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Worldwide survey of neurologists on approach to autoimmune encephalitis | Neurology Clinical Practice

Worldwide survey of neurologists on approach to autoimmune encephalitis | Neurology Clinical Practice | AntiNMDA | Scoop.it
Abstract Objective To explore practice differences in the diagnosis and management of autoimmune encephalitis (AE), which is complicated by issues with sensitivity/specificity of antibody testing, nonspecific MRI/EEG/CSF findings, and competing differential diagnoses. Methods We used a worldwide electronic survey with practice-related demographic questions and clinical questions about 2 cases: (1) a 20-year-old woman with a neuropsychiatric presentation strongly suspicious of AE and (2) a 40-year-old man with new temporal lobe seizures and cognitive impairment. Responses among different groups were compared using multivariable logistic regression. Results We received 1,333 responses from 94 countries; 12.0% identified as neuroimmunologists. Case 1: those treating >5 AE cases per year were more likely to send antibodies in both serum and CSF (adjusted odds ratio [aOR] vs 0 per year: 3.29, 95% CI 1.31–8.28, p = 0.011), pursue empiric immunotherapy (aOR: 2.42, 95% CI 1.33–4.40, p = 0.004), and continue immunotherapy despite no response and negative antibodies at 2 weeks (aOR: 1.65, 95% CI 1.02–2.69, p = 0.043). Case 2: neuroimmunologists were more likely to send antibodies in both serum and CSF (aOR: 1.80, 95% CI 1.12–2.90, p = 0.015). Those seeing >5 AE cases per year (aOR: 1.86, 95% CI 1.22–2.86, p = 0.004) were more likely to start immunotherapy without waiting for antibody results. Conclusions Our results highlight the heterogeneous management of AE. Neuroimmunologists and those treating more AE cases generally take a more proactive approach to testing and immunotherapy than peers. Results highlight the need for higher-quality cohorts and trials to guide empiric immunotherapy, and evidence-based guidelines aimed at both experts and nonexperts. Because the average AE patient is unlikely to be first seen by a neuroimmunologist, ensuring greater uniformity in our approach to suspected cases is essential to ensure that patients are appropriately managed. Autoimmune encephalitis (AE) is a type of noninfectious neuroinflammation that is an increasingly recognized cause of acute or subacute progressive alteration in mental status with various presentations. Some cases are associated with specific autoantibodies to cell surface molecules and intracellular targets.1 However, antibody testing is not always available at many institutions, and results are of variable sensitivity and specificity, depending in part on the type of assay performed and on whether antibody testing is performed in both the serum and CSF or only in one or the other.2 The diagnostic process is complicated by new antibodies being identified at a rapid pace3,4 and known antibodies being identified in less characteristic cases, such as a first presentation of isolated psychosis.5 As antibody testing can often be negative, clinicians often must make a diagnosis using a combination of clinical phenotypes, neuroimaging, electroencephalography (EEG), and CSF results. To complicate matters, antibody-mediated syndromes might not be associated with any evidence of inflammation in MRI and CSF studies in some patients, and EEG findings are often nonspecific.6 There are also several differential diagnoses to consider with AE-like presentations.2 Although some cases of suspected AE might respond positively to immunotherapy, this outcome is neither consistent nor specific to the diagnosis of AE—improvement with steroids, for example, often seen with lymphoma.7 There remains a paucity of high-quality diagnostic and treatment studies. Given these uncertainties regarding the diagnosis and management of AE, we recently interviewed experts from 3 different continents regarding the challenges of AE diagnosis and the role of antibody testing.8 Despite their different practice settings, all of them agreed that the diagnosis of AE should be driven primarily by the patient's clinical presentation and exclusion of key differential diagnoses, particularly infectious etiologies, and that workup should involve a thorough search for associated malignancies. They emphasized the importance of treating suspected AE cases with at least steroids while awaiting results of antibody testing. They agreed that antibody testing should be performed on both CSF and serum samples but cautioned against overreliance on these results. In particular, negative results for available antibodies would not dissuade them from treating patients with convincing presentations. This was in agreement with a recent position paper proposing a clinically grounded guideline for the diagnosis of AE.2 However, consensus among experts does not always reflect the “ground reality” of how neurologists approach these cases. Understanding how clinicians differ in their approach to complex diseases like AE can help inform not only further research but also educational initiatives and guideline development by highlighting enduring areas of uncertainty or clinical equipoise. Therefore, we explored practice differences in AE diagnosis and management using a worldwide electronic survey. Methods Survey The survey was launched by the Practice Current section of Neurology: Clinical Practice (neurology.org/collection/practice_current). We used an electronic survey that included 7 clinical and 8 demographic questions (appendix e-1, links.lww.com/CPJ/A113). The clinical questions pertained to 2 cases. Case 1 was deemed by 3 interviewed experts to be clinically convincing for autoimmune limbic encephalitis and consisted of a 20-year-old woman presenting with a neuropsychiatric syndrome, supportive brain MRI findings, and CSF lymphocytic pleocytosis.1 Respondents were asked whether they would send an autoantibody panel, and if so, in serum only or both serum and CSF. They were also asked whether they would start empiric treatment for AE with the autoantibody panel pending. Upon then being told that the panel has returned negative and the patient has still not improved with 2 weeks of first-line immunotherapy, respondents were asked whether they would continue immunotherapy (1st- and/or 2nd-line agents) or stop. Case 2 was more ambiguous and consisted of a 40-year-old man with new seizures, mild short-term memory impairment, right temporal lobe seizures, T2 hyperintensity in the right hippocampus, and negative infectious workup. However, the interviewed experts also deemed this case as suspicious enough for AE to warrant antibody testing and empiric immunotherapy.8 Respondents were asked whether they would send autoantibodies in the serum and/or CSF and whether they would start first-line immunotherapy. Those who did not start immunotherapy were asked if they would change their management, should the autoantibody panel return positive (low titer) for anti-NMDA receptor (NMDAR) antibodies in the serum and CSF in 2 weeks, with the patient experiencing focal seizures despite 2 adequately dosed antiepileptic drugs (AEDs). Demographic questions included whether respondents identified as neuroimmunologists, the number of cases of AE they would treat per year, the population treated (adults/children/both), years in practice, primary work setting, level of training, whether their practice was located in the United States or abroad, and in what US state or country. The survey was available online and was anonymous. Participation did not require membership in the American Academy of Neurology (AAN) or subscription to AAN journals. No compensation was offered. A link to the questionnaire was available in the Neurology® journals' webpages, in online ads and the print version of the journals, and in the Practice Current dedicated webpage. The survey was also advertised by the AAN and Neurology journals via social media. Individual internet protocol address was collected to ensure authenticity of responses. We opened the survey from November 28, 2017, to May 28, 2018, and all responses collected were included in the analysis. Statistical analysis The frequency of responses for each question/scenario was calculated for different demographic groups, focusing on (1) subspecialty status (neuroimmunologist vs not), (2) cases of AE treated over the past 12 months, (3) years in practice (trainee, <10-year experience, and >10-year experience), (4) practice population (children/adults/both), and (5) practice location (United States vs abroad). For case 1, we examined the proportion of respondents in each group who chose to (a) send an antibody panel, (b) send the panel in both serum and CSF (vs serum alone), (c) provide empiric immunotherapy without waiting for antibody results, and (d) continue immunotherapy despite no meaningful response to immunotherapy at 2 weeks and negative antibody testing. For case 2, we examined the proportion of respondents in each group who chose to (a) send an antibody panel in both serum and CSF, (b) provide empiric immunotherapy without waiting for antibody results, and (c) start immunotherapy (if initially not doing so) on being informed that the panel had returned with low-titer positive anti-NMDAR antibodies in the serum and CSF. For univariable analyses, we used the Fisher exact test. After identifying significant differences between the groups on univariable analysis, multivariable logistic regression was performed to adjust for all confounding variables, namely subspecialty status (neuroimmunologist vs not), AE cases per year (coded categorically as 0, 1–5, or >5), practice population (children/adults/both), and practice location (United States vs abroad). Statistical significance was set at 2-sided p < 0.050, except for subsequent 2 × 2 tests for significant associations in 3 × 2 tables, in which case significance was set at 2-sided p < 0.017 (Bonferroni correction p = 0.050/3). All analyses were performed using STATA 13.1. Standard protocol approvals, registrations, and patient consents The study was certified as exempt from review by Children's National Medical Center Institutional Review Board. Data availability Anonymized data will be shared by request from any qualified investigator. Results We received 1,333 responses from 94 countries, of which 1,084 (81.3%) were complete with all questions answered. The key respondent characteristics are shown in table 1. View inline View popup Table 1 Characteristics of the survey respondents (n = 1,128) Case 1 When presented case 1, 92.3% of respondents chose to send an autoimmune antibody panel. On univariable analysis, the population treated and years in practice were associated with the decision to send an antibody panel (table 2). On multivariable regression, those who reported treating more cases of AE in the past 12 months (adjusted odds ratio [aOR] for >5 cases per year vs 0: 3.29, 95% CI 1.31–8.28, p = 0.011) were more likely to send antibodies, whereas those working with both adults/children were less likely to do so than those working with adults alone (aOR: 0.46, 95% CI 0.25–0.84, p = 0.011, table e-1, links.lww.com/CPJ/A112). View inline View popup Table 2 Autoantibody panel sent for case 1 (1,128 respondents) Of those choosing to send an autoantibody panel, 91.6% chose to send the panel in both serum and CSF, whereas 8.4% chose to send it in the serum alone. On univariable analysis, respondents working with children were more likely to send antibodies in both serum and CSF rather than just serum compared with those working with both adults and children (table 3). However, on multivariable regression, no associations were found with this decision; respondents working with children alone were “dropped” because they all favored sending antibodies in both serum and CSF (table e-2, links.lww.com/CPJ/A112). View inline View popup Table 3 Autoantibody panel sent in both serum and CSF vs serum alone for case 1, among those choosing to send a panel (1,053 respondents) Of note, 85.1% of those choosing to send a panel said that they would treat the patient empirically for presumed AE, whereas 9.2% said that they would wait for the antibody panel to come back and treat only if it was positive at least in the serum, and 3.2% said that they would treat only if it was positive in both serum and CSF. Of note, 2.4% suggested alternative plans, including starting acyclovir (n = 12) or treating both with acyclovir and immunotherapy (n = 5). Although respondents were told that extended toxicology testing, CT of the chest/abdomen/pelvis, and extensive infectious workup were negative, a few wanted additional investigations before deciding on immunotherapy, such as obtaining EEG to look for supportive patterns like extreme delta brush (n = 2), further exclusion of infectious causes particularly herpes (n = 6), and a pelvic ultrasound to rule out ovarian teratoma (n = 2). A few others reported that their choice would depend on factors such as clinical disability (n = 2) or presence of additional signs like refractory seizures (n = 2). On univariable analysis, the number of AE cases managed annually (per respondent report) was associated with the decision to start empiric immunotherapy while awaiting antibody results (table 4). On multivariable regression, the number of AE cases per year remained associated with the decision to pursue empiric immunotherapy (aOR for 1–5 per year vs 0: 2.31, 95% 1.51–3.51, p < 0.001; >5 per year: aOR: 2.42, 95% CI 1.33–4.40, p = 0.004, table e-3, links.lww.com/CPJ/A112). View inline View popup Table 4 Empiric immunotherapy chosen in case 1 (1,147 respondents) If no meaningful improvement at 2 weeks with first-line immunotherapy and antibody panel negative in CSF and serum, 577/970 (59.5%) who favored empiric therapy said that they would continue immunotherapy (first- and second-line agents), whereas 367 (37.8%) said that they would stop immunotherapy and reassess for other causes. Of note, 2.7% proposed alternatives, including both continuing immunotherapy while reassessing for other causes (n = 12), repeating the lumbar puncture perhaps with extended antibody screening (n = 4), additional body cancer screening or consideration of brain biopsy (n = 2), long-term EEG monitoring (n = 1), waiting longer for delayed treatment effect before continuing (n = 1), or considering oophorectomy (n = 1). On univariable analysis, the number of AE cases per year was associated with the decision to continue immunotherapy despite no response at 2 weeks and negative antibody testing (table 5). On multivariable regression, respondents who reported seeing >5 AE cases per year were more likely to persist with immunotherapy (aOR: 1.65, 95% CI 1.02–2.69, p = 0.043, table e-4, links.lww.com/CPJ/A112). View inline View popup Table 5 Continued immunotherapy despite no meaningful response to immunotherapy at 2 weeks and negative antibody testing in case 1 (970 respondents) Case 2 For case 2, 846/1,237 (68.4%) chose to send antibodies in both serum and CSF, 117 (9.5%) in serum alone, whereas 264 (21.3%) chose not to send antibodies. Ten (0.8%) had independent responses including that they would only send antibodies if there was CSF leukocytosis (n = 3) or supportive features like contrast enhancement on MRI (n = 1), or refractory or exceptionally frequent seizures (n = 2). Three said that they would wait for herpes virus PCR to return negative. One respondent indicated that most of the time they could not afford antibody testing. On univariable analysis, respondents identifying as neuroimmunologists were more likely to send off antibodies in the serum and CSF (p = 0.003, table 6). On multivariable regression, identifying as a neuroimmunologist remained associated with sending antibodies in both serum and CSF (aOR: 1.80, 95% CI 1.12–2.90, p = 0.015, table e-5, links.lww.com/CPJ/A112). View inline View popup Table 6 Antibody panel sent in both serum and CSF in case 2 (1,237 respondents) When asked whether they would consider empiric immunotherapy, only 498 (40.3%) said that they would do so at this time, whereas 355 (28.7%) said that they would only do so if the antibody panel came back positive. Three hundred fifty-seven (28.9%) said that they would not treat. Twenty seven (2.2%) had independent responses including starting acyclovir (n = 4), starting both acyclovir and steroids (n = 1), ruling out infectious or CNS/body neoplastic processes (n = 4), only if refractory to antiepileptic drugs (n = 5), CSF suggestive of autoimmunity with oligoclonal bands, elevated protein, and/or pleocytosis (n = 6), or pending the development of new symptoms or signs (n = 1). On univariable analysis, respondents living outside the United States (p = 0.016) were more likely to choose immunotherapy without waiting for antibody results, and the number of AE cases per year was also associated with this decision (p = 0.040, table 7). On multivariable regression, seeing more AE cases per year and living outside the United States remained associated with choosing immunotherapy without waiting for antibody results (table e-6, links.lww.com/CPJ/A112). View inline View popup Table 7 Empiric immunotherapy chosen in case 2 without waiting for antibody results (1,237 respondents) On being informed that the antibody panel returned with low-titer positive anti-NMDAR antibodies in the serum and CSF while the patient was continuing to have focal seizures despite 2 appropriately dosed AEDs, 50/120 (41.7%) who initially said that they would not treat then said that they would treat with immunotherapy; 60 (50.0%) additionally said that they would make changes to the AEDs besides starting immunotherapy. Ten (8.3%) said that they would only change AEDs. On univariable analysis, living outside the United States was associated with choosing immunotherapy (p = 0.04); 100% of those who reported seeing >5 AE cases per year chose immunotherapy vs 76.2% of those reporting zero cases per year (p = 0.058, table e-7, links.lww.com/CPJ/A112). On multivariable regression, seeing more AE cases per year was associated with choosing immunotherapy with positive antibody results (aOR for 1–5 per year vs 0: aOR: 5.55, 95% CI 1.03–29.8, p = 0.046, table e-8, links.lww.com/CPJ/A112). Discussion In a large Practice Current worldwide survey of neurologists using representative cases, we identified considerable heterogeneity in the diagnosis and management of AE. In particular, neuroimmunologists and those treating more AE cases per year generally took a more proactive approach to testing and immunotherapy than peers. Our findings have implications for guideline development and educational initiatives, the design of future large-scale cohorts or trials of AE, and for estimates of AE prevalence. First, the considerable differences in approach between different groups of physicians, particularly between those identifying as neuroimmunologists vs as non-neuroimmunologists and between those encountering AE more vs less often, highlight the importance of further educational initiatives and evidence-based guidelines aimed at both experts and nonexperts. Both cases in our survey were deemed by interviewed experts to be suspicious enough for AE to warrant antibody testing and empiric immunotherapy,8 but clearly this opinion was not unanimous among survey respondents. This lack of uniformity is worrisome, as observational data indicate that AE can leave 20% of patients dependent for daily activities and that early treatment is a key predictor of good outcome.9 Because the typical patient with AE is unlikely to be seen first by a neuroimmunologist, ensuring greater uniformity in our approach to suspected cases is essential to ensure that patients are appropriately managed and investigated for this potentially devastating disease. The absolute difference in responses between those identifying as neuroimmunologists vs non-neuroimmunologists was much smaller for the less ambiguous case 1—which was very much in keeping with NMDAR antibody encephalitis1—and may reflect greater awareness of one form of AE among neurologists, encouragingly indicating the potential effectiveness of education in this regard. Second, the areas of relative disagreement identified by our survey may help inform the design of future large-scale cohorts or trials in AE, which need to be based on an understanding of practice patterns and attitudes of physician stakeholders to successfully recruit patients and help resolve practical uncertainties. In particular, it is unclear what the threshold should be to send an autoimmune panel and use immunotherapy in patients with new-onset, imaging-negative temporal lobe epilepsy, as in case 2. Although neuroimmunologists were more likely to send testing, this is not necessarily the most pragmatic or cost-effective option. Future cohort studies should assess the yield of testing such undifferentiated cases and the risks/benefits of early treatment vs waiting for positive antibody results. There is also the challenge of identifying patients presenting with psychotic or other neuropsychiatric symptoms who may warrant further investigation for AE. For example, in NMDAR antibody encephalitis, central psychopathologic features of mood and psychotic disorders consistently coexist within individual patients, although well-controlled prospective studies are needed to further advance this approach.10 The definition of acceptable treatment delay and “red flag” symptoms also requires further evidence-based clarification. For example, a recent cohort study found that delays to treatment longer than 4 weeks and lack of improvement in that time frame were both independently associated with poor 1-year functional outcome, in addition to intensive care unit admission, abnormal MRI, and CSF white blood cell count >20 cells/μL.11 A smaller retrospective cohort study found that treatment delays shorter than 60 days and the absence of status epilepticus were associated with better cognitive performance over a year after symptom onset.12 It may very well turn out that antibody testing is best reserved for patients with additional concerning features like status epilepticus, unambiguous cognitive impairment, or psychiatric manifestations and that waiting 2 weeks for more evidence from antibody results does not dramatically change outcomes. Third, the apparent discrepancies in our approach to AE cases will contribute to inaccurate estimates of the incidence/prevalence of AE and response to treatment, particularly if such data are derived from physician diagnostic codes or other administrative data. For example, missed cases of AE can lead to underestimates of incidence/prevalence, whereas overzealous diagnoses can lead to additional erroneous labels of immunotherapy failure. This can in turn compromise decisions about resource allocation and the development of AE treatment protocols. These challenges further emphasize the need for high-quality cohort studies that ideally incorporate direct clinical evaluations or at least comprehensive review of patient records guided by diagnostic criteria.13 Although our analysis has several strengths, including a large worldwide sample and representation of neurologists across specialties and levels of experience, there are important shortcomings. First, we could not represent the full spectrum of AE presentations and diagnostic/treatment conundrums needed for more granular analyses of physician decision making. The cases presented may not be generalizable to all practice settings. However, we chose to limit this survey to 2 cases in the interest of maximizing brevity and survey completion. Second, our survey-based study is vulnerable to selection bias; for instance, respondents more interested in autoimmune neurology may have been overrepresented. Third, respondents may have been biased by us framing the survey as related to AE, which may have resulted in an overestimate of the proportion of respondents who would investigate and treat the cases as AE. Fourth, we cannot be confident whether respondents chose an option because they thought it was the best course of action or because it seemed most feasible within their practice. Fifth, because we did not contact respondents ourselves, we could not verify the veracity of respondents' qualifications. However, by not limiting respondents to our network, we were able to capture a greater diversity of respondents. In conclusion, our results highlight the heterogeneous management of AE, the need for higher-quality cohorts and trials to guide empiric immunotherapy, and call for evidence-based guidelines aimed at both experts and nonexperts. Study funding No targeted funding reported. Disclosure A. Ganesh is a member of the editorial team of Neurology; has received speaker honoraria from The Meritas Seminar Series, Oxford; has served as a consultant for Adkins Research Group and Genome BC; has received research support from The Rhodes Trust and Wellcome Trust; and holds stock/stock options from SnapDx, TheRounds.ca, and Advanced Health Analytics (AHA Health Ltd). L. Bartolini is a Section Editor for Neurology Clinical Practice. Dr. Bartolini is an employee of the federal government. This manuscript was not a term of his employment, nor did he receive any compensation for the manuscript. S.F. Wesley has been a member of the editorial staff of the Resident and Fellow Section of Neurology. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. Appendix Authors Footnotes Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. Infographic: Npub.org/NCP/pc06-research Explore this topic: Npub.org/NCP/pc6 Interactive world map: NPub.org/NCP/map06 More Practice Current: NPub.org/NCP/practicecurrent Received March 7, 2019. Accepted May 16, 2019. © 2019 American Academy of Neurology References 1.↵Dalmau J, Geis C, Graus F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev 2017;97:839–887.OpenUrlCrossRefPubMed 2.↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.OpenUrlCrossRefPubMed 3.↵Gresa-Arribas N, Planaguma J, Petit-Pedrol M, et al. Human neurexin-3alpha antibodies associate with encephalitis and alter synapse development. Neurology 2016;86:2235–2242.OpenUrl 4.↵Sabater L, Gaig C, Gelpi E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 2014;13:575–586.OpenUrlCrossRefPubMed 5.↵Kayser MS, Titulaer MJ, Gresa-Arribas N, Dalmau J. Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-d-aspartate receptor encephalitis. JAMA Neurol 2013;70:1133–1139.OpenUrl 6.↵Escudero D, Guasp M, Arino H, et al. Antibody-associated CNS syndromes without signs of inflammation in the elderly. Neurology 2017;89:1471–1475.OpenUrl 7.↵Porter AB, Giannini C, Kaufmann T, et al. Primary central nervous system lymphoma can be histologically diagnosed after previous corticosteroid use: a pilot study to determine whether corticosteroids prevent the diagnosis of primary central nervous system lymphoma. Ann Neurol 2008;63:662–667.OpenUrlCrossRefPubMed 8.↵Ganesh A, Wesley SF. Practice Current: when do you suspect autoimmune encephalitis and what is the role of antibody testing? Neurol Clin Pract 2018;8:67–73. 9.↵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 10.↵Al-Diwani A, Handel A, Townsend L, et al. The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry 2019;6:235–246.OpenUrl 11.↵Balu R, McCracken L, Lancaster E, Graus F, Dalmau J, Titulaer MJ. A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 2019;92:e244–e252.OpenUrl 12.↵Hebert J, Day GS, Steriade C, Wennberg RA, Tang-Wai DF. Long-term cognitive outcomes in patients with autoimmune encephalitis. Can J Neurol Sci 2018;45:540–544.OpenUrl 13.↵Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018;83:166–177.OpenUrlCrossRefPubMed
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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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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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Longitudinal measurement of CSF neurofilament light in anti‐NMDAR encephalitis - Macher - - European Journal of Neurology

Longitudinal measurement of CSF neurofilament light in anti‐NMDAR encephalitis - Macher - - European Journal of Neurology | AntiNMDA | Scoop.it
Abstract Background Biomarkers reflecting the course of patients suffering from anti‐NMDAR encephalitis (anti‐NMDARE) are urgently needed. Neurofilament light chains (NfL) have been studied as a po...
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Brain researcher: It’s difficult to separate the physical and mental when it comes to our brains

Brain researcher: It’s difficult to separate the physical and mental when it comes to our brains | AntiNMDA | Scoop.it
Emotions, mental ailments, brain diseases: Everything happens in the brain. Technological advances have given us new perspectives on how the brain works, according to Norwegian brain researchers.
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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

Autoimmune encephalitis: When your body attacks your brain, and people think you’re going mad | AntiNMDA | Scoop.it
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

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B - ScienceDirect | AntiNMDA | Scoop.it
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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Seizure-related 6 homolog like 2 autoimmunity | Neurology Neuroimmunology & Neuroinflammation

Seizure-related 6 homolog like 2 autoimmunity | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
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Early clinical suspicion and treatment in a patient with anti-NMDA receptor encephalitis

Early clinical suspicion and treatment in a patient with anti-NMDA receptor encephalitis | AntiNMDA | Scoop.it
Anti-NMDA receptor encephalitis is a complicated disease associated with paraneoplastic syndromes and autoimmune conditions.This case report highlights the importance of early identification and reviews the common clinical manifestations, diagnostic studies, and treatment modalities for this potent...
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