mycophenolic-acid and Myasthenia-Gravis

To describe a case of coincident Castleman's disease and myasthenia gravis that initially presented as rapidly progressive dysphagia and dysphonia and to review the unique pathophysiology of these two uncommon diagnoses.. Case report and literature review.. Castleman's disease, angiofollicular or giant lymph node hyperplasia, is a rare benign lymphoid proliferation. Traditionally, the disease is classified based on histologic and clinical characteristics. Fewer than 10 cases with concurrent myasthenia gravis have been reported. Myasthenia gravis and thymic epithelial tumors are both associated with acetylcholine receptor antibody. While patients with isolated Castleman's disease are usually asymptomatic, those who have concurrent myasthenia gravis and undergo surgical treatment are at increased risk of postoperative myasthenic crisis. Both pre- and postoperative plasmapheresis are suggested to improve muscle strength and prevent severe postoperative complications.. In the setting of multiple cranial neuropathies including velopalatal insufficiency and bilateral ptosis it is important to consider myasthenia gravis. Castleman's disease occurs rarely in conjunction with myasthenia gravis but may increase the risk of myasthenic crisis.

Topics: Adolescent; Castleman Disease; Cholinesterase Inhibitors; Deglutition Disorders; Dysphonia; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Pyridostigmine Bromide; Thymectomy; Tomography, X-Ray Computed; Velopharyngeal Insufficiency

Therapies for myasthenia gravis (MG) include symptomatic and immunosuppressive/immunomodulatory treatment. Options for immunosuppression include corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, methotrexate, rituximab, cyclophosphamide, eculizumab, intravenous immunoglobulin, subcutaneous immunoglobulin, plasmapheresis, and thymectomy. The practical aspects of long-term immunosuppressive therapy in MG are critically reviewed in this article. Application of one or more of these specific therapies is guided based on known efficacy, adverse effect profile, particular disease subtype and severity, and patient co-morbidities.

Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Thymectomy

To update our current concepts of ocular myasthenia gravis medical management and to provide a short overview of upcoming treatments.. Cholinesterase inhibitors and corticosteroids have been the first-line treatment for ocular myasthenia gravis. Several studies on other immunosuppressants, either as a steroid-sparer, steroid adjuvant or initial monotherapy, have demonstrated significant clinical efficacy. Preventing progression to generalized myasthenia gravis is still under debate and needs to be further studied. Novel techniques that target specific components of the autoimmune cascade are forthcoming.. Currently, limited evidence favors the use of corticosteroids, azathioprine, and mycophenolate mofetil in ocular myasthenia gravis. There is a need for rigorous clinical trials on the efficacy and safety of these medical therapeutic options in improving ocular symptoms and decreasing the risk of developing generalized myasthenia gravis. Studies on emerging immunomodulators that dampen autoreactivity without affecting general immunity should be pursued.

Topics: Azathioprine; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid

The benefits of different immunosuppressants for myasthenia gravis (MG) are unclear.. Assessment of immunosuppressant drug efficacy in MG.. We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to July 2007), EMBASE (from January 1980 to July 2007), review and trial bibliographies and contacted trial authors.. Types of studies: Randomised and quasi-randomised controlled trials.. Any age, any type or severity of MG regardless of concomitant treatment. Types of interventions: Any immunosuppressive agent. Types of outcome measures: Primary: (1) Improvement or not at six months. Secondary: (1) Improvement or not at one year (2) Need for other treatment, for example corticosteroid dose, at six months (3) Number of exacerbations during the first year (4) Acetylcholine receptor antibody titre after at least six months (5) Occurrence of one or more adverse events at any time after the introduction of treatment.. One author extracted and two checked the data.. Seven trials are included but few reported the outcomes selected for this review. A meta-analysis of ciclosporin versus placebo from two trials (59 participants) - one as monotherapy (20 participants) and the other with corticosteroids (39 participants) - showed that it resulted in improvement of participants in the ciclosporin group compared with those in the placebo group, with a relative rate of improvement of 2.44 (95% confidence interval (CI) 1.13 to 5.27). In addition the weighted mean difference in QMG score between the ciclosporin and placebo groups was -0.34 (95% CI -0.52 to -0.17). Azathioprine (plus prednisolone for first month) had no significant benefit over prednisolone alone (41 participants). The effects of azathioprine plus prednisolone versus prednisolone plus placebo were similar (34 participants). Cyclophosphamide was reported to be statistically more efficacious than placebo at 12 months in corticosteroid-dependent participants (23 participants), but no raw data were available. Trials of mycophenolate mofetil and tacrolimus did not provide relevant endpoint data for this review. All trials had low numbers of participants. Adverse event reporting was variable. Trial protocol heterogeneity prevented comparison of the different immunosuppressants.. In generalised MG, limited evidence from small RCTs suggests that ciclosporin, as monotherapy or with corticosteroids, or cyclophosphamide with corticosteroids, significantly improve MG.Limited evidence from RCTs shows no significant benefit from azathioprine (as monotherapy or with steroids), mycophenolate mofetil (as monotherapy or with either corticosteroids or ciclosporin) or tacrolimus (with corticosteroids or plasma exchange). Bigger, better-designed, longer trials are needed.

Topics: Adrenal Cortex Hormones; Azathioprine; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Prednisolone; Randomized Controlled Trials as Topic; Tacrolimus

To review published literature evaluating the effectiveness of mycophenolate mofetil for the treatment of myasthenia gravis (MG).. Searches of MEDLINE (1966-August 2005) and Cochrane Database (1993-August 2005) were conducted. Studies conducted in humans and published in English were retrieved. Additional data were identified through subsequent bibliographic reviews.. Interruption of T- and B-lymphocyte proliferation in various autoimmune diseases has been investigated. Mycophenolate is known to inhibit lymphocyte proliferation and has shown improved clinical responses in several autoimmune diseases including lupus erythematosus, rheumatoid arthritis, and systemic vasculitis. Data suggesting similar benefits in MG treatment have been reported in case reports, retrospective analyses, an open-label trial, and a randomized, double-blind trial.. Limited evidence from retrospective analyses and clinical trials suggests that mycophenolate is a possible treatment option for patients with MG. Improvement in clinical symptoms and a steroid-sparing effect have been reported when mycophenolate is used in this patient population. Larger, randomized, controlled, and comparative trials are needed to establish optimal dose, time to effect, specific therapeutic role, and long-term safety for mycophenolate when used for treating MG.

Topics: Clinical Trials as Topic; Databases, Factual; Humans; Immunosuppressive Agents; MEDLINE; Myasthenia Gravis; Mycophenolic Acid; Treatment Outcome

Myasthenia gravis (MG) represents the prototypic autoimmune disorder with well characterized immunopathology. Advances in the diagnosis and treatment of this neuromuscular transmission disorder have significantly improved the management of myasthenic patients. Unfortunately the currently available immunomodulating treatments have significant side effects and some patients do not tolerate them or adequately respond to them. Therefore the possibility of a new immunosuppressant agent that is safe, effective and has steroid-sparing effect is very appealing. Mycophenolate mofetil (MMF) has shown promising effects in MG patients in preliminary studies and is currently being studied in two prospective, randomized, double-blind, placebo controlled, multicenter trials to better establish its role in the treatment of MG.

Topics: Cholinesterase Inhibitors; Humans; Immunoglobulins, Intravenous; Immunosuppression Therapy; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Plasmapheresis; Thymectomy

Myasthenia gravis is probably the most thoroughly understood of all human autoimmune diseases. The basic mechanism of the disease is an antibody-mediated autoimmune attack that decreases the acetylcholine receptor density at the neuromuscular junction. Current therapies aim to restore the available acetylcholine receptors, deplete the autoantibodies or suppress the immune system. Prolonged drug treatment is required, but this carries a potential risk of severe adverse effects. Therefore, the ideal treatment for myasthenia would eliminate the abnormal autoimmune response without interfering with the immune system.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Plasma Exchange; Rituximab; Thymectomy

In the past decade, the therapeutic choices for patients with myasthenia gravis (MG) have not changed, except for the introduction of rituximab. There have been three placebo-controlled randomized trials in the past fifteen years, namely, those on azathioprine (AZP), mycophenolate mofetil (MMF) and tacrolimus. The trial for AZP was carried out on a relatively small number of patients (AZP, 15; placebo, 19), and its outcome showed the therapeutic effectiveness of AZP. The MMF trial was carried out on a large number of patients (MMF, 88; placebo, 88). The result showed no effect on primary and secondary endpoints. The tacrolimus trial was carried out in Japan on a relatively large number of patients (tacrolimus, 40; placebo, 40). Although the study could not reveal an effect on the primary endpoint, several secondary endpoints turned out to be affected. In all three studies, the therapeutic drugs were used in combination with steroid, and the safety and tolerability of the drugs were shown. In diseases with a relatively small affected population, such as MG, successful execution of well-designed clinical trials is difficult. We have to learn how to collect pieces of valuable information wisely from previous studies. The utilization of clinical literacy will be important in this medical practice.

Topics: Azathioprine; Humans; Myasthenia Gravis; Mycophenolic Acid; Tacrolimus

Topics: Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasmapheresis; Treatment Outcome

We determined the strength of correlation among, and responsiveness of, outcome measures used in a multicenter, double-blind, placebo-controlled trial of mycophenolate mofetil in combination with prednisone in myasthenia gravis (MG). The primary efficacy measure was the change from baseline in the Quantitative MG (QMG) score at week 12. Secondary outcome measures included the MG-Activities of Daily Living profile (MG-ADL) and MG Manual Muscle Test (MMT). The measures were collected at baseline and at weeks 4, 8, and 12 in the blinded study and at weeks 16, 20, 28, and 36 in an optional open-label extension. At baseline, the QMG was moderately correlated with the MG-ADL (r=0.55, P<0.0001) and the MMT (r=0.53, P<0.0001), but the correlation between the MG-ADL and the MMT was lower (r=0.30, P=0.007). These findings were similar at weeks 4, 8, and 12. Similar correlations were found among the changes in scores from baseline at weeks 12 and 36. The MMT and MG-ADL appeared to be the most sensitive measures for changes in MG status at weeks 12 and 36. Although a task force has recommended use of the QMG in prospective MG trials, the MMT and MG-ADL appear to be suitable alternatives and offer potential advantages. No special training or equipment is required, and they take less time.

Topics: Activities of Daily Living; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Outcome Assessment, Health Care; Psychomotor Performance; Retrospective Studies; Seveso Accidental Release; Time Factors

To study the safety and tolerability of mycophenolate mofetil (MM), since this steroid-sparing immunomodulatory agent with less side effects, compared to corticosteroids, may be considered for long-term management of ocular myasthenia (OMG).. Consecutive patients with OMG started on MM between December 2000 and December 2002 were followed up to December 2006.. All of the 31 patients with OMG were treated with prednisone at 40-60 mg/d while MM was increased up to the target of 1.0 g/d. After symptoms completely resolved, all patients were then tapered off prednisone over a period of 4 weeks. Eighty-seven percent (27/31) of patients continued on MM during the study. Mycophenolate mofetil discontinuation occurred in 4/31 (13%) of patients within the first four months of starting the drug. Of the patients who continued on MM, 93% (25/27) remained at stage I of the disease. The 7% (2/27) of patients on MM who generalized in our study did so by 2 years and were treated with additional prednisone. MM-related adverse events included nausea in 9 of 31 patients, diarrhea in 5 of 31 patients, and vomiting in 1/31 patients. No cases of infections, cytopenias, or malignancies were observed.. Eighty-seven percent of OMG patients on corticosteroids who were switched to MM remained at Stage I of the disease over a mean period of 4.2 years. MM at 1.0 g/d was safe and tolerable as a long-term immunosuppressant for OMG.

Topics: Adult; Autoantibodies; Drug Administration Schedule; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Oculomotor Muscles; Patient Compliance; Prednisone; Prospective Studies; Receptors, Cholinergic; Treatment Outcome

This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG).. Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety.. A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%).. Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.

Topics: Female; Humans; Immunosuppressive Agents; International Cooperation; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Prospective Studies

To test the hypothesis that mycophenolate mofetil (MMF) with prednisone provides better control of myasthenic weakness than prednisone alone in the initial management of generalized myasthenia gravis (MG).. Eighty immunosuppression naïve subjects with mild to moderate generalized, acetylcholine receptor positive MG at 13 centers were randomized to 2.5 g/day MMF plus 20 mg/day prednisone (n = 41) or placebo plus 20 mg/day prednisone (n = 39) and followed in a double-blind fashion for 12 weeks. Subjects over 18 years of age were included if judged to be candidates for immunosuppression; excluded were those with thymoma or severe oropharyngeal or respiratory muscle weakness. The primary measure of efficacy was change in the quantitative MG (QMG) score from baseline to week 12. Study completers could take open-label MMF for an additional 24 weeks, while prednisone was reduced to the minimally effective dosage.. The mean change in QMG score was similar in the treated (-4.4 +/- 5.1) and placebo (-3.6 +/- 5.0) groups (p = 0.71). The dosage of prednisone was reduced by a similar amount in both groups during the open-label phase. Subjects tolerated the study drug well, without unexpected adverse events.. This study demonstrated no benefit of mycophenolate mofetil (MMF) with 20 mg/day prednisone compared to 20 mg/day of prednisone alone after 12 weeks. This may be due to greater than predicted benefit from the prednisone dosage used, the short duration of the study, or the absence of any benefit of MMF in this population of patients with myasthenia gravis.

Topics: Double-Blind Method; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Prednisone

Mycophenolate mofetil (MM) is an immunosuppressive agent developed and originally used to prevent acute rejection of solid-organ transplantation. There have been preliminary reports of its successful use in the treatment of autoimmune myasthenia gravis (MG). We conducted a double-blind, placebo-controlled pilot trial of MM in the treatment of suboptimally controlled, stable MG. Results of this pilot study are promising and suggestive of greater improvement in the patients who received MM compared to placebo.

Topics: Adult; Aged; Antibodies; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Neurologic Examination; Pilot Projects; Receptors, Cholinergic; Treatment Outcome

In an open-label study, 12 patients with refractory MG or who were taking only corticosteroids and required additional immunosuppression received mycophenolate mofetil 1 g twice daily for 6 months. A reduction of three points in a quantified MG score and two points in a manual muscle test or a reduction of 50% in corticosteroid dose defined efficacy. Eight patients improved, beginning after 2 weeks to 2 months. No major side effects were observed.

Topics: Adult; Aged; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Pilot Projects; Treatment Outcome

We report favorable results of the long term use of mycophenolate in the treatment of three patients with myasthenia gravis (MG), two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with secondary polymyositis (PM), and one patient with inclusion body myositis (IBM). Side effects were mild. Mycophenolate appears to be a useful addition to the armamentarium of immunosuppressants for treatment of chronic immunologically mediated neuromuscular diseases.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chronic Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Myositis, Inclusion Body; Polyneuropathies; Prednisone; Treatment Outcome

To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG).. A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (. After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (. For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Topics: Activities of Daily Living; Child; Glucocorticoids; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Retrospective Studies; Tacrolimus

Topics: Humans; Iatrogenic Disease; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Lymphoproliferative Disorders; Myasthenia Gravis; Mycophenolic Acid

Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Retrospective Studies

Topics: Aged; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immunocompromised Host; Immunogenicity, Vaccine; Immunosuppressive Agents; Male; Myasthenia Gravis; Mycophenolic Acid; Prednisone; SARS-CoV-2

Topics: Adult; Betacoronavirus; Cholinesterase Inhibitors; Coronavirus Infections; COVID-19; Disease Progression; Female; Glucocorticoids; Humans; Hypercapnia; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Myasthenia Gravis; Mycophenolic Acid; Pandemics; Plasma Exchange; Pneumonia, Viral; Prednisone; Pyridostigmine Bromide; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2; Severity of Illness Index; Thymectomy; Tomography, X-Ray Computed

To compare long-term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real-world settings.. This is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.. Among 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0-62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower-dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).. Rituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.

Topics: Adult; Aged; Azathioprine; China; Clinical Decision-Making; Cohort Studies; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Immunotherapy; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Retrospective Studies; Rituximab; Tacrolimus

The Myasthenia Gravis Patient Registry (MGR) is a voluntary, patient-submitted database dedicated to improve understanding of care/burden of myasthenia gravis (MG).. In this study we present analyses of baseline records through July 2017 (n = 1140) containing data on the MG-Activities of Daily Living (MG-ADL) and the MG 15-item Quality of Life (MG-QOL15) instruments, two validated scales assessing quality of life in MG patients at sign-up into the MGR.. Most registrants reported moderate to severe impairment of health-related quality of life, with a median MG-ADL score of 6 and a median MG-QOL15 score of 21. Seventy-one percent of the patients had received pyridostigmine. Corticosteroids, mycophenolate mofetil, and azathioprine were the most common immunomodulators/immunosuppressants, with 85% of participants having ever using one of these agents. Forty-seven registrants reported receiving intravenous immunoglobulin, and 30% received plasma exchange. Twelve percent reported other treatments, and 40% were unsure whether they received less common therapies. Forty percent had undergone thymectomy.. The MGR data correlate well with other MG cohorts. Many MG patients remain negatively impacted despite treatment.

Topics: Activities of Daily Living; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Cholinesterase Inhibitors; Cross-Sectional Studies; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasma Exchange; Pyridostigmine Bromide; Quality of Life; Registries

The number of contrast media-related procedures is ever increasing due to the widespread availability of theoretically safe, low osmolar iodinated contrast material. Although intravenously administered contrast is known to precipitate myasthenic crisis, oral contrast aspiration as a causative factor is not yet documented as such. A 48-year-old Sinhalese man diagnosed as having myasthenia gravis, was evaluated for progressive dysphagia with an upper gastrointestinal contrast study. Iodinated contrast material (iohexol) was used as the contrast medium and there was direct evidence of contrast aspiration during the study. Several minutes after the procedure, severe respiratory distress with evidence of myasthenic crisis requiring intubation and intensive care admission was noted. Treatment with intravenous immunoglobulin, high-dose steroids, and broad-spectrum intravenously administered antibiotics led to an uneventful recovery, although the latter part of the clinical course was complicated with total left lung collapse. Myasthenic crisis can be precipitated by various factors and a successful recovery requires mechanical respiratory support with immunomodulatory and steroid therapy. This is the first reported case that describes the development of myasthenic crisis following iohexol-associated aspiration pneumonitis.

Topics: Cholinesterase Inhibitors; Contrast Media; Deglutition Disorders; Disease Progression; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Iohexol; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Pneumonia, Aspiration; Pneumothorax; Prednisolone; Pyridostigmine Bromide; Respiration, Artificial; Respiratory Aspiration; Respiratory Insufficiency

Topics: Diaphragm; Dyspnea; Humans; Immunosuppressive Agents; Male; Myasthenia Gravis; Mycophenolic Acid; Oximetry; Plasma Exchange; Point-of-Care Testing; Prednisone; Respiration, Artificial; Respiratory Function Tests; Respiratory Insufficiency; Treatment Outcome; Ultrasonography; Young Adult

Symposia dedicated to myasthenia gravis and related disorders date back to 1947 and serve as markers of the progress for the field. We provide a brief historical review of therapy development through the lens of the publications that arose from the close to quinquennial meetings that have been supported nearly since their inception by the Myasthenia Gravis Foundation of America and the New York Academy of Sciences. One can appreciate great advances, false starts, and dead ends that are found in all fields of medicine. We tally up the score card for MG and find points scored, but the win is not yet close.

Topics: Enzyme Inhibitors; History, 20th Century; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Tacrolimus

To determine whether discontinuation or marked reduction of mycophenolate mofetil (MMF) in patients with myasthenia gravis (MG) causes MG exacerbations.. We identified 88 patients with MG who took MMF during the 5-year period 2007-2011 at our MG clinic. We then performed detailed chart reviews and recorded all MG exacerbations and their relationship to MMF and other treatment changes. We also recorded demographic data and disease characteristics (including antibody status and Myasthenia Gravis Foundation of America status).. There were 14 patients who had an MG exacerbation during the study period. Of these, 13 had discontinued MMF therapy, with a median time until exacerbation of 16 weeks after discontinuation (9 patients) or marked dose reduction (4 patients) of MMF therapy (exacerbation in the absence of change in any other component of the immunosuppressive regimen). Using the cluster option in a Cox regression analysis, the MMF coefficient was -5.32, with a standard error of 1.05 and a p value of 0.0002, corresponding to an estimated hazard ratio of 204.. This retrospective cohort study suggests that discontinuation/marked reduction of MMF therapy may increase the risk of MG exacerbation many fold, supporting the hypothesis that MMF plays a role in the maintenance of MG remission/minimal manifestation status.. This study provides Class IV evidence that in patients with MG taking MMF, discontinuation or marked reduction of MMF causes MG exacerbation.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Disease Progression; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Retrospective Studies; Withholding Treatment; Young Adult

Topics: Humans; Immunosuppressive Agents; Insurance Coverage; Myasthenia Gravis; Mycophenolic Acid; Off-Label Use; Treatment Outcome; United States

Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well-controlled patients.. This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed.. Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months).. Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Retrospective Studies; Treatment Outcome

Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Combined Modality Therapy; Cyclosporine; Female; Graft vs Host Disease; Hearing Loss, Sensorineural; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant; Myasthenia Gravis; Mycophenolic Acid; Piebaldism; Pigmentation Disorders; Plasma Exchange; Remission Induction; Rituximab; Transplantation, Homologous; Treatment Outcome

Obstructive sleep apnea (OSA) in patients with myasthenia gravis (MG) may be caused by reduced pharyngeal dilator muscle activity. We report a patient with anti-muscle kinase receptor MG with severe OSA and hypoventilation that resolved upon successful treatment of MG despite a 60-lb weight gain.

Topics: Anti-Inflammatory Agents; Female; Follow-Up Studies; Humans; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasma Exchange; Prednisone; Sleep Apnea, Obstructive; Treatment Outcome; Weight Gain

Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis (MG). Although there are numerous data on associated infection and prophylaxis in transplant patients who are on MMF, data in MG remains lacking. We report two elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year, respectively. Chronic MMF therapy in MG patients may trigger life-threatening infections including CMV and EBV diseases, especially in the elderly. Similar to the practice in transplant patients, viral serology testing and appropriate prophylactic regimen with antiviral agents should be considered, particularly in older MG patients.

Topics: Aged, 80 and over; Antiviral Agents; Cytomegalovirus Infections; Encephalitis, Viral; Enteritis; Epstein-Barr Virus Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Opportunistic Infections

OBJECTIVE-To compare clinical outcome in dogs with serologically diagnosed acquired myasthenia gravis (MG) treated with pyridostigmine bromide (PYR) with that of dogs treated with mycophenolate mofetil (MMF) and PYR (MMF + PYR). DESIGN-Retrospective case series. ANIMALS-27 dogs. PROCEDURES-Medical records from August 1999 through February 2008 were reviewed to identify dogs with serologically diagnosed acquired MG treated with PYR or MMF + PYR. Data collected for each dog included signalment, whether the dog had megaesophagus or pneumonia (or both), thyroid hormone concentration, remission, time to remission, and survival time. Rates for detection of clinical signs and survival time were compared. Survival time was estimated via the Kaplan-Meier method. Influence of drug treatment protocol on likelihood of remission, time to remission, and survival time was examined. Effects of MMF treatment, megaesophagus, pneumonia, and low serum thyroid hormone concentration on time to remission and survival time were also analyzed. RESULTS-12 dogs were treated with PYR, and 15 were treated with MMF + PYR. Mortality rates were 33% (PYR) and 40% (MMF + PYR). There was pharmacological remission in 5 and 6 dogs in the PYR and MMF + PYR groups, respectively. No significant differences were detected between treatment groups for remission rate, time to remission, or survival time. Megaesophagus, pneumonia, and low serum thyroid hormone concentration had no significant effect on time to remission or survival time for either treatment group. CONCLUSIONS AND CLINICAL RELEVANCE-The results did not support routine use of MMF for the treatment of dogs with acquired MG.

Topics: Animals; Dog Diseases; Dogs; Drug Therapy, Combination; Enzyme Inhibitors; Female; Immunosuppressive Agents; Male; Myasthenia Gravis; Mycophenolic Acid; Pyridostigmine Bromide; Retrospective Studies; Time Factors; Treatment Outcome

Two recent randomized, controlled trials failed to demonstrate a benefit of mycophenolate mofetil (MMF) over prednisone in the treatment of myasthenia gravis (MG). We reviewed our experience with MMF in MG to determine whether these trials may have been unsuccessful because of their short duration and the unpredicted benefit of prednisone. We reviewed outcomes and prednisone dosage for all our acetylcholine-receptor (AChR)-antibody positive MG patients treated with MMF alone or with prednisone for at least 3 months. The percentage of patients with a desirable outcome (MG-specific Manual Muscle Test score <4 or Myasthenia Gravis Foundation of America post-invention status of minimal manifestations or better) began to increase after 6 months; 80% of those followed for >24 months had a desirable outcome. Prednisone dose decreased after 12 months; after 25 months, 54.5% of patients took no prednisone and 75% took <7.5 mg/day. This retrospective analysis provides class IV evidence that MMF begins to improve AChR-positive MG after 6 months, both with prednisone and as monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Outcome Assessment, Health Care; Prednisone; Randomized Controlled Trials as Topic; Receptors, Cholinergic; Retrospective Studies; Treatment Outcome; Young Adult

To describe the use of IV and oral mycophenolate mofetil (MMF) as adjunctive therapy in 3 dogs with severe generalized myasthenia gravis.. Three dogs suffering from severe generalized myasthenia gravis as confirmed by acetylcholine antibody titers were treated with MMF as part of their treatment regimens. All 3 dogs had radiographic evidence of megaesophagus and suffered from severe regurgitation. Each dog was initially treated with pyridostigmine and supportive agents. When clinical remission was not achieved, IV MMF was administered to all dogs. Signs of clinical remission were apparent within 48 hours and all dogs were later maintained on oral MMF following resolution of regurgitation.. This is the first report of the use of IV MMF as adjunctive treatment in dogs with severe generalized myasthenia gravis. Outcome was favorable in all 3 dogs and no adverse effects were noted from the MMF.

Topics: Animals; Dog Diseases; Dogs; Emergencies; Female; Immunosuppressive Agents; Infusions, Intravenous; Male; Myasthenia Gravis; Mycophenolic Acid; Severity of Illness Index

Immunosuppressive therapies are critical in the management of numerous conditions including myasthenia gravis. Mycophenolate mofetil is a widely used, oral immunosuppressive agent that is considered to have few adverse effects compared with similar drugs. We report the case of a patient who developed T-cell lymphoproliferative lesions following long-term treatment with mycophenolate mofetil and prednisone for myasthenia gravis. The lesions resolved following cessation of the treatment. This case highlights a serious complication of a commonly used drug.

Topics: Aged; Biomarkers; Epstein-Barr Virus Infections; Female; Genitalia, Female; Gingiva; Gingivitis; Humans; Immunosuppressive Agents; Lymphoproliferative Disorders; Mouth; Myasthenia Gravis; Mycophenolic Acid; Positron-Emission Tomography; Prednisone; T-Lymphocytes

The preferred immunosuppressive drug for long term treatment of myasthenia gravis (MG) is azathioprine (AZA). Mycophenolate mofetil (MMF) was suggested as an effective and safe second line alternative to AZA.. In a prospective open-label study, 11 patients with acetylcholine receptor antibody (AChR-ab) positive MG (n=4 ocular MG, n=7 generalized MG) were treated with MMF which replaced AZA. Reasons for the change of immunosuppressant therapy were side effects (n=9) or unresponsiveness under AZA (n=3).. Mean duration of MMF treatment was 16.9 months (6-46 months). During MMF treatment AZA side effects resolved in 8/9 patients, concomitant therapy could be discontinued in 4 patients and reduced in 5 patients, and 5 patients remitted and 3 remained in remission. One MMF-refractory patient required add-on IVIG therapy and another with ocular MG showed signs of generalization after 20 months of MG treatment. One patient was diagnosed with bronchial carcinoma after 10 months of MMF treatment.. Due to its favourable spectrum of side effects compared to AZA MMF might serve as a second-line immunosuppressant in those MG patients who have not tolerated AZA.

Topics: Adult; Aged; Azathioprine; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Prospective Studies

Two randomized controlled trials of mycophenolate mofetil (MMF) in the treatment of myasthenia gravis (MG) were recently completed. Although neither study demonstrated efficacy of MMF in the population of patients studied, there are valuable lessons in the way these studies were developed and performed. After reviewing the design and results of these trials, we discuss possible reasons leading to negative results and the lessons learned, which should be useful for future clinical trials in MG.

Topics: Drug Therapy, Combination; Humans; Immunotherapy; Myasthenia Gravis; Mycophenolic Acid; Prednisolone; Randomized Controlled Trials as Topic

We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the "gold standard," the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG.

Topics: Activities of Daily Living; Health Surveys; Humans; Myasthenia Gravis; Mycophenolic Acid; Psychometrics; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires

Topics: Drug Therapy, Combination; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Prednisone

Topics: Cholinesterase Inhibitors; Fatal Outcome; Female; Genetic Predisposition to Disease; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Methylprednisolone; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Pyridostigmine Bromide; Siblings; Thymectomy; Young Adult

Myasthenia gravis (MG) is an autoimmune disease that leads to muscular weakness, which can significantly affect the patient's daily functions. If left untreated, the mortality rate can be as high as 30%. Effective immunosuppression is the cornerstone of treatment of MG, although most currently available immunomodulatory drugs are associated with unacceptable side effects, delayed onset of therapeutic action, or both. Mycophenolate mofetil (MMF) might be better tolerated than other immunosuppressants and many case reports and uncontrolled trials have indicated that it is effective in MG. However, two recently concluded clinical trials failed to demonstrate the efficacy of MMF in MG. This paper critically reviews the existing evidence on the efficacy of MMF in MG and provides the authors' view of its role in current practice.

Topics: Animals; Clinical Trials as Topic; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Treatment Outcome

Mycophenolate mofetil (MM) has been successfully used for the treatment of immune-mediated diseases, including myasthenia gravis (MG). We compare our experience treating Taiwanese myasthenic patients with MM to analogous Caucasian series.. From October 2003 to April 2008, we treated 6 myasthenic patients with MM for at least one year at Shin Kong Wu Ho-Su Memorial Hospital. The inclusion criteria for MM treatment included poor responses to previous treatment or intolerance to the side effects of previous immunosuppressive therapies. The MM was given orally with a dose of 1 g twice per day. Mandatory surveillance laboratory studies and clinical assessment were performed periodically.. Three of our six patients responded well to MM treatment in terms of improvement in MG score and achievement of minimal manifestation status. The fourth patient showed delayed onset of response 12 months after commencement of MM treatment. Steroid-sparing effect could be demonstrated in 4 patients. The overall response rate (66%) was slightly lower than that reported for Caucasian series. Clinical improvement generally began in the second to four months. MM was well tolerated.. MM was well tolerated by our six treated patients. Although the clinical response was modest, MM has its advantage of a relatively rapid response onset and steroid-sparing effect.

Topics: Adult; Female; Humans; Immunosuppressive Agents; Middle Aged; Myasthenia Gravis; Mycophenolic Acid

Immunosuppressive pharmacologic agents are associated with a diverse array of adverse drug reactions. One of these agents, mycophenolate mofetil, is indicated for prevention of allogeneic organ transplant rejection and has recently been evaluated for treatment of autoimmune disease states, including myasthenia gravis. Although the prescribing information for mycophenolate mofetil reports depression as an adverse event, no descriptions of the onset or manifestation of this idiosyncratic reaction have been published. This case report describes a 64-year-old woman with myasthenia gravis who received mycophenolate mofetil and developed a severe depressive disorder requiring hospitalization 4 days after the start of therapy. The drug was discontinued, and she was treated with sertraline, quetiapine, and clonazepam. Within 2 days after mycophenolate mofetil discontinuation, the patient's depressive symptoms had markedly improved. Eight days later, mycophenolate mofetil was reintroduced under direct observation. After day 2 of this rechallenge, the patient reported a substantial increase in her depressive symptoms. Treatment was discontinued again, with improvement in the patient's symptoms within 2 days. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of depression and mycophenolate mofetil therapy. Future evaluations of mycophenolate mofetil should include an assessment of psychological adverse effects. In addition, postmarketing surveillance should be encouraged to further delineate the association between depression and mycophenolate mofetil therapy.

Topics: Depressive Disorder; Female; Hospitalization; Humans; Immunosuppressive Agents; Middle Aged; Myasthenia Gravis; Mycophenolic Acid

We report our experience, using mycophenolate mofetil (MyM) as an adjunctive immunosuppressive therapy in patients with severe, refractory and high dose steroid-dependent myasthenia gravis (MG). Five patients were commenced on MyM in addition to other immunosuppressive therapies. All had significant clinical improvement and no subsequent myasthenic crisis requiring intensive care unit admission. MyM was well tolerated and no serious adverse effects were observed. MyM is an effective adjunctive therapy for the treatment of severe, refractory and steroid-dependent MG in our experience.

Topics: Adult; Aged; Cholinesterase Inhibitors; Drug Resistance; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Prednisolone; Pyridostigmine Bromide; Severity of Illness Index; Singapore

Severe autoimmune myasthenia gravis is difficult to manage and may require immunosuppression with cyclosporine. However, cyclosporine dependency is associated with the risk of nephrotoxicity. Mycophenolate mofetil is a non-nephrotoxic alternative which should be considered to rescue cyclosporine-dependent, severe myasthenia gravis sufferers with renal impairment from progression to end-stage renal failure. However, the evidence is limited and studies have not assessed the outcome of a direct substitution in these cyclosporine-dependent patients. We study three such patients who successfully converted to mycophenolate mofetil, and briefly examine the evidence behind this option. We believe that total cyclosporine withdrawal is feasible, but strongly recommend overlapping mycophenolate mofetil treatment with cyclosporine.

Topics: Adult; Cyclosporine; Diabetic Nephropathies; Drug Evaluation; Female; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasma Exchange; Prednisolone; Recurrence; Thymectomy

Topics: Clinical Trials as Topic; Etanercept; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Receptors, Tumor Necrosis Factor

Topics: Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Brain; Cholinesterase Inhibitors; Electroencephalography; Epilepsy; Female; Humans; Immunoglobulins, Intravenous; Memory Disorders; Muscle Weakness; Muscle, Skeletal; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Pyridostigmine Bromide; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Treatment Outcome

If myasthenia gravis is not a usual complication of interferon therapy, several cases have been described with the use of theses molecules in the treatment of hepatitis C, cancer or multiple sclerosis. We report a new case of serious myasthenia gravis during interferon alpha and ribavirin therapy for hepatitis C.

Topics: Aged; Antiviral Agents; Cholinesterase Inhibitors; Follow-Up Studies; Glucocorticoids; Hepatitis C, Chronic; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon-alpha; Male; Myasthenia Gravis; Mycophenolic Acid; Prednisone; Pyridostigmine Bromide; Ribavirin

We report on a 56-year-old woman with muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia with predominant bulbar symptoms and respiratory insufficiency. Conventional immunosuppression (prednisolone, azathioprine, mycophenolate mofetil) could not maintain the clinical improvement initially achieved by repeated plasma exchanges. Therefore, treatment with rituximab was initiated. After 2 months of rituximab treatment, remarkable clinical improvement correlating with a reduction of MuSK serum antibodies was seen. The patient continued to remain stable 12 months after initiation of therapy. This case report demonstrates that rituximab may be an effective and tolerable treatment in MuSK antibody-positive myasthenia gravis.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antibodies; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; B-Lymphocytes; Female; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasma Exchange; Prednisolone; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Rituximab; T-Lymphocytes

Important progress has been made in our understanding of the cellular and molecular processes underlying the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (peripheral nerve hyperexcitability; Isaacs syndrome). To prepare consensus guidelines for the treatment of the autoimmune NMT disorders. References retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts and a patient representative. The proposed practical treatment guidelines are agreed upon by the Task Force: (i) Anticholinesterase drugs should be the first drug to be given in the management of MG (good practice point). (ii) Plasma exchange is recommended as a short-term treatment in MG, especially in severe cases to induce remission and in preparation for surgery (level B recommendation). (iii) Intravenous immunoglobulin (IvIg) and plasma exchange are equally effective for the treatment of MG exacerbations (level A Recommendation). (iv) For patients with non-thymomatous autoimmune MG, thymectomy (TE) is recommended as an option to increase the probability of remission or improvement (level B recommendation). (v) Once thymoma is diagnosed TE is indicated irrespective of the severity of MG (level A recommendation). (vi) Oral corticosteroids is a first choice drug when immunosuppressive drugs are necessary in MG (good practice point). (vii) In patients where long-term immunosuppression is necessary, azathioprine is recommended together with steroids to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (level A recommendation). (viii) 3,4-diaminopyridine is recommended as symptomatic treatment and IvIg has a positive short-term effect in LEMS (good practice point). (ix) All neuromyotonia patients should be treated symptomatically with an anti-epileptic drug that reduces peripheral nerve hyperexcitability (good practice point). (x) Definitive management of paraneoplastic neuromyotonia and LEMS is treatment of the underlying tumour (good practice point). (xi) For immunosuppressive treatment of LEMS and NMT it is reasonable to adopt treatment procedures by analogy with MG (good practice point).

Topics: Adrenal Cortex Hormones; Autoimmune Diseases of the Nervous System; Azathioprine; Humans; Immunosuppressive Agents; Lambert-Eaton Myasthenic Syndrome; MEDLINE; Myasthenia Gravis; Mycophenolic Acid; Neuromuscular Junction Diseases; Plasma Exchange; Thymectomy

A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.

Topics: Adult; Cyclosporine; Female; Humans; Immunoglobulins; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Plasmapheresis; Prednisolone; Thymectomy

Mycophenolate mofetil (MM), an immunosuppressant used after organ transplantation, is also used for treatment of autoimmune myasthenia gravis (MG). A patient with generalized MG was effectively managed with MM but developed CNS lymphoma after 3 years of treatment. Primary CNS lymphoma regressed on withdrawal of MM. Despite minimal short-term side effects and apparent efficacy, chronic treatment of MG with MM may be associated with increased risk of lymphoproliferative disorders.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Brain Neoplasms; Cell Transformation, Neoplastic; Drug Therapy, Combination; Female; Frontal Lobe; Humans; Immunity, Cellular; Immunosuppressive Agents; Lymphoma, B-Cell; Magnetic Resonance Imaging; Myasthenia Gravis; Mycophenolic Acid; Parietal Lobe; Prednisone; Pyridostigmine Bromide; Rituximab; T-Lymphocytes; Treatment Outcome

The authors report a retrospective analysis of the use of mycophenolate mofetil (MyM) in 85 patients with autoimmune myasthenia gravis. The Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) was used to characterize the treatment response in each patient. Sixty-two patients (73%) achieved a PIS status indicating improvement. Quantitative strength testing performed on the majority of patients before and after treatment also improved. Side effects to MyM were observed in 27% of patients but required discontinuation in only 6%.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Retrospective Studies; Treatment Outcome

The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Myositis; Retrospective Studies; Treatment Outcome

Topics: Adult; Female; Hepatitis C; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Myasthenia Gravis; Mycophenolic Acid; Syndrome

Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.

Topics: Aged; Anemia, Hemolytic; Autoantibodies; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Neurologic Examination; Receptors, Cholinergic; Treatment Outcome

We report a patient with myasthenia gravis (MG) who had marked clinical benefit in response to treatment with mycophenolate mofetil as documented by serial quantitative measures of strength and muscle fatigue. Our patient had experienced either adverse side effects or a suboptimal response to the usual immunosuppressive agents used in MG. Mycophenolate mofetil was used in combination with cyclosporine and prednisone and allowed for significant reductions in dosage of these immunosuppressants. We conclude that mycophenolate mofetil deserves further study as a therapeutic agent in MG. In particular, its role as a steroid-sparing agent and as a drug to be used in combination immunotherapy in more severe or refractory cases of MG should be investigated.

Topics: Adult; Anti-Inflammatory Agents; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Prednisolone

Topics: Adolescent; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Myasthenia Gravis; Mycophenolic Acid