Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P < 0.05). NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

Objective: To determine the clinical and antibody response after therapeutic plasma exchange (TPE) in patients with severe refractory antibody‐associated autoimmune encephalitis (AE).Methods: This single‐center prospective cohort included all patients consecutively admitted to our hospital because of severe refractory AE over the period from July 2014 to June 2019. All patients received immunotherapy (steroids, intravenous immunoglobulin (IVIG), and/or TPE). The primary outcome was evaluated at 1‐ and 2‐month postenrollment, and the long‐term outcome was followed up at 6 and 12 months. AE antibody titers in the cerebrospinal fluid and plasma were evaluated before and after TPE/IVIG.Results: This study enrolled 57 patients with severe refractory AE, including anti‐NMDA receptor encephalitis (n = 51), anti‐GABAb receptor encephalitis (n = 3), anti‐LGI 1 encephalitis (n = 2), and anti‐AMPA receptor encephalitis (n = 1). Of all 57 patients, 33 patients received TPE for a total of 193 procedures, and 24 patients with contraindications or refusal of TPE were in the non‐TPE group. Compared with the non‐TPE group, the TPE group exhibited greater clinical improvement: 21 (37%) versus 8 (14%) after 1 month (P = 0.03) and 31 (54%) versus 16 (28%) after 2 months (P = 0.01), respectively. Complications and adverse events associated with TPE occurred in 91 procedures (47%) without serious adverse events associated with the use of TPE.Interpretation: TPE might be an effective rescue therapy associated with rapid functional improvement in patients with severe steroid/IVIG refractory antibody‐associated AE from this nonrandomized control trial.

The objective of the present study was to assess the efficacy of therapeutic plasma exchange (TPE) in patients with severe refractory anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis. Patients with severe anti-NMDA receptor encephalitis who showed no improvement after steroids and/or intravenous immunoglobulin treatment for at least 10 days were enrolled. All patients received immunotherapy and were divided into a TPE group and a non-TPE group according to treatment received. Each patient in the TPE group received at least 1 TPE course. NMDA receptor antibody titers in the cerebrospinal fluid (CSF) and plasma were evaluated within 1 week after the last TPE procedure. The clinical efficacy of treatment was evaluated after 1 month, 2 months, 3 months, 6 months, and 12 months. Forty patients were enrolled: 19 in the TPE group and 21 in the non-TPE group. Nineteen patients received TPE for a total of 118 procedures. NMDA receptor antibody titers in the CSF and/or plasma decreased or were negative after the last TPE procedure in 18 patients (94.7%). Compared with the non-TPE group, the TPE group exhibited greater clinical improvement after 1 month and 2 months following treatment (P < 0.05). After 3 months, 6 months, and 12 months, there were no significant differences in the outcomes between the TPE group and non-TPE group. The results suggest that TPE might rapidly improve the clinical manifestations in patients with severe refractory anti-NMDA receptor encephalitis, and we believe that TPE should be considered as a first-line treatment.

Moyamoya disease (MMD) is an idiopathic disease associated with recurrent stroke. However, the pathogenesis of MMD remains unknown. Therefore, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in blood samples from MMD patients (N = 15) and healthy controls (N = 10). A total of 880 differentially expressed lncRNAs (3649 probes) and 2624 differentially expressed mRNAs (2880 probes) were obtained from the microarrays of MMD patients and healthy controls (P < 0.05; Fold Change >2.0). Gene ontology (GO) and pathway analyses showed that upregulated mRNAs were enriched for inflammatory response, Toll-like receptor signaling pathway, chemokine signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway among others, while the downregulated mRNAs were enriched for neurological system process, digestion, drug metabolism, retinol metabolism and others. Our results showed that the integrated analysis of lncRNA-mRNA co-expression networks were linked to inflammatory response, Toll-like signaling pathway, cytokine-cytokine receptor interaction and MAPK signaling pathway. These findings may elucidate the pathogenesis of MMD, and the differentially expressed genes could provide clues to find key components in the MMD pathway.

Background: Ischemic events are the most common postoperative complication in bypass surgery for moyamoya disease (MMD), but the risk factors for pediatric MMD remain unclear. The goal of the study was to investigate the risk factors for postoperative ischemic complications in pediatric MMD patients. Methods: We retrospectively reviewed a consecutive series of pediatric MMD cases at Beijing Tiantan Hospital, Capital Medical University from June 2010 through June 2019. Preoperative clinical variables and radiographic findings were recorded, and logistic regression analysis was carried out to identify the risk factors for postoperative ischemic events. Results: A total of 533 operations in 336 patients were included in this study. Postoperative complications occurred after 51 operations (9.6%), including 40/447 indirect bypass procedures, 9/70 direct bypass procedures, and 2/16 combined bypass procedures. Postoperative ischemic events were the most common complication and occurred in 30 patients after 31 procedures (8.9% per patient; 5.8% per operation), including 26/447 indirect bypass procedures, 4/70 direct bypass procedures, and 1/16 combined bypass procedures, and the incidence of these events did not differ significantly between indirect and non-indirect bypass (5.8% vs 5.8%; p = 0.999). Multivariate logistic regression analyses revealed that older age at operation (OR 1.129, 95% CI 1.011–1.260, p = 0.032) and posterior cerebral artery involvement (OR 2.587, 95% CI 1.030–6.496, p = 0.043) were significantly associated with postoperative ischemic events. Conclusion: We speculate that older age at operation and posterior cerebral artery involvement are risk factors for postoperative ischemic events in pediatric MMD patients.