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Immunotherapy controls 81% of anti-NMDA autoimmune encephalitis

The anti-NMDA autoimmune encephalitis is a disease described in 2005 by a team led by Dr. Josep Dalmau at the University of Pennsylvania (USA). In this disorder the patient's immune system attacks the NMDA receptors in the brain, which are important for neuronal plasticity. It triggers a wide range of symptoms such as psychosis, behavioral disturbances, memory deficit or loss of consciousness that may be confused with severe psychiatric disorders. The disease affects mainly women, especially young ones. Nowadays Dr. Josep Dalmau heads, thanks to a senior ICREA contract, the Autoimmunity against synaptic antigens IDIBAPS group. In collaboration with colleagues at the University of Pennsylvania, where he keeps collaborating, and other international partners, his team published in Lancet Neurology the keys to successfully treat over 80% of these patients. The first author is Dr. Maarten Titulaer, a Dutch researcher who works at Dr. Dalmau’s IDIBAPS team.

The study included 577 patients with ages ranged from 8 months to 88 years (median age 21 years). The suggested treatment consists, in the first place, in detecting whether patients have a tumor, because in previous works the same team found this autoimmune disease to be related with presenting a benign tumor, especially an ovarian teratoma. When a tumor is detected they proceed to remove it. All patients, including the ones without a tumor, received a first-line combination immunotherapy including steroids, intravenous immunoglobulin or plasmapheresis. With this strategy one half of the patients improved considerably within a 4 weeks period. Most of the patients who did not respond well to the treatment underwent a more intensive immunotherapy, comprising administration of rituximab or cyclophosphamide. Patients medicated with intense immunotherapy improved more than those who did not receive it. 81% of patients had completely overcome the disease or suffered minimal alterations after 24 months.

It is an unusual fact that the same research team describes a new disease, how to diagnose it, its molecular mechanisms and how to treat it successfully. The group led by Dr. Josep Dalmau is an international reference, at University of Pennsylvania for many years and at IDIBAPS and the Neurology Service of the Hospital Clínic for the last 18 months. Here he and his team work hard in collaboration with Dr. Francesc Graus’ team in identifying new diseases and mechanisms that can trigger autoimmune processes in the brain. Patients admitted to intensive care units, or even in a long term coma, could benefit from this innovative approach. From their new facilities in the CELLEX Biomedical Research Centre, this IDIBAPS research group continues to study synaptic autoimmune diseases thanks to different funding sources, such as the National Institutes of Health (U.S.), the Dutch Cancer Society (Netherlands), Fondo de Investigaciones Sanitarias (Spain) or the Marató de TV3 (Catalonia).

Reference: Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurology. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1.