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In this case series, we describe the diagnosis of post-COVID-19 myocarditis in asymptomatic patients with Duchenne Muscular Dystrophy (DMD) and a mild COVID-19 disease course. These patients were referred for CMR due to electrocardiographic and echocardiographic alterations, which did not exist before COVID-19 infection. CMR identified the presence of severe myocardial inflammation in all patients based on abnormally elevated myocardial T2 ratio, late gadolinium enhancement, native T1 mapping, T2 mapping, and extracellular volume fraction. This was paired with concurrent impairment of left ventricular function. Appropriate treatment was initiated in all cases. Two of the four patients developed episodes of ventricular tachycardia during the following 6 months, and a defibrillator was implanted. Despite the mild clinical presentation, this case series demonstrates the diagnostic strength of CMR in the diagnosis and evaluation of post-COVID-19 myocarditis and serves to increase awareness of this potential complication amongst treating physicians.
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Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.
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Evaluate the safety and tolerability of losmapimod in the treatment for FSHD. FSHD is a relentless, variably progressive disease leading to accumulation of disability over decades. Fulcrum is developing losmapimod, a small molecule p38 alpha/beta MAPK inhibitor, to treat FSHD. Losmapimod has been generally well-tolerated in more than 3,600 subjects across multiple clinical studies, including >100 subjects with FSHD. Fulcrum has assessed losmapimod in FSHD in one completed phase 1 study (FIS 001-2018) and two ongoing Phase 2 studies in the open label extension period (FIS 001-2019 and FIS 002-2019). Subjects aged 18-65 years with genetically confirmed FSHD1, clinical severity score 2-4, and MRI-eligible muscles for biopsy were exposed to losmapimod 7.5 or 15 mg twice daily PO for 14 days and up to 76 weeks. In study FIS 001-2018, 6 subjects were exposed to 7.5 mg and 11 subjects to 15 mg twice daily dosing for 14 consecutive days. In studies FIS 001-2019 and FIS 002-2019, 14 and 77 subjects respectively, received at least one dose of losmapimod 15 mg twice daily for up to 76 weeks. A total of 108 subjects with FSHD1 have been exposed to losmapimod, with approximately 131 patient-years of exposure. Fifty-seven subjects have been exposed to losmapimod for 12 to 18 months, and 30 have been exposed for over 18 months. Most adverse events (AEs) observed during the studies were considered of mild to moderate in severity. The most common AEs were alanine aminotransferase (ALT) increase, headache, dizziness, dry skin, eczema and gastrointestinal disorders. The majority of AEs resolved with continued dosing. Dosing has been paused for 14 days in four subjects (3 in FIS 001-2019 and 1 in FIS 002-2019) subjects due to COVID-19 infection. There were no reported drug related SAEs, deaths, discontinuations due to AEs, or clinically significant changes in vital signs, clinical laboratory results, or ECG parameters. Losmapimod given as up to 15 mg twice daily in >100 subjects with FSHD1 for up to 76 weeks has been generally well-tolerated, consistent with that previously reported in other patient populations. Therefore, the benefit-risk profile of losmapimod for the treatment of FSHD remains favorable.Copyright © 2022
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The proceedings contain 23 papers. The topics discussed include: Mg and skeletal system: a link to osteoporosis and osteoarthritis;a putative impact of IL-6 on the expression of magnesiotropic genes through the activation of the JAK/STAT3 pathway;magnesium in pain therapy - historical notes and current aspects;Alzheimer's-associated variant rs708727 might be connected to dementia in Parkinson's disease;effect of magnesium citrate supplementation on the brain tissue of patients with Miyoshi dysferlinopathy measured by 31P magnetic resonance spectroscopy;clinical status of magnesium implants;Ionized magnesium: update 2022;magnesium in the treatment of selected types of muscular dystrophy;magnesium speciation analysis in blood serum;epigenetically-induced modulation of the HPA axis might improve resilience to chronic stress;magnesium status in patients with fibromyalgia syndrome;and post-covid-syndrome and transient microvascular pathology in pulse-wave-analysis - association with Mg/Ca ratio and magnesium therapy-options.
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Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.
Subject(s)
COVID-19 , Neuromuscular Diseases , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Male , RNA, Messenger , SARS-CoV-2ABSTRACT
Outcomes: 1. Illustrate increased moral distress associated with removing unwanted aggressive interventions for conscious patients compared to unconscious patients. 2. Demonstrate the importance of the interdisciplinary team in supporting providers experiencing moral distress. When providing end-of-life care, removing unwanted aggressive intervention is more challenging in a conscious patient. If the intent to provide comfort and reduce suffering is the same, why does it feel different when the patient is conscious? This case examines the moral distress experienced by the palliative care team who assisted a conscious patient with Duchenne muscular dystrophy achieve his goal of liberation from the ventilator. A 41-year-old male with Duchenne muscular dystrophy and prior COVID-19 infection presented with respiratory failure. The patient had COVID-19 infection in April 2022 and was ventilator dependent since then. The palliative care team was consulted for goals of care discussion. After extensive discussion with the patient and his family, the patient decided to be disconnected from the ventilator and wanted a peaceful passing because long-term ventilatory support was no longer acceptable to him. He was afraid of being aware of struggling to breathe and requested to be asleep throughout this process. Specifically, he said he wanted "to close my eyes and see [my family] on the other side." When the patient was comfortable and asleep as he and his family desired, he was disconnected from the ventilator and died peacefully with his family around him. During this process, the palliative care team's intent was clear: follow the patient's wishes and provide comfort. Ethically, there is no difference in removing unwanted aggressive interventions between conscious and unconscious patients, but the team experienced significantly more distress in this case. After the patient's death, the interdisciplinary team provided support to help the palliative care team work through the distress experienced.Copyright © 2023
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The aim of this study is to examine the results of physiotherapy in a patient with critical illness polyneuropathy (CIP) due to coronavirus disease 2019 (CO-VID-19). The 48-year-old male patient with CIP due to COVID-19 was enrolled in a physiotherapy program for 3 months with 5 sessions/week. Pain intensity, motor skills, daily living activities, fatigue level, cognitive status, and decubitus ulcer were evaluated with a visual analogue scale, the Medical Research Coun-cil-Sum Score, the Functional Independence Scale, the Fatigue Severity Scale, the Standardized Mini-Mental Test, and pressure wound staging, respectively. Positive improvements were achieved in functional level, fatigue, pain, and pressure sores with the physiotherapy program for this patient with CIP due to COVID-19. This report provides an idea about the effects of physiotherapy programs for COVID-19-related CIP to academics and clinicians working in this field.Copyright © 2022, Derman Medical Publishing. All rights reserved.
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INTRODUCTION/AIMS: Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease-2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD. METHODS: We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28 to 30 days after the second dose, and antibody titers were measured. RESULTS: Overall, 104 (60.8%) and 115 (67.6%) patients had side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.12 to 0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI, 159.3 to 358.7). Older age (relative risk [RR] = 0.97; 95% CI, 0.95 to 0.99) and bedridden state (RR = 0.27; 95% CI, 0.14 to 0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR = 0.42; 95% CI, 0.21 to 0.85). DISCUSSION: COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs.
Subject(s)
COVID-19 Vaccines , COVID-19 , Muscular Dystrophies , Myotonic Dystrophy , Humans , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Inpatients , RNA, MessengerABSTRACT
PURPOSE: To investigate experiences and reflections on challenges in everyday life of people living with limb-girdle muscular dystrophy (LGMD) and chronic pain in order to improve rehabilitation services. MATERIALS AND METHODS: The design for this study was qualitative using the Interpretive Description methodology and the salutogenic theory of Sense of Coherence as the theoretical framework. Four semi-structured focus group interviews were conducted with 19 adults with LGMD from April to May 2021. The interviews were conducted online due to COVID-19. RESULTS: Living with chronic pain and LGMD affected everyday life in terms of the participants' overall Sense of Coherence. Beneficial or unfavorable coping strategies were identified within four interrelated categorical themes: pain management, normality comprehension, affected emotional sentiment and altered identity. CONCLUSION: Healthcare professionals should acknowledge possible chronic pain secondary to LGMD. Chronic pain appears to be a prevalent problem in people with LGMD with negative impact on everyday life, yet patients with LGMD did not receive sufficient information and necessary tools from health professionals to cope with chronic pain. Thus, adequate pain management appeared to be a difficult and self-taught process. Educating health professionals on how to support patients with LGMD and chronic pain is needed.IMPLICATIONS FOR REHABILITATIONHealth professionals should acknowledge and address the possibility of chronic pain secondary to limb-girdle muscular dystrophy (LGMD) and educate patients in pain management.Physiotherapy, energy management and engagement in meaningful activities may help patients gain some control of pain and limit the consequences of pain on everyday life.Supporting patients to accept pain and to shift focus towards their current capabilities may potentially improve pain management.Educating health professionals on how to support patients with LGMD and chronic pain is needed.
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Muscular dystrophies (MDs) are a category of hereditary illnesses characterized by the gradual malfunction and/or weakening of the skeletal muscles. This disease of the muscles also results in hypotonia and joint contracture, along with raised serum creatine kinase (CK) levels. To prevent complications, continuous physiotherapy is advised for children with muscular dystrophy, which is even asked to perform at home as a home exercise program (HEP). As a result, the home exercise program (HEP) is critical in maintaining the optimal health of children with Duchenne muscular dystrophy (DMD). The present coronavirus (COVID-19) pandemic has adversely affected these children as there was very little scope to get direct help from a physiotherapist. Meanwhile, the home program was continued by many to compensate for the direct benefit. However, because of the lack of specific guidelines and structured methodology to follow for a home program, there was a deterioration in the health status of many children. There is a need to understand how the children are getting affected and the way the home program can be refined to help needy children with muscular dystrophy. Our scoping review aims to identify the present home program patterns being followed for children with DMD and their scope for refinement. The data were collected from electronic databases including PubMed, ProQuest, Cochrane, and Web of Science. We searched four electronic databases until September 2021. We included the published case studies, observational and experimental studies that described the positive impact of home exercise programs, and the methodology they followed as an alternative to institution-based physiotherapy. One hundred thirty-eight titles were screened, and 58 met the inclusion criteria. Along with regular physiotherapy, the incorporation of HEP helped in early complication prevention in patients with muscular dystrophy. The HEP was found to be a successful adjunct in the COVID-19 scenario. This review presents different therapeutic measures that can be taken for the prevention of complications in patients with MD and how the HEP plays an important role in removing the gaps on how HEP is beneficial in the COVID-19 scenario and a scope to refine the present methodologies for more accurate management.
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Duchenne muscular dystrophy (DMD) is a rare genetic disorder that affects about 0.8 million Indian children. The incidence rate of 1:3500 male births is the most common form of all muscular dystrophies. Covid-19 pandemic cause profound devastation to the lives of DMD children. The muscles are weaker in DMD, and the children are more prone to lung infections. Coronavirus (COVID-19) is a severe lung infection that disturbs the entire function of the World. DMD already has weakness in major muscles, including the respiratory. So, the study aims to identity the effect of low-intensity aerobic exercises in children with DMD. This is a home-based pilot study with 11 DMD children and wheelchair dependent since, for ten years, they have been on continuous rehabilitation and monitoring. When the pandemic was declared in India in March 2020, all children were given clear notes on the disease and its severity to the parents. Self-created quarantine exercise protocol, which includes Limb exercises, breathing exercises, trunk mobility exercises, and positioning, was taught along with a logbook given to all the children. Video calls, and WhatsApp videos, were used to monitor them regularly. The physiotherapist made a personal visit in June 2020 to review the exercises, and subsequently on Aug 20, Oct 20, Dec 20, Feb 21, and May 21. Observations are detailed here. The infection rate was 3 out of 9, and they got admitted to the hospital for other illnesses. All the children noted Flu infection but recovered within ten days without hospitalization. The parents monitored their SPo2 and temperature and updated them in the logbook. A lung function test was done using a handheld incentive spirometer during the personnel visit by the therapist and found satisfactory. The study concluded a significant improvement in the DMD children following low-intensity and quarantine exercises.
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The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information about myotonic dystrophy type 1 (DM1) and type 2 (DM2). The registry was established in May 2012 with support from Muscular Dystrophy UK and the Myotonic Dystrophy Support Group and is coordinated Newcastle University. The registry aims to facilitate academic and clinical research, better characterise and understand DM, and disseminate information relating to upcoming studies and research advancements. The registry is used to capture longitudinal, selfreported data through an online portal available to patients and clinicians. Where specialised clinical or genetic information is required, the neuromuscular specialist involved in the patient's care can be invited to provide some additional information and the patient can select them from a pre-populated list at the registration stage. The registry is a Core Member of the TREAT-NMD Global Registries Network for DM1. Between May 2012 and January 2022, there were 834 patient registrations. On average there are 5 new registrations per month. For those reporting a clinical diagnosis, 96% have DM1 (of which 14% have a diagnosis of congenital DM) and 4% have DM2. Overall, 40% of patients have had genetic confirmation of their condition provided. The registry has previously supported almost 30 research enquiries to date. Since 2020, the registry has facilitated 11 enquiries including an industry enquiry, three COVID-19 surveys, and various surveys capturing information on dysphagia, pregnancy, patient preferences for future treatments and the patient/ caregiver experience. The registry continues to be a versatile, cost-effective research tool, helping facilitate and advance a range of DM research. Additional work continues to be done to improve reporting of genetic information on the registry and there are future data linkage plans between the registry and the Newcastle Research Biobank for Rare and Neuromuscular Diseases.
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The UK Facioscapulohumeral Muscular Dystrophy (FSHD) Patient Registry is a patient self-enrolling online database collecting clinical and genetic information about FSHD type 1 (FSHD1) and type 2 (FSHD2). The registry was established in May 2013 with support from Muscular Dystrophy UK and is coordinated by Newcastle University. The registry aims to facilitate academic and clinical research, better characterise and understand FSHD, and disseminate information relating to upcoming studies and research advancements. The registry is used to capture longitudinal, selfreported data through an online portal available to patients and clinicians. Where specialised clinical or genetic information is required, the neuromuscular specialist involved in the patient's care can be invited to provide some additional information and the patient can select them from a pre-populated list at the registration stage. The registry is a Core Member of the TREAT-NMD Global Registries Network for FSHD. Between May 2013 and January 2022, there were 1,074 patient registrations, with 84% based in the UK. On average, there are 9 new registrations per month. For those reporting a clinical diagnosis, 97% have FSHD or FSHD1, and 3% have FSHD2. Overall, 46% of patients have had genetic confirmation of FSHD1 provided. The registry has previously supported almost 30 registry enquiries to date. Since 2020, the registry has facilitated 12 enquiries including, three COVID-19 surveys, and various surveys capturing information on dysphagia, pregnancy, sleep and the patient/caregiver experience. The registry is currently one of the largest national FSHD patient registries and is an example of a versatile, cost-effective research tool, helping facilitate and advance a wide range of FSHD research. Additional work continues to be done to improve reporting of genetic information on the registry and there are future data linkage plans between the registry and the Newcastle Research Biobank for Rare and Neuromuscular Diseases.
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Objective: Evaluate the safety and tolerability of losmapimod in the treatment for FSHD. Background: FSHD is a relentless, variably progressive disease leading to accumulation of disability over decades. Fulcrum is developing losmapimod, a small molecule p38 α/β MAPK inhibitor, to treat FSHD. Losmapimod has been generally well-tolerated in more than 3,600 subjects across multiple clinical studies, including >100 subjects with FSHD. Fulcrum has assessed losmapimod in FSHD in one completed phase 1 study (FIS 001-2018) and two ongoing Phase 2 studies in the open label extension period (FIS 001-2019 and FIS 002-2019). Methods: Subjects aged 18-65 years with genetically confirmed FSHD1, Clinical Severity Score 2-4, and MRI-eligible muscles for biopsy were exposed to losmapimod 7.5 or 15 mg twice daily PO for 14 days and up to 76 weeks. In study FIS 001-2018, 6 subjects were exposed to 7.5 mg and 11 subjects to 15 mg twice daily dosing for 14 consecutive days. In studies FIS 001-2019 and FIS 002-2019, 14 and 77 subjects respectively, received at least one dose of losmapimod 15 mg twice daily for up to 76 weeks. Results: A total of 108 subjects with FSHD1 have been exposed to losmapimod, with approximately 131 patient-years of exposure. Fifty-seven subjects have been exposed to losmapimod for 12 to 18 months, and 30 have been exposed for over 18 months. Most adverse events (AEs) observed during the studies were considered of mild to moderate in severity. The most common AEs were alanine aminotransferase (ALT) increase, headache, dizziness, dry skin, eczema and gastrointestinal disorders. The majority of AEs resolved with continued dosing. Dosing has been paused for 14 days in four subjects (3 in FIS 001-2019 and 1 in FIS 002-2019) subjects due to COVID-19 infection. There were no reported drug related SAEs, deaths, discontinuations due to AEs, or clinically significant changes in vital signs, clinical laboratory results, or ECG parameters. Conclusion: Losmapimod given as up to 15 mg twice daily in >100 subjects with FSHD1 for up to 76 weeks has been generally well-tolerated, consistent with that previously reported in other patient populations. Therefore, the benefit-risk profile of losmapimod for the treatment of FSHD remains favorable.
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Introduction: Information on COVID-19 infection prevention measures and vaccines for patients with neuromuscular diseases has been sufficiently disseminated, but the details of the actual course of infected patients are rarely directly involved by neurologists. We report four cases of COVID-19 with neuromuscular diseases and were able to observe their progress. Subjects: 1 case of multiple sclerosis (MS), 1 case of chronic inflammatory demyelinating polyradiculoneuropathy / dermatitis (CIDP / DM), 1 case of limb-girdle muscular dystrophy (LGMD) and one Duchenne muscular dystrophy carrier (DMD-C) were examined. Result: MS: A 32-year-old man who was taking fingolimod, but improved by waiting at home, and he did not relapse. CIDP / DM: 54-year-old female, PSL, taking tacrolimus, using remdesivir for pneumonia. After recovery, peripheral neuropathy worsened, and steroid pulse treatment was added. LGMD: 48-year-old female Although she had pneumonia, she did not need to be ventilated and improved with only oxygen administration and favipiravir without deterioration of% VC. DMD-C: 59-year-old female, improved only by oxygen administration. The DMD (second son, 29 years old) who were cared by her was hospitalized because no one could care him. Discussion: All cases were affected prior to vaccination. Regarding CIDP, there was a case report of deterioration after illness, and this case also deteriorated and required treatment. LGMD / DMD-C did not show any deterioration in respiratory function. It is a study of a small number of cases, and it is necessary to accumulate future cases.
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The Covid-19 pandemic has highlighted the diffi- culty in the management of neuromuscular patients and the need for continued implementation of the standard of care. With the new pandemia psychometrically robust but quick outcome measures are needed to monitor patients' clinical status. The slow progressive nature of several muscle disorders and the wide pattern of involvement in muscular dystrophies and myopathies make it difficult to establish the prognosis, predict clinical evolution and perform trials and define the impact of natural history, and use new therapies that are becoming available. We constructed a motor function test that is easy and quick to use. This quick Motor Function test: Gait, Stair, Gower's, Chair (GSGC) was constructed based on the clinical expertise of several physicians involved in the care of DMD;LGMD, and Pompe patients. The GSGC score can be integrated by the use of the motor function of the upper motor limbs with the arm function test (GSGCA). It consists of a simple standardized functional test which grades the ability of the patient to raise their upper arms over the head. Grade 0 corresponds to a full circle of arm abduction, while with grade 6 the patients cannot raise their arms to their mouth and effectively use their hands. The Gardner-Medwin Walton (GMW) scale even modifi ed appears in comparison rather insensitive. The GSGC test includes 4 items. The test provides a detailed picture of motor function by including a quantitative measure of four performances i.e. time to perform four activities: Gait =walking for 10 meters, S=climbing 4 steps on a Stair, G= Gower's maneuver, C= rising from a Chair (Figure) The GSGC final score is obtained by adding the grades of the four functional tests and ranges from a minimum of 4 (normal performance) to a maximum of 27 (worst performance).GSGCA test includes 5 tests (total score from 5 to 32). Validity and test reliability were determined in a cohort of 9 adult Pompe patients (15 to 54 years of age) and then validated in 40 LOPD cases by a collaborative group. The responsiveness of the GSGCA scale to changes in clinical course over time was examined in a subgroup of 13 LGMD 2B/R2 untreated patients. Interrater and intrarater reliabilities were most usually confirmatory. The motor outcomes are different in various myopathies and depend on a correct diagnosis, while exercise in myopathy patients should be moderate, but not necessarily discouraged. The muscle MRI imaging might be helpful for follow-up of the proximal or distal muscle involvement, to detect fat, and connective tissue replacement, which might be usually absent in metabolic myopathies, except for LOPD. Diet and exercise in LOPD might be an additional therapeutic option synergistic to ERT. In this presentation, we examine the use of the GSGC scale in LOPD, DMD, and GSGCA scales in the natural history of LGMD R2. The development of smart care using telemedicine and eHealth technologies to share images, clinical data, reports, and video meetings of collaborative groups should be implemented. Keywords: GSGC scale, Covid-19, DMD, LGMD, Pompe.
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BackgroundWe describe a proband and her son who have proximal limb and facial weakness and marked hand involvement. A congenital myopathy panel demonstrated two RYR1 variants and the p.Ile289Phe novel variant in ACTA1.Cases: The proband had initially been diagnosed with SMA following premature birth, late milestones, scoliosis and proximal and distal weakness which was relatively static until age 40. EMG as a child was neurogenic. Her son had poor feeding after birth, delayed motor milestones, intellectual delay, and by his teens, severe facial weakness and distal upper limb wasting particularly the finger flexors and extensors, with hip flexion of grade 3. Repeat neurophysiological evaluation of the proband at age 60, demonstrated a neurogenic pattern but also brief polyphasic motor units, raising suspicion of an addi- tional myopathic process.DiscussionZukosky and colleagues1 also described a family with a different missense mutation in the ACTA1 gene who had been diagnosed with SMA on the basis of neurogenic EMG findings. Our additional family confirms that myopathy can be accompanied by neurogenic EMG changes in ACTA1 associated myopathy.Reference1. Zukosky K, Meilleur K, Traynor BJ, Dastgir J, Medne L, Devoto M, et al. Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family. JAMA Neurol. 2015 Jun 1;72(6):689–98.carolynnedoherty@doctors.org.uk;NIHR Bursary
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BACKGROUND: In patients with Duchenne Muscular Dystrophy (DMD), the respiratory system determines the quality and length of life; therefore, the search for easy and safe everyday monitoring of the pulmonary function is currently extremely important, particularly in the COVID-19 pandemic. The aim of the study was to evaluate the influence of a three-month home electronic spirometry (e-spirometry) monitoring of the pulmonary function and strength of respiratory muscles as well as the patients' benefits from this telemetric program. METHODS: Twenty-one boys with DMD (aged 7-22; non-ambulatory-11) received a remote electronic spirometer for home use with a special application dedicated for patients and connected with a doctor platform. Control of the hospital spirometry (forced vital capacity-FVC, forced expiratory volume in 1 second-FEV1, peak expiratory flow-PEF) and respiratory muscle strength (maximal inspiratory-MIP and expiratory pressures-MEP) before and after the three-month monitoring were performed as well telemonitoring benefit survey. RESULTS: A total of 1403 measurements were performed; 15 of the participants were able to achieve correct attempts. There were no differences between the hospital and the home spirometry results as well as between respiratory muscle strength during v1 vs. v2 visits for the whole study group (all parameters p > 0.05); the six participants achieved increased value of FVC during the study period. There was a positive correlation between ΔFVC and the number of assessments during the home spirometry (r = 0.7, p < 0.001). Differences between FVC and MIPcmH2O (r = 0.58; p = 0.01), MEPcmH2O (r = 0.75; p < 0.001) was revealed. The mean general satisfaction rating of the telemonitoring was 4.46/5 (SD 0.66) after one month and 4.91/5 (SD 0.28) after three months. The most reported benefit of the home monitoring was the improvement in breathing (38% of participants after one month, 52% after three months of telemonitoring). Forgetting about the procedures was the most common reason for irregular measurements; the participants reported also increased motivation but less time to perform tests. CONCLUSIONS: The study indicates high compliance of the home telemonitoring results with the examination in the hospital. Benefits from home spirometry were visible for all participants; the most important benefit was breathing improvement. The remote home spirometry is usable for everyday monitoring of the pulmonary function in DMD patients as well can be also treated as respiratory muscle training.
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BACKGROUND: Dysferlinopathy refers to a heterogenous group of autosomal recessive disorders that affect a skeletal muscle protein called dysferlin. These mutations are associated with limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, asymptomatic hyperCKemia, and distal myopathy with anterior tibial onset. CASE PRESENTATION: A 16 year old female presented with myalgia, weakness and dark urine one week after her second BNT162b2 mRNA (Pfizer) vaccine. Initial serum creatine kinase (CK) was measured at 153,000 IU/L, eventually up-trending to over 200,000 IU/L. However, stable renal function precluded hemodialysis allowing discharge after 10 days of intravenous (IV) hydration and alkaline diuresis. Just two years prior to the current presentation, the patient was hospitalized following Group A Streptococcal pharyngitis infection complicated by rhabdomyolysis. She presented with fatigue, lower extremity weakness, and dark oliguria with CK measuring 984,800 IU/L. IV hydration was attempted however hemodialysis was ultimately required throughout her 24-day hospital stay. Her episode was presumed to be idiopathic and no further work-up was performed at that time. During the patient's current hospitalization, she reported similar symptomology (myalgias and weakness) following her first quadrivalent Gardasil vaccine at age 11. No hospitalization was required at that time. A comprehensive workup was now initiated while the patient was being treated for her suspected second or third non-exertional, non-traumatic rhabdomyolysis. Rheumatologic, metabolic, infectious, and endocrinologic workup were all unremarkable. Patient eventually had whole exome sequencing performed which revealed a heterozygous pathogenic variant in the DYSF gene (DYSF c.2643 + 1G > A) encoding dysferlin. No clinically significant sequelae occurred thus far. CONCLUSIONS: While there have been reports of symptomatic heterozygote carriers of dysferlinopathies, to our knowledge none have been associated with recurrent rhabdomyolysis after immunogenic stimuli. This unique case presentation highlights the importance of a multi-disciplinary care team, the utility of modern whole-exome gene sequencing, and the future challenges of balancing vaccine risk vs benefit.