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Frontiers in Neurology 2020Algorithms for the detection of a malignancy in patients with unclear neurologic symptoms of suspicious paraneoplastic origins are not universally applied. Frequently,...
Algorithms for the detection of a malignancy in patients with unclear neurologic symptoms of suspicious paraneoplastic origins are not universally applied. Frequently, circulating tumor markers (TMs) are considered a valuable tool for cancer diagnosis in patients with paraneoplastic neurologic syndromes (PNS). Our aim was to extract the recommendations on the use of TMs and onconeural antibodies (Abs) for the diagnosis of malignancies in PNS from clinical practice guidelines and put them forward as evidence in a common framework to facilitate diffusion, dissemination, and implementation. Systematic literature searches were performed for guidelines on both oncology and PNS published since 2007. Guidelines containing information and recommendations for clinical practice pertaining to the screening and diagnosis of PNS were selected. Information on circulating TMs and onconeural Abs was extracted and synthesized in consecutive steps of increasing simplification. We retrieved 799 eligible guidelines on oncology for the potential presence of information on PNS but only six covered treated diagnosis or the screening of cancer in PNS, which were then selected. Seventy-nine potentially relevant guidelines on PNS were identified as eligible and 15 were selected. Synoptic tables were prepared showing that classical TMs are not recommended for the screening or the diagnosis of a malignancy in patients with a suspected PNS. Neither should onconeural Abs be considered to screen for the presence of a malignancy, although they could be helpful to define the probability of the paraneoplastic origin of a neurologic disorder. The present work of synthesis may be a useful tool in the diffusion, dissemination, and implementation of guideline recommendations, potentially facilitating the decrease of the inappropriate use of circulating biomarkers for cancer screening in the presence of PNS.
PubMed: 33536995
DOI: 10.3389/fneur.2020.607553 -
Frontiers in Immunology 2022To summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells in the pathogenic mechanism.
METHODS
The PubMed, Cochrane Library, Embase, and Web of Science databases were searched for various articles that assessed the concentrations of cytokines/chemokines in the unstimulated cerebrospinal fluid (CSF) or serum of patients with NMDAR-E in this systematic review and meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by Stata17.0.
RESULTS
A total of 19 articles were included in the systematic review from 260 candidate papers, and cytokine/chemokine levels reported in the CSF/serum were examined in each article. This meta-analysis included 17 eligible studies comprising 579 patients with NMDAR-E, 367 patients with noninflammatory neurological disorders, and 42 healthy controls from China, Spain, South Korea, Australia, Czechia, and Sweden. The results indicated that the levels of different cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, IL-13, IL-1β, IL-12, and IL-17 and chemokine C-X-C motif ligand (CXCL)10 in the CSF were significantly higher in NMDAR-E patients with a large effect size. In addition, B cell activating factor (BAFF), CXCL13, and interferon (IFN)-γ levels in the CSF were higher in NMDAR-E patients with a middle effect size. In contrast, levels of IL-2 and IL-4 in the CSF and CXCL13 and BAFF in the serum did not show a significant difference between cases and controls.
CONCLUSIONS
These analyses showed that the central immune response in NMDAR-E is a process that involves multiple immune cell interactions mediated by cytokines/chemokines, and T cells play an important role in the pathogenesis of immunity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022342485).
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Chemokines; Cytokines; Interleukin-12; Interleukin-6; Tumor Necrosis Factor-alpha
PubMed: 36761173
DOI: 10.3389/fimmu.2022.1064007 -
Frontiers in Immunology 2023A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A series of clinical trials support the effectiveness of monoclonal antibodies for generalized myasthenia gravis (MG) compared to the placebo, but the priority among drugs remains unclear. Therefore, we conduct a frequentist network meta-analysis (NMA) to compare the relative effects of different drugs for generalized MG.
METHODS
PubMed, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched for eligible studies up to 1 June 2023. The primary outcome was efficacy (Myasthenia Gravis Activities of Daily Living [MG-ADL] score and Quantitative Myasthenia Gravis [QMG] score) and safety (adverse events [AEs]). Mean difference (MD) and risk ratio (RR) with their 95% credible intervals (95%CrIs) were used to show the effect size of continuous and categorical variables, respectively. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirteen studies involving 1167 individuals were identified for NMA. For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively). For safety outcomes, belimumab achieved the highest SUCRA value (89.8%) with significant statistical difference compared to rozanolixzumab 7mg/kg (RR 0.08, 95%CrI 0.01 to 0.94) and rozanolixzumab 10mg/kg (RR 0.08, 95%CrI 0.01 to 0.86).
CONCLUSION
While all monoclonal antibodies were superior to the placebo, rozanolixzumab and batoclimab might be the most effective for generalized MG. However, rozanolixzumab was associated with higher incidence of AEs. Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/?s=202370112, identifier 202370112.
Topics: Adult; Humans; Antibodies, Monoclonal; Activities of Daily Living; Bayes Theorem; Myasthenia Gravis
PubMed: 38022544
DOI: 10.3389/fimmu.2023.1280226 -
Current Oncology (Toronto, Ont.) Mar 2024Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic... (Review)
Review
Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing's Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival.
Topics: Male; Humans; Aged; Prostatic Neoplasms; Androgen Antagonists; Paraneoplastic Syndromes
PubMed: 38534956
DOI: 10.3390/curroncol31030123 -
Biomedicines May 2023Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and... (Review)
Review
Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) ( < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson's R = -0.88, < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France ( = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk.
PubMed: 37371620
DOI: 10.3390/biomedicines11061525 -
Brain and Behavior Jan 2023Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are identified as significant psychiatric problems that MG people face. However, there is no sufficient epidemiological information about depression and anxiety-based publication. Due to this limitation, the aim of this study was to review the prevalence of depression and anxiety in MG patients.
METHODS
Original and international databases were searched to find papers about the estimation of anxiety and depression. Random-effects analysis was used for calculating the proportions of anxiety and depression. For estimating anxiety and depression based the severity, instruments, type of studies, and study regions, subgroup analysis was performed.
RESULTS
38 studies met inclusion criteria and entered study. The pooling of the prevalence of depression was found at 36%, (95% CI 28% to 45%). Also, prevalence of anxiety was found at 33%, (95% CI 25% to 42%). Prevalence of depression based on mild, moderate, and severe level was 27%, 14%, and 9%, respectively.
CONCLUSIONS
Anxiety and depression are a major concern among MG individuals. The estimation of both anxiety and depression are high even when compared to other autoimmune diseases. It seems depression and anxiety are important issues and more attention needs to be paid to these psychiatric disorders.
Topics: Humans; Depression; Prevalence; Anxiety; Anxiety Disorders; Myasthenia Gravis
PubMed: 36495116
DOI: 10.1002/brb3.2840 -
Journal of Neurology Feb 2022Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association... (Review)
Review
BACKGROUND
Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association between CNS demyelination and viral infection has long been documented, and this link was recently reported following SARS-CoV-2 infection as well.
OBJECTIVES
In this systematic review, we aim to investigate the existing literature on CNS demyelination associated with SARS-CoV-2, and the proposed pathophysiological mechanisms.
METHODS
We conducted a systematic review of articles in PubMed, SCOPUS, EMBASE, Cochrane, Google Scholar and Ovid databases, from 1 January 2020 until June 15, 2021. The following keywords were used: "COVID-19", "SARS-CoV-2", "demyelination", "demyelinating disease", "multiple sclerosis", "neuromyelitis optica", and "transverse myelitis".
RESULTS
A total of 60 articles were included in the final analysis of this systematic review and included 102 patients: 52 (51%) men and 50 (49%) women, with a median age of 46.5 years. The demyelination mimicked a variety of conditions with a picture of encephalitis/encephalomyelitis being the most common. At the same time other patterns were less frequently reported such as MS, NMOSD and even MOGAD. Longitudinally extensive transverse myelitis (LETM) was the most frequently reported pattern of spinal cord involvement.
CONCLUSION
A growing body of literature has shown an association between SARS-CoV-2 infection and the development of different types of CNS demyelination. Although causality cannot readily be inferred, this review may suggest a probable causal relationship, through a para-infectious or post-infectious immune-mediated etiology in COVID-19 patients. This relationship needs to be clarified in future research.
Topics: COVID-19; Female; Humans; Male; Middle Aged; Myelitis, Transverse; Neuromyelitis Optica; Pandemics; SARS-CoV-2
PubMed: 34386902
DOI: 10.1007/s00415-021-10752-x -
Frontiers in Immunology 2022The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world, affecting people's lifestyle, economy, and livelihood. Recently, with the...
The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world, affecting people's lifestyle, economy, and livelihood. Recently, with the development of vaccines, the number of infected cases has decreased. Many case reports have revealed that COVID-19 may induce other serious comorbidities such as anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis. Anti-NMDA receptor encephalitis is an acute autoimmune disease that occurs more commonly in women than in men. To explore the association between COVID-19 and anti-NMDA receptor encephalitis, the microRNA (miRNA) biomarkers of COVID-19, anti-NMDA receptor encephalitis, and other related diseases from the literature are reviewed; then on the basis of these miRNA biomarkers, the relationship between COVID-19 and anti-NMDA receptor encephalitis is discussed. miRNAs are small non-coding RNAs that play important roles in cell differentiation, development, cell-cycle regulation, and apoptosis. miRNAs have been used as biological biomarkers for many diseases. The results in this study reveal that the relationship between anti-NMDA receptor encephalitis and COVID-19 infection or COVID-19 vaccination cannot be excluded; however, the risk that COVID-19 triggers the anti-NMDA receptor encephalitis is not high.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Biomarkers; COVID-19; COVID-19 Vaccines; Female; Humans; Male; MicroRNAs
PubMed: 35392089
DOI: 10.3389/fimmu.2022.825103 -
The Journal of Thoracic and... Jul 2020Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and...
OBJECTIVE
Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and paraneoplastic syndromes over the past half century.
METHODS
A primary PubMed/MEDLINE search was used to identify published articles describing paraneoplastic syndromes associated with thymomas from 1960 to 2019. A secondary search identified additional articles referenced in the articles found in the primary search. Kaplan-Meier and log-rank test were used for time-to-event data analyses.
RESULTS
From 407 articles describing 507 patients, 123 different paraneoplastic syndromes were associated with thymoma. The 5 most common paraneoplastic syndromes were myasthenia gravis, pure red cell aplasia, lichen planus, Good syndrome, and limbic encephalitis. Complete or partial resolution of paraneoplastic syndrome symptoms after surgery was noted in 76% of patients, of whom 21% had a relapse or new paraneoplastic syndrome onset after surgery. The most common adjunctive therapy associated with resolution of paraneoplastic syndrome was corticosteroids (30%). For all patients after surgery, thymoma recurrence was observed in 17% of cases, whereas recurrence of paraneoplastic syndrome was observed in 34% of cases, and both were observed in approximately 11% of cases. The 5- and 10-year overall survivals were 78% and 66%, respectively. Improved overall survival was associated with patients who had total resolution from paraneoplastic syndrome.
CONCLUSIONS
A comprehensive assessment of publications over the past half century suggests that a multimodal treatment approach that includes surgical resection of thymomas is able to achieve paraneoplastic syndrome resolution in a majority of patients. Onset of new paraneoplastic syndromes after surgery is associated with the recurrence of the first paraneoplastic syndrome, and resolution of paraneoplastic syndrome is associated with improved overall survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Neoplasm Recurrence, Local; Paraneoplastic Syndromes; Thymoma; Treatment Outcome; Young Adult
PubMed: 31982129
DOI: 10.1016/j.jtcvs.2019.11.052 -
BMC Neurology Dec 2023Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and...
BACKGROUND
Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination.
METHODS
We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies.
RESULTS
A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based.
CONCLUSION
COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.
Topics: Adult; Humans; Female; Male; COVID-19 Vaccines; COVID-19; Neuromuscular Diseases; Myasthenia Gravis; Guillain-Barre Syndrome; Bell Palsy; Facial Paralysis
PubMed: 38082244
DOI: 10.1186/s12883-023-03486-y