Abstracts

Rationale: Rasmussen encephalitis (RE), a chronic inflammatory disease, affects and subsequently destroys one cerebral hemisphere leading to intractable focal onset seizures and progressive neurological deficits. It is currently understood that Granzyme B mediated T-cell cytotoxicity directed at neurons plays a pivotal role in the pathogenic mechanisms of RE. Whereas anticonvulsive pharmacotherapy is poorly effective, surgical deafferentiation of the affected hemisphere can be used for seizure treatment, but is often withheld until later stages of the disease when a fixed hemiparesis has developed. Due to the assumptive pathogenesis various forms of immunotherapy are applied to prevent progressive loss of neurological function. Methods: We describe the case of a 25 year old female patient with biopsy proven RE who was treated with a combination of immunoadsorptions and rituximab, a monoclonal antibody against the protein CD20, in addition to antiepileptic polytherapy for the course of five years. After diagnosis of RE seven years earlier numerous regimens of antiepileptic and anti-inflammatory drugs had not lead to control of seizures even though progression of hemiatrophy was relatively mild. Results: After the first application of immunoadsorption followed by administration of rituximab (375 mg/m2 intravenously once a week over four weeks) seizures ceased completely and for the first time since disease onset the patient remained seizure free for 6 months. During the following five years the patient repeatedly presented with focal status epilepticus or with increasing and daily life impairing seizures. We administered either immunoadsorptions, rituximab or a combination of both, which lead to complete cessation of seizures or to a reduction to only minor, not impairing seizures for up to six months. Antiepileptic treatment could successively be reduced down to triple therapy without sedative or cognition impairing medication. Immunoadsorptions were done when the patient presented with focal status epilepticus, which made a fast treatment response necessary. In case that seizures could not be controlled with immunoadsorptions alone a treatment with rituximab was added. Rituximab alone was administered three times in a prophylactic approach and the seizure free intervals could thereby be extended. However, seizure aggravation or status epilepticus always reoccurred after several months. Rituximab was well tolerated except for an increased occurrence of minor infections. Immunoadsorption was associated with more side effects such as infections and occlusions of the shunt and once cardio-pulmonary-reanimation was necessary after an iatrogenic uncontrolled citrate infusion. Conclusions: This observation challenges the traditional view that non-surgical seizure treatment is largely unsuccessful and demonstrates a therapeutic approach that is able to control seizures and tissue loss. Furthermore, it indicates that therapeutic approaches other than those primarily directed at cellular immunity, such as rituximab and immunoadsorption, can be beneficial in Rasmussen encephalitis.