BMC Neuroscience | |
In vitro neuronal network activity in NMDA receptor encephalitis | |
Marcel Dihné1  Rüdiger J Seitz1  Hans-Peter Hartung1  Dag Scherfeld1  Sebastian Illes1  Kim Quasthoff1  Claudia Wach2  Stefano Ferrea2  Sabine U Jantzen3  | |
[1] Department of Neurology, Medical Faculty, Heinrich-Heine University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany;Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine, University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany;Department of Neurology, LVR-Klinikum Duesseldorf, Bergische Landstrasse 2, 40629, Duesseldorf, Germany | |
关键词: Anti-NMDA-antibody; Paraneoplastic syndrome; Neuropsychological assessment; Encephalitis; Autoimmune disease; | |
Others : 1140451 DOI : 10.1186/1471-2202-14-17 |
|
received in 2012-05-24, accepted in 2013-01-30, 发布年份 2013 | |
![]() |
【 摘 要 】
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.
【 授权许可】
2013 Jantzen et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150325022036430.pdf | 1170KB | ![]() |
|
Figure 3. | 48KB | Image | ![]() |
Figure 2. | 56KB | Image | ![]() |
Figure 1. | 68KB | Image | ![]() |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, et al.: Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007, 61(1):25-36.
- [2]Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR: Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008, 7(12):1091-1098.
- [3]Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R: Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011, 10(1):63-74.
- [4]Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, Campen CJ, Moss H, Peter N, Gleichman AJ, et al.: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009, 66(1):11-18.
- [5]Day GS, High SM, Cot B, Tang-Wai DF: Anti-NMDA-receptor encephalitis: case report and literature review of an under-recognized condition. J Gen Intern Med 26(7):811-816.
- [6]Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR, Dalmau J, Balice-Gordon RJ: Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010, 30(17):5866-5875.
- [7]Lau CG, Zukin RS: NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 2007, 8(6):413-426.
- [8]Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS: Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994, 51(3):199-214.
- [9]Weiner AL, Vieira L, McKay CA, Bayer MJ: Ketamine abusers presenting to the emergency department: a case series. J Emerg Med 2000, 18(4):447-451.
- [10]Otto F, Illes S, Opatz J, Laryea M, Theiss S, Hartung HP, Schnitzler A, Siebler M, Dihne M: Cerebrospinal fluid of brain trauma patients inhibits in vitro neuronal network function via NMDA receptors. Ann Neurol 2009, 66(4):546-555.
- [11]Schwarz CS, Ferrea S, Quasthoff K, Walter J, Gorg B, Haussinger D, Schnitzler A, Hartung HP, Dihne M: Ammonium chloride influences in vitro-neuronal network activity. Exp Neurol 235(1):368-373.
- [12]Illes S, Theiss S, Hartung HP, Siebler M, Dihne M: Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations. BMC Neurosci 2009, 10:93. BioMed Central Full Text
- [13]Woolson R: CW: Statistical Methods for the Analysis of Biomedical Data. New York: Wiley-Interscience; 2002.
- [14]Schwarz CS, Ferrea S, Quasthoff K, Walter J, Gorg B, Haussinger D, Schnitzler A, Hartung HP, Dihne M: Ammonium chloride influences in vitro-neuronal network activity. Exp Neurol 2012, 235(1):368-373.
- [15]Illes S, Fleischer W, Siebler M, Hartung HP, Dihne M: Development and pharmacological modulation of embryonic stem cell-derived neuronal network activity. Exp Neurol 2007, 207(1):171-176.