's inability to speak, and commonly observed by their family members, caregi ...
(a language disorder in which a person does not speak despite evidence of speech ability in the past, often part of a larger neurological or psychiatric disorder) *
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
*
irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
or
malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
*
drooling Drooling, or slobbering, is the flow of saliva outside the mouth. Drooling can be caused by excess production of saliva, inability to retain saliva within the mouth (incontinence of saliva), or problems with swallowing (dysphagia or odynophagia) ...
*
strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...
(a condition in which the eyes are not properly aligned with each other) *
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
* sleep disturbances * emotional disturbances (including fits of
rage Rage may refer to: * Rage (emotion), an intense form of anger Games * Rage (collectible card game), a collectible card game * Rage (trick-taking card game), a commercial variant of the card game Oh Hell * ''Rage'' (video game), a 2011 first-per ...
) About half of all OMS cases occur in association with
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
(a cancer of the sympathetic nervous system usually occurring in infants and children).


Disease course and clinical subtypes

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 As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
may begin weeks or months earlier.


Cause

In children, most 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. In adults, most cases are associated with breast carcinoma or small-cell lung carcinoma. It is one of the few
paraneoplastic A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
(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
viral Viral means "relating to viruses" (small infectious agents). Viral may also refer to: Viral behavior, or virality Memetic behavior likened that of a virus, for example: * Viral marketing, the use of existing social networks to spread a marke ...
infection (perhaps
St. Louis encephalitis Saint Louis encephalitis is a disease caused by the mosquito-borne Saint Louis encephalitis virus. Saint Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the family ''Flaviviridae''. This disease mainly affe ...
,
Chikungunya Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a ra ...
, Epstein-Barr,
Coxsackie B Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illness ranging from gastrointestinal distress to full-fledged pericarditis and myocarditis ( coxsackievirus-induced cardiomyopathy) ...
,
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it ma ...
, or just a flu) causes the remaining cases, though a direct connection has not been proven. Rare cases of Opsoclonus myoclonus syndrome associated with
Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...
have also been reported. OMS is not generally considered an
infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
. OMS is not passed on genetically.


Diagnosis

Because OMS is so rare and occurs at an average age of 19 months (6 to 36 months), a
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
can be slow. Some cases have been diagnosed as having been caused by a
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
. After a diagnosis of OMS is made, an associated neuroblastoma is discovered in half of cases, with median delay of 3 months. The interictal
EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
pattern is usually normal.


Treatment

There is no known definitive cure for OMS. However, several drugs have proven to be effective in their treatment. Some of medication used to treat the symptoms are: *
ACTH Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
has shown improvements in symptoms but can result in an incomplete recovery with residual deficits. *
Corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s (such as ''
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
'' or ''
methylprednisolone Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol) is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high ...
'') used at high dosages (500 mg - 2 g per day
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
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 Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
s (IVIg) are often used with varying results. * Several other immunosuppressive drugs, such as
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
and
azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
, may be helpful in some cases. * Chemotherapy for
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
may be effective, although data is contradictory and unconvincing at this point in time. *
Rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric p ...
has been used with encouraging results. * Other medications are used to treat symptoms without influencing the nature of the disease (symptomatic treatment): **
Trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, fe ...
can be useful against irritability and sleep problems * Additional treatment options include
plasmapheresis Plasmapheresis (from the Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulati ...
for severe, steroid-unresponsive
relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...
s
The National Organization for Rare Disorders
(NORD) recommends FLAIR therapy consisting of a three-agent protocol involving front-loaded high-dose
ACTH Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important co ...
,
IVIg Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
, and
rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric p ...
that was developed by th
National Pediatric Myoclonus Center
and has the best-documented outcomes. Almost all patients (80-90%) show improvement with this treatment and the relapse rate appears to be about 20%. A more detailed summary of current treatment options can be found a

The following medications should probably be avoided: *
Midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of a ...
- Can cause irritability. *
Melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
- Is known to stimulate the immune system. * Also, see for more details


Prognosis

Currently, there are no clinically established laboratory investigations available to predict prognosis or therapeutic response. Tumors in children who develop OMS tend to be more mature, showing favorable histology and absence of n-myc oncogene amplification than similar tumors in children without symptoms of OMS. 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. The three-year survival rate for children with non-metastatic neuroblastoma and OMS was 100% according to Children's Cancer Group data (gathered from 675 patients diagnosed between 1980 and 1994); three-year survival in comparable patients with OMS was 77%. Although the symptoms of OMS are typically steroid-responsive and recovery from acute symptoms of OMS can be quite good, children often experience lifelong neurologic sequelae that impair motor, cognitive, language, and behavioral development. Most children will experience a relapsing form of OMS, though a minority will have a monophasic course and may be more likely to recover without residual deficits. 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. Studies have generally asserted that 70-80% of children with OMS 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 OMS. One study concludes that: ''"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 OMA needs further clarification".'' Another study states that: ''"Residual behavioral, language, and cognitive problems occurred in the majority".''


Research

The National Institute of Neurological Disorders and Stroke (NINDS) conducts and supports research on various movement disorders, including opsoclonus myoclonus. These studies are focused on finding ways to prevent, treat, and cure these disorders, as well as increasing knowledge about them.


Nomenclature

OMS was first described by
Marcel Kinsbourne Marcel Kinsbourne (born 1931) is an Austrian-born pediatric Neurology, neurologist and Cognitive neuroscience, cognitive neuroscientist who was an early pioneer in the study of brain lateralization. Kinsbourne obtained his Doctor of Medicine, M.D. d ...
in 1962. (The term 'Opsoclonus' was coined by Orzechowski in 1913, but it was classically described and associated with neuroblastoma by Kinsbourne). Other names for OMS include: * Dancing Eyes-Dancing Feet syndrome * Dancing Eyes syndrome (see also
Nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...
) * Kinsbourne syndrome * Myoclonic Encephalopathy of Infants (MEI), not to be confused with
Early myoclonic encephalopathy Early myoclonic encephalopathy (EME) is a rare neonatal-onset epilepsy developmental and epileptic encephalopathy (DEE) with an onset at neonatal period or during the first 3 months of life. This syndrome is now included as part of the Early infa ...
(EME) * Opsoclonic Cerebellopathy * Opsoclonus-Myoclonus-Ataxia (OMA) * Paraneoplastic Opsoclonus-Myoclonus Ataxia (POMA)


References


Further reading

* * *


External links

{{DEFAULTSORT:Opsoclonus Myoclonus Syndrome Autoimmune diseases Neurological disorders Rare syndromes