Efficacy of steroid therapy in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis: a case report and literature review.

Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis.

BACKGROUND: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. METHODS: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). RESULTS: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. CONCLUSIONS: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

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.

Safety of Obinutuzumab in Children With Autoimmune Encephalitis and Early B-Cell Repopulation on Rituximab.

BACKGROUND: Rituximab (RTX) resistance or early B-cells repopulation were observed in children but only few publications reported the use of Obinutuzumab and no recommendations were made concerning the dosage for children. METHODS: This study was a single-center retrospective cohort study of all the children followed-up in the Pediatric Neurology Department of Necker-Enfants malades Hospital in Paris, France, and treated with obinutuzumab, between November 1, 2019, and November 1, 2021. RESULTS: A total of eight children (three females, median age 4.5 years) were treated. Seven patients presented with autoimmune encephalitis and one with myeloradiculitis. The median delay of B-cell repopulation after a course of RTX was 87 days (range 41 to 160). A switch to obinutuzumab (anti-CD20) was performed for eight children. The median duration between the first RTX infusion and obinutuzumab administration was 6.6 months. The dosage regimen for obinutuzumab was one infusion of 1000 mg/1.73 m2, that is to say 580 mg/m2 (maximum 1000 mg/infusion), by extrapolation from the adult dosage. The median delay of B-cell repopulation after one course of obinutuzumab was 230 days (range 66 to 303 days) vs 87 days after one course of RTX (P < 0.01). None of the patients presented side effects with obinutuzumab treatment. All patients had a favorable evolution at the last-follow up. Median follow-up was 1.6 years. CONCLUSIONS: This study reports the use of obinutuzumab in neurological inflammatory diseases in a pediatric population. Obinutuzumab seems to have a better biological efficacy than RTX with a longer time of B-cell repopulation.

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.

Antipsychotic medications associated with increased length of hospital stay in autoimmune encephalitis and multiple sclerosis: A retrospective study.

BACKGROUND: Antipsychotic medications (APMs) and selective serotonin reuptake inhibitors (SSRIs) are frequently utilized in patients with neuroinflammatory disorders, such as autoimmune encephalitis and multiple sclerosis (MS). This retrospective study investigates how in-hospital treatment with APMs and SSRIs in patients with these neuroinflammatory diseases are associated with differences in hospital length-of-stay (LOS) and mortality. METHODS: We evaluated all the inpatients in the Stanford University Hospital from 2008 to 2023 diagnosed with either non-infectious encephalitis or MS and subdivided them into those who did or did not receive APMs or SSRIs while hospitalized. We then analyzed whether hospital LOS and mortality differed with these medications. RESULTS: Among inpatients with non-infectious encephalitis (n = 114), those who were exposed to APMs had a significantly increased mean LOS (11.8 vs 20.9 days, p < 0.01). For inpatients with MS (n = 1095), treatment with an APM was associated with a significant increase in mean LOS (2.8 vs. 7.1, p < 0.00001). When comparing typical to atypical APMs given to subjects with MS, those who received atypical APMs showed a significant increase in LOS (4.3 vs 10.5, p < 0.01), although typical APMs showed significantly increased risk of mortality (p < 0.05). For inpatients with MS and SSRI use, there was a significant increase in mean hospital LOS (3.5 vs 5.3, p < 0.01), with a significant difference found in those who received fluoxetine or citalopram, but not sertraline or escitalopram. Finally, several healthcare disparities were found, including that Black patients were more likely to receive APMs, and those with MS were more likely to receive typical rather than atypical APMs. Conversely, Black patients with MS were less likely to receive SSRI treatment. CONCLUSIONS: There was a statistically significant increase in LOS associated with APM use in non-infectious encephalitis and MS, as well as with SSRI use in MS. These data reflect the importance of these medications in these neuroinflammatory disorders and suggest that further investigation into their risks and benefits would be warranted.

Acetazolamide as an effective treatment for pilomotor seizures in autoimmune encephalitis.

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti-LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE-associated pilomotor seizures. Six patients with AE (five anti-LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2-days-ON, 4-days-OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self-reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged .56 seizures/day ON, and 3.81 seizures/day OFF (p = .004). The two outpatients reported seizure reductions from 3-5/day to 2/week, and 15-20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings.

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.

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.

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.

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.

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.

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.

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.

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.