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Neurological Review |

Diagnostic and Pathogenic Significance of Glutamate Receptor Autoantibodies FREE

David Pleasure, MD
[+] Author Affiliations

Author Affiliation:Departments of Neurology and Pediatrics, University of California, Davis, School of Medicine, Sacramento.


Section Editor: David E. Pleasure, MD

More Author Information
Arch Neurol. 2008;65(5):589-592. doi:10.1001/archneur.65.5.589.
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Published online

Autoantibodies against glutamate receptors, first reported in Rasmussen encephalitis, have been observed in other focal epilepsies, central nervous system ischemic infarcts, transient ischemic attacks, sporadic olivopontocerebellar atrophy, systemic lupus erythematosus, and paraneoplastic encephalopathies. The detection of glutamate receptor autoantibodies is not useful in the evaluation of Rasmussen encephalitis but may be a biomarker for brain ischemia, and it is helpful in diagnosing certain paraneoplastic encephalopathies. Passive transfer of glutamate receptor autoantibodies from patients with systemic lupus erythematosus or paraneoplastic encephalopathy suggests that glutamate receptor autoantibodies can actively contribute to neurologic dysfunction.

More than 100 autoantibodies that recognize known antigens have been documented in human diseases, and many of these autoantibody-associated diseases involve the nervous system. Some autoantibodies (eg, those against nicotinic acetylcholine receptors in myasthenia gravis) have been established as the proximate cause of neurologic deficits. Others (eg, anti-HuD in paraneoplastic encephalomyelitis), although not known to be pathogenic, are helpful in differential diagnosis.1

In 1994, autoantibodies against the ionotropic glutamate receptor protein GluR3 were reported in 3 of 4 children with Rasmussen encephalitis.2Plasma exchange resulted in transient improvement in seizure control and cognition in 1 of the 3 autoantibody-positive children. Since that initial article, plasma and cerebrospinal fluid autoantibodies that recognize GluR3 and other glutamate receptor proteins have been described in focal epilepsies, systemic lupus erythematosus (SLE), central nervous system (CNS) ischemia, and paraneoplastic encephalopathies. We discuss the diagnostic utility and pathophysiologic significance of these autoantibodies.

Glutamate receptors transduce excitatory signals from glutamatergic presynaptic terminals to postsynaptic neurons. Glutamate receptors are also expressed by nonneuronal cells, including neuroglia and T lymphocytes, where, as in neurons, they serve to convey glutamate signals across the plasma membrane. Glutamate receptors are classified into 2 broad groups based on their structures and modes of operation: ionotropic glutamate receptors are heterotetrameric or homotetrameric channels that are opened by glutamate, thus causing sodium influx and plasma membrane depolarization, and metabotropic glutamate receptors are plasma membrane homodimers that modulate enzyme and channel functions and gene transcription via second messenger–dependent mechanisms. The composition and some properties of these receptors are outlined in Table 1.

Table Graphic Jump LocationTable 1. Glutamate Receptor Protein Subunit Composition and Properties

Table 2summarizes the neurologic disorders in which GluR autoantibodies have been reported. Since the initial publication by Rogers et al,2the case for an association between Rasmussen encephalitis and GluR3 autoantibodies has been weakened by the failure to detect GluR3 antibodies in many patients who meet the clinical and pathologic criteria for diagnosis of this disorder and by the demonstration of GluR3 autoantibodies in patients with noninflammatory focal epilepsies.37Serum and cerebrospinal fluid NR2B autoantibodies have been reported in patients with Rasmussen encephalitis and were found in other forms of chronic epilepsia partialis continua and in nonherpetic acute limbic encephalitis but not in patients with the Lennox-Gastaut syndrome or infantile spasms (West syndrome). In patients in whom serial autoantibody assays were available, IgM antibodies appeared after the onset of seizures and later became undetectable.8,9NR2A/NR2B autoantibodies are detectable in more than a third of patients with SLE.10,11Whether titers of these autoantibodies correlate with abnormalities in cognition and other neuropsychiatric complications of SLE remains controversial.1116

Table Graphic Jump LocationTable 2. Glutamate Receptor Autoantibodies Reported in Human Neurologic Disorders

Elevated titers of IgG autoantibodies against an NR2A/NR2B peptide have been reported in patients with acute ischemic infarction or transient ischemic attack. These autoantibodies were not present in patients with intracerebral hemorrhage or hypertension without neurologic deficits. There was a strong correlation between antibody titer and severity of neurologic deficits in the ischemic infarction group.17The same laboratory has subsequently reported that an elevated preoperative titer of NR2 autoantibodies was highly predictive of poor neurologic outcome after cardiac surgery in high-risk surgical patients.18These results suggest that N-methyl-D-aspartate receptor autoantibodies are biomarkers for CNS ischemia, but this requires confirmation by other laboratories. Furthermore, the 2-fold increase in IgG autoantibody titers within 12 hours after admission to the intensive stroke unit that these investigators reported in patients with ischemic infarction17seems unusually rapid for even a memory B-cell antibody response.

Autoantibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) subunit proteins GluR1 and GluR4, the kainate receptor subunit protein GluR5, the N-methyl-D-aspartate receptor NR1/NR2 heteromers, and the metabotropic receptor subunit protein mGluR1 have been well characterized in paraneoplastic syndromes.1922Antibodies that bound to NR1/NR2B heteromers but not to individual N-methyl-D-aspartate receptor subunit proteins were found in the serum samples and cerebrospinal fluid of 12 women with teratomas and paraneoplastic encephalitis but not in patients with other paraneoplastic and nonparaneoplastic forms of encephalitis.22

Whereas CNS-specific antigens are normally shielded from the systemic immune system, infarction and other pathologic processes in which cellular necrosis occurs could result in the release of antigenic glutamate receptor peptides from the CNS for processing by the peripheral immune system. In Rasmussen encephalitis and other inflammatory disorders, release of glutamate receptor antigens to the periphery might not be required. Instead, antigen presentation and autoantibody production could be initiated by immune cells already resident in the CNS. Peripheral tissues may also provide glutamate receptor peptides to antigen-presenting cells. For example, T lymphocytes express GluR3-containing AMPARs, and their GluR3 undergoes proteolytic cleavage during T-lymphocyte activation.23In the paraneoplastic encephalopathy associated with ovarian teratomas, glutamate receptors expressed by neurons in the teratomas may serve as the source of N-methyl-D-aspartate receptor heteromers for autoantibody production.22Finally, glutamate receptor autoantibody production might be a result of molecular mimicry. This phenomenon has been well documented in mice that develop autoantibodies against multiple AMPAR subunit proteins when infected with murine leukemia virus.24A well-documented example in rabbits and mice that may occur in humans with SLE is the production of autoantibodies that recognize double-stranded DNA epitopes and NR2A/NR2B after sensitization to an NR2 peptide.10,14,25,26

Are glutamate receptor autoantibodies pathogenic? Animal studies suggest that they can be. Rabbits immunized with an NR2B or GluR3 peptide develop seizures, and rabbit GluR3 autoantibodies can activate AMPARs expressed by transfected oocytes and cultured neuronal AMPARs and kill the cultured neurons by means of a complement-dependent mechanism.2,2729Mouse anti-GluR3 peptide antibodies activate AMPARs and induce excitotoxicity in cultured neurons,30and mice immunized with either NR2/NR3 or GluR3 peptides demonstrate CNS neuronal loss in vivo.26,30One study31argues that glutamate receptor antibodies can also be neuroprotective; rats expressing high-titer NR1 autoantibodies were refractory to kainate-induced seizures and were partially protected against forebrain ischemic infarction. This observation requires confirmation by other laboratories.

With respect to the pathogenicity of human glutamate receptor autoantibodies, more than a decade has passed since the initial report of a therapeutic response to plasma exchange in Rasmussen syndrome, but support for the pathogenicity of glutamate receptor autoantibodies in this disorder is still equivocal. Many patients with Rasmussen encephalitis do not have detectable GluR3 autoantibodies, and a consensus has not yet been reached as to whether progressive CNS damage in this disorder is mediated by autoantibodies, pathogenic T lymphocytes, or both.32

There is preliminary evidence of the neuropathogenicity of glutamate receptor autoantibodies in SLE, sporadic olivopontocerebellar atrophy, and paraneoplastic encephalopathies. Stereotaxic injection of autoantibodies prepared from the brain specimen of a patient with SLE and severe encephalopathy killed mouse hippocampal neurons.14Encephalopathic patients with NR2A/NR2B autoantibodies showed diffusion-weighted imaging abnormalities in the amygdala that were not present in encephalopathic patients who do not express this class of autoantibodies.13GluR2 autoantibodies from a patient with sporadic olivopontocerebellar atrophy activated AMPARs in cultured mouse neurons,33and GluR5 autoantibodies from a group of patients with paraneoplastic encephalopathy activated kainate receptor–mediated currents,19thus suggesting that these autoantibodies are capable of inducing neuronal excitotoxicity. Perhaps the strongest evidence of a pathophysiologic role for glutamate receptor autoantibodies was obtained in 2 patients who, while in remission from Hodgkin disease, developed severe cerebellar ataxia and expressed mGluR1 autoantibodies that blocked glutamate-induced inositol phosphate formation. These autoantibodies, when administered intrathecally to mice, elicited reversible ataxia.20,21

Correspondence:David Pleasure, MD, University of California, Davis, School of Medicine, c/o Shriners Hospital Northern California, 2425 Stockton Blvd, Sacramento, CA 95817 (david.pleasure@ucdmc.ucdavis.edu).

Accepted for Publication:August 8, 2007.

Financial Disclosure:None reported.

Funding/Support:This study was supported by grant RO1 NS25044 from the National Institutes of Health.

Vincent  ALang  BKleopa  KA Autoimmune channelopathies and related neurological disorders. Neuron 2006;52 (1) 123- 138
PubMed
Rogers  SWAndrews  PIGahring  LC  et al.  Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science 1994;265 (5172) 648- 651
PubMed
Wiendl  HBien  CGBernaconi  P  et al.  GluR3 antibodies: prevalence in focal epilepsy, but no specificity for Rasmussen's encephalitis. Neurology 2001;57 (8) 1511- 1514
PubMed
Mantegazza  RBernasconi  PBaggi  F  et al.  Antibodies against GluR3 peptides are not specific for Rasmussen's encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol 2002;131 (1-2) 179- 185
PubMed
Watson  RJiang  YBermudez  I  et al.  Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen's encephalitis. Neurology 2004;63 (1) 43- 50
PubMed
Ganor  YGoldberg-Stern  HLerman-Sagie  T  et al.  Autoimmune epilepsy: distinct subpopulations of epilepsy patients harbor serum autoantibodies to either glutamate/AMPA receptor GluR3, glutamate/NMDA receptor subunit NR2A or double-stranded DNA. Epilepsy Res 2005;65 (1-2) 11- 22
PubMed
Kimura  ASakurai  TSuzuki  Y  et al.  Autoantibodies against glutamate receptor ε2-subunit detected in a subgroup of patients with reversible autoimmune limbic encephalitis. Eur Neurol 2007;58 (3) 152- 158
PubMed
Takahashi  YMori  HMishina  M  et al.  Autoantibodies to NMDA receptor in patients with chronic forms of epilepsia partialis continua. Neurology 2003;61 (7) 891- 896
PubMed
Mochizuki  YMizutani  TIsozaki  E  et al.  Acute limbic encephalitis: a new entity? Neurosci Lett 2006;394 (1) 5- 8
PubMed
DeGiorgio  LAKnostantinov  KNLee  SC  et al.  A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 2001;7 (11) 1189- 1193
PubMed
Husebye  ESSthoeger  ZMDayan  M  et al.  Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann Rheum Dis 2005;64 (8) 1210- 1213
PubMed
Yoshio  TOnda  KNara  HMinota  S Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2006;54 (2) 675- 681
PubMed
Emmer  BJvan der Grond  JSteup-Beekman  GMHuizinga  TWvan Buchem  MA Selective involvement of the amygdala in systemic lupus erythematosus. PLoS Med 2006;3 (12) e499
PubMed10.1371/journal.pmed.0030499
Kowal  CDeGiorgio  LALee  JY  et al.  Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 2006;103 (52) 19854- 19859
PubMed
Lapteva  LNowak  MYarboro  CH  et al.  Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 2006;54 (8) 2505- 2514
PubMed
Steup-Beekman  GSteens  Svan Buchem  MHuizinga  T Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 2007;16 (5) 329- 334
PubMed
Dambinova  SAKhounteev  GAIzykenova  GA  et al.  Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem 2003;49 (10) 1752- 1762
PubMed
Bokesch  PMIzykenova  GAJustice  JB  et al.  NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke 2006;37 (6) 1432- 1436
PubMed
Carlson  NGGahring  LCRogers  SW Identification of the amino acids on a neuronal glutamate receptor recognized by an autoantibody from a patient with paraneoplastic syndrome. J Neurosci Res 2001;63 (6) 480- 485
PubMed
Coesmans  MSillevis Smitt  PALinden  DJ  et al.  Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol 2003;53 (3) 325- 336
PubMed
Sillevis Smitt  PKinoshita  ADe Leeuw  B  et al.  Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 2000;342 (1) 21- 27
PubMed
Dalmau  JTüzün  EWu  H-Y  et al.  Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61 (1) 25- 36
PubMed
Ganor  YTeichberg  VILevite  M TCR activation eliminates glutamate receptor GluR3 from the cell surface of normal human T cells, via an autocrine/paracrine granzyme B-mediated proteolytic cleavage. J Immunol 2007;178 (2) 683- 692
PubMed
Koustova  ESei  YFossom  L  et al.  LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. J Clin Invest 2001;107 (6) 737- 744
PubMed
Rai  GRay  SShaw  RE  et al.  Models of systemic lupus erythematosus: development of autoimmunity following peptide immunizations of noninbred pedigreed rabbits. J Immunol 2006;176 (1) 660- 667
PubMed
Huerta  PTKowal  CDeGiorgio  LA  et al.  Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A 2006;103 (3) 678- 683
PubMed
Cohen-Kashi Malina  KGanor  YLevite  MTeichberg  VI Autoantibodies against an extracellular peptide of the GluR3 subtype of AMPA receptors activate both homomeric and heteromeric AMPA receptor channels. Neurochem Res 2006;31 (10) 1181- 1190
PubMed
He  X-PPatel  MWhitney  KD  et al.  Glutamate receptor GluR3 antibodies and death of cortical cells. Neuron 1998;20 (1) 153- 163
PubMed
Levite  MFleidervish  IASchwarz  A  et al.  Autoantibodies to the glutamate receptor kill neurons via activation of the receptor ion channel. J Autoimmun 1999;13 (1) 61- 72
PubMed
Ganor  YGottlieb  MEilam  R  et al.  Immunization with the glutamate receptor-derived peptide GluR3B induces neuronal death and reactive gliosis, but confers partial protection from pentylenetetrazole-induced seizures. Exp Neurol 2005;195 (1) 92- 102
PubMed
During  MJSymes  CWLawlor  PA  et al.  An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science 2000;287 (5457) 1453- 1460
PubMed
Bien  CGGranata  TAntozzi  C  et al.  Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005;128 (pt 3) 454- 471
PubMed
Gahring  LCRogers  SWTwyman  RE Autoantibodies to glutamate receptor subunit GluR2 in nonfamilial olivopontocerebellar degeneration. Neurology 1997;48 (2) 494- 500
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Glutamate Receptor Protein Subunit Composition and Properties
Table Graphic Jump LocationTable 2. Glutamate Receptor Autoantibodies Reported in Human Neurologic Disorders

References

Vincent  ALang  BKleopa  KA Autoimmune channelopathies and related neurological disorders. Neuron 2006;52 (1) 123- 138
PubMed
Rogers  SWAndrews  PIGahring  LC  et al.  Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science 1994;265 (5172) 648- 651
PubMed
Wiendl  HBien  CGBernaconi  P  et al.  GluR3 antibodies: prevalence in focal epilepsy, but no specificity for Rasmussen's encephalitis. Neurology 2001;57 (8) 1511- 1514
PubMed
Mantegazza  RBernasconi  PBaggi  F  et al.  Antibodies against GluR3 peptides are not specific for Rasmussen's encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol 2002;131 (1-2) 179- 185
PubMed
Watson  RJiang  YBermudez  I  et al.  Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen's encephalitis. Neurology 2004;63 (1) 43- 50
PubMed
Ganor  YGoldberg-Stern  HLerman-Sagie  T  et al.  Autoimmune epilepsy: distinct subpopulations of epilepsy patients harbor serum autoantibodies to either glutamate/AMPA receptor GluR3, glutamate/NMDA receptor subunit NR2A or double-stranded DNA. Epilepsy Res 2005;65 (1-2) 11- 22
PubMed
Kimura  ASakurai  TSuzuki  Y  et al.  Autoantibodies against glutamate receptor ε2-subunit detected in a subgroup of patients with reversible autoimmune limbic encephalitis. Eur Neurol 2007;58 (3) 152- 158
PubMed
Takahashi  YMori  HMishina  M  et al.  Autoantibodies to NMDA receptor in patients with chronic forms of epilepsia partialis continua. Neurology 2003;61 (7) 891- 896
PubMed
Mochizuki  YMizutani  TIsozaki  E  et al.  Acute limbic encephalitis: a new entity? Neurosci Lett 2006;394 (1) 5- 8
PubMed
DeGiorgio  LAKnostantinov  KNLee  SC  et al.  A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 2001;7 (11) 1189- 1193
PubMed
Husebye  ESSthoeger  ZMDayan  M  et al.  Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann Rheum Dis 2005;64 (8) 1210- 1213
PubMed
Yoshio  TOnda  KNara  HMinota  S Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 2006;54 (2) 675- 681
PubMed
Emmer  BJvan der Grond  JSteup-Beekman  GMHuizinga  TWvan Buchem  MA Selective involvement of the amygdala in systemic lupus erythematosus. PLoS Med 2006;3 (12) e499
PubMed10.1371/journal.pmed.0030499
Kowal  CDeGiorgio  LALee  JY  et al.  Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 2006;103 (52) 19854- 19859
PubMed
Lapteva  LNowak  MYarboro  CH  et al.  Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 2006;54 (8) 2505- 2514
PubMed
Steup-Beekman  GSteens  Svan Buchem  MHuizinga  T Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 2007;16 (5) 329- 334
PubMed
Dambinova  SAKhounteev  GAIzykenova  GA  et al.  Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. Clin Chem 2003;49 (10) 1752- 1762
PubMed
Bokesch  PMIzykenova  GAJustice  JB  et al.  NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke 2006;37 (6) 1432- 1436
PubMed
Carlson  NGGahring  LCRogers  SW Identification of the amino acids on a neuronal glutamate receptor recognized by an autoantibody from a patient with paraneoplastic syndrome. J Neurosci Res 2001;63 (6) 480- 485
PubMed
Coesmans  MSillevis Smitt  PALinden  DJ  et al.  Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol 2003;53 (3) 325- 336
PubMed
Sillevis Smitt  PKinoshita  ADe Leeuw  B  et al.  Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 2000;342 (1) 21- 27
PubMed
Dalmau  JTüzün  EWu  H-Y  et al.  Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61 (1) 25- 36
PubMed
Ganor  YTeichberg  VILevite  M TCR activation eliminates glutamate receptor GluR3 from the cell surface of normal human T cells, via an autocrine/paracrine granzyme B-mediated proteolytic cleavage. J Immunol 2007;178 (2) 683- 692
PubMed
Koustova  ESei  YFossom  L  et al.  LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. J Clin Invest 2001;107 (6) 737- 744
PubMed
Rai  GRay  SShaw  RE  et al.  Models of systemic lupus erythematosus: development of autoimmunity following peptide immunizations of noninbred pedigreed rabbits. J Immunol 2006;176 (1) 660- 667
PubMed
Huerta  PTKowal  CDeGiorgio  LA  et al.  Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A 2006;103 (3) 678- 683
PubMed
Cohen-Kashi Malina  KGanor  YLevite  MTeichberg  VI Autoantibodies against an extracellular peptide of the GluR3 subtype of AMPA receptors activate both homomeric and heteromeric AMPA receptor channels. Neurochem Res 2006;31 (10) 1181- 1190
PubMed
He  X-PPatel  MWhitney  KD  et al.  Glutamate receptor GluR3 antibodies and death of cortical cells. Neuron 1998;20 (1) 153- 163
PubMed
Levite  MFleidervish  IASchwarz  A  et al.  Autoantibodies to the glutamate receptor kill neurons via activation of the receptor ion channel. J Autoimmun 1999;13 (1) 61- 72
PubMed
Ganor  YGottlieb  MEilam  R  et al.  Immunization with the glutamate receptor-derived peptide GluR3B induces neuronal death and reactive gliosis, but confers partial protection from pentylenetetrazole-induced seizures. Exp Neurol 2005;195 (1) 92- 102
PubMed
During  MJSymes  CWLawlor  PA  et al.  An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science 2000;287 (5457) 1453- 1460
PubMed
Bien  CGGranata  TAntozzi  C  et al.  Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005;128 (pt 3) 454- 471
PubMed
Gahring  LCRogers  SWTwyman  RE Autoantibodies to glutamate receptor subunit GluR2 in nonfamilial olivopontocerebellar degeneration. Neurology 1997;48 (2) 494- 500
PubMed

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