Journal of Neuromuscular Diseases - Volume 9, issue 3

Authors: Landfeldt, E. | Ferizović, N. | Buesch, K.

Article Type: Systematic Review

Abstract: Background: Clinical medical management guidelines of Duchenne muscular dystrophy (DMD) emphasize prevention and early identification and treatment. Objective: The objective of our study was to review, synthesize, and grade published evidence of the impact of the timing of clinical interventions in DMD. Methods: We searched PubMed, Embase, and the Cochrane Library for records published from inception up until November 19, 2021, reporting evidence of the impact of the timing of clinical interventions in DMD. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Results: We included …12 publications encompassing 1,623 patients with DMD from seven countries (Australia, France, Germany, Italy, Japan, the United Kingdom, and the United States of America). Six (50%) studies reported evidence of an impact of the timing of initiation of glucocorticoids on loss of ambulation, cardiomyopathy, fractures, forced vital capacity, and height and BMI; four (33%) of cardiac medication (i.e., angiotensin-converting enzyme inhibitors, β-blockers, and eplerenone) on left ventricular size and function and survival; one (8%) of lower limb surgery on motor quotient and loss of ambulation; and one (8%) of ataluren on lower extremity and motor function. The overall quality of the body of evidence was low. Conclusion: While there is a clinical rationale for anticipatory diagnostic and therapeutic strategies, evidence of the impact of the timing of initiation of treatments in patients with DMD is still emerging. Further research of this topic is warranted to inform treatment guidelines in this indication. Show more

Keywords: Therapeutics, guideline, GRADE approach, muscular dystrophy, duchenne

DOI: 10.3233/JND-220804

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 353-364, 2022

Authors: Narayan, S. | Pietrusz, A. | Allen, J. | DiMarco, M. | Docherty, K. | Emery, N. | Ennis, M. | Flesher, R. | Foo, W. | Freebody, J. | Gallagher, E. | Grose, N. | Harris, D. | Hewamadduma, C. | Holmes, S. | James, M.K. | Maidment, L. | Mayhew, A. | Moat, D. | Moorcroft, N. | Muni-Lofra, R. | Nevin, K. | Quinlivan, R. | Slimming, J. | Sodhi, J. | Stuart, D. | Julien, Y. | on behalf of the ANSN

Article Type: Research Article

DOI: 10.3233/JND-210707

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 365-381, 2022

Authors: van Doormaal, Perry T.C. | Warendorf, Janna K. | Visser, Nora A. | de Vries, Jeanne H.M. | Notermans, Nicolette C. | Vrancken, Alexander F.J.E.

Article Type: Research Article

Abstract: Background: In recent years, an increasing number of people adapt to a vegetarian, pescatarian or flexitarian dietary pattern that reduces the consumption of meat and fish. Although these dietary patterns have a risk for developing vitamin B12 deficiency associated polyneuropathy, it is unknown whether this risk is still increased when vitamin B12 levels are adequate. Objective: To examine whether a vegetarian, pescatarian or flexitarian dietary pattern is associated with an increased risk for idiopathic axonal polyneuropathy. Methods: We conducted a case-control study that included 256 idiopathic axonal polyneuropathy patients with adequate vitamin B12 blood levels and …630 controls. We used questionnaire data to determine the frequency of meat and fish consumption and defined dietary patterns. Results: The vegetarian (no meat or fish consumption) and the pescatarian (fish consumption, no meat consumption) dietary patterns showed no increased risk of axonal polyneuropathy. Frequency-effect analysis and quantity-effect analysis also did not show that a reduction of meat or fish consumption (flexitarian dietary pattern), either small or large, changed the risk of axonal polyneuropathy. Conclusions: We did not find an increased risk for axonal polyneuropathy among people with a vegetarian, pescatarian or flexitarian diet and an adequate vitamin B12 level. Show more

Keywords: Polyneuropathies, vegetarian diet, risk factors, case-control studies

DOI: 10.3233/JND-210775

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 383-388, 2022

Authors: Schwartz, Oliver | Kölbel, Heike | Blaschek, Astrid | Gläser, Dieter | Burggraf, Siegfried | Röschinger, Wulf | Schara, Ulrike | Müller-Felber, Wolfgang | Vill, Katharina

Article Type: Research Article

Abstract: Background: Prompt treatment after genetic NBS for SMA substantially improves outcome in infantile SMA. However, deficiency of SMN-protein can cause damage of motor neurons even prior to birth. Objective: To describe the neurological status at the time of NBS and the reversibility of neurological deficits in a cohort of patients with only two copies of the SMN2 gene. Methods: We present motor, respiratory, and bulbar outcomes of 21 SMA patients identified in newborn screening projects in Germany. Inclusion criteria was initiation of SMN targeted medication at less than 6 weeks of age and a minimum …age of 9 months at last examination. Results: Twelve patients (57%) developed completely normally, reaching motor milestones in time and having no bulbar or respiratory problems. Three children (14.5%) caught up after initial delay in motor development. Six patients (29%) developed proximal weakness despite early treatment: Three of them (14.5%) achieved the ability to walk with assistance and the other three (14.5%) showed an SMA type 2 phenotype at the age of 16–30 months. One patient (4.8%) had respiratory problems. Three children (14.5%) had mild chewing problems and two individuals (9.5%) needed feeding via gastrotube. Initial CHOP-INTEND values below 30 could be indicative of a less favourable outcome, whereas values above 50 could indicate a good outcome, however in-depth statistic due to the small case number is not predictive. Conclusion: More than 70% of SMA patients with two SMN2 copies can achieve independent ambulation with immediate initiation of therapy. However, caregivers and paediatricians must be informed about the possibility of less favourable outcomes when discussing therapeutic strategies. Show more

Keywords: Spinal muscular atrophy, 2 SMN2 copies, outcome, CHOP INTEND, newborn screening, motor milestones

DOI: 10.3233/JND-220789

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 389-396, 2022

Authors: Habets, Laura E. | Bartels, Bart | Asselman, Fay-Lynn | Hulzebos, Erik H.J. | Stegeman, Dick F. | Jeneson, Jeroen A.L. | van der Pol, W. Ludo

Article Type: Research Article

Abstract: Background: Exercise intolerance is an important impairment in patients with SMA, but little is known about the mechanisms underlying this symptom. Objective: To investigate if reduced motor unit and capillary recruitment capacity in patients with SMA contribute to exercise intolerance. Methods: Adolescent and adult patients with SMA types 3 and 4 (n  = 15) and age- and gender matched controls (n  = 15) performed a maximal upper body exercise test. We applied respiratory gas analyses, non-invasive surface electromyography (sEMG) and continuous wave near-infrared spectroscopy (CW-NIRS) to study oxygen consumption, arm muscle motor unit- and capillary recruitment, respectively. …Results: Maximal exercise duration was twofold lower (p  < 0.001) and work of breathing and ventilation was 1.6- and 1.8-fold higher (p  < 0.05) in patients compared to controls, respectively. Regarding motor unit recruitment, we found higher normalized RMS amplitude onset values of sEMG signals from all muscles and the increase in normalized RMS amplitudes was similar in the m. triceps brachii , m. brachioradialis and m. flexor digitorum in SMA compared to controls. Median frequency, onset values were similar in patients and controls. We found a similar decrease in median frequencies of sEMG recordings from the m. biceps brachii , a diminished decrease from the m. brachioradialis and m. flexor digitorum, but a larger decrease from the m. triceps brachii . With respect to capillary recruitment, CW-NIRS recordings in m. biceps brachii revealed dynamics that were both qualitatively and quantitatively similar in patients and controls. Conclusion: We found no evidence for the contribution of motor unit and capillary recruitment capacity of the upper arm muscles in adolescent and adult patients with SMA types 3 and 4 as primary limiting factors to premature fatigue during execution of a maximal arm-cycling task. Show more

Keywords: Arm-cycling, spinal muscular atrophy, surface electromyography, near infrared spectroscopy, respiratory gas exchange, motor unit, capillaries, fatigability

DOI: 10.3233/JND-210765

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 397-409, 2022

Authors: Nishadham, Vikas | Bardhan, Mainak | Polavarapu, Kiran | Vengalil, Seena | Nashi, Saraswati | Menon, Deepak | Ganaraja, Valakunja Harikrishna | Preethish-Kumar, Veeramani | Valasani, Ravi Kiran | Huddar, Akshata | Unnikrishnan, Gopi Krishnan | Thomas, Abel | Saravanan, Akshaya | Kulanthaivelu, Karthik | Nalini, Atchayaram | Nandeesh, Bevinahalli Nanjegowda

Article Type: Research Article

Abstract: Background and Objectives: Thymic pathology is common in Myasthenia Gravis(MG) and plays a crucial role in its pathogenesis and clinical outcome. This study aims to discuss the clinicohistopathological spectrum of thymic lesions in MG. Methods: In this retrospective study, MG patients who underwent thymectomy from 2011 to 2020 were included. Clinical, radiological, serological, and histopathological details are described. Results: Of 83 patients(F  = 45; M  = 38), 7(8%) had ocular myasthenia, and the remaining 76(92%) had the generalized form. At onset, the median age was 36 years(M  = 44; F  = 31). AChR antibody was positive in 71/79 patients. RNST …showed decrement response in 68/78 patients. The histopathological study demonstrated thymoma in 44(53%), thymic hyperplasias [32(38%)], involuted thymus [5(6%)], thymic cyst (1) and thymic lipoma (1). WHO grading of thymoma: B2- 48%, AB-18%, B-18%, B3-14%, A-2.3%. In these, capsular infiltration was noted in 11/44, 9 had focal and 2 had diffuse infiltration. Active germinal centers were present in 20/32 patients with thymic hyperplasia and 4/44 with thymoma. Thymomas were predominant in males and thymic hyperplasia in females. The age of onset and antibody positivity rate was higher in thymoma patients. Conclusion: In our cohort, there is a female preponderance. Thymoma was the commonest pathology followed by hyperplasia. We observed earlier onset of myasthenia in females. AChR antibody positivity rate was more frequent in thymomas. This study indicates that clinico-radiological evaluation adequately supported by serology and histopathology can effectively recognize the type of thymic pathology that can guide these patients’ treatment planning, management, prognosis and follow-up. Show more

Keywords: Myasthenia gravis, thymoma, thymic hyperplasia, thymectomy, histopathology

DOI: 10.3233/JND-210785

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 411-422, 2022

Authors: Nair, Kavya S. | Lott, Donovan J. | Forbes, Sean C. | Barnard, Alison M. | Willcocks, Rebecca J. | Senesac, Claudia R. | Daniels, Michael J. | Harrington, Ann T. | Tennekoon, Gihan I. | Zilke, Kirsten | Finanger, Erika L. | Finkel, Richard S. | Rooney, William D. | Walter, Glenn A. | Vandenborne, Krista

Article Type: Research Article

Abstract: Background: Muscles of boys with Duchenne muscular dystrophy (DMD) are progressively replaced by fatty fibrous tissues, and weakness leads to loss of ambulation (LoA). Step activity (SA) monitoring is a quantitative measure of real-world ambulatory function. The relationship between quality of muscle health and SA is unknown in DMD. Objective: To determine SA in steroid treated boys with DMD across various age groups, and to evaluate the association of SA with quality of muscle health and ambulatory function. Methods: Quality of muscle health was measured by magnetic resonance (MR) imaging transverse magnetization relaxation time constant (MRI-T2 …) and MR spectroscopy fat fraction (MRS-FF). SA was assessed via accelerometry, and functional abilities were assessed through clinical walking tests. Correlations between SA, MR, and functional measures were determined. A threshold value of SA was determined to predict the future LoA. Results: The greatest reduction in SA was observed in the 9– < 11years age group. SA correlated with all functional and MR measures.10m walk/run test had the highest correlation with SA. An increase in muscle MRI-T2 and MRS-FF was associated with a decline in SA. Two years prior to LoA, SA in boys with DMD was 32% lower than age matched boys with DMD who maintained ambulation for more than two-year period. SA monitoring can predict subsequent LoA in Duchenne, as a daily step count of 3200 at baseline was associated with LoA over the next two-years. Conclusion: SA monitoring is a feasible and accessible tool to measure functional capacity in the real-world environment. Show more

Keywords: Step activity, MRI, fat fraction, duchenne muscular dystrophy, 10m walk/run test

DOI: 10.3233/JND-210746

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 423-436, 2022

Authors: Andries, Aristomo | Van Walsem, Marleen R. | Ørstavik, Kristin | Frich, Jan C.

Article Type: Research Article

Abstract: Background: Physical activity may help to promote health in patients with Limb-girdle muscular dystrophy (LGMD) and Charcot-Marie-Tooth disease (CMT). Objective: To investigate associations between functional ability and other variables, with physical activity in people with LGMD and CMT grouped according to the International Classification of Functioning, Disability, and Health (ICF). Methods: We did a cross-sectional study, recruiting respondents from the Norwegian registry of inherited neuromuscular disorders. We used the Norwegian version of Barthel index of Activities of Daily Living (ADL) to measure functional ability and the International Physical Activity Questionnaire –short form (IPAQ-sf) to classify physical …activity. We used multivariable logistic regression analysis to investigate associations between variables. Results: 145 subjects were recruited (79 with CMT and 66 with LGMD). 55.6% of the subjects met a minimum recommendation of physical activity. Participants with moderate to severe functional ability were more likely to be physically inactive compared to those with normal functional ability (OR 19.7; 95% CI 3.1–127.2). Mildly decreased functional ability also showed higher odds of being physically inactive compared to participants with normal functional ability (OR 4.1; 95% CI 1.1–15.6). Higher education was associated with inactivity. Fatigue, participation in physiotherapy, and participation in adapted physical activity programs were not associated with physical activity. Conclusions: Low functional ability was associated with physical inactivity in both LGMD and CMT. Association between higher education and inactivity might indicate the need to provide more understanding about physical activity benefit in this group. Show more

Keywords: Neuromuscular diseases, muscular dystrophies, charcot-marie-tooth disease, exercise, physical functional performance

DOI: 10.3233/JND-210677

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 437-446, 2022

Authors: Peay, Holly L. | Do, Barbara T. | Khosla, Neil | Paramsothy, Pangaja | Erickson, Stephen W. | Lamb, Molly M. | Whitehead, Nedra | Fox, Deborah J. | Pandya, Shree | Kinnett, Kathi | Wolff, Jodi | Howard, James F.

Article Type: Research Article

Abstract: Background: Youth with Duchenne and Becker muscular dystrophy (DBMD) experience challenges in attaining adult roles, which may impact quality of life. New interventions and treatments may facilitate adult role attainment through improved function. Historical data on adult role attainment is important to assess the impact of new interventions on teens and young adults with DBMD. This study assesses medical knowledge, independence and employment, and relationships among adolescents and young adults with DBMD. Methods: This study uses data from a 2013 Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet ) survey on adult transition. Males with DBMD aged …16–30 years were included. Results: Sixty-five of 258 eligible males participated; we report results on 60 participants with an MD STARnet case definition of DMD or BMD. Individuals with BMD reported higher rates than those with DMD of frequently staying home without supervision (50% BMD; 14% DMD), independently performing daily physical needs (93% BMD; 7% DMD) and being employed full or part time (33% BMD; 4% DMD). Most participants understood medication and physical therapy goals; less than half indicated being often or always responsible for scheduling DMBD-related management and refilling medications. Most had not been in a romantic relationship but reported desiring such relationships. Conclusions: Our data reinforce the impact of DMD (and to a lesser extent, BMD) on transition to adult roles. These results provide an important historical comparator for teen and adult patients who are trying new interventions and therapies. Such data are important for assessing the quality-of-life impact of new treatments and to inform support and training programs for people with DBMD as they transition to new adult roles and responsibilities. Show more

Keywords: Muscular dystrophies, transition to adult care, transfer from pediatric to adult care, self-care, adolescent

DOI: 10.3233/JND-210709

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 447-456, 2022

Authors: Montano, Vincenzo | Mancuso, Michelangelo | Simoncini, Costanza | Torri, Francesca | Chico, Lucia | Ali, Greta | Rocchi, Anna | Baldinotti, Fulvia | Caligo, Maria Adelaide | Lattanzi, Giovanna | Mattioli, Elisabetta | Cenacchi, Giovanna | Barison, Andrea | Siciliano, Gabriele | Ricci, Giulia

Article Type: Case Report

Abstract: Background: Proximal muscle weakness may be the presenting clinical feature of different types of myopathies, including limb girdle muscular dystrophy and primary mitochondrial myopathy. LGMD1B is caused by LMNA mutation. It is characterized by progressive weakness and wasting leading to proximal weakness, cardiomyopathy, and hearth conduction block. Objective: In this article, we describe the case of a patient who presented with limb-girdle weakness and a double trouble scenario –mitochondrial DNA single deletion and a new LMNA mutation. Methods: Pathophysiological aspects were investigated with muscle biopsy, Western Blot analysis, NGS nuclear and mtDNA analysis and …neuromuscular imaging (muscle and cardiac MRI). Results: Although secondary mitochondrial involvement is possible, a “double trouble” syndrome can not be excluded. Conclusion: Implication deriving from hypothetical coexistence of two different pathological conditions or the possible secondary mitochondrial involvement are discussed. Show more

Keywords: Muscle disorders, myopathies, LMNA-associated diseases, mitochondria

DOI: 10.3233/JND-220802

Citation: Journal of Neuromuscular Diseases, vol. 9, no. 3, pp. 457-462, 2022