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Multiplex family with GAD65-Abs neurologic syndromes

Multiplex family with GAD65-Abs neurologic syndromes | AntiNMDA | Scoop.it
Abstract Objective: Neurologic autoimmune syndromes associated with anti–glutamate acid decarboxylase 65 antibodies (GAD65-Abs) are rare and mostly sporadic. Methods: We describe a niece and her aunt with GAD65-Abs neurologic syndromes. High-resolution HLA typing of Class I and Class II alleles was performed using next-generation sequencing. Results: The proband had cerebellar ataxia and probable limbic encephalitis features, whereas her niece had stiff-person syndrome. Both had a high titer of GAD65-Abs in serum and CSF and showed signs of inflammation in CSF. Both affected members carried the same rare recombinant DRB1*15:01:01∼DQA1*01:02:01∼DQB1*05:02:01 haplotype, which may or may not be involved in disease susceptibility. Of interest, other unaffected members of the family either had the same HLA haplotype but normal serum GAD65-Abs or had different HLA types but a high titer of serum GAD65-Abs without neurologic symptoms, suggesting cumulative effects. Conclusions: This unique association strengthens the concept that hereditary factors, possibly including specific HLA haplotypes, play a role in neurologic syndromes associated with GAD65-Abs. GLOSSARY GAD=glutamic acid decarboxylase; IgG=immunoglobulin G; SPS=stiff-person syndrome; T1DM=type 1 diabetes mellitus; TG=antithyroglobulin; TPO=antithyroperoxidase Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the production of γ-aminobutyric acid, the main inhibitory neurotransmitter of the CNS. GAD is also expressed in pancreatic islet β-cells.1 Anti-GAD65 antibodies (GAD65-Abs) have been described as a biological marker in patients with type 1 diabetes mellitus (T1DM), but also in some patients with neurologic diseases, such as stiff-person syndrome (SPS), cerebellar ataxia, or limbic encephalitis.2,–,7 Although rare, the concept of neurologic syndromes with GAD65-Abs is now well established, most cases reported so far being sporadic.8 Few experimental studies suggest a possible pathogenic role of GAD65-Abs.9,–,11 We describe 2 members of the same family with GAD65-Abs neurologic syndromes in combination with a rare recombinant HLA haplotype and 2 other members without the same haplotype and with a high level of GAD65-Abs but no neurologic symptoms. These results suggest that there may be a genetic basis for susceptibility of the development of GAD-antibody autoimmunity. METHODS Written informed consent was obtained from all HLA-tested members, and this study was approved by the Institutional Review Board of University Claude Bernard Lyon 1 and Hospices Civils de Lyon. Samples are deposited in the collection of biological samples named “Neurobiotec” registered as the biobank of the Hospices Civils de Lyon. Full HLA next-generation sequencing–based typing was performed based on long-range PCRs detailed by Wang in 2012.12 RESULTS Cases reports. The first patient (II3, figure), a 68-year-old woman without a medical history, first developed acute dizziness and vomiting. Neurologic clinical examination revealed an ataxic gait with enlargement of the sustentation polygon and nystagmus. The rest of the physical examination was normal. Videonystagmography revealed a left vestibular deficit. Brain MRI showed no cerebellar atrophy, but hypersignal intensity on fluid attenuation inversion recovery sequences restricted to both hippocampi (nevertheless, no acute clinical signs of limbic encephalitis were observed). CSF examination showed elevated protein levels at 0.71 g/L without white blood cells and a normal immunoglobulin G (IgG) index (0.5; normal <0.7), but few oligoclonal bands (<5) were present. GAD65-Abs were positive in CSF at 250 IU/mL as well as in the serum above 1,200 IU/mL (ELISA Medipan, cutoff positivity: 5 IU/mL). Antithyroperoxidase (TPO) and antithyroglobulin (TG) antibodies were also positive (Varelisa; Thermo Fischer Scientific, Waltham, MA) (718 and 283 IU/mL, respectively, cutoff of positivity for both Abs: 60 IU/mL). No other biological abnormalities were detected. Body fluorodeoxyglucose–PET and mammography were also normal. A diagnosis of cerebellar ataxia with GAD65-Abs was proposed, and treatment with monthly IV immunoglobulin was initiated. After 6 months, the patient stabilized, while still exhibiting a mild cerebellar syndrome. GAD65-Abs remained positive during 15 years of follow-up. Brain MRI performed 4 years after onset showed cerebellar and diffuse brain atrophy. The patient developed late-onset T1DM and a progressive dementia without significant clinical progression of cerebellar ataxia. HLA typing revealed the presence of an unusual haplotype DRB5*01:01:01∼DRB1*15:01:01∼DQA1*01:02:01 ∼DQB1*05:02:01, together with a classical type 1 diabetes–associated haplotype DRB1*03:01:01∼DQA1*05:01:01∼DQB1*02:01:01 (figure). DRB5*01:01:01∼DRB1*15:01:01∼DQA1*01:02:01 ∼DQB1*05:02:01 is very unusual. In large samples from north European countries, the frequency is typically below 1 for 1,000 patients. We identified no patient with this haplotype in more than 100 French people. In our estimation, the frequency of this haplotype in France must be less than 1 for 5,000 patients. Figure Family tree with the HLA haplotyping of 6 members of the family The colors indicate the bioclinical characteristics of the patients. Black circle: patients with GAD65-Abs without neurologic syndromes (III3 and III4). Red circle: patient with GAD65-Abs and cerebellar ataxia (II3). Blue circle: patient with GAD65-Abs and stiff-person syndrome (III5). Green circle: patients with TPO-Abs (II3, III3, and III5). Her niece (III5, figure) developed signs of progressive muscular rigidity with superimposed spasms at the age of 42 years. The right leg was first affected, followed by the trunk and the left leg. Her medical history was notable for Hashimoto thyroiditis (with anti-TPO at 1,966 IU/mL and anti-TG-Abs at 12,786 IU/mL). Medullary and brain MRI were normal. The CSF study revealed a normal IgG index (0.61; normal <0.7) with many oligoclonal bands (>5) and GAD65-Abs at 250 IU/mL. Serum GAD65-Abs were also positive with a titer above 2,000 IU/mL. EMG confirmed the suspicion of SPS with continuous motor activity and cocontraction of agonist and antagonist muscles of the thigh, hip, and back muscles. Five years later, no diabetes mellitus was observed and no cancer has been found. The patient has been treated with benzodiazepines, immunoglobulins, and cyclophosphamide and experienced only partial recovery. HLA typing revealed that this patient also carried the unusual DRB5*01:01:01∼DRB1*15:01:01∼DQA1*01:02:01∼DQB1*05:02:01 haplotype, together with DRB3*02:02:01∼DRB1*11:04:01∼DQA1*05:05:01∼DQB1*03:01:01 (figure). Familial history. After identification of these 2 index cases, we reviewed the entire family history and extended HLA typing to 6 other members of the family (figure). The entire family is of Caucasian ethnicity. The father of II3 developed dementia and diabetes mellitus, but we have no more information. Of interest, 2 relatives (III3 and III4) without the rare DRB5*01:01:01∼DRB1*15:01:01∼DQA1*01:02:01, ∼DQB1*05:02:01 haplotype had serum GAD65-Abs titer higher than 250 IU/mL. One (III3), the sister of the patient III5 with SPS, developed pernicious anemia with intrinsic antibodies, breast cancer, and thyroiditis, and her brother (III4) had no particular medical history. All the members of the family were examined by JH and had no abnormalities on neurologic examination. No other disease was reported in the other members of the family. Conversely, 4 other members of the family (III 6, 7, 8, and 9) shared the rare DRB5*01:01:01∼DRB1*15:01:01∼DQA1*01:02:01∼DQB1*05:02:01 haplotype but had no GAD65-Abs and no neurologic symptoms. The father of II3 developed dementia and diabetes mellitus, and his HLA haplotype was not characterized. DISCUSSION Very little is known regarding genetic predisposition to autoimmune neurologic syndromes with GAD65-Abs. HLA genetic predisposition to SPS has been studied only in 1 large study of 18 patients, with unremarkable findings, although weak association with DQB1*02 (DQB1*02:01 and DQB1*02:02) was suggested.13 In this study, however the presence of DQB1*06:02, a strong protective allele for type 1 diabetes, was present in some patients with SPS without type 1 diabetes but in none with cooccurring diabetes.13,14 However, a few familial occurrences of neurologic conditions associated with GAD65-Abs have been previously described, 2 families with multiplex familial SPS15,16 and 1 family with 2 sibling sisters with cerebellar ataxia and GAD65-Abs,17 suggesting that genetic factors may be involved (HLA typing was not performed in these cases). In our 2 cases, DQB1*02 was present only in 1 affected case, but both carried an unusual haplotype HLA-DRB1*15:01∼DQA1*01:02∼DQB1*05:02. This haplotype is likely the result from recombination of HLA DRB1*15:01:01∼DQA1*01:02:01∼DQB1*06:02:01 with DRB1*16:01/2∼DQA1*01:02:02∼DQB1*05:02:01, 2 common Caucasian haplotypes. We can also speculate that the father of II3 who developed dementia and diabetes mellitus may also have had this rare haplotype. Although reported rarely in the literature, except in a few patients of Romani people, Northern Indian, and Chinese origin,18,–,20 this haplotype is extremely rare in US and French Caucasians (<0.1%)21 and thus unlikely to be present by chance in these 2 affected patients.20 The rare haplotype, if involved, is however not the sole determinant of disease, as 4 relatives (III 6, 7, 8, and 9) with the haplotype do not have neurologic symptoms or GAD65-Abs. Surprisingly, we also found 2 other relatives (III3 and III4) having high GAD65-Abs titers without neurologic symptoms. This is also unlikely to be a chance phenomenon, as GAD65-Abs are found only in around 1.7% of the general population with or without neurologic disorders.22,23 Of interest, the presence of GAD65-Abs in the general asymptomatic population (including asymptomatic individuals from families with prevalent type 1 diabetes) also correlates with typical type 1 diabetes–associated HLA DRB1*03:01∼DQA1*05:01∼DQB1*02:01 and DRB1*04∼DQA1*03∼DQB1*03:02, notably when both haplotypes are in trans of each other.23,24 In our family, the 2 asymptomatic patients with high GAD65-Abs do not share the same extended HLA subtypes with both affected patients, suggesting that GAD65-Abs are unlinked with HLA alone and that the sole presence of high titers of GAD65-Abs is insufficient to develop neurologic symptoms. One reason could be that GAD65-Abs in affected vs unaffected patients target different epitopes, as has been shown for type 1 diabetes vs SPS.25,–,27 Of interest, a recent study in 6,556 type 1 diabetes cases has shown strong genetic association for the presence of GAD65-Abs not with an HLA region, but with other genes, notably in IFIH1, a locus associated with positivity for TPO and GAD65-Abs28 and involved in other immune phenotypes.29,30 A similar complex genetic susceptibility has already been discussed in neuromyelitis optica (NMO), another autoimmune neurologic disorder associated with antineural antibodies.31 In NMO, around 3% of patients have a familial occurrence of the disease, and familial NMO is indistinguishable from sporadic NMO.31 Furthermore, the association with a specific HLA haplotyping is also highly debated.32 Our family with GAD65-Abs and all the data of the literature suggest that coincident complex genetic factors in the HLA and non-HLA regions should be carefully studied in autoimmune neurologic disorders associated with antineural antibodies. AUTHOR CONTRIBUTIONs Aude Belbezier contributed to the acquisition of data, analysis, interpretation of the data, drafting the manuscript for intellectual contents. Bastien Joubert contributed to the acquisition of data, analysis, interpretation of the data, critical revision of the manuscript for intellectual content. Gonzalo Montero-Martin contributed to the acquisition of data, analysis, interpretation of the data, critical revision of the manuscript for intellectual content. Marcelo Fernandez-Vina contributed to the acquisition of data, analysis, interpretation of the data, critical revision of the manuscript for intellectual content. Nicole Fabien contributed to the acquisition of data. Véronique Rogemond contributed to the acquisition of data. Emmanuel Mignot contributed to the interpretation of the data and critical revision of the manuscript for intellectual content. Jérôme Honnorat contributed to the study concept and design of the study, critical revision of manuscript for intellectual content, study supervision. STUDY FUNDING This study is supported by research grants from ANR (ANR-14-CE15-0001-MECANO), the Federation pour la recherche sur le cerveau (FRC-Neurodon2014), the Fondation pour la Recherche Médicale (Programme “équipe FRM” DEQ20170336751), and CSL Behring France. DISCLOSURE A. Belbezier, B. Joubert, and G. Montero-Martin report no disclosures. M. Fernandez-Vina serves on the editorial board of Human Immunology and received research support from NIH-NIAID. N. Fabien and V. Rogemond report no disclosures. E. Mignot served on the scientific advisory board of FDA, Kleine-Levin Syndrome Foundation, National Academy of Sciences, Institute of Medicine, Board on Neuroscience and Behavioral Health, Study Task Force on Sleep Research and Member, Membership Committee Section, NIH/NIMH, National Advisory Mental Health Council, Mood Disorders Workgroup, Board of Scientific Counselors, and Restless Leg Syndrome Foundation; served on the editorial board of Journal of Neuropsychopharmacology, Public Library of Sciences—Biology, Sleep, Sleep Medicine, Sleep Research Online, and Molecular Biology; receives publishing royalties from Informa Healthcare; consulted for Jazz Pharmaceuticals; received research support from GlaxoSmithKline, Novo Nordisk, Jazz Pharmaceuticals, NIH, National Institute of Neurological Disorders and Stroke, NSBRI, CORI, NASA, and HHMI; and held stock in ResMed. J. Honnorat served on the scientific advisory board of Bristol-Myers Squibb; holds patent for and receives royalties from licensing fees to Athena Diagnostics, Euroimmun, and Ravo Diagnostika for a patent for the use of CV2/CRMP5 as diagnostic tests; and received research support from CSL Behring France. Go to Neurology.org/nn for full disclosure forms. ACKNOWLEDGMENT The authors thank Dr. Michel Gouttard for his help to collect clinical data. Footnotes Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the ADR05 INSERM, France. Received May 23, 2017. Accepted in final form October 2, 2017. Copyright © 2017 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.↵Solimena M, Folli F, Aparisi R, et al. Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl J Med 1990;322:1555–1560.OpenUrlCrossRefPubMed 2.↵Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain J Neurol 2008;131:2553–2563.OpenUrlCrossRefPubMed 3.↵Honnorat J, Saiz A, Giometto B, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001;58:225–230.OpenUrlCrossRefPubMed 4.↵Malter MP, Elger CE, Surges R. Diagnostic value of CSF findings in antibody-associated limbic and anti-NMDAR-encephalitis. Seizure 2013;22:136–140.OpenUrlCrossRefPubMed 5.↵Falip M, Carreño M, Miró J, et al. Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies. Eur J Neurol 2012;19:827–833.OpenUrlPubMed 6.↵Peltola J, Kulmala P, Isojärvi J, et al. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology 2000;55:46–50.OpenUrlPubMed 7.↵Tilikete C, Vighetto A, Trouillas P, et al. Potential role of anti-GAD antibodies in abnormal eye movements. Ann NY Acad Sci 2005;1039:446–454.OpenUrlCrossRefPubMed 8.↵Dayalu P, Teener JW. Stiff Person syndrome and other anti-GAD-associated neurologic disorders. Semin Neurol 2012;32:544–549.OpenUrl 9.↵Manto MU, Laute MA, Aguera M, et al. Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol 2007;61:544–551.OpenUrlCrossRefPubMed 10.↵Manto M, Honnorat J, Hampe CS, et al. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions. Front Behav Neurosci 2015;9:78.OpenUrl 11.↵Gresa-Arribas N, Ariño H, Martínez-Hernández E, et al. Antibodies to inhibitory synaptic proteins in neurological syndromes associated with glutamic acid decarboxylase autoimmunity. PLoS One 2015;10:e0121364.OpenUrlPubMed 12.↵Wang C, Krishnakumar S, Wilhelmy J, et al. High-throughput, high-fidelity HLA genotyping with deep sequencing. Proc Natl Acad Sci USA 2012;109:8676–8681. 13.↵Pugliese A, Solimena M, Awdeh ZL, et al. Association of HLA-DQB1*0201 with stiff-man syndrome. J Clin Endocrinol Metab 1993;77:1550–1553.OpenUrlCrossRefPubMed 14.↵Pugliese A, Gianani R, Eisenbarth GS, et al. Genetics of susceptibility and resistance to insulin-dependent diabetes in stiff-man syndrome. Lancet 1994;344:1027–1028.OpenUrlPubMed 15.↵Burns TM, Jones HR, Phillips LH, et al. Clinically disparate stiff-person syndrome with GAD65 autoantibody in a father and daughter. Neurology 2003;61:1291–1293.OpenUrl 16.↵Xiao Z, Shan J, Huang X, et al. Familial case reports of stiff-person syndrome. Clin Neurophysiol 2015;126:2408–2409.OpenUrl 17.↵Kuchling J, Shababi-Klein J, Nümann A, et al. GAD antibody-associated late-onset cerebellar ataxia in two female siblings. Case Rep Neurol 2014;6:264–270.OpenUrl 18.↵Rani R, Fernandez-Viña MA, Stastny P. Associations between HLA class II alleles in a North Indian population. Tissue Antigens 1998;52:37–43.OpenUrlPubMed 19.↵Cerná M, Fernandez-Viña M, Ivásková E, et al. Comparison of HLA class II alleles in Gypsy and Czech populations by DNA typing with oligonucleotide probes. Tissue Antigens 1992;39:111–116.OpenUrlPubMed 20.↵Han F, Lin L, Li J, et al. HLA-DQ association and allele competition in Chinese narcolepsy. Tissue Antigens 2012;80:328–335.OpenUrlCrossRefPubMed 21.↵Gragert L, Madbouly A, Freeman J, et al. Six-locus high resolution HLA haplotype frequencies derived from mixed-resolution DNA typing for the entire US donor registry. Hum Immunol 2013;74:1313–1320.OpenUrlCrossRefPubMed 22.↵Dahm L, Ott C, Steiner J, et al. Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol 2014;76:82–94.OpenUrlCrossRefPubMed 23.↵Sørgjerd EP, Thorsby PM, Torjesen PA, et al. Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study. BMJ Open Diabetes Res Care 2015;3:e000076.OpenUrlPubMed 24.↵Rolandsson O, Hägg E, Janer M, et al. High GAD65 autoantibody levels in nondiabetic adults are associated with HLA but not with CTLA-4 or INS VNTR. J Intern Med 2003;253:447–453.OpenUrlCrossRefPubMed 25.↵Kim J, Namchuk M, Bugawan T, et al. Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. J Exp Med 1994;180:595–606. 26.↵Chéramy M, Hampe CS, Ludvigsson J, et al. Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals. Clin Exp Immunol 2013;171:247–254.OpenUrlCrossRefPubMed 27.↵Lohmann T, Londei M, Hawa M, et al. Humoral and cellular autoimmune responses in stiff person syndrome. Ann NY Acad Sci 2003;998:215–222.OpenUrlCrossRefPubMed 28.↵Brorsson CA, Pociot F; Type 1 Diabetes Genetics Consortium. Shared genetic basis for type 1 diabetes, islet autoantibodies, and autoantibodies associated with other immune-mediated diseases in families with type 1 diabetes. Diabetes Care 2015;38(suppl 2):S8–S13.OpenUrlFREE Full Text 29.↵Bronson PG, Chang D, Bhangale T, et al. Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nat Genet 2016;48:1425–1429.OpenUrl 30.↵Melki I, Crow YJ. Novel monogenic diseases causing human autoimmunity. Curr Opin Immunol 2015;37:1–5.OpenUrl 31.↵Matiello M, Kim HJ, Kim W, et al. Familial neuromyelitis optica. Neurology 2010;75:310–315.OpenUrlCrossRef 32.↵Zéphir H, Fajardy I, Outteryck O, et al. Is neuromyelitis optica associated with human leukocyte antigen? Mult Scler 2009;15:571–579.OpenUrlCrossRefPubMed
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BREAKING NEWS! First Clinical Trial for Anti-NMDA Receptor Encephalitis

BREAKING NEWS! First Clinical Trial for Anti-NMDA Receptor Encephalitis | AntiNMDA | Scoop.it
In the spring of 2020, the Foundation expressed its strong support for the first-ever Clinical Trial for a promising new drug to treat anti-NMDA receptor encephalitis. Fast forward to the Fall of 2021, when we learned that the Trial was approved and will be funded by the National Institutes of Health (NIH).
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Autoimmune encephalitis with coexistent LGI1 and GABABR1 antibodies: case report | BMC Neurology | Full Text

Autoimmune encephalitis with coexistent LGI1 and GABABR1 antibodies: case report | BMC Neurology | Full Text | AntiNMDA | Scoop.it
Background Autoimmune encephalitis (AE) with multiple auto-antibodies is of great clinical significance because its complex clinical manifestations and atypical imaging increase the difficulty of diagnosis, differential diagnosis and treatment, which may aggravate the disease, increase the recurrence rate and mortality. The coexistence of anti-Leucinie-rich Glioma Inactivated 1 (LGI1) and anti-γ-aminobutyric acid-beta-receptor 1 (GABABR1) has not been published before. Case presentation We herein present the case of a 60-year-old man with slow response, behavioral changes, psychosis and sleep disorders. Laboratory test included serum hyponatremia, positive serum LGI1 and GABABR1 antibodies using transfected cell-based assays. Electroencephalogram exhibited moderate diffusion abnormality. The patient responded well to steroid impulse treatment and sodium supplement therapy, and did not recur during the follow-up. Conclusions Here we report the first AE characterized by positive LGI1 and GABABR1 antibodies, as well as summarizing AE with multiple auto-antibodies reported so far, hopefully to provide experience for clinical practice.
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EEG Contribution to the Diagnosis of Antibody-Negative Autoimmune Encephalitis: A Case Report - FullText - Case Reports in Neurology 2021, Vol. 13, No. 3 - Karger Publishers

Autoimmune encephalitis (AE) is a group of inflammatory brain diseases that are characterized by prominent neuropsychiatric symptoms. Early therapeutic intervention is important for AE.Therefore, wit...
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Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology

Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis | Neurology | AntiNMDA | Scoop.it
We appreciate the interest in our research.1 According to Pollak and colleagues,2 criteria of possible autoimmune psychosis (AP) are fulfilled if a patient has abrupt onset psychotic symptoms with at least one of the following: the presence of a tumor, movement disorder (dyskinesias, catatonia), adverse response to antipsychotics, “severe or disproportionate” cognitive dysfunction, decreased level of consciousness, unexplained seizures, and significant autonomic dysfunction.2 Fulfilment of these criteria should lead to additional tests such as EEG, MRI, and serum or CSF investigations. In our series of 105 patients with first episode of psychosis (FEP), 20% fulfilled these criteria but never developed AP.1 We confirm that 2 of 3 patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis presenting with FEP did not fulfill any of these criteria, including catatonia, which is a complex syndrome with its own set of 12 criteria that include echolalia.3 Thus, catatonia and echolalia should not be used as interchangeable terms.
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Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach | AntiNMDA | Scoop.it
Autoimmune-mediated encephalitis is a disease that often encompasses psychiatric symptoms as its first clinical manifestation’s predominant and isolated characteristic. Novel guidelines even distinguish autoimmune psychosis from autoimmune encephalitis.
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Vennada's Story: Recovery from Anti-NMDA Receptor Encephalitis

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The grey zone between autoimmune encephalitis and autoimmune‐associated epilepsy - Morano - - Epilepsia Open

The grey zone between autoimmune encephalitis and autoimmune‐associated epilepsy - Morano - - Epilepsia Open | AntiNMDA | Scoop.it
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A Brain on Fire: Laura's Battle with Autoimmune Encephalitis

A Brain on Fire: Laura's Battle with Autoimmune Encephalitis | AntiNMDA | Scoop.it
Laura Martin, a strong student and standout goalie at Transylvania University, hit a sudden wall as things turned worse. Diagnosis: Autoimmune Encephalitis.
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Frontiers | Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis | Immunology

Frontiers | Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis | Immunology | AntiNMDA | Scoop.it
Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy.
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Frontiers | Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report | Neurology

Frontiers | Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report | Neurology | AntiNMDA | Scoop.it
Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis has been reported after SARS-CoV-2 infection, but not after SARS-CoV-2 vaccination. We report the first known case of anti-NMDAR encephalitis after SARS-CoV-2 immunization in a young female presenting with acute psychosis,...
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Lauren's Healing Story (Autoimmune Encephalitis) - Phoenix Helix

Lauren's Healing Story (Autoimmune Encephalitis) - Phoenix Helix | AntiNMDA | Scoop.it
When you have a disease only recently discovered and most doctors don't know it exists, it takes strong self-advocacy to get the help you need.
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CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis

CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis | AntiNMDA | Scoop.it
CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated ...
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Physical Therapy Interventions and Outcome Measures for a Patient Diagnosed with Anti-NMDA Receptor Encephalitis

Physical Therapy Interventions and Outcome Measures for a Patient Diagnosed with Anti-NMDA Receptor Encephalitis | AntiNMDA | Scoop.it
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common cause of
autoimmune encephalitis after acute demyelinating encephalitis. Patients usually present
with acute behavioral changes, psychosis, and abnormal limb movements and can also
...
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Meet Ambassador Jayden Liuzza

The Foundation is very proud to introduce our first and the world’s youngest Ambassador for Anti-NMDA receptor encephalitis, Jayden Liuzza. You may remember seeing Jayden ...Read More...
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Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical Illness (Review)

Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical Illness (Review) | AntiNMDA | Scoop.it
Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis.
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Frontiers | Risk Factors and Brain Metabolic Mechanism of Sleep Disorders in Autoimmune Encephalitis | Immunology

Frontiers | Risk Factors and Brain Metabolic Mechanism of Sleep Disorders in Autoimmune Encephalitis | Immunology | AntiNMDA | Scoop.it
BackgroundSleep disorders (SDs) in autoimmune encephalitis (AE) have received little attention and are poorly understood. We investigated the clinical characteristics, risk factors, and cerebral metabolic mechanism of SD in AE.MethodsClinical, laboratory, and imaging data were retrospectively...
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A peculiar case of psychosis: anti-NMDAr encephalitis | International Journal of Emergency Medicine | Full Text

A peculiar case of psychosis: anti-NMDAr encephalitis | International Journal of Emergency Medicine | Full Text | AntiNMDA | Scoop.it
Background Psychosis in pregnancy is rare and could be life-threatening. It requires prompt evaluation and proper management accordingly. Anti-N-methyl-d-aspartate receptor (anti-NMDAr) encephalitis following herpes simplex virus (HSV) infection is a rare cause of psychosis during pregnancy.
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Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report - PMC

Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report - PMC | AntiNMDA | Scoop.it
Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis has been reported after SARS-CoV-2 infection, but not after SARS-CoV-2 vaccination. We report the first known case of anti-NMDAR encephalitis after SARS-CoV-2 immunization in a young ...
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Anti-NMDAR Autoantibodies Disrupt Ionotropic Receptor Signaling –

Anti-NMDAR Autoantibodies Disrupt Ionotropic Receptor Signaling – | AntiNMDA | Scoop.it
Vignesh Subramanian '24 Figure 1: The N-methyl-D-aspartate receptor (NMDAR) functions as an ion channel. N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels whose signaling enables higher-order functions, such as learning and memory, throughout the brain.
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Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience | Canadian Journal of Neurological Sciences

Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience - Volume 48 Issue 6
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The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis | Journal of Neuroinflammation | Full Text

The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis | Journal of Neuroinflammation | Full Text | AntiNMDA | Scoop.it
Autoimmune encephalitis (AE) is an inflammatory brain disease which is frequently associated with antibodies (Abs) against cell-surface, synaptic or intracellular neuronal proteins. There is increasing evidence that dendritic cells (DCs) are implicated as key modulators in keeping the balance...
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Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies | Read by QxMD

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies | Read by QxMD | AntiNMDA | Scoop.it
RESULTS: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n=11), case series (n=83), and case reports (n=103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called "cryptogenic NORSE". Among adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular, and degenerative conditions have been also described.
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Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis

Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis | AntiNMDA | Scoop.it
Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised...
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Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis | Neurology Neuroimmunology & Neuroinflammation

Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Immunotherapeutic strategies for GAD65-AE remain highly controversial.27 Most patients are considered to require immunotherapy, and early immunotherapy has been found to be associated with a better outcome.10,28 However, the different neurologic manifestations of SPS, CA, and LE appear to respond...
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Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline | American Academy of Pediatrics

Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline | American Academy of Pediatrics | AntiNMDA | Scoop.it
Knowledge about the diagnosis of autoimmune encephalitis (AE) is rapidly expanding. In the last 15 years, multiple new antibodies have been described. Anti-N-methyl-D-aspartate receptor (NMDAR)–antibody-mediated encephalitis, in particular, has been found to be common among teenagers and young adults1 and accounts for up to 86% of AE in patients aged <18 years.2 Other antibodies associated with AE (leucine-rich glioma-inactivated 1, contactin-associated protein-like 2, glutamic acid decarboxylase 65-kilodalton isoform, γ-aminobutyric acid A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) are reported in children as case reports or series and with less clear typical clinical syndromes.3–9
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