Efficacy of Tacrolimus and I.V.-Immunoglobulins in Rasmussen Encephalitis

• Status: Unknown status
• Trial end date: 2010-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Rasmussen encephalitis (RE) is a rare but severe chronic inflammatory brain disease of unknown origin affecting one brain hemisphere. It is usually accompanied by intractable epilepsy. In addition, it often leads to severe disability due to functional deficits caused by atrophy of one brain hemisphere. Hemispherectomy is an effective means of surgical treatment of the epilepsy. It renders the patient, however, hemiplegic, hemianopic and (if the language dominant hemisphere is affected) aphasic. To slow down or even stop the progressive inflammatory damage to the affected brain hemisphere, immunotherapies may be beneficial. According to a literature survey, tacrolimus (twice daily intake of capsules) and intravenous immunoglobulins (monthly infusions) are the most promising compounds for this. In the investigators' study, these two types of treatment are randomly assigned to patients with disease onset within the last year and not too far advanced disability or hemispheric brain injury. The patients are followed to assess prospectively the functional and brain MRI course of the disease.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Bonn
• Collaborators: Astellas Pharma GmbH; Octapharma
• Treatments: Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Tacrolimus

Criteria

Inclusion Criteria:

• Patients meeting at least two of the following three criteria:

1. Clinical: Epilepsia partialis continua or progressive* hemiparesis

2. MRI: Progressive* cerebral hemiatrophy

3. Histopathology: T cell dominated encephalitis with activated microglial cells (typically, but not necessarily forming nodules) and reactive astrogliosis. Numerous macrophages, B cells or plasma cells or positive signs of viral infections (viral inclusion bodies or immunohistochemical demonstration of viral protein) exclude the diagnosis of RE.

• "Progressive" means that at least two sequential clinical examinations or MRI studies documenting increasing deficits or tissue loss are required to meet the respective criteria.

Exclusion Criteria:

• Neuroradiological signs of a bihemispheric encephalitis.

• Wave-like course with history of repeated remissions.

• Infectious disease as a contraindication to an immunosuppressive therapy.

• Paraneoplastic encephalitis.

• Previous treatment with > 3 weeks of corticosteroids or tacrolimus or > 1,2 g/kg IVIG or > 5 PEX/PAI within the last three months.

• Onset of acute disease stage more than 12 months ago.

• Patient already in residual stage, i.e., stable neurological deficit since >6 months.

• Hemispheric Ratio < 80% (< 90% in patients > 11 years)

• Histopathological evidence of cerebral inclusion bodies indicating a viral infection