• Frank Leypoldt, Romana Höftberger, Maarten J Titulaer, Thaís Armangue, Nuria Gresa-Arribas, Holger Jahn, Kevin Rostásy, Wolfgang Schlumberger, Thomas Meyer, Klaus-Peter Wandinger, Myrna R Rosenfeld, Francesc Graus, and Josep Dalmau.
• August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Service of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain2Institute of Clinical Chemistry, Neuroimmunology Unit, Department of Neurology, University Medical Center Schleswi.
• JAMA Neurol. 2015 Feb 1; 72 (2): 180-6.

ImportanceAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable autoimmune encephalitis affecting mainly young adults and children. The lack of suitable biomarkers of disease activity makes treatment decisions and identification of relapses challenging.ObjectiveTo determine the levels of the B-cell-attracting C-X-C motif chemokine 13 (CXCL13) in serum samples and cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis and whether they can be used as biomarkers of treatment response and outcome.Design, Settings, And ParticipantsRetrospective cohort study of 167 patients consecutively diagnosed as having anti-NMDAR encephalitis between May 1, 2008, and January 31, 2013. Concentration of CXCL13 was determined with enzyme-linked immunosorbent assay in all available patients' samples (272 CSF and 55 serum samples). Samples from 25 patients with noninflammatory neurological disorders and 9 with neuroborreliosis served as controls. Expression of CXCL13 in the brain biopsy of a patient with anti-NMDAR encephalitis was determined by immunohistochemistry.Main Outcomes And MeasuresPercentage of patients with anti-NMDAR encephalitis and elevated CXCL13 in CSF.ResultsCompared with control individuals, 70% of patients with early-stage anti-NMDAR encephalitis had increased CXCL13 in CSF (>7 pg/mL; P < .001) but none in serum samples (>1047 pg/mL; P > .99). High concentration of CSF CXCL13 was associated with the presence of prodromal fever or headache (P = .01), limited response to therapy (P = .003), clinical relapses (P = .03), and intrathecal NMDAR-antibody synthesis (P < .001). Among patients with monophasic disease assessed 2 to 6 months after starting treatment, 10 of 15 with limited treatment response vs 0 of 13 with favorable response had increased CSF CXCL13 (specificity, 100%; 95% CI, 75-100 and sensitivity, 67%; 95% CI, 38-88; P = .02). Six of 12 patients had elevated CSF CXCL13 at relapse including 3 with previously normal levels. In brain, abundant mononuclear cells in perivascular infiltrates and scattered intraparenchymal microglia expressed CXCL13.Conclusions And RelevanceSeventy percent of patients with early-stage anti-NMDAR encephalitis had increased CSF CXCL13 concentration that correlated with intrathecal NMDAR-antibody synthesis. Prolonged or secondary elevation of CXCL13 was associated with limited response to treatment and relapses. CXCL13 is a potentially useful biomarker of treatment response and outcome in anti-NMDAR encephalitis.

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