7,183 research outputs found
Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China
No full textTing He,1,* Kangzhi Chen,1,* Yi Li,1 Zhaohui Luo,1 Mengchuan Luo,2 Huan Yang1 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan Yang, Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email [email protected]: To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab).Patients and Methods: A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis.Results: Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037– 0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16– 0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04– 0.94; P = 0.042) as an independent risk factor for MMS achievement.Conclusion: DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.Keywords: double-seropositive myasthenia gravis, muscle-specific kinase antibody, acetylcholine receptor antibody, minimal manifestation status, myasthenia gravis activities of daily livin
Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis
No full textBackground: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. Methods: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. Results: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen’s kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. Conclusion: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice
Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis
No full textBackground: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG.
Methods: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups.
Results: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation.
Conclusion: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice
MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK
No full textSera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1 +, IgG2 + and IgG3 + peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. (C) 2016 Elsevier B.V. All rights reserved
Repetitive Nerve Stimulation in MuSK-Antibody-Positive Myasthenia Gravis
No full textBACKGROUND AND PURPOSE: Responses to repetitive nerve stimulation (RNS) in patients with muscle-specific tyrosine kinase (MuSK) antibody (Ab)-positive myasthenia gravis (MG) vary depending on the muscles tested. We analyzed the RNS responses of limb and facial muscles in MuSK-Ab-positive and acetylcholine receptor (AChR)-Ab-negative MG (MuSK MG) and MuSK-Ab-negative and AChR-Ab-negative [double-seronegative (DSN)] MG patients.
METHODS: We retrospectively compared RNS responses between 45 MuSK MG and 29 DSN MG. RNS was applied to the abductor digiti minimi, flexor carpi ulnaris, trapezius, orbicularis oculi, and nasalis muscles.
RESULTS: Abnormal RNS responses in limb muscles were observed in 22.2 and 58.6% of MuSK MG and DSN MG patients, respectively, with abnormal facial responses observed in 77.8 and 65.5%, and abnormal responses observed in any of the five muscles in 86.7 and 72.4%. Abnormal RNS responses in the abductor digiti minimi or flexor carpi ulnaris were less frequent in MuSK MG (8.9 and 15.6%, respectively) than in DSN MG (37.9 and 55.2%), whereas the findings for other muscles were not significantly different between the groups. Abnormal facial responses but normal limb responses were independently associated with MuSK MG (odds ratio=5.224, 95% confidence interval=1.300-20.990).
CONCLUSIONS: Abnormal RNS responses primarily in facial muscles without involvement of limb muscles were more pronounced in MuSK MG than in DSN MG. RNS of both facial and limb muscles in AChR-Ab-negative MG can increase the test sensitivity and aid in early suspicion of MuSK MG.ope
Familial autoimmune MuSK positive myasthenia gravis
No full textThe familial occurrence of autoimmune myasthenia gravis
(MG) with anti-acetylcholine receptor antibodies (AChR
Ab) has been rarely reported. Different antibody
specificity in family members has also been described. To our knowledge, a familial form of MuSK Ab positive MG has never been reported. We studied the HLA allele profile in a family with two sisters affected by MuSK positive MG
Clinical and Electrophysiologic Responses to Acetylcholinesterase Inhibitors in MuSK-Antibody-Positive Myasthenia Gravis: Evidence for Cholinergic Neuromuscular Hyperactivity
No full textBACKGROUND AND PURPOSE:
Patients with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-Ab)-positive myasthenia gravis (MG) show distinct responses to acetylcholinesterase inhibitors (AChEIs). Although clinical responses to AChEIs in MuSK-Ab MG are reasonably well known, little is known about the electrophysiologic responses to AChEIs. We therefore investigated the clinical and electrophysiologic responses to AChEIs in MuSK-Ab-positive MG patients.
METHODS:
We retrospectively reviewed the medical records and electrodiagnostic findings of 17 MG patients (10 MuSK-Ab-positive and 7 MuSK-Ab-negative patients) who underwent electrodiagnostic testing before and after a neostigmine test (NT).
RESULTS:
The frequency of intolerance to pyridostigmine bromide (PB) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (50% vs. 0%, respectively; p=0.044), while the maximum tolerable dose of PB was lower in the former (90 mg/day vs. 480 mg/day, p=0.023). The frequency of positive NT results was significantly lower in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (40% vs. 100%, p=0.035), while the nicotinic side effects of neostigmine were more frequent in the former (80% vs. 14.3%, p=0.015). Repetitive compound muscle action potentials (R-CMAPs) developed more frequently after NT in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (90% vs. 14.3%, p=0.004). The frequency of a high-frequency-stimulation-induced decrement-increment pattern (DIP) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (100% vs. 17.7%, p=0.003).
CONCLUSIONS:
These results suggest that MuSK-Ab-positive MG patients exhibit unique and hyperactive responses to AChEIs. Furthermore, R-CMAP and DIP development on a standard AChEI dose may be a distinct neurophysiologic feature indicative of MuSK-Ab-positive MG.ope
MuSK-Ab positive myasthenia: Not always grave
No full textAntibodies (Abs) to muscle-specific tyrosine kinase (MuSK) are detected in approximately 40% of generalized acetylcholine receptor antibody-negative myasthenia gravis (MG). Anti-MuSK Abs are nearly always associated with generalized symptoms, with prevalent involvement of craniobulbar, cervical and respiratory muscles and with a striking preponderance in women. The typical course of MuSK-MG is acute onset, rapid progression, brittle course in the first years, early respiratory crises and unprovoked relapses in spite of high-dose immunosuppression. Patients often require long-term management with multiple immunosuppressive (IS) agents and many of them remain dependent on IS treatment. The majority of anti-MuSK Abs are of the non-complement-binding IgG4 subclass. We report the case of a Greek female MuSK-MG patient with typical phenotype but clearly atypical clinical course during 12 years of follow-up. The patient received only corticosteroid treatment for one year and showed mild and stable MG symptoms under no treatment for the rest of the observation period, except for postpartum mild and short-lived exacerbation. In mildly symptomatic stable state, anti-MuSK Abs were of the IgG4 subclass and no other immunological peculiarity was detected. © 2013 Published by Elsevier B.V
Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes
No full textObjective: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes. Methods: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative and single-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens with histological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear gene POLG1 was sequenced. Results: Five AChR-Ab seropositive [AChR(+)] and 5 seronegative [AChR(-)] patients were MuSK-Ab seropositive [MuSK(+)]. Five of 7 neurophysiologically examined MuSK(+) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(-)/AChR(+) patients (23%) (P=0.012). SFEMG was abnormal in all examined MuSK(+) patients. All 7 biopsied MuSK(+) and 32 MuSK(-) patients (89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(+) and 13 of 20 MuSK(-) patients analyzed had multiple mtDNA deletions but no POLG1 mutations. Conclusions: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(+) and AChR(+) patients. Proximal myopathy was over-represented in MuSK(+) patients; however, both MuSK(+) and MuSK(-) patients had mild myopathy with frequent mitochondrial abnormalities. Significance: The weakness in MuSK(+) patients is most likely due to disturbed neuromuscular transmission. The frequently encountered mitochondrial dysfunction in MG warrants further study. © 2006 International Federation of Clinical Neurophysiology
IgG-specific cell-based assay detects potentially pathogenic MuSK-Abs in seronegative MG
No full textObjective:To increase the detection of MuSK-Abs using a CBA and test their pathogenicity.Methods:Sera from 69 MuSK-RIA–positive patients with myasthenia gravis (MG) (Definite MuSK-MG), 169 patients negative for MuSK-RIA and AChR-RIA (seronegative MG, SNMG), 35 healthy individuals (healthy controls, HCs), and 16 NMDA receptor-Ab–positive (NMDAR-Ab) disease controls were tested for binding to MuSK on a CBA using different secondary antibodies.Results:Initially, in addition to 18% of SNMG sera, 11% of HC and 19% of NMDAR-Ab sera showed positive binding to MuSK-transfected cells; this low specificity was due to anti-IgG(H+L) detection of IgM bound nonspecifically to MuSK. Using an IgG Fc gamma-specific secondary antibody, MuSK-Abs were detected by CBA in 68/69 (99%) of Definite MuSK-MG, 0/35 HCs, 0/16 NMDAR-Ab, and 14/169 (8%) of SNMG sera, providing increased sensitivity with high specificity. The RIA-negative, CBA-positive MuSK-IgG sera, but not IgM-MuSK–binding sera, reduced agrin-induced AChR clustering in C2C12 myotubes, qualitatively similar to RIA-positive MuSK-Abs.Conclusions:An IgG-specific MuSK-CBA can reliably detect IgG MuSK-Abs and increase sensitivity. In the MuSK-CBA, IgG specificity is essential. The positive sera demonstrated pathogenic potential in the in vitro AChR-clustering assay, although less effective than Definite MuSK-MG sera, and the patients had less severe clinical disease. Use of IgG-specific secondary antibodies may improve the results of other antibody tests.Classification of evidence:This study provides Class III evidence that an IgG-specific MuSK-CBA identifies patients with MG.</jats:sec
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