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

Hans-Christian Hansen, MD; Christine Klingbeil; Josep Dalmau, MD, PhD; Wenhan Li, MD; Benedikt Weißbrich, MD; Klaus-Peter Wandinger, MD
JAMA Neurol. 2013;70(1):117-119. doi:10.1001/jamaneurol.2013.585.
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Background  Anti– N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder characterized by high intrathecal antibody synthesis. Little is known about the long-term follow-up of the cerebrospinal fluid antibody status.

Objective  To describe persistent intrathecal antibody synthesis in a clinically healthy person 15 years after recovering from anti-NMDAR encephalitis.

Design  Case report.

Setting  Academic medical center.

Patient  A 40-year-old woman who had been diagnosed as having encephalitis of unknown origin in 1995.

Main Outcome Measures  Clinical evaluation and NMDAR antibody testing.

Results  On reexamination in 2011, the patient had fully recovered. Investigation of archived as well as follow-up serum and cerebrospinal fluid samples revealed intrathecal synthesis of NMDAR antibodies.

Conclusions  This is the longest follow-up on a patient with anti-NMDAR encephalitis. Our findings emphasize that intrathecal antibody synthesis does not necessarily reflect disease activity and that the significance of NMDAR antibody titers needs to be interpreted for each patient according to the clinical context.

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Figures

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Grahic Jump Location

Figure 1. Time course of clinical features and antibody titers in the cerebrospinal fluid (CSF) and serum. Disease onset in 1995-1996 is associated with high N -methyl-D-aspartate receptor (NMDAR) antibody titers in the CSF and serum, intrathecal antibody synthesis (NMDAR-specific antibody index), lymphocytic pleocytosis, and oligoclonal bands (OCB) in the CSF. Fifteen years after recovery from clinical symptoms, NMDAR antibodies persist in the serum and CSF, with an NMDAR-specific antibody index of 57 reflecting intrathecal antibody synthesis. EEG indicates electroencephalography; MRI, magnetic resonance imaging; and PSWC, periodic sharp wave complexes.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Reactivity of the patient's cerebrospinal fluid at disease onset (A and B) and 15 years thereafter (C and D) and a negative control (E and F). Comparisons of the immunofluorescence pattern on hippocampal sections of mouse brain (A, C, and E; original magnification ×50) and NR1-transfected cells (B, D, and F; original magnification ×200; insets, original magnification ×400) are shown.

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