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Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ζ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efficacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, reflecting MuSK-specific B cell depletion. Specific off-target interactions of MuSK-CAART were not identified in vivo, in primary human cell screens or by high-throughput human membrane proteome array. These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG.

Immune checkpoint inhibitors cause rare but potentially fatal neuromuscular complications, leading to a concern to use these agents in cancer patients with pre-existing autoimmune or inflammatory neuromuscular diseases. We report two such patients with paraneoplastic dermatomyositis and "seronegative" paraneoplastic demyelinating neuropathy, respectively, who have been successfully treated with immune checkpoint inhibitor monotherapy as well as maintenance intravenous immunoglobulin. While controlling the paraneoplastic or autoimmune neuromuscular diseases, the use of intravenous immunoglobulin did not compromise the anti-cancer effect of immune checkpoint inhibitor.

Background: Previous research has shown that post-secondary collegiate vocational educational programs often have positive effects on employment outcomes for young adults with intellectual and developmental disabilities. Aims: Using secondary data of a program in the United States collected over several years, we examined which intervention components of a postsecondary education transition program predicted subsequent employment for young adults with intellectual and developmental disabilities. Materials & Methods: The sample consisted of 56 individuals that participated in a transition-services collegiate program; Crossing Points, University of Alabama. Results: Results were able to robustly indicate that acquiring job-specific skills was a much better predictor than global measures of intellectual or adaptive behaviour. Additionally, survival curve analyses as an innovative approach to this population showed that there was a positive relation between the number of job-specific training sessions and eventual community employment. Discussion: Results are discussed in relation to a historical parallel movement to expand inclusion of students with intellectual and developmental disabilities in the least restrictive educational setting for primary and secondary public education years. Conclusion: In conclusion, the results of the current study suggest positive findings with job-skills training both specific and general. [Transition and Postsecondary Programs for Students with Intellectual Disabilities provided funding for this report.]

ObjectiveTo determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG).MethodsThe B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks.ResultsOf the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs. 56% on placebo. The study reached its futility endpoint (p=0.03) suggesting that the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified.ConclusionsWhile rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase-3 trial of mild-moderately symptomatic AChR-Ab+ gMG.Classification of evidenceThis study provides Class I evidence that for mild-to-moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.Trial registrationClinicalTrials.gov Identifier: NCT02110706.

ObjectiveTo update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature.MethodsIn October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness method was used to develop consensus recommendations pertaining to 7 treatment topics. In February 2019, the international panel was reconvened with the addition of one member to represent South America. All previous recommendations were reviewed for currency, and new consensus recommendations were developed on topics that required inclusion or updates based on the recent literature. Up to 3 rounds of anonymous e-mail votes were used to reach consensus, with modifications to recommendations between rounds based on the panel input. A simple majority vote (80% of panel members voting "yes") was used to approve minor changes in grammar and syntax to improve clarity.ResultsThe previous recommendations for thymectomy were updated. New recommendations were developed for the use of rituximab, eculizumab, and methotrexate as well as for the following topics: early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment.ConclusionThis updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for patients with MG worldwide.

ObjectivesTo approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.DesignRetrospective cohort study.SettingClinics across North America.ParticipantsThe study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.MethodsPhenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.ResultsAmong 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.DiscussionThe familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

Thirty to fifty percent of patients with acetylcholine receptor (AChR) antibody (Ab)-negative myasthenia gravis (MG) have Abs to muscle specific kinase (MuSK) and are referred to as having MuSK-MG. MuSK is a 100 kD single-pass post-synaptic transmembrane receptor tyrosine kinase crucial to the development and maintenance of the neuromuscular junction. The Abs in MuSK-MG are predominantly of the IgG4 immunoglobulin subclass. MuSK-MG differs from AChR-MG, in exhibiting more focal muscle involvement, including neck, shoulder, facial and bulbar-innervated muscles, as well as wasting of the involved muscles. MuSK-MG is highly associated with the HLA DR14-DQ5 haplotype and occurs predominantly in females with onset in the fourth decade of life. Some of the standard treatments of AChR-MG have been found to have limited effectiveness in MuSK-MG, including thymectomy and cholinesterase inhibitors. Therefore, current treatment involves immunosuppression, primarily by corticosteroids. In addition, patients respond especially well to B cell depletion agents, e.g., rituximab, with long-term remissions. Future treatments will likely derive from the ongoing analysis of the pathogenic mechanisms underlying this disease, including histologic and physiologic studies of the neuromuscular junction in patients as well as information derived from the development and study of animal models of the disease.

INTRODUCTION:There are no validated, practical, and quantitative measures of disease severity in Lambert-Eaton myasthenia (LEM). METHODS:Data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up-and-go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. RESULTS:The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4-diaminopyridine free base. Worsening patient-reported Weakness Self-Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. DISCUSSION:The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM.

INTRODUCTION:3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS:We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS:Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P

Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. For patients who present with an acute stroke despite dabigatran therapy, clinical data on the use of intravenous tissue plasminogen activator (IV-tPA) is limited. There is an anticipated increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in patients on dabigatran therapy. In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran. Dabigatran reversal with idarucizumab before administration of IV-tPA might reduce the risk of sICH. We report a case of a 69-year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who presented with an initial National Institutes of Health Stroke Scale (NIHSS) of 12. There was no early evidence of ischemic stroke or hemorrhage on head computed tomography, and coagulation studies implied therapeutic dabigatran levels. After controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA was administrated beginning 197 minutes after he was last seen at his baseline. Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated that he was at his prestroke baseline, except for a complaint of worsened short-term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and should be considered for acute stroke patients arriving in the IV-tPA time window.

ObjectiveTo develop formal consensus-based guidance for the management of myasthenia gravis (MG).MethodsIn October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input.ResultsGuidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy.ConclusionThis is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide.

ObjectiveTo determine whether discontinuation or marked reduction of mycophenolate mofetil (MMF) in patients with myasthenia gravis (MG) causes MG exacerbations.MethodsWe 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).ResultsThere 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.ConclusionsThis 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.Classification of evidenceThis study provides Class IV evidence that in patients with MG taking MMF, discontinuation or marked reduction of MMF causes MG exacerbation.

BACKGROUND: Attentional deficits in Autism spectrum disorder (ASD) are often noted, but their specific nature remains unclear. OBJECTIVE: The present study used the child Attentional Network Task (Child ANT) in combination with functional magnetic resonance imaging (fMRI) to determine if the consistently cited deficits of orienting attention are truly due to dysfunctions of orienting-based networks. We hypothesized that these observations are, in fact, a reflection of executive dysfunctions. As such, we expected that although ASD adolescents would perform worse on the orienting portion of the Child ANT, the strongest differences in activation between them and the neurotypical (NT) control group would be in areas classically associated with executive functioning (e.g., the frontal gyri and anterior cingulate cortex). METHOD: The brain activity of six high-functioning adolescents with ASD and six NT adolescents was recorded while these individuals performed the three subcomponents of the Child ANT. RESULTS: ASDs were shown to be more accurate than NTs for the alerting, less accurate for the orienting, and similar in accuracy for the executive portions of the Child ANT. fMRI data showed increased bilateral frontal gyri recruitment, areas conventionally associated with executive control, during the orienting task for the ASD group. CONCLUSION: We submit that the increased activations represent neurocorrelates of signal fixation attributable to the subset of executive control responsible for sustained maintenance signals, not the main components of orienting. Therefore, excessive fixation in ASD adolescents is likely due to dysfunctions of executive control and not the orienting subcomponent of the attention network.

Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20-28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs.

Pre-clinical evaluations often provide the rationale for therapeutic assessments in humans; however, in many diseases an agent found successful in animal models does not show efficacy in human subjects. Our contention is that the approach of rigorous, clinical trials can be used to inform how preclinical assessments should be performed. Clinical trials in humans are carefully designed investigations executed with consideration of critical methodological issues, such as pre-specified entrance criteria and validated, outcome measures coupled with power analysis to identify sample size. Blinding of evaluators of subjective measures and randomization of subjects are also critical aspects of trial performance. Investigative agents are also tested in subjects with active disease, rather than prior to disease induction as in some pre-clinical assessments. Application of standard procedures, including uniform reporting standards, would likely assist in reproducibility of pre-clinical experiments. Adapting methods of clinical trial performance will likely improve the success rate of therapeutics to ultimately achieve human use.

ImportanceMyasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.ObjectiveTo identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study.Design, setting, and participantsDNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication.Main outcomes and measuresWe calculated P values for association between 8,114,394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0×10(-8) was set for genome-wide significance after Bonferroni correction for multiple testing.ResultsIn the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P=3.98×10(-8); odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P=1.08×10(-8); odds ratio, 2.31; 95% CI, 2.02-2.60), and TNFRSF11A (rs4263037; P=1.60×10(-9); odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P=1.32×10(-12); odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 (HLA-DQA1; rs9271871; P=7.02×10(-18); odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases (HLA-DQA1; rs601006; P=2.52×10(-11); odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases.Conclusions and relevanceOur genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease.

Richman et al. ("J Appl Behav Anal" 48:131-152, 2015) completed a meta-analytic analysis of single-case experimental design data on noncontingent reinforcement (NCR) for the treatment of problem behavior exhibited by individuals with developmental disabilities. Results showed that (1) NCR produced very large effect sizes for reduction in problem behavior, (2) NCR implemented with the functional reinforcer resulted in a slightly larger effect size compared to NCR using nonfunctional reinforcers, and (3) schedule thinning for the delivery of reinforcers typically produced temporary and modest increases in levels of problem behavior. The purpose of the current study was to conduct follow-up analyses to determine whether treatment implementation setting, topography, or the function of problem behavior influenced the treatment effect size for problem behavior exhibited by individuals with developmental disabilities. Follow-up analyses showed that NCR effect sizes were very similar across inpatient and outpatient settings and across aggression and property destruction versus self-injurious behaviors. Results showed that NCR effect size for treatment of problem behavior maintained by a form of social reinforcement was slightly greater than problem behavior maintained by automatic reinforcement. Results are discussed in terms of applying NCR in school settings as an initial treatment for problem behaviors that can interfere with academic, adaptive, and vocational skill acquisition for students with developmental disabilities.

The efficacy and efficiency of telehealth and in-person training were compared while teaching seven undergraduate students to implement components of discrete trial training. A multiple-baseline design across skills with elements of multiple probe and delayed multiple baseline combined with an alternating-treatments design was used to evaluate the effects of behavioral skills training (BST) on (a) implementing a multiple stimulus without replacement preference assessment, (b) setting up an instructional context, (c) delivering antecedent prompts, and (d) delivering consequences for accurate and inaccurate responding. Two skills were trained via telehealth and two skills were trained in-person using BST procedures with a mock student. All participants provided high acceptability ratings for both training procedures. Results also showed that telehealth training was as efficacious and efficient as in-person training for all skills across all participants. Five of six participants showed high levels of maintenance of the newly acquired skills; these five also exhibited the skills during a novel instructional task.

Stereotypic behavior exhibited by a third grade boy with autism was maintained by automatic reinforcement and occurrences of stereotypy were brought under stimulus control. The intervention consisted of pairing a green discriminative stimulus card (SD) with free access to stereotypy and a red card (SD absent) with vocal redirection and blocking stereotypy. After exposure to discrimination training, the student rarely engaged in stereotypy with the SD card absent, but he almost continuously engaged in stereotypy when the SD card was present. Experimental control over stereotypic behavior was demonstrated via a combination of within session sequential alternating treatments design and withdrawal design across sessions. (Contains 3 figures.)

The current meta-analysis examines the previous research on the utility of the Social Communication Questionnaire as a screening instrument for autism spectrum disorder. Previously published reports have highlighted the inconsistencies between Social Communication Questionnaire-screening results and formal autism spectrum disorder diagnoses. The variations in accuracy resulted in some researchers questioning the validity of the Social Communication Questionnaire. This study systematically examined the accuracy of the Social Communication Questionnaire as a function of the methodological decisions made by researchers screening for autism spectrum disorder over the last 15 years. Findings from this study suggest that the Social Communication Questionnaire is an acceptable screening instrument for autism spectrum disorder (area under the curve = 0.885). Variations in methodological decisions, however, greatly influenced the accuracy of the Social Communication Questionnaire in screening for autism spectrum disorder. Of these methodological variations, using the Current instead of the Lifetime version of the Social Communication Questionnaire resulted in the largest detrimental effect (d = -3.898), followed by using the Social Communication Questionnaire with individuals younger than 4 years of age (d = -2.924) and relying upon convenience samples (d = -4.828 for clinical samples, -2.734 for convenience samples, and -1.422 for community samples). Directions for future research and implications for using the Social Communication Questionnaire to screen for autism spectrum disorder are discussed.

In analyzing data from the National Database for Autism Research, we utilized Mokken scaling techniques as a means of creating a more effective and efficient screening procedure for autism spectrum disorder (ASD) via the Social Communication Questionnaire (SCQ). With a sample of 1,040, approximately 80% (n = 827) of the sample were males while approximately 20% (n = 213) were females. In regard to ethnicity, approximately 68% of the sample were White/Caucasian, while 7% were African American, 16% were Hispanic, 4% were Asian, and 1% were Native American or American Indian. As the "Diagnostic and Statistical Manual of Mental Disorders" (5th ed.; "DSM-5") states that, "individuals with a well-established "DSM-IV" diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified should be given the diagnosis of autism spectrum disorder," (American Psychiatric Association, 2013, p. 51), the primary labeling difference between the "DSM-IV" and the "DSM-5" would appear to be in identifying social communication disorder as a newly introduced disorder in the "DSM-5," which we discuss. Though school psychologists are not dependent on the "DSM" to the same extent as clinical psychologists to provide services, school psychology is invested in the effective and efficient assessment of ASD. The current study demonstrates how Mokken scaling procedures may be utilized with respect to ASD identification via the SCQ as well as providing information regarding the prevalence of potential social communication disorder as a new disorder and its discrimination with ASD.

The prognosis of myasthenia gravis (MG) has improved dramatically due to advances in critical-care medicine and symptomatic treatments. Its immunopathogenesis is fundamentally a T-cell-dependent autoimmune process resulting from loss of tolerance toward self-antigens in the thymus. Thymectomy is based on this immunological background. For MG patients who are inadequately controlled with sufficient symptomatic treatment or fail to achieve remission after thymectomy, remission is usually achieved through the addition of other immunotherapies. These immunotherapies can be classified into two groups: rapid induction and long-term maintenance. Rapid induction therapy includes intravenous immunoglobulin (IVIg) and plasma exchange (PE). These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the perioperative period. High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIg and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants (ISs) are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by three mechanisms: 1) blocking the synthesis of DNA and RNA, 2) inhibiting T-cell activation and 3) depleting the B-cell population. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials. It is hoped that well-organized studies and newer experimental trials will lead to improved treatments.