RARE DISEASE
NMDA receptor encephalitis
NMDA receptor encephalitis
NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Drug discovery
2
drugs
With orphan designations
Overview
Anti-NMDA receptor encephalitis is an autoimmune disorder mediated by IgG antibodies against the GluN1 subunit of NMDA receptors, causing synaptic dysfunction and neuropsychiatric symptoms (e.g., psychosis, seizures, dyskinesias, autonomic instability, and coma). Diagnosis requires CSF antibody testing, though MRI/EEG may support evaluation. Early immunotherapy (corticosteroids, IVIG, plasma exchange) and tumor resection (if present) improve outcomes, though recovery often spans months to years [1][4][8][17].
Population
Primarily affects young adults (median age 23–24 years) and children, with 4:1 female predominance [6][10].
Racial disparities: Higher incidence in Black (2.94/million/year), Hispanic (2.17), and Asian/Pacific Islander (2.02) vs. White individuals (0.40) [2][6].
Ovarian teratomas are identified in ~31% of cases, particularly in Black females (58%) [2][6][13].
Therapies
First-line: High-dose corticosteroids, IVIG, and plasmapheresis [3][5][17].
Second-line: Rituximab or cyclophosphamide for refractory cases [3][7][9].
Tumor-directed: Resection of ovarian teratomas improves prognosis [6][13].
- Maintenance immunosuppression (e.g., mycophenolate) is reserved for relapsing/severe cases [3][7].
Categories: rare neurological diseases
Research Papers
1,128 drug discovery papers about NMDA receptor encephalitis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,128 drug discovery papers about NMDA receptor encephalitis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-12 | A hemicrania continua‑like headache as an early signal of anti‑NMDA receptor encephalitis: a case report
Trigeminal autonomic cephalalgia (TAC) syndromes, although rare in the spectrum of headache disorders, are of great importance to recognize, because they can be debilitating and may be linked to potentially serious underlying causes. We present a patient with a TAC-like headache, where the diagnostic workup revealed a new secondary cause for TAC syndromes. A 62-year-old male patient has been referred with a complaint of experiencing a new-onset severe headache located in the left orbitofrontal region. Each episode lasted 15 min and was repeated 3 to 4 times a day with mild continuous pain between episodes. Severe pain was associated with psychomotor agitation and ipsilateral cranial autonomic symptoms. Brain and vascular imaging showed mild pachymeningeal enhancement. Cerebrospinal fluid pressure and analysis were normal except for a high protein level. Further investigation for a secondary cause revealed a positive result for serum anti-N-methyl D-aspartate (NMDA) receptor antibody. The headaches were resolved after 5 days of intravenous methylprednisolone followed by oral prednisolone. There are various etiologies for secondary TACs. Most of them are structural lesions, especially in the sella turcica region, and vascular disorders such as dissection or aneurysm. To our knowledge, this is the first case of TAC associated with autoimmune encephalitis antibodies that responded significantly to corticosteroids. This patient, along with cases of Neuromyelitis Optica-Spectrum Disorder (NMO-SD) with TAC presentation, highlights the role of autoimmunity in TAC syndromes.
2026-08-15 | Symptom evolution, persistence, and pharmacological management in paediatric NMDA receptor antibody encephalitis.
To characterise symptom onset, progression, and persistence in paediatric N-methyl-D-aspartate receptor antibody encephalitis (NMDARE) using the Paediatric Autoimmune encephalitis Severity Scale (PASS), and to describe real-world symptomatic pharmacological management. We performed a retrospective study of children (<18 years) with confirmed NMDARE admitted to two tertiary centres (2012-2024). Disease severity was assessed using the modified Rankin Scale (mRS) and PASS at nadir, discharge, one year, and last follow-up. Symptomatic treatments and their timings, clinician-rated benefits and adverse events were recorded, with adverse event:benefit ratios calculated. Thirty-five patients were included (median age 8 years [IQR 4-13]; 71% female). Median peak severity was mRS 5 and PASS 22/30. Seizures and psychiatric manifestations were the most frequent presenting symptoms, whereas movement disorders, motor deficits, and autonomic dysfunction typically appeared later. Younger children (<12 years) presented with a more florid neurological picture, whereas older patients more often presented with psychiatric features; both groups progressed to similar multisystem severity at nadir. At one year, 68% achieved mRS 0-1 (median PASS 3/30), increasing to 87% at last follow-up (median 5 years). PASS identified persistent impairments in activities of daily living (26%), speech/communication (17%), and sleep (14%) at last follow-up. Symptom-directed treatments showed high perceived benefit across drug classes; second-generation antipsychotics were generally well tolerated, except risperidone, which showed higher adverse event rates. Persistent neurocognitive and functional deficits are common following NMDARE, captured better by PASS than mRS. Symptom-directed treatments showed overall favourable tolerability, with second-generation antipsychotics except risperidone demonstrating good safety.
2026-07-31 | When mania is not primary: A case report on anti-NMDA receptor encephalitis presenting during early pregnancy
Anti-NMDA receptor encephalitis is the most common subtype of autoimmune encephalitis, predominantly affecting young females and often presenting with psychiatric symptoms, leading to diagnostic challenges. We report a 27-year-old pregnant female presenting with first-episode mania and recurrent seizures. During hospitalisation, she developed drowsiness, orofacial dyskinesia and emerging catatonia, raising suspicion of autoimmune encephalitis. Initial EEG, MRI brain and CSF studies were normal, but CSF testing later confirmed anti-NMDA receptor antibodies. She was treated with intravenous methylprednisolone followed by mycophenolate mofetil resulting in significant recovery. This case highlights the need to consider autoimmune encephalitis in new-onset psychiatric presentations with neurological features.
2026-07-30 | Lethargy With Reversible Bilateral Basal Ganglia and Substantia Nigra Lesions in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a neuroinflammatory disorder characterized by a broad spectrum of neuropsychiatric symptoms, and the optimal treatment strategy for atypical or refractory cases has not been well established. We report the case of a 26-year-old woman with anti-NMDAR encephalitis associated with an ovarian teratoma who presented with acute psychiatric and neurological manifestations. The patient underwent tumor resection followed by first-line immunotherapies, including corticosteroids, intravenous immunoglobulin, and plasma exchange. Because of persistent neurological symptoms, second-line immunotherapy with cyclophosphamide was initiated, leading to gradual clinical improvement. However, she subsequently developed lethargy and upper-limb tremors, accompanied by bilateral basal ganglia and substantia nigra abnormalities on MRI. Notably, both her clinical symptoms and radiological abnormalities improved following an additional course of cyclophosphamide treatment. This report highlights a rare clinical and radiological manifestation and suggests that additional immunotherapy may be effective for delayed neurological worsening.
2026-07-24 | Fifteen years of autoimmune encephalitis in Denmark: incidence, epidemiology, and trends in treatment.
Despite increasing awareness of autoimmune encephalitis (AE), real-world, population-based epidemiological data are scarce. Using 15 years of nationwide, centralized testing data, we aimed to (1) characterize all Danish patients with neuronal cell-surface antibodies (NSAbs), GAD65, and GFAP; (2) estimate AE incidence in Denmark; and (3) assess temporal trends in treatment strategies. Nationwide testing data from 2009 to 2023 were obtained from the Danish centralized antibody test center, and the medical records for antibody-positive patients were reviewed. National and regional incidence rates were calculated using census data, and trends in testing, incidence, and treatment were analyzed. A total of 198 patients were included. The most prevalent antibody was NMDAR (n = 79), followed by LGI1 (n = 37), GAD65 (n = 20), and CASPR2 (n = 19). The national average crude incidence rate (IR) in 2019-2023 was 2.8 cases per million person-years. Incidence increased by 10% annually during the study period (IRR 1.10, 95% CI 1.04-1.17, P = 0.001). The highest regional IR was observed in the region hosting the national testing center. Second-line treatment in NMDARE increased from 24% in 2009-2013 to 48% in 2019-2023. In contrast, use of steroid-sparing therapy declined from 41 to 26% in NMDARE and from 39 to 0% in LGI1. In this nationwide cohort, Danish AE patients were comparable to previously reported cohorts and incidence estimates were similar to those reported in other national studies. Higher incidence in the testing region suggests that local expertise improves case ascertainment. Treatment patterns evolved over time, likely reflecting increasing clinical experience with AE.
cell therapies
2026-07-26 | Lymphoplasmapheresis for Refractory Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is generally responsive to immunotherapy, but some patients remain refractory despite treatment escalation. Lymphoplasmapheresis (LPE), a modified apheresis technique that removes both plasma components and circulating lymphocytes, may offer a salvage option in selected cases. We report a 61-year-old woman with refractory anti-NMDAR encephalitis who showed limited improvement after corticosteroids, intravenous immunoglobulin, and ofatumumab. After a prolonged interval following ofatumumab induction, she remained severely impaired with persistent disease activity and elevated cerebrospinal fluid and serum anti-NMDAR IgG titers. Three sessions of LPE were performed over 5 days. Clinical improvement was observed after LPE, accompanied by a decline in antibody titers. At 5-month follow-up after LPE, she maintained sustained recovery, with a Clinical Assessment Scale in Autoimmune Encephalitis score of 6 and a modified Rankin Scale score of 2. This case supports a close temporal association between LPE and clinical and immunological improvement, although causality cannot be definitively established from a single case.
2026-05-27 | Anti-NMDA Receptor Encephalitis with Predominant Psychiatric Symptomatology and Diagnostic Dilemmas: A Case Report.
Background and Clinical Significance: NMDAR autoimmune encephalitis is a rare but potentially life-threatening autoimmune disorder that can be hard to recognize initially because it has nonspecific symptoms. In the early phase of the disease, clinical presentation is often dominated by psychiatric symptoms, which can be misleading. A diagnosis is established by demonstrating specific anti-NMDA receptor antibodies, with cerebrospinal fluid analysis considered the most reliable diagnostic method. Timely initiation of immunomodulatory therapy, including corticosteroids, intravenous immunoglobulins, and therapeutic plasmapheresis, significantly improves disease outcomes, while second-line therapies are used in refractory cases. Case Presentation: A 21-year-old female patient (M.B.) was admitted to the Psychiatry Clinic at the University Clinical Center of Vojvodina due to the sudden onset of behavioral changes, including social withdrawal, absence of verbal communication, and unusual orofacial grimacing. During hospitalization, the patient was intermittently in a state of severe psychomotor agitation and poorly communicative, with pronounced orofacial dyskinesias and involuntary tongue movements. Anti-NMDA receptor autoantibodies were detected in both serum and cerebrospinal fluid, and the patient was subsequently transferred to the Intensive Care Unit of the Neurology Clinic. Due to the lack of an adequate clinical response to pulse corticosteroid therapy, six cycles of therapeutic plasmapheresis were performed. Following this treatment, significant clinical improvement was observed. Conclusions: Timely recognition of this condition and a multidisciplinary approach allow for early initiation of immunomodulatory therapy and significantly improve treatment outcomes.
2026-03-13 | CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising approach for B cell-driven neurological autoimmune disorders, particularly those characterized by pathogenic autoantibodies that target key neural structures. These conditions, including neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis, can be categorized based on their primary autoantigens into (1) extracellular antigen-associated (e.g., AQP4, AChR, NMDAR, MOG, VGCC), (2) intracellular antigen-associated (e.g., GAD65, DAGLA), or (3) unidentified antigenic origin (as seen in multiple sclerosis). This distinction is essential for guiding therapeutic strategies and exploring novel principles represented in distinct treatment approaches and their corresponding therapeutic outcomes. In this review, we propose a classification of CAR T cell therapies designed for different target antigens, including: CD19/20/BCMA-directed CAR T cells targeting general B cell-mediated pathogenesis, regulatory T cells modified with CARs, and the design of chimeric autoantibody receptors (CAARs) to selectively deplete pathogenic B cells directly associated with disease progression while preserving immune tolerance. We further discuss preclinical and clinical advancements, key challenges such as safety concerns and neurotoxicity, and the future landscape of CAR T applications in neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis according to the latest research, case and trial data. CAR T cell therapy potentially offers a highly specific and effective method with thorough elimination of autoreactive B cells, representing a rapidly evolving field with the potential to transform the treatment of autoimmune neurological disorders. As CAR T technology advances, it holds the potential to become a groundbreaking immunoablative strategy with so-far disclosed controllable side effects; however, further long-term follow-up data are still needed to validate its application in autoimmune disorders.
2025-12-18 | Comparison of the Efficacy of Polyvalent Intravenous Immunoglobulins and Therapeutic Plasma Exchange in Anti-NMDAR Encephalitis in the ICU.
Anti-N-methyl D-aspartate-receptor encephalitis (anti-NMDARe) is a severe disease with a favorable outcome when immunomodulatory management is started rapidly. The main objective of this study is to compare the early efficacy of the two most frequently used therapeutics, i.e., intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE), in intensive care patients admitted for anti-NMDARe. This is an observational retrospective study of patients hospitalized in a tertiary medical neurointensive care unit for severe anti-NMDARe. Patients were categorized according to the modality of first-line immunomodulatory therapies associated with corticosteroids: TPE, IVIG, or IVIG followed by TPE. The primary end point was the effectiveness of the first-line immunomodulatory treatment. Treatment was considered effective when no other immunomodulatory therapy was introduced and the patient met the following three conditions: response to simple commands, absence of epileptic seizures, and absence of abnormal movements. Thirty-seven patients were included in the study from January 2007 to December 2022: 8 were treated with TPE alone, 13 were treated with IVIG alone, and 16 were treated with IVIG followed by TPE. Of the 29 patients treated with IVIG, 13 showed improvement, with a median latency to treatment response of 36 days, whereas 16 were switched to TPE, with a median latency to treatment response of 30 days due to a lack of improvement. All eight patients treated with TPE improved, with a latency to treatment response of 31 days. TPE was significantly more effective than IVIG. This study raises the hypothesis that immunotherapies may have differential response rates among patients with NMDARe. Although the retrospective nature of the analysis may be subject to bias and confounding, the potential for therapeutic impact deserves prospective evaluation.
2025-11-30 | Management of Refractory Status Epilepticus and Profoundly Impaired Consciousness in Anti-NMDA Receptor Autoimmune Encephalitis
Introduction: Autoimmune encephalitis is a major cause of non-infectious encephalitis and remains challenging to diagnose based solely on clinical presentation. Confirmation is particularly difficult in antibody-negative cases despite strong clinical suspicion, requiring comprehensive diagnostic workup. Case Description: A 25-year-old male presented with progressive altered mental status and seizures preceded by behavioral changes for 10 days. EEG showed no epileptiform activity, cerebrospinal fluid analysis excluded infection, and brain CT was unremarkable. Serum and CSF HSV IgG/IgM were non-reactive. Anti-NMDA receptor antibodies in CSF were strongly positive. The patient developed refractory status epilepticus requiring mechanical ventilation, deep sedation with propofol, and multiple anti-seizure medications including phenytoin. Empirical acyclovir was administered for 10 days without improvement. High-dose methylprednisolone (1 g/day for 5 days) was given as first-line immunotherapy but yielded no neurological recovery. On day 14, plasma exchange was initiated for three sessions, resulting in marked clinical improvement with recovery of consciousness and seizure control. Conclusion: This case highlights the critical importance of considering autoimmune encephalitis even when initial antibody results are pending or imaging is normal. Early escalation to second-line immunotherapy, particularly plasma exchange, can be lifesaving in anti-NMDAR encephalitis presenting with refractory status epilepticus and profound coma.
proteins
2026-06-09 | Peptides to Specifically Inhibit Anti-NMDA Receptor Autoantibodies Using Molecular Mimicry to Treat Anti-NMDA Receptor Autoimmune Encephalitis (P8-1.008)
We aim to design peptides to specifically inhibit anti-NMDA receptor autoantibodies using molecular modelling in-silico.
2025-11-02 | Dynamics of sleep-wake cycles and architecture in anti-NMDAR encephalitis.
Sleep disturbances in anti-NMDAR encephalitis evolve dynamically across disease phases. We monitored a patient longitudinally from the acute phase through remission, relapse, and recovery, using video-EEG and polysomnography. No sleep complaints were reported during the prodromal phase, whereas coma was characterized by rhythmic theta-delta activity devoid of sleep patterns. Sleep stages gradually emerged after teratoma removal and immunotherapy, paralleling clinical improvement. A second teratoma caused relapse with severe sleep disruption and agrypnia excitata, then residual status dissociatus persisted before normalization. Sleep changes mirrored disease progression, suggesting that sleep patterns may serve as biomarkers and potential therapeutic targets in anti-NMDAR encephalitis.
2025-10-18 | HBEGF/EGFR pathway activation by hUC-MSCs improves cognitive outcomes in anti-NMDAR encephalitis.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder that impairs cognitive function. In this study, we investigated the impact of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive recovery in anti-NMDAR encephalitis. Our findings demonstrate that heparin-binding epidermal growth factor-like growth factor (HBEGF), a key functional factor secreted by hUC-MSCs, plays a pivotal role in ameliorating cognitive dysfunction. We elucidated that the HBEGF/epidermal growth factor receptor (EGFR) signaling pathway contributes to the enhancement of cognitive function following hUC-MSC exposure. Importantly, we employed a novel exosome-based intracellular therapeutic protein delivery technology-the mMaple3-mediated protein loading and release from exosomes (MAPLEX) system-for targeted HBEGF delivery. This approach facilitated a controlled, light-induced release of HBEGF from the exosomal membrane. Collectively, these findings support the involvement of HBEGF in mediating cognitive improvement in anti-NMDAR encephalitis induced by hUC-MSCs. Additionally, the MAPLEX system emerges as an effective delivery platform for HBEGF, potentially opening new avenues for the treatment of anti-NMDAR encephalitis.
2025-09-29 | Telitacicept as a novel B cell-targeted therapy in autoimmune encephalitis: a case report.
Autoimmune encephalitis (AE) comprises immune-mediated neuroinflammatory disorders presenting diverse neuropsychiatric symptoms and antibody-specific manifestations. Despite standard immunotherapy, residual disability, treatment intolerance, and relapse risks highlight unmet clinical needs. Telitacicept, a dual target fusion protein that inhibits B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), suppresses pathogenic B cell activation and autoantibody production, presenting a mechanism-driven therapeutic potential for AE management. Three AE cases with distinct therapeutic complexities are detailed in our study: (1) An anti-N-methyl-D-aspartate receptor (NMDAR) antibody-positive patient experienced recurrent relapses and was a comorbid individual with upper gastrointestinal bleeding. (2) An anti-leucine-rich glioma inactivated 1 (LGI1) antibody patient resisted corticosteroids, intravenous immunoglobulin, and ofatumumab treatment. (3) A newly diagnosed, anti-LGI1 antibody and anti-contactin-associated protein 2 (CASPR2) antibody dual-positive patient required sequential therapy to consolidate the remission and facilitate prednisone tapering. Telitacicept administration achieved symptom remission across all cases, accompanied by reduced antibody titers and stable outcomes over six months. Our case series evaluates the use of telitacicept in AE patients with varied antibody subtypes, particularly for patients with relapsed or refractory disease, intolerance to CD20-targeted agents, or steroid-related complications. Moreover, telitacicept may serve as an effective sequential therapy to sustain remission and reduce long-term steroid dependency.
2025-08-28 | Comparative efficacy of intravenous immunoglobulin and protein A immunoadsorption in severe anti-NMDAR encephalitis.
To compare the differential effects of intravenous immunoglobulin (IVIg) and protein A immunoadsorption (PAIA) on neurological functional improvement in patients with severe anti-NMDAR encephalitis. We retrospectively evaluated patients with severe anti-NMDAR encephalitis (modified Rankin scale, mRS ≥ 3) at the Second People's Hospital of Hunan from January 1, 2019, to December 31, 2024. Clinical efficacy was compared between the IVIg and PAIA groups. Clinical improvement (ΔmRS ≥ 1) and favorable functional outcomes (mRS 0-2) at 30 days and 90 days were evaluated as primary outcomes. Secondary outcomes included changes in mRS and the Clinical Assessment Scale for Autoimmune Encephalitis (ΔCASE) at 30 and 90 days, length of ICU stay, and antibody titers in cerebrospinal fluid (CSF) and serum. This study enrolled 53 patients with severe anti-NMDAR encephalitis, of whom 30 patients received IVIg and 23 patients received PAIA. The PAIA group showed a significantly higher rate of clinical improvement at 30 days after treatment compared to the IVIg group (82.61% vs. 50%, p = 0.014). However, no significant difference was found at 90 days after treatment (95.65% vs. 96.67%, p > 0.05). Furthermore, favorable functional outcomes at 30 days (17.39% vs. 6.67%) and 90 days (91.30% vs. 80.00%) showed no significant differences between the two groups (p > 0.05). Significant differences were observed in ΔmRS1 (p = 0.005), ΔmRS2 (p = 0.03), and ΔCASE1 (p = 0.027), but not in ΔCASE2 (p > 0.05). PAIA was associated with a greater reduction in antibody titers in both CSF and serum and a shorter ICU stay. Our study demonstrates that both IVIg and PAIA are effective treatments for patients with severe anti-NMDAR encephalitis. However, PAIA demonstrates several distinct advantages, including earlier clinical improvement, faster antibody clearance, and a potential reduction in ICU stay.
antibodies
2026-09-26 | Anti-NMDA Receptor Encephalitis Associated with Ovarian Teratoma: A Comprehensive Review.
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR-E) is a severe autoimmune encephalitis that predominantly affects young women and is frequently associated with ovarian teratomas. Increasing evidence indicates that these tumors play a central role in disease initiation by providing a peripheral immunological trigger. This comprehensive review summarizes current knowledge on the immunopathogenesis, clinical manifestations, diagnostic approach, therapeutic strategies, and long-term outcomes of ovarian teratoma-associated anti-NMDAR-E. We discuss the unique immunogenic properties of ovarian teratomas, including the presence of neuroglial tissue expressing the GluN1 receptor subunit (formerly known as NR1) of the N-methyl-D-aspartate receptor (NMDAR), dense immune cell infiltrates, and tertiary lymphoid structure-like formations that support local antibody production. These features are thought to promote molecular mimicry and loss of immune tolerance, leading to B-cell activation, intrathecal antibody synthesis, and antibody-mediated neuronal dysfunction. Furthermore, we review the characteristic multistage clinical course, key diagnostic findings in cerebrospinal fluid, imaging and electrophysiology, and the importance of early tumor removal combined with immunotherapy. Emerging therapeutic approaches and experimental models that provide insight into disease mechanisms and novel treatment targets are also highlighted. An improved understanding of tumor-driven neuroimmunological interactions is essential for earlier diagnosis, optimized treatment strategies, and better long-term outcomes in affected patients.
2026-09-25 | Ofatumumab Therapy and Long-Term Seizure Outcomes of Patients With Relapsing Anti-NMDA Receptor Encephalitis.
There is a lack of studies on seizure outcomes associated with ofatumumab therapy in patients for relapsing anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. We aimed to evaluate long-term seizure outcomes of ofatumumab therapy for relapsing anti-NMDA receptor encephalitis. This is a prospective cohort study, Compared patients with relapsing anti-NMDA receptor encephalitis who had received at least 1 ofatumumab dose and a control cohort of non-ofatumumab-treated patients, continuous follow-up for 24 months. The primary outcome was the seizure outcomes (including both seizure reduction and seizure freedom; seizure reduction is defined as a reduction in seizure frequency to 50% or more of the baseline level, seizure freedom is defined as having no seizures) at the follow-up. The secondary outcomes included modified Rankin Scale (mRS) scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the 24-month follow-up. We enrolled 93 patients with relapsing anti-NMDA receptor encephalitis. A total of 76 patients met the requirements after the inclusion and exclusion criteria. The 38 patients received ofatumumab therapy, and the other 38 patients received non-ofatumumab therapy. Follow-up after 6 months, the ofatumumab therapy group demonstrated favorable seizure outcomes (63.16% vs. 36.84%, p < 0.05). Follow-up after 12 months, this improvement of seizure outcomes was more pronounced (78.95% vs. 60.53%, p < 0.05). Follow-up after 24 months, this difference between the two groups widened further (94.74% vs. 78.95%, p < 0.05), compared with the non-ofatumumab therapy group. Follow-up after 6 months, the ofatumumab group demonstrated a faster mRS scores (2.85 ± 0.65 vs. 3.75 ± 0.55, p < 0.05) and CASE scores (11.80 ± 1.65 vs. 13.75 ± 1.55, p < 0.05). Follow-up after 12 months, the ofatumumab group demonstrated a faster mRS scores (1.68 ± 0.45 vs. 2.39 ± 0.35, p < 0.05) and CASE scores (6.75 ± 1.45 vs. 9.39 ± 1.35 p < 0.05). Follow-up after 24 months, the ofatumumab group demonstrated a faster mRS scores (1.25 ± 0.35 vs. 1.68 ± 0.45, p < 0.05) and CASE scores (4.25 ± 0.75 vs. 6.68 ± 1.35, p < 0.05). And no serious adverse events associated with ofatumumab treatment were reported. Furthermore, Multivariate logistic regression analysis identified that early initiation of ofatumumab therapy, psychiatric symptoms, and abnormal brain MRI findings may be associated with seizure outcomes. Ofatumumab showed substantial improvement in long-term seizure outcomes in patients with relapsing anti-NMDA receptor encephalitis, particularly those presenting with seizures as a predominant clinical feature.
2026-09-21 | Regulation of protein kinase pathways in primary neuron model of anti-NMDA receptor encephalitis
Abstract The most common form of autoimmune encephalitis is associated with antibodies that target N-methyl-D-aspartic acid receptors (NMDARs). NMDARs play a pivotal role in neurotransmission and synaptic plasticity. Mounting evidence has shown that antibody targeting of the NMDAR GluN1 subunit, as in anti-NMDAR encephalitis, leads to NMDAR cross-linking and receptor internalization. However, the underlying signaling pathways affected by antibodies targeting NMDARs remain to be explored. We previously demonstrated that a human GluN1 monoclonal antibody 5F5 (GluN1 mAb 5F5) rapidly localizes to and regulates synaptic NMDAR function at native synapses of primary hippocampal neurons. Here, we sought to explore signaling targets of GluN1 mAb 5F5 in primary cortical neurons of either sex using subcellular fractionation, Western blotting, and label-free quantitative phosphoproteomics by mass spectrometry. We find that human GluN1 mAb 5F5 does not change NMDAR abundance or surface levels of GluN1 on primary cortical neurons at 2 hr. Despite this, we observe that GluN1 mAb 5F5 alters the phosphoproteome in synaptoneurosomes and regulates numerous synapse-related biological processes and protein kinase activities. Bioinformatic analyses suggest that these phosphoproteomic changes are positively correlated with NMDAR activation and negatively correlated with NMDAR inhibition. Together, these data suggest that GluN1 mAb 5F5 alters intracellular kinase signaling pathways in primary cortical neurons, likely by activating the NMDAR. These studies may help to identify novel therapeutic strategies for anti-NMDAR encephalitis and other antibody-mediated encephalitides targeting cell surface antigens. Significance statement Anti-NMDAR encephalitis is the most common form of autoimmune encephalitis. The pathophysiology of this clinical syndrome remains poorly defined but is currently thought to involve pathogenic antibodies that crosslink and internalize NMDARs. We identify intracellular signaling pathways targeted by human NMDAR antibodies in primary cortical neurons. Our key findings are obtained using specific, patient-derived human monoclonal antibodies with high affinity to the GluN1 subunit of NMDARs, which have been shown to induce key pathogenic effects of anti-NMDAR encephalitis (Sharma, Al-Saleem, Panzer, et al. 2018; Taraschenko, Fox, Eldridge, et al. 2021; Taraschenko, Fox, Zekeridou, et al. 2021; Dean et al. 2022). These studies expand the underlying pathophysiological molecular mechanisms involved in anti-NMDAR encephalitis.
2026-09-21 | Third-line tocilizumab for refractory pediatric anti-NMDA receptor encephalitis: a single-center case series.
Tocilizumab has been proposed as a third-line therapy for refractory autoimmune encephalitis; pediatric Latin American data remain limited. To evaluate the efficacy and safety of tocilizumab in pediatric patients with severe or refractory anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We retrospectively reviewed pediatric patients with definite anti-NMDAR encephalitis treated with tocilizumab after inadequate response to previous therapy. Six patients (four males, median age at onset 4.5 years). All had severe disease (modified Rankin Scale [mRS] 4-5; Clinical Assessment Scale in Autoimmune Encephalitis [CASE] ≥10). All received first-line therapy, five received rituximab before tocilizumab. Tocilizumab was initiated 2-3 months after the last rituximab infusion. At 12 months, all achieved favorable outcomes (mRS 2; CASE ≤4). Adverse events included varicella-zoster virus infection, mild cytopenia, and dyslipidemia. Tocilizumab was associated with favorable outcomes and acceptable safety in this small pediatric series of refractory anti-NMDAR encephalitis. The CASE scale was a sensitive and reliable instrument for longitudinal functional assessment.
2026-09-18 | Bilateral pulmonary embolism in anti-NMDA receptor encephalitis presenting as acute psychosis.
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder that frequently presents with prominent psychiatric manifestations, often leading to misdiagnosis as a primary psychiatric illness. Early recognition is critical, as timely immunotherapy significantly improves outcomes. A 26-year-old previously healthy man presented with acute psychosis following significant emotional stress and first-time marijuana use 3 days earlier. Initially diagnosed with brief psychotic disorder, he developed catatonia and fever. Cerebral spinal fluid (CSF) and serum anti-NMDA receptor antibodies confirmed the diagnosis. His course was complicated by bilateral pulmonary emboli and drug-induced liver injury. Treatment with intravenous immunoglobulin (IVIG) and high-dose corticosteroids resulted in marked improvement. Malignancy work-up was negative. This case underscores the importance of considering autoimmune encephalitis in young patients presenting with new-onset psychosis, in the apparent absence of malignancy. A high index of suspicion and early CSF evaluation can prevent diagnostic delay and improve patient outcomes.
other
2026-08-30 | Narrative Medicine in Pediatric anti‑NMDA Receptor Encephalitis: A Mixed‑methods Evaluation of Triadic Outcomes Among Children, Parents, and Healthcare Providers.
Pediatric anti-NMDAR encephalitis can cause severe disability and profound caregiver distress. Narrative medicine has been proposed as a humanistic intervention, but its impact across the complete caregiving triad of children, parents, and healthcare providers has not been systematically evaluated. This exploratory study aimed to assess the multidimensional impact of narrative medicine interventions in this setting. This retrospective mixed-methods study included five children with severe anti-NMDAR encephalitis (admission mRS ≥4), their mothers, two physicians, and six nurses. Narrative medicine interventions included daily bedside narrative attention, parallel chart writing, family conferences, nurse-led narrative communication, and weekly sharing sessions. Quantitative outcomes included child mRS, parental anxiety (SAS), depression (SDS), caregiver burden (ZBI), and provider empathy (IRI), burnout (NBS), and meaningful work (WAMI). Qualitative data from parallel charts, reflective writings, and family interviews were analyzed thematically. All five children showed favourable neurological improvement (median mRS: 5→1 at 6 months; p=0.039); three returned to school. Parental outcomes showed substantial improvements: SAS (42.8→23.4, p<0.001, d=9.7), SDS (54.8→27.4, p<0.001, d=6.5), and ZBI (59.6→29.6, p<0.001, d=3.4). Nurses (n=6) showed increased empathy (IRI: 63.7→78.0, p=0.003, d=1.9) and reduced burnout (NBS: 73.0→56.3, p=0.002, d=2.1); physicians showed parallel improvements. Thematic analysis identified three potential mechanisms: clinical narrative signals, a window of narrative intervention (weeks 2-4), and bidirectional healing. In this small, exploratory retrospective case series, narrative medicine interventions were temporally associated with favourable trends in neurological outcomes, parental psychological states, and provider well-being. The proposed concepts of clinical narrative signals, a window of narrative intervention, and bidirectional healing offer a preliminary framework for integrating narrative practices into pediatric neurocritical care. These findings are hypothesis-generating and warrant prospective investigation in larger controlled studies.
2026-05-30 | Glycine-modulating Slc6a20a-ASO restores NMDA receptor function in SHANK2 and SHANK3-mutant mice and cortical organoids.
Suppressed NMDA receptor (NMDAR) function contributes to multiple brain disorders, including schizophrenia, autism spectrum disorder (ASD), and NMDAR encephalitis. Previous attempts to restore NMDAR activity by increasing ambient glycine, a critical co-agonist, through GlyT1 inhibition have yielded mixed outcomes, partly due to GlyT1's extensive expression in essential brainstem regions. Slc6a20a, a glycine transporter widely expressed in cognition-relevant regions such as the cortex and hippocampus, offers a targeted alternative. Here we show that antisense oligonucleotide (ASO)-mediated Slc6a20a inhibition (Slc6a20a-ASO) normalizes ASD-related phenotypes in male Shank2- and Shank3-mutant mice, with model-dependent rescue profiles. Slc6a20a-ASO rescues NMDAR hypofunction and synaptic phospho-proteomic profiles in the prefrontal cortex. Furthermore, ASO targeting human SLC6A20 rescues suppressed NMDAR function in cortical organoids harboring SHANK2 or SHANK3 mutations. These findings underscore the potential and limitations of Slc6a20a/SLC6A20-ASO for treating disorders characterized by NMDAR hypofunction.
2025-12-19 | Paediatric myelin oligodendrocyte glycoprotein antibody-associated disease with NMDA receptor encephalitis: overlap syndrome and challenges in the antibody testing.
We report the case of a middle childhood female child who presented with acute encephalopathy following multiple episodes of projectile vomiting and subsequently developed progressive cognitive decline, behavioural changes, visual impairment and motor regression. Neurological evaluation and imaging revealed multifocal demyelination with bilateral optic neuritis. Further work-up uncovered the coexistence of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and N-methyl-d-aspartate receptor encephalitis. Early initiation of immunotherapy with intravenous methylprednisolone and intravenous immunoglobulin led to significant clinical improvement. The case underscores the importance of screening for coexisting autoimmune conditions in demyelinating disorders, given the therapeutic and prognostic implications.
2025-09-01 | Refractory "status dyskineticus" in a child with post-herpes simplex virus 1 N-methyl-D-aspartate receptor encephalitis: a case report.
Herpes simplex virus 1 (HSV-1) encephalitis may result in relapsing neurological symptoms secondary to immune-mediated processes, including anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Refractory status dyskineticus (RSD), a severe subset of status dystonicus, is characterized by a hyperkinetic movement disorder phenotype alongside dystonic features. This critical condition presents substantial challenges in neurocritical care. The present case highlights the importance of prompt intervention and immunotherapy escalation in managing severe movement disorders due to pediatric autoimmune encephalitis. A previously healthy 2-year-old boy was admitted with HSV-1 encephalitis, confirmed by brain MRI and cerebrospinal fluid (CSF) analysis. When initially treated with acyclovir, the patient achieved partial recovery but later developed encephalopathy, vomiting, behavioral regression, and severe dyskinetic movements. Upon transfer to our center, NMDAR antibodies were detected in the CSF, with no evidence of HSV reactivation. Despite first-line immunotherapy with intravenous steroids and immunoglobulins, his condition deteriorated, progressing to status dyskineticus (SD), with dystonia, hyperthermia, and hypercapnia, requiring intensive care management and mechanical ventilation. A treatment escalation regimen including both immunotherapy with rituximab, rapamycin, bortezomib, and multiple symptomatic therapies resulted in gradual improvement and resolution of the movement disorder. This case underscores the crucial role of neurocritical care in managing refractory movement disorders associated with autoimmune encephalitis. Early recognition and immunotherapy escalation are essential to improve outcomes in children with complex, life-threatening neurological conditions. A comprehensive, multidisciplinary approach in the neurocritical care setting is key to achieving recovery and minimizing long-term neurological damage.
2025-07-30 | Effects and Mechanisms of NMDAR-EphB2 on Synapses in Mice by Active Immunization with a GluN1 Peptide.
This study investigated the expression of N-methyl-D-aspartate receptor(NMDAR)-EphB2 and associated changes in hippocampal neuronal dendritic spines and synaptic ultrastructure in an anti-NMDAR encephalitis mouse model. Utilizing the GluN1359-378 antigen, which targets the amino terminal domain of the NMDAR GluN1 subunit, we initially established an anti-NMDAR encephalitis mouse model. Subsequently, pentylenetetrazol (PTZ) was intraperitoneally injected and their seizure susceptibility was observed. Furthermore, Western blot was employed to detect the expression of GluN1, postsynaptic density protein 95 (PSD-95), EphrinB2 and EphB2 in hippocampal tissues. Immunofluorescence was used to detect the expression and co-localization of GluN1 and EphB2 in the hippocampus. Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure of hippocampal neurons, and Golgi-Cox staining was performed to examine the morphology of dendritic spines. GluN1359-378 mice exhibited increased seizure susceptibility. Furthermore, GluN1359-378 mice demonstrated significantly reduced expression of GluN1 membrane protein, as well as EphrinB2 and EphB2 proteins in hippocampal tissues. Additionally, the co-localization coefficient of GluN1 and EphB2 was decreased. Synaptic cleft width, postsynaptic density thickness, active zone length, and dendritic spine density were reduced. In conclusion, the anti-NMDAR encephalitis mouse model, established via active immunization with a GluN1 peptide antigen, exhibits increased seizure susceptibility. This heightened susceptibility may result from the disruption of the NMDAR-EphB2 interaction by NMDAR antibodies, which subsequently reduces NMDAR expression on the cell membrane and leads to alterations in synaptic structure.
small molecules
2026-09-12 | A hemicrania continua‑like headache as an early signal of anti‑NMDA receptor encephalitis: a case report
Trigeminal autonomic cephalalgia (TAC) syndromes, although rare in the spectrum of headache disorders, are of great importance to recognize, because they can be debilitating and may be linked to potentially serious underlying causes. We present a patient with a TAC-like headache, where the diagnostic workup revealed a new secondary cause for TAC syndromes. A 62-year-old male patient has been referred with a complaint of experiencing a new-onset severe headache located in the left orbitofrontal region. Each episode lasted 15 min and was repeated 3 to 4 times a day with mild continuous pain between episodes. Severe pain was associated with psychomotor agitation and ipsilateral cranial autonomic symptoms. Brain and vascular imaging showed mild pachymeningeal enhancement. Cerebrospinal fluid pressure and analysis were normal except for a high protein level. Further investigation for a secondary cause revealed a positive result for serum anti-N-methyl D-aspartate (NMDA) receptor antibody. The headaches were resolved after 5 days of intravenous methylprednisolone followed by oral prednisolone. There are various etiologies for secondary TACs. Most of them are structural lesions, especially in the sella turcica region, and vascular disorders such as dissection or aneurysm. To our knowledge, this is the first case of TAC associated with autoimmune encephalitis antibodies that responded significantly to corticosteroids. This patient, along with cases of Neuromyelitis Optica-Spectrum Disorder (NMO-SD) with TAC presentation, highlights the role of autoimmunity in TAC syndromes.
2026-08-15 | Symptom evolution, persistence, and pharmacological management in paediatric NMDA receptor antibody encephalitis.
To characterise symptom onset, progression, and persistence in paediatric N-methyl-D-aspartate receptor antibody encephalitis (NMDARE) using the Paediatric Autoimmune encephalitis Severity Scale (PASS), and to describe real-world symptomatic pharmacological management. We performed a retrospective study of children (<18 years) with confirmed NMDARE admitted to two tertiary centres (2012-2024). Disease severity was assessed using the modified Rankin Scale (mRS) and PASS at nadir, discharge, one year, and last follow-up. Symptomatic treatments and their timings, clinician-rated benefits and adverse events were recorded, with adverse event:benefit ratios calculated. Thirty-five patients were included (median age 8 years [IQR 4-13]; 71% female). Median peak severity was mRS 5 and PASS 22/30. Seizures and psychiatric manifestations were the most frequent presenting symptoms, whereas movement disorders, motor deficits, and autonomic dysfunction typically appeared later. Younger children (<12 years) presented with a more florid neurological picture, whereas older patients more often presented with psychiatric features; both groups progressed to similar multisystem severity at nadir. At one year, 68% achieved mRS 0-1 (median PASS 3/30), increasing to 87% at last follow-up (median 5 years). PASS identified persistent impairments in activities of daily living (26%), speech/communication (17%), and sleep (14%) at last follow-up. Symptom-directed treatments showed high perceived benefit across drug classes; second-generation antipsychotics were generally well tolerated, except risperidone, which showed higher adverse event rates. Persistent neurocognitive and functional deficits are common following NMDARE, captured better by PASS than mRS. Symptom-directed treatments showed overall favourable tolerability, with second-generation antipsychotics except risperidone demonstrating good safety.
2026-07-31 | When mania is not primary: A case report on anti-NMDA receptor encephalitis presenting during early pregnancy
Anti-NMDA receptor encephalitis is the most common subtype of autoimmune encephalitis, predominantly affecting young females and often presenting with psychiatric symptoms, leading to diagnostic challenges. We report a 27-year-old pregnant female presenting with first-episode mania and recurrent seizures. During hospitalisation, she developed drowsiness, orofacial dyskinesia and emerging catatonia, raising suspicion of autoimmune encephalitis. Initial EEG, MRI brain and CSF studies were normal, but CSF testing later confirmed anti-NMDA receptor antibodies. She was treated with intravenous methylprednisolone followed by mycophenolate mofetil resulting in significant recovery. This case highlights the need to consider autoimmune encephalitis in new-onset psychiatric presentations with neurological features.
2026-07-30 | Lethargy With Reversible Bilateral Basal Ganglia and Substantia Nigra Lesions in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a neuroinflammatory disorder characterized by a broad spectrum of neuropsychiatric symptoms, and the optimal treatment strategy for atypical or refractory cases has not been well established. We report the case of a 26-year-old woman with anti-NMDAR encephalitis associated with an ovarian teratoma who presented with acute psychiatric and neurological manifestations. The patient underwent tumor resection followed by first-line immunotherapies, including corticosteroids, intravenous immunoglobulin, and plasma exchange. Because of persistent neurological symptoms, second-line immunotherapy with cyclophosphamide was initiated, leading to gradual clinical improvement. However, she subsequently developed lethargy and upper-limb tremors, accompanied by bilateral basal ganglia and substantia nigra abnormalities on MRI. Notably, both her clinical symptoms and radiological abnormalities improved following an additional course of cyclophosphamide treatment. This report highlights a rare clinical and radiological manifestation and suggests that additional immunotherapy may be effective for delayed neurological worsening.
2026-07-24 | Fifteen years of autoimmune encephalitis in Denmark: incidence, epidemiology, and trends in treatment.
Despite increasing awareness of autoimmune encephalitis (AE), real-world, population-based epidemiological data are scarce. Using 15 years of nationwide, centralized testing data, we aimed to (1) characterize all Danish patients with neuronal cell-surface antibodies (NSAbs), GAD65, and GFAP; (2) estimate AE incidence in Denmark; and (3) assess temporal trends in treatment strategies. Nationwide testing data from 2009 to 2023 were obtained from the Danish centralized antibody test center, and the medical records for antibody-positive patients were reviewed. National and regional incidence rates were calculated using census data, and trends in testing, incidence, and treatment were analyzed. A total of 198 patients were included. The most prevalent antibody was NMDAR (n = 79), followed by LGI1 (n = 37), GAD65 (n = 20), and CASPR2 (n = 19). The national average crude incidence rate (IR) in 2019-2023 was 2.8 cases per million person-years. Incidence increased by 10% annually during the study period (IRR 1.10, 95% CI 1.04-1.17, P = 0.001). The highest regional IR was observed in the region hosting the national testing center. Second-line treatment in NMDARE increased from 24% in 2009-2013 to 48% in 2019-2023. In contrast, use of steroid-sparing therapy declined from 41 to 26% in NMDARE and from 39 to 0% in LGI1. In this nationwide cohort, Danish AE patients were comparable to previously reported cohorts and incidence estimates were similar to those reported in other national studies. Higher incidence in the testing region suggests that local expertise improves case ascertainment. Treatment patterns evolved over time, likely reflecting increasing clinical experience with AE.
cell therapies
2026-07-26 | Lymphoplasmapheresis for Refractory Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is generally responsive to immunotherapy, but some patients remain refractory despite treatment escalation. Lymphoplasmapheresis (LPE), a modified apheresis technique that removes both plasma components and circulating lymphocytes, may offer a salvage option in selected cases. We report a 61-year-old woman with refractory anti-NMDAR encephalitis who showed limited improvement after corticosteroids, intravenous immunoglobulin, and ofatumumab. After a prolonged interval following ofatumumab induction, she remained severely impaired with persistent disease activity and elevated cerebrospinal fluid and serum anti-NMDAR IgG titers. Three sessions of LPE were performed over 5 days. Clinical improvement was observed after LPE, accompanied by a decline in antibody titers. At 5-month follow-up after LPE, she maintained sustained recovery, with a Clinical Assessment Scale in Autoimmune Encephalitis score of 6 and a modified Rankin Scale score of 2. This case supports a close temporal association between LPE and clinical and immunological improvement, although causality cannot be definitively established from a single case.
2026-05-27 | Anti-NMDA Receptor Encephalitis with Predominant Psychiatric Symptomatology and Diagnostic Dilemmas: A Case Report.
Background and Clinical Significance: NMDAR autoimmune encephalitis is a rare but potentially life-threatening autoimmune disorder that can be hard to recognize initially because it has nonspecific symptoms. In the early phase of the disease, clinical presentation is often dominated by psychiatric symptoms, which can be misleading. A diagnosis is established by demonstrating specific anti-NMDA receptor antibodies, with cerebrospinal fluid analysis considered the most reliable diagnostic method. Timely initiation of immunomodulatory therapy, including corticosteroids, intravenous immunoglobulins, and therapeutic plasmapheresis, significantly improves disease outcomes, while second-line therapies are used in refractory cases. Case Presentation: A 21-year-old female patient (M.B.) was admitted to the Psychiatry Clinic at the University Clinical Center of Vojvodina due to the sudden onset of behavioral changes, including social withdrawal, absence of verbal communication, and unusual orofacial grimacing. During hospitalization, the patient was intermittently in a state of severe psychomotor agitation and poorly communicative, with pronounced orofacial dyskinesias and involuntary tongue movements. Anti-NMDA receptor autoantibodies were detected in both serum and cerebrospinal fluid, and the patient was subsequently transferred to the Intensive Care Unit of the Neurology Clinic. Due to the lack of an adequate clinical response to pulse corticosteroid therapy, six cycles of therapeutic plasmapheresis were performed. Following this treatment, significant clinical improvement was observed. Conclusions: Timely recognition of this condition and a multidisciplinary approach allow for early initiation of immunomodulatory therapy and significantly improve treatment outcomes.
2026-03-13 | CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising approach for B cell-driven neurological autoimmune disorders, particularly those characterized by pathogenic autoantibodies that target key neural structures. These conditions, including neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis, can be categorized based on their primary autoantigens into (1) extracellular antigen-associated (e.g., AQP4, AChR, NMDAR, MOG, VGCC), (2) intracellular antigen-associated (e.g., GAD65, DAGLA), or (3) unidentified antigenic origin (as seen in multiple sclerosis). This distinction is essential for guiding therapeutic strategies and exploring novel principles represented in distinct treatment approaches and their corresponding therapeutic outcomes. In this review, we propose a classification of CAR T cell therapies designed for different target antigens, including: CD19/20/BCMA-directed CAR T cells targeting general B cell-mediated pathogenesis, regulatory T cells modified with CARs, and the design of chimeric autoantibody receptors (CAARs) to selectively deplete pathogenic B cells directly associated with disease progression while preserving immune tolerance. We further discuss preclinical and clinical advancements, key challenges such as safety concerns and neurotoxicity, and the future landscape of CAR T applications in neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis according to the latest research, case and trial data. CAR T cell therapy potentially offers a highly specific and effective method with thorough elimination of autoreactive B cells, representing a rapidly evolving field with the potential to transform the treatment of autoimmune neurological disorders. As CAR T technology advances, it holds the potential to become a groundbreaking immunoablative strategy with so-far disclosed controllable side effects; however, further long-term follow-up data are still needed to validate its application in autoimmune disorders.
2025-12-18 | Comparison of the Efficacy of Polyvalent Intravenous Immunoglobulins and Therapeutic Plasma Exchange in Anti-NMDAR Encephalitis in the ICU.
Anti-N-methyl D-aspartate-receptor encephalitis (anti-NMDARe) is a severe disease with a favorable outcome when immunomodulatory management is started rapidly. The main objective of this study is to compare the early efficacy of the two most frequently used therapeutics, i.e., intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE), in intensive care patients admitted for anti-NMDARe. This is an observational retrospective study of patients hospitalized in a tertiary medical neurointensive care unit for severe anti-NMDARe. Patients were categorized according to the modality of first-line immunomodulatory therapies associated with corticosteroids: TPE, IVIG, or IVIG followed by TPE. The primary end point was the effectiveness of the first-line immunomodulatory treatment. Treatment was considered effective when no other immunomodulatory therapy was introduced and the patient met the following three conditions: response to simple commands, absence of epileptic seizures, and absence of abnormal movements. Thirty-seven patients were included in the study from January 2007 to December 2022: 8 were treated with TPE alone, 13 were treated with IVIG alone, and 16 were treated with IVIG followed by TPE. Of the 29 patients treated with IVIG, 13 showed improvement, with a median latency to treatment response of 36 days, whereas 16 were switched to TPE, with a median latency to treatment response of 30 days due to a lack of improvement. All eight patients treated with TPE improved, with a latency to treatment response of 31 days. TPE was significantly more effective than IVIG. This study raises the hypothesis that immunotherapies may have differential response rates among patients with NMDARe. Although the retrospective nature of the analysis may be subject to bias and confounding, the potential for therapeutic impact deserves prospective evaluation.
2025-11-30 | Management of Refractory Status Epilepticus and Profoundly Impaired Consciousness in Anti-NMDA Receptor Autoimmune Encephalitis
Introduction: Autoimmune encephalitis is a major cause of non-infectious encephalitis and remains challenging to diagnose based solely on clinical presentation. Confirmation is particularly difficult in antibody-negative cases despite strong clinical suspicion, requiring comprehensive diagnostic workup. Case Description: A 25-year-old male presented with progressive altered mental status and seizures preceded by behavioral changes for 10 days. EEG showed no epileptiform activity, cerebrospinal fluid analysis excluded infection, and brain CT was unremarkable. Serum and CSF HSV IgG/IgM were non-reactive. Anti-NMDA receptor antibodies in CSF were strongly positive. The patient developed refractory status epilepticus requiring mechanical ventilation, deep sedation with propofol, and multiple anti-seizure medications including phenytoin. Empirical acyclovir was administered for 10 days without improvement. High-dose methylprednisolone (1 g/day for 5 days) was given as first-line immunotherapy but yielded no neurological recovery. On day 14, plasma exchange was initiated for three sessions, resulting in marked clinical improvement with recovery of consciousness and seizure control. Conclusion: This case highlights the critical importance of considering autoimmune encephalitis even when initial antibody results are pending or imaging is normal. Early escalation to second-line immunotherapy, particularly plasma exchange, can be lifesaving in anti-NMDAR encephalitis presenting with refractory status epilepticus and profound coma.
proteins
2026-06-09 | Peptides to Specifically Inhibit Anti-NMDA Receptor Autoantibodies Using Molecular Mimicry to Treat Anti-NMDA Receptor Autoimmune Encephalitis (P8-1.008)
We aim to design peptides to specifically inhibit anti-NMDA receptor autoantibodies using molecular modelling in-silico.
2025-11-02 | Dynamics of sleep-wake cycles and architecture in anti-NMDAR encephalitis.
Sleep disturbances in anti-NMDAR encephalitis evolve dynamically across disease phases. We monitored a patient longitudinally from the acute phase through remission, relapse, and recovery, using video-EEG and polysomnography. No sleep complaints were reported during the prodromal phase, whereas coma was characterized by rhythmic theta-delta activity devoid of sleep patterns. Sleep stages gradually emerged after teratoma removal and immunotherapy, paralleling clinical improvement. A second teratoma caused relapse with severe sleep disruption and agrypnia excitata, then residual status dissociatus persisted before normalization. Sleep changes mirrored disease progression, suggesting that sleep patterns may serve as biomarkers and potential therapeutic targets in anti-NMDAR encephalitis.
2025-10-18 | HBEGF/EGFR pathway activation by hUC-MSCs improves cognitive outcomes in anti-NMDAR encephalitis.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder that impairs cognitive function. In this study, we investigated the impact of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive recovery in anti-NMDAR encephalitis. Our findings demonstrate that heparin-binding epidermal growth factor-like growth factor (HBEGF), a key functional factor secreted by hUC-MSCs, plays a pivotal role in ameliorating cognitive dysfunction. We elucidated that the HBEGF/epidermal growth factor receptor (EGFR) signaling pathway contributes to the enhancement of cognitive function following hUC-MSC exposure. Importantly, we employed a novel exosome-based intracellular therapeutic protein delivery technology-the mMaple3-mediated protein loading and release from exosomes (MAPLEX) system-for targeted HBEGF delivery. This approach facilitated a controlled, light-induced release of HBEGF from the exosomal membrane. Collectively, these findings support the involvement of HBEGF in mediating cognitive improvement in anti-NMDAR encephalitis induced by hUC-MSCs. Additionally, the MAPLEX system emerges as an effective delivery platform for HBEGF, potentially opening new avenues for the treatment of anti-NMDAR encephalitis.
2025-09-29 | Telitacicept as a novel B cell-targeted therapy in autoimmune encephalitis: a case report.
Autoimmune encephalitis (AE) comprises immune-mediated neuroinflammatory disorders presenting diverse neuropsychiatric symptoms and antibody-specific manifestations. Despite standard immunotherapy, residual disability, treatment intolerance, and relapse risks highlight unmet clinical needs. Telitacicept, a dual target fusion protein that inhibits B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), suppresses pathogenic B cell activation and autoantibody production, presenting a mechanism-driven therapeutic potential for AE management. Three AE cases with distinct therapeutic complexities are detailed in our study: (1) An anti-N-methyl-D-aspartate receptor (NMDAR) antibody-positive patient experienced recurrent relapses and was a comorbid individual with upper gastrointestinal bleeding. (2) An anti-leucine-rich glioma inactivated 1 (LGI1) antibody patient resisted corticosteroids, intravenous immunoglobulin, and ofatumumab treatment. (3) A newly diagnosed, anti-LGI1 antibody and anti-contactin-associated protein 2 (CASPR2) antibody dual-positive patient required sequential therapy to consolidate the remission and facilitate prednisone tapering. Telitacicept administration achieved symptom remission across all cases, accompanied by reduced antibody titers and stable outcomes over six months. Our case series evaluates the use of telitacicept in AE patients with varied antibody subtypes, particularly for patients with relapsed or refractory disease, intolerance to CD20-targeted agents, or steroid-related complications. Moreover, telitacicept may serve as an effective sequential therapy to sustain remission and reduce long-term steroid dependency.
2025-08-28 | Comparative efficacy of intravenous immunoglobulin and protein A immunoadsorption in severe anti-NMDAR encephalitis.
To compare the differential effects of intravenous immunoglobulin (IVIg) and protein A immunoadsorption (PAIA) on neurological functional improvement in patients with severe anti-NMDAR encephalitis. We retrospectively evaluated patients with severe anti-NMDAR encephalitis (modified Rankin scale, mRS ≥ 3) at the Second People's Hospital of Hunan from January 1, 2019, to December 31, 2024. Clinical efficacy was compared between the IVIg and PAIA groups. Clinical improvement (ΔmRS ≥ 1) and favorable functional outcomes (mRS 0-2) at 30 days and 90 days were evaluated as primary outcomes. Secondary outcomes included changes in mRS and the Clinical Assessment Scale for Autoimmune Encephalitis (ΔCASE) at 30 and 90 days, length of ICU stay, and antibody titers in cerebrospinal fluid (CSF) and serum. This study enrolled 53 patients with severe anti-NMDAR encephalitis, of whom 30 patients received IVIg and 23 patients received PAIA. The PAIA group showed a significantly higher rate of clinical improvement at 30 days after treatment compared to the IVIg group (82.61% vs. 50%, p = 0.014). However, no significant difference was found at 90 days after treatment (95.65% vs. 96.67%, p > 0.05). Furthermore, favorable functional outcomes at 30 days (17.39% vs. 6.67%) and 90 days (91.30% vs. 80.00%) showed no significant differences between the two groups (p > 0.05). Significant differences were observed in ΔmRS1 (p = 0.005), ΔmRS2 (p = 0.03), and ΔCASE1 (p = 0.027), but not in ΔCASE2 (p > 0.05). PAIA was associated with a greater reduction in antibody titers in both CSF and serum and a shorter ICU stay. Our study demonstrates that both IVIg and PAIA are effective treatments for patients with severe anti-NMDAR encephalitis. However, PAIA demonstrates several distinct advantages, including earlier clinical improvement, faster antibody clearance, and a potential reduction in ICU stay.
antibodies
2026-09-26 | Anti-NMDA Receptor Encephalitis Associated with Ovarian Teratoma: A Comprehensive Review.
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR-E) is a severe autoimmune encephalitis that predominantly affects young women and is frequently associated with ovarian teratomas. Increasing evidence indicates that these tumors play a central role in disease initiation by providing a peripheral immunological trigger. This comprehensive review summarizes current knowledge on the immunopathogenesis, clinical manifestations, diagnostic approach, therapeutic strategies, and long-term outcomes of ovarian teratoma-associated anti-NMDAR-E. We discuss the unique immunogenic properties of ovarian teratomas, including the presence of neuroglial tissue expressing the GluN1 receptor subunit (formerly known as NR1) of the N-methyl-D-aspartate receptor (NMDAR), dense immune cell infiltrates, and tertiary lymphoid structure-like formations that support local antibody production. These features are thought to promote molecular mimicry and loss of immune tolerance, leading to B-cell activation, intrathecal antibody synthesis, and antibody-mediated neuronal dysfunction. Furthermore, we review the characteristic multistage clinical course, key diagnostic findings in cerebrospinal fluid, imaging and electrophysiology, and the importance of early tumor removal combined with immunotherapy. Emerging therapeutic approaches and experimental models that provide insight into disease mechanisms and novel treatment targets are also highlighted. An improved understanding of tumor-driven neuroimmunological interactions is essential for earlier diagnosis, optimized treatment strategies, and better long-term outcomes in affected patients.
2026-09-25 | Ofatumumab Therapy and Long-Term Seizure Outcomes of Patients With Relapsing Anti-NMDA Receptor Encephalitis.
There is a lack of studies on seizure outcomes associated with ofatumumab therapy in patients for relapsing anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. We aimed to evaluate long-term seizure outcomes of ofatumumab therapy for relapsing anti-NMDA receptor encephalitis. This is a prospective cohort study, Compared patients with relapsing anti-NMDA receptor encephalitis who had received at least 1 ofatumumab dose and a control cohort of non-ofatumumab-treated patients, continuous follow-up for 24 months. The primary outcome was the seizure outcomes (including both seizure reduction and seizure freedom; seizure reduction is defined as a reduction in seizure frequency to 50% or more of the baseline level, seizure freedom is defined as having no seizures) at the follow-up. The secondary outcomes included modified Rankin Scale (mRS) scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the 24-month follow-up. We enrolled 93 patients with relapsing anti-NMDA receptor encephalitis. A total of 76 patients met the requirements after the inclusion and exclusion criteria. The 38 patients received ofatumumab therapy, and the other 38 patients received non-ofatumumab therapy. Follow-up after 6 months, the ofatumumab therapy group demonstrated favorable seizure outcomes (63.16% vs. 36.84%, p < 0.05). Follow-up after 12 months, this improvement of seizure outcomes was more pronounced (78.95% vs. 60.53%, p < 0.05). Follow-up after 24 months, this difference between the two groups widened further (94.74% vs. 78.95%, p < 0.05), compared with the non-ofatumumab therapy group. Follow-up after 6 months, the ofatumumab group demonstrated a faster mRS scores (2.85 ± 0.65 vs. 3.75 ± 0.55, p < 0.05) and CASE scores (11.80 ± 1.65 vs. 13.75 ± 1.55, p < 0.05). Follow-up after 12 months, the ofatumumab group demonstrated a faster mRS scores (1.68 ± 0.45 vs. 2.39 ± 0.35, p < 0.05) and CASE scores (6.75 ± 1.45 vs. 9.39 ± 1.35 p < 0.05). Follow-up after 24 months, the ofatumumab group demonstrated a faster mRS scores (1.25 ± 0.35 vs. 1.68 ± 0.45, p < 0.05) and CASE scores (4.25 ± 0.75 vs. 6.68 ± 1.35, p < 0.05). And no serious adverse events associated with ofatumumab treatment were reported. Furthermore, Multivariate logistic regression analysis identified that early initiation of ofatumumab therapy, psychiatric symptoms, and abnormal brain MRI findings may be associated with seizure outcomes. Ofatumumab showed substantial improvement in long-term seizure outcomes in patients with relapsing anti-NMDA receptor encephalitis, particularly those presenting with seizures as a predominant clinical feature.
2026-09-21 | Regulation of protein kinase pathways in primary neuron model of anti-NMDA receptor encephalitis
Abstract The most common form of autoimmune encephalitis is associated with antibodies that target N-methyl-D-aspartic acid receptors (NMDARs). NMDARs play a pivotal role in neurotransmission and synaptic plasticity. Mounting evidence has shown that antibody targeting of the NMDAR GluN1 subunit, as in anti-NMDAR encephalitis, leads to NMDAR cross-linking and receptor internalization. However, the underlying signaling pathways affected by antibodies targeting NMDARs remain to be explored. We previously demonstrated that a human GluN1 monoclonal antibody 5F5 (GluN1 mAb 5F5) rapidly localizes to and regulates synaptic NMDAR function at native synapses of primary hippocampal neurons. Here, we sought to explore signaling targets of GluN1 mAb 5F5 in primary cortical neurons of either sex using subcellular fractionation, Western blotting, and label-free quantitative phosphoproteomics by mass spectrometry. We find that human GluN1 mAb 5F5 does not change NMDAR abundance or surface levels of GluN1 on primary cortical neurons at 2 hr. Despite this, we observe that GluN1 mAb 5F5 alters the phosphoproteome in synaptoneurosomes and regulates numerous synapse-related biological processes and protein kinase activities. Bioinformatic analyses suggest that these phosphoproteomic changes are positively correlated with NMDAR activation and negatively correlated with NMDAR inhibition. Together, these data suggest that GluN1 mAb 5F5 alters intracellular kinase signaling pathways in primary cortical neurons, likely by activating the NMDAR. These studies may help to identify novel therapeutic strategies for anti-NMDAR encephalitis and other antibody-mediated encephalitides targeting cell surface antigens. Significance statement Anti-NMDAR encephalitis is the most common form of autoimmune encephalitis. The pathophysiology of this clinical syndrome remains poorly defined but is currently thought to involve pathogenic antibodies that crosslink and internalize NMDARs. We identify intracellular signaling pathways targeted by human NMDAR antibodies in primary cortical neurons. Our key findings are obtained using specific, patient-derived human monoclonal antibodies with high affinity to the GluN1 subunit of NMDARs, which have been shown to induce key pathogenic effects of anti-NMDAR encephalitis (Sharma, Al-Saleem, Panzer, et al. 2018; Taraschenko, Fox, Eldridge, et al. 2021; Taraschenko, Fox, Zekeridou, et al. 2021; Dean et al. 2022). These studies expand the underlying pathophysiological molecular mechanisms involved in anti-NMDAR encephalitis.
2026-09-21 | Third-line tocilizumab for refractory pediatric anti-NMDA receptor encephalitis: a single-center case series.
Tocilizumab has been proposed as a third-line therapy for refractory autoimmune encephalitis; pediatric Latin American data remain limited. To evaluate the efficacy and safety of tocilizumab in pediatric patients with severe or refractory anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We retrospectively reviewed pediatric patients with definite anti-NMDAR encephalitis treated with tocilizumab after inadequate response to previous therapy. Six patients (four males, median age at onset 4.5 years). All had severe disease (modified Rankin Scale [mRS] 4-5; Clinical Assessment Scale in Autoimmune Encephalitis [CASE] ≥10). All received first-line therapy, five received rituximab before tocilizumab. Tocilizumab was initiated 2-3 months after the last rituximab infusion. At 12 months, all achieved favorable outcomes (mRS 2; CASE ≤4). Adverse events included varicella-zoster virus infection, mild cytopenia, and dyslipidemia. Tocilizumab was associated with favorable outcomes and acceptable safety in this small pediatric series of refractory anti-NMDAR encephalitis. The CASE scale was a sensitive and reliable instrument for longitudinal functional assessment.
2026-09-18 | Bilateral pulmonary embolism in anti-NMDA receptor encephalitis presenting as acute psychosis.
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder that frequently presents with prominent psychiatric manifestations, often leading to misdiagnosis as a primary psychiatric illness. Early recognition is critical, as timely immunotherapy significantly improves outcomes. A 26-year-old previously healthy man presented with acute psychosis following significant emotional stress and first-time marijuana use 3 days earlier. Initially diagnosed with brief psychotic disorder, he developed catatonia and fever. Cerebral spinal fluid (CSF) and serum anti-NMDA receptor antibodies confirmed the diagnosis. His course was complicated by bilateral pulmonary emboli and drug-induced liver injury. Treatment with intravenous immunoglobulin (IVIG) and high-dose corticosteroids resulted in marked improvement. Malignancy work-up was negative. This case underscores the importance of considering autoimmune encephalitis in young patients presenting with new-onset psychosis, in the apparent absence of malignancy. A high index of suspicion and early CSF evaluation can prevent diagnostic delay and improve patient outcomes.
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2026-08-30 | Narrative Medicine in Pediatric anti‑NMDA Receptor Encephalitis: A Mixed‑methods Evaluation of Triadic Outcomes Among Children, Parents, and Healthcare Providers.
Pediatric anti-NMDAR encephalitis can cause severe disability and profound caregiver distress. Narrative medicine has been proposed as a humanistic intervention, but its impact across the complete caregiving triad of children, parents, and healthcare providers has not been systematically evaluated. This exploratory study aimed to assess the multidimensional impact of narrative medicine interventions in this setting. This retrospective mixed-methods study included five children with severe anti-NMDAR encephalitis (admission mRS ≥4), their mothers, two physicians, and six nurses. Narrative medicine interventions included daily bedside narrative attention, parallel chart writing, family conferences, nurse-led narrative communication, and weekly sharing sessions. Quantitative outcomes included child mRS, parental anxiety (SAS), depression (SDS), caregiver burden (ZBI), and provider empathy (IRI), burnout (NBS), and meaningful work (WAMI). Qualitative data from parallel charts, reflective writings, and family interviews were analyzed thematically. All five children showed favourable neurological improvement (median mRS: 5→1 at 6 months; p=0.039); three returned to school. Parental outcomes showed substantial improvements: SAS (42.8→23.4, p<0.001, d=9.7), SDS (54.8→27.4, p<0.001, d=6.5), and ZBI (59.6→29.6, p<0.001, d=3.4). Nurses (n=6) showed increased empathy (IRI: 63.7→78.0, p=0.003, d=1.9) and reduced burnout (NBS: 73.0→56.3, p=0.002, d=2.1); physicians showed parallel improvements. Thematic analysis identified three potential mechanisms: clinical narrative signals, a window of narrative intervention (weeks 2-4), and bidirectional healing. In this small, exploratory retrospective case series, narrative medicine interventions were temporally associated with favourable trends in neurological outcomes, parental psychological states, and provider well-being. The proposed concepts of clinical narrative signals, a window of narrative intervention, and bidirectional healing offer a preliminary framework for integrating narrative practices into pediatric neurocritical care. These findings are hypothesis-generating and warrant prospective investigation in larger controlled studies.
2026-05-30 | Glycine-modulating Slc6a20a-ASO restores NMDA receptor function in SHANK2 and SHANK3-mutant mice and cortical organoids.
Suppressed NMDA receptor (NMDAR) function contributes to multiple brain disorders, including schizophrenia, autism spectrum disorder (ASD), and NMDAR encephalitis. Previous attempts to restore NMDAR activity by increasing ambient glycine, a critical co-agonist, through GlyT1 inhibition have yielded mixed outcomes, partly due to GlyT1's extensive expression in essential brainstem regions. Slc6a20a, a glycine transporter widely expressed in cognition-relevant regions such as the cortex and hippocampus, offers a targeted alternative. Here we show that antisense oligonucleotide (ASO)-mediated Slc6a20a inhibition (Slc6a20a-ASO) normalizes ASD-related phenotypes in male Shank2- and Shank3-mutant mice, with model-dependent rescue profiles. Slc6a20a-ASO rescues NMDAR hypofunction and synaptic phospho-proteomic profiles in the prefrontal cortex. Furthermore, ASO targeting human SLC6A20 rescues suppressed NMDAR function in cortical organoids harboring SHANK2 or SHANK3 mutations. These findings underscore the potential and limitations of Slc6a20a/SLC6A20-ASO for treating disorders characterized by NMDAR hypofunction.
2025-12-19 | Paediatric myelin oligodendrocyte glycoprotein antibody-associated disease with NMDA receptor encephalitis: overlap syndrome and challenges in the antibody testing.
We report the case of a middle childhood female child who presented with acute encephalopathy following multiple episodes of projectile vomiting and subsequently developed progressive cognitive decline, behavioural changes, visual impairment and motor regression. Neurological evaluation and imaging revealed multifocal demyelination with bilateral optic neuritis. Further work-up uncovered the coexistence of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and N-methyl-d-aspartate receptor encephalitis. Early initiation of immunotherapy with intravenous methylprednisolone and intravenous immunoglobulin led to significant clinical improvement. The case underscores the importance of screening for coexisting autoimmune conditions in demyelinating disorders, given the therapeutic and prognostic implications.
2025-09-01 | Refractory "status dyskineticus" in a child with post-herpes simplex virus 1 N-methyl-D-aspartate receptor encephalitis: a case report.
Herpes simplex virus 1 (HSV-1) encephalitis may result in relapsing neurological symptoms secondary to immune-mediated processes, including anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Refractory status dyskineticus (RSD), a severe subset of status dystonicus, is characterized by a hyperkinetic movement disorder phenotype alongside dystonic features. This critical condition presents substantial challenges in neurocritical care. The present case highlights the importance of prompt intervention and immunotherapy escalation in managing severe movement disorders due to pediatric autoimmune encephalitis. A previously healthy 2-year-old boy was admitted with HSV-1 encephalitis, confirmed by brain MRI and cerebrospinal fluid (CSF) analysis. When initially treated with acyclovir, the patient achieved partial recovery but later developed encephalopathy, vomiting, behavioral regression, and severe dyskinetic movements. Upon transfer to our center, NMDAR antibodies were detected in the CSF, with no evidence of HSV reactivation. Despite first-line immunotherapy with intravenous steroids and immunoglobulins, his condition deteriorated, progressing to status dyskineticus (SD), with dystonia, hyperthermia, and hypercapnia, requiring intensive care management and mechanical ventilation. A treatment escalation regimen including both immunotherapy with rituximab, rapamycin, bortezomib, and multiple symptomatic therapies resulted in gradual improvement and resolution of the movement disorder. This case underscores the crucial role of neurocritical care in managing refractory movement disorders associated with autoimmune encephalitis. Early recognition and immunotherapy escalation are essential to improve outcomes in children with complex, life-threatening neurological conditions. A comprehensive, multidisciplinary approach in the neurocritical care setting is key to achieving recovery and minimizing long-term neurological damage.
2025-07-30 | Effects and Mechanisms of NMDAR-EphB2 on Synapses in Mice by Active Immunization with a GluN1 Peptide.
This study investigated the expression of N-methyl-D-aspartate receptor(NMDAR)-EphB2 and associated changes in hippocampal neuronal dendritic spines and synaptic ultrastructure in an anti-NMDAR encephalitis mouse model. Utilizing the GluN1359-378 antigen, which targets the amino terminal domain of the NMDAR GluN1 subunit, we initially established an anti-NMDAR encephalitis mouse model. Subsequently, pentylenetetrazol (PTZ) was intraperitoneally injected and their seizure susceptibility was observed. Furthermore, Western blot was employed to detect the expression of GluN1, postsynaptic density protein 95 (PSD-95), EphrinB2 and EphB2 in hippocampal tissues. Immunofluorescence was used to detect the expression and co-localization of GluN1 and EphB2 in the hippocampus. Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure of hippocampal neurons, and Golgi-Cox staining was performed to examine the morphology of dendritic spines. GluN1359-378 mice exhibited increased seizure susceptibility. Furthermore, GluN1359-378 mice demonstrated significantly reduced expression of GluN1 membrane protein, as well as EphrinB2 and EphB2 proteins in hippocampal tissues. Additionally, the co-localization coefficient of GluN1 and EphB2 was decreased. Synaptic cleft width, postsynaptic density thickness, active zone length, and dendritic spine density were reduced. In conclusion, the anti-NMDAR encephalitis mouse model, established via active immunization with a GluN1 peptide antigen, exhibits increased seizure susceptibility. This heightened susceptibility may result from the disruption of the NMDAR-EphB2 interaction by NMDAR antibodies, which subsequently reduces NMDAR expression on the cell membrane and leads to alterations in synaptic structure.
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Drug Discovery Landscape
2 orphan drug designations for NMDA receptor encephalitis.
2 orphan drug designations for NMDA receptor encephalitis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Humanized one-armed monoclonal antibody | antibodies | FDA | Arialys Therapeutics, Inc. | |
satralizumab-mwge | antibodies | FDA | Genentech, Inc. |
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