The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index; 17 of the 23 sources its claims cite were checked for support.
Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study
Open accessAbstract
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. Methods In this multi-institutional observational study (2007-2012), all patients with GluN1 antibodies were assessed at symptom onset and 4, 8, 12, 18, and 24 months using the modified Rankin Scale (mRS). Treatment included first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumor removal. Predictors of outcome were determined at the Universities of Pennsylvania and Barcelona using generalized linear mixed models with binary distribution. Results 577 patients (1-85 years, median 21) were studied, 212 were children (<18 years). Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%). Of 221 patients who failed first-line therapy, 125 (57%) received second-line immunotherapy resulting in better outcome than those who did not (OR 2·69, CI 1·24-5·80, p=0·012). During the first 24 months, 394/501 reached good outcome (mRS 0-2; median 6 months), and 30 died. At 24 month follow-up 204/252 (81%) had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment (OR 0·62, CI 0·50-0·76, p<0·0001) and lack of ICU admission (OR 0.12, CI 0·06-0·22,p<0·0001). 45 patients had one or multiple relapses (representing a 12% risk within 2 years); 46/69 (67%) relapses were milder than previous episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were comparable to those of the entire cohort. Conclusions Patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line therapies fail. Recovery can take more than 18 months.
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Written from the paper’s full text.
TL;DR
In this multi-institutional observational cohort of 577 patients with anti-NMDAR encephalitis, immunotherapy and tumor removal produced good outcome (mRS 0–2) in 394/501 within 24 months, and second-line immunotherapy improved outcomes after first-line failure. Early treatment and no ICU admission predicted good outcome.
Key findings
- 577 patients (1–85 years, median 21) were studied; 211 (37%) were younger than 18 in the Results (the abstract states 212 children). Of 501 assessable patients, 472 (94%) received first-line immunotherapy or tumor removal, and 251 (53%) improved within four weeks.
- Of 221 patients who failed first-line therapy, 125 (57%) received second-line immunotherapy, which was associated with better outcome than no second-line therapy (OR 2·69, CI 1·24–5·80, p=0·012).
- During the first 24 months, 394/501 reached mRS 0–2 (median 6 months); at 24-month follow-up 203/252 (81%) had good outcome, and 24 (9·5%) died in the Results (the abstract reports 30 died). Predictors of good outcome were early treatment (OR 0·62, CI 0·50–0·76, p<0·0001) and lack of ICU admission (OR 0·12, CI 0·06–0·22, p<0·0001).
- 45 patients had relapses, representing a 12% risk within 2 years; 46/69 (67%) relapses were milder than previous episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of second-line immunotherapy effect were comparable to the entire cohort (OR 3·35, CI 0·86–12·98, p=0·081).
Methods
- Multi-institutional observational study (2007–2012) of patients with GluN1 antibodies from the Universities of Pennsylvania and Barcelona and samples from 200 centers worldwide (32 countries); 577 patients were included for demographic analyses, and 501 had follow-up of at least 4 months (median 24 months, range 4–186).
- Patients were assessed at symptom onset and 4, 8, 12, 18, and 24 months using the modified Rankin Scale (mRS); symptoms were categorized into 8 groups. First-line immunotherapy was steroids, IVIg, or plasma exchange; second-line was rituximab or cyclophosphamide; tumor removal was also assessed. Treatment failure was no sustained improvement within four weeks and mRS ≥4.
- Statistical analysis used Fisher exact, Fisher-Freeman-Halton, or Mann-Whitney U tests; univariable binary logistic regression followed by generalized linear mixed models with binary distribution, subject as random effect, and time point from disease onset included; SAS GLIMMIX version 9.3.
Limitations
- The paper states the study was not randomized, was observational, and selection bias cannot be ruled out; individual treatments (e.g., plasma exchange vs IVIg or rituximab) could not be compared side-by-side statistically.
- The paper states there was no predefined protocol establishing order or combination of treatments, and treatment decisions were made by treating physicians based on clinical symptoms, family acceptance of side effects, and drug availability.
- The paper states that ending follow-up at 24 months likely underestimates recovery and overestimates mortality; imputation analysis estimated 7% mortality at 24 months. The text also shows inconsistent counts between abstract and Results for deaths, children, and 24-month good outcome, which is evident from the paper.
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Claims the paper makes
66 Own result · 11 Own interpretation · 10 Partly supported · 9 Own method · 2 Supported · 2 Sources not found · 2 No basis given · 1 Supported so far · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The lower frequency of neurological relapses (12% versus 20-24% reported in previous studies)11, 18 is likely due to better recognition of the disorder, earlier treatment, and increasing use of second-line immunotherapy.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
What the sources say
- Supportedcites [11] Irani, 2010, N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes, Brain source
The Results (Relapses; page not provided) report 10 patients with relapses, and the Results (Clinical outcomes; page not provided) identify a cohort of 44—about 23%, within the cited 20–24% range. The citation is attached to the previous-studies relapse rate; the proposed reasons for the lower rate are the citing authors’ interpretation. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [18] Gabilondo, 2011, Analysis of relapses in anti-NMDAR encephalitis, Neurology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 501- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“46/69 (67%) relapses were milder than previous episodes (p<0·0001).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 45 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Predictors of good outcome were early treatment (OR 0·62, CI 0·50-0·76, p<0·0001)”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plaincorrelationaln = 577 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“lack of ICU admission (OR 0.12, CI 0·06-0·22,p<0·0001)”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 221 patients who failed first-line therapy, 125 (57%) received second-line immunotherapy resulting in better outcome than those who did not (OR 2·69, CI 1·24-5·80, p=0·012).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 221 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the first 24 months, 394/501 reached good outcome (mRS 0-2; median 6 months), and 30 died.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 30- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 24 month follow-up 204/252 (81%) had good outcome.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plaindirectn = 472- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“577 patients (1-85 years, median 21) were studied, 212 were children (<18 years).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 212- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 27
- It may state two separate claims as one. 44
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Experiments where patients’ antibodies were added to cultures of hippocampal neurons or infused into the hippocampus of rodents showed specific antibody-mediated internalization of NMDAR and alteration of the mechanisms of synaptic plasticity.9, 10”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Partly supportedcites [9] Hughes, 2010, Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis, J Neurosci sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [10] Mikasova, 2012, Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis, Brain source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“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”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Supportedcites [3] Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol source
The Discussion says the disorder largely affects young people, that children can be affected, and that 41% of patients had no clinically detectable tumour. The Results document children both with and without teratoma, while the reported patient age range of 5–76 years supports occurrence across a broad span of ages. (LLM, conf=0.91)
- Supportedcites [4] Florance, 2009, Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents, Ann Neurol source
The Abstract’s Interpretation describes the disorder in adults, frequently young women, and says it also occurs in children and patients without teratoma. The Results report patients as young as 23 months and document teratomas in some, but not all, female patients in both age groups. Together, these passages support the citing sentence’s broad description of age and teratoma status. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Partly supportedcites [3] Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a center focused in the study of encephalitis of unclear etiology the frequency of anti-NMDAR encephalitis surpassed that of any specific viral etiologies in young individuals.6”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Supportedcites [6] Gable, 2012, The Frequency of autoimmune N-Methyl-D-Aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project, Clin Infect Dis source
The Frequency and Demographics section reports that, among CEP referrals aged 30 or younger with encephalitis of uncertain etiology, 32 had anti-NMDAR encephalitis, compared with 30 with enterovirus and fewer with each other listed viral cause. This supports the claim within the CEP cohort, not as a population-wide frequency estimate. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Despite the severity of the disease, patients often improve after intensive care support, immunotherapy, and prolonged hospitalizations that require multidisciplinary care.3, 11”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Supportedcites [3] Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol source
The Discussion reports that, despite severe symptoms requiring multidisciplinary care, 75 of 100 patients recovered or had mild deficits. The Results describe ventilatory support, immunotherapy, and a median hospitalisation of 2.5 months, consistent with the claim's account of intensive support and prolonged care. (LLM, conf=0.90)
- Partly supportedcites [11] Irani, 2010, N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes, Brain sourceExperimental — accuracy not yet measured
The Results (Clinical outcomes and serial estimations of antibodies; page unavailable) document severe disability, an average hospital stay of 160 days, immunotherapy, and improvement associated with earlier treatment. The Discussion (page unavailable) describes prolonged ventilation and intensive-care admissions. The paper does not establish that multidisciplinary care was required or that intensive-care support itself led to improvement. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Epidemiological studies suggest that this disorder is the most common cause of autoimmune encephalitis after acute demyelinating encephalomyelitis (ADEM).5”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Partly supportedcites [5] Granerod, 2010, Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study, Lancet Infect Dis sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says that about a fifth of patients had immune-mediated encephalitis, mostly ADEM, and reports 16 antibody-associated cases. The Results (page unavailable) identify NMDA receptor antibodies among the causes, but the passages do not establish that anti-NMDAR encephalitis was more common than the other antibody-associated cause after ADEM. (LLM, conf=0.78)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Follow-up information was obtained at regular intervals (4, 8, 12, 18, and 24 months) after symptom onset; neurological status was assessed with the modified Rankin scale (mRS).12”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Patients, diagnostic studies, and assessment of treatment and outcome
What the sources say
- Partly supportedcites [12] van Swieten, 1988, Interobserver agreement for the assessment of handicap in stroke patients, Stroke sourceExperimental — accuracy not yet measured
The Subjects and Methods section says the researchers used the modified Rankin scale to assess handicap in stroke patients. It does not report follow-up at 4, 8, 12, 18, and 24 months; its patients were assessed within the first week or within five months after stroke. (LLM, conf=0.89)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Moreover, studies suggest that the syndrome and response to treatment may differ between children and adults.4”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Introduction
What the sources say
- Partly supportedcites [4] Florance, 2009, Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents, Ann Neurol sourceExperimental — accuracy not yet measured
The Discussion describes differences between children and adults in symptom frequency and presentation, supporting the syndrome portion. It reports mixed responses to immunotherapy in children and suggests this could relate to their lower rate of tumors, but it does not establish a difference in treatment response between children and adults. Page numbers were not available in our copy. (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“If a tumor is found, removal is important because it expedites improvement and decreases relapses.3, 17”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
What the sources say
- Partly supportedcites [3] Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [17] Sabin, 2008, Case records of the Massachusetts General Hospital. Case 26-2008. A 26-year-old woman with headache and behavioral changes, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Antibody studies
What the sources say
- Partly supportedcites [3] Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The discovery of anti-NMDAR encephalitis has changed the diagnostic and treatment approach to several neurologic and psychiatric disorders, and has led to the identification of an expanding group of autoimmune encephalitis related to antibodies against synaptic proteins.19”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
What the sources say
- Partly supportedcites [19] Lancaster, 2012, Neuronal autoantigens—pathogenesis, associated disorders and antibody testing, Nat Rev Neurol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Rapidly progressive alterations of memory, behavior, cognition, and psychosis previously thought to be idiopathic or viral-induced are now known to be autoimmune.20-23”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
What the sources say
- Not checked — no full text of the sourcecites [20] Chapman, 2011, Anti-NMDA receptor encephalitis: diagnosis, psychiatric presentation, and treatment, Am J Psychiatry source
- Partly supportedcites [21] Kayser, 2011, The emerging link between autoimmune disorders and neuropsychiatric disease, J Neuropsychiatry Clin Neurosci sourceExperimental — accuracy not yet measured
The “Autoimmune Synaptic Encephalitis” section says limbic encephalitides once thought viral or paraneoplastic commonly have an autoimmune cause and can develop over days to weeks with memory and psychiatric symptoms. The claim overgeneralizes this finding: the paper does not say that rapidly progressive changes of these kinds are all now known to be autoimmune, and it describes some cases as idiopathic autoimmune processes rather than formerly thought idiopathic. (LLM, conf=0.84)
- Partly supportedcites [22] Pruss, 2012, IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment, Neurology sourceExperimental — accuracy not yet measured
The Discussion says synaptic autoimmunity can cause acute, severe changes in memory, behavior, and cognition, and the Index patient section describes delusions and hallucinations. But this paper primarily studies slowly progressive impairment; the Clinical course section says none of its seven patients had acute symptoms resembling classic anti-NMDAR encephalitis. Our copy does not establish that these conditions were previously thought to be viral-induced. (LLM, conf=0.88)
- Partly supportedcites [23] Pruss, 2012, NMDA receptor antibodies in herpes simplex encephalitis, Ann Neurol sourceExperimental — accuracy not yet measured
The Abstract’s Interpretation and the Discussion report NMDAR autoantibodies in some patients with herpes simplex encephalitis and suggest that autoimmunity may contribute to their symptoms. They do not establish that the listed memory, behavioral, cognitive, and psychotic symptoms—previously considered idiopathic or viral-induced—are now known to be autoimmune; the Discussion says clinical differences between antibody-positive and antibody-negative patients were not established. Page numbers are unavailable in our copy. (LLM, conf=0.87)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“45 patients had one or multiple relapses (representing a 12% risk within 2 years)”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 45- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 501- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were comparable to those of the entire cohort.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plainn = 177- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the first 24 months, 394/501 reached good outcome (mRS 0-2; median 6 months), and 30 died.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the 501 patients with at least 4 months follow-up, 461 (92%) were treated with first-line immunotherapy, 134 (27%) with second-line immunotherapy (Figure 2 and Table 2), 10 (2%) with tumor removal without immunotherapy, and 29 (6%) were not treated (see below).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Treatments and outcome
plainn = 501- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the first month of the disease, 498 of 571 (87%) patients developed four or more of the 8 categories of symptoms; only 6 (1%) remained mono-symptomatic (Table 1).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Clinical and diagnostic features
plainn = 571- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 197 patients with teratoma, 189 (96%) had tumor resection, 20 (11%) of them at neurological relapse or after recovery.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Treatments and outcome
plainn = 197- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MRI of the brain, EEG and CSF studies were abnormal in 180/540 (33%), 432/482 (90%) and 418/532 (79%) patients, respectively.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Clinical and diagnostic features
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence of a tumor predominated in patients between 12 and 45 years; only 4 females younger than 12 years (6%), and 7 males (6%, all adults) had a tumor (p<0·0005).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among patients who received second line immunotherapy, 84/125 reached an mRS 0-2 during the first 24 months, while among those who did not receive second line immunotherapy 49/96 reached an mRS 0-2 (median 10 and 15 months, respectively); at 24 month follow-up 43/55 (78%) and 32/58 (55%) had a good outcome (Figure 3C and 3D).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Analysis of effects of immunotherapy
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ten studies and one extended review describing at least three patients were identified; five of them included at least twenty-five patients.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Systematic review
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eighty-two of 177 (46%) children failed first-line immunotherapy; in these patients, the magnitude of the effects of second-line immunotherapy (used in 53 cases, 65%; Table S5) was comparable to that of the entire cohort although due to the smaller sample size it did not reach significance (Table S6B, OR 3·35, CI 0·86-12·98, p=0·081).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Treatment and outcome in patients younger than 18 years
plaincorrelationaln = 53- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the 24 month follow-up, 45 patients (representing a 12% risk) had clinical relapses, which in 15 patients (33%) were multiple (Table S4).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Relapses
plainn = 45- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It confirms the female preponderance, the high frequency of the disease in children, and a higher risk for an underlying teratoma in African-Americans.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“however, “ICU stay” and “time from symptom onset until initiation of treatment” were identified as significant prognostic factors.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two hundred and seven tumors (94%) were ovarian teratomas, 4 (2%) extraovarian teratomas, and 9 (4%) other tumors (two of each, lung, breast, testicular; one ovarian carcinoma, one thymic carcinomas, and one pancreatic cancer).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two hundred and eleven (37%) of all 577 patients were younger than 18 years, and 28 (5%) were 45 or older.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plainn = 577- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the first 24 months 241/251 reached an mRS 0-2 (median 3 months); at 24 month follow-up 111/115 (97%) of these patients had a good outcome (Figure 3B).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Analysis of effects of immunotherapy
plainn = 251- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 16 relapses (23%) the severity of symptoms was comparable to that of the initial episode, and in 7 (10%) was worse.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Relapses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The assessment of disease severity showed that 495/571 patients (87%) had a maximum mRS of 5, and 435 (77%) were admitted to the ICU.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Clinical and diagnostic features
plainn = 571- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with the initial episode, 46/69 (67%) relapses were less severe (as reflected by a lower mRS score measured at the stage of maximum severity), more frequently mono-symptomatic (24, 35%), and resulted in fewer admissions (12, 17%) to the ICU (all p<0·0001).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Relapses
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two hundred and eleven (37%) of all 577 patients were younger than 18 years, and 28 (5%) were 45 or older.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plainn = 577- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Four hundred and sixty-eight patients were female (81%; Figure 1A and Table S1).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plainn = 468- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While movement disorders were more frequent in children, memory deficits and central hypoventilation occurred more often in adults (Figure 1C).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Clinical and diagnostic features
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the current study, the frequency of relapses was somewhat less frequent than in previous reports; in addition, the milder nature of the symptoms compared with the initial episodes was noted in most relapses.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First-line immunotherapy was often insufficient to control the disease; in this group of patients the addition of second-line immunotherapy proved to associate significantly with a better outcome compared with those who did not receive second-line immunotherapy.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at 24 month follow-up 43/55 (78%) and 32/58 (55%) had a good outcome (Figure 3C and 3D).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Analysis of effects of immunotherapy
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second-line immunotherapy was well tolerated; only 4 patients had serious adverse effects, all reversible (Table 2).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two hundred and twenty (38%) patients had an underlying neoplasm; of these, 213 were women (representing 46% of all women).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plainn = 213- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In univariable analysis, the factors associated with good outcome included, no need for ICU (p<0·0001), early treatment (p=0·009), and low severity of disease within four weeks of onset (maximum mRS, p=0·011).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Treatments and outcome
plaincorrelationaln = 501 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Six of the nine patients with tumors other than teratomas were older than 45 years.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two hundred and thirty-eight adults (65%) presented with behavioral problems, while 55 children below 12 years (50%) presented with seizures or movement disorders (Figure 1B).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Clinical and diagnostic features
plainn = 238- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The frequency of males was higher in age groups below 12 years (43: 39%) and above 45 (12: 43%, p<0·0001).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Background
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Factors associated with a good outcome (p<0·1) were included in generalized linear mixed models with binary distribution, declaring the subject as random and the other factors as fixed effects.13”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Statistical analysis
What the sources say
- Not matchedcites [13] Verbeke, 2005
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, after failing first-line immunotherapy, all these patients remained in a similar poor neurological status, enabling the comparison between those who subsequently received second-line immunotherapy with those who did not.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All mRS scores at defined time points were used (4, 8, 12, 18, and 24 months; e.g. each patient’s follow-up could provide a maximum of 5 scores). The “time point from onset of disease” was included as an additional variable, allowing us to analyze patients with different duration of follow-up.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study has the limitations of not being randomized but sets the base for future trials to determine the efficacy of each individual treatment (e.g., steroids, IVIg, plasmapheresis, rituximab, and cyclophosphamide) and duration of immunotherapy.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After creation of this model, the effect of second-line immunotherapy was determined by adding second-line immunotherapy to the same model applied to only those patients who had failed first-line immunotherapy.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Statistical analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Symptom presentation varied between children and adults (“more neurological in children”, “more psychiatric in adults”), but in most cases the progression of symptoms evolved towards a similar syndrome.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By establishing the last follow-up assessment at 24 months, our study likely underestimates the frequency and level of recovery because some patients had a shorter follow-up, others continued to improve after 24 months, and those with substantial improvement tended to discontinue follow-ups (Figure S5A and B).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is the first study to provide extensive and structured follow-up and prognostic factors determining outcome.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the same reasons, the frequency of mortality is likely overestimated; imputation analysis estimated 7% mortality at 24 months (Figure S5C).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although selection bias cannot be ruled out in observational studies like this, we could not identify obvious bias between patients who after failing first-line therapies were treated with second-line therapy and those who did not: the severity of symptoms and duration of ICU stay was similar (92% vs 88%, and 88% vs 87%, respectively), and there were no differences in age, gender, ethnicity, and”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study extends epidemiological and clinical knowledge on anti-NMDAR encephalitis.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Research in context > Interpretation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All patients tested positive for NMDAR antibodies were included in the study without selection criteria other than availability of clinical information.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Patients, diagnostic studies, and assessment of treatment and outcome
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Factors influencing outcome were assessed by univariable binary logistic regression (good outcome defined as mRS 0-2) independently of the treatments given.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Statistical analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients with a follow-up shorter than 4 months were excluded from analysis of effects of treatment and outcome.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Methods > Patients, diagnostic studies, and assessment of treatment and outcome
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, second-line immunotherapy with rituximab, cyclophosphamide or both significantly improved the outcome of those who did not respond to first-line therapy, and decreased the frequency of relapses.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This large, observational study demonstrates that immunotherapy and tumor removal if applicable, result in substantial neurological improvement in 81% of patients with anti-NMDAR encephalitis after a median follow-up of 24 months.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The use of immunotherapy and the long-term outcome in anti-NMDAR encephalitis have not been defined.
“Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined.”
The paper relies on this without support.
The efficacy of immunotherapy and its impact in the long-term outcome have not been established.
“However, the efficacy of immunotherapy and its impact in the long-term outcome have not been established.”
The paper relies on this without support.
A substantial number of patients fail to respond to first-line immunotherapy, and for these patients the treatment strategy and outcome are unknown.
“A substantial number of patients fail to respond to first-line immunotherapy, such as steroids, plasmapheresis, and intravenous immunoglobulins (IVIg) and for these patients the treatment strategy and outcome are unknown.”
The authors state this as an assumption.
A systematic analysis of the effects of sequential immunotherapy and their impact on long-term outcome has not been previously done in any of these disorders or other antibody-mediated neurological diseases.
“To our knowledge, a systematic analysis of the effects of sequential (first-, second-line) immunotherapy and their impact on long-term outcome has not been previously done in any of these disorders or other antibody-mediated neurological diseases.”
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
“577 patients (1-85 years, median 21) were studied, 212 were children (<18 years).”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Demographics
“Two hundred and eleven (37%) of all 577 patients were younger than 18 years”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Abstract > Results
“At 24 month follow-up 204/252 (81%) had good outcome.”
§ Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis: a cohort study > Results > Treatments and outcome
“At 24 month follow-up 203/252 (81%) had a favorable outcome”
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Neurobiology of Neuroimmune Encephalitic Disorders
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Dujmović, I., & Howard, J. F. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95702-1.00230-x
Recurrent Anti‐NMDAR Encephalitis Necessitating Oophorectomy in an Adolescent Patient: A Case Report
Shadowen, C. R., Nidhi, A., Alexa, F., Cole, M., Terasaki, L., Hannah, A., Aaron, G., & Lindsey, P. (2024) · Case Reports in Obstetrics and Gynecology · doi:10.1155/2024/6150107
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Autoimmune Encephalopathies Presenting in the ICU
Banks, S. A., & Rabinstein, A. A. (2024) · Springer eBooks · doi:10.1007/978-3-031-62220-5_30 · Cited by 1
Anti-NMDAR1 antibody impairs dendritic branching in immature cultured neurons
Jorratt, P., & Petrušková, A. (2024) · Journal of Applied Biomedicine · doi:10.32725/jab.2024.019
Sharma, N. R., Pokhrel, M., Prabal, K. C., Paudel, S., Lamichhane, P., Boadla, M. E. R., & Alvarez, B. (2024) · Cureus · doi:10.7759/cureus.72415
Immune-mediated neurological syndromes associated with childhood cancers
Rossor, T. E., Tewari, S., Gadian, J., Kaliakatsos, M., Angelini, P., & Lim, M. J. (2024) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2024.10.013
Psychiatric Camouflage: A Case Series
Sreedevi, S., Thekkethil, D. P., & Menon, B. (2024) · Cureus · doi:10.7759/cureus.72912
Encefalitis autoinmune por anticuerpos antirreceptor de NMDA: a propósito de un caso
Velásquez-Acebey, V. G., & Sellart-Altisent, M. (2024) · Psiquiatría Biológica · doi:10.1016/j.psiq.2024.100541
Paraneoplastic Neurological Syndromes
Muñiz‐Castrillo, S., Villagrán‐García, M., & Honnorat, J. (2024) · Springer eBooks · doi:10.1007/978-3-031-60006-7_14
Autoimmune Limbic Encephalitis
Shelly, S., Narayan, R., & Dubey, D. (2024) · Springer eBooks · doi:10.1007/978-3-031-60006-7_18
Becherano, G., Podgaetz, E., Ahmed, S., Ringenberg, S., & Schwartz, G. (2024) · The Cardiothoracic Surgeon · doi:10.1186/s43057-024-00140-2
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Late relapse of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis: a case report
Amiri, H., Karimi, M., & Shariatmadari, F. (2024) · Journal of Medical Case Reports · doi:10.1186/s13256-024-04886-5
Encephalitis: from mechanisms to management
Kolchinski, A., Li, M., & Venkatesan, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19130-5.00037-x
Farina, A., Campetella, L., Luque, J. A., Villagrán‐García, M., & Honnorat, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19130-5.00036-8
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Kamath, A. G., Baskaran, D., & Sastry, U. R. (2025) · BMJ Case Reports · doi:10.1136/bcr-2024-262095
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Immunomediated Encephalitis: New Diagnoses on the Neurology–Psychiatry Interface
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Metadata
- Authors
- Titulaer, M. J., McCracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., Honig, L. S., Benseler, S. M., Kawachi, I., Martinez-Hernandez, E., Aguilar, E., Gresa-Arribas, N., Ryan-Florance, N., Torrents, A., Saiz, A., Rosenfeld, M. R., Balice-Gordon, R., Graus, F., & Dalmau, J.
- Affiliations
- Hospital of the University of Pennsylvania (US)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- California Department of Public Health (US)
- Kitasato University Hospital (JP)
- Columbia University (US)
- University of Toronto (CA)
- Brain Research Institute, Niigata University (JP)
- Hospital Clínic de Barcelona (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Dalmau, Josep
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 12
- Issue
- 2
- Pages
- 157-165
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC3563251
- OpenAlex
- W2163022996
- Semantic Scholar
- 620c73775fc208276d59ab7e761fc4b6da598ff4
- Cited by
- 3,165
- References
- 28
- Citations by year
- 2026: 225 · 2025: 231 · 2024: 249 · 2023: 239 · 2022: 287 · 2021: 329 · 2020: 296 · 2019: 274 · 2018: 222 · 2017: 193 · 2016: 202 · 2015: 169 · 2014: 152 · 2013: 90
- FWCI
- 129.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (23591236)
- National Institute on Aging (P50AG008702)
- National Institute of Mental Health (R01MH094741)
- National Cancer Institute (R01CA089054, R56CA089054, R01CA107192)
- National Institute of Neurological Disorders and Stroke (RC1NS068204, R01NS077851)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- anti-NMDA receptor encephalitis, NMDA receptor antibodies, immunotherapy, rituximab, cyclophosphamide, plasmapheresis, intravenous immunoglobulin, corticosteroids, tumor resection, long-term outcomes, prognostic factors, modified Rankin Scale, autoimmune encephalitis, children, adults
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Autoantibodies, Child, Child, Preschool, Female, Humans, Immunotherapy, Infant, Male, Middle Aged, Retrospective Studies, Time Factors, Cohort Studies, Logistic Models, Receptors, N-Methyl-D-Aspartate, Immunoglobulins, Intravenous, Treatment Outcome, Observation, Young Adult, Anti-N-Methyl-D-Aspartate Receptor Encephalitis
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.
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