POI06 Rituximab in neuropsychiatric systemic lupus erythematosus: a retrospective study of the Cambridge experience (M Zandi et al, Journal of Neurology, Neurosurgery & Psychiatry, 2010)
Abstract: "The monoclonal B cell depleting antibody, rituximab, has shown promise in open-label studies of refractory neuropsychiatric (NP) lupus. Here, we show our tertiary referral centre experience in patients with CNS syndromes probably causally related to active SLE, and in those with past CNS symptoms treated for non-NP SLE. Consensus criteria proposed by Hanly et al (Arth Rheum 2007) were used to classify patients into those likely to have attributable disease or not. Some patients have been previously reported (Smith et al Arth Rheum 2006). Four patients received rituximab for CNS symptoms attributable to active lupus (two psychosis, one neuropsychiatric syndrome, one neuromyelitis optica). The baseline clinical, imaging and laboratory features, clinical responses and adverse events are reported. A summary is provided of our other patients given rituximab for active non-NP SLE, with previous possible attributable NP disease, including anti-phospholipid syndrome. All patients had other organ disease, received prior and concomitant immunotherapy, and most were retreated. Rituximab appears effective with attributable disease and limited prior damage, with limited effect on symptoms due to static deficits. A randomised, double-blind placebo-controlled trial of rituximab, in patients with early attributable disease and limited established damage, is required. There is also a need to study the natural history of NP involvement in SLE and discover and develop biomarkers to aid attribution."
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N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes (Irani et al, Brain, 2010)
Abstract: "Antibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid, and a quantitative fluorescent immunoprecipitation assay for serial studies. Although there was marked intrathecal synthesis of N-methyl-d-aspartate receptor antibodies, the absolute levels of N-methyl-d-aspartate receptor antibodies were higher in serum than in cerebrospinal fluid. N-methyl-d-aspartate receptor antibodies were of the immunoglobulin G1 subclass and were able to activate complement on N-methyl d-aspartate receptor-expressing human embryonic kidney cells. From questionnaires returned on 44 N-methyl-d-aspartate receptor antibody-positive patients, we identified a high proportion without a detected tumour (35/44, 80%: follow-up 3.6–121 months, median 16 months). Among the latter were 15 adult females (43%), 10 adult males (29%) and 10 children (29%), with four in the first decade of life. Overall, there was a high proportion (29%) of non-Caucasians. Good clinical outcomes, as defined by reductions in modified Rankin scores, correlated with decreased N-methyl-d-aspartate receptor antibody levels and were associated with early" (
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