Management of Autoimmune Encephalitis in a 7-Year-Old Child With CTLA-4 Haploinsufficiency and AMPA Receptor Antibodies: A Case Report.

OBJECTIVES: We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding. METHODS: This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist. RESULTS: A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation. DISCUSSION: This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions. CLASSIFICATION OF EVIDENCE: This provides Class IV evidence. It is a single observational study without controls.

Chronic Treatment with Nigella sativa Oil Exerts Antimanic Properties and Reduces Brain Inflammation in Rats.

Nigella sativa (NS) is a native herb consumed habitually in several countries worldwide, possessing manifold therapeutic properties. Among them, anti-inflammatory features have been reported, presumably relating to mechanisms involved in the nuclear factor kappa-B pathway, among others. Given the observed association between neuroimmune factors and mental illness, the primary aim of the present study was to examine the effects of chronic NS use on manic-like behavior in rats, as well as analyze levels of brain inflammatory mediators following NS intake. Using male and female rats, baseline tests were performed; thereafter, rats were fed either regular food (control) or NS-containing food (treatment) for four weeks. Following intervention, behavioral tests were induced (an open field test, sucrose consumption test, three-chamber sociality test, and amphetamine-induced hyperactivity test). Subsequently, brain samples were extracted, and inflammatory mediators were evaluated, including interleukin-6, leukotriene B4, prostaglandin E2, tumor necrosis factor-α, and nuclear phosphorylated-p65. Our findings show NS to result in a marked antimanic-like effect, in tandem with a positive modulation of select inflammatory mediators among male and female rats. The findings reinforce the proposed therapeutic advantages relating to NS ingestion.

Anti-leucine-rich Glioma-inactivated 1 Protein-antibody Positive Encephalitis with Extensive Unilateral Cerebral Cortex and White Matter Lesions.

Encephalitis caused by antibodies targeting the leucine-rich glioma-inactivated 1 protein receptor, which belongs to the anti-voltage-gated potassium channel receptor complex, is characterized by hyponatremia, progressive cognitive impairment, seizures, and psychiatric disorders. The patient initially presented with faciobrachial dystonic seizures and subsequently developed encephalopathy. Brain magnetic resonance imaging revealed atypical unilateral hyperintense signals in the cerebral cortex and white matter. Intravenous corticosteroid pulse therapy effectively improved faciobrachial dystonic seizures and brain lesions.

Mycophenolate mofetil reduces the risk of relapse in anti-leucine-rich glioma-inactivated protein 1 encephalitis: a prospective observational cohort study.

BACKGROUND: Mycophenolate mofetil (MMF) is frequently used in the treatment of neurological autoimmune disorders. However, its effect on the relapse risk in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis is not well studied. METHODS: In this prospective observational cohort study, anti-LGI1 encephalitis patients were grouped according to MMF treatment status (MMF and non-MMF groups). The primary outcome was relapse after disease onset. RESULTS: A total of 83 patients were included, with a median onset age of 60 years. Fifty-four patients were men (65.1%). The MMF group comprised 28 patients and the non-MMF group comprised 55. Median follow-up from symptom onset was 26 months. Relapse occurred in 43 patients (51.8%). Median modified Rankin scale (mRS) score at enrollment was significantly higher in the MMF group than the non-MMF group (3 vs. 2; p = 0.001). Median mRS score at last follow-up was comparable between groups (1 vs. zero; p = 0.184). Both MMF treatment (HR 0.463; 95% CI, 0.231-0.929; p = 0.030) and cognitive impairment at enrollment (HR 3.391; 95% CI, 1.041-11.044; p = 0.043) were independent predictors of relapse. Starting immunotherapy before development of cognitive impairment trended towards reducing relapse risk. Outcome at last follow-up was good (mRS score 0-2) in all patients except for one in the non-MMF group. Adverse events associated with MMF treatment were mild and transient. CONCLUSION: Although the outcome of anti-LGI1 encephalitis patients is generally favorable, relapse is common, especially in those with cognitive impairment. MMF treatment is well-tolerated and can significantly reduce the risk of relapse.

Learning from cerebrospinal fluid drug-resistant HIV escape-associated encephalitis: a case report.

BACKGROUND: In the era of antiretroviral therapy (ART), central nervous system (CNS) complications in patients with human immunodeficiency virus (HIV) infection are sometimes associated with cerebrospinal fluid (CSF) viral escape. Here, we reported a case of persistent CNS viral escape with recurrent symptomatic encephalitis, which had ultimate stabilization achieved by a combination of ART adjustment and corticosteroids. CASE PRESENTATION: A 27-year-old man with HIV infection complained of recurrent headaches during the last year. His magnetic resonance imaging (MRI) presented diffused bilateral white matter lesions, and laboratory tests confirmed elevated CSF protein level, lymphocytic pleocytosis, and detectable CSF HIV RNA (774 copies/mL). Plasma HIV RNA was well suppressed with tenofovir, lamivudine, and lopinavir/ritonavir. Prednisone 60 mg once daily was initiated to reduce intracranial inflammation, followed by a good clinical response, with CSF HIV RNA still detectable (31.1 copies/mL). During the gradual tapering of prednisone, his headache relapsed, and booming viral loads were detected in both CSF (4580 copies/mL) and plasma (340 copies/mL) with consistent drug-resistant mutations. Thereupon, prednisone was resumed and the ART regimen was switched to zidovudine, lamivudine, and dolutegravir according to drug resistance tests. Persistent clinical recovery of symptoms, neuroimaging, and laboratory abnormalities were observed in the follow-up visits. CONCLUSION: CSF and plasma HIV RNA and further drug resistance tests should be monitored in HIV-infected patients with neurologic symptoms, as opportunistic infections or tumors can be ruled out. ART optimization using a sensitive regimen may be crucial for addressing CSF viral escape and the related encephalitis.

A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.

Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases. Methods: For the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis. Case presentation: An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications. Results: Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death. Conclusion: Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.

Case Report: Autoimmune encephalitis and other neurological syndromes with rare neuronal surface antibody in children after hematopoietic stem cell transplantation.

Introduction: Neuronal surface antibody syndromes (NSAS) encompass a growing set of autoimmune neurological disorders, with their predominant clinical presentation being autoimmune encephalitis (AE). The most extensively documented form within NSAS is anti-N-methyl-D-aspartate receptor (NMDAR) autoimmunity. In contrast, other NSAS, such as anti-metabotropic glutamate receptor-5 (mGluR5) autoimmunity, are less common and less comprehensively characterized, particularly in pediatric cases. Case description: In this instance, we present the case of a 7-year-old girl who exhibited abnormal behaviors following hematopoietic stem cell transplantation (HSCT). She received a diagnosis of anti-mGluR5 AE, and her Electroencephalogram (EEG) displayed an increased number of generalized slow waves during wakefulness. Treatment involved intravenous administration of gamma globulin and methylprednisolone, followed by oral prednisone tablets. Levetiracetam was introduced as an antiepileptic therapy during the pulse steroid therapy. Notably, the abnormal behaviors exhibited significant improvement after treatment. Conclusions: To the best of our knowledge, this is the first report of rare pediatric NSAS involving anti-mGluR5 AE following HSCT. Enhancing our understanding and characterization of this condition may facilitate its recognition and treatment in children. Serum antibody testing could enable early identification and treatment of anti-mGluR5 AE.

[Spontaneous Remission of Encephalitis that Developed 17 Weeks After the Last Dose of Pembrolizumab: A Case Report].

We present a 73-year-old man with a history of lung adenocarcinoma and multiple metastases. He was treated with chemotherapy, including pembrolizumab, but treatment was interrupted due to concurrent drug-induced lung injury. Seventeen weeks after the last dose of pembrolizumab, he developed encephalitis, presenting with a disturbance of consciousness and right hemiplegia. However, his symptoms gradually improved spontaneously and disappeared three weeks after their onset. Late-onset encephalitis after the administration of immune checkpoint inhibitors is rare. In addition, this is the first report of a case in which severe encephalitis recovered spontaneously without leaving sequelae. (Received April 7, 2023; Accepted July 4, 2023; Published October 1, 2023).

A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.

Steroid responsive encephalopathy associated with autoimmune thyroiditis as a cause of acuteencephalopathy.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), known as Hashimoto's encephalopathy (HE), represents a heterogeneous group of neurological and neuropsychiatric symptoms associated with a presence of antithyroid antibodies in case of other causes of encephalopathy were excluded. Clinical symptoms most commonly includes acute onset of encephalopathy, behaviour changes and cognitive dysfunction, epileptic seizures as well as cerebellar and extrapyramidal symptoms. Corticoids provides rapid and sustained therapeutic benefit in most patients and only a few patients require other immunosuppressive therapy such as plasmapheresis, intravenous immunoglobulins, or others. We present the cases of two patients with acute onset of encephalopathy, status epilepticus based on SREAT, with rapid improvement after steroid treatment.

Survival Analysis of Immunotherapy Effects on Relapse Rate in Pediatric and Adult Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: Prior observational studies for autoimmune encephalitis (AE) have mostly focused on outcomes after acute immunotherapies with better outcomes associated with earlier immunotherapy use. However, the impact of long-term immunotherapy and its association with clinical relapse is not well known. METHODS: We conducted a retrospective study of consecutive patients meeting published clinical criteria for AE evaluated at UC San Diego and Rady Children's Hospital from January 2007 to November 2021. Survival analysis and Cox multivariable regression models were used to evaluate relapse risk using rituximab exposure as a time-dependent variable. Pooled and age-stratified analyses were performed. RESULTS: A total of 204 pediatric and 380 adult participants were screened of which 30 pediatric and 75 adult participants were included. The most common antibody subtype in both cohorts was anti-NMDA receptor (76% in pediatric, 34% in adult). Relapses occurred in 31% of pediatric antibody-positive, 40% of adult antibody-positive, and 20% of adult antibody-negative cases. Times to first relapse (TTFR) were 10.6 ± 7.4 months (pediatric antibody-positive), 13.1 ± 24.5 months (adult antibody-positive), and 6.9 ± 3.8 months (adult antibody-negative). Rituximab was the most common second-line immunotherapy used. Combining pediatric and adult data, rituximab use was associated with a 71% lower hazard for time to first relapse (hazard ratio [HR] 0.29, 95% CI 0.09-0.85) and 51% lower hazard for recurring relapses (HR 0.49, 95% CI 0.9-1.26). The HR for TTFR with rituximab use in children was 0.30 (95% CI 0.05-1.69), 0.29 (95% CI 0.07-1.29) in adults, 0.32 in non-NMDA antibody-positive encephalitis (95% CI 0.07-1.39), and 0.42 (95% CI 0.07-2.67) for anti-NMDAR. DISCUSSION: Relapses are common in pediatric and adult patients with AE, although less frequently in anti-NMDARE. Using a rigorous survival model, we demonstrate a substantial benefit of rituximab use for reducing relapse rates in AE, especially for the adult population. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab is associated with a lower hazard to relapse in patients with AE.

[Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults]. / Klinicheskie kharakteristiki i kratkosrochnye iskhody autoimmunnogo entsefalita u vzroslykh.

OBJECTIVE: To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. MATERIAL AND METHODS: Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). RESULTS: In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). CONCLUSIONS: The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

Leucine-rich glioma-inactivated protein 1 antibody-associated encephalitis in a 22-month-old girl: a case report.

BACKGROUND: LGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840-851, 2018). CASE PRESENTATION: Leucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient's neurological symptoms. CONCLUSIONS: The incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.

State of the Art: Acute Encephalitis.

Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Role of Early Intravenous Immunoglobulins in Halting Clinical and Radiographic Disease Progression in Rasmussen Encephalitis.

BACKGROUND: Rasmussen encephalitis (RE) is a rare progressive presumed autoimmune disorder characterized by pharmacoresistant epilepsy and progressive motor and cognitive deterioration. Despite immunomodulation, more than half of the patients with RE ultimately require functional hemispherotomy. In this study, we evaluated the potential beneficial effects of early initiation of immunomodulation in slowing disease progression and preventing the need for surgical interventions. METHODS: A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify patients with RE. Data were collected on seizure characteristics, neurological deficits, electroencephalography, brain magnetic resonance imaging results (including volumetric analyses for an objective assessment of radiographic progression), and treatment modalities. RESULTS: Seven patients met the inclusion criteria for RE. All patients received intravenous immunoglobulins (IVIGs) as soon as the diagnosis was entertained. Five patients with only monthly to weekly seizures at the time of IVIG initiation had favorable outcomes without resorting to surgery, along with a relative preservation of the gray matter volumes in the affected cerebral hemispheres. Motor strength was preserved in those patients, and three were seizure free at their last follow-up visit. The two patients who required hemispherotomy were already severely hemiparetic and experiencing daily seizures at the time of IVIG initiation. CONCLUSIONS: Our data suggest that the early initiation of IVIG as soon as a diagnosis of RE is suspected, and particularly before the appearance of motor deficits and intractable seizures, can maximize the beneficial effects of immunomodulation in terms of controlling seizures and reducing the rate of cerebral atrophy.

Case report: Anti-IgLON5 disease and anti-LGI1 encephalitis following COVID-19.

Anti-IgLON family member 5 (IgLON5) disease is a rare autoimmune encephalitis, characterized by sleep problems, cognitive decline, gait abnormalities, and bulbar dysfunction. Anti-leucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis is characterized by cognitive dysfunction, mental disorders, faciobrachial dystonic seizures (FBDS), and hyponatremia. Various studies report that coronavirus disease 2019 (COVID-19) have an effect on the nervous system and induce a wide range of neurological symptoms. Autoimmune encephalitis is one of the neurological complications in severe acute respiratory syndrome coronavirus 2 infection. Until now, autoimmune encephalitis with both anti-IgLON5 and anti-LGI1 receptor antibodies following COVID-19 is rarely reported. The case report described a 40-year-old man who presented with sleep behavior disorder, daytime sleepiness, paramnesia, cognitive decline, FBDS, and anxiety following COVID-19. Anti-IgLON5 and anti-LGI1 receptor antibodies were positive in serum, and anti-LGI1 receptor antibodies were positive in cerebrospinal fluid. The patient presented with typical symptoms of anti-IgLON5 disease such as sleep behavior disorder, obstructive sleep apnea, and daytime sleepiness. Moreover, he presented with FBDS, which is common in anti-LGI1 encephalitis. Therefore, the patient was diagnosed with anti-IgLON5 disease and anti-LGI1 autoimmune encephalitis. The patient turned better after high-dose steroid and mycophenolate mofetil therapy. The case serves to increase the awareness of rare autoimmune encephalitis after COVID-19.

[An Update on Therapeutic Management in Autoimmune Encephalitis].

In the last 15 years, the continual discovery of newly identified forms of autoimmune encephalitis (AE) associated with antibodies to the cell surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders. AE is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors or, infections, or it may be cryptogenic. These disorders can occur in children or young adults with or without cancer who develop psychosis, catatonic or autistic features, memory problems, abnormal movements, or seizures. Here, we review the therapeutic management of AE. The importance of early recognition and diagnosis of AE is paramount to the ultimate goal of optimal immunotherapy. Although no specific data are available for all autoantibody-mediated encephalitis syndromes, the two most common forms of AE, which are NMDA receptor encephalitis and LGI-1 encephalitis, are clear exemplars where improved patient outcomes are associated with early immunotherapy. First-line treatments for AE include intravenous steroids and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may remain refractory to treatment, thus representing a major clinical challenge. In these cases, the treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory AE include (1) cytokine-based drugs such as tocilizumab, and (2) plasma cell-depleting agents such as bortezomib.

Coupling of Cortical Hyperintense Signals and Increased Glucose Metabolism in a Case of Anti-GABAA Receptor Antibody-associated Encephalitis.

We herein report a case of anti-gamma aminobutyric acid type A receptor antibody-associated encephalitis (anti-GABAA-RE) with progressive aphasia and generalized tonic-clonic seizures. Cerebral magnetic resonance imaging (MRI) showed cortical brain lesions coupled with hypermetabolism on fluorodeoxyglucose-positron emission tomography. After two courses of methylprednisolone pulse therapy, improvements in neurological symptoms without sequelae and the total disappearance of MRI lesions were observed. Upon encountering patients with refractory status epilepticus, multifocal cerebral MRI lesions, and suspected autoimmune encephalitis, especially in cases with thymoma, it would be prudent to suspect anti-GABAA-RE and consider the evaluation of anti-GABAA receptor antibody and methylprednisolone pulse therapy.

A case of pediatric anti-leucine-rich glioma inactivated 1 encephalitis with faciobrachial dystonic seizure.

BACKGROUND: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of autoimmune encephalitis. A characteristic faciobrachial dystonic seizure (FBDS) is also frequently associated with this disease. Although primarily reported in the adult population, reports of its occurrence in the pediatric population are rare. Here, we describe a case of a 6-year-old girl diagnosed with anti-LGI1 encephalitis that presented with cognitive decline and FBDS. CASE PRESENTATION: The girl was referred to a pediatric neurology department for uncontrolled seizures and dyskinesia. She initially presented with a memory deficit, abnormal movement of the limbs and trunk, and ataxia. Her cerebrospinal fluid exam was unremarkable, but her brain MRI showed focal T2 high signal intensity in the left anterior putamen and right caudate nucleus. In addition, there were refractory episodes of brief tonic or dystonic movement of the face and arms that were suggestive of FBDS. She was initially treated with intravenous methylprednisolone and phenobarbital, then given another pulse of methylprednisolone and intravenous immunoglobulin as her symptoms persisted. Tests for neuronal autoantibodies revealed the presence of anti-LGI1 antibodies. Subsequent human leukocyte antigen (HLA) typing resulted in the identification of HLA-DRB1 DR7(*07:01 g) DR9(*09:01 g). Screening for thymoma and other neoplasms showed no signs of a tumor. She was treated with rituximab, tocilizumab, and antiseizure medications, including oxcarbazepine, valproic acid, and lamotrigine. Her FBDS and cognitive symptoms showed substantial improvements. CONCLUSION: While it is known that anti-LGI1 encephalitis responds well to immunotherapy, our patient showed an incomplete response, requiring further therapy. This is the first report of a pediatric patient with anti-LGI1 encephalitis treated with tocilizumab.