Opsoclonus myoclonus syndrome
Encyclopedia
Opsoclonus Myoclonus Syndrome (OMS) is a rare neurological 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 children with neuroblastoma
.
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:
About half of all OMS cases occur in association with neuroblastoma
(a cancer of the sympathetic nervous system usually occurring in infants and children).
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.
It is hypothesized that a viral
infection (perhaps St. Louis encephalitis, Epstein-Barr, Coxsackie B, or enterovirus) causes the remaining cases, though a direct connection has not been proven.
OMS is not generally considered an infectious disease
. OMS is not passed on genetically...
may begin weeks or months earlier.
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).
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).
One study (Medical and Pediatric Oncology 36:612-622,2001, see below) came to the conclusion 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 OMS needs further clarification.
Another study (Neuroepidemiologic Trends in 105 US Cases of Pediatric Opsoclonus-Myoclonus Elizabeth D. Tate, Michael R. Pranzatelli, Tyler Allison, Steven Verhurst, Springfield, IL states that:
Residual behavioral, language, and cognitive problems occurred in the majority.
Some of medication used to treat the symptoms are:
A more detailed summary of current treatment options can be found at http://www.omsusa.org/pranzatelli-medications.htm.
The following medications should probably be avoided:
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of unknown causes which appears to be the result of an autoimmune process involving the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. 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
Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
.
Nomenclature
OMS was first described by Marcel KinsbourneMarcel Kinsbourne
Marcel Kinsbourne is an Austrian-born pediatric neurologist and neuroscientist who was an early pioneer in the study of brain lateralization. He is presently a Professor of Psychology at both The New School in New York City and the Center for Cognitive Studies at Tufts University.Dr. Kinsbourne...
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:
- 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
Symptoms include:- opsoclonusOpsoclonusOpsoclonus refers to uncontrolled eye movement. Opsoclonus consists of rapid, involuntary, multivectorial , unpredictable, conjugate fast eye movements without intersaccadic intervals. It is also referred to as saccadomania or reflexive saccade...
(rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without intersaccadic [quick rotation of the eyes] intervals) - myoclonusMyoclonusMyoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
(brief, involuntary twitching of a muscle or a group of muscles) - cerebellar ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, 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 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
- irritabilityIrritationIrritation or exacerbation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant...
or malaiseMalaiseMalaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"... - droolingDroolingDrooling is when saliva flows outside the mouth...
- strabismusStrabismusStrabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
(a condition in which the eyes are not properly aligned with each other) - vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
- sleep disturbances
About half of all OMS cases occur in association with neuroblastoma
Neuroblastoma
Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
(a cancer of the sympathetic nervous system usually occurring in infants and children).
Diagnosis
Because OMS is so rare and occurs at an average age of 19 months (6 to 36 months), a diagnosisMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
can be slow. Some cases have been misdiagnosed as having been caused by a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
. After a diagnosis of OMS is made, an associated neuroblastoma is discovered in half of cases, with median delay of 3 months.
Cause
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 viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
infection (perhaps St. Louis encephalitis, Epstein-Barr, Coxsackie B, or enterovirus) causes the remaining cases, though a direct connection has not been proven.
OMS is not generally considered an infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
. OMS is not passed on genetically...
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 malaiseMalaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
may begin weeks or months earlier.
Prognosis
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).
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).
One study (Medical and Pediatric Oncology 36:612-622,2001, see below) came to the conclusion 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 OMS needs further clarification.
Another study (Neuroepidemiologic Trends in 105 US Cases of Pediatric Opsoclonus-Myoclonus Elizabeth D. Tate, Michael R. Pranzatelli, Tyler Allison, Steven Verhurst, Springfield, IL states that:
Residual behavioral, language, and cognitive problems occurred in the majority.
Treatment
There is no known definitive cure for OMS. However, several drugs have proven to be effective in its treatment.Some of medication used to treat the symptoms are:
- ACTH has shown improvements in symptoms but can result in an incomplete recovery with residual deficits.
- CorticosteroidCorticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s (such as prednisonePrednisonePrednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
or methylprednisoloneMethylprednisoloneMethylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....
) used at high dosages (500 mg - 2 g per day intravenously 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 ImmunoglobulinIntravenous immunoglobulinIntravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
s (IVIg) are often used with varying results. - Several other immunosuppressive drugs, such as cyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
and azathioprineAzathioprineAzathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, may be helpful in some cases. - Chemotherapy for neuroblastomaNeuroblastomaNeuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
may be effective, although data is contradictory and unconvincing at this point in time. - RituximabRituximabRituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
has been used with encouraging results. See 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
- Other medications are used to treat symptoms without influencing the nature of the disease (symptomatic treatment):
- TrazodoneTrazodoneTrazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...
can be useful against irritability and sleep problems
- Trazodone
- Additional treatment options include plasmapheresisPlasmapheresisPlasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
("washing the blood", showing similarities to dialysisDialysisIn medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
) for severe, steroid-unresponsive relapseRelapseRelapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
s.
A more detailed summary of current treatment options can be found at http://www.omsusa.org/pranzatelli-medications.htm.
The following medications should probably be avoided:
- MidazolamMidazolamMidazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
- Can cause irritability. - MelatoninMelatoninMelatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
- Is known to stimulate the immune system. - Also, see An Innovative Approach to the Problem of Sedating Children with Opsoclonus-Myoclonus Syndrome (Annals of Neurology. 1994;36(3):543-544) for more details
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.External links
- Awareness website for OMS
- Foundation for OMS awareness, research and family support
- An active OMS Support forum
- An active OMS Family Network Support Site
- short description of OMS
- Very Old - OMS Support Network
- The National Pediatric Myoclonus Center (US)
- Dancing eyes syndrome (UK name for OMS)
- National Organization for Rare Disorders, Inc.
- A blog about Amelia, an OMS patient diagnosed at 4.5 years (stage I neuroblastoma)
- The experience of a man who had OMS at age 32
- Chase Away OMS Foundation: A non-profit foundation dedicated to funding research to improve the diagnosis, treatment and ultimately find a cure for OMS
- Antibody information related to opsocponus
- http://www.videosilva.com/oms.html Brief overview of O.M.S. along with an OMS Message Board.
- http://www.fondationlaurieann.com Laurie-Ann Duchaine Foundation: a non-profit foundation dedicated to funding to help families, find more cases in the world.