Open Access Highly Accessed Research article

In vitro neuronal network activity in NMDA receptor encephalitis

Sabine U Jantzen1*, Stefano Ferrea23, Claudia Wach23, Kim Quasthoff2, Sebastian Illes2, Dag Scherfeld2, Hans-Peter Hartung2, Rüdiger J Seitz2 and Marcel Dihné2

Author Affiliations

1 Department of Neurology, LVR-Klinikum Duesseldorf, Bergische Landstrasse 2, 40629, Duesseldorf, Germany

2 Department of Neurology, Medical Faculty, Heinrich-Heine University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany

3 Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine, University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany

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BMC Neuroscience 2013, 14:17  doi:10.1186/1471-2202-14-17

Published: 5 February 2013

Abstract

Background

Anti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR) and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma.

Results

We describe effects of cerebrospinal fluid (CSF) from an anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patient on in vitro neuronal network activity (ivNNA). In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA) system.

The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF) taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease.

Conclusion

Patient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.

Keywords:
Autoimmune disease; Encephalitis; Neuropsychological assessment; Paraneoplastic syndrome; Anti-NMDA-antibody