Persistent Intrathecal Antibody Synthesis 15 Years After Recovering From Anti– N-methyl-D-aspartate Receptor Encephalitis

Hansen, Hans-Christian; Klingbeil, Christine; Dalmau, Josep; Wenhan, Li; Weißbrich, Benedikt; Wandinger, Klaus‐Peter

doi:10.1001/jamaneurol.2013.585

Cited by 68 publications

(54 citation statements)

References 8 publications

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“…Moreover, in patients with a history of anti-NMDAR encephalitis, the development of atypical or partial symptoms accompanied by elevation of CSF CXCL13 suggests a relapse. This is important considering that NMDAR-antibody titers can remain detectable for a long time 5,24 and their change along the course of the disease might be slower than that of CXCL13 levels.…”

Section: Discussionmentioning

confidence: 99%

Investigations on CXCL13 in Anti–N-Methyl-D-Aspartate Receptor Encephalitis

et al. 2015

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IMPORTANCE Anti-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.OBJECTIVE To 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 MEASURES Percentage of patients with anti-NMDAR encephalitis and elevated CXCL13 in CSF.RESULTS Compared 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 RELEVANCE Seventy 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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Section: Discussionmentioning

confidence: 99%

Investigations on CXCL13 in Anti–N-Methyl-D-Aspartate Receptor Encephalitis

et al. 2015

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“…14,19,23 There have been conflicting studies on whether anti-NMDAR antibody titers are associated with disease severity. 18,25 Prior studies examining the presence of anti-NMDAR antibodies in the setting of viral meningoencephalitis have found little to no cross-reactivity, 14,15 though a recent study suggests that an inflammatory cascade in the setting of a viral meningitis could lead to false-positive test results. 26 Early in our patient's course, we suspected that the positive anti-NMDAR antibodies were the result of an inflammatory cascade, which was supported by the nonspecific CSF antineuronal antibody.…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

The Diagnostic Conundrum and Treatment Dilemma of a Patient With a Rapidly Progressive Encephalopathy

Beatty

Creutzfeldt

Davis

et al. 2013

The Neurohospitalist

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“…In anti-neuropil associated AE, unlike antinuclear disorders, antibody titers often correlate with symptomatic improvement [4,93], but they can also decrease with time, even without therapy and irrespectively of clinical outcome [90,94], their levels fluctuate due to immunosupressants (particularly in serum), and they can remain elevated for years after recovery [66,92,95].…”

Section: Diagnostic Approachmentioning

confidence: 99%

Neuropsychiatric symptoms in autoimmune encephalopathies: a clinician’s guide

Carvalho¹,

Massano²,

Coelho³

2014

IJCNMH

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Background: The spectrum of central nervous system autoimmune disorders has recently expanded with the discovery of disorders associated with antibodies directed against the neuronal membrane surface. Although many of these disorders have an underlying malignancy and present with signs of dysfunction of the limbic system (paraneoplastic limbic encephalitis, PLE), a high proportion of cases is non-paraneoplastic. They may occur with milder symptoms, and present no abnormalities in the exams usually used in the investigation of PLE. A striking number of cases may be misdiagnosed as primary psychiatric or other neurological disorders. This paper aims to review the current knowledge on this topic, and provide physicians with an updated text on the neuropsychiatric presentation, diagnostic approach and current management of autoimmune encephalopathies.

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Persistent Intrathecal Antibody Synthesis 15 Years After Recovering From Anti– N-methyl-D-aspartate Receptor Encephalitis

Cited by 68 publications

References 8 publications

Investigations on CXCL13 in Anti–N-Methyl-D-Aspartate Receptor Encephalitis

Investigations on CXCL13 in Anti–N-Methyl-D-Aspartate Receptor Encephalitis

The Diagnostic Conundrum and Treatment Dilemma of a Patient With a Rapidly Progressive Encephalopathy

Neuropsychiatric symptoms in autoimmune encephalopathies: a clinician’s guide

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