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Multiple Sclerosis and Related Disorders Jul 2022Several studies have shown the efficacy of rituximab (RTX) in preventing relapses in patients suffering from Neuromyelitis Optica spectrum disorder (NMSOD) and have... (Review)
Review
INTRODUCTION
Several studies have shown the efficacy of rituximab (RTX) in preventing relapses in patients suffering from Neuromyelitis Optica spectrum disorder (NMSOD) and have explored different therapeutic schemes. Given the extreme inter-individual variability of the disease course, there is the need to identify biomarkers to tailor the retreatment schedule and dosage. This review aimed to identify the most useful biomarker to guide reinfusion and, in turn, the optimal retreatment schedule of RTX for NMSOD.
METHODS
The literature search was conducted in the Web of Science, Scopus and Pubmed electronic databases. We limited document type to articles written in English and published up to 28 February 2022. Inclusion criteria were: (i) Patients affected by NMSOD and treated with RTX, (ii) followed up for at least one year and for whom Annualized Relapse rate (ARR) was collected over a period of at least 12 months before and after therapy initiation and (iii) induction protocols consisting of 375 mg / m2 / week for four weeks or 1000 mg infused once or twice two weeks apart. Collected information was: first authors' name, publication year, study design, sample size, sex, age, percentage of patients positive for antibodies to aquaporin 4 (AQP4-IgG), maintenance regimen, primary outcome, mean ARR pre-therapy and mean ARR post-therapy initiation, percentage of relapse-free patients. The primary outcome that we considered was the ARR reduction. Further, we considered the number of relapses that occurred when B cells and memory B cells were under the chosen threshold and the percentage of relapse-free patients when available.
RESULTS
Among 31 potentially eligible studies, 9 fulfilled the inclusion criteria. ARR reduction was not comparable between studies. The studies that monitored CD19+ and CD27+ cell kinetics showed a higher number of relapses when CD19+ lymphocyte count was below the threshold compared to the number of relapses that occurred when CD27+ cell count was below the threshold. Further, a higher percentage of patients achieved the relapse-free condition with a reinfusion schedule when CD27+ reached 0, 05% of peripheral blood mononuclear cells (PBMCs) compared to the reinfusion when CD19+ reached 0, 1% of PBMCs.
CONCLUSIONS
To date, the optimal retreatment schedule for RTX in NMOSD has not yet been determined. However, the presented findings suggest that CD27+ B cells might be a reliable biomarker to guide retreatment in AQP4-IgG positive patients, at least in the first six months from the infusion. Further effort is needed to identify those factors influencing anti-CD20 therapy effectiveness to tailor dosage and treatment schedule to achieve the most favourable risk/benefit ratio.
Topics: Aquaporin 4; Biomarkers; Humans; Immunoglobulin G; Leukocytes, Mononuclear; Neuromyelitis Optica; Recurrence; Retreatment; Rituximab
PubMed: 35661568
DOI: 10.1016/j.msard.2022.103926 -
Journal of Neurovirology Apr 2022Neuromyelitis optica spectrum disorder (NMOSD) is a severe, inflammatory, immune-mediated astrocytopathy of the central nervous system, characterized by recurrent... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, inflammatory, immune-mediated astrocytopathy of the central nervous system, characterized by recurrent inflammatory events primarily involving optic nerves and the spinal cord. Recently, a triggering role of infectious events in the development of NMOSD has been suggested. Varicella zoster virus (VZV) is the agent most involved, although the linkage with anti-aquaporin-4 antibodies is so far unknown. A review of the literature on the association between NMOSD and VZV infection was carried out by searching PUBMED and EMBASE from 1975 to July 2020. A total of 13 articles concerning Herpes zoster preceding NMOSD were identified. All patients were female and the median age at NMOSD presentation was 28.5 (range 5-63) years. Four NMOSD cases occurred after chicken pox while the remaining ten after HZ. Full recovery occurred in 5/14 patients. From the review of the literature, we can infer that VZV seems to trigger LETM attacks and not the disease itself. The strict temporal relationship between VZV infection and NMOSD seems to exceed the pure chance and represents an unusual clinical scenario posing several diagnostic and management challenges.
Topics: Aquaporin 4; Autoantibodies; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Neuromyelitis Optica
PubMed: 35462584
DOI: 10.1007/s13365-022-01065-4 -
Multiple Sclerosis and Related Disorders Feb 2022The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and...
INTRODUCTION
The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports.
METHOD
Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared.
RESULT
Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status.
DISCUSSION
The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports.
CONCLUSION
Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals.
Topics: Adolescent; Adult; Humans; Middle Aged; Young Adult; Aquaporin 4; Autoantibodies; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Influenza A Virus, H1N1 Subtype; Neoplasm Recurrence, Local; Neuromyelitis Optica; SARS-CoV-2; Vaccination
PubMed: 35216789
DOI: 10.1016/j.msard.2021.103414 -
Multiple Sclerosis and Related Disorders Nov 2021NMOSD: is a disease shown to be highly associated with other diseases such as autoimmune diseases. There are a few reports of this association with cancer. So, this... (Review)
Review
UNLABELLED
NMOSD: is a disease shown to be highly associated with other diseases such as autoimmune diseases. There are a few reports of this association with cancer. So, this systematic review aimed to obtain a broad understanding on the cancers associated in NMOSD, including the source of common perceptions and assumptions in this regard.
METHODS
in this study, we systematically searched the PubMed, EMBASE, SCOPUS, Web of Sciences, Proquest, Ovid, conference proceedings, and reference lists of the retrieved articles. All NMOSD cases who met the last version of criteria for its diagnosis, which reported the patients with a history of cancer before or after the onset of neurological symptoms without time limitations, and those who were referred as paraneoplastic neuromyelitis optica in articles published in English language (both the abstract & full text), were assessed. Finally, each study was critically appraised.
RESULTS
Only 47 studies met the inclusion criteria, so they were assessed for qualitative synthesis. Considering the Euro network criteria, only 62 cases met this issue. The mean age of 52.21 ± 17.14 and 52.16 ± 17.21 was reported for cancer and NMOSD cases with female predominance (79%), respectively. The most reported organ in the cancer population were genitourinary (n = 14, 22.3%), breast (n = 12, 19.4%), lung (n = 12, 19.3%), gastrointestinal (n = 7, 11.3%), and hematology (n = 6, 9.7%), respectively.
CONCLUSION
In older NMOSD patients without suspicious symptoms, we recommend paying more attention to lung, breast and genitourinary (especially ovary) cancer screening. Also, cancer resection had positive effect on the attack numbers after receiving treatment and NMOSD recovery.
Topics: Adult; Aged; Aquaporin 4; Autoantibodies; Autoimmune Diseases; Female; Humans; Male; Middle Aged; Neoplasms; Neuromyelitis Optica
PubMed: 34536774
DOI: 10.1016/j.msard.2021.103227 -
Multiple Sclerosis and Related Disorders Oct 2021Neuromyelitis Optica Spectrum Disorder can be associated with parainfectious and post-infectious triggers. Dengue virus infection is one of the most common arbovirus...
BACKGROUND
Neuromyelitis Optica Spectrum Disorder can be associated with parainfectious and post-infectious triggers. Dengue virus infection is one of the most common arbovirus infections in the world, and may present with neurological manifestations.
OBJECTIVES
We present a case of DENV-associated with LETM and positive aquaporin-4 IgG, and a systematic review of published cases.
METHODS
Medline (Ovid) and PubMed were search through June 2021, for case reports, series and observational studies that described patients with DENV-associated LETM and/or NMOSD.
RESULTS
An adolescent girl who had recently immigrated from a Dengue-endemic region presented with a LETM with high positive AQP4-IgG titer and seropositive DENV IgM/IgG antibodies. She responded well to steroids and subsequently started maintenance rituximab for her NMOSD diagnosis.
LITERATURE REVIEW
22 publications describing 27 patients met inclusion criteria. In addition to this case, three published cases met current criteria for NMOSD with serological evidence of acute DENV infection.
CONCLUSIONS
It is unknown whether there is a pathophysiological association between DENV infection and NMOSD. Regardless, if an immune-mediated event is suspected, particularly NMOSD, appropriate immunotherapy should be considered early. Decision regarding long term immunotherapy may depend on index of suspicion of true NMOSD, and this is where AQP4-IgG status and follow-up is helpful.
Topics: Adolescent; Aquaporin 4; Autoantibodies; Dengue; Female; Humans; Immunoglobulin G; Myelitis, Transverse; Neuromyelitis Optica
PubMed: 34418736
DOI: 10.1016/j.msard.2021.103206 -
Multiple Sclerosis and Related Disorders Sep 2021the distinct MRI features of MOG-antibody disease (MOG-AD) and AQP4-NMOSD are still poorly defined. We performed a systematic review and meta-analysis to identify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
the distinct MRI features of MOG-antibody disease (MOG-AD) and AQP4-NMOSD are still poorly defined. We performed a systematic review and meta-analysis to identify specific patterns of MRI abnormalities able to discriminate between MOG-AD and AQP4-NMOSD.
METHODS
fourteen case-series (1028 patients) were included. Outcomes were MRI lesion patterns in optic nerve (ON), brain and spinal cord (SC) that were selected after a systematic literature review and analysed separately as the event rate for individual MRI lesions in MOG-AD (experimental group) and AQP4-NMOSD (control group) by using a random effect model.
RESULTS
MOG-AD showed a higher number of MRI lesions than AQP4-NMOSD patients in the retrobulbar ON (OR=5.67; 95%CI=2.11-15.24; p=0.0006) with ON head swelling (OR=8.20; 95%CI=4.13-16.28; p<0.00001), corpus callosum (OR=2.30; 95%CI=1.11-4.76; p=0.02), pons (OR=2.87; 95%CI=1.45-5.67; p=0.002), and lumbar/conus SC (OR=3.47; 95%CI=1.66-7.24; p=0.0009). Conversely, lesions in the canalicular (OR=0.42; 95%CI=0.18-0.98; p=0.05) and intracranial ON (OR=0.30; 95%CI=0.11=0.84; p=0.02), area postrema (OR=0.12; 95%CI=0.02-0.61; p=0.01), medulla (OR=0.40; 95%CI=0.20-0.78; p=0.007), and cervical SC (OR=0.29; 95%CI=0.09-0.92; p=0.04) were prominent in patients with AQP4-NMOSD. Participants' age was found to be a source of heterogeneity across studies.
CONCLUSION
our study provides further evidence that MOG-AD and AQP4-NMOSD have distinct MRI features that may help clinicians for an early differential diagnosis.
Topics: Aquaporin 4; Autoantibodies; Humans; Magnetic Resonance Imaging; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica
PubMed: 34246019
DOI: 10.1016/j.msard.2021.103118 -
Multiple Sclerosis and Related Disorders Aug 2021Despite inclusion in neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases are increasingly... (Meta-Analysis)
Meta-Analysis Review
The occurrence of myelin oligodendrocyte glycoprotein antibodies in aquaporin-4-antibody seronegative Neuromyelitis Optica Spectrum Disorder: A systematic review and meta-analysis.
BACKGROUND
Despite inclusion in neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases are increasingly recognized as an independent disease entity. In this study, we conducted a systematic review and meta-analysis to comprehensively update the rate of occurrence of MOG-Ab in Aquaporin4 (AQP4)-antibody seronegative NMOSD.
METHODS
We searched PubMed, EMBASE, and Cochrane databases for studies reporting the rates of patients with MOG-Ab in NMOSD. Fixed or random-effects models were used to pool results across studies.
RESULTS
Fourteen studies met the inclusion criteria. Overall, MOG-Abs positive patients comprised 9.3% of all NMO/NMOSD (95% confidence interval [CI] 7.9%-10.8%, I = 13.1%), 32.5% of all AQP4-Ab seronegative NMO/NMOSD (95% CI 25.7%-39.3%, I = 45.8%), and 41.6% of AQP4-Ab seronegative NMOSD cases diagnosed by IPND 2015 criteria (95% CI 35.1%-48.2%, I = 0.0%). The pooled prevalence of MOG-Ab was 31.0% among Asian AQP4-Ab seronegative NMO/NMOSD patients (95% CI 22.1%-39.9% I=54.1%) and 34.3% in European seronegative NMO/NMOSD (95% CI 21.9%-46.7%, I = 51.9%).
CONCLUSIONS
This study shows that MOG-Abs represent a substantial proportion of AQP4-Ab seronegative NMOSD patients despite different underlying mechanisms, clinical manifestations, and treatment response, suggesting MOG-Ab screening in AQP4-Ab seronegative NMOSD patients can facilitate accurate diagnoses and treatments.
Topics: Aquaporin 4; Autoantibodies; Humans; Mass Screening; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica
PubMed: 34118585
DOI: 10.1016/j.msard.2021.103030 -
MSystems Dec 2020The spread of carbapenem- and polymyxin-resistant poses a significant threat to public health, challenging clinicians worldwide with limited therapeutic options. This... (Review)
Review
The spread of carbapenem- and polymyxin-resistant poses a significant threat to public health, challenging clinicians worldwide with limited therapeutic options. This review describes the current coding and noncoding genetic and transcriptional mechanisms mediating carbapenem and polymyxin resistance, respectively. A systematic review of all studies published in PubMed database between 2015 to October 2020 was performed. Journal articles evaluating carbapenem and polymyxin resistance mechanisms, respectively, were included. The search identified 171 journal articles for inclusion. Different New Delhi metallo-β-lactamase (NDM) carbapenemase variants had different transcriptional and affinity responses to different carbapenems. Mutations within the carbapenemase (KPC) mobile transposon, Tn, affect its promoter activity and expression levels, increasing carbapenem resistance. Insertion of IS in increased imipenemase expression 53-fold. porin downregulation (mediated by and mutations), small RNA hyperexpression, efflux upregulation (mediated by , , , , , , etc.), and mutations in - mediated clinical carbapenem resistance when coupled with β-lactamase activity in a species-specific manner but not when acting without β-lactamases. Mutations in , , , and affect phosphorylation of lipid A of the lipopolysaccharide through the ( or ) cluster, leading to polymyxin resistance; inactivation also affected capsule structure. Mobile and induced , efflux hyperexpression and porin downregulation, and Ecr transmembrane protein also conferred polymyxin resistance and heteroresistance. Carbapenem and polymyxin resistance is thus mediated by a diverse range of genetic and transcriptional mechanisms that are easily activated in an inducing environment. The molecular understanding of these emerging mechanisms can aid in developing new therapeutics for multidrug-resistant isolates.
PubMed: 33323413
DOI: 10.1128/mSystems.00783-20 -
Lupus Mar 2021Myelin oligodendrocyte glycoprotein (MOG) is a nervous system protein expressed by oligodendrocytes to constitute the myelin sheath. Autoantibodies against MOG have been...
INTRODUCTION
Myelin oligodendrocyte glycoprotein (MOG) is a nervous system protein expressed by oligodendrocytes to constitute the myelin sheath. Autoantibodies against MOG have been widely described in neurological and autoimmune diseases such as MOG-IgG-associated disorder (MOGAD).Although underlying mechanisms have not yet been understood, an overlap of MOGAD and Systemic Lupus Erythematosus (SLE) has been shown in the literature.
OBJECTIVES
The aim of this systematic review was to assess the possible correlations between MOGAD and SLE based on reported features found in the literature that support the association of the two.
METHODS
A keyword-based literature search was conducted, applying a ten-year filter and using the following key-words: "MOG autoantibody-associated disease and Systemic Lupus Erythematosus"; "MOG and Systemic Lupus Erythematosus" "Anti-MOG and Lupus"; "MOG and SLE"; "MOG and LUPUS" on MEDLINE/PUBMED, ScienceDirect, SciELO, LILACS and Cochrane; and "MOG antibody-associated disease and SLE" on Google Scholar.
RESULTS
Eleven publications reporting on the MOGAD and SLE correlation were included in qualitative synthesis: animal experiment (1), cross-sectional (3), prospective (2), retrospective (1), non-systematic review (3), and case report (1) studies.
CONCLUSION
Not much is known about the connection between MOG-IgG-associated disorder and SLE. Unfortunately, only observational studies have been conducted in humans so far, providing us with limited data. While MOGAD features have been reported to develop in SLE patients, this is not an universal finding. In fact, many different issues impair these results, making it difficult to match the findings of different studies.
Topics: Animals; Aquaporin 4; Autoantibodies; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Observational Studies as Topic
PubMed: 33290135
DOI: 10.1177/0961203320978514 -
Journal of Neurology Nov 2021Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of... (Review)
Review
INTRODUCTION
Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of proteins which regulates water exchange, in particular AQP4 and 1. Alterations of glymphatic fluid circulation through AQPs variations are now emerging as central elements in the pathophysiology of different brain conditions, like hydrocephalus. This systematic review provides an insight about the role of AQPs in hydrocephalus establishment and compensation, investigating their possible role as diagnostic tools or therapeutic targets.
METHODS
PubMed database was screened searching for the relevant existing literature in English language published until February 29th 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.
RESULTS
A total of 40 articles met the inclusion criteria for our systematic analysis. AQP4 resulted the most studied water channel, followed by AQP1. The changes in cerebrospinal fluid (CSF), brain parenchyma and choroid plexus (CP) in different hydrocephalus type were analyzed. Moreover, important pharmacological interactions regarding AQP and molecules or conditions were discussed. A very interesting result is the general consensus on increase of AQP4 in hydrocephalic patients, unless in patients suffering from idiopathic normal pressure hydrocephalus, where AQP4 shows a tendency in reduction.
CONCLUSION
AQP seem to play a central role in the pathophysiology of hydrocephalus and in its compensation mechanisms. Further studies are required to definitively establish their precise roles and their quantitative changes to allow their utilization as diagnostic tools or therapeutic targets.
Topics: Aquaporin 4; Aquaporins; Brain; Humans; Hydrocephalus
PubMed: 32747978
DOI: 10.1007/s00415-020-10122-z