Exosomal miR-23a-3p derived from human umbilical cord mesenchymal stem cells promotes remyelination in central nervous system demyelinating diseases by targeting Tbr1/Wnt pathway.

Oligodendrocyte precursor cells are present in the adult central nervous system, and their impaired ability to differentiate into myelinating oligodendrocytes can lead to demyelination in patients with multiple sclerosis, accompanied by neurological deficits and cognitive impairment. Exosomes, small vesicles released by cells, are known to facilitate intercellular communication by carrying bioactive molecules. In this study, we utilized exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs-Exos). We performed sequencing and bioinformatics analysis of exosome-treated cells to demonstrate that HUMSCs-Exos can stimulate myelin gene expression in oigodendrocyte precursor cells. Functional investigations revealed that HUMSCs-Exos activate the Pi3k/Akt pathway and regulate the Tbr1/Wnt signaling molecules through the transfer of miR-23a-3p, promoting oligodendrocytes differentiation and enhancing the expression of myelin-related proteins. In an experimental autoimmune encephalomyelitis model, treatment with HUMSCs-Exos significantly improved neurological function and facilitated remyelination. This study provides cellular and molecular insights into the use of cell-free exosome therapy for central nervous system demyelination associated with multiple sclerosis, demonstrating its great potential for treating demyelinating and neurodegenerative diseases.

Ferroptosis and central nervous system demyelinating diseases.

Ferroptosis is a newly discovered programmed cell death caused by intracellular iron excess and glutathione (GSH) system imbalance, resulting in fatal lipid peroxidation. It is different from necrosis, apoptosis, autophagy, and other forms of cell death. Accumulating evidences suggest that brain iron overload is involved in the pathogenesis of demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM). The study of ferroptosis may provide a new understanding of demyelinating diseases and provide a novel therapeutic target for clinical treatment. Herein, we reviewed recent discoveries on mechanisms of ferroptosis, the effects of metabolic pathways on ferroptosis, and its involvement in CNS demyelinating diseases.

Lipid profiles and their potential inflammatory effects in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to perform a preliminary analysis to investigate the role of lipid profiles in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and to preliminarily explore the potential inflammatory effects of lipids on this disease by analyzing the association of lipid profiles with different inflammatory markers. METHODS: This retrospective study consisted of 40 anti-NMDAR encephalitis patients and 74 healthy controls. Serum lipid profiles and different inflammatory markers were analyzed upon admission and at each follow-up. Lipid profiles were compared among subgroups of patients, which were divided according to clinical characteristics. Correlations between lipid profiles and different inflammatory markers were assessed. RESULTS: The results showed that lipid profiles were abnormal and were correlated with both disease severity and prognosis in patients with anti-NMDAR encephalitis. Correlations between lipid profiles and different inflammatory markers were observed. After 12 months of treatment, inflammatory markers changed with lipid profiles, and these changes were significantly correlated. CONCLUSIONS: Lipid profiles are associated with pathogenesis and progression of anti-NMDAR encephalitis, and they are significantly correlated with different inflammatory markers, suggesting that the association of lipids with the disease might be influenced by the inflammatory response.

Genome-based analysis of SFTSV causing severe encephalitis with brain lesions.

Encephalitis is an infrequent manifestation in the various spectrums caused by severe fever with thrombocytopenia syndrome virus (SFTSV) infection. There are few data about the possible pathogenic mechanisms of SFTSV-associated encephalitis. Here, two SFTSV-infected patients with onset of encephalitis were enrolled. The whole genome of two SFTSV strains isolated from cerebrospinal fluid (CSF) was deeply sequenced by next-generation sequencing (NGS) and phylogenetic analysis was conducted. The specific mutations of M fragment were P98L and T665S respectively. The three-dimensional structure of glycoprotein Gn which was encoded by M fragment, an important virulence factor of SFTSV, was constructed by SWISS-MODEL. There was no significant variation in glycoprotein Gn of the two isolates comparing to other strains without encephalitis. Phylogenetic trees based on the complete sequences of M segment showed the two strains were highly identical to other local strains without encephalitis. Our study demonstrates that the virulence factors of SFTSV with encephalitis are not different from those without encephalitis. SFTSV itself is a neurotropic virus.

Thyroid Function and Autoimmune Indications in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

OBJECTIVE: Previous studies have shown that functional abnormalities of the thyroid are associated with the pathogenesis of several neurological diseases. However, their relationship in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis remains to be defined. METHODS: Forty-three patients with anti-NMDAR encephalitis were examined for thyroid function and autoimmune indications, in comparison with 225 healthy controls (CTL). Patients were further classified into 2 subgroups based on their free tri-iodothyronine (fT3) levels. Moreover, fT3 levels were also investigated after at least three months of follow-up. The clinical characteristics of the patients and CTL were described in detail. RESULTS: Serum levels of fT3 and thyroid-stimulating hormone (TSH) were found to be relatively lower in patients with anti-NMDAR encephalitis than in CTL (both p < 0.001). Low T3 syndrome also occurred more frequently in anti- NMDAR encephalitis (25.6 vs. 0.4%, p < 0.001). However, no statistical differences were detected between patients and CTL in terms of the positive rate of thyroid antibodies and other types of thyroid dysfunction. Patients with low T3 levels tended to have a longer hospital stay (p = 0.006), a higher rate of abnormal brain magnetic resonance imaging (MRI) findings (p = 0.033), a higher frequency of consciousness declination (p = 0.029), and a higher modified Rankin scale (mRS) score during hospitalization. Low fT3 levels were also associated with abnormal MRI findings, a decline in consciousness, and the mRS score on admission. In addition, fT3 seemed to gradually return to normal levels upon improvement of the mRS score (r = -0.649, p = 0.002). CONCLUSIONS: Low T3 syndrome often copresents in anti-NMDAR encephalitis and indicates a longer hospitalization, abnormal MRI findings, consciousness declination, and a higher clinical severity. However, fT3 levels do not seem to influence the prognosis of anti-NMDAR encephalitis.

Inverse relationship between cancer and Alzheimer's disease: a systemic review meta-analysis.

Alzheimer's disease (AD) and cancer are both prevalent in the elderly. Some epidemiological researches have reported the negative association between AD and cancer, but the results are controversial. The present meta-analysis is aimed to clarify the association between cancer and AD. PubMed, Web of knowledge and the Cochrane library databases were searched for eligible publications. The analysis indicated that history of cancer was associated with a reduced risk of AD (ES 0.62, 95 % CIs 0.53-0.74; p < 0.001), with no significance between-study heterogeneity and publication bias. Similar results were found in subgroup analysis by stratifying variables with education and APOEε4 carriers, years of follow-up and sample size of cases. The negative association was also found in analysis of risk of cancer among patients with AD (ES 0.59, 95 % CIs 0.42-0.82; p = 0.002), but with evidence of between-study heterogeneity and publication bias. In order to identify sources of the heterogeneity, subgroup analysis was performed by stratifying variable with or without education adjusted, sample size of cases and years of follow-up. Negative association was found in all subgroup analysis except in studies with less than 5-year follow-up and with heterogeneity disappeared only in the subgroup analysis stratified with sample size of cases. Our results in the present meta-analysis support the negative association between AD and cancer. But further well-designed perspective studies with strict control of confounding factors are needed to clarify the association between AD and cancer.

[Treatment of transplantation of NT-3 gene modified olfactory ensheathing cells on experimental autoimmune encephalomyelitis in rats].

OBJECTIVE: To explore the effects of transplantation of NT-3 gene modified olfactory ensheathing cells (OECs) on nerve function of rats with experimental autoimmune encephalomyelitis (EAE). METHODS: The experimental autoimmune encephalomyelitis model was established in Lewis rats. The animals were randomly divided into 3 group: blank control group (transplantation of saline), OECs transplanted group (transplantation of OECs), and OECs-NT-3 transplanted group (transplantation of NT-3 modified OECs). The neurological function was assessed and recorded every day. The migration and distribution of transplanted cells were observed. The nerve regeneration was valued in the aspect of morphological structure by means of immunohistochemistry and retrograde tracing technique of horseradish peroxidase (HRP). RESULTS: The neurological functional score of OECs-NT-3 transplanted group was obviously inferior to OECs transplanted group after transplantation (P < 0.05). A large number of OECs-NT-3 survived and migrated with axon in OECs-NT-3 transplanted group at Day 28. The number of nerve fibers in one microscopic field was much more in OECs-NT-3 transplanted group (38.8 ± 3.4, Day 28) than those in OECs transplanted group (32.5 ± 2.8, Day 28) (P < 0.05). The number of cortex neurons labeled by HRP in OECs-NT-3 transplanted group were significantly higher than those in OECs transplanted group, (P < 0.01). CONCLUSION: NT-3 gene modified OECs have better capacities of survival and migration in EAE rats. The transplanted OECs-NT-3 can promote the regeneration of axon, reduce the injury of cortical neurons and improve the motor functions of EAE rats.

[Effect of LINGO-1 gene silencing on movement function of EAE mice].

OBJECTIVE: To explore the effect of LINGO-1 silencing on movement function of experimental autoimmune encephalomyelitis (EAE) mice. METHODS: EAE was established by induction of MOG35-55 in female C57/BL6 mice. Then female EAE mice (n=105) were completely randomly divided into 5 groups: group A (n=21): 5 µl 5×10(9) Tu/ml lentiviral vectors encoding LINGO-1shRNA (LV/LINGO-1-shRNA) by intracerebroventricular (ICV) injection, group B (n=21): 5 µl 5×10(8)Tu/ml LV/LINGO-1-shRNA by ICV injection, group C (n=21): 5 µl 5×10(7) Tu/ml LV/LINGO-1-shRNA by ICV injection, group D (n=21): 5 µl LVCON053 by ICV injection and group E (n=21): untreated.The movement function was scored and the expression of LINGO-1 protein was detected by Western blot on day 1, 3, 7, 14, 21, 30 after ICV among different groups. Luxol fast blue staining was performed to know about conditions of myelin sheath on day 30. RESULTS: The expression of LINGO-1 in EAE mouse was obviously downregulated ever since day 7 after LV/LINGO-1-shRNA implantation.Group B and C achieved the most reduction of LINGO-1 expression (1.99±0.13, 2.08±0.10, P<0.05, P<0.01). Simultaneously, the movement functional score of group A, B and C was lowered at different levels from day 7 (3.11±0.13, 2.42±0.13, 2.96±0.10 vs 3.56±0.15, 3.87±0.12, P<0.01, P<0.01, P<0.05), with the most marked decrease in group B. The densities of myelin sheaths in group A and B were higher than untreated group on day 30 (0.72±0.09, 0.83±0.11 vs 0.56±0.10, P<0.05, P<0.01). CONCLUSION: LV/LINGO-1shRNA by ICV injection is an effective method to silence LINGO-1 expression. LINGO-1 silencing could ameliorate motor function and promote formation of myelin sheaths. But the effects do not enhance with the increase of LV/LINGO-1-shRNA dose.

[Treatment of autotransplantation of NT-3 gene modified OECs and NSCs complex adhering to scaffold on spontaneous cerebral hemorrhage].

OBJECTIVE: To explore the effects of autotransplantation of NT-3 gene modified olfactory ensheathing cell (OEC) and neural stem cell (NSC) complex adhering to collagen protein-heparin sulfate scaffold on motor function of rats with cerebral hemorrhage. METHODS: The cerebral hemorrhage model was established with caudate nucleus bleeding in Wistar rats. The animals were randomly divided into 4 groups: A (transplantation of NT-3 modified OEC-NSC complex adhering to scaffold), B (transplantation of NT-3 modified OEC-NSC complex), C (transplantation of scaffold) and D (blank control group). The motor function of hind limbs was assessed at Day 1, 3, 7, 14 and 30 post-transplantation respectively. The survival, distribution and differentiation of transplanted cells were tested by immunohistochemistry and fluorescent staining. RESULTS: The neurological functional score of group A (2.12 ± 0.12, 1.50 ± 0.11, 0.52 ± 0.08) or B (2.10 ± 0.16, 1.79 ± 0.09, 0.91 ± 0.10) was obviously inferior to group C/D at Days 7, 14 and 30. No significant difference existed between groups C and D (P > 0.05) . The scores of A were markedly lower than those of B at Days 14 and 30 (P < 0.05, P < 0.01) . The numbers of surviving NSCs and cells migrating to focal area after transplantation was much more in group A than those in other groups. CONCLUSION: Autotransplantation of NT-3 gene modified OEC-NSC complex adhering to collagen protein-heparin sulfate scaffold may markedly ameliorate the motor function of cerebral hemorrhagic in rats. And the transplanted NSCs have better capacities of survival, migration and differentiation.

[LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis mouse].

OBJECTIVE: To observe the changes of LINGO-1 expression with time after onset in EAE mouse. METHODS: C57/BL6 mice were completely randomly divided into EAE model group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1 expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed by Western blot. RESULTS: The LINGO-1mRNA levels in EAE model group were markedly higher than control group on day 1, 7and 14 after onset (4.63 ± 0.25, 2.72 ± 0.12, 1.98 ± 0.16, P < 0.01, P < 0.01, P < 0.05).On day 30, Lingo-1 mRNA was close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21, 30 were higher than control group (2.11 ± 0.15, 3.15 ± 0.09, 2.45 ± 0.12, 1.89 ± 0.17, 1.21 ± 0.05, P < 0.05, P < 0.01, P < 0.05, P < 0.05, P < 0.05. The levels of p-RhoA protein increased in EAE and the peak appeared on day 1 and day 7 (P < 0.01) . And there was no difference on RhoA expression among different groups. CONCLUSIONS: LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report.

p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, amyotrophic lateral sclerosis, frontotemporal dementia, and distal myopathy with rimmed vacuoles (MRV). Herein, we report a new phenotype of SQSTM1-associated proteinopathy, a novel frameshift mutation in SQSTM1 causing proximal MRV. A 44-year-old Chinese patient presented with progressive limb-girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. The magnetic resonance images showed fatty infiltration into muscles, predominantly in the thighs and medial gastrocnemius, sparing the tibialis anterior. Muscle histopathology revealed abnormal protein deposition, p62/SQSTM1-positive inclusions, and rimmed vacuoles. Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs*66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV.

Clinical characteristics and prognosis in patients with neuronal surface antibody-mediated autoimmune encephalitis: a single-center cohort study in China.

Objective: This retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy. Methods: Clinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis. Results: Overall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0-2), and 21 patients had a poor prognosis (mRS 3-6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p<0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733-0.961; p < 0.001). Conclusions: Different AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.

Long-term efficacy and safety of different corticosteroid courses plus mycophenolate mofetil for autoimmune encephalitis with neuronal surface antibodies without tumor.

Objective: To compare the efficacy and safety of different-course corticosteroids plus mycophenolate mofetil (MMF) as maintenance therapy in autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) without tumor and explore the optimal course of corticosteroids. Methods: Fifty-five patients with definite AE without tumor were enrolled consecutively between June 2015 and November 2020 and retrospectively divided three groups according to the course of treatment with corticosteroid, i.e., a group of patients with a course of 3-6 months (Group 3-6mo), 6-12 months (Group 6-12mo), and >12 months (Group >12mo). Demographic data, clinical manifestation and ancillary tests results were recorded. The dosage and courses of corticosteroid treatment, the recovery of neurological function, the occurrence of adverse effects, and relapses were followed up. Results: A total of 55 patients were included in the final analysis. The numbers of patients in Group 3-6 mo, Group 6-12 mo, and Group >12 mo was 14, 17, and 24, respectively. A significantly higher proportion of patients in Group >12 mo showed a decreased level of consciousness at the onset (12, 50%) than in Group 3-6 mo and Group 6-12 mo (2,14.3%; 3, 17.6%) (p = 0.033). The incidence of MRI abnormalities was significantly higher in Group 6-12 mo and Group >12 mo (10, 58.8%; 16, 66.7%) than in Group 3-6 mo (3, 21.4%) (P=0.023). Ordinal regression analysis indicated that decreased level of consciousness was associated with the course of corticosteroid (OR=3.838, 95% CI: 1.103-13.323, P=0.035). No significant difference was observed between the three groups regarding the cumulative dose of corticosteroids administered during the first three months of long-term treatment (P>0.05). Additionally, no significant difference in the cumulative dosage of corticosteroids was found between patients in Group 6-12 months and Group >12 months during the first 6 months after beginning long-term treatment. The mRS scores of the three groups were not statistically significant before and after first-line treatment or at the last follow-up. Bonferroni multiple comparison test indicated that the mRS scores of patients in Group 6-12 months and Group >12 months were not statistically significant at 3 months and 12 months after the start of long-term treatment. During the follow-up, 50 (90.9%) patients achieved satisfactory neurological function (mRS score ≤2). Five patients (9.1%) experienced a first relapse and 2 of them were overlapped with both anti-NMDA receptor and glial antibodies. The incidence of adverse effects was significantly higher in Group >12 mo (17, 70.8%) than in Group 3-6 mo (3, 21.4%) and Group 6-12 mo (5, 29.4%) (P=0.003). Conclusions: The beneficial effects of oral corticosteroid treatment may do not persist beyond 12 months and may even contribute to an increased incidence of adverse effects. In order to optimize the effectiveness and safety of treatment, we recommend a corticosteroid course of 3-12 months. Patients with reduced levels of consciousness may be more inclined to choose longer courses of corticosteroids for long-term treatment. Patients with an "overlapping syndrome" may require more intense immunotherapy to prevent relapse.

Clinical characteristics and short-term outcomes of Japanese encephalitis in pediatric and adult patients: a retrospective study in Northern China.

Objective: The study aimed to compare the clinical characteristics and short-term outcomes of pediatric and adult Japanese encephalitis (JE) patients in order to find out the differences. Methods: From August 2006 to October 2019, 107 patients (62 pediatric patients and 45 adult patients) with JE were enrolled. Clinical characteristics and short-term outcomes were analyzed. The short-term outcome of each patient was defined as a good outcome or poor outcome according to their Glasgow Coma Scale (GCS) scores (GCS > 8 vs. GCS ≤ 8) at discharge. Results: As for acute complications, the incidence of pulmonary infection was higher in 25 adults (25/45, 55.6%) than in 19 children (19/62, 30.6%; P = 0.01). Upper gastrointestinal bleeding was more common in patients with pulmonary infection, with 10 of these patients experiencing the symptom (10/44, 22.7%) compared to only one patient without pulmonary infection (1/63, 1.6%; P = 0.001). The proportion of mechanical ventilation and admission to the intensive care unit (ICU) for supportive care was higher in patients with pulmonary infection than in patients without infection (P < 0.001, P = 0.008, respectively). The GCS scores at discharge in patients with pulmonary infection (7, 4-12.75) were lower than in patients without pulmonary infection (14, 10-14; P < 0.001). Although the GCS scores at the admission of children (9.5, 7-13) were similar to that of adults (7, 6-13), the GCS scores at the discharge of adults (7, 3.5-13) were lower than that of children (13, 10.75-14; P < 0.001). Conclusion: The short-term outcome of JE was worse in adults. Pulmonary infection was correlated with a high incidence of upper gastrointestinal bleeding, mechanical ventilation, and ICU hospitalization in JE. Pulmonary infection is a prognostic predictor of short-term outcomes in patients with JE. Vaccination for adults should be initiated.

Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases.

Current treatments for central nervous system (CNS) inflammatory demyelinating diseases (IDDs) include corticosteroids, plasma exchange, intravenous immunoglobulin, and immunosuppressant drugs. However, some patients do not respond well to traditional therapies. In recent years, novel drugs, such as monoclonal antibodies, targeting the complement component C5, CD19 on B cells, and the interleukin-6 (IL-6) receptor, have been used for the treatment of patients with refractory CNS IDDs. Among these, tocilizumab and satralizumab, humanized monoclonal antibodies against the IL-6 receptor, have shown beneficial effects in the treatment of this group of diseases. In this review, we summarize current research progress and prospects relating to anti-IL-6 therapies in CNS IDDs.

Eculizumab treatment for myasthenia gravis subgroups: 2021 update.

Eculizumab is a recombinant humanized monoclonal antibody that targets the complement protein C5, inhibiting its cleavage into C5a and C5b and ultimately preventing the formation of C5b-9 membrane attack complex (MACs), thereby protecting the neuromuscular junction from the damage of complement activation. In 2017, eculizumab became the second FDA-approved medication for AchR-positive generalized myasthenia gravis (gMG) patients based on the successful results of a randomized, double-blinded, placebo-controlled, phase 2, phase 3 study (the REGAIN trial) and its open-label extension study. Despite the efficacy of eculizumab in treating AchR antibody-positive refractory gMG was demonstrated in the REGAIN study, there is few information on its efficacy in other subgroup of MG patients including seronegative MG, thymoma-associated MG and MG crisis. This narrative review summarizes current clinical studies of eculizumab in these refractory gMG patients, with a focus on the therapeutic efficacy and tolerability in different subgroup of MG.

Clinical Features, Treatment, and Prognostic Factors in Neuronal Surface Antibody-Mediated Severe Autoimmune Encephalitis.

Objective: This study aimed to determine the clinical characteristics and evaluate the efficacy of immunotherapy and the long-term prognosis of severe autoimmune encephalitis (AE) in China. Methods: Clinical features, laboratory or radiological findings, and treatment outcomes of 60 severe patients with AE from January 1, 2014, to December 31, 2020, were collected. Continuous variables were compared using the t-test and the nonparametric Mann-Whitney U test, as appropriate. Univariate and multivariable logistic regression analyses were performed to assess the correlations between factors, treatment responses, and prognosis of severe AE. Results: The median age of symptom onset was 35 years. Tumors were identified in 23.3% of patients, and 36/60 (60%) patients responded to first-line immunotherapy. Second-line immunotherapy was implemented in 26/60 (43.3%) patients. A significant clinical benefit was observed in 19/26 (73.1%) patients treated with lower dosage rituximab; seven patients were still refractory and received bortezomib as an add-on therapy. During the last follow-up, 48/60 (80%) patients achieved good outcomes (mRS, 0-2), and 10 died. Seventeen patients experienced relapses. A high CD19+ B-cell count (OR, 1.197; 95% CI [1.043-1.496]; p = 0.041) and a lower neutrophil-to-lymphocyte ratio (NLR; OR, 0.686; 95% CI [0.472-0.884]; p = 0.015) predict the response to first-line treatment and good prognosis, respectively. Conclusions: Patients with severe AE were in critical condition at baseline but could be salvaged after effective rescue immunotherapy. A lower dosage of rituximab could be an optimal option for severe AE. CD19+ B-cell count and NLR may provide prognostic information for predicting treatment response and outcome of severe AE.

Low high-density lipoprotein cholesterol and apolipoprotein A-I levels are associated with poor outcome and relapse in autoimmune encephalitis.

BACKGROUND: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to investigate the relationship between lipid profiles and prognosis of autoimmune encephalitis (AE) patients. METHODS: This retrospective study consisted of 114 AE patients from September 2014 to September 2020. Data of clinical parameters, including age, sex, body mass index (BMI), clinical features, comorbidities, therapeutic management, lipid profiles, modified Rankin scale (mRS) scores, outcomes, and relapses were collected. Logistic regression models were used to examine the associations between lipid profiles and outcomes of AE. Correlations between lipid profiles and C-reactive protein (CRP), which is an inflammatory marker, were assessed. RESULTS: In the univariate logistic analysis, sex (P = 0.030), mental behavior disorder (P = 0.004), disturbance of consciousness (P = 0.002), mRS at study entry (P = 0.020), tumor comorbidity (P = 0.028), high-density lipoprotein cholesterol (HDL-C) (P = 0.029), apolipoprotein A-I (apoA-I) (P = 0.012), apolipoprotein B (apoB) (P = 0.036) and apoA-I/apoB (P = 0.001) levels were all associated with the unfavorable outcomes of patients. After adjustment for age, sex and mRS at study entry, lower apoA-I and apoA-I /apoB levels were still significantly associated with the unfavorable outcomes of patients. Low HDL-C (P = 0.048) and apoA-I levels (P = 0.026) were also significantly associated with the relapse of AE patients. HDL-C and apoA-I levels were negatively correlated with CRP levels in correlation analysis. CONCLUSIONS: Lipid profiles, especially low HDL-C and apoA-I levels, are significantly associated with the poor outcomes and relapse of AE patients, and seem associated with inflammatory responses. HDL-C and apoA-I levels may be good candidates for predicting prognosis of AE patients.