NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis

Galli, Jonathan; Clardy, Stacey; Piquet, Amanda L.

doi:10.1007/s11908-017-0556-y

Cited by 29 publications

(12 citation statements)

References 34 publications

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“…The viral story comes back full circle to autoimmunity in that viral infection and viral-induced immunity may initiate autoimmune disease ( 170 ) through various mechanisms, such as direct bystander activation, epitope spreading, molecular mimicry, and release of cryptic epitopes ( 173 ). NMDAR encephalitis with positive CSF autoantibodies may follow HSV encephalitis several weeks later ( 174 ). Whether immunotherapy can prevent the development of autoimmunity following HSVE requires further study ( 174 ).…”

Section: Comparison Of Csf Ck/cytokine Immunomarker Profiles In Humanmentioning

confidence: 99%

“…NMDAR encephalitis with positive CSF autoantibodies may follow HSV encephalitis several weeks later ( 174 ). Whether immunotherapy can prevent the development of autoimmunity following HSVE requires further study ( 174 ). The concept of the “infectome”—referring to “…the collection of an individual’s exposures to infectious agents…”—was introduced to trace infectious triggers of autoimmunity and better the understanding of microbial/host interactions in autoimmune diseases ( 175 ).…”

Section: Comparison Of Csf Ck/cytokine Immunomarker Profiles In Humanmentioning

confidence: 99%

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Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Pranzatelli

2018

Front. Immunol.

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The concept and recognized components of “neuroinflammation” are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron–glia interactions and other mechanisms affecting neurotransmission. They issue the “help me” cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic). Human cerebrospinal fluid (CSF) studies have been instrumental in revealing soluble immunobiomarkers involved in immune dysregulation, their dichotomous effects, and the cells—often subtype specific—that produce them. CKs/cytokines continue to be attractive targets for the pharmaceutical industry with varying therapeutic success. This review summarizes the developing armamentarium, complexities of not compromising surveillance/physiologic functions, and insights on applicable strategies for neuroinflammatory disorders. The main approach has been using a designer monoclonal antibody to bind directly to the chemo/cytokine. Another approach is soluble receptors to bind the chemo/cytokine molecule (receptor ligand). Recombinant fusion proteins combine a key component of the receptor with IgG1. An additional approach is small molecule antagonists (protein therapeutics, binding proteins, and protein antagonists). CK neutralizing molecules (“neutraligands”) that are not receptor antagonists, high-affinity neuroligands (“decoy molecules”), as well as neutralizing “nanobodies” (single-domain camelid antibody fragment) are being developed. Simultaneous, more precise targeting of more than one cytokine is possible using bispecific agents (fusion antibodies). It is also possible to inhibit part of a signaling cascade to spare protective cytokine effects. “Fusokines” (fusion of two cytokines or a cytokine and CK) allow greater synergistic bioactivity than individual cytokines. Another promising approach is experimental targeting of the NLRP3 inflammasome, amply expressed in the CNS and a key contributor to neuroinflammation. Serendipitous discovery is not to be discounted. Filling in knowledge gaps between pediatric- and adult-onset neuroinflammation by systematic collection of CSF data on CKs/cytokines in temporal and clinical contexts and incorporating immunobiomarkers in clinical trials is a challenge hereby set forth for clinicians and researchers.

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Section: Comparison Of Csf Ck/cytokine Immunomarker Profiles In Humanmentioning

confidence: 99%

Section: Comparison Of Csf Ck/cytokine Immunomarker Profiles In Humanmentioning

confidence: 99%

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Pranzatelli

2018

Front. Immunol.

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“…When compared with nafcillin, oxacillin, or cefazolin, ceftriaxone has benefits in terms of lower costs, once- or twice-daily administration, and a favorable long-term side effect profile, making it an attractive drug for outpatient parenteral antibiotic therapy (OPAT) [ 4 , 6 ]. Whether once- or twice-daily ceftriaxone therapy results in acceptable outcomes for patients with MSSA BSI is an open question [ 9 , 10 ]. This study compared outcomes of MSSA BSI among patients discharged on ceftriaxone compared with oxacillin or cefazolin.…”

mentioning

confidence: 99%

Outcomes of Outpatient Parenteral Antimicrobial Therapy With Ceftriaxone for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections—A Single-Center Observational Study

Hamad

Connor

Bailey

et al. 2020

Open Forum Infectious Diseases

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Introduction Staphylococcus aureus blood stream infections (BSI) are associated with significant morbidity and mortality. Ceftriaxone is convenient for outpatient parenteral antimicrobial therapy (OPAT), but data for this indication are limited. Methods Adult patients with MSSA BSI discharged on OPAT with cefazolin, oxacillin, or ceftriaxone for at least 7 days were included. We compared outcomes of ceftriaxone vs either oxacillin or cefazolin. Ninety-day all-cause mortality, readmission due to MSSA infection, and microbiological failure were examined as a composite outcome and compared among groups. Rates of antibiotic switches due to intolerance were assessed. Results Of 243 patients included, 148 (61%) were discharged on ceftriaxone and 95 (39%) were discharged on either oxacillin or cefazolin. The ceftriaxone group had lower rates of ICU care, endocarditis, and shorter duration of bacteremia, but higher rates of cancer diagnoses. There was no significant difference in the composite adverse outcome in the oxacillin or cefazolin group vs the ceftriaxone group [18 (19%) vs 31 (21%), P 0.70] comprising microbiological failure [6 (6.3%) vs 9 (6.1%), P 0.94], 90-day all-cause mortality [7 (7.4%) vs 15 (10.1%), P 0.46] or readmission due to MSSA infection [10 (10.5%) vs 13 (8.8 %), P 0.65]. Antibiotic intolerance necessitating a change was similar between the two groups [4 (4.2%) vs 6 (4.1%), P 0.95]. Conclusion For patients with MSSA BSI discharged on OPAT, within the limitations of the small numbers and retrospective design we did not find a significant difference in outcomes for ceftriaxone therapy when compared to oxacillin or cefazolin therapy

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“…In particular, HSV infection was the most significantly enriched pathway in FUS-ALS patients associated with zinc-finger proteins as the major key involved genes. Notably, the majority of the enriched pathways in ALS patients have already been associated with ALS pathogenesis, such as immune/inflammatory response, T cell activation, viral infection and apoptosis [ 28 , 29 , 30 , 31 , 32 , 33 ]. The top significant pathways are given in Figure 2 B and the full list of all KEGG pathways is given in Table S3 .…”

Section: Resultsmentioning

confidence: 99%

Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis

Dash

Naumann

Sterneckert

et al. 2020

IJMS

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Amyotropic lateral sclerosis (ALS) is a lethally progressive and irreversible neurodegenerative disease marked by apparent death of motor neurons present in the spinal cord, brain stem and motor cortex. While more and more gene mutants being established for genetic ALS, the vast majority suffer from sporadic ALS (>90%). It has been challenging, thus, to model sporadic ALS which is one reason why the underlying pathophysiology remains elusive and has stalled the development of therapeutic strategies of this progressive motor neuron disease. To further unravel these pathological signaling pathways, human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from FUS- and SOD1 ALS patients and healthy controls were systematically compared to independent published datasets. Here through this study we created a gene profile of ALS by analyzing the DEGs, the Kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome and the transcription factor profiles (TF) that would identify altered molecular/functional signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs). Our findings suggest that FUS and SOD1 may develop from dysregulation in several unique pathways and herpes simplex virus (HSV) infection was among the topmost predominant cellular pathways connected to FUS and not to SOD1. In contrast, SOD1 is mainly characterized by alterations in the metabolic pathways and alterations in the neuroactive-ligand–receptor interactions. This suggests that different genetic ALS forms are singular diseases rather than part of a common spectrum. This is important for patient stratification clearly pointing towards the need for individualized medicine approaches in ALS.

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NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis

Cited by 29 publications

References 34 publications

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Outcomes of Outpatient Parenteral Antimicrobial Therapy With Ceftriaxone for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections—A Single-Center Observational Study

Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis

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