Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis.

Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.

MuSK-Associated Myasthenia Gravis: Clinical Features and Management.

Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare, frequently more severe, subtype of MG with different pathogenesis, and peculiar clinical features. The prevalence varies among countries and ethnic groups, affecting 5-8% of all MG patients. MuSK-MG usually has an acute onset affecting mainly the facial-bulbar muscles. The symptoms usually progress rapidly, within a few weeks. Early respiratory crises are frequent. The disease may lead to generalized muscle weakness up to muscle atrophy. The main bulbar involvement, the absence of significant thymus alterations, and the association with HLA class II DR14, DR16, and DQ5 alleles have been confirmed. Atypical onset, such as ocular involvement, lack of symptom fluctuations, acetylcholinesterase inhibitors failure, and negative results of electrophysiologic testing, if not specifically performed in the mainly involved muscle groups, makes MuSK-MG diagnosis challenging. In most cases, steroids are effective. Conventional immunosuppressants are not commonly able to replace steroids in maintaining a satisfactory long-term control of symptoms. However, the majority of MuSK-MG patients are refractory to treatment. In these cases, the use of rituximab showed promising results, resulting in sustained symptom control.

Myasthenia gravis: MuSK MG, late-onset MG and ocular MG.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction which affects all striated muscles, resulting in fluctuating weakness. Approaching MG as a disease with subgroups having different clinical, serological and genetic features is crucial in predicting the progression and planning treatment. Three relatively less frequently seen subtypes of MG are the subject of this review: MG with anti-MuSK antibodies (MuSK MG), non-thymomatous late-onset MG (LOMG), and ocular MG (OMG). In addition to reviewing the literature, mainly from a clinical point of view, our experience in each of the subgroups, based on close to 600 patients seen over a 10 year period, is related. MuSK MG is a severe disease with predominant bulbar involvement. It is more common in women and in early-onset patients. With the use of high dose corticosteroids, azathioprine and more recently rituximab, outcome is favorable, though the patients usually require higher maintenance doses of immunosuppressives. LOMG with onset ≥ 50 years of age is more common in men and ocular onset is common. Frequency of anti-AChR and anti-titin antibodies are high. Although it can be severe in some patients, response to treatment is usually very good. OMG is reported to be more frequent in men in whom the disease has a later onset. Anti-AChR antibodies are present in about half of the patients. Generalization is less likely when symptoms remain confined to ocular muscles for 2 years. Low dose corticosteroids are usually sufficient. Thyroid disease is the most common autoimmune disease accompanying all three subgroups.

Dysautonomia as the Presenting Symptom in Anti-Muscle-Specific Kinase Antibody Myasthenia Gravis.

In an minority of Myasthenia Gravis (MG) patients, the autoantibodies bind to muscle-specific kinase (MUSK). These MuSK antibody-mediated MG (MuSK MG) patients are not only immunologically distinct, but also have different characteristic clinical features. Dysautonomia in MG is rarely reported. We present a MuSK MG patient who suffered from life-threatening autonomic dysfunction. MuSK MG should be considered in the differential diagnosis in cases of unclarified dysautonomia, given the potential for treatment in those cases.

MuSK myasthenia gravis and pregnancy.

Muscle specific kinase (MuSK) myasthenia gravis (MG, MuSK-MG) is a rare subgroup of MG affecting mainly women during childbearing years. We investigated the influence of pregnancy in the course of MuSK-MG and pregnancy outcomes in females with MuSK-MG. A multicentre cohort of 17 women with MuSK-MG was studied retrospectively; 13 of them with ≥1 pregnancy. MuSK-MG onset age was 35,4 years; 23,0% had other autoimmune disorder; 46,2% were treatment refractory. Thirteen women experienced 27 pregnancies, either after MG onset (group I) (n = 4; maternal age at conception = 29.8 years) or before MG onset (group II) (n = 23; maternal age at conception = 26.2 years). In group I pregnancy occurred in average 9.8 years after the MG onset; it occurred in average 17.0 years before MG in group II. In group I, all were on steroids at time of conception, one on azathioprine and another receiving IVIG regularly. There were mild exacerbations that responded to treatment adjustments. There were no relapses in the 12 months following the delivery. There was no pre-eclampsia, birth defects or stillbirths in either group; 3 miscarriages in group II. One case of neonatal MG was recorded. In this small series, pregnancy did not seem to precipitate MuSK-MG or to have a major influence in the MuSK-MG course, and there was no apparent negative impact in pregnancy outcomes in those where pregnancy followed the MG onset. The weight was lower in the newborn of the group I mothers, although none had low birth weight.

Report of the ASFA apheresis registry on muscle specific kinase antibody positive myasthenia gravis.

BACKGROUND: Anti-muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti-acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. METHODS: The study collected detailed de-identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. RESULTS: A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 - 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty-one percent of patients responded poorly with minimal recovery. CONCLUSION: Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor-responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5-11, 2017. © 2016 Wiley Periodicals, Inc.

Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.

This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey.