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What

Rasmussen's encephalitis (RE) is an extremely rare neurological disorder characterized by frequent and severe seizures that are resistant to treatment, encephalitis (inflammation of the brain), hemiparesis (paralysis on one side of the body), dementia (loss of intellect and emotional disturbances), loss of motor skills and speech, and mental deterioration. This disorder affects one half of the brain or the other, and the frequency of either side being affected is the same. Recent data suggests the possibility of some degree of involvement of the opposite half of the brain, as well, based on the effect and type of seizure activity.

Who

The first symptoms of this disease usually begin before the age of 10, but the exact age of onset varies. In recent years, several cases of adult-onset Rasmussen’s encephalitis have been described. There is no major difference in incidence between boys and girls or between different ethnic groups.

Signs and Symptoms

The first signs of the disease are usually generalized “tonic clonic” seizures, described as whole body convulsions in which muscles alternate between relaxation and contraction, or partial seizures. Later, simple partial motor seizures and complex partial seizures are frequently observed. Not infrequently, children with Rasmussen’s exhibiting these symptoms are misdiagnosed as having epilepsy, but the corresponding treatments have no effect. The seizures continue and damage to the brain ensues. Another characteristic feature of this disorder is a slowly progressive neurological deterioration usually consisting of hemiparesis, or paralysis of one half of the body, as well as mental impairment. In addition, radiology studies, which yield images of the brain, eventually provide evidence of progressive brain atrophy or wasting that is greater than that observed in childhood epilepsies.

Possible Causes

Since first observed in 1958, there has been much speculation behind the cause of Rasmussen’s encephalitis. Proposed theories have included a viral infection, an immune response to a viral infection, and an autoimmune response of independent origin. Rasmussen’s encephalitis is today regarded as an autoimmune disorder. An autoimmune disease results when the body’s normal tolerance of its own protein disappears and is therefore followed by an active immune response against that protein. Autoantibodies are produced that attack normal cells thereby destroying tissue. In the last ten years, research has suggested that antibodies against a specific type of antigenic marker or cellular protein called the glutamate receptor, and abbreviated GluR3, are present in patients with Rasmussen’s encephalitis. It is likely that the body mounts an immune response to the GluR3 and that this leads to the development of the disease. However, there is no immunological test to confirm the diagnosis.

Diagnosis

The diagnosis of Rasmussen’s encephalitis has usually been based on the age of the patient, the clinical development, imaging data and biopsy studies, in which a sample of brain tissue is removed and examined under a microscope to determine abnormal changes at the cellular level. The child’s clinical history and physical examination are often most important. The characteristic biopsy results distinguishing Rasmussen’s encephalitis from other childhood seizure disorders reveal nodules of inflammatory cells distributed in a random manner through the outer surface of the affected brain hemisphere. CT and MRI scans over time reveal progressive atrophy of the affected hemisphere. In cases where this drastic change is clearly evident, a biopsy of the brain is not needed for diagnosis. It is also important to keep in mind that increasingly older individuals have been diagnosed with Rasmussen’s encephalitis, and the progression of the disease is highly variable.

Treatment

Conventional anti-epileptic drugs are ineffective at controlling the seizures and preventing the progression of the disease. Despite such treatments patients continue to deteriorate, experiencing loss of neurons and scar formation in their brain tissue. “Immunomodulation treatments” such as plasma exchange, which involves the removal and reinfusion of blood plasma, and intravenous administration of immunoglobulin, a protein type that acts like antibodies, have shown some beneficial effects but only on a short-term basis. The standard treatment for Rasmussen's encephalitis is surgery to disconnect the affected part of the brain, known as hemispherectomy. In this surgery, the affected side of the brain is disconnected but left in place. This stops the seizures and protects the rest of the brain from the damage caused by the continuous electrical activity. Though a large part of the brain is disconnected, children have enough growth and development left that they can recover much of their function, ultimately ending up somewhat “stiff” on one side or experiencing decreased vision, but still able to engage in most activities. Disconnecting smaller parts of the brain is not a viable alternative, as it does not completely stop the seizure activity.

Prognosis

Prognosis for individuals with Rasmussen's encephalitis varies. Untreated, the disorder may lead to severe neurological deficits including mental retardation and paralysis. Hemispherectomy is performed in order to eliminate the source of the seizures, and thus arrest brain tissue destruction. In most patients, this surgery eliminates the occurrence of seizures altogether. Postoperative treatment usually involves speech and physical therapy, though the degree required is based on which hemisphere was removed and on the severity of the deficits observed immediately following surgery. Because the brain is capable of some “re-wiring” the remaining hemisphere is able to “take-over” many of the functions of the removed hemisphere and thus compensate for it. The earlier the hemispherectomy takes place the greater the potential for recovery. Moreover, the earlier the unaffected hemisphere and remaining central nervous system is spared the damage from persistent seizure activity, the more effectively the remaining parts of the brain can develop to their maximal potential. For this reason, and in order to prevent further clinical deterioration, there is an urgent need for early diagnosis followed by treatment that stops the progression of the disease. Some experts in the field strongly recommend that the hemispherectomy be performed before a maximal motor or language deficit has developed. However, it is important to note that children as old as sixteen have shown remarkable recovery. Nonetheless, most patients are left with some paralysis and speech deficits.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

International League Against Epilepsy
The information presented here was co-authored by one of the world’s leading authorities into the disorder. Is detailed but easy to read.

National Institute of Neurological Disorders and Stroke
This information provided is well written and concise and includes links to ongoing clinical trials.

Epilepsy Foundation
This is a great site for learning about seizures and treatments. There is lots of information about support networks and ongoing research.

Rasmussen's Encephalitis Support Network
This site is sponsored by an organization whose primary objective is to provide support to families with loved ones with Rasmussen’s encephalitis.

Google Search for Rasmussen's Encephalitis (RE)

References and Sources

www.epilepsy.org/ctf/rasmussens_syndrome.html www.ninds.nih.gov/health_and_medical/disorders/rasmussn_doc.htm www.epilepsyfoundation.org/ www.medhelp.org/www/rasm.htm "The Child’s Brain: Syllable from Sound.” The Secret Life of the Brain: Episode Two. PBS, 2001.