Journal of Neuromuscular Diseases - Volume 6, issue 1

Authors: Strijkers, Gustav J. | Araujo, Ericky C.A. | Azzabou, Noura | Bendahan, David | Blamire, Andrew | Burakiewicz, Jedrek | Carlier, Pierre G. | Damon, Bruce | Deligianni, Xeni | Froeling, Martijn | Heerschap, Arend | Hollingsworth, Kieren G. | Hooijmans, Melissa T. | Karampinos, Dimitrios C. | Loudos, George | Madelin, Guillaume | Marty, Benjamin | Nagel, Armin M. | Nederveen, Aart J. | Nelissen, Jules L. | Santini, Francesco | Scheidegger, Olivier | Schick, Fritz | Sinclair, Christopher | Sinkus, Ralph | de Sousa, Paulo L. | Straub, Volker | Walter, Glenn | Kan, Hermien E.

Article Type: Review Article

Abstract: Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases. In 2013, the European Union funded the COST (co-operation in science and technology) action BM1304 called MYO-MRI (www.myo-mri.eu ), with the overall aim to advance novel MRI and MRS techniques for both diagnosis and quantitative monitoring …of neuromuscular diseases through sharing of expertise and data, joint development of protocols, opportunities for young researchers and creation of an online atlas of muscle MRI and MRS . In this report, the topics that were discussed in the framework of working group 3, which had the objective to: Explore new contrasts, new targets and new imaging techniques for NMD are described. The report is written by the scientists who attended the meetings and presented their data. An overview is given on the different contrasts that MRI can generate and their application, clinical needs and desired readouts, and emerging methods. Show more

Keywords: Neuromuscular disease, muscle, MRI, MRS, biomarker, outcome measure, myo-mri

DOI: 10.3233/JND-180333

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 1-30, 2019

Authors: Bowden, Sasigarn A. | Connolly, Anne M. | Kinnett, Kathi | Zeitler, Philip S.

Article Type: Review Article

Abstract: Long-term glucocorticoid therapy has improved outcomes in patients with Duchenne muscular dystrophy. However, the recommended glucocorticoid dosage suppresses the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency that may develop during severe illness, trauma or surgery, and after discontinuation of glucocorticoid therapy. The purpose of this review is to highlight the risk of adrenal insufficiency in this patient population, and provide practical recommendations for management of adrenal insufficiency, glucocorticoid withdrawal, and adrenal function testing. Strategies to increase awareness among patients, families, and health care providers are also discussed.

Keywords: Muscular dystrophy, adrenal crisis, adrenal suppression, cortisol, prednisone, deflazacort, ACTH

DOI: 10.3233/JND-180346

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 31-41, 2019

Authors: Finanger, Erika | Vandenborne, Krista | Finkel, Richard S. | Lee Sweeney, H. | Tennekoon, Gihan | Yum, Sabrina | Mancini, Maria | Bista, Pradeep | Nichols, Andrew | Liu, Hanlan | Fretzen, Angelika | Donovan, Joanne M.

Article Type: Research Article

Abstract: Background: Edasalonexent is an orally administered small molecule designed to inhibit NF-κ B, which is activated from infancy in Duchenne muscular dystrophy and is central to causing muscle damage and preventing muscle regeneration. Objective: Evaluate the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of three doses of edasalonexent in ambulatory males ≥4 to <8 years of age with genetically confirmed Duchenne muscular dystrophy. Methods: This was a 1-week, open-label, multiple-dose study with 3 sequential ascending doses (33, 67 and 100 mg/kg/day) of edasalonexent administered under different dietary conditions to 17 males with a mean age of 5.5 years. …Results: All doses of edasalonexent were well tolerated, with no serious adverse events, no drug discontinuations and no dose reductions. The majority of adverse events were mild, and the most common adverse events were gastrointestinal (primarily diarrhea). Edasalonexent was rapidly absorbed with peak levels observed 2–6 hours after dosing and exposures appeared to increase nearly proportionally to dose for the 2 lower and all 3 doses under low-fat and high-fat meal conditions, respectively. Only minor plasma accumulation of edasalonexent was observed with 7 days of dosing. After treatment with edasalonexent for 7 days, levels of NF-κ B-regulated genes and serum proteins were decreased. Conclusions: This first report of edasalonexent oral administration for one week in male pediatric patients with Duchenne muscular dystrophy showed that treatment was well tolerated and inhibited NF-kB pathways. Show more

Keywords: Duchenne muscular dystrophy, NF-κB, edasalonexent, CAT-1004

DOI: 10.3233/JND-180341

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 43-54, 2019

Authors: Fayssoil, Abdallah | Chaffaut, Cendrine | Ogna, Adam | Stojkovic, Tanya | Lamothe, Laure | Mompoint, Dominique | Meng, Paris | Prigent, Helene | Clair, Bernard | Behin, Anthony | Laforet, Pascal | Bassez, Guillaume | Carlier, Robert | Orlikowski, David | Amthor, Helge | Quijano Roy, Susana | Crenn, Pascal | Chevret, Sylvie | Eymard, Bruno | Lofaso, Frederic | Annane, Djillali

Article Type: Research Article

Abstract: Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD. Purpose: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV). Methods: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests. Results: There were 110 DMD patients and 17 …male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2 . DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p  = 0.005 for the right diaphragm, p  = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p  = 0.001 for the right side, p  < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p  < 0.0001). Conclusion: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD. Show more

Keywords: Duchenne muscular dystrophy, diaphragm failure, ultrasound

DOI: 10.3233/JND-180326

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 55-64, 2019

Authors: van de Velde, Nienke Marije | Roest, Arno Anne Willem | van Zwet, Erik Willem | Niks, Erik Harmen

Article Type: Research Article

Abstract: Background: Duchenne muscular dystrophy (DMD) is characterized by progressive cardiomyopathy. Left ventricular (LV) function may worsen by factors increasing LV afterload such as hypertension and obesity. Objective: To identify potential modifiable risk factors for progression of cardiomyopathy in Duchenne muscular dystrophy (DMD). Methods: We retrospectively analysed systolic blood pressures (SBP) and body-mass indexes (BMI) from 273 visits of 65 DMD patients aged 4–18 years between 2003 and 2016, divided in 14 age groups. Values were normalized using Z-scores (Z-SBP and Z-BMI). A linear mixed model was used to analyse correlations between Z-SBP and BMI, steroid use, …age, ambulatory status and cardiac medication (CM) use. To study the relationship between SBP and BMI and myocardial deformation prior to the onset of clinical cardiomyopathy, LV deformation, defined by global longitudinal strain (GLS), was quantified in a subset of 36 patients <11 years. Multiple linear regression was used to study the relation between GLS and clinical parameters. Results: Median follow-up was 5 years. SBP was significantly elevated in all age groups under 14 years (p ≤0.04) and 15–16 years (p  = 0.033) and correlated positively with BMI (p  = 0.001) and negatively with CM use over time (p  = 0.018). Z-BMI followed a bell-shaped distribution and plotted approximately one standard deviation above the mean in patients between 7 and 15 years. In the subset of younger patients, reduced GLS was associated with higher BMI (β = 0.348, p  = 0.004). Conclusions: SBP and BMI may be potentially modifiable factors to retard deterioration of LV function in DMD. Show more

Keywords: Duchenne muscular dystrophy, BMI, blood pressure, cardiomyopathy, global longitudinal strain, pediatric

DOI: 10.3233/JND-180340

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 65-73, 2019

Authors: Senesac, Claudia R. | Lott, Donovan J. | Willcocks, Rebecca J. | Duong, Tina | Smith, Barbara K.

Article Type: Research Article

Abstract: Background: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by progressive muscle weakness, multiple system involvement and premature mortality. Effective treatments for DMD through clinical trials and natural history studies are currently underway. Clinical trials in DMD typically include several outcome measures of motor function. Research sites and studies have been found to have slightly different operational definitions for a given functional outcome resulting in different procedures and protocols for these measurements. Objective: The goal of this study is to establish agreement among experts in the field around best practices in collecting functional outcome data in …DMD providing researchers and clinicians with guidance on best practices. Methods: A group of 30 experts in Duchenne Muscular Dystrophy (DMD) with experience in the development and/ or execution of lower extremity outcome measures for this population met face to face to identify incongruences in the collection of this data. This effort was based in the United States (US) and sponsored by Parent Project Muscular Dystrophy. Several discrepancies were categorized for each outcome which included: 6-minute walk test, 10-meter walk/run, supine to stand, ascend 4 stairs, sit to stand, and the NorthStar Ambulatory Assessment. Following this meeting an additional 32 experts in DMD (28 from the United States and 11 international participants) consented to participate in a Delphi Survey to reach consensus on the protocols and execution of lower extremity outcomes. Results: Round one: 70 operationally defined questions were surveyed with 45 (64%) reaching >70% consensus. Round two: 27 questions were operational, with 20 (74%) reaching >70% consensus. Those questions that did not reach consensus appear minor. Conclusion: With minor modifications in the collection of data across sites, outcomes could potentially be normalized across research studies. This would reduce excessive training for evaluators in trials and produce minimal differences between protocols. Consistency in protocols will promote more efficient study start up, less errors between administration of items across studies, and ultimately improve quality and reliability of the functional outcomes. The authors strongly advocate for the establishment of a “research network library ” that could be utilized by all those performing clinical assessments and trials in DMD. Show more

Keywords: Duchenne muscular dystrophy, lower extremity, outcome measures, Delphi survey, consensus, OutcomesDMD, research network library

DOI: 10.3233/JND-180337

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 75-83, 2019

Authors: O’Connor, Laura | Westerberg, Elisabet | Punga, Anna Rostedt

Article Type: Research Article

Abstract: Background: Notwithstanding the amount of deliberate exercise, the daily patterns of active versus sedentary behavior have a major influence on health outcomes [1 ]. Patterns of habitual active and sedentary behavior in Myasthenia Gravis (MG) patients, as well as their possible relations to disease activity, are not known. Objective: To evaluate baseline patterns of physical and sedentary behavior in MG patients. Methods: Activity patterns of twenty-seven MG patients were assessed by a Dynaport MoveMonitor (McRoberts) accelerometer, worn for seven consecutive days. The amount of time spent in moderate and vigorous intensity activities, physical activity level (PAL), …number of steps/day and sedentary time were assessed and correlations to disease severity were analyzed. The results were compared to general recommendations and published data of healthy individuals and to data of patients with the chronic disorders chronic obstructive pulmonary disease (COPD) and mitochondrial myopathy. Results: MG patients had sedentary behavior during 78±7% of the day. There was neither a correlation between disease severity and number of steps/day (R = –0.15; p  = 0.56) nor between disease severity and PAL (R = 0.33; p  = 0.26). Nevertheless, the MG patients met the recommendations of daily deliberate exercise (181±158 MET min/day). PAL was lower in MG patients (1.5±0.138) than in healthy individuals (1.67±0.145, p  < 0.00001). Conclusion: Although a majority of MG patients meet the recommendations of deliberate exercise, their baseline physical activity levels are dominated by sedentary behavior. In comparison with a healthy population, MG patients are less physically active, but the reason for this remains unclear with no correlations between disease severity and physical activity patterns. Show more

Keywords: Myasthenia gravis, physical exercise, physical activity level, sedentary behavior

DOI: 10.3233/JND-180355

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 85-91, 2019

Authors: Markvardsen, Lars K. | Carstens, Anne-Kathrine R. | Knak, Kirsten L. | Overgaard, Kristian | Vissing, John | Andersen, Henning

Article Type: Research Article

Abstract: Background: We have previously shown that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) improve muscle strength and aerobic capacity after resistance and aerobic exercise. Objective: The purpose of this study was to determine if muscle strength and aerobic capacity are preserved one year after discontinuation of regular exercise. Methods: All patients in the previous exercise study were eligible for a one-year follow-up with measurement of combined isokinetic muscle strength (cIKS) by dynamometry and maximal oxygen consumption velocity (VO2 -max). Data are presented as median (ranges). Results: Ten of 17 patients accepted to participate in …the follow-up study. Following the exercise study six patients discontinued exercise and at one-year follow-up cIKS had decreased by –13.0 % (–25.8 to –2.9) (p  = 0.03) and VO2 -max by –16.6 % (–18.8 to –12.6) (p  = 0.06). Four patients continued exercise (three with aerobic training and one with resistance training) and at one-year follow-up cIKS and VO2 -max were preserved compared to the end of the exercise study (11.6 % (–8.9 to 32.1) (p  = 0.88) and –8.4 % (–34.5 to –2.2) (p  = 0.13), respectively). Conclusions: Continuation of aerobic and resistance exercise may preserve gains in muscle strength and aerobic capacity in patients with CIDP. Show more

Keywords: CIDP, resistance training, immunoglobulin, aerobic training, muscle strength

DOI: 10.3233/JND-180344

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 93-97, 2019

Authors: Landon-Cardinal, Océane | Devilliers, Hervé | Chavarot, Nathalie | Mariampillai, Kuberaka | Rigolet, Aude | Hervier, Baptiste | Allenbach, Yves | Benveniste, Olivier

Article Type: Research Article

Abstract: Background: Manual muscle testing has been widely used for the evaluation of muscle strength in myositis, yet less attention has been devoted to the evaluation of muscle function and endurance. Objective: Our objective was therefore to compare the responsiveness to change of muscle strength, endurance and functional testing following induction therapy for severe myositis flare (requiring high-dose corticosteroids and combined immunotherapy) in patients with a diagnosis of dermatomyositis, immune-mediated necrotizing myopathy, or overlap myositis. Methods: Muscle status was assessed at baseline and after mean 6.4±1.9 months, using the MRC-5 scale, along with endurance (Barre and Mingazzini …maneuvers) and functional evaluation (e.g. chair rise) and responsiveness to change was evaluated using the Standardized Response Mean (SRM) and Standardized Mean Difference. Results: Among the 49 patients included, the strongest responsiveness to change was observed in the muscle testing of the psoas and deltoids (SRM: 1.23 and 1.16, respectively). Noticeably, endurance testing also demonstrated strong responsiveness (SRM: 1.05 and 0.96, respectively), compensating for the poor discriminatory ability of muscle testing and permitting to overcome its ceiling effect. Conclusion: Functional and endurance testing provide simple and reliable measures complementing the testing of select proximal muscle groups to evaluate responsiveness to intervention in myositis patients in daily clinical practice. Interest of functional and endurance testing should be evaluated prospectively as outcome measures in myositis clinical trials. Show more

Keywords: Idiopathic inflammatory myopathies, myositis, manual muscle testing, responsiveness, endurance, functional evaluation, outcome measures

DOI: 10.3233/JND-180358

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 99-107, 2019

Authors: Dunaway Young, Sally | Montes, Jacqueline | Kramer, Samantha S. | Podwika, Bernadette | Rao, Ashwini K. | De Vivo, Darryl C.

Article Type: Research Article

Abstract: Background: Fatigue is a common complaint in spinal muscular atrophy (SMA). Fatigability is well described in ambulatory SMA but the relationship to perceived fatigue has not been evaluated. Understanding this relationship has proven challenging for most disorders. Objective: To assess the relationship of perceived fatigue to fatigability, function, and quality of life in SMA. Methods: Thirty-two participants with SMA (21.9% type 2, 78.1% type 3) were recruited. Perceived fatigue and fatigability, function, and quality of life were assessed using standardized questionnaires and assessments. Associations were analyzed using Pearson correlation coefficients (p  = 0.05). Also, the effects of …age, type, and ambulatory status were determined on perceived fatigue. Results: All SMA participants reported fatigue. Perceived fatigue was not associated with function, quality of life, or fatigability in ambulatory SMA patients. Neither age, type, nor ambulatory status influenced perceived fatigue. Conclusions: Perceived fatigue can be quantified in SMA. Interestingly, perceived fatigue did not correlate with fatigability or function, suggesting that cognitive, homeostatic, or psychologic factors may be more relevant as co-morbid factors. Clinical trials targeting perceived fatigue in SMA should focus on these patient-reported assessments. A multilevel approach is required to separate the various mechanisms involved in perceived fatigue. Show more

Keywords: Spinal muscular atrophy, perceived fatigue, patient reported outcome measure, fatigability, clinical trials, fatigue

DOI: 10.3233/JND-180342

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 109-117, 2019

Authors: Pacione, Michelle | Siskind, Carly E. | Day, John W. | Tabor, Holly K.

Article Type: Research Article

Abstract: Background: Spinal muscular atrophy (SMA) is a genetic disorder characterized by muscle loss. In December 2016 the FDA approved the first and only treatment drug for SMA: Spinraza (nusinersen). Despite excitement and optimism, there are no published data on the perceptions of individuals with SMA and their families about the benefits, risks, and challenges associated with treatment. Objective: This qualitative interview study sought to characterize the perspectives of patients/families with SMA who did not want, or were unsure about, receiving this new innovative treatment for a previously untreatable and often fatal condition. Methods: …Individuals and families were recruited via advertisements on Facebook groups related to SMA and through the Stanford Neuromuscular Contact Registry. Participants completed a demographic questionnaire and participated in a semi-structured interview via voice conferencing. Interview questions focused on: 1) experiences with SMA, 2) opinions about Spinraza treatment, and 3) factors considered in decisions regarding treatment. Results: Thirteen people were interviewed: ten adults with SMA (ages 27–48, nine with Type II) and three parents of minor children with SMA (one each of Types I, II and III). Qualitative content analysis identified a range of opinions about Spinraza treatment: five were uninterested (2 adults, 3 parents), four adults were still deciding whether to pursue treatment, three adults were interested or in the process of pursuing treatment, and one adult was currently receiving the drug after overcoming significant reluctance. Participants described several key factors influencing their treatment decisions, including: concerns about risk factors and side effects, high cost, insurance coverage, time involvement, and lack of data about efficacy. Participants reported learning about most of these factors through parent/patient testimonials on SMA-specific social media groups. Conclusions: Participants reported basing decisions about pursuing Spinraza on a variety of practical and value-based considerations. They described carefully weighing the perceived potential benefits and risks of treatment through the lens of their current quality of life and prognosis. These findings suggest that providers should be aware that some patients and parents, especially those with Types II-IV, may approach treatment decisions differently than parents of children with SMA I. Informed treatment decisions can be supported through: 1) the collection and dissemination of better data on Spinraza treatment in these populations; 2) clear communication about risks, side effects and eligibility; 3) improved access to payment and treatment facilities; and 4) facilitation of discussions between providers and patients/families about identity and disability in the context of goals of care and other life and support challenges. Show more

Keywords: Spinal muscular atrophy, drug therapy, qualitative research, clinical decision making, health care costs, insurance coverage, health services accessibility, risk factors

DOI: 10.3233/JND-180330

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 119-131, 2019

Authors: Kuo, Anna | Todd, Joshua J. | Witherspoon, Jessica W. | Lawal, Tokunbor A. | Elliott, Jeffery | Chrismer, Irene C. | Shelton, Monique O. | Razaqyar, Muslima S. | Jain, Minal S. | Vasavada, Ruhi | Waite, Melissa | Drinkard, Bart | Michael, Darren | Richarte, Alicia | Bönnemann, Carsten G. | Meilleur, Katherine G.

Article Type: Research Article

Abstract: Background: RYR1 -related disorders (RYR1 -RD), are a spectrum of genetic neuromuscular disorders. Affected individuals frequently experience fatigue yet appropriate tools to assess RYR1 -RD-associated fatigue remain underdeveloped. Objective: This study assessed the reliability and validity of two self-report questionnaires, the multidimensional fatigue inventory (MFI-20) and adult/pediatric functional assessment of chronic illness-fatigue (FACIT-F/Peds-FACIT-F) as potential fatigue measures in RYR1 -RD affected individuals. Methods: Participants (n  = 37) were enrolled in an RYR1 -RD combined natural history study and clinical trial. At baseline, participants completed fatigue questionnaires, six-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and saliva collection …for fatigue biomarker index (FBI) quantification. Results: All questionnaires exhibited good test-retest reliability (n  = 18, ICC > 0.80). MFI-20 (n  = 37), and FACIT-F (n  = 28) also showed good internal consistency (Cronbach’s α > 0.80). All MFI-20 subscales, except mental fatigue, and FACIT-F demonstrated evidence of criterion validity when correlated against percent predicted 6MWT distance (MFI-20 n  = 37; r  = –0.34 to –0.47, all p  < 0.05, mental fatigue, r  = –0.16, p  = 0.35; FACIT-F n  = 28, r  = 0.41, p  = 0.03). This was not the case for percent predicted VO2 peak (all p  > 0.05). FBI correlated with MFI-20 general fatigue dimension only (r  = –0.35, p  = 0.03). Comparison of standardized questionnaire scores revealed that RYR1 -RD affected individuals experience significantly greater fatigue than the general population. Conclusions: MFI-20 and FACIT-F are valid and reliable tools for assessing RYR1 -RD-associated fatigue, a symptom centrally implicated in this rare disorder. Show more

Keywords: Fatigue, myopathy, RYR1, quality of life, ryanodine receptor

DOI: 10.3233/JND-180335

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 133-141, 2019

Authors: Jokela, Manu | Baumann, Peter | Huovinen, Sanna | Penttilä, Sini | Udd, Bjarne

Article Type: Case Report

Abstract: TRIM63 mutations have been described as a potential cause for cardiac and skeletal myopathy in only one family so far. We describe a new patient carrying the same homozygous TRIM63 nonsense mutation c.739 C>T p.Q247X, that was originally reported in two members of a Spanish family manifesting cardiac hypertrophy. One of these original patients also had an additional heterozygous mutation in TRIM54 and a much more severe phenotype also involving skeletal muscles, and a digenic inheritance was therefore suggested. Our case report confirms the role of TRIM63 as a new cardiac myopathy gene, although it is …unclear whether the homozygous p.Q247X mutation alone is sufficient to cause an additional skeletal myopathy. Show more

Keywords: Myopathy, cardiac hypertrophy, hypertrophic cardiomyopathy, TRIM63, myopathy with internalized capillaries, MuRF1

DOI: 10.3233/JND-180350

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 143-146, 2019

Authors: Aartsma-Rus, Annemieke | Morgan, Jennifer | Lonkar, Pallavi | Neubert, Hendrik | Owens, Jane | Binks, Michael | Montolio, Marisol | Phadke, Rahul | Datson, Nicole | Van Deutekom, Judith | Morris, Glenn E. | Rao, V. Ashutosh | Hoffman, Eric P. | Muntoni, Francesco | Arechavala-Gomeza, Virginia | on behalf of the workshop participants

Article Type: Meeting Report

Abstract: Representatives of academia, patient organisations, industry and the United States Food and Drug Administration attended a workshop on dystrophin quantification methodology. The aims of the workshop were to provide an overview of methods used to quantify dystrophin levels in human skeletal muscle and their applicability to clinical trial samples, outline the gaps with regards to validating the methods for robust clinical applications prior to regulatory agency review, and to align future efforts towards further optimizing these methods. The workshop facilitated a constructive but also critical discussion on the potential and limitations of techniques currently used in the field of translational …research (western blot and immunofluorescence analysis) and emerging techniques (mass spectrometry and capillary western immunoassay). Notably, all participants reported variation in dystrophin levels between muscle biopsies from different healthy individuals and agreed on the need for a common reference sample. Show more

DOI: 10.3233/JND-180357

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 147-159, 2019

Authors: Lochmüller, Hanns | Ambrosini, Anna | van Engelen, Baziel | Hansson, Mats | Tibben, Aad | Breukel, Alexandra | Sterrenburg, Ellen | Schrijvers, Guus | Meijer, Ingeborg | Padberg, George | Peay, Holly | Monaco, Lucia | Snape, Mike | Lennox, Anne | Mazzone, Elena | Bere, Nathalie | de Lemus, Mencia | Landfeldt, Erik | Willmann, Raffaella | on behalf of the 235th ENMC workshop study group

Article Type: Meeting Report

Abstract: In the era of patient-centered medicine, shared decision-making (SDM) – in which healthcare professionals and patients exchange information and preferences and jointly reach a decision – has emerged as the gold standard model for the provision of formal healthcare. Indeed, in many geographical settings, patients are frequently invited to participate in choices concerning the design and delivery of their medical management. From a clinical perspective, benefits of this type of patient involvement encompass, for example, enhanced treatment satisfaction, improved medical compliance, better health outcomes, and maintained or promoted quality of life. Yet, although the theory and enactment of SDM in …healthcare are well-described in the literature [1–3 ], comparatively less attention has been devoted to contextualizing questions relating to if, when, and how to include patients in decisions within medical research. In this context, patient involvement would be expected to be potentially relevant for and applicable to a wide range of activities and processes, from the identification of research priorities and development of grant applications, to the design of patient information and consent procedures, formulation of interventions, identification and recruitment of study sample populations, feasibility of a clinical trial, identification, selection, and specification of endpoints and outcomes in clinical trials and observational studies, data collection and analysis, and dissemination of results. To this end, 45 clinicians, healthcare professionals, researchers, patients, caregivers, and representatives from regulatory authorities and pharmaceutical companies from 15 different countries met to discuss the level of involvement of patients with neuromuscular diseases, specifically in the following settings of medical research for neuromuscular diseases: i) registries and biobanks; ii) clinical trials; and iii) regulatory processes. In this report, we present summaries of the talks that were given during the workshop, as well as discussion outcomes from the three topic areas listed above. Show more

Keywords: Patient participation, biomedical research, quality of life, consensus

DOI: 10.3233/JND-180368

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 161-172, 2019

Article Type: Announcement

DOI: 10.3233/JND-189002

Citation: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 173-174, 2019