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.

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.

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.

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.

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.

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.

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.

Insidious Attentional Deficits in Patients With Cerebral Small Vessel Disease Revealed by Attention Network Test.

Background: Several reports have indicated potential cognitive decline for cerebral small vessel disease (CSVD), especially in attention domain, whereas the attentional function at network level is still elusive. In this study, we used the attention network test (ANT) paradigm to characterize the efficiency of the alerting, orienting, and executive control networks in patients with CSVD and explore possible correlations between attention network efficiencies and obtained CSVD total score. Methods: A total of 31 patients with CSVD and 30 healthy controls matched for age, gender, and education level were recruited. After neuropsychological and anxiety/depression/somatization assessments, an original version of ANT containing different cue conditions and target stimuli was used to investigate independent attentional components, and then, behavioral performance (accuracy and reaction time) and network efficacy were recorded and analyzed. Results: Assessed by traditional neuropsychological scale (MoCA), we did not find difference between groups on general cognition. Nevertheless, the overall reaction time to targets of ANT was markedly prolonged in patients with CSVD, and similar phenomenon was observed for overall accuracy on ANT. Moreover, patients showed significantly lower orienting and executive control network efficiencies compared with controls, while not for alerting network. These impairments were correlated with total CSVD burdens, but not with anxiety, depression, or somatization. Conclusions: Although general and almost all individual cognitive function evaluated by MoCA seemed to remain intact, the orienting and executive control function was impaired in individuals with CSVD, which was modulated by lesion grades. Our observations implied insidious attentional deficits regarding CSVD. Given this, considering its simplicity and sensitivity, ANT could serve as an attractive tool for early diagnosis of cognitive dysfunction. Further investigations on the availability of ANT detection for CSVD are warranted.

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.

Influential Factors, Treatment and Prognosis of Autoimmune Encephalitis Patients With Poor Response to Short-Term First-Line Treatment.

Objective: This study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE). Methods: This retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed. Results: Of the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group (p < 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up (p < 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44-15.59, and p=0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65-47.16; and p = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups. Conclusion: Disease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.

Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study.

Purpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients. Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up. Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise. Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.

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.

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.

Afterdischarges in Myasthenia Gravis.

Introduction: This study aimed to analyze the clinical features of myasthenia gravis (MG) in combination with the afterdischarges and compare the characteristics of afterdischarges in MG with different serum antibodies. Methods: Ninety-two patients with MG were analyzed retrospectively. The afterdischarges were investigated using motor nerve conduction examination, F-wave examination, and repetitive nerve stimulation (RNS). Results: Afterdischarges were observed after the M wave in 14 of 92 patients. Three of these 14 patients tested positive for the muscle-specific tyrosine kinase antibody (MuSK-Ab), and 11 patients tested positive for the acetylcholine receptor antibody (AchR-Ab). The characteristics of the afterdischarges on RNS differed distinctly between the two antibody groups. The afterdischarges occurred on the first stimulation, but decreased on the second and subsequent stimulations in patients with MuSK-MG, while the afterdischarges continued to occur on each stimulation in patients with AchR-MG. Discussion: The characteristics of the afterdischarges on RNS enabled easy identification of their synaptic or neurogenic nature.

Efficacy and safety of bortezomib in rituximab-resistant anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis as well as the clinical characteristics: An observational study.

Treatment resistance leads to physiological, psychological, and economical effects among patients with anti-N-methyl d-aspartate receptor (anti-NMDAR) encephalitis, and the clinical and immune characteristics of these patients remain to be described. According to our clinical experience, bortezomib may be effective due to its plasma-cells depletion ability. Herein, the clinical presentations and immune parameters, including B cell and antibody secreting cell (ASC) abundance, of 5 enrolled treatment-resistant patients are described. When compared with 5 treatment-sensitive cases, the patients had serious clinical presentations but comparable B cells and ASCs. After receiving bortezomib, the ASC count and anti-NMDAR antibody titers decreased effectively. All 5 patients had a favorable prognosis (mRS ≤ 2) with a median follow-up of 31 months without severe side effects or relapse.

Complement C3 polymorphism is associated with the susceptibility of myasthenia gravis in Chinese adult patients.

Complement component 3 (C3) had been proved to be involved in the pathogenesis and exacerbation of both myasthenia gravis (MG) patients and experimental autoimmune myasthenia gravis (EAMG) models. We evaluated the underlying association between five SNPs (rs344555, rs7951, rs3745568, rs366510 and rs163913) in C3 gene and Chinese adult MG patients. Our study consisted of 409 adult MG patients and 487 healthy controls. Subgroups were classified by gender, onset age, thymoma, anti-AChR antibody, onset muscle involvement (ocular/generalized) and severity (Oosterhuis score at the maximal severity during the initial two years after the onset of MG). We found significant differences in allele frequencies between MG and the control group, between various MG subgroups and the control group in rs344555 and rs3745568. There were significant differences in genotype frequencies between MG group and the control group, between MG subgroups and the control group under the codominant and additive inheritance models in rs344555 and rs3745568. No association was found between the frequencies of these SNPs and the severity of MG. We also used a comprehensive classification which was close to the clinical scenario to minimize the interaction among clinical features. In rs344555, the T allele frequency in thymoma (-) AChR-Ab (+) subgroup was significantly higher than that in the control group. Our results indicated that rs344555 was associated with the susceptibility of Chinese adult MG patients; rs3745568 was probably associated with the susceptibility of Chinese adult MG patients. No association was found between the frequencies of these SNPs and the severity of MG.

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.