Journal of Neuromuscular Diseases - Volume 5, issue 2

Authors: Stålberg, Erik | Kouyoumdjian, João Aris | Paiva, Gabriel Pina | Yanaze, Larissa Luri | Sanders, Donald B.

Article Type: Research Article

Abstract: Comparing results from jitter studies performed with voluntary and electrical activation is difficult to perform quantitatively, particularly in complex signals as seen in reinnervation. High jitter values in individual spikes in these multispike signals can be missed with both activation methods, which introduces a bias towards more normal values. With voluntary activation, triggering on a spike from an abnormal end-plate in multispike potentials will overestimate individual jitter values and the number of abnormal jitter values. With electrical stimulation, artefactually-increased jitter may be caused by subliminal stimulation, which causes uncertainty at the stimulation point. Electrical stimulation also may activate …many axons, causing signal summation, with erroneous or impossible jitter estimation. Awareness of such pitfalls can improve the correct performance and interpretation of jitter recordings. Quantitative comparisons of results can be made between studies in reinnervated muscle performed with the same activation method, but not between results obtained with different activation methods. Show more

Keywords: Concentric needle electrode, SFEMG, jitter, reinnervation, electrical stimulation

DOI: 10.3233/JND-170289

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 225-230, 2018

Authors: Clausen, Lisa | Cossins, Judith | Beeson, David

Article Type: Research Article

Abstract: Background: Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular transmission disorders causing fatiguable muscle weakness. ADRB2 agonists have been observed to provide therapeutic benefit where destabilisation of NMJ structures is part of the underlying pathology, such as in DOK7, COLQ and MuSK CMS as well as in slow channel syndrome. However, very little is known about the molecular mechanisms underlying the effects of ADRB2 agonists in CMS. Objective: In vitro investigation into whether an ADRB2 agonist affects the AChR clustering pathway and has the potential to increase the number and stability of AChR clusters. …Methods: Cultured C2C12 mouse myotubes overexpressing the common DOK7 frameshift mutation c.1124_1127dupTGCC were incubated with salbutamol sulphate and the effect on AChR cluster numbers were investigated. Moreover, agrin-induced AChR clusters in C2C12 WT cells were left to disperse after agrin-wash-off, and the effects of incubation with salbutamol sulphate on AChR cluster numbers were explored. Results: Salbutamol sulphate induced a significant increase in the number of AChR clusters formed on C2C12 cells overexpressing c.1124_1127dupTGCC. Furthermore, significantly more clusters remained in C2C12 WT myotubes incubated with salbutamol sulphate following agrin wash-off. Conclusions: The results suggest that ADRB2 agonists directly affect proteins located at the neuromuscular junction and exert a stabilising effect on AChR clusters. Show more

Keywords: Myasthenic syndromes, congenital, adrenergic beta-2 receptor agonists, neuromuscular junction, DOK7 protein, human

DOI: 10.3233/JND-170293

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 231-240, 2018

Authors: Landon-Cardinal, Océane | Friedman, Diane | Guiguet, Marguerite | Laforêt, Pascal | Heming, Nicholas | Salort-Campana, Emmanuelle | Jouen, Fabienne | Allenbach, Yves | Boyer, Olivier | Chatenoud, Lucienne | Eymard, Bruno | Sharshar, Tarek | Benveniste, Olivier

Article Type: Research Article

Abstract: Background: Several retrospective case series have suggested rituximab (RTX) might improve patients with refractory Myasthenia Gravis (MG). Objective: In this study, we aimed to evaluate prospectively the efficacy of RTX on muscle function in refractory generalized anti-acetylcholine receptor (AChR) MG patients. Methods: Enrolled patients received 1 g of RTX at day 0, day 14, and 6-month follow-up (M6). The primary endpoint was improvement of muscle function at 12-month (M12) based on myasthenic muscle score (MMS). Secondary endpoints were an improvement of the MG Foundation of America Postintervention Status (MGFA-PIS), respiratory forced vital capacity, occurrences of acute …MG exacerbation and requirement of associated immunosuppressants and immunomodulatory agents. Results: Twelve patients were enrolled, and 11 completed the study. Only a single patient presented an improvement of at least 20 points on MMS at M12, although 2 patients displayed an increase of at least 18 points at M12. MGFA-PIS had improved in 55% of patients by M12. The clinical improvement was not associated with a reduction of immunosuppressant burden. Conclusions: These results provide data on the effect of RTX in patients with severe, refractory anti-AChR Abs generalized MG. Even though primary outcome was only reached in a single patient at M12, a beneficial effect of RTX on muscle function was seen in half of the patients at M12 and persisted in a third of patients at M18. Show more

Keywords: Myasthenia gravis, rituximab, refractory generalized myasthenia, anti-acetylcholine receptor antibodies, anti-AchR, anti-CD20 monoclonal antibodies

DOI: 10.3233/JND-180300

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 241-249, 2018

Authors: Cornwall, Kylie M. | Butterfield, Russell J. | Hernandez, Antonio | Heatwole, Chad | Johnson, Nicholas E.

Article Type: Short Communication

Abstract: Congenital muscular dystrophies (CMD) cause progressive muscle weakness resulting in severe motor disabilities. Previous studies focused on the effects of motor disability. Here, we explore other factors affecting health related quality-of-life (HRQOL) in CMD. Qualitative interviews were conducted with participant-parent dyads to identify symptoms having the greatest impact on HRQOL. Symptoms were classified into themes and domains representing physical, mental, social health, and disease specific issues. Social role limitations and specific activity impairment were frequently mentioned. A greater understanding of symptoms impacting HRQOL will provide a framework for improved clinical care and patient centered outcomes as new therapies are developed.

Keywords: Muscular dystrophy, quality of life, ullrich congenital muscular dystrophy, bethlem myopathy

DOI: 10.3233/JND-170252

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 251-255, 2018

Authors: Lornage, Xavière | Sabouraud, Pascal | Lannes, Béatrice | Gaillard, Dominique | Schneider, Raphaël | Deleuze, Jean-François | Boland, Anne | Thompson, Julie | Böhm, Johann | Biancalana, Valérie | Laporte, Jocelyn

Article Type: Short Communication

Abstract: Congenital myopathies are clinically and genetically heterogeneous, and are classified based on typical structural abnormalities on muscle sections. Recessive mutations in the striated muscle preferentially expressed protein kinase (SPEG ) were recently reported in patients with centronuclear myopathy (CNM) associated in most cases with dilated cardiomyopathy. Here we report the identification of novel biallelic truncating SPEG mutations in a patient with moderate congenital myopathy without clinical and histological hallmarks of CNM and without cardiomyopathy. This study expands the phenotypic spectrum of SPEG-related myopathy and prompts to consider SPEG for congenital myopathies without specific histological features.

Keywords: Centronuclear myopathy, myotubular myopathy, MTM1, myotubularin, SPEG, congenital myopathy

DOI: 10.3233/JND-170265

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 257-260, 2018

Authors: Strijbos, Ellen | Verschuuren, Jan J.G.M. | Kuks, Jan B.M.

Article Type: Case Report

Abstract: A patient with autoimmune myasthenia gravis and a clinical and serological follow-up of 13 years is described. In this unique case, serum samples were available up to two years before the clinical onset of the myasthenia gravis and showed gradual increase of acetylcholine receptor antibodies, starting two years before onset of the clinical symptoms.

Keywords: Myasthenia gravis, pregnancy, acetylcholine receptor antibodies, neuroimmunology

DOI: 10.3233/JND-180313

Citation: Journal of Neuromuscular Diseases, vol. 5, no. 2, pp. 261-264, 2018