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Multiple Sclerosis and Related Disorders May 2024Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD.
METHODS
This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses.
RESULTS
Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95 % CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95 % CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95 % CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95 % CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95 % CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo.
CONCLUSION
NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.
Topics: Neuromyelitis Optica; Humans; Aquaporin 4; Autoantibodies; Complement C5; Randomized Controlled Trials as Topic
PubMed: 38479045
DOI: 10.1016/j.msard.2024.105524 -
International Journal of Molecular... Feb 2024The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the... (Review)
Review
The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the manner of death and for the individuation of forensic markers for the timing of lesions and vitality of injury. In the literature, various tissues have been studied; the most investigated are the lungs, brain, kidneys, skin, and blood vessels. A systematic literature review on PubMed following PRISMA 2020 guidelines enabled the identification of 96 articles. In all, 34 of these were enrolled to identify Aquaporin-like (AQP-like) forensic markers. The analysis of the literature demonstrated that the most significant markers among the AQPs are as follows: for the brain, AQP4, which is very important in brain trauma and hypoxic damage; AQP3 in the skin lesions caused by various mechanisms; and AQP5 in the diagnosis of drowning. Other applications are in organ damage due to drug abuse and thrombus dating. The focus of this review is to collect all the data present in the literature about the forensic application of AQPs as forensic markers in the most important fields of application. In the current use, the individuation, validation, and application of markers in forensic investigation are very useful in real forensic applications in cases evaluated in court.
Topics: Humans; Aquaporins; Lung; Hypoxia; Brain; Skin
PubMed: 38473914
DOI: 10.3390/ijms25052664 -
World Neurosurgery May 2024Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation or even death. Current treatment strategies are limited to decompressive craniectomy and the intravascular administration of hypertonic drugs, which have significant side effects. Acetazolamide (ACZ) plays a therapeutic role in cerebral edema by inhibiting aquaporin-4 (AQP-4) and improving collateral circulation. This study aimed to perform a meta-analysis and systematic review of ACZ therapy for ischemic stroke and evaluate its efficacy in animal models.
METHODS
We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke.
RESULTS
After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, -2.00; 95% confidence interval, -3.57 to -0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference-1.46; 95% confidence interval, -2.01 to -0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals' neurological function is uncertain because of the limited research data.
CONCLUSIONS
ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function.
Topics: Acetazolamide; Ischemic Stroke; Animals; Brain Edema; Humans; Treatment Outcome; Aquaporin 4; Carbonic Anhydrase Inhibitors; Disease Models, Animal
PubMed: 38423457
DOI: 10.1016/j.wneu.2024.02.123 -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
Multiple Sclerosis and Related Disorders Dec 2023This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy.... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy. TCZ is the first monoclonal antibody against the IL-6 receptor for treating NMOSD, and its efficacy and safety vary in different studies. We collected English-language research literature until January 1, 2023, by searching databases such as PubMed, MEDLINE, Embase, Cochrane Library, and clinicaltrials.gov, and identified 9 studies involving 153 patients (139 female and 14 male) that met our inclusion criteria. In these studies, the average ARR ratio and EDSS score reduction values in the TCZ treatment group were -1.34 (95 % CI, -1.60 to -1.09) and -0.81 (95 % CI, -1.04 to -0.58), respectively. Based on the data we have collected, compared to the AQP4-IgG negative NMOSD patients, TCZ demonstrates a more pronounced effectiveness in AQP4-IgG positive NMOSD patients. The study also found that the effectiveness of TCZ in reducing NMOSD patients' ARR ratio was related to gender, race, and TCZ dosage, while the effectiveness of reducing EDSS score was not related to these factors. Among the 153 patients receiving TCZ treatment, 101 (66 %) experienced mild adverse reactions, and one patient experienced a severe adverse reaction (facial cellulitis). The comprehensive data indicate that TCZ treatment can reduce the frequency of NMOSD relapses, improve patients' neurological function, and have good safety. The effectiveness of TCZ in reducing NMOSD patients' ARR ratio is related to multiple factors.
Topics: Humans; Male; Female; Neuromyelitis Optica; Antibodies, Monoclonal, Humanized; Disability Evaluation; Immunoglobulin G; Aquaporin 4
PubMed: 37866020
DOI: 10.1016/j.msard.2023.105062 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Lupus Sep 2023Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those...
BACKGROUND
Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those of neuropsychiatric manifestations of SLE. Pathogenic anti-aquaporin-4 (AQP4) antibodies, commonly found in NMOSD, are responsible for the neuroinflammatory response and secondary demyelinating lesions. These anti-AQP4 antibodies can be the drivers of neuroinflammatory process in SLE patients, which is distinct from the immunopathogenesis seen in traditional neuropsychiatric SLE. The clinical course is often a relapsing one and is managed differently. In this review, we describe and outline the clinical course and outcomes of AQP4+ NMOSD/SLE overlap cases.
METHODS
To investigate the co-existence of SLE with AQP4+NMOSD, we conducted a systematic review of individual patient data from case reports and case series reported in major databases. The study extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both NMOSD and SLE.
RESULTS
In this overlap between SLE and AQP4+NMOSD, a high female preponderance was observed, with 42 out of 46 patients (91.3%) being female. Nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median of 5 years between the two diagnoses. Hematological manifestations were seen in the majority of patients (63%), as well as longitudinally extensive transverse myelitis (87%), and brainstem involvement on imaging (29.6%). Cerebrospinal fluid analysis showed a dominantly lymphocytic pleocytosis, with oligoclonal bands being reported scarcely. Although cyclophosphamide was the most common steroid sparing agent used for maintenance, robust evidence for both efficacy and safety in AQP4+NMOSD is available for mycophenolate mofetil, azathioprine, and rituximab. The majority of reported cases showed a relapsing course, while one patient had a monophasic course.
CONCLUSION
AQP4+NMOSD in SLE patients is a relapsing and neurologically disabling disorder that can mimic neuropsychiatric manifestations, frequently occurs after the onset of lupus or may predate, responds to immunosuppressants, and necessitates indefinite treatment.
Topics: Humans; Female; Male; Neuromyelitis Optica; Lupus Erythematosus, Systemic; Neoplasm Recurrence, Local; Aquaporin 4; Syndrome; Disease Progression; Autoantibodies
PubMed: 37487596
DOI: 10.1177/09612033231191180 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983