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BMC Psychiatry
Published in: BMC Psychiatry 1/2015

Open Access 01-12-2015 | Case report

Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report

Authors: Dominique Endres, Evgeniy Perlov, Oliver Stich, Sebastian Rauer, Simon Maier, Zora Waldkircher, Thomas Lange, Irina Mader, Philipp Tobias Meyer, Ludger Tebartz van Elst

Published in: BMC Psychiatry | Issue 1/2015

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Abstract

Background

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy (1H-MRS).

Case presentation

We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. 1H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET.

Conclusion

This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.
Literature
1.
Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol. 2005;58(4):594–604.CrossRefPubMedPubMedCentral
2.
Dalmau J, Tüzün E, Wu H, Masjuan J, Rossi JE, Voloschin A, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61(1):25–36.CrossRefPubMedPubMedCentral
3.
Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12(2):157–65.CrossRefPubMedPubMedCentral
4.
Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835–44.CrossRefPubMed
5.
Ramanathan S, Mohammad SS, Brilot F, Dale RC. Autoimmune encephalitis: Recent updates and emerging challenges. J Clin Neurosci. 2014;21(5):722–30.CrossRefPubMed
6.
Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091–8.CrossRefPubMedPubMedCentral
7.
Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30(17):5866–75.CrossRefPubMedPubMedCentral
8.
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.CrossRefPubMedPubMedCentral
9.
Bien CG, Bauer J. Pathophysiologie antikörperassoziierter ZNS-Erkrankungen. Nervenarzt. 2013;84(4):466–70.CrossRefPubMed
10.
Prüss H, Dalmau J, Arolt V, Wandinger K. Anti-NMDA-Rezeptor-Enzephalitis. Ein interdisziplinäres Krankheitsbild. Nervenarzt. 2010;81(4):396. 398, 400, passim.CrossRefPubMed
11.
Vincent A, Bien CG, Irani SR, Waters P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol. 2011;10(8):759–72.CrossRefPubMed
12.
Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012;79(11):1094–100.CrossRefPubMedPubMedCentral
13.
14.
Maeder-Ingvar M, Prior JO, Irani SR, Rey V, Vincent A, Rossetti AO. FDG-PET hyperactivity in basal ganglia correlating with clinical course in anti-NDMA-R antibodies encephalitis. J Neurol Neurosurg Psychiatr. 2011;82(2):235–6.CrossRefPubMed
15.
Pillai SC, Gill D, Webster R, Howman-Giles R, Dale RC. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis. Pediatr Neurol. 2010;43(3):217–20.CrossRefPubMed
16.
Llorens V, Gabilondo I, Gómez-Esteban JC, Agundez M, Mendibe M, Bergara JC, et al. Abnormal multifocal cerebral blood flow on Tc-99 m HMPAO SPECT in a patient with anti-NMDA-receptor encephalitis. J Neurol. 2010;257(9):1568–9.CrossRefPubMed
17.
Peery HE, Day GS, Dunn S, Fritzler MJ, Prüss H, de Souza C, et al. Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology. Autoimmun Rev. 2012;11(12):863–72.CrossRefPubMed
18.
Novotny EJ, Fulbright RK, Pearl PL, Gibson KM, Rothman DL. Magnetic resonance spectroscopy of neurotransmitters in human brain. Ann Neurol. 2003;54 Suppl 6:S25–31.CrossRefPubMed
19.
Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000;13(3):129–53.CrossRefPubMed
20.
Ross B, Bluml S. Magnetic resonance spectroscopy of the human brain. Anat Rec. 2001;265(2):54–84.CrossRefPubMed
21.
Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30(6):672–9.CrossRefPubMed
22.
Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14(4):260–4.CrossRefPubMed
23.
Baumgartner A, Rauer S, Mader I, Meyer PT. Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol. 2013;260(11):2744–53.CrossRefPubMed
24.
Leypoldt F, Buchert R, Kleiter I, Marienhagen J, Gelderblom M, Magnus T, et al. Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. J Neurol Neurosurg Psychiatr. 2012;83(7):681–6.CrossRefPubMedPubMedCentral
25.
Sekigawa M, Okumura A, Niijima S, Hayashi M, Tanaka K, Shimizu T. Autoimmune focal encephalitis shows marked hypermetabolism on positron emission tomography. J Pediatr. 2010;156(1):158–60.CrossRefPubMed
26.
Yamamoto S, Koide Y, Fujiwara M, Nakazawa K, Takahashi Y, Hara H. Subacute encephalitis associated with anti-glutamate receptor antibodies: serial studies of MRI, 1H-MRS and SPECT. Rinsho Shinkeigaku. 2008;48(3):196–201.CrossRefPubMed
27.
Kataoka H, Dalmau J, Taoka T, Ueno S. Reduced N-acetylaspartate in the basal ganglia of a patient with anti-NMDA receptor encephalitis. Mov Disord. 2009;24(5):784–6.CrossRefPubMed
28.
Manto M, Dalmau J, Didelot A, Rogemond V, Honnorat J. In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction. Orphanet J Rare Dis. 2010;5:31.CrossRefPubMedPubMedCentral
29.
Tebartz van Elst L, Maier S, Fangmeier T, Endres D, Mueller GT, Nickel K, et al. Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis. Mol Psychiatry. 2014;19(12):1314–25.
30.
van Elst LT, Maier S, Fangmeier T, Endres D, Mueller GT, Nickel K, et al. Magnetic resonance spectroscopy comparing adults with high functioning autism and above average IQ. Mol Psychiatry. 2014;19(12):1251.
31.
Tebartz van Elst L, Krishnamoorthy ES, Schulze-Bonhage A, Altenmüller D, Richter H, Ebert D, et al. Local area network inhibition: a model of a potentially important paraepileptic pathomechanism in neuropsychiatric disorders. Epilepsy Behav. 2011;22(2):231–9.
32.
Doelken MT, Mennecke A, Stadlbauer A, Kecskeméti L, Kasper BS, Struffert T, et al. Multi-voxel magnetic resonance spectroscopy at 3 T in patients with idiopathic generalised epilepsy. Seizure. 2010;19(8):485–92.CrossRefPubMed
33.
Zahr NM, Crawford ELF, Hsu O, Vinco S, Mayer D, Rohlfing T, et al. In vivo glutamate decline associated with kainic acid-induced status epilepticus. Brain Res. 2009;1300:65–78.CrossRefPubMedPubMedCentral
34.
Takaki J, Fujimori K, Miura M, Suzuki T, Sekino Y, Sato K. L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the 'collusion' hypothesis for increased extracellular L-glutamate concentration in neuroinflammation. J Neuroinflammation. 2012;9:275.CrossRefPubMedPubMedCentral
35.
Chang L, Munsaka SM, Kraft-Terry S, Ernst T. Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain. J Neuroimmune Pharmacol. 2013;8(3):576–93.CrossRefPubMedPubMedCentral
Metadata
Title
Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report
Authors
Dominique Endres
Evgeniy Perlov
Oliver Stich
Sebastian Rauer
Simon Maier
Zora Waldkircher
Thomas Lange
Irina Mader
Philipp Tobias Meyer
Ludger Tebartz van Elst
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2015
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-015-0552-4

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