Exploring the neuroprotective role of artesunate in mouse models of anti-NMDAR encephalitis: insights from molecular mechanisms and transmission electron microscopy.

BACKGROUND: The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. METHODS: Adult female mice aged 8-10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. RESULTS: In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART's therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. CONCLUSIONS: At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

Unmasking bipolarity in recurrent depressive disorder following herpes simplex virus triggered n-methyl-D-aspartate encephalitis.

OBJECTIVE: Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is known to affect the same brain regions as in secondary mania. METHOD: We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection. RESULT: HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements. CONCLUSION: A neurological insult predisposed our patient to the variable effects of antidepressant drugs.

Olanzapine vs. magnesium valproate vs. lamotrigine in anti-N-methyl-D-aspartic acid receptor encephalitis: a retrospective study.

BACKGROUND: This study aimed to compare the impact of olanzapine, magnesium valproate, and lamotrigine as adjunctive treatments for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. And it is expected to add supporting points related to the rebalance of neurotransmitters in the brain through adjuvant therapy in the clinical management of anti-NMDAR encephalitis. METHODS: This retrospective study included patients diagnosed with anti-NMDAR encephalitis who received standardized immunotherapy at Hunan Brain Hospital between January 2018 and December 2020. RESULTS: Compared to the olanzapine group, both the magnesium valproate and lamotrigine groups showed lower scores on the positive and negative symptom scale (PANSS) total score after 3 weeks of treatment (all P < 0.05). The Montreal Cognitive Assessment Scale (MoCA) scores in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group after 3 weeks and 3 months of treatment (all P < 0.05). After 3 months of treatment, the proportions of patients with a modified Rankin scale score (mRS) of 0-1 in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group (all P < 0.05). The electroencephalogram (EEG) abnormality ranks at 3 months were significantly lower in the magnesium valproate and lamotrigine groups compared with the olanzapine group (all P < 0.05). Furthermore, the Glx/Cr ratio significantly decreased after 3 months of treatment (all P < 0.05) in the magnesium valproate and lamotrigine groups, while the Glx/Cr ratio in the olanzapine group showed no significant change (P > 0.05). CONCLUSION: Compared with olanzapine, the addition of magnesium valproate or lamotrigine to immunotherapy might be associated with a lower PANSS score, higher MoCA score, and lower mRS score. The improvement of neurological functions and cognitive function may be related to the decreased Glx/Cr ratio.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Anti-NMDA Autoimmune Encephalitis Post-COVID-19 Vaccination in a Pediatric Patient: A Case Report.

Post-coronavirus disease 2019 (COVID-19) vaccination encephalitis is rarely reported particularly in the pediatric population. Herein, we report the first case of postvaccination anti-N-methyl-d-aspartate (NMDA) encephalitis in close temporal association with receiving COVID-19 vaccine in a pediatric patient. The patient is a 13-year-old female who received the first dose of the Pfizer-BioNTech COVID-19 vaccine and presented with subacute neurological and psychiatric symptoms and eventually confirmed the diagnosis of anti-NMDA autoimmune encephalitis. The patient recovered after receiving intravenous immunoglobulins and steroids.

Glucocorticoid-dependent multiple sclerosis overlapping anti-NMDA receptor encephalitis: a case report and literature review update.

BACKGROUND: Previous studies suggest a relationship between central nervous system inflammatory demyelinating diseases and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Also, the overlap between anti-NMDAR encephalitis and multiple sclerosis (MS) has been reported. However, the pathogenesis and clinical characteristics are still obscure. CASE PRESENTATION: A 33-year-old woman presented with diplopia and sensory ataxia at the onset. The cerebrospinal fluid (CSF) anti-NMDAR antibodies were positive (1:3.2), and nuclear magnetic resonance imaging (MRI) showed bilateral centrum ovale and lateral ventricle demyelinating lesions. Therefore, she was diagnosed with anti-NMDAR encephalitis. After administering intravenous immunoglobulin and oral prednisone, her lesions disappeared, and symptoms were relieved. The condition was maintained with a low dose of prednisone, but her lesions reappeared on MRI. Consequently, immunomodulatory therapy of mycophenolate mofetil was initiated. However, she developed dysarthria and right limb ataxia after 10 months with a positive CSF anti-NMDAR antibody (1:1) and positive oligoclonal band. The MRI showed symmetrical multiple demyelinating lesions. Considering the MS diagnosis, her neurological dysfunction again improved significantly after intravenous methylprednisolone. Unfortunately, her symptoms aggravated for the second time when teriflunomide was started. Finally, her condition was controlled again with oral prednisone. CONCLUSIONS: Consistent with previous cases of overlapping anti-NMDAR encephalitis and MS, patients often show atypical symptoms on MRIs and immunological tests. The overlap cannot be arbitrarily treated because of the recurrence of previous diseases. Long-term follow-up, dynamic antibody monitoring, and MRI examination are crucial for these patients. The special dependency of the patient on glucocorticoids in this study has been rarely reported, which may guide the treatment of insensitivity to disease-modifying therapy in recurrent overlapping anti-NMDAR encephalitis and MS.

The presence of human respiratory syncytial virus in the cerebrospinal fluid of a child with Anti-N-methyl-D-aspartate receptor encephalitis of unknown trigger.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an important type of brain inflammation caused by autoantibody. As one of the primary agents responsible for respiratory tract infection, the human respiratory syncytial virus (hRSV) has also been reported to be capable of causing extrapulmonary diseases. Here, we first describe a case of anti-NMDAR encephalitis when hRSV was shown to be present in the cerebrospinal fluid. CASE PRESENTATION: The child was noted to have ataxia and positive anti-NMDA receptors in the cerebrospinal fluid, diagnosed as anti-NMDA receptor encephalitis in combination with cranial MRI images. After high-dose hormone pulse therapy and medication, the disease improved, and he was discharged. However, a relapse occurred almost a year later, and the cranial MRI imaging showed progressive cerebellar atrophy. An hRSV strain from group B was detected in his cerebrospinal fluid, and the whole genome sequence was recovered using transcriptome sequencing. CONCLUSIONS: To our knowledge, this is the first report of hRSV being found in the cerebrospinal fluid of a patient with anti-NMDAR encephalitis. Even though more clinical records and experimental evidence are needed for validation, this work expands the types of diseases linked to hRSV and the likely cause of anti-NMDAR encephalitis.

Effectiveness of intra-thecal methotrexate in refractory Anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-d-aspartate "anti-NMDA" receptor encephalitis is one of the most common autoimmune encephalitis for which first- and second-line therapies have been recommended following international consensus. However, some refractory cases do not respond to the first- and second-line therapy and require further immune-modulatory therapies such as intra-thecal methotrexate. In this study, we reviewed six confirmed cases of refractory anti-NMDA receptor encephalitis from two tertiary centers in Saudi Arabia that required escalation of treatment and received a six-month course of intra-thecal methotrexate. The aim of this study was to evaluate the effectiveness of intra-thecal methotrexate as immunomodulatory therapy for refractory anti-NMDA receptor encephalitis. METHODS: We retrospectively evaluated six confirmed cases of refractory anti-NMDA receptor encephalitis who did not improve after first- and second-line therapy and received monthly intra-thecal methotrexate treatment course for six consecutive months. We reviewed patient demography, underlying etiologies, and compared their modified Rankin score prior to receiving intra-thecal methotrexate and six months after completing the treatment. RESULTS: Three of the six patients showed a marked response to intra-thecal methotrexate with a modified Rankin scale of 0-1 at 6-month follow-up. None of the patients experienced any side effects during or after intra-thecal methotrexate treatment, and no flareups were observed. CONCLUSION: Intra-thecal methotrexate may be a potentially effective and relatively safe escalation option for immunomodulatory therapy of refractory anti-NMDA receptor encephalitis. Future studies on intra-thecal methotrexate -specific treatment regimens may further support its utility, efficacy, and safety in treating refractory anti-NMDA receptor encephalitis.

Anti-N-methyl-d-aspartate receptor encephalitis: mimicker of lupus and multiple sclerosis.

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is a B-cell-mediated autoimmune encephalitis with wide non-specific symptoms like acute-onset psychiatric or neurological ones mimicking various other conditions. A careful history and appropriate workup, including cerebrospinal fluid analysis for anti-NMDAR antibodies, imaging, and electroencephalogram, should be conducted, considering all differential diagnoses that can mimic its presentation. Combination therapy with high-dose steroids, plasma exchange, or immunoglobulin therapy has been shown to be more efficacious. In patients who fail first-line therapy, rituximab or cyclophosphamide should be considered. It is essential to rule out ovarian teratoma or other occult malignancies that can cause NMDARE, as removal of the tumor itself resolves this condition. Timely diagnosis and early intervention are necessary to avoid an untoward outcome.

Atypical anti-NMDA receptor encephalitis associated with varicella zoster virus infection.

The triggering effect of herpes simplex virus infection on the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now well established. However, there are very few reports that has linked a varicella zoster virus (VZV) reactivation with anti-NMDAR encephalitis. In this report, we describe a case of a 57-year-old man presented with atypical clinical presentation of anti-NMDAR encephalitis with gait ataxia, complete ophtalmoplegia, and abolished reflexes followed by drowsiness and confusion. Initial diagnosis of Bickerstaff's brainstem encephalitis was suspected. Few days later, the patient developed herpes zoster in a localized right T1-T2 dermatome. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for VZV was negative. CSF anti-NMDA antibodies were proved positive. A diagnosis of anti-NMDAR encephalitis with concomitant VZV skin reactivation was retained. Favorable outcome with combined antiviral treatment and immunomodulatory therapy was observed. Concomitant VZV reactivation with autoimmune encephalitis is possible. Prognosis and therapeutic options in this rare condition remain to be clarified.

Efficacy and tolerability of intravenous immunoglobulin versus intravenous methylprednisolone treatment in anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND AND PURPOSE: The aim was to compare the effectiveness and safety of intravenous immunoglobulin (IVIg) or intravenous methylprednisolone (IVMP) versus IVIg plus IVMP (IPI) as initial therapy in anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: This was a multicenter study of prospectively identified NMDAR encephalitis individuals who presented from October 2011 to August 2020 to the study hospitals of western China, with a median follow-up of 3.9 years. Prespecified candidate variables were the prescriptions of IVIg, IVMP or IPI. Propensity score matching was also performed to control potential confounders. RESULTS: A total of 347 NMDAR encephalitis patients were finally analyzed in this study. After TriMatch for NMDAR encephalitis, 37 triplets were generated. Compared to IVIg or IVMP, the administration of IPI exhibited a significant benefit of a higher response rate (86.5% vs. 55.6% vs. 68.7%, pcorr < 0.01), improved modified Rankin Scale score at 3, 6 and 12 months (pcorr < 0.05), and reduced further recurrence rate (10 of 37 [27.0%] vs. 9 of 37 [24.3%] vs. 2 of 37 [5.4%]; p log rank = 0.01). There was no association between treatment superiority and patient sex or the presence of tumors (p ≥ 0.05). Patients treated with IVMP had a significantly higher number of adverse events, but 99% of adverse events were mild to moderate and did not lead to a change in treatment. CONCLUSION: In patients with NMDAR encephalitis, adequate response, favorable outcome and less recurrence were each more likely to occur in individuals treated with a combined immunotherapy than in monotherapy individuals.

Anti-NMDAR encephalitis with GFAPα IgG: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an inflammatory disease of the central nervous system (CNS) in which antibodies within the serum and cerebrospinal fluid (CSF) target NMDA receptors. Glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease affecting the central nervous system (CNS). Meningoencephalitis can affect any anatomical region rostrocaudally, from the optic nerve to the spinal cord. The clinical implications of NMDAR antibodies overlapping with other antibodies against glial or neuronal cell surface proteins have not been investigated. CASE PRESENTATION: A 35-year-old male presented with headaches along with amnesia, slurred and awkward speech, psychiatric symptoms, cognitive decline, and insomnia. His medical history revealed ankylosing spondylitis for six months. Ancillary findings included CSF pleocytosis and elevated protein levels. T2-weighted fluid attenuation inversion recovery was used to image high-intensity lesions of the bilateral paraventricular, radiate corona, semioval centre, and right subcortical regions. The CSF was positive for NMDAR and GFAP antibodies through transfected cell-based assays. A diagnosis of anti-GFAP encephalitis was made, although the prominent clinical features were of anti-NMDAR encephalitis. CONCLUSIONS: Herein, we describe a case of anti-NMDAR encephalitis with overlapping symptoms of GFAP antibody positivity. Patients with unusual symptoms of anti-NMDAR encephalitis should also be tested for anti-GFAP antibodies. However, because this was a single case study, caution should be exercised when interpreting the observations. Since the patient was diagnosed with autoimmune encephalitis, intravenous methylprednisolone was administered, which yielded a positive outcome.

Intravenous immunoglobulin bridging to rituximab in NMDAR encephalitis patients non-responders to first-line treatments.

BACKGROUND: The immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin cycles to bridge the 4-month period that the second-line drug rituximab needs to exert its full therapeutic effects. METHODS: Three patients with NMDAR encephalitis who were non-responders to first-line treatments entered the study. The protocol consisted of six monthly cycles of intravenous immunoglobulins (IVIG, 0.4 mg/kg/die for 5 days), starting 1 month after the last rituximab infusion (1000 mg at days 0 and 15). Brain MRI and [18F]-FDG-PET were performed at onset and at six and 18 months after onset. RESULTS: In the three patients, substantial improvements of disability or complete recovery were achieved, without modifications over the 30-to-50-month follow-up. No adverse events nor laboratory test abnormalities were recorded. Imaging findings paralleled the favorable disease courses. Brain [18F]-FDG-PET was more sensitive than MRI in detecting abnormalities. DISCUSSION: Our observations suggest that the herein-described protocol might be used in patients with NMDAR encephalitis at risk for poor prognosis in the mid-term when they need to shift to rituximab. [18F]-FDG-PET confirmed to be a sensitive tool to detect the minimal brain lesions that can underlie isolated cognitive and psychiatric symptoms.

A case of GFAP-IgG positivity followed by anti-NMDAR encephalitis.

BACKGROUND: In recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap. Case presentation The patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy. CONCLUSIONS: Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.

[Myelin oligodendrocyte glycoprotein antibody positive optic neuritis with anti-N-methyl-D-aspartate receptor encephalitis: a case report].

A 6-year-old girl had binocular vision loss with pain for one week. The patient presented with symptoms such as non-communication, language deterioration, dysphonia, and choking when drinking and eating during the course. The serum myelin oligodendrocyte glycoprotein antibody was positive. Both the serum and cerebrospinal fluid anti-N-methyl-D-aspartate receptor antibody were also positive. The diagnoses were myelin oligodendrocyte glycoprotein antibody positive optic neuritis and anti-N-methyl-D-aspartate receptor encephalitis. High-dose intravenous glucocorticoids were given. Recurrence was not observed during the 15-month clinical follow-up.

Clinical features and management of coexisting anti-N-methyl-D-aspartate receptor encephalitis and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis: a case report and review of the literature.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune encephalitis caused by antibodies targeting the GluN1 subunit of NMDA receptors. Myelin oligodendrocyte glycoprotein (MOG) antibody disorders are now widely accepted as peculiar neuroimmunological diseases with specific clinical and pathological features. Some rare cases of overlapping anti-NMDA receptor encephalitis and MOG antibody-associated diseases have been reported, presenting complex clinical symptoms that make the disease more difficult to recognize. METHOD: In accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, the terms "NMDAR" and "MOG," "NMDAR" and "demyelination," and "MOG" and "encephalitis" were searched in PubMed. Clinical cases with dual-positive anti-NMDA cerebrospinal fluid receptors and MOG serum antibodies during the disease course were included in this study. RESULTS: A total of 25 patients were analyzed in this study. The age at onset ranged from 3 to 54 years. The median number of relapses was 2.8. Administration of intravenous methylprednisolone and immunoglobulin was the most widely used treatment strategy (19/25 patients). Second-line treatments such as administration of mycophenolate mofetil, rituximab, interferon-ß, azathioprine, cyclophosphamide, and temozolomide were also reported, followed by good outcomes. CONCLUSIONS: The rates of coexisting anti-NMDA receptor encephalitis and MOG antibody-associated encephalomyelitis may be underestimated. Clinical symptoms such as seizures and cognitive decline accompanied by atypical central nervous system demyelination serve as warning signs of possible coexisting anti-NMDA receptor encephalitis and MOG antibody-associated encephalomyelitis. These patients could achieve good outcomes under proper immunotherapies.

HSV encephalitis triggered anti-NMDAR encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (AE) is a common cause of nonviral infectious encephalitis, which can be triggered by herpes simplex virus infection. Previous studies have shown that approximately 27% of herpes simplex encephalitis (HSE) patients produce anti-NMDAR antibodies within 3 months. Immunotherapy is recommended in this situation, but some symptoms usually remain in the 1-year follow-up. CASE PRESENTATION: A previously healthy 23-year-old Chinese young woman developed epileptic attack followed by psychiatric symptoms of confusion and irritation as well as cognitive deficits. Brain MRI showed hyperintense lesions of the right temporal lobe on DWI and T2 without contrast enhancement effects. Twenty-one days of acyclovir was administered based on the primary diagnosis of HSE. The anti-NMDAR antibody (IgG) was detected positively on day 11 after disease onset. She had improved cognitive function but suffered another grand mal epilepsy after the first course of intravenous immunoglobulin (IVIG) therapy combined with 1000 mg intravenous methylprednisolone. After discussion, another course of IVIG was started for 5 days. Her symptoms were well controlled with only mild cognitive deficits at the 1-year follow-up (mRS = 1). CONCLUSIONS: Our case indicated that anti-NMDAR antibodies could develop earlier after HSE compared with previous data from adults. We suggested detecting AE antibodies simultaneously with each CSF analysis. Meanwhile, the second course of IVIG therapy was reasonable when symptoms were not controlled after the first course of IVIG combined with IV steroid treatment.

Pharmacologic Treatment and Early Rehabilitation Outcomes in Pediatric Patients With Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To describe the immunotherapy and pharmacologic treatments administered to pediatric patients with N-methyl-D-aspartate receptor encephalitis (NMDARE) during inpatient rehabilitation as well as to examine clinical and demographic variables associated with early functional outcomes. DESIGN: Retrospective chart review and post hoc analysis. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Pediatric patients (N=26; mean age, 10.79±5.17y) admitted to an inpatient rehabilitation unit with a confirmed diagnosis of NMDARE. INTERVENTIONS: Inpatient rehabilitation; pharmacologic treatments. MAIN OUTCOME MEASURE: FIM for Children (WeeFIM) Developmental Functional Quotient (DFQ). RESULTS: All patients received first-line immunotherapies to treat NMDARE, and 69% also received second-line immunotherapies. Patients were prescribed an average of 8 medications for symptom management (range, 3-15 per patient), most often for the treatment of agitation (100%), psychiatric symptoms (92%), and seizures (65%). Sixty-five percent of patients demonstrated an improvement in Total WeeFIM DFQ over the course of inpatient rehabilitation, with 35% demonstrating limited to no change in Total WeeFIM DFQ ("unfavorable early outcome"). Those with unfavorable early outcome were significantly younger than those showing more favorable outcome. Pharmacologic treatment for seizures, movement disorders, and decreased arousal or level of consciousness were each associated with unfavorable early outcome independent of age differences. CONCLUSION: Findings highlight the symptomatic heterogeneity and polypharmacy involved in the care and treatment of patients with NMDARE, with patients receiving a variety of immunotherapies and medications for symptom management. The presence of (and treatment for) seizures, movement disorders, and deteriorated neurologic status may each be associated with poor early outcomes in this population. Further investigation is needed to better classify presentations and treatments for this disease and to determine how differences are associated with long-term outcomes.

Pediatric anti-NMDA receptor encephalitis associated with COVID-19.

Anti-N-methyl-D-aspartate receptor encephalitis is a clinical condition characterized by acute behavioral and mood changes, abnormal movements, autonomic instability, seizures, and encephalopathy. We describe a 7-year-old boy diagnosed with autoimmune encephalitis due to NMDAR antibody in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019) (COVID-19), without pulmonary involvement or fever. The patient presented with acute ataxia, rapidly developed encephalopathy, and autoimmune encephalitis was suspected. Steroid treatment was withheld because of lymphopenia and intravenous immunoglobulin was started. The absence of clinical response prompted plasmapheresis and, when lymphocyte counts improved, pulse steroid treatment was applied. The latter was followed by significant improvement and the patient was discharged in a conscious and ambulatory state. Autoimmune encephalitis should be considered in the presence of neurological symptoms accompanying SARS-CoV-2 infection and steroid treatment should be preferred unless limited by contraindications.

Determinants for Control of Status Epilepticus in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Treatment guideline for status epilepticus (SE) specifically in patients with anti-N-methyl- D-aspartate receptor (anti-NMDAR) encephalitis is insufficient. This study aimed to clarify the determinants for the control of SE in adult patients with anti-NMDAR encephalitis. METHODS: Medical records of all patients with anti-NMDAR encephalitis hospitalized between Jan. 2010 and Sep. 2019 were analyzed for the time sequence of seizures and treatments, and antiepileptic drug (AED) regimens related to SE. The outcomes were control of SE and seizures, and the discharge score of modified Rankin Scale (mRS). RESULTS: All eight patients had seizures and seven (87.5%) suffered from SE which lasted for 3.6 ± 3.9 days. Five patients (71.4%) had SE earlier than using IT, whose SE was controlled by AEDs alone (n = 4) or combined with teratomas resection (n = 1). Another two patients suffered from SE after receiving IT, and one of them had SE only for 1 hour. Moreover, all SE patients received increased types and dosages of AEDs at SE end. A shorter duration of refractory SE was associated with its later occurrence after seizure onset (p = 0.005) and longer duration of AEDs use before SE (p = 0.026). All cases achieved seizure freedom after receiving AEDs and IT. CONCLUSIONS: In these patients with anti-NMDAR encephalitis, all the SE which occurred before initiating IT was successfully controlled by AEDs alone or combined with teratoma resection, and later onset of refractory SE was associated with a shorter SE duration.