Case report: Shingles-associated probable Bickerstaff brainstem encephalitis with IgM anti-sulfatide positivity.

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.

Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin.

Background: Autoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis. Case description: The patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient's condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent. Conclusions: The current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.

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.

Encephalitis is an Important Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Diseases: A Single-Center Cohort Study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS: This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS: A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS: The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

Patient With Rigidity and Fasciculations: Steroid-Responsive Presentation of Anti-IgLON5 Disease

An 82-year-old man presented with 2-year lasting widespread muscular fasciculations, cramps, and limb stiffness, with spontaneous movements in the right lower limb, unsteady gait (Video 1), and falls. Neurophysiologic studies disclosed signs of neuromuscular hyperexcitability. CSF analysis showed high tau protein concentration (543 pg/mL; reference values, <404) and unique-to-CSF oligoclonal bands. Serum and CSF anti-IgLON5 antibodies were positive (Figure 1). He carried the anti-IgLON5 disease-associated HLA-DRB1*10:01 allele.1 Brain MRI, thoracoabdominal CT, whole-body FDG-PET, and video-polysomnography were unremarkable. No sleep disturbances, bulbar symptoms, parkinsonism, or dementia were detected. Intravenous methylprednisolone (500 mg/d for 5 days), followed by oral benzodiazepines, prompted rapid functional recovery, with limb stiffness and gait improvement (Video 1), which persisted at 6-month follow-up. Anti-IgLON5 disease has progressive course and protean clinical presentations,2 representative, in our patient, for overlapping signs and symptoms of neuromuscular hyperexcitability and rigidity. Identification of rare phenotypes is important because prompt recognition and treatment can improve prognosis.

Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical Gram-negative bacillary meningitis or ventriculitis: a systematic review and meta-analysis.

PURPOSE: Extensively-drug-resistant Gram-negative bacteria (XDR GNB)-related post-neurosurgical infection is closely related to mortality, which represents a major challenge for neurosurgeons. There is an urgent need to review and evaluate methods to reduce mortality. METHODS: Both international and Chinese databases were searched independently from their inception to 15 June 2023. A meta-analysis was conducted using RevMan 5.4 to compare the efficacy and safety of intravenous (IV) treatment in combination with intrathecal or intraventricular (ITH/IVT) treatment with IV treatment alone for post-neurosurgical meningitis or ventriculitis due to GNB. Mortality, microbiological clearance and adverse events were considered as primary outcomes. RESULTS: In total, 18 eligible studies involving 602 patients were included in the meta-analysis. The IV + ITH/IVT group was associated with significantly lower mortality (especially in the XDR GNB subgroup) and acceptable safety. In terms of microbiological clearance, a significant decrease was shown in the XDR GNB subgroup. Significant benefits were shown in laboratory parameters and clinical symptoms after patients were treated with ITH/IVT. CONCLUSION: Additional ITH/IVT treatment may promote XDR GNB clearance and reduce mortality. In addition, ITH/IVT administration can improve clinical symptoms and cerebrospinal fluid indicators of patients with post-neurosurgical infections. Significantly, ITH/IVT treatment does not increase the incidence of adverse events at the recommended dose.

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.

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.

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.

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial.

OBJECTIVE: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. DESIGN: Phase 3b multicentre, double-blind, randomised placebo-controlled trial. SETTING: Twenty-one hospitals in the UK. PARTICIPANTS: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. INTERVENTION: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment. MAIN OUTCOME MEASURE: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. SECONDARY OUTCOME MEASURES: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. RESULTS: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. CONCLUSIONS: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.

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).

Autoimmune GFAP astrocytopathy after viral encephalitis: a case report of bimodal overlapping encephalitis.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a treatable autoimmune disorder affecting the central nervous system. Despite extensive research, the exact etiology and pathogenesis of this condition remain unclear. In recent years, autoimmune encephalitis (AE) after viral encephalitis (VE) has gathered significant attention. Here, we present a case report of autoimmune GFAP astrocytopathy after VE in a 43-year-old Asian male with a history of oral and labial herpes. The patient presented with high-grade fever, headache, urinary retention, unresponsiveness, and apathy. Elevated levels of protein and GFAP-IgG were observed in the cerebrospinal fluid (CSF), and enhanced brain magnetic resonance imaging (MRI) revealed linear enhancement oriented radially to the ventricles. Treatment with intravenous immunoglobulin (IVIG) resulted in symptom relief, reduced lesion enhancement, and decreased protein levels. This case report highlights bimodal encephalitis with no discernible interval between VE and autoimmune GFAP astrocytopathy, which poses diagnostic challenges. Notably, autoimmune GFAP astrocytopathy is a novel form of autoimmune encephalitis, and its treatment lacks sufficient clinical experience. Intriguingly, our patient demonstrated sensitivity to IVIG, a treatment that differed from past reports. Therefore, further exploration of treatment strategies for this condition is warranted.

Mechanisms and Emerging Therapies for Treatment of Seizures in Pediatric Autoimmune Encephalitis and Autoinflammatory/Autoimmune-Associated Epilepsy.

There has been increasing understanding of the role of inflammation in seizures and epilepsy, as well as targeted immunomodulatory treatments. In children, immune-mediated seizures often present acutely in the setting of autoimmune encephalitis and are very responsive to immunotherapy with low rates of subsequent epilepsy. Conversely, seizures in autoimmune-associated epilepsies, such as Rasmussen syndrome, can remain refractory to multimodal therapy, including immunomodulation. In this review, the authors discuss the presentations of immune-mediated seizures in children, underlying mechanisms, and emerging therapies.

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.

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.

[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.