anti-MuSK Antibody-positive Myasthenia Gravis Research Articles

Long-term efficacy and safety of tacrolimus in anti-MuSK antibody-positive myasthenia gravis: a retrospective single-center cohort study.

To evaluate the long-term efficacy and safety of tacrolimus in patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG). We performed a retrospective, single-center, and cross-sectional study analyzing medical records of 18 MuSK-MG patients treated with tacrolimus for more than 1 year. The efficacy and safety of tacrolimus were evaluated by modified Osserman scale, Myasthenia Gravis Foundation of America post-intervention status, prednisone dosage, quantitative MG (QMG) scores, MG-activity of daily living (MG-ADL) scores, anti-MuSK antibody titers, blood routine, and serum biochemicals. After 4 weeks of tacrolimus treatment, there was a significant improvement in prednisone dose, QMG, and MG-ADL scores, which continued to improve over 1 year. In addition, clinical grade of modified Osserman scale was improved in all patients, 16 (88.9%) of whom were asymptomatic at the last visit. More importantly, the mean titers of anti-MuSK antibody were significantly decreased from 0.777 ± 0.381 to 0.283 ± 0.178 nmol/L after a median of 1.4 years of tacrolimus treatment in 9 patients with MuSK-MG (P = 0.015). All patients achieved minimal manifestations status (MMS) after tacrolimus treatment (range, 4-32 weeks). Subsequently, seven patients (38.9%) underwent a taper of tacrolimus dosage. However, four patients (57.1%) experienced an exacerbation. Adverse events occurred in 2 patients (11.1%), all of which were mild and resolved after the tacrolimus dose was adjusted or discontinued. Our results suggest that tacrolimus may be an effective and safe steroid-sparing treatment for patients with MuSK-MG. However, tacrolimus should be carefully tapered to avoid disease exacerbation.

Rituximab in the Management of Refractory Myasthenia Gravis and Variability of Its Efficacy in Anti-MuSK Positive and Anti-AChR Positive Myasthenia Gravis.

Myasthenia gravis affects the neuromuscular junction of the skeletal muscles. It results in muscle weakness involving skeletal muscles (diaphragm, extraocular muscles) and myasthenic crisis. Treatment options for myasthenia gravis management have expanded, including azathioprine, corticosteroids, plasma exchange, and tacrolimus. Unfortunately, a few cases of myasthenia gravis don't respond to conventional treatment modalities. Monoclonal antibodies, rituximab (RTX), are novel treatments that have garnered interest as of late due to their efficacy within the patient population presented with refractory form myasthenia gravis. This review aims to showcase how RTX is an effective treatment within different forms of myasthenia gravis. A limited review was performed using databases that include PubMed and Google Scholar. The following keywords were used: "myasthenia gravis," "rituximab," "monoclonal antibody," "anti-AChR antibody," and "refractory myasthenia." The review focused on case reports, human studies, or research surveys based on the inclusion criteria of human studies involving participants more than 18 years of age and published in English literature. Out of 69 articles, 14 were duplicates, and 29 were relevant and met the inclusion criteria. The findings from the study demonstrate that patients with refractory myasthenia gravis responded well to RTX treatment. Furthermore, RTX has been shown to decrease corticosteroid dependence, induce sustained remission, and have a favorable response to anti-MuSK antibody positive myasthenia gravis compared to anti-AChR antibody positive myasthenia gravis. This literature review suggests that patients with refractory myasthenia gravis can benefit from rituximab; however, it has a variable response in different forms of myasthenia gravis.

Serum high mobility group box 1 is upregulated in myasthenia gravis

ObjectiveHigh mobility group box 1 (HMGB1) functions as an inflammatory mediator and is implicated in the pathogenesis of various autoimmune diseases. Our primary aim is to determine whether HMGB1 is...

Videofluorographic detection of anti–muscle-specific kinase–positive myasthenia gravis

A 47-year-old woman with dysphagia and ptosis gradually developed dysarthria and muscular weakness. Magnetic resonance imaging, testing for anti–acetylcholine receptor antibodies, edrophonium chloride (EC) test, and electrophysiologic test revealed no abnormalities. A psychogenic reaction was suspected. Four months after disease onset, the patient presented to our hospital. In videofluoroscopic examination of swallowing (VF), there was no aspiration for swallowing of either liquid or soft food. It revealed, however, poor pharyngeal constriction, no epiglottis inversion, repeated swallowing movements, and large amounts of pharyngeal residue. Videofluoroscopic examination of swallowing after an intravenous injection of 10 mg EC showed improvements in all above observations; particularly, it was clear when swallowing soft food. Furthermore, the anti–muscle-specific kinase (MuSK) antibody titer was elevated, and anti-MuSK antibody–positive myasthenia gravis (MuSK-MG) was diagnosed. Thus VF during EC test may be helpful in diagnosing MuSK-MG in patients with dysphagia.

Childhood-onset anti-MuSK antibody positive myasthenia gravis demonstrates a distinct clinical course

Anti-muscle-specific tyrosine kinase antibody (MuSK-Ab) is the second most frequent autoantibody identified in adult patients with myasthenia gravis (MG). Adult patients with MuSK-Ab demonstrate characteristic clinical features but very little information is available for childhood-onset patients with MuSK-positive MG. We report a childhood-onset female patient with MuSK-positive MG. This patient showed basic clinical features compatible with adult-onset MuSK-positive MG, but some features, including spontaneous improvement, are distinct from those in adult patients. Serial examination of MuSK-Ab titers revealed a gross correlation with clinical severity despite significantly high titers throughout the clinical course. Therefore, childhood-onset MuSK-positive MG may demonstrate a distinct clinical characteristics in the early period of illness.

Treatment of anti-MuSK antibody positive myasthenia gravis

The authors report the case of a 27-year-old woman with muscle-specific receptor tyrosine kinase antibody positive myasthenia with predominantly ocular and bulbar symptoms. Both edrophonium and low dose (4×30 mg/day) pyridostigmin resulted in cholinergic side effects including fasciculation mainly in the facial and neck muscles, and excessive salivation. The patient responded well to a relatively high dose of chronic corticosteroid treatment (methyprednisolone 64mg/day), but the decrease of the corticosteroid dose below 16 mg/day induced exacerbation of the clinical symptoms. Immunosuppression with azathioprine and methotrexate failed to maintain the clinical improvement. However, plasma exchange was always very effective, and all clinical symptoms improved significantly. The authors conclude that patients with muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis should have an individual treatment protocol differing from those used in patients who do not have this antibody but are positive for acetylcholine-receptor antibody. Identification of the pathogenic antibody in the early stage of myasthenia gravis may help to develop the optimal, individualized treatment strategy, to avoid severe side effects, and to achieve fast improvement. Orv. Hetil., 2011, 152, 1586–1589.

A pregnant patient with anti-MuSK antibody positive myasthenia gravis and her infant with transient neonatal myasthenia gravis

A 30-year-old healthy woman experienced speech disturbance and swallowing difficulty at two months of pregnancy. She was diagnosed as myasthenia gravis (MG) with anti-MuSK antibodies. At eight months of pregnancy, bulbar palsy, eye movement disturbance, and muscle weakness worsened unexpectedly. Plasma exchange was performed three times daily starting from the 1st day of the 37th pregnancy week (2 L/day, albumin substitution of 5%) and the patient underwent caesarean section and gave birth to the girl safely. The infant had anti-MuSK antibodies in the serum and umbilical cord blood. The infant's suckling power was weak. The infant was diagnosed as transient neonatal myasthenia gravis. There is no case where management of MG has been performed from the period of pregnancy for anti-MuSK positive patients. For the control of Anti-MuSK positive patients in addition to normal care for Anti-AChR antibodies positive patients, it is important to carefully observe symptoms caused by bulbar palsy, draw attentions on malnutrition and polyhydramnios, and perform simple plasmapheresis on regular basis without any delay.

Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravis

Anti-muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) patients show various responses to conventional immunosuppressive treatment and some patients are resistant to these therapies. We report a 50-year-old Japanese man with anti-MuSK antibody-positive MG, who showed no or poor response to various therapies, including plasmapheresis, corticosteroid, and tacrolimus. The patient was then treated with intravenous immunoglobulin (IVIG), and showed a good response that persisted over 20 months. The outcome of this case suggests that IVIG treatment may be an effective therapeutic option for anti-MuSK antibody-positive MG, with a potentially long-term effect.