Fatigable Weakness Research Articles

COLQ-mutant Congenital Myasthenic Syndrome with Microcephaly: A Unique Case with Literature Review.

Congenital Myasthenic Syndrome (CMS) is a group of inherited neuromuscular junction disorders caused by defects in several genes. Clinical features include delayed motor milestones, recurrent respiratory illnesses and variable fatigable weakness. The central nervous system involvement is typically not part of the CMS. We report here a Saudi girl with genetically proven Collagen Like Tail Subunit Of Asymmetric Acetylcholinesterase (COLQ) mutation type CMS who has global developmental delay, microcephaly and respiratory failure. We have reviewed the literature regarding COLQ-type CMS and to the best of our knowledge this is the first ever reported association of congenital myasthenia syndrome with microcephaly.

Ocular vestibular evoked myogenic potential in patients with myasthenia gravis: A prospective clinical study

ObjectiveMyasthenia gravis (MG) is an archetypic disorder of neuromuscular junctions (NMJs) and autoantibody-mediated disease causing fatigable weakness of skeletal muscles with an ocular onset in up to 85%. The aim of this study was to detect extra ocular muscles (EOMs) abnormalities in MG patients using ocular vestibular evoked myogenic potential (oVEMP) n10 response. MethodsThe oVEMP was performed on 40 myasthenia gravis patients that were divided into three groups: newly diagnosed (10 patients), uncontrolled on treatment (15 patients) and controlled on treatment (15 patients) groups in addition to a control group of 10 subjects. Also a comparison of oVEMP response was held between patients with generalized and ocular MG. ResultsThe oVEMP n10 showed significant difference between the 3 study groups and the control. The n10 showed no significant difference between the newly diagnosed group and the other 2 groups. There was also significant difference between uncontrolled and controlled on treatment group and between generalized and ocular types of myasthenic patients. ConclusionThe oVEMP can be usefully used in diagnosis of new MG patients as regard n10 amplitude, threshold and AR except n10 latency with no therapeutic or monitoring value of oVEMP in MG.

A modular and adjustable ptosis crutch as a non-surgical, low cost solution for elevating the upper eyelid in Myasthenia Gravis

Myasthenia Gravis (MG) is an autoimmune disorder that affects the neuromuscular junction. MG is characterised by the fatigable weakness of skeletal muscles, commonly affecting the eye and facial muscles. Africans with MG, particularly juveniles, are more likely to develop treatment-resistance of their ocular muscles, including severe blepharoptosis. Blepharoptosis, or ptosis, describes the condition of a drooping upper eyelid(s). Surgical correction of ptosis is often contraindicated in MG patients. In these cases, a non-surgical solution to elevate the ptotic eyelid above the visual axis is required. Objective: To design a ptosis crutch to elevate the ptotic eyelid(s) of MG patients. The crutch should be low cost, modular and adjustable in nature. Method: A bottom-up approach was followed for the design of the ptosis crutch. The requirements were defined according to patient, clinician and designer specifications. It underwent numerous iterations before the final design was manufactured, using 3D printing. 87 design failures were observed before the final design was realised. It was the design, test, fail, redesign cycle that lead to the discovery of a device that satisfied the requirements. Results: The ptosis crutch attaches to the superior border of the spectacle frame and is adjustable along the x, y and z-axes to cater for the inter-individual variability of horizontal eye position, globe projection and the eyelid elevation required. Conclusion: MG patient feedback on the ptosis crutch has shown a promising outcome for the device. Future work will include obtaining long term user feedback on the ptosis crutch.

Detection of myasthenia gravis using electrooculography signals.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting from skeletal muscle weakness and fatigue. An early common symptom is fatigable weakness of the extrinsic ocular muscles; if symptoms remain confined to the ocular muscles after a few years, this is classified as ocular myasthenia gravis (OMG). Diagnosis of MG when there are mild, isolated ocular symptoms can be difficult, and currently available diagnostic techniques are insensitive, non-specific or technically cumbersome. In addition, there are no accurate biomarkers to follow severity of ocular dysfunction in MG over time. Single-fiber electromyography (SFEMG) and repetitive nerve stimulation (RNS) offers a way of detecting and measuring ocular muscle dysfunction in MG, however, challenges of these methods include a poor signal to noise ratio in quantifying eye muscle weakness especially in mild cases. This paper presents one of the attempts to use the electric potentials from the eyes or electrooculography (EOG) signals but obtained from three different forms of sleep testing to differentiate MG patients from age- and gender-matched controls. We analyzed 8 MG patients and 8 control patients and demonstrated a difference in the average eye movements detected between the groups. A classification accuracy as high as 68.8% was achieved using a linear discriminant analysis based classifier.

Overview and Update of Congenital Myasthenic Syndromes

Neuromuscular junction disorders, also called Myasthenic Syndromes (MS), are a rare heterogeneous group of acquired (Myasthenia Gravis, MG) and inherited (Congenital Myasthenic Syndromes, CMS) neuromuscular disorders associated with distinctive clinical, electrophysiological, laboratory and ultrastructural abnormalities. The genetic defects in CMS either impair neuromuscular transmission directly or result in secondary impairments, which eventually compromise the safety margin of neuromuscular transmission. CMS are clinically characterized by fatigable weakness with an onset at birth or in the first 3 years of life. More than 15 different genetic causes of CMS have now been identified, with the majority inherited in autosomal recessive traits. The most frequent genetic defects causing CMS are loss-of-function mutations of the CHRNE gene, encoding the epsilon subunit of the acetylcholine receptor, which leads to receptor deficiency at the endplate. More recently, we have identified two genes (DOK7, GFPT1) that cause fatigable weakness of muscles in a limb-girdle distribution, but rarely affecting facial or eye muscles. While many patients with CMS respond favorably to pharmacological treatment with acetylcholine esterase inhibitors, some do not or even deteriorate. This can be largely attributed to the underlying genetic defect, and other drugs such as salbutamol and ephedrine have been used successfully I patients refractory to esterase inhibitors. We will cover the significant progress made in understanding the molecular pathogenesis of CMS, which is important for both patients and clinicians in terms of reaching a definite diagnosis and selecting the most appropriate treatment.

Myasthenia gravis: a clinical-immunological update.

Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to acetylcholine receptors cause fatigable weakness of skeletal muscles. In the rest, a variable proportion possesses antibodies to muscle-specific tyrosine kinase while the remainder of seronegative MG is being explained through cell-based assays using a receptor-clustering technique and, to a lesser extent, proposed new antigenic targets. The incidence and prevalence of MG are increasing, particularly in the elderly. New treatments are being developed, and results from the randomised controlled trial of thymectomy in non-thymomatous MG, due for release in early 2016, will be of particular clinical value. To help navigate an evidence base of varying quality, practising clinicians may consult new MG guidelines in the fields of pregnancy, ocular and generalised MG (GMG). This review focuses on updates in epidemiology, immunology, therapeutic and clinical aspects of GMG in adults.

CLINICAL AND NEUROLOGICAL CRITERIA FOR THE DIAGNOSISOF MYASTHENIA GRAVIS

927 patients suffering from myasthenia gravis have been examined. A long-term follow-up analysis of the various forms of myasthenia in its clinical and neurological development has been conducted. Systematization and evaluation of the results have revealed major and frequent diagnostics criteria appropriate of myasthenia gravis. There are fatigable muscular weakness (92,3%), formula motor dis- turbances (91,9%), test with neostigmine (77,5%), generalized muscular weakness (76,3%), “flutter” and «migration» of the symptoms (71,1%), preservation of eye movements downward while it restricts in other directions (68,3%), combination ptosis and lagophthalmos on one side (50,1%). A diagram of clinical diagnostic, which help us to review a patient diagnosis of myasthenia gravis or suspect this exact disease has been developed.

A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers

Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberrations in nicotinic acetylcholine receptor (AChR) subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT littermates with classic clinical and electromyographic findings, and immunochemical confirmation of an approximately 90% reduction in AChR protein content. Loci encoding the 5 AChR subunits were evaluated using microsatellite markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of the splice sites and exons of both genes revealed a single base insertion in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We further demonstrated this pathogenic mutation in CHRNE in archival tissues from unrelated JRTs studied 34 years ago.

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice.

Characteristics of myasthenia gravis with antibodies to muscle‐specific kinase and low‐density lipoprotein‐related receptor protein 4

AbstractMyasthenia gravis (MG) is characterized by fatigable weakness of voluntary muscles caused by immunoglobulin G autoantibodies binding to post‐synaptic proteins at the neuromuscular junction. Antibodies specific for the acetylcholine receptor are detected in the great majority (85%) of MG patients. Serum immunoglobulin G binding to the muscle‐specific kinase (MuSK) are found in approximately 40% of anti‐acetylcholine receptor‐negative patients. Recently, the low‐density lipoprotein receptor‐related protein 4 (Lrp4), which is the MuSK co‐receptor for agrin, has been recognized as a new antigen in MG. Specific antibodies bind to the extracellular domains of MuSK and Lrp4 and, as experimental models have shown, interfere with the protein function. The present review describes the MuSK‐Lrp4 complex, and summarizes the effects of MuSK and Lrp4 antibodies at the neuromuscular junction. Furthermore, the epidemiological and clinical characteristics, the response to therapy and the controversies in management of the specific diseases are discussed.

Structural and Pathogenic Mechanisms Centered on Muscle-Specific Tyrosine Kinase in Autoimmune Neuromuscular Junction Disorders

Myasthenia gravis (MG), an autoimmune neuromuscular junction disorder characterized by fatigable weakness of voluntary muscles including ocular, facial, oropharyngeal, limb and respiratory muscles with a prevalence of about 150-200 per million, is a disease of the postsynaptic neuromuscular junction where acetylcholine receptors (AChRs) are targeted by autoantibodies in 80-85% of MG patients. We face unresolved issues in the efforts to clarify the pathogenesis of remaining MG patients (seronegative MG). In this regard, we have paied attention to the findings that part of seronegative MG patients have antibodies against other postsynaptic proteins: the muscle-specific tyrosine kinase (MuSK) which is activated by Dok-7 (muscle adaptor protein) and plays a key role in AChR clustering at the end-plate membrane, and the low-density lipoprotein receptor-related protein 4 (Lrp4) which is the agrin receptor and mediates the neural signal to MuSK. To search a clue to further understanding of the immunopathological mechanisms underlying postsynaptic junction disorders, we need to understand a complex architecture formed by diversity of elements through signals orchestrated by sophisticated interactions in the synapse. The present review focuses on the signaling downstream from MuSK which is originated from the activation by agrin/Lrp4 signaling (via MuSK immunoglobulin-like domains 1 and 2) and by Wnt signaling (via MuSK cysteine-rich domain (CRD)), and also focuses on the synaptic stability by extracellular matrix proteins (such as collagen Q, perlecan and biglycan) and their receptors (via dystroglycans). Also, the review may shed light on possible mechanisms (including Wnt/MuSK CRD, Lrp4 and laminin-network) to modify the presynaptic function in autoimmune postsynaptic disorders. Keywords: Acetylcholine receptor, Agrin, laminin-network, Lrp4, MuSK, myasthenia gravis, neuromuscular junction, Wnts.

Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.

Background and ObjectiveCongenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia.MethodsWe used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed in vitro and a knockdown zebrafish model was generated to assess neuromuscular junction development.ResultsWe identified a novel homozygous missense mutation in the SLC25A1 gene, encoding the mitochondrial citrate carrier. Mutant SLC25A1 showed abnormal carrier function. SLC25A1 has recently been linked to a severe, often lethal clinical phenotype. Our patients had a milder phenotype presenting primarily as a neuromuscular (NMJ) junction defect. Of note, a previously reported patient with different compound heterozygous missense mutations of SLC25A1 has since been shown to suffer from a neuromuscular transmission defect. Using knockdown of SLC25A1 expression in zebrafish, we were able to mirror the human disease in terms of variable brain, eye and cardiac involvement. Importantly, we show clear abnormalities in the neuromuscular junction, regardless of the severity of the phenotype.ConclusionsBased on the axonal outgrowth defects seen in SLC25A1 knockdown zebrafish, we hypothesize that the neuromuscular junction impairment may be related to pre-synaptic nerve terminal abnormalities. Our findings highlight the complex machinery required to ensure efficient neuromuscular function, beyond the proteomes exclusive to the neuromuscular synapse.

The co-existence of myasthenia gravis in patients with myositis: A case series

ObjectiveMyositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients. MethodsWe identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features. ResultsAll 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%) patients. High-dose steroids were associated with worsening weakness in 2/6 (33%) patients. ConclusionsProminent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis–MG overlap, high-dose steroids may exacerbate symptoms and pyridostigmine may play an important therapeutic role.

P.12.4 Great phenotypic variability in two siblings affected by congenital myasthenic syndrome associated with mutations in MUSK

Congenital myasthenic syndromes (CMS) are rare genetic diseases, in which neuromuscular transmission is impaired. To date 17 CMS disease genes have been identified with mutations in MUSK reported in only 8 patients. Here, we describe clinical, neurophysiological, and molecular features of two Italian siblings who carrying compound heterozygous mutations in MUSK. The first sibling is a 27-year-old woman. As a neonate, she had laryngeal stridor and respiratory failure requiring mechanical ventilation and tube feedings. Her subsequent clinical course was characterized by bilateral eyelid ptosis, paresis of lateral and vertical gaze, mild tongue weakness and atrophy, and severe weakness of the facial, neck flexor, and proximal limb muscles. Treatment with 3,4-diaminopyridine was of mild benefit, while pyridostigmine worsened her symptoms. The second sibling is a 29-year-old man. He had bilateral eyelid ptosis since birth but later only mild fatigable weakness of the proximal leg muscles which did not limit his daily activities and participation in sports. Examination at age of 28 years only revealed mild tongue weakness and atrophy, mild bilateral eyelid ptosis, limitation of lateral and vertical gaze, and mild facial and proximal leg muscle weakness. Mutation analysis of MUSK revealed 2 mutations: a previously identified c.2368G > A (p.Val790Met) mutation, reported by Chevassier et al., and a novel c.467delA (p.Lys156Argfsstop20) mutation. Thus, the phenotypic expression of the identical MUSK mutations was markedly different in the two siblings with the sister being more severely affected. To our knowledge a mild phenotype in one of two siblings harbouring the same mutations has never been documented in MuSK–MG.

Muscle specific kinase autoimmune myasthenia gravis in children: A case series

We report clinical, neurophysiological and autoantibody profiles of 9 children presenting with fatigable weakness and MuSK autoantibody seropositivity. Eight were female, 3 were black; median onset age was 8years. Diplopia or bulbar dysfunction were common presenting symptoms. Half of the patients experienced moderate to severe weakness of bulbar, facial and respiratory muscles (including exacerbations requiring mechanical ventilation). Muscle AChR antibodies were detected transiently in 2 patients but no other autoantibodies were detected. Clinical response to treatment was variable and incomplete. No thymic abnormalities were noted by CT or pathologically (3 underwent thymectomy). Electromyographic (EMG) abnormalities (decrement of compound muscle action potential amplitude during slow repetitive nerve stimulation and variation in individual motor unit potentials) were limited to clinically weak muscles. Single fiber EMG demonstrated abnormalities in an asymptomatic muscle in the single patient studied. As in adults, MuSK autoimmune MG presents more commonly in females, and weakness preferentially affects bulbar, facial and respiratory muscles. Morbidity is significant and responses to standard therapies are variable and incomplete. Neurophysiological confirmation is more challenging in children because testing of weak muscles (cranial nerve-innervated and respiratory) may require moderate sedation and monitoring.

Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous disorders characterized by a neuromuscular transmission defect. In recent years, causative mutations have been identified in atleast 15 genes encoding proteins of the neuromuscular junction. Mutations in MUSK are known as a very rare genetic cause of CMS and have been described in only three families, world-wide. Consequently, the knowledge about efficient drug therapy is very limited. We identified a novel missense mutation (p.Asp38Glu) heteroallelic to a genomic deletion affecting exons 2–3 of MUSK as cause of a limb-girdle CMS in two brothers of Turkish origin. Clinical symptoms included fatigable limb weakness from early childhood on. Upon diagnosis of a MUSK-related CMS at the age of 16 and 13years, respectively, treatment with salbutamol was initiated leading to an impressive improvement of clinical symptoms, while treatment with esterase inhibitors did not show any benefit. Our findings highlight the importance of a molecular diagnosis in CMS and demonstrate considerable similarities between patients with MUSK and DOK7-related CMS in terms of clinical phenotype and treatment options.

Foodborne Botulism Treated with Heptavalent Botulism Antitoxin

To report a case of foodborne botulism and subsequent use of the investigational heptavalent botulism antitoxin (H-BAT). A 60-year-old man was hospitalized with blurred vision, diplopia, and dysarthria. On hospital day 2, the patient was transferred to the intensive care unit for progressive fatigable weakness with ptosis, dysphagia, dysarthria, and nausea. Secondary to worsening respiratory distress, the patient was intubated and placed on a ventilator. The patient could open his eyes only with assistance but still had normal strength in all extremities. H-BAT was administered 48 hours after presentation for possible botulism. The patient then revealed that he consumed home-canned corn several days prior to admission. On hospital day 8, botulinum neurotoxin was confirmed in the patient's serum and the home-canned corn. The patient slowly regained muscle strength and was discharged to a long-term acute care facility on hospital day 22. Foodborne botulism is caused by a neurotoxin from Clostridium botulinum and usually occurs after the consumption of improperly prepared home-canned food. Botulism is characterized by symmetrical descending paralysis that may progress to respiratory arrest. The standard confirmatory test for botulism is a mouse bioassay to prove the presence of botulinum neurotoxin. Outside of supportive care, the treatment options for botulism are limited. Individuals with botulism often require intensive care unit monitoring and potentially ventilatory support. H-BAT, the only treatment available for botulism in patients older than 1 year, is a purified and despeciated equine-derived immunoglobulin active against all known botulinum neurotoxins. H-BAT's despeciation significantly reduces the risk of hypersensitivity reactions, anaphylaxis, and serum sickness. In a confirmed case of foodborne botulism treated with H-BAT, the patient tolerated H-BAT and did not develop any hypersensitivity reactions or serum sickness.

Congenital Myasthenic Syndrome Due to Choline Acetyltransferase Mutations in Infants

Congenital myasthenic syndromes are inherited disorders caused by various defects in neuromuscular transmission. Although the typical presentation is fatigable weakness with prominent cranial involvement, neonates can lack these hallmark manifestations, and in those with choline acetyltransferase gene mutations, basal electrophysiological testing can yield negative findings. The authors report the case of a male infant presenting at birth with oculomotor and bulbofacial weakness, hypotonia, clubfoot, and severe respiratory insufficiency. Electromyography showed myogenic signs, and basal repetitive nerve stimulation yielded negative findings. Since age 6 months, the infant had progressively improved, acquiring autonomous respiration. Prolonged subtetanic repetitive nerve stimulation disclosed a marked decremental response compatible with suspected congenital myasthenic syndrome with episodic apnea. Genetic testing identified 2 novel choline acetyltransferase mutations (R470X, F580C). Keeping a high clinical suspicion of this rare condition and undertaking early comprehensive electrophysiological assessments including prolonged repetitive nerve stimulation (10 Hz for 5 minutes) can expedite the diagnosis.

Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations

Congenital myasthenic syndromes due to DOK7 mutations cause fatigable limb girdle weakness. Treatment with ephedrine improves muscle strength. Salbutamol, a β(2)-adrenergic receptor agonist with fewer side effects and more readily available, has been effective in adult and anecdotal childhood cases. This study reports the effects of salbutamol on motor function in childhood DOK7 congenital myasthenic syndrome. Nine children (age range 5.9-15.1years) were treated with oral salbutamol, 2-4mg TDS. The effect on timed tests of motor function, pre- and up to 28months post-treatment, was audited retrospectively. All 9 reported functional benefit within 1month, with progressive improvement to a plateau at 12-18months. Within the first month, all 3 non-ambulant children resumed walking with assistance. Although improvements were seen in some timed tests (timed 10m, arm raise time, 6min walk time) this did not fully reflect the observed functional benefits in daily living activities. No major side effects were reported. We conclude that oral salbutamol treatment significantly improves strength in children with DOK7 congenital myasthenic syndrome and is well tolerated. Outcome measures need to be refined further, both to accurately reflect functional abilities in children and to document progress and treatment response.

Myasthenia Gravis

Myasthenia gravis (MG) is the most common disorder of the neuromuscular junction (NMJ), with an estimated prevalence between 25 and 142 per million. It characteristically presents with fatigable weakness, often initially involving the ocular muscles and manifesting as intermittent ptosis and diplopia. Ultimately, the disease generalizes in two-thirds of patients, leading to weakness of bulbar, neck, limb, and respiratory muscles. The majority of patients with generalized MG, and roughly half of patients with purely ocular disease, harbor antibodies to skeletal muscle nicotinic acetylcholine receptors. A subset of patients with generalized disease have antibodies to muscle-specific receptor tyrosine kinase (MuSK). Acetylcholinesterase inhibitors are often the first modality of therapy for MG. As an immune-mediated disorder, MG can respond to several immunosuppressive agents, such as corticosteroids, azathioprine, mycophenolate mofetil, and cyclosporin. Thymectomy is a key component of management in appropriately chosen MG patients and those with thymoma. Newer or alternative immunotherapies including tacrolimus, rituximab, methotrexate, and complement inhibiting agents are an area of active investigation.