Anti-NMDA receptor encephalitis: epidemiological differences and common challenges.
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ABSTRACT:
SUBMITTER: Ceanga M
PROVIDER: S-EPMC7327341 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Anti-NMDA receptor encephalitis: epidemiological differences and common challenges.
Ceanga Mihai M Chung Ha-Yeun HY Geis Christian C
Annals of translational medicine 20200601 11
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Project description:ObjectiveTo describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients ≥45 years old.MethodObservational cohort study.ResultsIn a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients ≥45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs. 12%, p < 0.0001), had lower frequency of tumors (23% vs. 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p = 0.009) and treatment (7 vs. 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs. 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05-0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47-0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04-0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10-7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.ConclusionsAnti-NMDAR encephalitis is less severe in patients ≥45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.
| S-EPMC3795591 | biostudies-literature
Project description:Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.
| S-EPMC5297824 | biostudies-literature
Project description:ObjectiveTo evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy.MethodsWe consecutively enrolled patients with anti-NMDA receptor encephalitis who remained bedridden after first-line immunotherapy (steroids and intravenous immunoglobulin), second-line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib. Clinical response, functional recovery, and changes in antibody titer in the serum and cerebrospinal fluid were measured.ResultsBefore the bortezomib treatment, the five patients with severe refractory anti-NMDA receptor encephalitis were in a vegetative state. During the 8 months of follow-up period, three patients improved to minimally conscious states within 2 months of bortezomib treatment, one failed to improve from a vegetative state. However, no patient achieved functional recovery as measured by the modified Rankin Scale score (mRS). Three patients advanced to a cyclophosphamide with bortezomib and dexamethasone regimen, which only resulted in additional adverse events, without mRS improvement. Among the four patients whose antibody titer was followed, two demonstrated a twofold decrease in the antibody titer in serum and/or cerebrospinal fluid after 2 cycles of bortezomib.InterpretationAlthough there were some improvements in severe refractory patients, clinical response to bortezomib was limited and not clearly distinguishable from the natural course of the disease. The clinical benefit of bortezomib in recent studies requires further validation in different clinical settings.
| S-EPMC5945964 | biostudies-literature
Project description: Not available
| S-EPMC3039209 | biostudies-literature
Project description:IntroductionOvarian teratoma is a common occurrence in patients with anti-NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe-associated teratomas and non-encephalitic control teratomas.Materials and methodsA prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole-exome sequencing data and pathologic findings between NMDARe-associated teratomas and control teratomas.ResultsWe found 18 NMDARe-associated teratomas from 15 patients and compared them with 17 non-encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non-encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non-encephalitic teratomas (n = 18). However, rituximab-naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non-encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab-treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab-naïve encephalitic teratomas (P = 0.048 and 0.023, respectively).DiscussionThese results suggest that the initiation of immunopathogenesis in NMDARe-associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma.
| S-EPMC10791014 | biostudies-literature
Project description:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most recognized form of autoimmune encephalitis. It is characterized by a constellation of neurologic and psychiatric features along with positive NMDAR antibody, which is more sensitive and specific in CSF than serum. All patients should be screened at least once for neoplasm, with ovarian teratoma being found in most tumor-related cases. In the acute phase, first-line immunotherapy, often a combination of high-dose steroids, immunoglobulins, and/or plasma exchange, is strongly recommended. When first-line therapy fails, escalation to second-line immunotherapy, particularly rituximab, can further improve outcomes and prevent relapses. In refractory cases, additional complementary immunotherapies, such as cyclophosphamide, bortezomib and/or tocilizumab may be considered. Relapses occur in 10-30% of cases, mostly within the first two years from onset. Individuals should be followed up to determine if chronic maintenance therapy is required.
| S-EPMC9826635 | biostudies-literature
Project description:BackgroundClinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.MethodsForty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.ResultsNon-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.ConclusionsAnti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.
| S-EPMC5899027 | biostudies-literature
Project description: Not available
| S-EPMC3806918 | biostudies-literature
Project description:We recently described a severe, potentially lethal, but treatment-responsive encephalitis that associates with autoantibodies to the NMDA receptor (NMDAR) and results in behavioral symptoms similar to those obtained with models of genetic or pharmacologic attenuation of NMDAR function. Here, we demonstrate that patients' NMDAR antibodies cause a selective and reversible decrease in NMDAR surface density and synaptic localization that correlates with patients' antibody titers. The mechanism of this decrease is selective antibody-mediated capping and internalization of surface NMDARs, as Fab fragments prepared from patients' antibodies did not decrease surface receptor density, but subsequent cross-linking with anti-Fab antibodies recapitulated the decrease caused by intact patient NMDAR antibodies. Moreover, whole-cell patch-clamp recordings of miniature EPSCs in cultured rat hippocampal neurons showed that patients' antibodies specifically decreased synaptic NMDAR-mediated currents, without affecting AMPA receptor-mediated currents. In contrast to these profound effects on NMDARs, patients' antibodies did not alter the localization or expression of other glutamate receptors or synaptic proteins, number of synapses, dendritic spines, dendritic complexity, or cell survival. In addition, NMDAR density was dramatically reduced in the hippocampus of female Lewis rats infused with patients' antibodies, similar to the decrease observed in the hippocampus of autopsied patients. These studies establish the cellular mechanisms through which antibodies of patients with anti-NMDAR encephalitis cause a specific, titer-dependent, and reversible loss of NMDARs. The loss of this subtype of glutamate receptors eliminates NMDAR-mediated synaptic function, resulting in the learning, memory, and other behavioral deficits observed in patients with anti-NMDAR encephalitis.
| S-EPMC2868315 | biostudies-other
Project description:ObjectiveThe goal of this study was to examine whether the static functional connectivity (FC) of the executive control network (ECN) and the temporal properties of dynamic FC states in the ECN can characterize the underlying nature of anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis and their correlations with cognitive functions.MethodsIn total, 21 patients with anti-NMDA receptor encephalitis past the acute stage and 23 healthy controls (HCs) underwent a set of neuropsychological tests and participated in a resting-state fMRI study to analyse the static FC of the ECN and the temporal properties of dynamic FC states in the ECN. In addition, correlation analyses were performed to determine the correlations between the FC metrics and cognitive performance.ResultsPatients with anti-NMDA receptor encephalitis past the acute stage showed significant cognitive impairments compared to HCs. In accord with the results of neuropsychological tests, static intrinsic FC alterations and changed dynamic FC metrics of ECN were observed in the patients. Importantly, we observed significant correlations between altered ECN metrics and working memory, information processing speed, executive function performance in the patients.InterpretationOur findings suggest that cognitive impairments in patients with anti-NMDA receptor encephalitis past the acute stage are likely related to altered static and dynamic ECN connectivity. These observations may enhance our understanding of the pathophysiological mechanisms underlying cognitive function in this population.
| S-EPMC8791804 | biostudies-literature