Persistent seropositivity in oophorectomy-resistant anti-NMDA receptor encephalitis

2021 ◽  
Vol 14 (9) ◽  
pp. e241878
Author(s):  
Susmit Tripathi ◽  
Nara M Michaelson ◽  
Alan Segal
Keyword(s):  
Clinical Decision Making ◽  
Serum Antibody ◽  
Disease Patient ◽  
Clinical Decision ◽  
High Serum ◽  
Nmda Receptor Encephalitis ◽  
Resistant Disease ◽  
Nmdar Encephalitis ◽  
Antibody Titres ◽  
Case Basis

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood–brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.

Anti-NMDAR encephalitis presenting after immature teratoma resection

2021 ◽  
Vol 14 (11) ◽  
pp. e244637
Author(s):  
Deandra Kimberly Chetram ◽  
Kelsey Pan ◽  
Aisha Elfasi ◽  
Merry Markham
Keyword(s):  
Cancer Diagnosis ◽  
Psychiatric Symptoms ◽  
Serum Antibody ◽  
Immature Teratoma ◽  
High Dose ◽  
Intravenous Methylprednisolone ◽  
Nmda Receptor Encephalitis ◽  
Positive Serum ◽  
Antibody Titres ◽  
Significant Clinical Improvement

This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.

scholarly journals Emerging role of free triiodothyronine in patients with anti-N-methyl-D-aspartate receptor encephalitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tuo Ji ◽  
Zhi Huang ◽  
Yajun Lian ◽  
Chengze Wang ◽  
Qiaoman Zhang
Keyword(s):  
Clinical Decision Making ◽  
Clinical Decision ◽  
Nonparametric Tests ◽  
Clinical Prediction ◽  
Free Triiodothyronine ◽  
Icu Admission ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis

AbstractWe aimed to investigate the role of free triiodothyronine (FT3) in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. 137 consecutive inpatients (2016–2019) were registered prospectively and followed up for 12 months. 96 eligible patients were included in the study. The modified Rankin scale (mRS) score was collected, and the score of 3–6 was defined as a poor outcome. The patients were equally classified into 3 subgroups based on their FT3 levels obtained within 24 h of admission, and the subgroup differences were analyzed by parametric or nonparametric tests as appropriate. Logistic regression analysis was performed. We found that there was no difference in the mRS scores upon admission among 3 subgroups, however, patients in the low-FT3 subgroup tended to have higher disease severity during hospitalization and worse outcome in follow-up visits, represented by higher chances of intense care unit (ICU) admission (P < 0.001), longer hospital stay (P < 0.001), greater maximum mRS scores during hospitalization (P = 0.011), lower rates of getting clinical improvement within 4 weeks of starting treatment (P = 0.006), and higher percentages of poor 1-year outcome (P = 0.002). The level of FT3 was an independent factor correlated with ICU admission (P = 0.002) and might be a potential predictor for 1-year outcome. Our preliminary results suggest that the FT3 may be a risk factor involved in the evolution and progression of anti-NMDAR encephalitis, whereas the underline mechanisms remain to be explored. Attention should be paid to these patients with relatively low FT3 upon admission, which might possibly aid clinical prediction and guide clinical decision-making.

Variation in the absorption of a colostrally secreted marker antibody in piglets

1967 ◽  
Vol 9 (3) ◽  
pp. 385-391 ◽  
Author(s):  
G. C. Perry ◽  
J. H. Watson
Keyword(s):  
Weight Gain ◽  
Serum Antibody ◽  
Late Pregnancy ◽  
High Serum ◽  
Marked Variation ◽  
Litter Weight ◽  
Antibody Titres ◽  
Piglet Serum ◽  
Salmonella Pullorum ◽  
Serum Antibody Titre

1. Sixteen sows were immunised in late pregnancy with Salmonella pullorum antigen. Sows showed marked differences in serum antibody titre at parturition.2. Twelve hours after birth, serum antibody titres in the 173 piglets born to the 16 sows were measured. They were positively related to the serum titres of their mother.3. Marked variation existed in the antibody titres of colostra from different teats and from different sows. No relationship was found between colostral titres and the titres in sow or piglet sera.4. Sow and piglet serum titres were negatively related to piglet and litter weight gain from birth to 7 days of age.5. Those piglets with high serum antibody titres at 12 hr. after birth displayed better growth rates and enjoyed lower mortality than piglets with low antibody titres.

scholarly journals Current Status of Biomarkers in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

2021 ◽  
Vol 22 (23) ◽  
pp. 13127
Author(s):  
Nicolás Lundahl Ciano-Petersen ◽  
Pablo Cabezudo-García ◽  
Sergio Muñiz-Castrillo ◽  
Jérôme Honnorat ◽  
Pedro Jesús Serrano-Castro ◽  
...  
Keyword(s):  
Treatment Response ◽  
Rare Diseases ◽  
Clinical Decision Making ◽  
Autoimmune Disorder ◽  
Clinical Score ◽  
Clinical Decision ◽  
Current Status ◽  
Clinical Activity ◽  
Aspartate Receptor ◽  
Nmdar Encephalitis

The discovery of biomarkers in rare diseases is of paramount importance to allow a better diagnosis, improve predictions of outcomes, and prompt the development of new treatments. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disorder associated with the presence of antibodies targeting the GluN1 subunit of the NMDAR. Since it was discovered in 2007, large efforts have been made towards the identification of clinical, paraclinical, and molecular biomarkers to better understand the immune mechanisms that govern the course of the disease as well as to define predictors of treatment response and long-term outcomes. However, most of these biomarkers are still in an exploratory phase, with only a few candidates reaching the final phases of the always-complex process of biomarker development, mainly due to the low incidence of the disease and its recent description. Clinical and paraclinical markers are probably the most widely explored in anti-NMDAR encephalitis, five of them combined in a clinical score to predict 1 year outcome. On the contrary, soluble molecules, such as persistent antibody positivity, antibody titers, cytokines, and other inflammatory mediators, have been proposed as biomarkers of clinical activity, inflammation, prognosis, and treatment response, but further studies are required for their clinical validation including larger and more homogenous cohorts of patients. Similarly, genetic susceptibility biomarkers are still in the exploratory phase and, therefore, weak conclusions can for now only be achieved. Thus, further studies are warranted to define biomarkers and unravel the underlying mechanisms driving rare diseases such as anti-NMDAR encephalitis. Future international collaborative studies with prospective designs that enable the enrollment of large cohorts will allow for the identification and validation of novel biomarkers for clinical decision-making.

scholarly journals Assessing whether COVID-19 patients will benefit from critical care, and an objective approach to capacity challenges during a pandemic: An Intensive Care Society clinical guideline

2020 ◽  
pp. 175114372094853 ◽  
Author(s):  
J Montgomery ◽  
HJ Stokes-Lampard ◽  
MD Griffiths ◽  
D Gardiner ◽  
D Harvey ◽  
...  
Keyword(s):  
Decision Making ◽  
Critical Care ◽  
Clinical Decision Making ◽  
Clinical Guideline ◽  
Resource Limitation ◽  
Clinical Decision ◽  
Mutual Aid ◽  
Ethical Frameworks ◽  
Available Information ◽  
Case Basis

This national professional society guidance lays out operational and ethical principles for decision-making during a pandemic, in the immediate context of COVID-19 in the early 2020 surge iteration but with potential ongoing relevance. It identifies the different phases of a pandemic and the implications for capacity and mutual aid within a national healthcare system, and introduces a revised CRITCON-PANDEMIC framework for shared operational responsibilities and clinical decision-making. Usual legal and ethical frameworks should continue to apply while capacity and mutual aid are available (CRITCON-PANDEMIC levels 0-3); clinicians should focus on current clinical needs and should not treat patients differently because of anticipated future pressures. In conditions of resource limitation (CRITCON-PANDEMIC 4), a structured and equitable approach is necessary and an objective Decision Support Aid is proposed. In producing this guidance, we emphasise that all patients must be treated with respect and without discrimination, because everyone is of equal value. The guidance has been put together with input from patient and public groups and aims to provide standards that are fair to everyone. We acknowledge that COVID-19 is a new disease with a partial and evolving knowledge base, and aim to provide an objective clinical decision-making framework based on the best available information. It is recognised that a factual assessment of likely benefit may take into account age, frailty and comorbidities, but the guidance emphasises that every assessment must be individualised on a balanced, case by case, basis and may inform clinical judgement but not replace it. The effects of a comorbidity on someone's ability to benefit from critical care should be individually assessed. Measures of frailty should be used with care, and should not disadvantage those with stable disability.

Clinical Decision-Making in Palliative Care

2018 ◽  
Author(s):  
Eduardo Bruera
Keyword(s):  
Decision Making ◽  
Palliative Care ◽  
Clinical Decision Making ◽  
Disease Patient ◽  
Family Care ◽  
Clinical Decision ◽  
Care Patient ◽  
Cost Of Care ◽  
Decisional Control ◽  
Quality Cancer Care

Clinical decision making preference is defined as “an individual’s expectation of having the power to participate in decisions in order to obtain desirable consequences.” Understanding patients decisional control preferences is important as it improves patient-clinician communication, quality cancer care, patient satisfaction, and reduces cost of care. Palliative care decision-making differs from that of many other disease-oriented specialties. Palliative care clinical teams focus on personhood and family care rather than on disease management. Therefore, palliative care clinicians require a combination of disease, patient, and family information before decisions can be made. This chapter reviews various aspects essential for clinical decision-making in palliative care.

scholarly journals Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis

2020 ◽  
Vol 7 (2) ◽  
pp. e659 ◽  
Author(s):  
Mar Guasp ◽  
Yasmina Módena ◽  
Thaís Armangue ◽  
Josep Dalmau ◽  
Francesc Graus
Keyword(s):  
Nmda Receptor ◽  
Clinical Features ◽  
Serum Antibody ◽  
Independent Variables ◽  
Nmda Receptor Encephalitis ◽  
Retrospective Assessment ◽  
Nmdar Encephalitis ◽  
Paired Serum ◽  
Detectable Serum ◽  
Hospital Clinic

ObjectiveTo determine the frequency of anti-NMDA receptor encephalitis without detectable serum NMDAR antibodies and to compare the clinical features of these patients with those with NMDAR antibodies in serum and CSF.MethodsThis is a retrospective assessment of serum antibody status and clinical features of 489 patients with anti-NMDAR encephalitis, defined by the presence of NMDAR antibodies in the CSF, and available paired serum/CSF samples examined at Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi I Sunyer, Barcelona, between January 2007 and December 2017. NMDAR antibodies were determined with rat brain immunostaining, in-house cell-based assay (CBA), and a commercial CBA. Patients were considered seronegative if NMDAR antibodies were undetectable with the 3 indicated techniques.ResultsSerum NMDAR antibodies were not detected in 75 of 489 (15%) patients. Compared with the 414 seropositive patients, the seronegative were older (23.5 years [interquartile range (IQR): 17–43] vs 20.5 [IQR: 14–31]; p < 0.0001) and less frequently women (39 [52%] vs 313 [76%]; p < 0.001) and had less tumors (6 [9%] vs 128 [32%]; p < 0.001). In multivariate analysis, older age at diagnosis (odds ratio [OR]: 1.35 [per decade]; 95% confidence interval [CI]: 1.10–1.67), absence of tumor (OR: 0.14; 95% CI: 0.05–0.43), and less need for intensive care unit admission (OR: 0.35; 95% CI: 0.18–0.69) were independent variables associated with the absence of serum NMDAR antibodies. Time to diagnosis, treatment with immunotherapy, relapses, and outcome were similar in seronegative and seropositive patients.ConclusionsNMDAR antibodies are not detected in the serum of 15% of the patients with anti-NMDAR encephalitis. These patients appear to be older and have milder neurologic symptoms with less frequency of tumors.

108 Comparing autoimmune encephalitis variants in a pediatric cohort from Hamilton, Ontario

2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e76-e78
Author(s):  
Mark Grinberg ◽  
Michelle Schneeweiss ◽  
Christopher Povolo ◽  
Jeyanth Inkaran ◽  
Kevin Jones
Keyword(s):  
Nmda Receptor ◽  
Clinical Decision Making ◽  
Group Analysis ◽  
Autoimmune Encephalitis ◽  
Clinical Decision ◽  
Subject Area ◽  
Residual Symptoms ◽  
Receptor Antibody ◽  
Nmda Receptor Encephalitis ◽  
Csf Analysis

Abstract Primary Subject area Neurology Background Autoimmune Encephalitis (AE) is an emerging cause of epilepsy with numerous variants, including anti NMDA-receptor encephalitis, for which there is a detectable antibody. However, it is believed that there are many variants of AE for which an antibody has not yet been discovered. Objectives This study aimed to determine the differences in disease course of AE patients with and without detectable anti-NMDA receptor antibody. Design/Methods This retrospective analysis is part of a Canada-wide project aimed at evaluating the epidemiology and characteristics of AE. Cases with suspected AE were retrieved and screened by two independent reviewers against AE criteria. Those that met criteria were analyzed for trends and stratified into NMDA receptor antibody positive (NMDAr) and negative categories for inter-group analysis. Of 23 cases reviewed, 11 met criteria (aged 1-17 years, 27% males), of which 7 were NMDAr positive. Results The NMDAr subgroup was characterized by behavioural changes, focal seizures, and prodromal fever on presentation, whereas the receptor negative subset had a much higher variability of symptoms, without any distinctive patterns. On average, the NMDAr positive group showed an increase in white blood cell count on CSF analysis, and a slight increase in the proportion of patients presenting with supratentorial lesions on MRI. Both groups had abnormal findings on EEG. However, despite the lack of gross differences in findings, all of the NMDAr positive cases received IVIG (most with corticosteroids as well) while only 2 NMDAr negative patients received immunomodulatory therapy. At discharge 6/7 of the NMDAr patients had some form of residual movement disorder while the NMDAr negative group had more variable residual symptoms at discharge. Conclusion Our findings show that a high index of suspicion in the diagnosis of AE is required due to the indistinct distribution and variety in its presentation. Negative antibody findings should not rule out AE due to the possibility of unidentified antibodies. Future studies should explore why differences in treatment between the two groups exist, and if slight differences in presentation influence clinical decision-making.

scholarly journals P.072 The spectrotemporal characteristics of NMDA receptor encephalitis

2016 ◽  
Vol 43 (S2) ◽  
pp. S38-S38
Author(s):  
A Richard ◽  
T Zanos ◽  
F Dubeau ◽  
E de Villers-Sidani
Keyword(s):  
Nmda Receptor ◽  
Clinical Decision Making ◽  
Clinical Status ◽  
Power Spectra ◽  
Disease Status ◽  
Autoimmune Disorder ◽  
Clinical Decision ◽  
Disease Progress ◽  
Nmda Receptor Encephalitis ◽  
Before And After

Background: NMDA receptor encephalitis (NMDA-RE) is an autoimmune disorder caused by antibodies to the NR1-NR2B heterodimer of the NMDA receptor. Currently, disease status is tracked primarily by the presence of auto-antibodies in the cerebrospinal fluid (CSF) and serum. Using serological and CSF markers along with clinical parameters to track disease progress can be challenging since patient symptoms and disease progress can vary widely. Methods: EEGs were reviewed in a 31 year old male patient with proven NMDA-RE. EEG data were sampled from various times before and after diagnosis, as well as during various stages of treatment. All analyses were performed using Matlab (Mathworks). Results: We showed that using a simple 1/f model of spectral behaviour (Buzsaki and Draguhn, 2004), we could fit the power spectra of the raw data at various instances during routine EEGs. We have demonstrated that the values of specific fitting parameters vary in relationship to the patient’s clinical status across various stages of illness. Conclusions: The aim of this project was to explore the potential utility of EEG as a complement to the usual clinical metrics used in monitoring NMDA-RE. The analysis techniques presented here highlight the use of EEG as a practical, minimaly-invasive tool to monitor progress and potentially aid in clinical decision making.

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