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Paraneoplastic anti-NMDA receptor encephalitis in 1830? | Neurology Neuroimmunology & Neuroinflammation

Paraneoplastic anti-NMDA receptor encephalitis in 1830? | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Abstract Objective Our aim was to identify patients with probable anti-NMDA receptor encephalitis among historical medical cases. Method A case report published in leading Hungarian-, German- and Italian-language medical journals in the early 1840s was revisited. Results In 1830, an 18-year-old, healthy woman suffered epileptic seizures, followed by a 6-day-long state characterized by catalepsy, unresponsiveness, motionless, and light breathing. Her symptoms regularly returned in the following 1.5 years. Meanwhile, a progressively growing huge abdominal tumor appeared. One day, she suddenly started vomiting a large amount of foul-smelling pus mixed with blood, accompanied by bone fragments. Pus mixed blood with some membranous substance was also evacuated through the anus and vagina. After this event, she completely recovered; 1.5 years later, she married and later gave birth to 3 healthy children. The patient remained healthy during the 11-year follow-up. Conclusions We suggest that in the description of a paraneoplastic case, an anti-NMDA receptor encephalitis can be dated back as far as to the 19th century, with an especially rare type of resolution: the disappearance of the symptoms after the spontaneous elimination of an ovarian teratoma. Anti-NMDA receptor encephalitis was discovered by Dalmau et al.1,2 in 2005/2007, although cases were probably described already in 1997.3,4 Moreover, because of revisiting published cases dating back as far as the 19th century, more and more cases are suggested to be of anti-NMDA receptor encephalitis etiology. Merwick et al.5 pointed out that from the case series published by Bickerstaff—in which Bickerstaff encephalitis was described—in one patient, the symptoms were indicative of anti-NMDA receptor encephalitis. In the late 1800s, ovariotomy (Battey's operation) was introduced as a treatment of—among others—“histeroepilepsy.”6 In the course of the recent revisitation of these published cases, symptoms can also be attributed to anti-NMDA receptor encephalitis in more than one patient; this suggestion is also supported by the observation of Battey, namely that “cystic degeneration” was common in the resected ovaries.6 This is the most common autoimmune encephalitis, where 80% of patients are women with a median age of 21.7 Epileptic seizures occur in 76%,8 catatonia-like episodes in 70%,9 whereas hypoventilation in 66% of patients.8 In adult women patients, anti-NMDA receptor encephalitis is associated with ovarian teratoma in 58% of cases.7 Other tumors are rare: in paraneoplastic cases, 94% of the underlying tumor is ovarian teratoma.7 We found an interesting case report published in leading Hungarian-, German- and Italian-language medical journals referring to a presentation at the 3rd Meeting of the Italian Scientists in Florence held in 1841.10,–,12 We suggest that the description of an anti-NMDA receptor encephalitis can be dated back as far as to the 19th century. Case On September 17, 1841, the case was presented by Dr. Odoardo Linoli (figure).10,–,12 In 1830, an 18-year-old, hitherto healthy female patient suffered epileptic seizures, followed by a strange 6-day-long state characterized by a “catalepsy” pose and an unresponsive motionless state. The only sign of life was a very light breathing. Epileptic seizures and the catalepsy regularly returned in the following 1.5 years. Meanwhile, a progressively growing huge abdominal tumor appeared, which reached the level of the chest on the left side. One day, she suddenly started vomiting a large amount of coffee-colored liquid. Two weeks later, she vomited a foul-smelling pus mixed with blood. This was accompanied by more than 100 bone fragments. Some of these fragments were flat, others were long- or ball-shaped. Pus-mixed blood with some membranous substance was also evacuated through the anus and vagina. After this event, both epileptic seizures and “catalepsy” states disappeared, and she apparently became healthy again; 1.5 years later, she married and later gave birth to 3 healthy children. At the time of Dr. Linoli's presentation (11 years after the disease onset), she was in excellent health. During the discussion, Dr. Linoli argued that the abdominal tumor was probably a “fetal cyst” or “fetus in fetu.” Prof. Carlo Burci—the chairman of the section—suggested that the tumor could have been a “skin cyst,” whereas others speculated that it could have been an extrauterine pregnancy. Figure Case presentation The title page of the Österreichische Medizinische Wochenschrift from 1843 (A) and the case presentation in German (B). Available at the Bayerische Staatsbibliothek München, H.misc. 33 t-16, S. 244, urn:nbn:de:bvb:12-bsb10737557-2. Discussion The medical language in the first half of the 19th century was certainly different from today. The reliability of the description is enhanced by the fact that the case has been described in 3 different languages in the 1840s.10,–,12 The case was presented by Odoardo Linoli (1801–1886), a well-known surgeon from Pietrasanta,13 and discussed by Carlo Burci,14 who was the professor of surgery at the University of Pisa, indicating that the case was observed and discussed by the most prestigious professionals of that time. We tried to interpret this case report according to today's medical concepts. Although catatonia was not described as such until 1874, the described motionless and unresponsive state accompanied by catalepsy meet the criteria of a catatonia.15 Another issue is the type of the described huge abdominal tumor that contained bone fragments. According to Dr. Linoli's interpretation, it was a “fetus in fetu.” Fetus in fetu is extremely rare in adulthood16 and should contain vertebral axis or limbs, otherwise it should classify as teratoma.17 Dr. Burci suggested that the tumor was a “skin cyst.” According to today's nomenclature, dermoid cyst (i.e., skin-like cyst) is a synonym for teratoma. The presence of bone is not unusual in teratoma.18 Based on the presence of bone, a teratoma was diagnosed during a paleopathological examination of a female skeleton from the late Roman age.19 Ovarian teratomas without treatment can reach a huge size, some of them can be up to 30 cm in diameter.18 Not only the size, localization, and the presence of bone but also the strange elimination of the tumor through the gastrointestinal system and vagina may also support the concept of teratoma. Teratomas (dermoid cysts) can perforate into the adjacent organs including bowel and vagina.20,–,23 For example, Flood et al.22 reported a 23-year-old woman who discovered teeth-like structures in her underwear, which were the contents of an ovarian teratoma excreted in the vagina through a fistula. Mitui et al.23 reported a 72-year-old woman whose diarrhea, in which she found hair, was caused by an ovarian teratoma perforating into the bowels. Summarizing our interpretation, a young woman had newly onset seizures, followed by catatonia-like symptoms and hypoventilation. This was associated with an abdominal tumor, which was probably a teratoma. The symptoms disappeared after the spontaneous elimination of the tumor, and the patient remained healthy during the 11-year follow-up. According to a recent position study, new-onset seizures and altered mental status (unresponsive state) with subacute onset meet the criteria for “possible autoimmune encephalitis.”24 Epileptic seizures, altered mental status, abnormal posturing, and hypoventilation meet the symptoms criteria for “possible anti-NMDA receptor encephalitis.”24 The young age and female sex as well as the presence of ovarian teratoma also strengthen our assumption that Dr. Linoli's case study might be the first description of anti-NMDA receptor encephalitis. In paraneoplastic anti-NMDA receptor encephalitis, the symptoms usually resolve after tumor removal, may that be either ovarian or extraovarian.7,25 Regarding Dr. Linoli's patient, the symptoms were present when the tumor was present and disappeared after the tumor also disappeared. Thus, we state that the description of a paraneoplastic story can be dated back as far as to 1830, ahead of the description of Trousseau's syndrome in 1865.26 Study funding Study funded by the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002), NKFIH EFOP-3.6.2-16-2017-00008 government-based funds. Our research was partly financed by the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary, within the framework of the 5th thematic program of the University of Pécs, Hungary (20765/3/2018/FEKUSTRAT). The study was furthermore supported by the University of Pécs Medical School. Disclosure None of the authors report anything to disclose. Go to Neurology.org/NN for full disclosures. Appendix Authors Footnotes Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. The Article Processing Charge was funded by University of Pécs. Received July 30, 2020. Accepted in final form August 12, 2020. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. References 1.↵Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61:25–36.OpenUrlCrossRefPubMed 2.↵Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 2005;58:594–604.OpenUrlCrossRefPubMed 3.↵Nokura K, Yamamoto H, Okawara Y, Koga H, Osawa H, Sakai K. Reversible limbic encephalitis caused by ovarian teratoma. Acta Neurol Scand 1997;95:367–373.OpenUrlCrossRefPubMed 4.↵Okamura H, Oomori N, Uchitomi Y. An acutely confused 15-year-old girl. Lancet 1997;350:488.OpenUrlCrossRefPubMed 5.↵Merwick A, Dalmau J, Delanty N. Insights into antibody-associated encephalitis—Bickerstaff's 1950's papers revisited. J Neurol Sci 2013;334:167–168.OpenUrlPubMed 6.↵Komagamine T, Kokubun N, Hirata K. Battey's operation as a treatment for hysteria: a review of a series of cases in the nineteenth century. Hist Psychiatry 2020;31:55–66.OpenUrl 7.↵Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157–165.OpenUrlCrossRefPubMed 8.↵Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7:1091–1098.OpenUrlCrossRefPubMed 9.↵Espinola-Nadurille M, Flores-Rivera J, Rivas-Alonso V, et al. Catatonia in patients with anti-NMDA receptor encephalitis. Psychiatry Clin Neurosci 2019;73:574–580.OpenUrl 10.↵Linoli O. Fall von Epilepsie mint Katalepsie [A case of epilepsy with catalepsy, German]. Österreichische Medizinische Wochenschrift 1843;12:319. Available at (free access): opacplus.bsb-muenchen.de/Vta2/bsb10086743/bsb:5976959?page=325. Accessed June 23, 2020.OpenUrl 11.↵Third Meeting of Italian Scientists in Florence. Annali Universali di Medicina 1842;40:17–20. Available at (free access): archive.org/details/s12id13209690/page/17. Accessed June 23, 2020.OpenUrl 12.↵Bugát P, Flór F. Kivonatok idegen lapokbul és munkákbul. Kór- és gyógytudomány. Nehézkor dermengéssel. [Extracts from foreign works. Pathology and medicine. Epilepsy with catalepsy, Hungarian] Orvosi Tár 1843;17:295. Available at (free access): library.hungaricana.hu/hu/view/ORSZ_ORVO_OT_1843_04/. Accessed June 23, 2020.OpenUrl 13.↵Wikipedia article. Available at: treccani.it/enciclopedia/odoardo-linoli_(Dizionario-Biografico)/. Accessed June 12, 2020. 14.↵Wikipedia article. Available at: it.wikipedia.org/wiki/Carlo_Burci. Accessed June 12, 2020. 15.↵Tandon R, Heckers S, Bustillo J, et al. Catatonia in DSM-5. Schizophr Res 2013;150:26–30.OpenUrlCrossRefPubMed 16.↵Kumar A, Paswan SS, Kumar B, Kumar P. Fetus in fetu in an adult woman. BMJ Case Rep 2019;12:e230835.OpenUrl 17.↵Willis RA. The structure of teratoma. J Pathol Bacteriol 1935;40:1–36.OpenUrlCrossRef 18.↵Caruso PA, Marsh MR, Minkowitz S, Karten G. An intense clinicopathologic study of 305 teratomas of the ovary. Cancer 1971;27:343–348.OpenUrlCrossRefPubMed 19.↵Armentano N, Subirana M, Isidro A, Escala O, Malgosa A. An ovarian teratoma of late Roman age. Int J Paleopathol 2012;2:236–239.OpenUrl 20.↵von-Walter AR, Nelken RS. Benign cystic ovarian teratoma with a fistula into the small and large bowel. Obstet Gynecol 2012;119:434–436.OpenUrlPubMed 21.↵Zarain García F. Teratoma quístico del ovario con absceso y fístula a vagina (Cystic teratoma of the ovary with abscess and fistula in the vagina [in Spanish]). Ginecol Obstet Mex 1974;36:49–53.OpenUrlPubMed 22.↵Flood K, Breathnach F, Gleeson N. An unusual presentation of a dermoid cyst. J Obstet Gynaecol 2010;30:72–73.OpenUrlPubMed 23.↵Mitui AH, Fujita R, Sugata F, Kienebuchi M, Suzuki K, Sagawa F. A case of ovarian dermoid cyst with malignant transformation perforated into the rectosigmoid colon and small intestine. Endoscopy 1983;15:331–333.OpenUrlCrossRefPubMed 24.↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.OpenUrlCrossRefPubMed 25.↵Kümpfel T, Gerdes LA, Heck C, Prüss H. Delayed diagnosis of extraovarian teratoma in relapsing anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm 2016;3:e250. doi: 10.1212/NXI.0000000000000250. 26.↵Darnell RB, Posner JB. Paraneoplastic Syndromes. Oxford/New York: Oxford University Press; 2011.
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Neural Antibody Testing in Patients with Suspected Autoimmune Encephalitis | Clinical Chemistry | Oxford Academic

Neural Antibody Testing in Patients with Suspected Autoimmune Encephalitis | Clinical Chemistry | Oxford Academic | AntiNMDA | Scoop.it
AbstractBackground. Autoimmunity is an increasingly recognized cause of encephalitis with a similar prevalence to that of infectious etiologies. Over the past d
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Ten Point Guide to Mental State Examination (MSE) in Psychiatry

Ten Point Guide to Mental State Examination (MSE) in Psychiatry | AntiNMDA | Scoop.it
This 10 point guide to mental state exam (MSE) enhaces your psychiatric evaluation skills. An accurate MSE assists in the diagnosis of mental illness.
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Hallucinations Lead to Ovarian Cancer Diagnosis for Young Woman

Hallucinations Lead to Ovarian Cancer Diagnosis for Young Woman | AntiNMDA | Scoop.it
Lauren went from a psychiatric ward in a local hospital to the ICU....
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Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors - Alberto Vogrig, Sergio Muñiz-Castrillo, Virginie Desestret, Bastien Joubert, Jérôme Hon...

Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors - Alberto Vogrig, Sergio Muñiz-Castrillo, Virginie Desestret, Bastien Joubert, Jérôme Hon... | AntiNMDA | Scoop.it
Paraneoplastic neurological syndromes (PNSs) are rare complications of systemic cancers that can affect all parts of the central and/or peripheral nervous system. A body of experimental and clinica...
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Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis

Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first episode psychosis | AntiNMDA | Scoop.it
When psychosis develops in NMDAR antibody encephalitis it usually has an acute or
subacute onset, and antipsychotic treatment may be ineffective and associated with
adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first episode psychosis (FEP), but their...
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https://www.researchgate.net/publication/343817904_Anti-N-methyl-D-Aspartate_NMDA_Receptor_Encephalitis_A_Case_Report

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Defying the odds, U of T's Carisse Samuel to graduate after spending five months in a coma

Defying the odds, U of T's Carisse Samuel to graduate after spending five months in a coma | AntiNMDA | Scoop.it
When Carisse Samuel joins her fellow graduates at the University of Toronto’s virtual convocation this Saturday, the celebration will be both an academic and personal victory.
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Clinical features which predict neuronal surface autoantibodies in new-onset focal epilepsy: implications for immunotherapies | Journal of Neurology, Neurosurgery & Psychiatry

Introduction Neuronal surface-directed antibodies (NSAbs) are considered pathogenic in patients with autoimmune encephalitis (AE). AE commonly presents with prominent seizures and neuropsychiatric features and shows a preferential response to immunotherapies versus anti-seizure medications (ASMs).1–4 This has prompted the introduction of ‘epilepsy of immune aetiology’ within the International League Against Epilepsy (ILAE) 2017 classification.5 The same NSAbs, as well as high levels of antibodies to intraneuronal glutamic acid decarboxylase-65 (GAD65), are also described in the serum of people with more isolated forms of epilepsy, without core features of encephalitis.6–8 In this context, their clinical, aetiological and therapeutic relevance is unclear, but of major potential importance to all neurologists who manage new-onset epilepsy. In our large, prospective, real-world study of new-onset focal epilepsy, we predicted that formes frustes of AE would help identify clinical features suggesting the presence of NSAbs and asked whether detection of these NSAbs should alter patient management. Materials and methods Between 9 December 2011 and 4 November 2015, consecutive adult patients (≥18 years) with a diagnosis of new-onset focal epilepsy and their first seizure within the previous 12 months were prospectively recruited from the routine practice of two epileptologists at the Oxford University Hospitals NHS Foundation Trust. Written informed consent and sera were obtained (Ethical approvals: Oxfordshire RECA 07/Q160X/28 and REC16/YH/0013). Clinical data gathered at onset (online supplemental table 1) included detailed phenotype and investigation results, Quality of Life in Epilepsy-31, Hospital Anxiety and Depression Score, Addenbrooke’s Cognitive Examination (ACE) and modified Rankin Score (mRS); as well as information to inform the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score (online supplemental table 2)9 10 and diagnostic criteria for possible or definite AE.11 Subsequently, 1-year and 3-year mRS were ascertained from patients with NSAbs. Supplemental material For NSAbs, sera were tested against autoantigen-expressing live HEK293 cells (live cell-based assay; online supplemental table 3), and for reactivity with the surface of live cultured hippocampal neurons, using sensitive protocols.12 13 Autoantibodies to GAD65 were determined using a commercial radioimmunoprecipitation assay. Statistical analysis was conducted in R (V.3.6.1). Dimensionality reduction was performed using Multiple Factor Analysis in ‘FactoMineR’ with up to 10% missing data imputed using missForest. Stepwise Bayesian general linear modelling analysis was undertaken using ‘arm’. Wilson 95% CIs with continuity correction were calculated using ‘DescTools’. Results NSAb findings Of 241 recruited patients, 22 were excluded (online supplemental table 4). Of the remaining 219, median age was 49 years (range 16–91) and 109 (49.8%) were female. In 23/219 (10.5%) patients, serum NSAbs were detected across candidate and novel autoantigens (table 1) including roughly equal frequencies against leucine-rich glioma inactivated-1 (LGI1), contactin-associated protein-like 2 (CASPR2), plus the N-methyl-d-aspartate receptor (NMDAR) and γ-aminobutyric acid A/B receptors (GABAAR and GABABR). An additional five patients had antibodies to the surface of live neurons, without an established autoantigen. Autoantibodies to contactin-2, the glycine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) were each found in one patient. No dipeptidyl-peptidase-like protein 6 (DPPX) or high-titre GAD65 antibodies were detected. Overall, from the 23 people with NSAbs, 9 had a clinical diagnosis of AE (7/9 fulfilling published criteria).11 By contrast, none of the 196 without NSAbs had a clinical diagnosis of AE (p<0.0001; Fisher’s exact test). VIEW INLINE VIEW POPUP Table 1 Clinical and laboratory features of patients with epilepsy and positive neuronal surface autoantibodies Factors associated with the presence of NSAbs and AE Dimensionality reduction with multiple factor analysis showed that patients were highly heterogeneous and the modest clustering of those with NSAbs was largely driven by a clinical diagnosis of AE (figure 1A,B). Univariate analysis identified 11 clinical parameters that differed significantly between patients with and without NSAbs: age (p=0.04), ictal piloerection (p=0.02), lesional MRI (p=0.04), self-reported mood disturbance (p=0.007), ACE attention domain (p=0.01), ACE total score (p=0.04), QOLIE-31 score (p=0.02), self-reported neuropsychiatric features (p=0.03), epilepsy risk factors (p=0.05), inflammatory cerebrospinal fluid (CSF; p=0.004) and limbic system lesions on MRI (p=0.0002). A multivariate stepwise regression model allocated weighted scores to six of these: age ≥54 years=+1, self-reported mood disturbance=+1, limbic system lesions on MRI=+2, ictal piloerection=+2.5, ACE attention score ≥16=−1.5 and epilepsy risk factors=−1.5 (figure 1C). The probability of NSAb positivity increased with higher scores (Spearman’s ρ=0.99, p<0.0001; figure 1C) and receiver operating characteristic (ROC) analysis confirmed these features strongly predicted NSAb status (area under the curve (AUC)=0.83; total score ≥0; sensitivity=66.7%, specificity=84.9%; figure 1D). By contrast, the APE2 score performed less well in predicting NSAb status (sensitivity 43.5%, specificity 79.1%, AUC=0.68) and more accurately predicted criteria-defined AE, particularly if associated with NSAbs (sensitivity 85.7%, specificity 78.8%, AUC=0.94; figure 1E). Figure 1 Clinical phenotypes associated with NSAb status in new-onset focal epilepsy. The first two dimensions are shown, highlighting: (A) NSAb-positive (red) or NSAb-negative (grey) status and (B) NSAb-positive (pale red) or NSAb-negative (grey) without encephalitis (dots), or NSAb-positive (dark red) with clinically diagnosed autoimmune encephalitis (triangles). (C) The proportion of patients by total model score. Error bars show 95% CIs. The inset shows the weighting and SE of each factor within the regression model. (D) Receiver operator characteristic (ROC) curve of the total model score for predicting NSAb status across all patients. (E) ROC curve of the APE2 score for predicting NSAb status across all patients (black), patients not meeting the criteria for autoimmune encephalitis (blue), patients meeting the criteria for autoimmune encephalitis (red) and predicting NSAb-positive criteria-confirmed autoimmune encephalitis across all patients. (F) Scatter plot of modified Rankin score in NSAb-positive patients by immunotherapy status over time (Mann-Whitney U test p values<0.05). AE, autoimmune encephalitis; APE2, Antibody Prevalence in Epilepsy and Encephalopathy; epilepsy RF, epilepsy risk factors; MRI limbic Δ, changes within the limbic system on MRI. Comparisons of those with and without AE From 23 patients with NSAbs (table 1), a comparison of those with (n=9) and without (n=14) a clinical diagnosis of AE revealed several differences in the AE cohort: more ASMs (median of 3 vs 1; p=0.0073), more frequent immunotherapies (7/9 vs 0/14, p=0.0001), higher APE2 scores (median of 6 vs 2; p<0.0001), more frequent MRI limbic inflammation (6/9 vs 0/14; p=0.0008) and a trend towards greater positivity of serum IgGs targeting the surface of live neurons (7/9 vs 5/14, p=0.09). Compared with the seven patients administered immunotherapy, those with NSAbs who were not administered immunotherapy showed lower disability after 1 and 3 years (both p<0.05), and 11/16 (68.8%) were asymptomatic at 3-year follow-up (mRS=0 ; figure 1F). Hence, despite no immunotherapy, patients with NSAbs, but without AE, generally showed good outcomes. Discussion In this prospective study of 219 consecutive adults with new-onset focal epilepsy, NSAb status was best predicted by a combination of clinical parameters which closely resemble features observed in AE. Almost half of our patients with NSAbs were diagnosed with AE, and ~30% fulfilled stringent criteria for AE.11 Of those with NSAbs and more isolated forms of epilepsy, without individual features of AE, almost all were treated with ASMs alone and typically remained asymptomatic at long-term follow-up. Overall, these findings suggest that detection of NSAbs in patients with new-onset seizures, but without features of AE, should not alter current clinical management. Our observations should help guide the frequent clinical dilemma of which patients with new-onset seizures to test for autoantibodies and subsequently treat with immunotherapy. Taken together, our data suggest the clinical phenotype is paramount in guiding the relevance of autoantibody results, and provide data to address an outstanding question from a recent ILAE consensus statement.7 This ILAE statement also highlighted controversy over the term ‘autoimmune epilepsy’.7 In routine clinical practice, this nomenclature acts as a valuable signpost and aide memoire when seeing patients with seizures.2 14 However, ‘epilepsy’ carries several social stigmata and is defined by an enduring tendency to seizures. In AE, this lifelong risk is refuted by a recent study,4 despite several forms of AE commonly leading to hippocampal atrophy.2–4 7 10 The alternative concept of acute symptomatic seizures may more accurately capture the nature of seizures in patients with AE. Data-driven modifications to nomenclature will benefit from longer-term follow-up studies. Ictal piloerection, low mood and attention and MRI limbic system changes are recognised features of late-onset AE, particularly in association with LGI1 antibodies.2 4 14 15 The absence of movement disorders or more diffuse cognitive impairment as predictive factors in our model suggests the overall syndrome may reflect a formes frustes of AE. This contrasts with APE2 score parameters,9 which appear to largely reflect more florid features seen in classical AE. Our observational study has several limitations. These include limited CSF autoantibody measurements, which reflected UK practice particularly at the start of the study period. Yet,w ithout this valuable parameter, a diagnosis of NMDAR-antibody encephalitis is still possible.11 Yet, two of our four patients with serum NMDAR antibodies did not have features consistent with encephalitis, likely suggesting detection of clinically unrelated serum antibodies in these cases. In addition, our series in total only identified nine AE cases, although this may be considered substantial given the largely outpatient-based recruitment. This, and the high (~10%) seroprevalence rate, may reflect a referral bias given Oxford’s interest in AE, but is well aligned with other available estimates.6 9 10 Our serological data identified some samples with NSAbs proven by live cell-based assays, but without concomitant cell surface neuronal reactivities. This was especially evident in the cohort without a clinical diagnosis of AE, and perhaps these antibodies reflect low-affinity or low-titre autoantibodies which are not disease relevant. Their specificity, however, remains reassuring given their typical selectivity for just one of eight surface-expressed autoantigens. In the future, our prediction model will benefit from validation in independent, larger studies which may compare the risk of enduring seizures in the NSAb-positive versus NSAb-negative populations, with and without AE, something which we did not survey at follow-up. Hence, we cannot comment on long-term seizure status in the 5/16 patients (31%) who had NSAbs, no diagnosis of AE and 3-year mRS >0. In these patients, it remains possible that immunotherapy would have led to a greater benefit. However, in our view, this finding is more likely to be consistent with the predicted ~30% of all people with epilepsy who are known to become ASM resistant: this provides a testable hypothesis for a future randomised controlled trial. Overall, our observations support the concept that, in patients who present with new-onset focal seizures, clinical features which are consistent with a ‘mild encephalitis’ helps identify those with NSAbs which should alter patient management. This clinico-serological syndrome appeared characteristic and its recognition will improve detection and treatment of these patients. These findings should discourage widespread screening strategies to identify patients with autoantibodies among unselected seizure cohorts. References ↵Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.doi:10.1002/ana.22307 ↵Thompson J, Bi M, Murchison AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 2018;141:348–56.doi:10.1093/brain/awx323OpenUrlCrossRef ↵Geis C, Planagumà J, Carreño M, et al. Autoimmune seizures and epilepsy. J Clin Invest 2019;129:926–40.doi:10.1172/JCI125178OpenUrlPubMed ↵de Bruijn MAAM, van Sonderen A, van Coevorden-Hameete MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology 2019;92:e2185–96.doi:10.1212/WNL.0000000000007475pmid:30979857OpenUrlPubMed ↵Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512–21.doi:10.1111/epi.13709pmid:http://www.ncbi.nlm.nih.gov/pubmed/28276062OpenUrlPubMed ↵Brenner T, Sills GJ, Hart Y, et al. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 2013;54:1028–35.doi:10.1111/epi.12127pmid:http://www.ncbi.nlm.nih.gov/pubmed/23464826OpenUrlCrossRefPubMed ↵Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: conceptual definitions. Epilepsia 2020;61:1341–51.doi:10.1111/epi.16571pmid:http://www.ncbi.nlm.nih.gov/pubmed/32544279OpenUrlPubMed ↵von Podewils F, Suesse M, Geithner J, et al. Prevalence and outcome of late-onset seizures due to autoimmune etiology: a prospective observational population-based cohort study. Epilepsia 2017;58:1542–50.doi:10.1111/epi.13834pmid:http://www.ncbi.nlm.nih.gov/pubmed/28681401OpenUrlPubMed ↵Dubey D, Alqallaf A, Hays R, et al. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol 2017;74:397–402.doi:10.1001/jamaneurol.2016.5429pmid:http://www.ncbi.nlm.nih.gov/pubmed/28166327OpenUrlPubMed ↵Dubey D, Kothapalli N, McKeon A, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol 2018;323:62–72.doi:10.1016/j.jneuroim.2018.07.009pmid:http://www.ncbi.nlm.nih.gov/pubmed/30196836OpenUrlPubMed ↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.doi:10.1016/S1474-4422(15)00401-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/26906964OpenUrlCrossRefPubMed ↵Makuch M, Wilson R, Al-Diwani A, et al. N-Methyl-D-aspartate receptor antibody production from germinal center reactions: therapeutic implications. Ann Neurol 2018;83:553–61.doi:10.1002/ana.25173pmid:http://www.ncbi.nlm.nih.gov/pubmed/29406578OpenUrlPubMed ↵Ramberger M, Berretta A, Tan JMM, et al. Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain 2020;143:1731–45.doi:10.1093/brain/awaa104pmid:http://www.ncbi.nlm.nih.gov/pubmed/32437528OpenUrlPubMed ↵Quek AML, Britton JW, McKeon A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012;69:582–93.doi:10.1001/archneurol.2011.2985pmid:http://www.ncbi.nlm.nih.gov/pubmed/22451162OpenUrlCrossRefPubMed ↵Rocamora R, Becerra JL, Fossas P, et al. Pilomotor seizures: an autonomic semiology of limbic encephalitis? Seizure 2014;23:670–3.doi:10.1016/j.seizure.2014.04.013pmid:http://www.ncbi.nlm.nih.gov/pubmed/24890932OpenUrlCrossRefPubMed
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Sleep disorders in autoimmune encephalitis

Sleep disorders in autoimmune encephalitis | AntiNMDA | Scoop.it
Sleep disorders in people with autoimmune encephalitis have received little attention,
probably overshadowed by the presence of other neurological and psychiatric symptoms
in this group of conditions.
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Cerebrospinal fluid CD20 positive B-cell expansion in a case of anti-NMDAR encephalitis - ScienceDirect

Cerebrospinal fluid CD20 positive B-cell expansion in a case of anti-NMDAR encephalitis - ScienceDirect | AntiNMDA | Scoop.it
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a potentially fatal autoimmune encephalitis with a strong B-cell response. We measured the …
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Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis | AntiNMDA | Scoop.it
Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.
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What the acute physician needs to know about Anti-NMDA receptor encephalitis: two case presentations. - The University of Liverpool Repository

What the acute physician needs to know about Anti-NMDA receptor encephalitis: two case presentations. - The University of Liverpool Repository | AntiNMDA | Scoop.it
These case reports look at two patients with anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis presenting to the same acute medical unit within a month of each other. The following covers the characteristic signs, symptoms and timeline associated with this condition and discusses whether we...
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Clinical features which predict neuronal surface autoantibodies in new-onset focal epilepsy: implications for immunotherapies | Journal of Neurology, Neurosurgery & Psychiatry

Introduction Neuronal surface-directed antibodies (NSAbs) are considered pathogenic in patients with autoimmune encephalitis (AE). AE commonly presents with prominent seizures and neuropsychiatric features and shows a preferential response to immunotherapies versus anti-seizure medications (ASMs).1–4 This has prompted the introduction of ‘epilepsy of immune aetiology’ within the International League Against Epilepsy (ILAE) 2017 classification.5 The same NSAbs, as well as high levels of antibodies to intraneuronal glutamic acid decarboxylase-65 (GAD65), are also described in the serum of people with more isolated forms of epilepsy, without core features of encephalitis.6–8 In this context, their clinical, aetiological and therapeutic relevance is unclear, but of major potential importance to all neurologists who manage new-onset epilepsy. In our large, prospective, real-world study of new-onset focal epilepsy, we predicted that formes frustes of AE would help identify clinical features suggesting the presence of NSAbs and asked whether detection of these NSAbs should alter patient management. Materials and methods Between 9 December 2011 and 4 November 2015, consecutive adult patients (≥18 years) with a diagnosis of new-onset focal epilepsy and their first seizure within the previous 12 months were prospectively recruited from the routine practice of two epileptologists at the Oxford University Hospitals NHS Foundation Trust. Written informed consent and sera were obtained (Ethical approvals: Oxfordshire RECA 07/Q160X/28 and REC16/YH/0013). Clinical data gathered at onset (online supplemental table 1) included detailed phenotype and investigation results, Quality of Life in Epilepsy-31, Hospital Anxiety and Depression Score, Addenbrooke’s Cognitive Examination (ACE) and modified Rankin Score (mRS); as well as information to inform the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score (online supplemental table 2)9 10 and diagnostic criteria for possible or definite AE.11 Subsequently, 1-year and 3-year mRS were ascertained from patients with NSAbs. Supplemental material For NSAbs, sera were tested against autoantigen-expressing live HEK293 cells (live cell-based assay; online supplemental table 3), and for reactivity with the surface of live cultured hippocampal neurons, using sensitive protocols.12 13 Autoantibodies to GAD65 were determined using a commercial radioimmunoprecipitation assay. Statistical analysis was conducted in R (V.3.6.1). Dimensionality reduction was performed using Multiple Factor Analysis in ‘FactoMineR’ with up to 10% missing data imputed using missForest. Stepwise Bayesian general linear modelling analysis was undertaken using ‘arm’. Wilson 95% CIs with continuity correction were calculated using ‘DescTools’. Results NSAb findings Of 241 recruited patients, 22 were excluded (online supplemental table 4). Of the remaining 219, median age was 49 years (range 16–91) and 109 (49.8%) were female. In 23/219 (10.5%) patients, serum NSAbs were detected across candidate and novel autoantigens (table 1) including roughly equal frequencies against leucine-rich glioma inactivated-1 (LGI1), contactin-associated protein-like 2 (CASPR2), plus the N-methyl-d-aspartate receptor (NMDAR) and γ-aminobutyric acid A/B receptors (GABAAR and GABABR). An additional five patients had antibodies to the surface of live neurons, without an established autoantigen. Autoantibodies to contactin-2, the glycine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) were each found in one patient. No dipeptidyl-peptidase-like protein 6 (DPPX) or high-titre GAD65 antibodies were detected. Overall, from the 23 people with NSAbs, 9 had a clinical diagnosis of AE (7/9 fulfilling published criteria).11 By contrast, none of the 196 without NSAbs had a clinical diagnosis of AE (p<0.0001; Fisher’s exact test). VIEW INLINE VIEW POPUP Table 1 Clinical and laboratory features of patients with epilepsy and positive neuronal surface autoantibodies Factors associated with the presence of NSAbs and AE Dimensionality reduction with multiple factor analysis showed that patients were highly heterogeneous and the modest clustering of those with NSAbs was largely driven by a clinical diagnosis of AE (figure 1A,B). Univariate analysis identified 11 clinical parameters that differed significantly between patients with and without NSAbs: age (p=0.04), ictal piloerection (p=0.02), lesional MRI (p=0.04), self-reported mood disturbance (p=0.007), ACE attention domain (p=0.01), ACE total score (p=0.04), QOLIE-31 score (p=0.02), self-reported neuropsychiatric features (p=0.03), epilepsy risk factors (p=0.05), inflammatory cerebrospinal fluid (CSF; p=0.004) and limbic system lesions on MRI (p=0.0002). A multivariate stepwise regression model allocated weighted scores to six of these: age ≥54 years=+1, self-reported mood disturbance=+1, limbic system lesions on MRI=+2, ictal piloerection=+2.5, ACE attention score ≥16=−1.5 and epilepsy risk factors=−1.5 (figure 1C). The probability of NSAb positivity increased with higher scores (Spearman’s ρ=0.99, p<0.0001; figure 1C) and receiver operating characteristic (ROC) analysis confirmed these features strongly predicted NSAb status (area under the curve (AUC)=0.83; total score ≥0; sensitivity=66.7%, specificity=84.9%; figure 1D). By contrast, the APE2 score performed less well in predicting NSAb status (sensitivity 43.5%, specificity 79.1%, AUC=0.68) and more accurately predicted criteria-defined AE, particularly if associated with NSAbs (sensitivity 85.7%, specificity 78.8%, AUC=0.94; figure 1E). Figure 1 Clinical phenotypes associated with NSAb status in new-onset focal epilepsy. The first two dimensions are shown, highlighting: (A) NSAb-positive (red) or NSAb-negative (grey) status and (B) NSAb-positive (pale red) or NSAb-negative (grey) without encephalitis (dots), or NSAb-positive (dark red) with clinically diagnosed autoimmune encephalitis (triangles). (C) The proportion of patients by total model score. Error bars show 95% CIs. The inset shows the weighting and SE of each factor within the regression model. (D) Receiver operator characteristic (ROC) curve of the total model score for predicting NSAb status across all patients. (E) ROC curve of the APE2 score for predicting NSAb status across all patients (black), patients not meeting the criteria for autoimmune encephalitis (blue), patients meeting the criteria for autoimmune encephalitis (red) and predicting NSAb-positive criteria-confirmed autoimmune encephalitis across all patients. (F) Scatter plot of modified Rankin score in NSAb-positive patients by immunotherapy status over time (Mann-Whitney U test p values<0.05). AE, autoimmune encephalitis; APE2, Antibody Prevalence in Epilepsy and Encephalopathy; epilepsy RF, epilepsy risk factors; MRI limbic Δ, changes within the limbic system on MRI. Comparisons of those with and without AE From 23 patients with NSAbs (table 1), a comparison of those with (n=9) and without (n=14) a clinical diagnosis of AE revealed several differences in the AE cohort: more ASMs (median of 3 vs 1; p=0.0073), more frequent immunotherapies (7/9 vs 0/14, p=0.0001), higher APE2 scores (median of 6 vs 2; p<0.0001), more frequent MRI limbic inflammation (6/9 vs 0/14; p=0.0008) and a trend towards greater positivity of serum IgGs targeting the surface of live neurons (7/9 vs 5/14, p=0.09). Compared with the seven patients administered immunotherapy, those with NSAbs who were not administered immunotherapy showed lower disability after 1 and 3 years (both p<0.05), and 11/16 (68.8%) were asymptomatic at 3-year follow-up (mRS=0 ; figure 1F). Hence, despite no immunotherapy, patients with NSAbs, but without AE, generally showed good outcomes. Discussion In this prospective study of 219 consecutive adults with new-onset focal epilepsy, NSAb status was best predicted by a combination of clinical parameters which closely resemble features observed in AE. Almost half of our patients with NSAbs were diagnosed with AE, and ~30% fulfilled stringent criteria for AE.11 Of those with NSAbs and more isolated forms of epilepsy, without individual features of AE, almost all were treated with ASMs alone and typically remained asymptomatic at long-term follow-up. Overall, these findings suggest that detection of NSAbs in patients with new-onset seizures, but without features of AE, should not alter current clinical management. Our observations should help guide the frequent clinical dilemma of which patients with new-onset seizures to test for autoantibodies and subsequently treat with immunotherapy. Taken together, our data suggest the clinical phenotype is paramount in guiding the relevance of autoantibody results, and provide data to address an outstanding question from a recent ILAE consensus statement.7 This ILAE statement also highlighted controversy over the term ‘autoimmune epilepsy’.7 In routine clinical practice, this nomenclature acts as a valuable signpost and aide memoire when seeing patients with seizures.2 14 However, ‘epilepsy’ carries several social stigmata and is defined by an enduring tendency to seizures. In AE, this lifelong risk is refuted by a recent study,4 despite several forms of AE commonly leading to hippocampal atrophy.2–4 7 10 The alternative concept of acute symptomatic seizures may more accurately capture the nature of seizures in patients with AE. Data-driven modifications to nomenclature will benefit from longer-term follow-up studies. Ictal piloerection, low mood and attention and MRI limbic system changes are recognised features of late-onset AE, particularly in association with LGI1 antibodies.2 4 14 15 The absence of movement disorders or more diffuse cognitive impairment as predictive factors in our model suggests the overall syndrome may reflect a formes frustes of AE. This contrasts with APE2 score parameters,9 which appear to largely reflect more florid features seen in classical AE. Our observational study has several limitations. These include limited CSF autoantibody measurements, which reflected UK practice particularly at the start of the study period. Yet,w ithout this valuable parameter, a diagnosis of NMDAR-antibody encephalitis is still possible.11 Yet, two of our four patients with serum NMDAR antibodies did not have features consistent with encephalitis, likely suggesting detection of clinically unrelated serum antibodies in these cases. In addition, our series in total only identified nine AE cases, although this may be considered substantial given the largely outpatient-based recruitment. This, and the high (~10%) seroprevalence rate, may reflect a referral bias given Oxford’s interest in AE, but is well aligned with other available estimates.6 9 10 Our serological data identified some samples with NSAbs proven by live cell-based assays, but without concomitant cell surface neuronal reactivities. This was especially evident in the cohort without a clinical diagnosis of AE, and perhaps these antibodies reflect low-affinity or low-titre autoantibodies which are not disease relevant. Their specificity, however, remains reassuring given their typical selectivity for just one of eight surface-expressed autoantigens. In the future, our prediction model will benefit from validation in independent, larger studies which may compare the risk of enduring seizures in the NSAb-positive versus NSAb-negative populations, with and without AE, something which we did not survey at follow-up. Hence, we cannot comment on long-term seizure status in the 5/16 patients (31%) who had NSAbs, no diagnosis of AE and 3-year mRS >0. In these patients, it remains possible that immunotherapy would have led to a greater benefit. However, in our view, this finding is more likely to be consistent with the predicted ~30% of all people with epilepsy who are known to become ASM resistant: this provides a testable hypothesis for a future randomised controlled trial. Overall, our observations support the concept that, in patients who present with new-onset focal seizures, clinical features which are consistent with a ‘mild encephalitis’ helps identify those with NSAbs which should alter patient management. This clinico-serological syndrome appeared characteristic and its recognition will improve detection and treatment of these patients. These findings should discourage widespread screening strategies to identify patients with autoantibodies among unselected seizure cohorts. References ↵Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.doi:10.1002/ana.22307 ↵Thompson J, Bi M, Murchison AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 2018;141:348–56.doi:10.1093/brain/awx323OpenUrlCrossRef ↵Geis C, Planagumà J, Carreño M, et al. Autoimmune seizures and epilepsy. J Clin Invest 2019;129:926–40.doi:10.1172/JCI125178OpenUrlPubMed ↵de Bruijn MAAM, van Sonderen A, van Coevorden-Hameete MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology 2019;92:e2185–96.doi:10.1212/WNL.0000000000007475pmid:30979857OpenUrlPubMed ↵Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512–21.doi:10.1111/epi.13709pmid:http://www.ncbi.nlm.nih.gov/pubmed/28276062OpenUrlPubMed ↵Brenner T, Sills GJ, Hart Y, et al. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 2013;54:1028–35.doi:10.1111/epi.12127pmid:http://www.ncbi.nlm.nih.gov/pubmed/23464826OpenUrlCrossRefPubMed ↵Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: conceptual definitions. Epilepsia 2020;61:1341–51.doi:10.1111/epi.16571pmid:http://www.ncbi.nlm.nih.gov/pubmed/32544279OpenUrlPubMed ↵von Podewils F, Suesse M, Geithner J, et al. Prevalence and outcome of late-onset seizures due to autoimmune etiology: a prospective observational population-based cohort study. Epilepsia 2017;58:1542–50.doi:10.1111/epi.13834pmid:http://www.ncbi.nlm.nih.gov/pubmed/28681401OpenUrlPubMed ↵Dubey D, Alqallaf A, Hays R, et al. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol 2017;74:397–402.doi:10.1001/jamaneurol.2016.5429pmid:http://www.ncbi.nlm.nih.gov/pubmed/28166327OpenUrlPubMed ↵Dubey D, Kothapalli N, McKeon A, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol 2018;323:62–72.doi:10.1016/j.jneuroim.2018.07.009pmid:http://www.ncbi.nlm.nih.gov/pubmed/30196836OpenUrlPubMed ↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.doi:10.1016/S1474-4422(15)00401-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/26906964OpenUrlCrossRefPubMed ↵Makuch M, Wilson R, Al-Diwani A, et al. N-Methyl-D-aspartate receptor antibody production from germinal center reactions: therapeutic implications. Ann Neurol 2018;83:553–61.doi:10.1002/ana.25173pmid:http://www.ncbi.nlm.nih.gov/pubmed/29406578OpenUrlPubMed ↵Ramberger M, Berretta A, Tan JMM, et al. Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain 2020;143:1731–45.doi:10.1093/brain/awaa104pmid:http://www.ncbi.nlm.nih.gov/pubmed/32437528OpenUrlPubMed ↵Quek AML, Britton JW, McKeon A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012;69:582–93.doi:10.1001/archneurol.2011.2985pmid:http://www.ncbi.nlm.nih.gov/pubmed/22451162OpenUrlCrossRefPubMed ↵Rocamora R, Becerra JL, Fossas P, et al. Pilomotor seizures: an autonomic semiology of limbic encephalitis? Seizure 2014;23:670–3.doi:10.1016/j.seizure.2014.04.013pmid:http://www.ncbi.nlm.nih.gov/pubmed/24890932OpenUrlCrossRefPubMed
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Specialists and Care Centers for Autoimmune Encephalitis

Specialists and Care Centers for Autoimmune Encephalitis | AntiNMDA | Scoop.it
The Northwestern Medicine Autoimmune Encephalitis and Paraneoplastic Disorders clinic takes a multidiscplinary approach to the diagnosis and care of patients affected by these disorders.
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Neurologic Emergencies at the Extremes of Age

Neurologic Emergencies at the Extremes of Age | AntiNMDA | Scoop.it
The diagnosis and management of neurologic conditions are more complex at the extremes
of age than in the average adult. In the pediatric population, neurologic emergencies
are somewhat rare and some may require emergent consultation.
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(PDF) Anti-N-methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Case Report

(PDF) Anti-N-methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Case Report | AntiNMDA | Scoop.it
PDF | We report case of a 42 years old female who came with a constellation of behavioral symptoms, delirium, body stiffness, and fever for one week....| Find, read and cite all the research you need on ResearchGate...
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RACGP - Old doc, new disease: Anti-NMDA receptor encephalitis

RACGP - Old doc, new disease: Anti-NMDA receptor encephalitis | AntiNMDA | Scoop.it
Dr Casey Parker reflects on an intriguing presentation that made him ask: What else do I not know?
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Cost-Effectiveness of Routine Screening for Autoimmune Encephalitis in Patients With First-Episode Psychosis in the United States |J Clin Psychiatry

Autoimmune encephalitis (AE) is a highly treatable neurologic condition that can cause psychosis. This study estimated the cost-effectiveness of routine screening for AE compared with clinically targeted screening in first-episode psychosis patients.
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Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartate-receptor encephalitis: A case report | Read by QxMD

Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartate-receptor encephalitis: A case report | Read by QxMD | AntiNMDA | Scoop.it
Create a free QxMD account to take advantage of the features offered by Read like saving your papers and creating collections. Get Started Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartate-receptor encephalitis: A case report Norrapat Onpoaree, Montida Veeravigrom, Anapat Sanpavat, Narissara Suratannon, Palittiya Sintusek World Journal of Clinical Cases 2020 October 26, 8 (20): 4866-4875 BACKGROUND: Asymptomatic cytomegalovirus (CMV) infection is common in children; in contrast, in children with a weakened immune system, invasive CMV can occur. This is the first case report of a severe manifestation of CMV esophago-enterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis who received only a moderate dose of corticosteroid therapy. CASE SUMMARY: A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d. Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis. Hence, she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day. On day 42 of corticosteroid therapy, she developed unremitting vomiting and diarrhoea. Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract. Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis. Therefore, the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk. Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment. Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day. After this repeated pulse methylprednisolone treatment, surprisingly, diarrhoea subsided. Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results. CONCLUSION: Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy, implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis. Full Text Links We have located links that may give you full text access. Additional links Discussion You are not logged in. Sign Up or Log In to join the discussion. Trending Papers Colchicine in Patients with Chronic Coronary Disease. Stefan M Nidorf, Aernoud T L Fiolet, Arend Mosterd, John W Eikelboom, Astrid Schut, Tjerk S J Opstal, Salem H K The, Xiao-Fang Xu, Mark A Ireland, Timo Lenderink, Donald Latchem, Pieter Hoogslag, Anastazia Jerzewski, Peter Nierop, Alan Whelan, Randall Hendriks, Henk Swart, Jeroen Schaap, Aaf F M Kuijper, Maarten W J van Hessen, Pradyot Saklani, Isabel Tan, Angus G Thompson, Allison Morton, Chris Judkins, Willem A Bax, Maurits Dirksen, Marco M W Alings, Graeme J Hankey, Charley A Budgeon, Jan G P Tijssen, Jan H Cornel, Peter L Thompson New England Journal of Medicine 2020 August 31 Extracorporeal life support for adults with acute respiratory distress syndrome. Alain Combes, Matthieu Schmidt, Carol L Hodgson, Eddy Fan, Niall D Ferguson, John F Fraser, Samir Jaber, Antonio Pesenti, Marco Ranieri, Kathryn Rowan, Kiran Shekar, Arthur S Slutsky, Daniel Brodie Intensive Care Medicine 2020 November 2 Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Ewan C Goligher, Annemijn H Jonkman, Jose Dianti, Katerina Vaporidi, Jeremy R Beitler, Bhakti K Patel, Takeshi Yoshida, Samir Jaber, Martin Dres, Tommaso Mauri, Giacomo Bellani, Alexandre Demoule, Laurent Brochard, Leo Heunks Intensive Care Medicine 2020 November 2 Emergency Department Management of COVID-19: An Evidence-Based Approach. Nicholas M McManus, Ryan Offman, Jason D Oetman Western Journal of Emergency Medicine 2020 September 25 Glucocorticoids: surprising new findings on their mechanisms of actions. Frank Buttgereit Annals of the Rheumatic Diseases 2020 November 8 Prone position in ARDS patients: why, when, how and for whom. Claude Guérin, Richard K Albert, Jeremy Beitler, Luciano Gattinoni, Samir Jaber, John J Marini, Laveena Munshi, Laurent Papazian, Antonio Pesenti, Antoine Vieillard-Baron, Jordi Mancebo Intensive Care Medicine 2020 November 10 Severe organising pneumonia following COVID-19. István Vadász, Faeq Husain-Syed, Peter Dorfmüller, Fritz C Roller, Khodr Tello, Matthias Hecker, Rory E Morty, Stefan Gattenlöhner, Hans-Dieter Walmrath, Friedrich Grimminger, Susanne Herold, Werner Seeger Thorax 2020 November 11 Analgesia and sedation in patients with ARDS. Gerald Chanques, Jean-Michel Constantin, John W Devlin, E Wesley Ely, Gilles L Fraser, Céline Gélinas, Timothy D Girard, Claude Guérin, Matthieu Jabaudon, Samir Jaber, Sangeeta Mehta, Thomas Langer, Michael J Murray, Pratik Pandharipande, Bhakti Patel, Jean-François Payen, Kathleen Puntillo, Bram Rochwerg, Yahya Shehabi, Thomas Strøm, Hanne Tanghus Olsen, John P Kress Intensive Care Medicine 2020 November 10
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Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report | AntiNMDA | Scoop.it
Myelin oligodendrocyte glycoprotein antibody-associated disease has been proposed as a separate inflammatory demyelinating disease of the central nervous system (CNS) since the discovery of pathogenic antibodies against myelin oligodendrocyte glycoprotein ...
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The Anti-NMDA Receptor Encephalitis Foundation Newsletter

The Anti-NMDA Receptor Encephalitis Foundation Newsletter | AntiNMDA | Scoop.it
On your Marks, Get Set, Register for the WORLD ENCEPHALITIS DAY CONFERENCE 2021 From...
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Autoimmune encephalitis: When your body attacks your brain, and people think you’re going mad

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Four PhD candidates from Monash University, who are already Doctors of the medical kind, are conducting research on a rare and debilitating neurological illness affecting the Australian population. It’s described as feeling like your brain is on fire.
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Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B - ScienceDirect

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To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminal…
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