Liba Z, Sebronova V, Komarek V, Sediva A, Sedlacek P. Lancet Neurology. 2013 May;12(5):424–5. doi: 10.1016/S1474-4422(13)70070-X. IF: 23.917
Department of Paediatric Neurology
We have been treating an 8-year-old girl with anti-NMDAR encephalitis for more than 1 year. The disease manifested with movement disorder mimicking polyradiculomyelitis. During the first week of hospital admission, the girl received intravenous immunoglobulin with no clinical response. Within 3 weeks, she developed deep coma with autonomic instability. Her serum and CSF were positive for anti-NMDAR antibodies. Plasma exchange and high-dose corticosteroids were immediately applied, followed by rituximab, with no effect. Therefore, cyclophosphamide treatment was started of which she received seven cycles. Three cycles stabilised her autonomic system, but she developed intractable motor restlessness and remained in coma. Four subsequent cycles were strengthened by removal of antibodies from peripheral blood with immunoadsorptions; nevertheless, the girl's neurological status remained unchanged.
After 9 months of thorough treatment and intensive care, we changed our therapeutic approach. With a focus on the pathogenesis of the disease, we decided to use alemtuzumab, an anti-CD52 monoclonal antibody that affects memory B cells and T cells. Alemtuzumab has previously been used in oncology, patients receiving transplants, and in clinical trials in adults with multiple sclerosis. To our knowledge, this drug had not been used to treat severe anti-NMDAR encephalitis. Therefore, approval from our hospital, the University Hospital Ethics Committee, and the State Institute for Drug Control had to be obtained, together with informed parental consent.
To support immunosupression behind the blood-brain barrier, we gave the patient both a 1 mg/kg total dose of intravenous alemtuzumab, and intrathecal methotrexate. Aimless restlessness ceased within a few days after this treatment. The patient gradually began to be more perceptive and, 4 weeks after treatment, she surprised the staff with a short purposeful reaction.
The effect of alemtuzumab on memory B cells and T cells in peripheral blood persisted and we thus repeated intrathecal methotrexate. 7 weeks after treatment with alemtuzumab, and after almost 12 months in the coma, the patient suddenly woke up. Despite still being severely immunocompromised, she is doing well and her cognitive functions are restored. At present she has gait difficulties, has tremor in the hands, and is emotionally instable. We will continue with long-term immunosuppressive therapy with mycophenolatemophetil, symptomatic treatment, and physiotherapy.
We hope that our experience with this patient will bring some hope to those patients with anti-NMDAR encephalitis who survive with severe neurological disability, and to the people who care for them.
