About opsoclonic encephalopathy

What is opsoclonic encephalopathy?

Opsoclonus-myoclonus syndrome (OMS) is a paraneoplastic neurological disorder. It is characterized by associated ocular, motor, behavioral, sleep, and language disturbances. The onset is usually abrupt, often severe, and can become chronic.

What are the symptoms for opsoclonic encephalopathy?

The component features of OMS include repeated, random and rapid eye movements in both horizontal, vertical and diagonal directions (opsoclonus); unsteady gait or loss of ability to stand and walk (ataxia); brief, repeated, shock-like Spasms of several muscles within the arms, legs (myoclonus), or tremor interfering with hand use. Behavioral and sleep disturbances, including extreme irritability, inconsolable crying, reduced and fragmented sleep (insomnia) and rage attacks are common. Difficulty articulating speech (dysarthria), sometimes with complete loss of speech and language may occur. Additional symptoms such as Decreased muscle tone (hypotonia) and Vomiting are common.

What are the causes for opsoclonic encephalopathy?

The most common cause of OMS in young children is paraneoplastic. A small, often hidden tumor presumably provokes the immune system into attacking the nervous system, which may also control the tumor or even cause it to regress. Tumors are NOT in the brain, but are in other areas of the body, usually in chest or abdomen. In 50-80 percent of affected young children, a tumor of embryonic nerve cells (neuroblastoma or ganglioneuroblastoma) is responsible for the symptoms associated with OMS. In other affected individuals, the disorder has been designated ‘idiopathic’ or attributed to various mostly viral infections. However, the high rate of spontaneous tumor regression means that the tumor may be gone before it is looked for. In older children or teens, viral infections are the most frequent apparent cause of OMS. In adults, paraneoplastic etiology is more common, most due to lung or breast cancers. In contrast to paraneoplastic OMS in infants and young children, whose tumors are biologically inactive and often benign, the tumors in adults are commonly malignant, often disseminated.

What are the treatments for opsoclonic encephalopathy?

The goal of treatment of OMS is early and aggressive immunotherapy with the goal of gaining a durable complete neurological remission. If a tumor is present, surgical resection is standard. The tumors in young children are usually low stage neuroblastomas or ganglioneuroblastomas (stage I or II), and tumor chemotherapy or radiation therapy are not generally indicated. Tumor resection does not usually provide sufficient clinical benefit for OMS, however.

OMS treatment, which is usually continued over at least 1-2 years, should involve combined immunotherapies as soon as possible after diagnosis. A three-agent protocol involving initial use of high-dose ACTH (corticotropin), IVIg, and rituximab has the best-documented outcomes for moderately severe and severe cases. Rituximab is a monoclonal antibody against B cells (anti-CD20). Almost all patients (80-90%) show improvement with this treatment, but maintaining sustained improvement may require additional treatment and very gradual weaning. Over time, treatment with ACTH may have substantial cortisol-related adverse effects that must be monitored carefully, particularly weight gain, hypertension, and reductions in bone density. Monthly pulse dose dexamethasone instead of ACTH is an option in mild and more moderate cases. The use of prednisone-type oral steroids is not recommended, because they are the least effective of the steroids for pediatric OMS. For OMS relapse, low-dose IV cyclophosphamide (3-6 cycles) or repeated courses of rituximab (1-2 cycles) are given. Oral weekly methotrexate may be a useful steroid sparer in chronic relapse.

What are the risk factors for opsoclonic encephalopathy?

OMS is a rare disorder: 1 per million individuals worldwide. It usually affects infants and young children, although it is also known to affect adults. The peak age in children is about 18 months, with very few diagnosed before 1 year, and a long tail out to about 5 – 6 years. Occurrence of opsoclonus in infants under 6 months old is quite uncommon, and opsoclonus in that age group, when isolated, is usually from another cause. OMS occurs in only slightly more girls than boys. It occurs in about 3% of all children with neuroblastomas.

Is there a cure/medications for opsoclonic encephalopathy?

Almost all children with neuroblastoma and OMS survive their tumor, which usually does not behave aggressively, though some tumors may be large and pose difficulties for resection. In contrast, the tumors that are associated with OMS in adults are often aggressive and are sometimes fatal. The OMS relapse rate in children treated with only conventional agents is 50-75%. Increased immunosuppression has improved neurodevelopmental outcomes in OMS. With more aggressive initial therapies in children, the relapse rate appears to be much lower. OMS onset in the first two years of life is particularly damaging to expressive speech and language development, and may result in a higher incidence of residual cognitive impairment. The best responders appear to be those who received early combination therapy and were only of mild to moderate severity. Failure to achieve complete neurological remission and multiple relapses may result in chronic-progressive OMS, with permanent deficits, such as attention deficient disorder (ADD) attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and irreversible cognitive impairment (low IQ). Children in the chronic sick role can become oppositional, depressed, and aggressive, and attention to these issues often helps to improve quality of life. Parents with a severely ill infant or child may develop “fragile child syndrome” and have difficulty ever seeing their child as a normal, thriving individual, with “ordinary” behavioral issues of childhood. These parents may benefit from counselling to gradually adjust their management of their child’s ongoing behavioral and developmental issues.

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