Subclinical Myasthenia Gravis Research Articles

Anesthetic management of a patient with subclinical myasthenia gravis who underwent a thymectomy: a case report

BackgroundSome individuals with subclinical myasthenia gravis (MG) are positive for serum anti-acetylcholine receptor antibodies, without neurological symptoms. There are no anesthetic management guidelines for subclinical MG. We report the anesthetic management of a patient with subclinical MG who underwent a thymectomy.Case presentationA 57-year-old female with subclinical MG was scheduled for an extended thymectomy. Anesthesia was induced and maintained with mainly propofol and remifentanil. We administrated the minimum amount of rocuronium with reference to train-of-four (TOF) monitoring when a neuromuscular relaxant is needed. Although the prolonged effect of rocuronium was observed, the TOF ratio had already recovered to 100% before the tracheal extubation. Postoperative analgesia was performed by a continuous epidural infusion of levobupivacaine.ConclusionWe reported the anesthetic management of a patient with subclinical MG who underwent a thymectomy. Further research is necessary to clarify subclinical MG patients' sensitivity to rocuronium.

Refractory post-thymectomy myasthenia gravis with onset at MGFA stage V: a case report

BackgroundPost-thymectomy myasthenia gravis (PTMG) is defined as thymoma patients without signs of myasthenia gravis (MG) pre-operation, but develop MG after radical surgical resection. PTMG might be misdiagnosed not only because of its rare incidence, but also the uncertain interval between the removal of thymoma and the new onset MG. Additionally, some surgeons and anesthesiologists pay less attention to those asymptomatic thymoma patients in perioperative management, leading to the neglect of new onset PTMG, and miss the best time to treat it.Case presentationMajority of cases of PTMG with onset at stage I–II on the basis of Myasthenia Gravis Foundation of America (MGFA) classification have been reported, but rarely at stage V, which requiring intubation or non-invasive ventilation to avoid intubation. Herein, we presented a 70-year-old male with PTMG onset at MGFA stage V, meanwhile, he had severe pulmonary infection interfering with the diagnosis of PTMG, and eventually progressed to refractory PTMG, which requiring much more expensive treatments and longer hospital stays.ConclusionIn the perioperative management of asymptomatic thymoma patients, careful preoperative evaluation including physical examination, electrophysiological test and acetylcholine receptor antibodies (AChR-Ab) level should be done to identify subclinical MG. Complete resection should be performed during thymectomy, if not, additional postoperative adjuvant therapy is neccessary to avoid recurrence. It’s important to identify PTMG at a early stage, especially when being interfered with by postoperative complications, such as lung infection, so that treatments could be initiated as soon as possible to avoid developing to refractory PTMG.

AB001. Subclinical myasthenia gravis in thymomas

Background: A proportion of thymoma-patients without a history of myasthenia gravis (MG) before thymectomy, appears to have positive anti-AChR-antibodies in the serum. These subclinical MG-patients could be underdiagnosed because analyzation of anti-AChR-antibodies in thymomas is not always performed in patients who did not experience neurological symptoms. The prevalence and long-term outcomes of subclinical MG are never described in literature yet.

Subclinical myasthenia gravis in thymomas

BackgroundA proportion of thymoma-patients without a history of myasthenia gravis (MG) before thymectomy, appears to have positive anti-AChR-antibodies in the serum. These subclinical MG-patients could be underdiagnosed because analyzation of anti-AChR-antibodies in thymomas is not always performed in patients who did not experience neurological symptoms. The prevalence and long-term outcomes of subclinical MG are never described in literature yet. MethodsWe retrospectively analyzed 398 consecutive patients who underwent a robotic-assisted thoracoscopic surgery at the Maastricht University Medical Center+ (MUMC+) between April 2004 and December 2018. In the MUMC+, a robotic approach is the standard surgical approach in patients with thymic diseases. Inclusion criteria were thymomas, thymectomy performed in the MUMC + with a follow-up of at least one year and age above 18 years old. Exclusion criteria were patients with thymic carcinomas, refused participation, or those who were lost to follow-up. ResultsOf the 102 included thymoma-patients, 87 patients (85 %) were tested for anti-AChR-antibodies before thymectomy, of which 57 patients were diagnosed with clinical MG and seven subclinical MG-patients were found. Of the 15 patients who were not tested for anti-AChR-antibodies, four more subclinical MG-patients were discovered in the years after thymectomy. The median follow-up time was 62 months. In total, 11 subclinical MG-patients were found, with a mean age of 54 years and predominantly females (64 %). Ten subclinical MG-patients (91 %) developed clinical-MG, within six years after thymectomy. Immunosuppressive drugs were prescribed in five patients. Four patients were diagnosed with a recurrence of the thymoma. No surgical mortality was reported. Two patients died due to a myasthenic crisis. ConclusionsThe prevalence of subclinical MG in thymomas was found to be 10.8 %. One in four patients who experienced no neurological symptoms before thymectomy, appeared to have anti-AChR-antibodies and 91 % of these patients developed clinical MG within six years after the thymectomy. Analyzing anti-AChR-antibodies in the serum is recommended in all suspected thymomas before a thymectomy is performed.

The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients.

Background: Anti-programmed cell death 1 (PD-1) monoclonal antibodies (Abs) unleash an immune response to cancer. However, a disruption of the immune checkpoint function by blocking PD-1/PD-ligand 1(PD-L1) signaling may trigger myasthenia gravis (MG) as a life-threatening immune-related adverse event. MG is a neuromuscular disease and is closely associated with being positive for anti-acetylcholine receptor (anti-AChR) Abs, which are high specific and diagnostic Abs for MG. Methods: A 72-year-old man was diagnosed with chemotherapy-refractory lung squamous cell carcinoma and nivolumab was selected as the third-line regimen. We describe the first report of an anti-AChR Ab-seropositive lung cancer patient achieving a durable complete response (CR) to an anti-PD-1 antibody therapy. To further explore this case, we performed multiplex immunofluorescence analysis on a pretreatment tumor. Results: The patient achieved a durable CR without developing MG. However, the levels of anti-AChR Abs were elevated during two years of anti-PD-1 antibody therapy. The tumor of the subclinical MG patient had high PD-L1 expression and an infiltrated–inflamed tumor immune microenvironment. Conclusions: This study suggests that immune checkpoint inhibitors can be safely used and provide the benefits for advanced cancer patients with immunologically ‘hot’ tumor even if anti-AChR Abs are positive. Although careful monitoring clinical manifestation in consultation with neurologist is needed, immune checkpoint inhibitors should be considered as a treatment option for asymptomatic anti-AChR Ab-seropositive cancer patients.

AB011. OA02.02: The importance of measuring acetylcholine receptor antibodies in thymomas

Background: Myasthenia gravis (MG) is a severe auto-immune muscle disease with a potential deadly outcome due to a respiratory myasthenic crisis. A myasthenic crisis can be triggered by: sickness, pregnancy, (surgical) interventions and stress. MG is diagnosed by the neurologist by checking the case history, electromyography and the level of antibodies against the acetylcholine receptor (anti-AChR) in the serum. Previous research showed an average prevalence of 15–30% of MG in thymomas. In thymoma patients, anti-AChR-serum levels are not frequently measured. The presence of AChR-antibodies makes the diagnosis MG more likely and is easy to check in an ordinary check-up before thymectomy by a pulmonologist or surgeon. A positive titer should aware the clinical team for the possibility of a myasthenic crisis and warn the anesthetist to use an appropriate dose of muscle relaxants during a thymectomy. Patients without pre-surgical MG-symptoms but with positive anti-AChR-serum levels, are described as subclinical myasthenia gravis in this study. The aim of this study was to investigate the presence of subclinical myasthenia gravis in thymomas.

Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by invivo electroporation. Subclinical MG was subsequently induced with a low dose of anti-AChR monoclonal antibody 35. Neuromuscular transmission was significantly impaired in Dok-7-siRNA-electroporated legs compared with the contralateral control legs, which correlated with a reduction of AChR protein levels at the neuromuscular junction (approximately 25%) in Dok-7-siRNA-electroporated muscles, compared with contralateral control muscles. These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack.

Subclinical Myasthenia Gravis causing increased sensitivity to botulinum toxin therapy

In rare patients receiving botulinum toxin (BT) therapy the potency of the BT drug may be increased by pre-existent impairment of neuromuscular transmission (INT). Appropriate dose adjustment may correct for this. Subclinical INT has previously been described by us for the first time in a patient with Lambert-Eaton myasthenic syndrome. We are now describing subclinical INT for the first time in a patient with ocular myasthenia gravis. Due to its unpredictability subclinical INT may pose a risk to patients receiving BT therapy.

Cancer-associated retinopathy associated with invasive thymoma

PURPOSE: To report a case of cancer-associated retinopathy associated with invasive thymoma. DESIGN: Interventional case report METHOD: A 41-year-old Japanese woman was observed between February 1998 and May 2001. Ophthalmologic examinations and systemic examinations were performed. The patient received treatment including corticosteroid pulse therapy, plasmapheresis, and thymectomy. RESULTS: The patient developed progressive visual dysfunction including bilateral visual acuity loss, concentric contraction of visual fields, and color vision loss. In both eyes, retinal vessel attenuation and retinal pigment epithelium degeneration were observed with fundus ophthalmoscopy and fluorescein angiography. Response in electroretinogram was reduced, suggesting both rod and cone dysfunction. Autoantibody against 23-kD cancer-associated retinopathy (CAR) antigen (antirecoverin antibody) was detected in the patient’s serum. A mediastinal tumor that was histopathologically diagnosed as invasive thymoma was detected and was surgically resected. During more than 3 years of follow-up, no other malignancy was detected despite extensive systemic evaluation. The patient also suffered from subclinical myasthenia gravis. Although temporary improvement of visual function was observed after treatment with steroid pulse therapy and plasmapheresis’ light perception of each eye was lost in the end. CONCLUSIONS: The patient was diagnosed as having CAR. Invasive thymoma was considered to be the causative tumor because there had been no evidence that suggested other systemic malignancy during more than 3 years of follow-up.

Measurement of antiacetylcholine receptor antibody in patients with thymoma without myasthenia gravis complications.

Some patients with thymoma reported to show higher antiacetylcholine receptor antibody titers without the preoperative occurrence of myasthenia gravis and some have suffered postoperative complications of myasthenia gravis despite being negative for antiacetylcholine receptor antibody preoperatively. We evaluated changes in antiacetylcholine receptor antibody titers and the occurrence of myasthenia gravis in thymoma patients. Subjects were 31 of 44 patients with thymoma undergoing thymothymectomy at Tokyo Women's Medical University Hospital between 1987 to 1999 in whom antiacetylcholine receptor antibody titers were measured preoperatively. We studied postoperative changes in antiacetylcholine receptor antibody titers and the presence or absence of myasthenia gravis. Eight patients were positive for antiacetylcholine receptor antibody preoperatively, suggesting the presence of subclinical myasthenia gravis. Neither postoperative changes in antiacetylcholine receptor antibody titers nor the occurrence of myasthenia gravis was observed in these 8 patients. Recurrent thymoma and rapid elevation of antiacetylcholine receptor antibody titers were observed postoperatively in 1 patient negative for antiacetylcholine receptor antibody preoperatively, resulting in manifestation of myasthenia gravis symptoms. We found no correlation between preoperative titers and myasthenia gravis symptoms. Rapid titer elevation indicates the occurrence of myasthenia gravis symptoms or the recurrence of thymoma.

D-Penicillamine-induced myasthenia gravis in primary biliary cirrhosis

A 62-yr-old woman with recently diagnosed primary biliary cirrhosis was started on d-penicillamine, 250 mg twice daily. Within 9 mo, she developed myasthenia gravis, associated with elevated antiacetylcholine receptor antibody titers and abnormalities of single-fiber electromyography. The d-penicillamine was withdrawn and pyridostigmine bromide was prescribed. The latter drug was slowly reduced, and at the end of 6 mo stopped, after a full recovery by the patient. The clinical response was paralleled by a fall in the antiacetylcholine receptor antibody titer into the normal range and reversal of the previously abnormal single-fiber electromyographic findings. The human leukocyte antigen type of the patient was not that typically associated with classic myasthenia gravis. It is suggested that d-penicillamine-induced myasthenia gravis is due to an independent effect of the drug on the immune system rather than to the unmasking of subclinical myasthenia gravis.

The diagnostic significance of autoantibodies to the acetylcholine receptor

The predictive value of the assay for antibodies to the acetylcholine receptor (anti-AChR) is dependent upon the reference range used and the question being asked by the clinician. A reference range has been established after assaying sera from 200 healthy individuals, 314 patients with diseases often considered in the differential diagnosis of myasthenia gravis (MG) or found in association with MG, and 72 patients with active adult onset MG. If the assay is to be used to screen at unselected population for MG a conservative cut off point (2 units) should be used. After establishment of a differential diagnosis more significant may be attributed to a lower result (1 unit or greater). A negative result does not exclude MG. In patients with Systemic Lupus Erythematosus, Graves' disease or thymoma anti-AChR has been demonstrated in the absence of signs of MG. Such patients may have latent or subclinical MG. Two such patients subsequently developed clinically evident MG concomitant with a rise in anti AChR titre above their particular ‘biological threshold’.

Myasthenia Gravis Associated With Wasp Sting

A clinical picture indistinguishable fro, but not therefore identical with, myasthenia gravis (ocular form) developed within 24 hours of a wasp sting. Because of the close temporal association of events, operative mechanisms may be either an immediate hypersensitivity reaction to some components of wasp venom or a direct toxic effect of these substances on acetylcholine synthesis, release, or degradation. Theoretical considerations from the literature and the lack of immunologic abnormalities in the patient suggest that the latter may be correct. Unique host conditions must have been present at the time of the sting, implying latent or subclinical myasthenia gravis.