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Muscle & Nerve Aug 2017Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from... (Review)
Review
Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20 B-cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56: 185-196, 2017.
Topics: Humans; Immunologic Factors; Myasthenia Gravis; Rituximab
PubMed: 28164324
DOI: 10.1002/mus.25597 -
Multiple Sclerosis and Related Disorders Jun 2022There are increasing reports of COVID-19 related neurological complications which may be due to direct viral invasion, or immune mediated inflammatory diseases such as... (Review)
Review
INTRODUCTION
There are increasing reports of COVID-19 related neurological complications which may be due to direct viral invasion, or immune mediated inflammatory diseases such as autoimmune encephalitis and ADEM (acute demyelinating encephalomyelitis). In this study, a systematic review is presented of the reported cases infected by the COVID-19 who were diagnosed with various forms of autoimmune encephalitis (AE).
METHODS
The authors searched three databases including PubMed, Scopus, and Web of science for extracting original articles on coronavirus/ COVID-19 and AE.
RESULTS
Eighteen articles were considered in this study, including 15 case reports, and three case series with a total of 81 patients. Among the studies, 19 cases were reported with AE including 7 (37%) cases of limbic encephalitis, 5 (26%) patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 2 (11%) with AE presenting as new-onset refractory status epilepticus (NORSE), 1 (5%) case of steroid-responsive encephalitis, and 4 (21%) cases with an unknown type of AE.
CONCLUSION
Our systematic review revealed evidence on AE development in patients infected with the COVID-19. Clinicians should be aware of the possible diagnosis of AE when considering other neurological differential diagnosis in SARS-CoV-2 infected patients.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; COVID-19; Encephalitis; Hashimoto Disease; Humans; SARS-CoV-2
PubMed: 35472834
DOI: 10.1016/j.msard.2022.103795 -
JAMA Neurology Jul 2021Encephalitis is a severe immune-related adverse event secondary to treatment with immune checkpoint inhibitors (ICIs). The spectrum of ICI-induced encephalitis (ICI-iE)...
IMPORTANCE
Encephalitis is a severe immune-related adverse event secondary to treatment with immune checkpoint inhibitors (ICIs). The spectrum of ICI-induced encephalitis (ICI-iE) ranges from disease that resolves fully to lethal forms. Moreover, ICIs may unmask a paraneoplastic encephalitis. To our knowledge, the factors associated with ICI-iE prognosis are unknown.
OBJECTIVES
To evaluate the presentation of ICI-iE and to identify features helpful in assessing outcomes.
EVIDENCE REVIEW
This systematic review pooled case series from the published literature (n = 77) and medical records from 1 center (n = 5) to assess the association between the form of ICI-iE presentation and its prognosis. Eligibility criteria included references identified by searches of PubMed and Web of Knowledge databases in the English literature from June 2000 (first patient dose of ipilimumab) to April 17, 2020, that examined patients with encephalitis with presumed autoimmune etiologic features induced by ICIs. Information regarding clinical, cerebrospinal fluid, and neuroimaging (magnetic resonance imaging) features, as well as treatment given, were extracted.
FINDINGS
A total of 82 patients (52 men [63%]; median age, 61.0 years [interquartile range, 52.5-70.0 years]) were included. Most patients presented with focal syndromes (39 [48%]) or meningoencephalitis (36 [44%]). Seven patients (9%) had nonclassifiable ICI-iE. Neuronal autoantibodies were detected in 23 patients with focal syndromes and 1 patient with nonclassifiable ICI-iE. Most autoantibodies were onconeuronal (17 of 24 [71%]), targeting intracellular antigens. Patients without a focal syndrome or with a negative-antibody focal syndrome had a good prognosis (49 of 55 [89%]). Among patients with autoantibodies, those with anti-glutamic acid decarboxylase or anticell surface responded to treatment and had a favorable prognosis (100%). However, patients with other autoantibodies had poor outcomes (17 of 24 [71%]). Antineuronal autoantibodies (13 of 24 [54%] vs 5 of 41 [12%]; P < .001), focal syndrome (16 of 39 [41%] vs 4 of 43 [9%]; P = .001), and abnormal magnetic resonance imaging findings (14 of 39 [36%] vs 4 of 32 [13%]; P = .02) were associated with poor outcomes. Conversely, fever (21 of 23 [91%] vs 41 of 59 [70%]; P = .04) and more inflammatory changes in cerebrospinal fluid (30 of 31 [97%] vs 21 of 33 [64%]; P = .001) were associated with a better prognosis.
CONCLUSIONS AND RELEVANCE
Immune checkpoint inhibitors may induce mainly 2 different encephalitic syndromes: a focal limbic or extralimbic encephalitis and a meningoencephalitis. Immune checkpoint inhibitor-induced encephalitis is associated with an overall favorable outcome, with a low rate of fatal events. An undetected preexisting paraneoplastic encephalitic syndrome may be triggered by ICIs, and this type of syndrome has the worst outcome among all the different types of ICI-induced encephalitis syndromes. Clinical presentation and systematic measurement of autoantibodies will be a helpful guide for the therapeutic strategy and for counseling regarding prognosis.
Topics: Adult; Aged; Autoantibodies; Encephalitis; Female; Humans; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Magnetic Resonance Imaging; Male; Melanoma; Middle Aged; Nivolumab
PubMed: 33720308
DOI: 10.1001/jamaneurol.2021.0249 -
Neurology Apr 2021To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).
OBJECTIVE
To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).
METHODS
Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; < 0.001). Anti-programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; = 0.005) and less common in meningitis (2/13, 15%; < 0.001) and cranial neuropathies (13/31, 42%; = 0.005). Anti-cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; < 0.001) and less common in encephalitis (2/56, 4%; = 0.009) and myositis (12/136, 9%; = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; = 0.003) and less common in encephalitis (19/56, 34%; = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%).
CONCLUSION
Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Nervous System Diseases
PubMed: 33653902
DOI: 10.1212/WNL.0000000000011795 -
European Journal of Neurology Feb 2022New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active... (Review)
Review
BACKGROUND AND PURPOSE
New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions.
METHODS
A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome.
RESULTS
Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described.
CONCLUSIONS
Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.
Topics: Adult; Child; Drug Resistant Epilepsy; Encephalitis; Epileptic Syndromes; Humans; Retrospective Studies; Status Epilepticus
PubMed: 34661330
DOI: 10.1111/ene.15149 -
Journal For Immunotherapy of Cancer Nov 2019Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication.
METHODS
We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases.
RESULTS
Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011).
CONCLUSIONS
MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Biomarkers; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Molecular Targeted Therapy; Myasthenia Gravis; Neoplasms; Symptom Assessment
PubMed: 31753014
DOI: 10.1186/s40425-019-0774-y -
Autoimmunity Reviews Mar 2022Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement.
OBJECTIVE
To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis.
METHODS
A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study.
RESULTS
Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13).
CONCLUSION
IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.
Topics: Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Myasthenia Gravis; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 34920107
DOI: 10.1016/j.autrev.2021.103019 -
European Journal of Neurology Dec 2023Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn)... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. The aim of this study was to perform a meta-analysis and network meta-analysis of randomized and placebo-controlled trials of innovative therapies in MG with available efficacy data.
METHODS
We assessed statistical heterogeneity across trials based on the Cochrane Q test and I values, and mean differences were pooled using the random-effects model. Treatment efficacy was assessed after 26 weeks of eculizumab and ravulizumab, 28 days of efgartigimod, 43 days of rozanolixizumab, 12 weeks of zilucoplan, and 16, 24 or 52 weeks of rituximab treatment.
RESULTS
We observed an overall mean Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) score change of -2.17 points (95% confidence interval [CI] -2.67, -1.67; p < 0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti-FcRn treatment (p = 0.16). The change in Quantitative Myasthenia Gravis scale (QMG) score was -3.46 (95% CI -4.53, -2.39; p < 0.001), with a higher reduction with FcRns (-4.78 vs. -2.60; p < 0.001). Rituximab did not significantly improve the MG-ADL (-0.92 [95% CI -2.24, 0.39]; p = 0.17) or QMG scores (-1.9 [95% CI -3.97, 0.18]; p = 0.07). In the network meta-analysis, efgartigimod had the highest probability of being the best treatment, followed by rozanolixizumab.
CONCLUSION
Anti-complement and FcRn treatments both proved to be effective in MG patients, whereas rituximab did not show a significant benefit for patients. Within the limitations of this meta-analysis, including efficacy time points, FcRn treatments showed a greater effect on QMG score in the short term. Real-life studies with long-term measurements are needed to confirm our results.
Topics: Infant, Newborn; Humans; Rituximab; Network Meta-Analysis; Activities of Daily Living; Myasthenia Gravis; Complement Inactivating Agents; Therapies, Investigational
PubMed: 37204031
DOI: 10.1111/ene.15872 -
Journal of Translational Medicine Dec 2021Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies on the epidemiology of myasthenia gravis in different parts of the world and the effectiveness of common drugs in its treatment, but there has been no comprehensive study of the efficacy of common drugs in the treatment of myasthenia gravis. Therefore, this study aimed to determine the epidemiology of myasthenia gravis globally and the effectiveness of common drugs in its treatment using systematic review and meta-analysis.
METHODS
Research studies were extracted from IranDoc, MagIran, IranMedex, SID, ScienceDirect, Web of Sciences (WoS), ProQuest, Medline (PubMed), Scopus and Google Scholar based on Cochran's seven-step guidelines using existing keywords extracted in MeSH browser. The I test was used to calculate the heterogeneity of studies, and Begg and Mazumdar rank correlation tests were used to assess publication bias. Data were analyzed using Comprehensive Meta-Analysis software (Version 2).
RESULTS
In the search for descriptive studies based on the research question, 7374 articles were found. After deleting articles unrelated to the research question, finally, 63 articles with a sample size of 1,206,961,907 people were included in the meta-analysis. The prevalence of MG worldwide was estimated to be 12.4 people (95% CI 10.6-14.5) per 100,000 population. For analytical studies on the effectiveness of common myasthenia gravis drugs, 4672 articles were found initially, and after removing articles unrelated to the research question, finally, 20 articles with a sample size of 643 people in the drug group and 619 people in the placebo group were included in the study. As a result of the combination of studies, the difference between the mean QMGS score index after taking Mycophenolate and Immunoglobulin or plasma exchange drugs in the group of patients showed a significant decrease of 1.4 ± 0.77 and 0.62 ± 0.28, respectively (P < 0.01).
CONCLUSION
The results of systematic review of drug evaluation in patients with myasthenia gravis showed that Mycophenolate and Immunoglobulin or plasma exchange drugs have positive effects in the treatment of MG. It also represents the positive effect of immunoglobulin or plasma exchange on reducing SFEMG index and QMGS index and the positive effect of Mycophenolate in reducing MG-ADL index, SFEMG and Anti-AChR antibodies index. In addition, based on a meta-analysis of the random-effect model, the overall prevalence of MG in the world is 12.4 people per 100,000 population, which indicates the urgent need for attention to this disease for prevention and treatment.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Plasma Exchange; Prevalence
PubMed: 34930325
DOI: 10.1186/s12967-021-03185-7 -
The Oncologist Dec 2021The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be...
BACKGROUND
The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immune-related adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature.
MATERIALS AND METHODS
Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.
RESULTS
A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICIs (38%). The most-reported symptoms were fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9,645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. Sixty percent of the patients died in hospital because of acute complications.
CONCLUSION
IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition.
IMPLICATIONS FOR PRACTICE
Clinicians should suspect coexisting myositis and/or myasthenia gravis in all patients with immune checkpoint inhibitor-induced myocarditis, given their propensity to occur together. Early recognition and prompt treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.
Topics: Aged; Humans; Immune Checkpoint Inhibitors; Myasthenia Gravis; Myocarditis; Myositis
PubMed: 34378270
DOI: 10.1002/onco.13931