Rasmussen's encephalitis, also termed Rasmussen's syndrome, is a rare degenerative brain disease that initially affects only one side of the brain. It first manifests in childhood with the onset of epileptic seizures . Later, it progresses to paralysis of one side of the body (hemiparesis), blindness in one eye (hemianopsia ), and loss of mental function. The seizures in Rasmussen's encephalitis usually resist therapy with anticonvulsant drugs, but respond well to hemispherectomy, the surgical removal of the entire affected side of the brain.
Rasmussen's encephalitis usually appears in children, but may also strike in adulthood. It initially affects only one side (hemisphere) of the brain. The disease causes uncontrollable seizures and other symptoms that become progressively worse. The affected hemisphere shows changes characteristic of chronic inflammation, including long-term atrophy or shrinkage, hence, the term encephalitis (inflammation of the brain). Unless the affected hemisphere is removed, the disorder eventually spreads to the brain's other hemisphere.
Rasmussen's encephalitis is very rare; between 1958, when the syndrome was first identified, and 2000, barely 100 cases were identified. The medical literature does not describe a higher incidence of this disease in either gender or in any particular racial group or geographical area.
Causes and symptoms
For many years, the cause of Rasmussen's encephalitis was a mystery. It seemed to resemble a viral infection, but despite much research, no organism could be consistently found in the brains of those who had suffered from the disorder. Finally, in the early 1990s, it was discovered that Rasmussen's encephalitis is an autoimmune disease, that is, a disorder in which the body is attacked by its own immune system.
Specifically, the body responds to one of the glutamate receptors, GluR3, as if it were an invading organism. Glutamate is a neurotransmitter, or one of the chemicals that neurons use to signal to each other. A receptor is a complex molecule embedded in the cell membrane of a neuron that detects the presence of a specific neurotransmitter and responds by causing some change in the neuron itself, such as admitting a flow of sodium, potassium, or calcium ions into the cell. There are at least 20 distinct receptors for glutamate in the brain, one of which is denoted GluR3. In Rasmussen's encephalitis, the body (for reasons still unknown) produces anti-GluR3 antibodies. Attracted by these antibodies, groupings of special immune system proteins, termed complement, gather on neurons in the affected parts of the brain, eventually forming "membrane attack complexes" that damage the neurons. It is not known why this autoimmune response attacks only one side of the brain at first, but it was hypothesized that a breach in the blood-brain barrier in one part of the brain might allow initial access of antibodies to neurons. The arrival of lymphocytes in the affected area, with consequent swelling of tissues, may then cause further damage to the blood-brain barrier and allow more anti-GluR3 antibodies access to the neurons. Finally, it remains possible that infection by cytomegalovirus may play a role in triggering the autoimmune processes of Rasmussen's encephalitis. Cytomegalovirus DNA has been detected in the brains of some patients.
The first symptom of Rasmussen's encephalitis is seizures, usually beginning suddenly before the age of 10. Loss of control over voluntary movements, loss of speech ability (aphasia ), hemiparesis (weakness on one side of the body), dementia, mental retardation , and eventually, death, will follow if untreated.
Rasmussen's encephalitis is diagnosed by the sudden onset of epileptic seizures in childhood, gradual worsening of seizures, gradual intellectual deterioration, the onset of hemiparesis and other one-sided symptoms, and the elimination of other possible causes for these symptoms.
Early in the progress of Rasmussen's encephalitis, anticonvulsant drugs may help control seizures. Use of the anti-cytomegalovirus drug ganciclovir early in the syndrome produces improvement in some patients. Also, some patients have shown dramatic positive response to removal of anti-GluR3 antibodies from the blood by a process known as plasmapheresis. Currently, researchers are studying the hypothesis that drugs to prevent the formation of membrane-attack complexes might slow or halt the progression of Rasmussen's encephalitis as well as of other neurodegenerative diseases. However, the treatment of choice remained hemispherectomy, surgical removal of the affected half of the brain.
Remarkably, children may show little or no change in personality and no loss of intelligence or memory after having half their brain removed. Some children are irritable, withdrawn, or depressed immediately after surgery, but these symptoms are not permanent. So flexible is brain development that a child with a hemispherectomy may become fluent in one or more languages even if the left side of the brain, where the speech centers are usually located, is removed. Blindness or vision loss in one eye usually results from hemispherectomy, but normal hearing in both ears may be recovered. The older the patient is when the surgery is performed, however, the more likely they are to suffer permanent sensory, speech, and motor losses.
Recovery and rehabilitation
Rehabilitation begins immediately after hemispherectomy with passive range-of-motion exercises. Physical, occupational, and speech therapists are required. For children of school age, neuropsychological testing can help determine what academic setting or grade level is best. Children with hemispherectomies are often able to participate in school at the level appropriate for their age.
The prognosis for children below the age of 10 who are treated early in the course of the syndrome is good. This group can often achieve normal psychosocial and intellectual functioning. Without hemispherectomy, however, persons with Rasmussen's encephalitis eventually suffer near-continuous seizures, mental retardation, and death.
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National Organization for Rare Disorders (NORD). P.O. Box 1968 (55 Kenosia Avenue), Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-NORD; Fax: (203) 798-2291. [email protected] <http://www.rarediseases.org>.
Larry Gilman, PhD