NMDA receptor antibody encephalitis presenting as Transient Epileptic Amnesia

Transient Epileptic Amnesia (TEA) is a subtype of temporal lobe epilepsy, typically presenting in a person's early 60s, and of unknown aetiology. Encephalitis caused by antibodies to NMDA receptors (NMDARE) has not previously been documented in TEA. We describe a 47-year-old male who satisfied criteria for TEA, but given his atypical symptoms, was also screened for autoimmune epilepsy. High levels of serum NMDAR antibodies were found, suggesting NMDARE. Immunosuppressive treatment gradually eliminated the NMDA receptor antibodies. Our case extends the clinical spectrum associated with neuronal cell-surface autoantibodies to include atypical cases of TEA.This article is freely available via Open Access. Click on the Publisher URL to access the full text

Impact of rituximab treatment regime on time to relapse in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder.

BACKGROUND: Aquaporin-4 (AQP4) antibody associated neuromyelitis optica (NMOSD) requires long-term immunosuppression. Rituximab is increasingly used worldwide, however the optimal regime is not established. METHODS: We retrospectively examined different rituximab regimens in AQP4-NMOSD. Standard monotherapy (SM; 6 monthly infusions), SM plus oral steroids (SM+S), extended interval dosing (EID; guided by CD19 repopulation) and EID with oral steroids (EID+S) were compared. The primary outcome was time to first clinical relapse. Potential confounders including age, gender, number of previous relapses, and onset phenotype were included. RESULTS: 77 patients were included: 67 females, median onset age 35.6, median DSS at rituximab initiation 5.0. 39 were on SM+S, 20 SM, 6 EID, and 12 EID+S. 25/77 patients relapsed during a median follow-up of 44.0 months. No significant difference in time to first relapse was observed between any rituximab regimen. Pooled analyses to compare regimens that use standard monotherapy (SM and SM+S) against those that use extended interval dosing (EID and EID+S) showed no significant difference. Pooled analysis of regimens using steroids with those not using steroids also showed no significant difference. Adjusted Cox proportional hazard model revealed no significant difference between rituximab regimens or influence of demographic factors. 9 significant adverse events were recorded, 5 in the SM group and 4 in SM+S. CONCLUSIONS: This study provides some basis for further exploring EID as a viable option for long term treatment of AQP4-NMOSD. This may improve patient experience and consolidate use of hospital resources

Organic Matter Composition of Manure and Its Potential Impact on Plant Growth

Since the advent of flush toilet systems, the aquatic environment has received a massive contaminant flow. Furthermore, the perception of human feces has changed from a useful nutrient source for agriculture to a harmful contaminant. In this study, we compared the nutritional quality of five samples: (1) human manure (HM), (2) human manure from a family mainly eating organic food (HMO), (3) cow manure (CM), (4) poultry manure (PM), and (5) commercial nursery media (CNM). Samples were analyzed in terms of organic and inorganic nutrient contents, molecular composition, seed germination, and chlorophyll concentration. Pyrolysis gas chromatography/mass spectrometry (GC/MS) was used to describe the differences in molecular composition. Three-dimensional excitation and emission matrix fluorescence spectroscopy characterized the organic composition of water extracts. From the results, CNM, PM, and HMO showed humic- and fluvic-like substance peaks, the highest values of potassium and sulfate ions, and of C/N ratios, indicating greater plant growth potential. This was confirmed by their higher chlorophyll concentrations and germination index values. These results contribute knowledge about the positive effects of manure, changing the negative perception of human excreta from waste to resource. This work provides a reference for reducing the wastewater loading rate in society

Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis

Neurological and psychiatric practice frequently lack diagnostic probes that can assess mechanisms of neuronal communication non-invasively in humans. In N-methyl-D-aspartate (NMDA) receptor antibody encephalitis, functional molecular assays are particularly important given the presence of NMDA antibodies in healthy populations, the multifarious symptomology and the lack of radiological signs. Recent advances in biophysical modelling techniques suggest that inferring cellular-level properties of neural circuits from macroscopic measures of brain activity is possible. Here, we estimated receptor function from EEG in patients with NMDA receptor antibody encephalitis (n = 29) as well as from encephalopathic and neurological patient controls (n = 36). We show that the autoimmune patients exhibit distinct fronto-parietal network changes from which ion channel estimates can be obtained using a microcircuit model. Specifically, a dynamic causal model of EEG data applied to spontaneous brain responses identifies a selective deficit in signalling at NMDA receptors in patients with NMDA receptor antibody encephalitis but not at other ionotropic receptors. Moreover, though these changes are observed across brain regions, these effects predominate at the NMDA receptors of excitatory neurons rather than at inhibitory interneurons. Given that EEG is a ubiquitously available clinical method, our findings suggest a unique re-purposing of EEG data as an assay of brain network dysfunction at the molecular level

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes—including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)—led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools

A study of referral bias in NMOSD and MOGAD cohorts.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare disorders often seen in highly specialized services or tertiary centres. We aimed to assess if cohort characteristics depend on the origin of the referral catchment areas serviced by our centre (i.e. local, regional or national). METHODS: Retrospective cohort study using a national referral service database including local (Oxfordshire), regional (Oxfordshire and neighbouring counties), and national patients. We included patients with the diagnosis of NMOSD, seronegative NMOSD or MOGAD, followed at the Oxford Neuromyelitis Optica Service. RESULTS: We included 720 patients (331 with MOGAD, 333 with aquaporin-4 antibody (AQP4)-NMOSD, and 56 with seronegative NMOSD. The distribution of diagnoses was similar across referral cohorts. There were no significant differences in the proportion of pediatric onset patients, sex, or onset phenotype; more White AQP4-NMOSD patients were present in the local than in the national cohort (81 % vs 52 %). Despite no differences in follow-up time, more relapsing MOGAD disease was present in the national than in the local cohort (42.9 % vs. 24 %, p = 0.029). CONCLUSION: This is the first study assessing the impact of potential referral bias in cohorts of NMOSD or MOGAD. The racial difference in the AQP4-NMOSD cohorts likely reflects the variation in the population demographics rather than a referral bias. The over representation of relapsing MOGAD patients in the national cohort probably is a true referral bias and highlights the need to analyze incident cohorts when describing disease course and prognosis. It seems reasonable therefore to compare MOGAD and NMOSD patients seen withing specialised centres to general neurology services, provided both use similar antibody assays