Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Open accessAbstract
Summary Background A severe form of encephalitis associated with antibodies against NR1–NR2 heteromers of the NMDA receptor was recently identified. We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures. Methods We describe the clinical characteristics of 100 patients with encephalitis and NR1–NR2 antibodies. HEK293 cells ectopically expressing single or assembled NR1–NR2 subunits were used to determine the epitope targeted by the antibodies. Antibody titres were measured with ELISA. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Findings Median age of patients was 23 years (range 5–76 years); 91 were women. All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation. 58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma. Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) and fewer neurological relapses (p=0.009) than the rest of the patients. 75 patients recovered or had mild deficits and 25 had severe deficits or died. Improvement was associated with a decrease of serum antibody titres. The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit. Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal. Interpretation A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies.
AI snapshot
Written from the paper’s full text.
TL;DR
This case series characterizes 100 patients with anti-NMDA-receptor encephalitis and shows that antibodies target the extracellular N-terminal domain of NR1, reduce cell-surface NMDA receptors and postsynaptic receptor clusters, and that early tumour treatment is associated with better outcome and fewer relapses. The disorder is severe but often reversible, with 75 patients recovering or having mild deficits and 25 having severe deficits or dying.
Key findings
- Among 100 patients, median age was 23 years (range 5–76) and 91 were women; all presented with psychiatric symptoms or memory problems, 76 had seizures, 88 unresponsiveness, 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.
- 58 (59%) of 98 assessed patients had tumours, most commonly ovarian teratoma; early tumour treatment was associated with better outcome (p=0.004) and fewer neurological relapses (p=0.009) than in other patients.
- 75 patients recovered or had mild deficits and 25 had severe deficits or died; improvement was associated with a decrease in serum antibody titres.
- Patients’ antibodies mainly targeted the extracellular N-terminal domain of NR1 and decreased cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect reversed by antibody removal.
Methods
- Observational case series of 100 patients with encephalitis and NR1–NR2 antibodies; clinical information was obtained by authors or referring physicians, with control samples from 20 healthy individuals and 230 patients with suspected autoimmune or paraneoplastic encephalitis or tumours without encephalitis.
- HEK293 cells expressing single or assembled NR1–NR2 subunits were used to map the antibody epitope; antibody titres were measured by ELISA, and effects on neuronal cultures were assessed by quantitative confocal analysis of NMDA-receptor clusters and by biotinylation/immunoblot of cell-surface NR1.
- Statistical analyses used Fisher’s two-sided exact test, Kruskal-Wallis and Wilcoxon rank-sum tests with Bonferroni correction, and Kruskal-Wallis non-parametric ANOVA with Dunn’s pairwise comparison.
Limitations
- The paper states that follow-up CSF titres were not obtained in most patients after improvement, and that future studies should clarify the best type and duration of immunotherapy, the role of prodromal events, and the molecular mechanisms decreasing NMDA receptors.
- Evident from the text: this is an observational case series without randomized treatment allocation, so associations between early tumour treatment and outcome may be confounded; some clinical and laboratory data are reported as “data not shown.”
- Evident from the text: the pathogenic evidence relies partly on in-vitro rat hippocampal neuronal cultures and HEK293 assays, which may not fully capture human disease mechanisms.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 27 cited sources checked · 0 supported · 0 flagged
- Findingown data
76 of the 100 patients with anti-NMDA-receptor encephalitis had seizures.
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
- Also stated in: § Results · plain
“During the first 3 weeks of symptom presentation, 76 patients had seizures.”
Quote in the paperNot a substantial claim - Also stated in: § Results · plain
- Findingown data
91 of the 100 patients with anti-NMDA-receptor encephalitis were women.
“Median age of patients was 23 years (range 5–76 years); 91 were women.”
Quote in the paperNot a substantial claim - Findingown data
The median age of the 100 patients with anti-NMDA-receptor encephalitis was 23 years (range 5-76 years).
“Median age of patients was 23 years (range 5–76 years); 91 were women.”
Quote in the paperNot a substantial claim - Findingown data
All 100 patients with anti-NMDA-receptor encephalitis presented with psychiatric symptoms or memory problems.
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
Quote in the paperNot a substantial claim - Findingown data
77% of the 92 patients with extensive EEG monitoring had generalised or predominantly frontotemporal slow or disorganised activity (delta-theta) without epileptic discharges.
“92 patients had extensive EEG monitoring, 77% had generalised or predominantly frontotemporal slow or disorganised activity (delta-theta) without epileptic discharges.”
Quote in the paperNot a substantial claim
- Findingown data
20 (27%) of the patients had prominent sleep dysfunction, including hypersomnia and inversion of sleep patterns.
“20 (27%) had prominent sleep dysfunction, including hypersomnia and inversion of sleep patterns.”
Quote in the paperNot a substantial claim - Findingown data
23 patients presented with short-term memory loss or seizures alone or associated with psychiatric manifestations.
“23 presented with short-term memory loss or seizures alone or associated with psychiatric manifestations.”
Quote in the paperNot a substantial claim - Findingown data
The median duration of hospitalisation was 2.5 months (range 1-14 months).
“The median duration of hospitalisation was 2.5 months (range 1–14 months).”
Quote in the paperNot a substantial claim - Findingown data
In six patients, the tumour was diagnosed after recovery from the encephalitis (56-380 months).
“In six patients, the tumour was diagnosed after recovery from the encephalitis (56–380 months).”
Quote in the paperNot a substantial claim - Findingown data
The main epitope targeted by anti-NMDA-receptor antibodies is in the extracellular N-terminal domain of the NR1 subunit.
“The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit.”
- Also stated in: § Results · plain
“Hence the main epitope region recognised by all patients’ antibodies lies within the extracellular region of the NR1 subunit (webtable 3).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
Patients with anti-NMDA-receptor encephalitis who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) than the rest of the patients.
“Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) and fewer neurological relapses (p=0.009) than the rest of the patients.”
- Also stated in: § Results · plain
“Patients whose tumour was identified and removed within the first 4 months of the onset of the neurological disease had better outcome than the rest of the patients (figure 2).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
The most common tumour in patients with anti-NMDA-receptor encephalitis was ovarian teratoma.
“58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma.”
Quote in the paperNot a substantial claim - Findingown data
Follow-up studies in 70 patients showed that many of those who recovered or were left with mild deficits had improved or normalised MRI.
“Follow-up studies in 70 patients showed that many of those who recovered or were left with mild deficits had improved or normalised MRI (webappendix).”
Quote in the paperNot a substantial claim - Findingown data
Improvement in patients with anti-NMDA-receptor encephalitis was associated with a decrease of serum antibody titres.
“Improvement was associated with a decrease of serum antibody titres.”
Quote in the paperSubstantial claim - Findingown data
58 (59%) of 98 patients with anti-NMDA-receptor encephalitis for whom oncological assessments were available had tumours.
“58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma.”
- Also stated in: § Results · plain
“58 (59%) of 98 patients had a neoplasm (table 2); two died before tumour assessment.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
66 of the 100 patients with anti-NMDA-receptor encephalitis had hypoventilation.
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
Quote in the paperNot a substantial claim - Findingown data
The effect of patients' antibodies on NMDA receptors could be reversed by antibody removal.
“Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal.”
Quote in the paperSubstantial claim - Findingown data
77 patients presented with prominent psychiatric symptoms, including anxiety, agitation, bizarre behaviour, delusional or paranoid thoughts, and visual or auditory hallucinations.
“77 patients presented with prominent psychiatric symptoms, including anxiety, agitation, bizarre behaviour, delusional or paranoid thoughts, and visual or auditory hallucinations.”
Quote in the paperNot a substantial claim - Findingown data
Patients with anti-NMDA-receptor encephalitis who received early tumour treatment had fewer neurological relapses (p=0.009) than the rest of the patients.
“Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) and fewer neurological relapses (p=0.009) than the rest of the patients.”
- Also stated in: § Results · plain
“Relapses were less common in patients with early tumour treatment (1 of 36) than in other patients (14 of 64; p=0.009), including patients whose tumour was treated late (six of 22; p=0.009) and patients without tumour (eight of 42; p=0.03).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
25 of the 100 patients with anti-NMDA-receptor encephalitis had severe deficits or died.
“75 patients recovered or had mild deficits and 25 had severe deficits or died.”
Quote in the paperNot a substantial claim - Findingown data
75 of the 100 patients with anti-NMDA-receptor encephalitis recovered or had mild deficits.
“75 patients recovered or had mild deficits and 25 had severe deficits or died.”
Quote in the paperNot a substantial claim - Findingown data
86 of the 100 patients with anti-NMDA-receptor encephalitis had dyskinesias.
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
Quote in the paperNot a substantial claim - Findingown data
The median time of ventilatory support in patients with anti-NMDA-receptor encephalitis was 8 weeks (range 2-40 weeks).
“During this clinical stage, large proportions of patients developed dyskinesias, autonomic instability, and central hypoventilation (median time of ventilatory support, 8 weeks; range 2–40 weeks).”
Quote in the paperNot a substantial claim - Findingown data
Ovarian teratoma identified with CT, MRI, or ultrasound was a common tumour type (median size 6 cm, range 1-22 cm).
“Ovarian teratoma identified with CT, MRI, or ultrasound was a common tumour type (median size 6 cm, range 1–22 cm).”
Quote in the paperNot a substantial claim - Findingown data
55 of the 100 patients had increased signal on MRI fluid-attenuated inversion recovery or T2 sequences.
“Of the 100 patients, 55 had increased signal on MRI fluid-attenuated inversion recovery or T2 sequences; 14 of these patients had faint or transient contrast enhancement of the cerebral cortex, overlaying meninges, or basal ganglia.”
Quote in the paperNot a substantial claim - Findingown data
After discharge, 64 (85%) of the 75 patients who were left with mild deficits or eventually attained full recovery had signs of frontal-lobe dysfunction including poor attention and planning, impulsivity, and behavioral dysinhibition.
“After discharge, 64 (85%) of the 75 patients who were left with mild deficits or eventually attained full recovery had signs of frontal-lobe dysfunction including poor attention and planning, impulsivity, and behavioral dysinhibition;”
Quote in the paperNot a substantial claim - Findingown data
Patients' antibodies decreased the numbers of cell-surface NMDA receptors.
“Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal.”
Quote in the paperSubstantial claim - Findingown data
88 of the 100 patients with anti-NMDA-receptor encephalitis had unresponsiveness (decreased consciousness).
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
- Also stated in: § Results · plain
“88 patients developed decreased consciousness, progressing to a catatonic-like state, with periods of akinesis alternating with agitation, and diminished or paradoxical responses to stimuli (eg, no response to pain but resisting eye opening).”
Quote in the paperNot a substantial claim - Also stated in: § Results · plain
- Findingown data
Patients' antibodies decreased NMDA-receptor clusters in postsynaptic dendrites.
“Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal.”
Quote in the paperSubstantial claim - Findingown data
86 patients who could be assessed had headache, low-grade fever, or a non-specific viral-like illness within 2 weeks before hospital admission.
“86 patients who could be assessed had headache, low-grade fever, or a non-specific viral-like illness within 2 weeks before hospital admission.”
Quote in the paperNot a substantial claim - Findingown data
14 of the patients with increased MRI signal had faint or transient contrast enhancement of the cerebral cortex, overlaying meninges, or basal ganglia.
“Of the 100 patients, 55 had increased signal on MRI fluid-attenuated inversion recovery or T2 sequences; 14 of these patients had faint or transient contrast enhancement of the cerebral cortex, overlaying meninges, or basal ganglia.”
Quote in the paperNot a substantial claim - Findingown data
69 of the 100 patients with anti-NMDA-receptor encephalitis had autonomic instability.
“All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation.”
Quote in the paperNot a substantial claim - Findingown data
Patients whose tumour was identified and removed within the first 4 months of the onset of the neurological disease had better outcome than the rest of the patients.
“Patients whose tumour was identified and removed within the first 4 months of the onset of the neurological disease had better outcome than the rest of the patients (figure 2).”
Quote in the paperSubstantial claim - Findingown data
Metastases were identified only in one man with immature teratoma of the testis.
“Metastases were identified only in one man with immature teratoma of the testis.”
Quote in the paperNot a substantial claim - Findingown data
All but one of the patients with a neoplasm developed neurological symptoms before the tumour diagnosis (median 8 weeks, range 1-380 weeks).
“All but one of these patients developed neurological symptoms before the tumour diagnosis (median 8 weeks, range 1–380 weeks).”
Quote in the paperNot a substantial claim - Findingown data
The median time between initial presentation and last relapse was 18 months (1-84 months).
“The median time between initial presentation and last relapse was 18 months (1–84 months).”
Quote in the paperNot a substantial claim - Findingown data
Of 58 patients with paired serum and CSF available, 53 had preserved integrity of the blood-brain barrier.
“Of 58 patients with paired serum and CSF available, 53 had preserved integrity of the blood–brainbarrier.”
Quote in the paperSubstantial claim - Findingown data
A characteristic feature of patients who recover from anti-NMDA-receptor encephalitis is a persisting amnesia of the entire process.
“A characteristic feature of patients who recover from anti-NMDA-receptor encephalitis is a persisting amnesia of the entire process (data not shown).”
Quote in the paperNot a substantial claim - Findingown data
All 53 patients with preserved blood-brain barrier integrity had higher concentrations of antibodies in CSF than in sera, indicating intrathecal synthesis of antibodies.
“Analysis of normalized concentrations of IgG showed that all 53 patients had higher concentrations of antibodies in CSF than in sera, indicating intrathecal synthesis of antibodies (figure 3).”
Quote in the paperSubstantial claim - Findingown data
Patients' antibodies labelled nearly all clusters of NMDA receptors.
“Patients’ antibodies labelled nearly all clusters of NMDA receptors (figure 4).”
Quote in the paperSubstantial claim - Findingown data
15 patients had one to three relapses of encephalitis.
“15 patients had one to three relapses of encephalitis (webtable 2).”
Quote in the paperNot a substantial claim - Findingown data
The main epitope region recognised by all patients' antibodies lies within the extracellular region of the NR1 subunit.
“Hence the main epitope region recognised by all patients’ antibodies lies within the extracellular region of the NR1 subunit (webtable 3).”
Quote in the paperSubstantial claim - Findingown data
41% of patients with anti-NMDA-receptor encephalitis do not have a clinically detectable tumour.
“Our study indicates that 41% of patients with anti-NMDA-receptor encephalitis do not have a clinically detectable tumour, and that men and children can also be affected.”
Quote in the paperSubstantial claim - Findingown data
None of the patients was receiving immunotherapy at the time of the neurological relapse.
“None of the patients was receiving immunotherapy at the time of the neurological relapse.”
Quote in the paperSubstantial claim - Findingown data
Patients' antibodies did not change the concentrations of the postsynaptic protein PSD-95.
“Patients’ antibodies did not change the concentrations of the postsynaptic protein PSD-95 (figure 5).”
Quote in the paperSubstantial claim - Findingown data
Neurons treated for 3 days with patients' CSF followed by 4 days with control CSF had similar numbers of clusters of NMDA receptors to those in neurons treated only with control CSF.
“By contrast, neurons treated for 3 days with patients’ CSF followed by 4 days with control CSF had similar numbers of clusters of NMDA receptors to those in neurons treated only with control CSF (figure 5).”
Quote in the paperSubstantial claim - Findingown data
Antibody binding did not cause apoptosis.
“This antibody binding did not cause apoptosis (data not shown).”
Quote in the paperSubstantial claim - Findingown data
Neurons treated with patients' CSF for 3 days or 7 days had fewer clusters of NMDA receptors per length of postsynaptic dendrite than neurons treated with control CSF.
“Neurons treated with patients’ CSF for 3 days or 7 days had fewer clusters of NMDA receptors per length of postsynaptic dendrite than neurons treated with control CSF.”
Quote in the paperSubstantial claim - Findingcitation
13 of 17 patients unresponsive to corticosteroids, plasma exchange, or intravenous immunoglobulin responded to cyclophosphamide, rituximab, or both.
“Furthermore, 13 of 17 patients unresponsive to the above therapies, responded to cyclophosphamide (five), rituximab (six), or both (two; data not shown), drugs that are effective in other immune-mediated disorders of the CNS.29,30”
Quote in the paperSubstantial claim0 of 2 sources checked - Findingown data
Adding patients' IgG to rat hippocampal neuronal cultures produced a concentration-dependent decrease of the cell-surface fraction of NMDA receptors.
“However, adding patients’ IgG to rat hippocampal neuronal cultures produced a concentration-dependent decrease of the cell-surface fraction of NMDA receptors (figure 5).”
Quote in the paperSubstantial claim - Findingcitation
In a few patients whose CSF was obtained during neurological improvement, the decrease of CSF antibody titres was substantially slower than that of serum titres.
“For example, in a few patients whose CSF was obtained during neurological improvement, the decrease of CSF antibody titres was substantially slower than that of serum titres.9”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Seki, 2008, Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis, J Neurol Neurosurg Psychiatry source
Not checked in the free run.
- Findingown data
In only one of seven patients who underwent exploratory laparotomy was a tumour found.
“however, in only one of seven patients who underwent exploratory laparotomy was a tumour found (sex-cord stromal tumour; data not shown).”
Quote in the paperNot a substantial claim - Findingown data
Of the 83 patients whose CSF was available, those with tumours had higher antibody titres than those without.
“Of the 83 patients whose CSF was available, those with tumours had higher antibody titres than those without (figure 3).”
Quote in the paperNot a substantial claim - Findingown data
IgG from patients with high antibody titres produced a greater decrease of NMDA receptors than IgG from patients with low antibody titres.
“IgG from patients with high antibody titres produced a greater decrease of NMDA receptors than IgG from patients with low antibody titres (data not shown).”
Quote in the paperSubstantial claim - Interpretationreasoning
Selective disruption of receptors containing NR2B would not explain the extensive deficits of patients with anti-NMDA-receptor encephalitis.
“However, selective disruption of receptors containing NR2B, which are predominantly expressed in the forebrain and hippocampus, would not explain the extensive deficits of patients.”
Quote in the paperSubstantial claim - Interpretationown data
A well-defined set of clinical characteristics is associated with anti-NMDA-receptor encephalitis.
“A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis.”
Quote in the paperSubstantial claim - Interpretationown data
The pathogenesis of anti-NMDA-receptor encephalitis seems to be mediated by antibodies.
“The pathogenesis of the disorder seems to be mediated by antibodies.”
Quote in the paperSubstantial claim - Interpretationown data
The immune response eventually predominates in the nervous system in anti-NMDA-receptor encephalitis, as suggested by the high frequency of pleocytosis, oligoclonal bands, and intrathecal synthesis of NR1 antibodies.
“Nevertheless, the immune response eventually predominates in the nervous system as suggested by the high frequency of pleocytosis, oligoclonal bands, and intrathecal synthesis of NR1 antibodies.”
Quote in the paperSubstantial claim - Interpretationcitation
The persisting amnesia in patients who recover from anti-NMDA-receptor encephalitis is compatible with disruption of the mechanisms of synaptic plasticity, thought to underlie learning and memory, in which NMDA receptors play a key part.
“This feature is compatible with disruption of the mechanisms of synaptic plasticity, thought to underlie learning and memory, in which the NMDA receptors play a key part.4”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Lau, 2007, NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders, Nat Rev Neurosci source
Not checked in the free run.
- Premisereasoning
NMDA-receptor antagonists such as MK801, ketamine, and phencyclidine cause symptoms similar to anti-NMDA-receptor encephalitis, including psychotic behaviour, signs of involvement of dopaminergic pathways, and autonomic dysfunction.
“Consistent with this antibody-induced decrease in the numbers of NMDA receptors, several NMDA-receptor antagonists such as MK801, ketamine, and phencyclidine cause symptoms similar to anti-NMDA-receptor encephalitis, including psychotic behaviour,21,22 signs of involvement of dopaminergic pathways (rigidity, dystonia, orofacial movements, tremor)22–25 and autonomic dysfunction (cardiac dysrhythmia”
Quote in the paperSubstantial claim0 of 7 sources checked- cites [21] Manahan-Vaughan, 2008, A single application of MK801 causes symptoms of acute psychosis, deficits in spatial memory, and impairment of synaptic plasticity in rats, Hippocampus source
Not checked in the free run.
- cites [22] McCarron, 1981, Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases, Ann Emerg Med source
Not checked in the free run.
- cites [23] Ilkiw, 1996, The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats, J Vet Pharmacol Ther source
Not checked in the free run.
- cites [24] Marco, 1992, A ketamine-induced rat model of tardive dyskinesia, Prog Neurobiol source
Not checked in the free run.
- cites [25] Hallett, 2005, Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTP-lesioned primate model of Parkinson's disease, Neuropharmacology source
Not checked in the free run.
- cites [26] Taittonen, 1998, The effect of clonidine or midazolam premedication on perioperative responses during ketamine anesthesia, Anesth Analg source
Not checked in the free run.
- cites [27] Heinz, 2006, Is atropine needed with ketamine sedation? A prospective, randomised, double blind study, Emerg Med J source
Not checked in the free run.
- Interpretationown data
Patients' antibodies produce a selective and reversible decrease of NMDA-receptor clusters in postsynaptic dendrites.
“Together, these findings show that patients’ antibodies produce a selective and reversible decrease of NMDA-receptor clusters in postsynaptic dendrites.”
Quote in the paperSubstantial claim - Interpretationown data
In general, patients with an underlying tumour develop more robust immune responses than those without a tumour.
“In general, patients with an underlying tumour develop more robust immune responses than those without a tumour.”
Quote in the paperNot a substantial claim - Interpretationown data
Direct viral pathogenesis of anti-NMDA-receptor encephalitis is unlikely because extensive studies of CSF samples, brain biopsies, and autopsies were negative for viruses.
“Direct viral pathogenesis is unlikely because extensive studies of CSF samples, brain biopsies, and autopsies were negative for viruses (data not shown).”
Quote in the paperSubstantial claim - Premisecitation
Disruption of NR1 in animals results in hypoventilation.
“Furthermore, disruption of NR1 in animals results in hypoventilation.28”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Forrest, 1994, Curran T. Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death, Neuron source
Not checked in the free run.
- Interpretationreasoning
A possible explanation for the slow recovery from anti-NMDA-receptor encephalitis could be the inability of most commonly used treatments to result in a rapid and sustained control of the immune response within the CNS.
“A possible explanation for the slow recovery could be the inability of most commonly used treatments (corticosteroids, plasma exchange, intravenous immunoglobulin) to result in a rapid and sustained control of the immune response within the CNS.”
Quote in the paperSubstantial claim
- May combine two claims. 30
- Classified as probably not a substantial claim. 8
May combine two claims.
Findingown dataOne boy (11 years old, without tumour) and 21 women and girls were younger than 19 years (median 15 years, range 5-18 years); 12 had an ovarian teratoma (five with immature features), and nine had no tumour.
“One boy (11 years old, without tumour) and 21 women and girls were younger than 19 years (median 15 years, range 5–18 years); 12 had an ovarian teratoma (five with immature features), and nine had no tumour.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data14 patients had brain biopsy: findings for two were normal, 12 showed mild perivascular lymphocytic cuffing, and ten microglial activation.
“14 patients had brain biopsy: findings for two were normal, 12 showed mild perivascular lymphocytic cuffng, and ten microglial activation.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe median time from symptom presentation to initial signs of improvement was 8 weeks (range 2-24 weeks) for the group with early tumour treatment, 11 weeks (4-40 weeks) for the group whose tumour was treated late or not treated, and 10 weeks (2-50 weeks) for the group without tumour (Kruskal-Wallis, p=0.10).
“The median time from symptom presentation to initial signs of improvement was 8 weeks (range 2–24 weeks) for the group of patients with early tumour treatment, 11 weeks (4–40 weeks) for the group whose tumour was treated late or not treated, and 10 weeks (2–50 weeks) for the group without tumour (Kruskal-Wallis, p=0.10)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAll brain biopsies had negative results for neuronophagic nodules and viral assays.
“All had negative results for neuronophagic nodules and viral assays.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data37 patients had cardiac dysrhythmias, including tachycardia or bradycardia, with prolonged pauses in seven patients; four needed pacemakers.
“37 patients had cardiac dysrhythmias, including tachycardia or bradycardia, with prolonged pauses in seven patients; four needed pacemakers.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataWhile hospitalised, seven patients had high levels of serum creatine kinase, six developed pulmonary embolism, six transient aphasia, four hemiparesis, and four tetraparesis.
“While hospitalised, seven patients had high levels of serum creatine kinase, six developed pulmonary embolism, six transient aphasia, four hemiparesis, and four tetraparesis.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMedian follow-up was 17 months (1-194 months): 47 patients had full recovery, 28 mild stable deficits, 18 severe deficits, and seven died as a result of the neurological disorder.
“Median follow-up was 17 months (1–194 months): 47 patients had full recovery, 28 mild stable deficits, 18 severe deficits, and seven died as a result of the neurological disorder.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data52 patients had dyskinesias, autonomic instability, and hypoventilation, 27 had two of these symptoms, and 14 had just one; the remaining seven developed a milder syndrome of seizures and psychiatric symptoms.
“52 patients had dyskinesias, autonomic instability, and hypoventilation, 27 patients had two of these symptoms, and 14 had just one; the remaining seven patients developed a milder syndrome of seizures and psychiatric symptoms.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAll teratomas contained nervous tissue; 25 were examined for expression of NMDA receptors, and all were positive.
“All teratomas contained nervous tissue; 25 were examined for expression of NMDA receptors, and all were positive (data not shown).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataEight patients had bilateral teratomas; four were synchronous, two had history of a contralateral teratoma, and two developed contralateral teratomas before recurrence of the encephalitis.
“Eight patients had bilateral teratomas; four were synchronous, two had history of a contralateral teratoma, and two developed contralateral teratomas before recurrence of the encephalitis.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMRI findings were limited to a single area of the brain in 19 patients: 16 had abnormalities in medial temporal lobes, two in the corpus callosum, and one in the brainstem.
“These findings were limited to a single area of the brain in 19 patients: 16 had abnormalities in medial temporal lobes, two in the corpus callosum, and one in the brainstem.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataPatients who improved had a parallel decrease of serum titres, whereas those who did not improve maintained high titres in CSF and serum.
“Patients who improved had a parallel decrease of serum titres, whereas those who did not improve maintained high titres in CSF and serum (figure 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataRelapses were less common in patients with early tumour treatment (1 of 36) than in other patients (14 of 64; p=0.009), including patients whose tumour was treated late (six of 22; p=0.009) and patients without tumour (eight of 42; p=0.03).
“Relapses were less common in patients with early tumour treatment (1 of 36) than in other patients (14 of 64; p=0.009), including patients whose tumour was treated late (six of 22; p=0.009) and patients without tumour (eight of 42; p=0.03).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMen and children can also be affected by anti-NMDA-receptor encephalitis.
“Our study indicates that 41% of patients with anti-NMDA-receptor encephalitis do not have a clinically detectable tumour, and that men and children can also be affected.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataFour patients who died and whose CSF was available were among the group with the highest titres, whereas the seven patients with milder syndromes had the lowest titres.
“Four patients who died and whose CSF was available were among the group with the highest titres, whereas the seven patients with milder syndromes had the lowest titres (data not shown).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe use of NR1d4-NR2B heteromers abrogated the reactivity of sera or CSF from 92 patients, and substantially decreased the reactivity of the samples of the remaining eight cases.
“The use of these heteromers abrogated the reactivity of sera or CSF from 92 patients’, and substantially decreased the reactivity of the samples of the remaining eight cases.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataWhile poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients.
“While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAntibody reactivity was not modified by changing the NR2 subunit (A, B, C, or D) and was retained by homomers of NR1.
“Analysis of the reactivity of patients’ sera or CSF against the indicated NMDA-receptor subunits or heteromers showed that antibody reactivity was not modified by changing the NR2 subunit (A, B, C, or D) and was retained by homomers of NR1 (webtable 3).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNMDA receptors are heteromers of NR1 subunits that bind glycine and NR2 subunits that bind glutamate.
“The receptors are heteromers of NR1 subunits that bind glycine and NR2 (A, B, C, or D) subunits that bind glutamate.1”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Lynch, 1994, N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents, Mol Pharmacol source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationPreliminary studies suggested the target epitopes were located in extracellular regions of NR1-NR2B NMDA receptors.
“Preliminary studies suggested the target epitopes were located in extracellular regions of NR1–NR2B NMDA receptors.5”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Dalmau, 2007, Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma, Ann Neurol source
Not checked in the free run.
May combine two claims.
PremisecitationPatients with anti-NMDA-receptor encephalitis often recovered after tumour removal and immunotherapy, suggesting an immune-mediated pathogenesis.
“Despite the severity of the disorder, patients often recovered after tumour removal and immunotherapy, suggesting an immune-mediated pathogenesis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Dalmau, 2007, Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma, Ann Neurol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNMDA receptors are ligand-gated cation channels with crucial roles in synaptic transmission and plasticity.
“NMDA receptors are ligand-gated cation channels with crucial roles in synaptic transmission and plasticity.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Lynch, 1994, N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents, Mol Pharmacol source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenAll patients had brain MRI, radiological screening for a systemic neoplasm, and serological or CSF studies that ruled out other disorders.
“All patients had brain MRI, radiological screening for a systemic neoplasm, and serological or CSF studies that ruled out other disorders (webappendix).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOveractivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke.
“Overactivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke, whereas low activity produces symptoms of schizophrenia.2–4”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [2] Coyle, 2006, Glutamate and schizophrenia: beyond the dopamine hypothesis, Cell Mol Neurobiol source
Not checked in the free run.
- cites [3] Waxman, 2005, N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease, Neuroscientist source
Not checked in the free run.
- cites [4] Lau, 2007, NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders, Nat Rev Neurosci source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationSerum and CSF were tested for antibodies against the NMDA receptor and considered positive if three immunohistochemical criteria were fulfilled.
“Serum and CSF were tested for antibodies against the NMDA receptor,5 and considered positive if three immunohistochemical criteria were fulfilled (figure 1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Dalmau, 2007, Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma, Ann Neurol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLow activity of NMDA receptors produces symptoms of schizophrenia.
“Overactivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke, whereas low activity produces symptoms of schizophrenia.2–4”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [2] Coyle, 2006, Glutamate and schizophrenia: beyond the dopamine hypothesis, Cell Mol Neurobiol source
Not checked in the free run.
- cites [3] Waxman, 2005, N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease, Neuroscientist source
Not checked in the free run.
- cites [4] Lau, 2007, NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders, Nat Rev Neurosci source
Not checked in the free run.
May combine two claims.
PremisecitationThe first patients identified with anti-NMDA-receptor encephalitis were young women with ovarian teratoma who presented with psychosis or memory problems, rapidly progressing to multiple neurological deficits requiring prolonged intensive care support.
“The first patients identified were young women with ovarian teratoma who presented with psychosis or memory problems, rapidly progressing to multiple neurological deficits requiring prolonged intensive care support.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Dalmau, 2007, Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma, Ann Neurol source
Not checked in the free run.
May combine two claims.
PremisecitationAnti-NMDA-receptor encephalitis associates with antibodies against NR1-NR2 heteromers and results in a characteristic neuropsychiatric syndrome.
“We recently identified a disorder, designated anti-NMDA-receptor encephalitis, that associates with antibodies against NR1–NR2 heteromers and results in a characteristic neuropsychiatric syndrome.5”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Dalmau, 2007, Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma, Ann Neurol source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationNeurological outcome was assessed with the modified Rankin scale (MRS) and mini-mental state examination (MMSE).
“Neurological outcome was assessed with the modified Rankin scale (MRS)10 and mini-mental state examination (MMSE).11”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [10] van Swieten, 1988, Interobserver agreement for the assessment of handicap in stroke patients, Stroke source
Not checked in the free run.
- cites [11] Folstein, 1975, “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician, J Psychiatr Res source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe decrease in postsynaptic clusters of NMDA receptors caused by patients' antibodies was reversed by removing the antibodies from the cultures, explaining the potential reversibility of patients' symptoms.
“The latter effect was reversed by removing the antibodies from the cultures, explaining the potential reversibility of patients’ symptoms.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataAnti-NMDA-receptor encephalitis represents a new category of immune-mediated disorder that is often paraneoplastic, treatable, and can be diagnosed serologically.
“Anti-NMDA-receptor encephalitis represents a new category of immune-mediated disorder that is often paraneoplastic, treatable, and can be diagnosed serologically.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningAlthough the presence of a tumour that expresses NMDA receptors likely contributes to breaking immune tolerance, other unknown immunological triggers seem to be involved in anti-NMDA-receptor encephalitis.
“Therefore, although the presence of a tumour that expresses NMDA receptors likely contributes to breaking immune tolerance, other unknown immunological triggers seem to be involved.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataRecovery from anti-NMDA-receptor encephalitis is typically slow, and symptoms may relapse, especially in patients with undetected or recurrent tumours and patients with no associated tumours.
“Recovery from this disorder is typically slow, and symptoms may relapse, especially in patients with undetected or recurrent tumours and patients with no associated tumours.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataA pathogenic role of patients' antibodies in anti-NMDA-receptor encephalitis is suggested by the correlation between antibody titres and neurological outcome and by the decrease in number of postsynaptic clusters of NMDA receptors caused by patients' antibodies.
“A pathogenic role of patients’ antibodies is suggested by the correlation between antibody titres and neurological outcome and by the decrease in number of postsynaptic clusters of NMDA receptors caused by patients’ antibodies.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The effects of patients’ antibodies on rat hippocampal neuronal cultures reflect the effects of those antibodies on human neurons in anti-NMDA-receptor encephalitis.
“To assess the effect of patients’ antibodies on neuronal cultures, we first determined the extent of immunolabelling of NR1 (or NMDA receptor) clusters in postsynaptic dendrites.”
The paper relies on this without support.
HEK293 cells ectopically expressing recombinant NR1 or NR1–NR2B subunits present the same epitopes as native NMDA receptors for patients’ antibodies.
“Antibody titres were measured with ELISA on HEK293 cell lysates ectopically expressing NR1 or NR1–NR2B heteromers (webappendix).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Patients usually present with acute behavioral change, psychosis and catatonia that evolve to include seizures, memory deficit, dyskinesias, speech problems, and autonomic and breathing dysregulation.
“Patients usually present with acute behavioral change, psychosis and catatonia that evolve to include seizures, memory deficit, dyskinesias, speech problems, and autonomic and breathing dysregulation.3”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [3]
The Results (page not supplied) report that most patients presented with psychiatric symptoms and later developed seizures, dyskinesias, autonomic instability, and hypoventilation; some also had speech disturbances. The claimed sequence is not fully supported: the paper describes a catatonic-like state developing after decreased consciousness, while some patients had memory loss at presentation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIf a tumor is found, removal is important because it expedites improvement and decreases relapses.
“If a tumor is found, removal is important because it expedites improvement and decreases relapses.3, 17”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [3]
The Results report fewer relapses after early tumour treatment (1 of 36 versus 14 of 64) and better outcomes when tumours were removed within four months. Initial improvement occurred sooner in the early-treatment group (median 8 versus 11 weeks), but that difference was not statistically significant (p=0.10). The claim overstates the evidence by saying removal itself expedites improvement and decreases relapses; early treatment usually also included immunotherapy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSamples were considered positive if they fulfilled previously reported criteria including a characteristic pattern of immunostaining of the neuropil of rat brain and specific reactivity with HEK293 cells expressing GluN1 subunits of the NMDAR.
“Samples were considered positive if they fulfilled previously reported criteria3 including (1) a characteristic pattern of immunostaining of the neuropil of rat brain, and (2) specific reactivity with HEK293 cells expressing GluN1 (also known as NR1) subunits of the NMDAR.”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [3]
The Methods (Patients and procedures; page unavailable) say samples were considered positive when three immunohistochemical criteria were met, and describe testing sera and CSF against NR1-expressing HEK293 cells. Our copy does not specify that rat-brain neuropil immunostaining was one of those positivity criteria, so that part of the attributed description remains unsupported. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe disorder has been recognized in patients of all ages, but more frequently in young adults and children with or without teratoma.
“The disorder, named “anti-NMDAR encephalitis”, has since been recognized in patients of all ages, but more frequently in young adults and children with or without teratoma.3, 4”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [3]
Despite the severity of the disease, patients often improve after intensive care support, immunotherapy, and prolonged hospitalizations that require multidisciplinary care.
“Despite the severity of the disease, patients often improve after intensive care support, immunotherapy, and prolonged hospitalizations that require multidisciplinary care.3, 11”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [3]
Psychotomimetic models, especially ketamine-based, support the E/I imbalance hypothesis.
“Psychotomimetic models (eg, models that mimic the symptoms of psychosis), especially those based on ketamine (an antagonistic agent of NMDA-R), also support the E/I imbalance hypothesis.”
From Are hallucinations due to an imbalance between excitatory and inhibitory influences on the brain? (2016) · cites this paper as [14]
Autoimmune diseases associated with anti-NMDAR antibodies are associated with severe psychosis.
“Recently, autoimmune diseases associated with anti-NMDAR antibodies were reported to be associated with severe psychosis 14 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Tumour-diagnosis intervals conflict in units and range
MinorThe maximum interval from neurological symptoms to tumour diagnosis is given as 380 weeks, but six patients diagnosed after recovery are said to have intervals reaching 380 months. Both cannot describe the same diagnosis intervals.
“All but one of these patients developed neurological symptoms before the tumour diagnosis (median 8 weeks, range 1–380 weeks).”
“In six patients, the tumour was diagnosed after recovery from the encephalitis (56–380 months).”
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
Interobserver agreement for the assessment of handicap in stroke patients
van Swieten, J. C., Koudstaal, P. J., Visser, M. C., Schouten, H. J., & van Gijn, J. (1988) · Stroke · doi:10.1161/01.str.19.5.604 · Cited by 6,512 · see citing works
Dalmau, J., Tüzün, E., Wu, H., Masjuan, J., Rossi, J. E., Voloschin, A., Baehring, J. M., Shimazaki, H., Koide, R., King, D., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21050 · Cited by 2,492 · see citing works
Self-citationB-cell depletion with rituximab in relapsing-remitting multiple sclerosis
Hauser, S. L., Waubant, E., Arnold, D. L., Vollmer, T., Antel, J., Fox, R. J., Bar-Or, A., Panzara, M., Sarkar, N., Agarwal, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706383 · Cited by 2,439 · see citing works
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
Lau, C. G., & Zukin, R. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2153 · Cited by 1,159 · see citing works
Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis
Coyle, J. T. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9062-8 · Cited by 917 · see citing works
Tibbling, G., Link, H., & Ohman, S. (1977) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365517709091496 · Cited by 863 · see citing works
Tibbling, G., Link, H., & Ohman, S. (1977) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517709091496 · Cited by 813 · see citing works
Anti-NMDA receptor encephalitis in Japan
Iizuka, T., Sakai, F., Ide, T., Monzen, T., Yoshii, S., Iigaya, M., Suzuki, K., Lynch, D. R., Suzuki, N., Hata, T., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000278388.90370.c3 · Cited by 517 · see citing works
Self-citationTargeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death
Forrest, D., Yuzaki, M., Soares, H. D., Ng, L., Luk, D. C., Sheng, M., Stewart, C. L., Morgan, J. I., Connor, J. A., & Curran, T. (1994) · Neuron · doi:10.1016/0896-6273(94)90350-6 · Cited by 491 · see citing works
Kowal, C., DeGiorgio, L. A., Nakaoka, T., Hetherington, H. P., Huerta, P. T., Diamond, B., & Volpe, B. T. (2004) · Immunity · doi:10.1016/j.immuni.2004.07.011 · Cited by 403 · see citing works
N-Methyl-d-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease
Waxman, E. A., & Lynch, D. R. (2005) · The Neuroscientist · doi:10.1177/1073858404269012 · Cited by 372 · see citing works
Self-citationImmunity and behavior: Antibodies alter emotion
Huerta, P. T., Kowal, C., DeGiorgio, L. A., Volpe, B. T., & Diamond, B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510055103 · Cited by 293 · see citing works
A patient with encephalitis associated with NMDA receptor antibodies
Sansing, L. H., Tüzün, E., Ko, M. W., Baccon, J., Lynch, D. R., & Dalmau, J. O. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0493 · Cited by 290 · see citing works
Self-citationHallett, P. J., Dunah, A. W., Ravenscroft, P., Zhou, S., Bezard, E., Crossman, A. R., Brotchie, J. M., & Standaert, D. G. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.11.008 · Cited by 192 · see citing works
Elmariah, S. B., Oh, E. J., Hughes, E. G., & Balice‐Gordon, R. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3980-04.2005 · Cited by 182 · see citing works
Self-citationLynch, D. R., Anegawa, N. J., Verdoorn, T., & Pritchett, D. B. (1994) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10028-x · Cited by 173 · see citing works
Self-citationAcute phencyclidine intoxication: incidence of clinical findings in 1,000 cases
McCarron, M. M., Schulze, B. W., Thompson, G. A., Conder, M. C., & Goetz, W. A. (1981) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(81)80047-9 · Cited by 163 · see citing works
Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus‐induced myocarditis
Fairweather, D., Frisancho‐Kiss, S., & Rose, N. R. (2005) · Reviews in Medical Virology · doi:10.1002/rmv.445 · Cited by 155 · see citing works
Manahan‐Vaughan, D., von Haebler, D., Winter, C., Juckel, G., & Heinemann, U. (2008) · Hippocampus · doi:10.1002/hipo.20367 · Cited by 149 · see citing works
Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis
Seki, M., Suzuki, S., Iizuka, T., Shimizu, T., Nihei, Y., Suzuki, N., & Dalmau, J. (2008) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.136473 · Cited by 147 · see citing works
Self-citationMeddows, E., Bourdellès, B. L., Grimwood, S., Wafford, K. A., Sandhu, S., Whiting, P. J., & McIlhinney, R. A. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101382200 · Cited by 116 · see citing works
Is atropine needed with ketamine sedation? A prospective, randomised, double blind study
Heinz, P. (2006) · Emergency Medicine Journal · doi:10.1136/emj.2005.028969 · Cited by 113 · see citing works
Viruses, cytokines, antigens, and autoimmunity.
Gianani, R., & Sarvetnick, N. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2257 · Cited by 101 · see citing works
Wu, H.-Y., Hsu, F., Gleichman, A. J., Baconguis, I., Coulter, D. A., & Lynch, D. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700624200 · Cited by 87 · see citing works
Self-citationLambert-Eaton Myasthenic Syndrome
Newsom–Davis, J. (2004) · Revue Neurologique · doi:10.1016/s0035-3787(04)70888-7 · Cited by 61 · see citing works
Taittonen, M. T., Kirvela, O. A., Aantaa, R., & Kanto, J. H. (1998) · Anesthesia & Analgesia · doi:10.1213/00000539-199807000-00034 · Cited by 41 · see citing works
Primary angiitis of the central nervous system
Molloy, E. S., & Hajj-Ali, R. A. (2007) · Current Treatment Options in Neurology · doi:10.1007/bf02938406 · Cited by 39 · see citing works
Kataoka, H., Dalmau, J. O., & Ueno, S. (2007) · European Journal of Neurology · doi:10.1111/j.1468-1331.2007.02005.x · Cited by 22 · see citing works
Self-citationILKIW, J. E., SUTER, C. M., McNEAL, D., FARVER, T. B., & STEFFEY, E. P. (1996) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.1996.tb00041.x · Cited by 14 · see citing works
A ketamine-induced rat model of tardive dyskinesia
Marco, L. A., & Joshi, R. S. (1992) · Progress in Neurobiology · doi:10.1016/0301-0082(92)90042-d · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A clinical approach to diagnosis of autoimmune encephalitis
Graus, F., Titulaer, M. J., Balu, R., Benseler, S. M., Bien, C. G., Cellucci, T., Cortese, I. C. M., Dale, R. C., Gelfand, J. M., Geschwind, M. D., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00401-9 · Cited by 4,580 · see citing works
Self-citationTitulaer, M. J., McCracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., Honig, L. S., Benseler, S. M., Kawachi, I., Martinez-Hernandez, E., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70310-1 · Cited by 3,165 · see citing works
Self-citationNMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · see citing works
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Dalmau, J. O., Lancaster, E., Martínez‐Hernández, E., Rosenfeld, M. R., & Balice‐Gordon, R. J. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70253-2 · Cited by 2,428 · see citing works
Self-citationThe role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876 · see citing works
Lai, M., Huijbers, M. G. M., Lancaster, E., Graus, F., Bataller, L., Balice‐Gordon, R. J., Cowell, J. K., & Dalmau, J. O. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70137-x · Cited by 1,348 · see citing works
Self-citationGresa‐Arribas, N., Titulaer, M. J., Torrents, A., Aguilar, E., McCracken, L., Leypoldt, F., Gleichman, A. J., Balice‐Gordon, R. J., Rosenfeld, M. R., Lynch, D. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70282-5 · Cited by 1,306 · see citing works
Self-citationVenkatesan, A., Tunkel, A. R., Bloch, K. C., Lauring, A. S., Sejvar, J. J., Bitnun, A., Stahl, J. ‐., Mailles, A., DREBOT, M. A., Rupprecht, C. E., et al. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit458 · Cited by 1,223 · see citing works
Granerod, J., Ambrose, H. E., Davies, N. W., Clewley, J. P., Walsh, A. L., Morgan, D., Cunningham, R., Zuckerman, M., Mutton, K. J., Solomon, T., et al. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70222-x · Cited by 1,358 · see citing works
Kwan, P., Schachter, S. C., & Brodie, M. J. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1004418 · Cited by 1,113 · see citing works
Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis
Hughes, E. G., Peng, X., Gleichman, A. J., Lai, M., Zhou, L., Tsou, R., Parsons, T. D., Lynch, D. R., Dalmau, J., & Balice-Gordon, R. J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0167-10.2010 · Cited by 1,143 · see citing works
Self-citationLancaster, E., Lai, M., Peng, X., Hughes, E. G., Constantinescu, R., Raizer, J. J., Friedman, D. J., Skeen, M. B., Grisold, W., Kimura, A., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70324-2 · Cited by 920 · see citing works
Self-citationDalmau, J. O., Armangué, T., Planagumà, J., Radosevic, M., Mannara, F., Leypoldt, F., Geis, C., Lancaster, E., Titulaer, M. J., Rosenfeld, M. R., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30244-3 · Cited by 918 · see citing works
Self-citationMoshé, S. L., Perucca, E., Ryvlin, P., & Tomson, T. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60456-6 · Cited by 905 · see citing works
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents
Florance, N. R., Davis, R. L., Lam, C., Szperka, C., Zhou, L., Ahmad, S., Campen, C. J., Moss, H., Peter, N., Gleichman, A. J., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21756 · Cited by 1,090 · see citing works
Self-citationIrani, S. R., Bera, K., Waters, P., Zuliani, L., Maxwell, S., Zandi, M. S., Friese, M. A., Galea, I., Kullmann, D. M., Beeson, D., et al. (2010) · Brain · doi:10.1093/brain/awq113 · Cited by 1,035 · see citing works
AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location
Lai, M., Hughes, E. G., Peng, X., Zhou, L., Gleichman, A. J., Shu, H., Matà, S., Kremens, D. E., Vitaliani, R., Geschwind, M. D., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21589 · Cited by 803 · see citing works
Self-citationAutoimmune encephalitis epidemiology and a comparison to infectious encephalitis
Dubey, D., Pittock, S. J., Kelly, C. R., McKeon, A. B., Lopez-Chiriboga, A. S., Lennon, V. A., Gadoth, A., Smith, C. Y., Bryant, S. C., Klein, C. J., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25131 · Cited by 797 · see citing works
Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment
Pelosof, L. C., & Gerber, D. E. (2010) · Mayo Clinic Proceedings · doi:10.4065/mcp.2010.0099 · Cited by 779 · see citing works
Neuroinflammation and psychiatric illness
Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733 · see citing works
Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia
Lancaster, E., Huijbers, M. G. M., Bar, V., Boronat, A., Wong, A., Martínez‐Hernández, E., Wilson, C., Jacobs, D. A., Lai, M., Walker, R., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22297 · Cited by 729 · see citing works
Self-citationSchmitt, S. E., Pargeon, K. L., Frechette, E. S., Hirsch, L. J., Dalmau, J. O., & Friedman, D. (2012) · Neurology · doi:10.1212/wnl.0b013e3182698cd8 · Cited by 714 · see citing works
Self-citationImmunopathology of autoantibody-associated encephalitides: clues for pathogenesis
Bien, C. G., Vincent, A. C., Barnett, M. H., Becker, A. J., Blümcke, I., Graus, F., Jellinger, K. A., Reuss, D. E., Ribalta, T., Schlegel, J., et al. (2012) · Brain · doi:10.1093/brain/aws082 · Cited by 695 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
B cell depletion therapies in autoimmune disease: advances and mechanistic insights
Lee, D. S. W., Rojas, O. L., & Gommerman, J. L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00092-2 · Cited by 666 · see citing works
Armangué, T., Spatola, M., Vlagea, A. D., Mattozzi, S., Carceles‐Cordon, M., Martínez‐Heras, E., Llufriú, S., Muchart, J., Erro, M. E., Abraira, L., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30244-8 · Cited by 665 · see citing works
Self-citationvan Sonderen, A., Thijs, R. D., Coenders, E. C., Jiskoot, L. C., Sánchez, E., de Bruijn, M. A. A. M., van Coevorden‐Hameete, M. H., Wirtz, P. W., Schreurs, M. W. J., Smitt, P. A. E. S., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003173 · Cited by 663 · see citing works
Gable, M. S., Sheriff, H., Dalmau, J., Tilley, D. H., & Glaser, C. A. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cir1038 · Cited by 733 · see citing works
Self-citationDalmau, J. O., Geis, C., & Graus, F. (2017) · Physiological Reviews · doi:10.1152/physrev.00010.2016 · Cited by 631 · see citing works
Self-citationRetrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin
Prüß, H., Dalmau, J. O., Harms, L., Höltje, M., Ahnert‐Hilger, G., Borowski, K., Stoecker, W., & Wandinger, K. (2010) · Neurology · doi:10.1212/wnl.0b013e3181fc2a06 · Cited by 627 · see citing works
Self-citationPetit‐Pedrol, M., Armangué, T., Peng, X., Bataller, L., Cellucci, T., Davis, R. A., McCracken, L., Martínez‐Hernández, E., Mason, W. P., Kruer, M. C., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70299-0 · Cited by 616 · see citing works
Self-citationThe diagnosis of young-onset dementia
Rossor, M. N., Fox, N. C., Mummery, C. J., Schott, J. M., & Warren, J. D. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70159-9 · Cited by 585 · see citing works
Sabater, L., Gaig, C., Gelpí, E., Bataller, L., Lewerenz, J., Torres-Vega, E., Contreras, A., Giometto, B., Compta, Y., Embid, C., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70051-1 · Cited by 563 · see citing works
Self-citationAutoantibodies associated with diseases of the CNS: new developments and future challenges
Vincent, A. C., Bien, C. G., Irani, S. R., & Waters, P. J. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70096-5 · Cited by 536 · see citing works
Carvajal-González, A., Leite, M. I., Waters, P. J., Woodhall, M. R., Coutinho, E., Balint, B., Lang, B., Pettingill, P., Carr, A. S., Sheerin, U., et al. (2014) · Brain · doi:10.1093/brain/awu142 · Cited by 530 · see citing works
Screening for tumours in paraneoplastic syndromes: report of an EFNS Task Force
Titulaer, M. J., Soffietti, R., Dalmau, J. O., Ne, G., Giometto, B., Graus, F., Grisold, W., Honnorat, J., Smitt, P. A. E. S., Tănăsescu, R., et al. (2010) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.03220.x · Cited by 528 · see citing works
Self-citationInfections, inflammation and epilepsy
Vezzani, A., Fujinami, R. S., White, H. S., Preux, P., Blümcke, I., Sander, J. W. A. S., & Löscher, W. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1481-5 · Cited by 526 · see citing works
Overlapping demyelinating syndromes and anti–N‐methyl‐D‐aspartate receptor encephalitis
Titulaer, M. J., Höftberger, R., Iizuka, T., Leypoldt, F., McCracken, L., Cellucci, T., Benson, L. A., Shu, H., Irioka, T., Hirano, M., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24117 · Cited by 518 · see citing works
Self-citationAntibodies to glutamic acid decarboxylase define a form of limbic encephalitis
Malter, M. P., Helmstaedter, C., Urbach, H., Vincent, A. C., & Bien, C. G. (2009) · Annals of Neurology · doi:10.1002/ana.21917 · Cited by 510 · see citing works
Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice
Planagumà, J., Leypoldt, F., Mannara, F., Cuesta, J., Martín‐García, E., Aguilar, E., Titulaer, M. J., Petit‐Pedrol, M., Jain, A., Balice‐Gordon, R. J., et al. (2014) · Brain · doi:10.1093/brain/awu310 · Cited by 489 · see citing works
Self-citationMechanisms of Autoantibody-Induced Pathology
Ludwig, R. J., Vanhoorelbeke, K., Leypoldt, F., Kaya, Z., Bieber, K., McLachlan, S. M., Komorowski, L., Luo, J., Cabral-Marques, O., Hammers, C. M., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00603 · Cited by 475 · see citing works
Encephalitis and GABA B receptor antibodies
Höftberger, R., Titulaer, M. J., Sabater, L., Döme, B., Rózsás, A., Hegedűs, B., Hoda, M. A., László, V., Ankersmit, H. J., Harms, L., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a9585f · Cited by 472 · see citing works
Self-citationHerpes simplex virus encephalitis is a trigger of brain autoimmunity
Armangué, T., Leypoldt, F., Málaga, I., Raspall‐Chaure, M., Martí, I., Nichter, C. A., Pugh, J., Vicente-Rasoamalala, M., Hidalgo, M. L., Macaya, A., et al. (2013) · Annals of Neurology · doi:10.1002/ana.24083 · Cited by 467 · see citing works
Self-citationSolomon, T., Michael, B. D., Smith, P. E., Sanderson, F., Davies, N. W. S., Hart, I. J., Holland, M., Easton, A., Buckley, C. J., Kneen, R., et al. (2011) · Journal of Infection · doi:10.1016/j.jinf.2011.11.014 · Cited by 466 · see citing works
Neuronal autoantigens—pathogenesis, associated disorders and antibody testing
Lancaster, E., & Dalmau, J. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.99 · Cited by 512 · see citing works
Self-citationLesca, G., Rudolf, G., Bruneau, N., Lozovaya, N., Labalme, A., Boutry‐Kryza, N., Salmi, M., Tsintsadze, T. S., Addis, L., Motte, J. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2726 · Cited by 433 · see citing works
Irani, S. R., Stagg, C. J., Schott, J. M., Rosenthal, C. R., Schneider, S. A., Pettingill, P., Pettingill, R., Waters, P. J., Thomas, A. G., Voets, N., et al. (2013) · Brain · doi:10.1093/brain/awt212 · Cited by 432 · see citing works
Leypoldt, F., Armangué, T., & Dalmau, J. O. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12553 · Cited by 424 · see citing works
Self-citationKayser, M. S., Titulaer, M. J., Gresa‐Arribas, N., & Dalmau, J. O. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.3216 · Cited by 419 · see citing works
Self-citationArmangué, T., Titulaer, M. J., Málaga, I., Bataller, L., Gabilondo, I., Graus, F., & Dalmau, J. O. (2012) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2012.10.011 · Cited by 418 · see citing works
Self-citationEncephalitis and antibodies to synaptic and neuronal cell surface proteins
Lancaster, E., Martínez‐Hernández, E., & Dalmau, J. O. (2011) · Neurology · doi:10.1212/wnl.0b013e318224afde · Cited by 400 · see citing works
Self-citationAntibodies and neuronal autoimmune disorders of the CNS
Graus, F., Saiz, A., & Dalmau, J. O. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5431-9 · Cited by 388 · see citing works
Self-citationAntibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders
Dale, R. C., Merheb, V., Pillai, S. C., Wang, D., Cantrill, L. C., Murphy, T. K., Ben‐Pazi, H., Varadkar, S., Aumann, T. D., Horne, M. K., et al. (2012) · Brain · doi:10.1093/brain/aws256 · Cited by 387 · see citing works
N‐methyl‐ <scp>D</scp> ‐aspartate receptor antibodies in herpes simplex encephalitis
Prüss, H., Finke, C., Höltje, M., Hofmann, J., Klingbeil, C., Probst, C., Borowski, K., Ahnert‐Hilger, G., Harms, L., Schwab, J. M., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23689 · Cited by 422 · see citing works
Self-citationEncephalitis and AMPA receptor antibodies
Höftberger, R., van Sonderen, A., Leypoldt, F., Houghton, D. J., Geschwind, M. D., Gelfand, J. M., Paredes, M. F., Sabater, L., Saiz, A., Titulaer, M. J., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001682 · Cited by 381 · see citing works
Self-citationSteiner, J. H., Walter, M., Glanz, W., Sarnyai, Z., Bernstein, H., Vielhaber, S., Kästner, A., Skalej, M., Jordan, W., Schiltz, K., et al. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.86 · Cited by 379 · see citing works
Paraneoplastic Neurologic Syndrome in the PNS Euronetwork Database
Giometto, B. (2010) · Archives of Neurology · doi:10.1001/archneurol.2009.341 · Cited by 373 · see citing works
Pittock, S. J., Debruyne, J., Krecke, K. N., Giannini, C., van den Ameele, J., Herdt, V. D., McKeon, A. B., Fealey, R. D., Weinshenker, B. G., Aksamit, A. J., et al. (2010) · Brain · doi:10.1093/brain/awq164 · Cited by 372 · see citing works
Boronat, A., Gelfand, J. M., Gresa‐Arribas, N., Jeong, H., Walsh, M., Roberts, K., Martínez‐Hernández, E., Rosenfeld, M. R., Balice‐Gordon, R. J., Graus, F., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23756 · Cited by 372 · see citing works
Self-citationAnalysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis
Martínez‐Hernández, E., Horvath, J. E., Shiloh‐Malawsky, Y., Sangha, N. S., Martinez‐Lage, M., & Dalmau, J. O. (2011) · Neurology · doi:10.1212/wnl.0b013e318228c136 · Cited by 371 · see citing works
Self-citationAcute mechanisms underlying antibody effects in anti–N‐methyl‐D‐aspartate receptor encephalitis
Moscato, E. H., Peng, X., Jain, A., Parsons, T. D., Dalmau, J. O., & Balice‐Gordon, R. J. (2014) · Annals of Neurology · doi:10.1002/ana.24195 · Cited by 361 · see citing works
Self-citationQuek, A. M. L. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.2985 · Cited by 360 · see citing works
Tüzün, E., Zhou, L., Baehring, J. M., Bannykh, S., Rosenfeld, M. R., & Dalmau, J. O. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0582-4 · Cited by 355 · see citing works
Self-citationOhkawa, T., Fukata, Y., Yamasaki, M., Miyazaki, T., Yokoi, N., Takashima, H., Watanabe, M., Watanabe, O., & Fukata, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3506-13.2013 · Cited by 352 · see citing works
Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00028 · Cited by 351 · see citing works
Cognitive deficits following anti-NMDA receptor encephalitis
Finke, C., Kopp, U. A., Prüß, H., Dalmau, J. O., Wandinger, K., & Ploner, C. J. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-300411 · Cited by 350 · see citing works
Self-citationSeroprevalence of autoantibodies against brain antigens in health and disease
Dahm, L., Ott, C., Steiner, J. H., Stepniak, B., Teegen, B., Saschenbrecker, S., Hammer, C., Borowski, K., Begemann, M., Lemke, S., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24189 · Cited by 348 · see citing works
B cells in autoimmune and neurodegenerative central nervous system diseases
Sabatino, J. J., Pröbstel, A., & Zamvil, S. S. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0233-2 · Cited by 347 · see citing works
A Clinical Review of the Treatment of Catatonia
Sienaert, P. A., Dhossche, D. M., Vancampfort, D., Binder, M. D., & Gazdag, G. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00181 · Cited by 344 · see citing works
Hammer, C., Stepniak, B., Schneider, A., Papiol, S., Tantra, M., Begemann, M., Sirén, A.-L., Pardo, L. A., Sperling, S., Mohd Jofrry, S., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.110 · Cited by 342 · see citing works
Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis
Mikasova, L., De Rossi, P., Bouchet, D., Georges, F., Rogemond, V., Didelot, A., Meissirel, C., Honnorat, J., & Groc, L. (2012) · Brain · doi:10.1093/brain/aws092 · Cited by 341 · see citing works
Disease-relevant autoantibodies in first episode schizophrenia
Zandi, M. S., Irani, S. R., Lang, B., Waters, P. J., Jones, P. B., McKenna, P. J., Coles, A. J., Vincent, A. C., & Lennox, B. (2010) · Journal of Neurology · doi:10.1007/s00415-010-5788-9 · Cited by 333 · see citing works
Investigations in GABA A receptor antibody-associated encephalitis
Spatola, M., Petit‐Pedrol, M., Simabukuro, M. M., Armangué, T., Castro, F. J., Artigues, M. I. B., Juliá, M. R., Benson, L. A., Gorman, M., Felipe‐Rucián, A., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003713 · Cited by 333 · see citing works
Self-citationBrilot, F., Dale, R. C., Selter, R., Grummel, V., Kalluri, S. R., Aslam, M., Busch, V., Zhou, D., Cepok, S., & Hemmer, B. (2009) · Annals of Neurology · doi:10.1002/ana.21916 · Cited by 324 · see citing works
A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis
Balu, R., McCracken, L., Lancaster, E., Graus, F., Dalmau, J. O., & Titulaer, M. J. (2018) · Neurology · doi:10.1212/wnl.0000000000006783 · Cited by 312 · see citing works
Self-citationLinking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
The blood–brain barrier in psychosis
Pollak, T. A., Drndarski, S., Stone, J. M., David, A. S., McGuire, P. K., & Abbott, N. J. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30293-6 · Cited by 304 · see citing works
Manford, M. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8394-2 · Cited by 302 · see citing works
Gleichman, A. J., Spruce, L. A., Dalmau, J. O., Seeholzer, S. H., & Lynch, D. R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0064-12.2012 · Cited by 292 · see citing works
Self-citationZuliani, L., Graus, F., Giometto, B., Bien, C. G., & Vincent, A. C. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-301237 · Cited by 292 · see citing works
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis
Gable, M., Gavali, S. S., Radner, A. B., Tilley, D. H., Lee, B., Dyner, L., Collins, A. R., Dengel, A., Dalmau, J. O., & Glaser, C. A. (2009) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-009-0799-0 · Cited by 289 · see citing works
Self-citationThe glutamate hypothesis of schizophrenia: evidence from human brain tissue studies
Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12547 · Cited by 286 · see citing works
New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis
Yang, A. C., & Tsai, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081689 · Cited by 286 · see citing works
Inflammation and the two-hit hypothesis of schizophrenia
Feigenson, K. A., Kusnecov, A., & Silverstein, S. M. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.006 · Cited by 280 · see citing works
Williams, T. J., Benavides, D. R., Patrice, K.-A., Dalmau, J. O., Avila, A., Le, D. T., Lipson, E. J., Probasco, J. C., & Mowry, E. M. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.1399 · Cited by 279 · see citing works
Self-citationFink, M., & Taylor, M. A. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.141 · Cited by 278 · see citing works
Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors
Graus, F., & Dalmau, J. O. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0194-4 · Cited by 278 · see citing works
Self-citationThe origin of NMDA receptor hypofunction in schizophrenia
Nakazawa, K., & Sapkota, K. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107426 · Cited by 277 · see citing works
Autoimmune post–herpes simplex encephalitis of adults and teenagers
Armangué, T., Morís, G., Extremera, V. C., Conde, C. E., Rostasy, K. M., Erro, M. E., Portilla-Cuenca, J. C., Turón‐Viñas, E., Málaga, I., Cabello, B. M., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000002125 · Cited by 272 · see citing works
Self-citationImaging of autoimmune encephalitis – Relevance for clinical practice and hippocampal function
Heine, J., Prüß, H., Bartsch, T., Ploner, C. J., Paul, F., & Finke, C. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.037 · Cited by 272 · see citing works
Treatment strategies for autoimmune encephalitis
Shin, Y., Lee, S., Park, K., Jung, K., Jung, K., Lee, S. K., & Chu, K. (2017) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285617722347 · Cited by 272 · see citing works
Inflammatory mediators in human epilepsy: A systematic review and meta-analysis
de Vries, E. E., van den Munckhof, B., Braun, K. P. J., van Royen‐Kerkhof, A., de Jager, W., & Jansen, F. E. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.02.007 · Cited by 271 · see citing works
Steriade, C., Britton, J. W., Dale, R. C., Gadoth, A., Irani, S. R., Linnoila, J., McKeon, A. B., Shao, X., Venegas, V., & Bien, C. G. (2020) · Epilepsia · doi:10.1111/epi.16571 · Cited by 271 · see citing works
GABA B receptor antibodies in limbic encephalitis and anti-GAD–associated neurologic disorders
Boronat, A., Sabater, L., Saiz, A., Dalmau, J. O., & Graus, F. (2011) · Neurology · doi:10.1212/wnl.0b013e31820e7b8d · Cited by 269 · see citing works
Self-citationEncephalitis hospitalization rates and inpatient mortality in the United States, 2000-2010
George, B. P., Schneider, E. B., & Venkatesan, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104169 · Cited by 263 · see citing works
Red Flags: Clinical Signs for Identifying Autoimmune Encephalitis in Psychiatric Patients
Herken, J., & Prüß, H. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00025 · Cited by 255 · see citing works
Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors
Hanada, T. (2020) · Biomolecules · doi:10.3390/biom10030464 · Cited by 252 · see citing works
Immunity and Inflammation in EpilepsyPreprint
Vezzani, A., Lang, B., & Aronica, E. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a022699 · Cited by 251 · see citing works
Neuroinflammation: Ways in Which the Immune System Affects the Brain
Ransohoff, R. M., Schafer, D. P., Vincent, A. C., Blachère, N. E., & Bar‐Or, A. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0385-3 · Cited by 245 · see citing works
Neuroimaging Biomarkers in Schizophrenia
Kraguljac, N. V., McDonald, W. M., Widge, A. S., Rodríguez, C. I., Tohen, M. F., & Nemeroff, C. B. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.20030340 · Cited by 244 · see citing works
- Authors
- Dalmau, J., Gleichman, A. J., Hughes, E. G., Rossi, J. E., Peng, X., Lai, M., Dessain, S. K., Rosenfeld, M. R., Balice-Gordon, R., & Lynch, D. R.
- Affiliations
- University of Pennsylvania (US)
- Lankenau Institute for Medical Research (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Dalmau, Josep
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 7
- Issue
- 12
- Pages
- 1091-1098
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC2607118
- OpenAlex
- W2146199022
- Semantic Scholar
- dd855374110d7c7789974ad4472f335d53b94cd9
- Cited by
- 3,488
- References
- 35
- Citations by year
- 2026: 117 · 2025: 130 · 2024: 170 · 2023: 140 · 2022: 198 · 2021: 239 · 2020: 233 · 2019: 525 · 2018: 213 · 2017: 207 · 2016: 227 · 2015: 196 · 2014: 182 · 2013: 196 · 2012: 169
- FWCI
- 72.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (F31MH083395, R56MH057683, R01MH057683, R21 MH057683)
- National Cancer Institute (R01CA089054, R56CA089054, R01CA107192)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- anti-NMDA receptor encephalitis, NMDA receptor antibodies, autoimmune encephalitis, ovarian teratoma, psychiatric symptoms, seizures, dyskinesia, autonomic instability, hypoventilation, antibody epitopes, cancer immunotherapy
- MeSH terms
- Adolescent, Adult, Aged, Animals, Epitopes, Autoantibodies, Autoantigens, Brain, Cell Line, Cells, Cultured, Child, Child, Preschool, Encephalitis, Epilepsy, Female, Humans, Male, Middle Aged, Ovarian Neoplasms, Teratoma, Receptors, N-Methyl-D-Aspartate, Neurocognitive Disorders, Autoimmune Diseases of the Nervous System, Paraneoplastic Syndromes, Nervous System, Protein Subunits, Rats, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
