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The Cochrane Database of Systematic... Oct 2014In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic... (Review)
Review
BACKGROUND
In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic transmission. Acetylcholinesterase inhibitors provide temporary symptomatic treatment of muscle weakness but there is controversy about their long-term efficacy, dosage and side effects. This is the second update of a review published in The Cochrane Library Issue 2, 2011.
OBJECTIVES
To evaluate the efficacy of acetylcholinesterase inhibitors in all forms of myasthenia gravis.
SEARCH METHODS
On 8 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE for randomised controlled trials and quasi-randomised controlled trials regarding usage of acetylcholinesterase inhibitors in myasthenia gravis. Two authors scanned the articles for any study eligible for inclusion. We also contacted the authors and known experts in the field to identify additional published or unpublished data and searched clinical trials registries for ongoing trials.
SELECTION CRITERIA
The types of studies were randomised or quasi-randomised trials. Participants were myasthenia gravis patients diagnosed by an internationally accepted definition. The intervention was treatment with any form of acetylcholinesterase inhibitor. Types of outcome measures Primary outcome measureImprovement in the presenting symptoms within one to 14 days of the start of treatment. Secondary outcome measures(1) Improvement in the presenting symptoms more than 14 days after the start of treatment.(2) Change in impairment measured by a recognised and preferably validated scale, such as the quantitative myasthenia gravis score, within one to 14 days and more than 14 days after the start of treatment.(3) Myasthenia Gravis Association of America post-intervention status more than 14 days after start of treatment.(4) Adverse events including muscarinic side effects.
DATA COLLECTION AND ANALYSIS
One author (MMM) extracted the data, which were checked by a second author. We contacted study authors for extra information and collected data on adverse effects from the trials.
MAIN RESULTS
We did not find any large randomised or quasi-randomised trials of acetylcholinesterase inhibitors in generalised myasthenia gravis either for the first version of this review or this update. One cross-over randomised trial using intranasal neostigmine in a total of 10 participants was only available as an abstract. It included three participants with ocular myasthenia gravis and seven with generalised myasthenia gravis. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase. Lack of detail in the report meant that the risk of bias was unclear. Adverse events were minor.
AUTHORS' CONCLUSIONS
Except for one small and inconclusive trial of intranasal neostigmine, no other randomised controlled trials have been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. The response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in a placebo arm of treatment would be difficult to justify.
Topics: Administration, Intranasal; Cholinesterase Inhibitors; Humans; Myasthenia Gravis; Neostigmine; Randomized Controlled Trials as Topic
PubMed: 25310725
DOI: 10.1002/14651858.CD006986.pub3 -
Neurological Sciences : Official... Nov 2023Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous... (Review)
Review
The temporal relationship of paraneoplastic aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and breast cancer: a systematic review and meta-analysis.
OBJECTIVE
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous system and is mediated by aquaporin-4 (AQP4) immunoglobulin (IgG). AQP4-IgG may also be present in paraneoplastic syndromes secondary to malignancy such as breast cancer.
METHODS
A systematic review and meta-analysis of the literature were completed using PubMed, Scopus, and ScienceDirect databases (CRD42022352109).
RESULTS
A total of 12 publications, which included 19 cases, met the inclusion criteria and were assessed in both the qualitative and quantitative synthesis. The mean age was 51.26 years (SD: 13.12, SEM: 3.01), and 100% of the cases were reported in women. Speech abnormalities and symptoms of myelopathy were the most observed neurological manifestations. MRI often revealed longitudinally extensive transverse myelitis (LETM) involving the cervical spine. Three of 19 (15.9%) cases were diagnosed with NMOSD and breast cancer within the same month. Five of 19 (26.1%) cases had a diagnosis of breast cancer preceding that of NMOSD. Eight of 19 (42.1%) cases were diagnosed with breast cancer after NMOSD. The median time of breast cancer diagnosis was 1.0 months (range 216 months) after NMOSD.
CONCLUSIONS
The diagnosis of breast cancer most often occurs after the onset of the paraneoplastic NMOSD symptoms. However, a wide time range for the diagnosis of breast cancer was observed both before and after the onset of neurological symptoms. Older women with a new diagnosis of NMOSD should be considered for frequent breast cancer screening.
PubMed: 37453952
DOI: 10.1007/s10072-023-06952-0 -
The Journal of Clinical Endocrinology... Jul 2022Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is...
CONTEXT
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign, and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far.
EVIDENCE ACQUISITION
On June 26, 2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia." There were no language restrictions. This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria.
EVIDENCE RESULTS
Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared with TIO women. The TIO-causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO-causing neoplasms were equally located in bone and soft tissues; the latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in > 90% of patients). Promising nonsurgical therapies are treatments with burosumab in TIO patients with elevated fibroblast growth factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques.
CONCLUSION
TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located in soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising nonsurgical therapies.
Topics: Adult; Data Analysis; Female; Fibroblast Growth Factors; Humans; Hypophosphatemia; Male; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes; Receptors, Somatostatin; Somatostatin
PubMed: 35468192
DOI: 10.1210/clinem/dgac253 -
Frontiers in Immunology 2022Anti--methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis... (Review)
Review
Anti--methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Female; Humans; Male; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Receptors, N-Methyl-D-Aspartate
PubMed: 35837405
DOI: 10.3389/fimmu.2022.857443 -
Frontiers in Immunology 2021Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system... (Review)
Review
Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system involvement. Since the AChR on the postsynaptic membrane is destroyed by an immune attack, sufficient endplate potential cannot be generated, resulting in the development of a synaptic transmission disorder at the neuromuscular junction and in muscle weakness. The role of the complement system in MG has been demonstrated in animal models and clinical tests, and it has been determined that complement inhibition in patients with MG can prevent disease induction and reverse its progression. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and prevents autoimmune damage; additionally, it has received subsequent approval by the Federal Drug Administration of the United States for MG treatment. However, various concerns regarding the use of eculizumab persist. In this review, we have discussed the treatment time, cost effectiveness, long-term efficacy, and tolerability of eculizumab for MG treatment. We have also summarized historical information and have presented perspectives on this new therapeutic modality.
Topics: Animals; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Combined Modality Therapy; Complement Inactivating Agents; Complement System Proteins; Disease Management; Disease Susceptibility; Drug Development; Humans; Myasthenia Gravis; Treatment Outcome
PubMed: 34456922
DOI: 10.3389/fimmu.2021.715036 -
Frontiers in Endocrinology 2023Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To...
Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To identify key considerations in comprehensive management of SCLC patients complicated with PCS, we conducted a systematic review of relevant reports on PubMed and Web of Science, focusing on SCLC with PCS cases. The systematic review analyzed 61 reports published between 1985 and 2022 with a total of 157 SCLC patients included. Out of the 157 patients, 132 (84.1%) patients across 58 (95.1%) reports were diagnosed with ectopic Cushing's syndrome. The immunohistochemical (IHC) staining for adrenocorticotropic hormone (ACTH) was performed on 30 (19.1%) patients across 22 (36.1%) reports and demonstrated encouraging performance. For treatment, chemotherapy and ketoconazole were utilized in 50 (81.97%) and 24 (39.34%) reports, respectively. Regarding cause of death, infection and cancer were equally frequent, each being recorded in 17 (27.87%) reports. To conclude, the majority of PCS cases in SCLC patients were caused by ectopic hormone secretion. In order to make a differential diagnosis, it is recommended to utilize IHC staining for a specific hormone such as ACTH or corticotropin-releasing hormone. In the comprehensive treatment of SCLC with PCS patients, effective management of hypercortisolism and potent safeguarding against infection play two crucial roles. Ultimately, further confirmations are required regarding the specificity and accuracy of IHC staining technique as well as the efficacy and safety of immunotherapy in the treatment of SCLC with PCS patients.
Topics: Humans; Cushing Syndrome; Small Cell Lung Carcinoma; Lung Neoplasms; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Paraneoplastic Syndromes
PubMed: 37916144
DOI: 10.3389/fendo.2023.1177125 -
Journal of Nuclear Medicine : Official... Jul 2017The purpose of this study was to assess the diagnostic performance of whole-body F-FDG PET or F-FDG PET/CT for detection of underlying malignancy in patients with... (Comparative Study)
Comparative Study Meta-Analysis Review
The purpose of this study was to assess the diagnostic performance of whole-body F-FDG PET or F-FDG PET/CT for detection of underlying malignancy in patients with clinically suspected neurologic and nonneurologic paraneoplastic syndromes. A systematic search was performed in PubMed (Medline), Embase, and Scopus (last updated November 2016) to identify relevant published studies reporting the performance of F-FDG PET or F-FDG PET/CT in patients with suspected paraneoplastic syndrome. Histopathologic confirmation or clinical follow-up was considered as the reference standard. Pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, and diagnostic odds ratio were calculated. A summary receiver-operating-characteristic curve was constructed, and the area under the curve (AUC) was determined along with the Q* index. Twenty-one studies including a total of 1,293 individual patients suspected of having a paraneoplastic syndrome and who underwent F-FDG PET or F-FDG PET/CT examinations met our inclusion criteria. There was moderate to high heterogeneity among the included studies. The pooled sensitivity, specificity, and diagnostic odds ratio of F-FDG PET or F-FDG PET/CT for the detection of underlying malignancy were 0.81 (95% CI, 0.76-0.86), 0.88 (95% CI, 0.86-0.90), and 34.03 (95% CI, 18.76-61.72), respectively. The AUC and the Q* index were 0.916 (SE, 0.018) and 0.849, indicating excellent diagnostic accuracy. The diagnostic accuracy was slightly improved after studies with high applicability concerns were excluded (AUC, 0.931; SE, 0.020). In a subgroup analysis, F-FDG PET/CT was found to have a significantly higher specificity (0.89 vs. 0.79) than F-FDG PET alone, with no evidence of significant difference in the overall performance (AUC, 0.930 vs. 0.891; 2-tailed value for difference, 0.31). This meta-analysis of available studies demonstrates that whole-body F-FDG PET or F-FDG PET/CT has high diagnostic accuracy and moderate to high sensitivity and specificity for detection of underlying malignancy in patients suspected of having a paraneoplastic syndrome.
Topics: Fluorodeoxyglucose F18; Incidence; Paraneoplastic Syndromes; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prevalence; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Whole Body Imaging
PubMed: 27980049
DOI: 10.2967/jnumed.116.183905 -
Seminars in Arthritis and Rheumatism Aug 2014To analyse clinical, laboratory, and imaging characteristics of all patients with palmar fasciitis and polyarthritis syndrome (PFPAS) described in the literature. (Review)
Review
OBJECTIVE
To analyse clinical, laboratory, and imaging characteristics of all patients with palmar fasciitis and polyarthritis syndrome (PFPAS) described in the literature.
METHOD
Comparison of the clinical presentation of one patient with acute onset of PFAPS with 99 other published cases identified through a PubMed literature research.
RESULTS
Since the original description in 1982 by Medsger et al., there have been numerous case reports and small case series in the literature. In total, 73 articles in English, French and Spanish language were included in the analysis. PFPAS is a rare but characteristic paraneoplastic syndrome in rheumatology. Its distinct clinical feature is a painful swelling of both the hands caused by an inflammation of the palmar fascia, tendon sheaths and small joints of fingers and wrist, and flexion contractures develop rapidly. Since the subcutaneous tissues become indurated and hard, the illustrative term "woody hands" was coined. The most frequent underlying malignancy is ovarian cancer but adenocarcinomas of the breast, gastrointestinal tract and other organs can also cause this syndrome. A helpful diagnostic procedure in order to identify the nature of the underlying malignancy in many cases has been the determination of various serum tumour markers. In cases when a complete removal of the malignancy is possible, PFPAS can also undergo complete remission.
CONCLUSIONS
Knowledge of the distinct features of this rare paraneoplastic syndrome facilitates early diagnosis and potentially life-saving therapeutic interventions.
Topics: Adenocarcinoma; Arthritis; Fasciitis; Female; Humans; Ovarian Neoplasms; Paraneoplastic Syndromes
PubMed: 24684975
DOI: 10.1016/j.semarthrit.2014.03.005 -
Neurology Oct 2023Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary generalized myasthenia gravis (SGMG) reported in the literature has been varied. The aim of this systematic review was to determine the clinical characteristics of patients with OMG and the proportion of SGMG conversion.
METHODS
We conducted an electronic database search for randomized controlled trials, prospective nonrandomized studies, observational studies, and retrospective studies in EMBASE, CENTRAL, MEDLINE, and Web of Science. We included studies with patients with OMG who initially presented with ocular symptoms and signs only and were seen in clinical practice, reporting on the characteristics and outcomes of SGMG. We excluded studies with pediatric and congenital myasthenia gravis populations. Eligible studies included articles written in any language and containing data on patients with OMG. The main outcome measured was the proportion of patients with OMG who converted to SGMG and risk factors associated with secondary generalization of OMG. Two independent reviewers screened titles and abstracts and extracted data from full texts, reporting findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology was evaluated using the Joanna Briggs Institute critical appraisal forms. PROSPERO registration number: CRD2021285257.
RESULTS
Thirty-one studies were included in the quantitative and qualitative analysis. The proportion of generalization ranged from 11% to 84%. The pooled proportion was 39% (95% CI 32%-47%, = 95.86%, < 0.001 unweighted, low certainty). The pooled risk ratio of female sex for conversion to SGMG was 1.06 (95% CI 0.96-1.17, = 0% = 0.614, 21 studies included, very low certainty), and the pooled risk ratio of acetylcholine receptor (AChR) positivity was 1.30 (95% CI 1.05-1.56, = 0% = 0.455, 16 studies included, very low certainty).
DISCUSSION
Risk factors such as female sex and anti-AChR positivity have been identified to have possible associations with SGMG, but there are not enough quality observational studies. There is a need for a prospective global database of patients with OMG, including all countries with different populations.
Topics: Humans; Female; Child; Retrospective Studies; Myasthenia Gravis; Receptors, Cholinergic; Risk Factors; Blepharoptosis
PubMed: 37643888
DOI: 10.1212/WNL.0000000000207642 -
Surgical Endoscopy May 2023Thymectomy has been utilized as a treatment for Myasthenia Gravis (MG) for many decades, with both open and minimally invasive surgical (MIS) techniques currently used.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Thymectomy has been utilized as a treatment for Myasthenia Gravis (MG) for many decades, with both open and minimally invasive surgical (MIS) techniques currently used. Although MIS has shown improved short-term results, long-term effects remain uncertain. This systematic review and meta-analysis aim to compare the post-operative and long-term outcomes of MIS versus open thymectomy in MG patients.
METHODS
MEDLINE, EMBASE and CENTRAL databases were searched from inception till January 2022 for keywords related to MG and open or MIS thymectomy. Primary outcome was complete stable remission (CSR), and secondary outcomes were clinical improvement, complications, length of stay, operation time, and blood loss. Grading of recommendations, assessment, development, and evaluation was used to assess the certainty of evidence.
RESULTS
26 studies with 3588 patients were included in the analysis. At 1, 3 and 5 years, there was no statistical difference noted in CSR between open versus MIS thymectomy. However, CSR was improved at 1 year for MIS thymectomy in non-thymomatous MG (P = 0.03). There was no significant difference in rates of partial clinical improvement between techniques at 1-year. Although analyses on length of hospital stay and blood loss showed improvement following MIS thymectomy, operative time was shorter for open thymectomy.
CONCLUSION
This is the first systematic review and meta-analysis assessing long-term effects of MIS versus open thymectomy in MG patients. Given the lack of significant differences noted, either MIS or open thymectomy can be performed, based on surgeon preference. Further high-level, long-term research should be conducted to determine the benefit of each technique.
Topics: Humans; Thymectomy; Myasthenia Gravis; Remission Induction; Length of Stay; Minimally Invasive Surgical Procedures; Treatment Outcome; Retrospective Studies
PubMed: 36539629
DOI: 10.1007/s00464-022-09757-y