Clinical significance of soluble adhesion molecules in anti-NMDAR encephalitis patients.
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ABSTRACT:
SUBMITTER: Ding Y
PROVIDER: S-EPMC6529932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate the nature of prodromal headache in anti-NMDA receptor (NMDAR) encephalitis.MethodsRetrospective review of the clinical information of 39 patients with anti-NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12-47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report.ResultsTwenty-two patients (65%) reported headache either transiently (n = 5) or continuously (n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1-29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/?l [range, 6-311/?l] vs. 30/?l [range, 2-69/?l], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them.ConclusionsHeadache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody-mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking "dissociative anesthesia," we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.
| S-EPMC6043713 | biostudies-literature
Project description:The performance of anti-NMDAR Encephalitis One-Year Functional Status (NEOS) in predicting the 1-year functional status in Chinese patients with anti-NMDAR encephalitis is unknown. We recruited patients with anti-NMDAR encephalitis from the Multicenter and Prospective Clinical Registry Study of Anti-NMDAR Encephalitis in Beijing Area. Patients were followed up for 1 year. We defined the poor functional status as a modified Rankin Scale score of more than 2 and good functional status as a modified Rankin Scale score of no more than 2. We performed a receiver-operator characteristic analysis to assess the discriminatory power of the NEOS score in predicting the 1-year functional status by using the area under the curve (AUC). Calibration was assessed by Pearson correlation coefficient and Hosmer-Lemeshow tests. Among the 111 patients with anti-NMDAR encephalitis recruited from 364 potentially eligible participants, 87 (78.4%) had good functional status at 1 year, whereas the remaining 24 (21.6%) had poor functional status. The AUC of the NEOS score for 1-year poor functional status was 0.86 (95% CI 0.78-0.93, p < 0.001). The increased NEOS was associated with higher risk of 1-year poor functional status in patients with anti-NMDAR encephalitis. The NEOS score is considered a reliable predictor of the risk of 1-year poor functional status in Chinese patients with anti-NMDAR encephalitis. This score could help to estimate the velocity of clinical improvement in advance. NCT02443350. This study provides Class III evidence that in patients with anti-NMDAR encephalitis, the NEOS score predicts 1-year functional status.
| S-EPMC7413709 | biostudies-literature
Project description:ObjectiveTo evaluate the presence of immunoglobulin A (IgA) subtype of anti-NMDA receptor (NMDAR) antibodies (IgA-NMDAR-Abs) in the CSF of patients with immunoglobulin G (IgG)-NMDAR-Ab encephalitis and to describe the potential association with a specific clinical pattern.MethodsThe retrospective analysis for the presence of IgA-NMDAR-Abs in 94 CSF samples from patients with anti-NMDAR encephalitis diagnosed between October 2007 and February 2014 was conducted at the French Reference Centre on Paraneoplastic Neurological Syndrome. This observational study compared 39 patients with both IgA- and IgG-NMDAR-Abs to 55 patients with only IgG-NMDAR-Abs.ResultsIn the retrospective cohort, 41% of the patients with NMDAR-Ab encephalitis had both CSF IgG- and IgA-NMDAR-Abs. Approximately half of the IgA-NMDAR-Ab-positive patients (18/38, 49%) definitively possessed associated tumors, primarily ovarian teratomas (17/18, 94%), compared with only 5% (3/55) of the patients in the IgA-NMDAR-Ab-negative group (p < 0.001). In the adult female population at risk for ovarian teratoma, the detection of CSF IgA-NMDAR-Ab positivity showed 85% sensitivity, 70% specificity, a 57% positive predictive value, and a 90% negative predictive value for the diagnosis of ovarian teratoma. No other specific clinical features or clinical outcome were associated with CSF IgA-NMDAR-Ab positivity.ConclusionThese results suggest that in patients with IgG-NMDAR-Ab encephalitis, CSF IgA-NMDAR-Abs could be used as a biological marker for the presence of an ovarian teratoma.
| S-EPMC4630685 | biostudies-literature
Project description:Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. Methods Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann–Whitney U test (nonparametric), Student’s t test (parametric), and chi-squared test were used to analyse the differences between the two groups. Results Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). Conclusions Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia. Supplementary Information The online version contains supplementary material available at 10.1186/s12888-022-04505-x.
| S-EPMC9903498 | biostudies-literature
Project description:IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the IRAK4 gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of IRAK4 mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.
| S-EPMC7846526 | biostudies-literature
Project description: Not available
| S-EPMC6353486 | biostudies-literature
Project description:ObjectivesMost patients with anti-NMDA receptor (NMDAR) encephalitis have intrathecal synthesis of antibodies, which cause a decrease of cell surface and synaptic NMDAR. Antibodies are immunoglobulin G (IgG)1 and IgG3 subtypes and can potentially activate complement. We examined whether complement immunoreactivity and antibody-secreting cells (plasma cells/plasmablasts) are present in the brain of these patients.MethodsCultured rat hippocampal neurons were used in an immunocytochemical assay to test whether patients' antibodies can fix complement. Using the same reagents (antibodies to C9neo, C(5b-9), C3), complement immunoreactivity was determined in the brain of 5 patients, the teratoma of 21 patients, and appropriate control tissues. A set of markers for B (CD20), T (CD3, CD4, CD8) and antibody-secreting cells (plasma cells/plasmablasts, CD138) were used to examine the brain inflammatory infiltrates.ResultsPatients' antibodies were able to bind complement in vitro, but deposits of complement were not detected in patients' brain. Parallel experiments with teratomas showed that in contrast to the brain, the neural tissue of the tumors contained complement. Analysis of the inflammatory infiltrates in brain samples from autopsy or biopsy performed 3-4 weeks after symptom presentation demonstrated numerous antibody-secreting cells (CD138+) in perivascular, interstitial, and Virchow-Robin spaces, and B and T cells predominantly located in perivascular regions.ConclusionsComplement-mediated mechanisms do not appear to play a substantial pathogenic role in anti-NMDAR encephalitis. In contrast, there are copious infiltrates of antibody-secreting cells (plasma cells/plasmablasts) in the CNS of these patients. The demonstration of these cells provides an explanation for the intrathecal synthesis of antibodies and has implications for treatment.
| S-EPMC3149153 | biostudies-literature
Project description:ObjectiveTo investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs).MethodsThe clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months.ResultsA total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026].ConclusionATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.
| S-EPMC8456002 | biostudies-literature
Project description:Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination. Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination. Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid. Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.
| S-EPMC7943444 | biostudies-literature
Project description:To report the clinical features of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients < or = 18 years old.Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1.Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were < or =18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls < or =18 years old (p = 0.05), and 9% in girls < or =14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients < or =18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03).Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11-18.
| S-EPMC2826225 | biostudies-literature