Mobile Information System for Determining the Level of Creatine in Food Products

The study of food products to determine the level of creatine in them is an actual task, taking into account the need for this substance for patients with Covid'19 and spinal muscular atrophy. The purpose of our research is to develop a mobile information system for determining the level of creatine in food products. The developed method for determining the level of creatine in food products by the user and the method for determining the level of creatine in food products using a mobile information system provide the user with the opportunity to quickly, conveniently, cheaply and effectively assess the presence and level of creatine in any food products, on the basis of which to build a rational diet from the point vision of body saturation with creatine. The proposed mobile information system for determining the level of creatine in food products provides convenience, low-cost, celerity, miniaturization and automation for measurement of concentration of creatine in any food products. The conclusion obtained from the system regarding the presence and level of creatine in this or that food product is useful and extremely important when preparing the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy. The proposed approach and mobile information system for determining the level of creatine in food products can be used not only for drawing up the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy, from the point vision of body saturation with creatine, but also for example, to check the quality of meat products. © 2023 Copyright for this paper by its authors.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

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.

Commencing Novel Therapies for Adult Sma Patients: Experience from a Hybrid Clinic

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that affect both adults and children. Two novel therapies were approved for patients in England by NICE (Nusinersen via Management Access Agreement (MAA) and Risdiplam via Early Access to Medicine scheme (EAMS)). Setting up baseline assessments, designing new pathways, acquiring personnel and resources have been challenging. We present a pathway analysis of the new clinic set-up, process of patient choice, risk minimisation in intro- ducing the two novel therapies, and the impact therapies have had on adult cohort of SMA patients. Total of 58 patients included (31 had type 2 SMA and 27 had type 3[only 11/27 were ambulant]. The average age of patients with type 2 and 3 SMA was 25 and 33 respectively. 19 patients chose risdiplam (oral) and 22 are on nusinersen (intra thecal). We analysed factors that govern patients' treatment decisions. We report factors that helped early success in our hybrid clinic set-up. Set criteria on each scheme;but potential side effects, information availability, route of administration (mainly previous spinal surgery), speed at treatment initiation but not COVID directed many patients' treatment decisions. A battery of outcome measures were analysed to establish treatment impact at 12 months.

Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy.

Background: Spinal muscular atrophy (SMA) results from a loss-of-function mutation in the SMN1 gene. SMA patients suffer progressive motor disability, although no intellectual impairments have been described. Three drugs have been recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). These drugs result in longer life expectancy for SMA type 1 (SMA1) patients. Objective: The objective of the study was to assess longitudinally the psychomotor development of patients with SMA1 treated after the symptom onset and of patients treated presymptomatically. Design: Longitudinal, monocentric, noninterventional, prospective study. Methods: Our study included 11 SMA1 patients and seven presymptomatic SMA patients. The SMA1 patients were treated with an approved drug beginning after onset of symptoms; treatment for the presymptomatic patients was begun before symptom onset. They were longitudinally evaluated between September 2018 and January 2022 using the Bayley Scales of Infant and Toddler Development™ - Third Edition. Results: At each time point, all patients treated presymptomatically scored above those treated postsymptomatically on the motor scale. The cognitive scores of six of the seven patients treated presymptomatically were average; one patient was in the low average range. In the 11 postsymptomatically treated patients, four scored either in the low average or the abnormal range on the cognitive scale, but a positive trend was observed during the follow-up. Conclusion: A significant proportion of patients treated postsymptomatically scored below average on cognitive and communicative scales, with most significant concerns raised about the age of 1 year. Our study indicates that intellectual development should be considered as an important outcome in treated SMA1 patients. Cognitive and communicative evaluations should be performed as part of standard of care, and guidance should be provided to parents for optimal stimulation.

Risdiplam for the treatment of adults with spinal muscular atrophy: Experience of the Northern Ireland neuromuscular service.

INTRODUCTION/AIMS: Risdiplam is the newest available treatment for patients with spinal muscular atrophy (SMA). There is little information on its use in adults. We present the clinical experience of adults with SMA treated with risdiplam through the Early Access to Medicines Scheme (EAMS) in Northern Ireland. METHODS: All adults with Type 2 SMA attending the regional neuromuscular clinic were offered risdiplam treatment. Patients had assessments of respiratory function, the Epworth Sleepiness Scale (ESS), Quality of Life Measure for People with Slowly Progressive and Genetic Neuromuscular Disease (QOLM), and Egen Klassifikation 2 (EK2) every 3 mo and the Revised Upper Limb Module for SMA (RULM) at baseline and 6 mo. All assessments other than the RULM were carried out virtually. RESULTS: Six of seven patients who were offered risdiplam consented to treatment through the EAMS (five female, one male, mean age 33.7 y). It was generally well tolerated other than skin photosensitivity in all patients. All patients remained on therapy at 9 mo. All reported meaningful improvements in overall strength, sense of wellbeing, and speech quality. There was no change in respiratory function, daytime hypersomnolence, or upper limb function (all p > .05). There was improvement in the QOLM (p = .027) and EK2 (p = .009). DISCUSSION: Our study raises hopes that risdiplam may be efficacious in adults; however, more systematic studies in larger cohorts are needed before drawing any definitive conclusions. This study also demonstrated the feasibility of virtual assessments.

Long-term efficacy of nusinersen and its evaluation in adolescent and adult patients with spinal muscular atrophy types 1 and 2.

BACKGROUNDS: The efficacy of nusinersen and its evaluation in patients with spinal muscular atrophy (SMA) has been established in clinical trials only for pediatric patients, not for adolescent and adult patients who developed SMA in infancy or early childhood. We report a long-term follow-up in adolescent and adult patients with SMA types 1 and 2. METHODS: Nusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. We compared baseline motor function tests with those after the final treatment. Physical and occupational therapists performed Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale-Expanded (HFMSE), and Revised Upper Limb Module (RULM). The Landau and Galant reflexes were not performed in CHOP-INTEND. Meaningful improvement was defined as CHOP-INTEND, 4; HFSME, 3; and RULM, 2. RESULTS: Seven patients with SMA (type 1, 1; type 2, 6) with a median age of 23 (range, 12-40)years were treated with nusinersen for 3.55 (1.78-4.53)years. Improvement was detected in CHOP-INTEND (pre, 5 [0-31]; post, 21 [0-39]; difference, 5 [0-26]; p = 0.100) without significance, although not in HFMSE (pre, 0 [0-3]; post, 0 [0-5]; difference, 0 [0-2]; p = 0.346) and RULM (pre, 1 [0-20]; post, 3 [0-21]; difference, 1 [0-2]; p = 0.089). Owing to prolonged treatment intervals with the COVID-19 pandemic, RULM worsened in two patients. CONCLUSION: Nusinersen was effective in long-term follow-up. Only CHOP-INTEND showed meaningful improvement. The interval between doses of nusinersen should not be prolonged even with the COVID-19 pandemic.

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.

The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

Establishment of Hong Kong Neuromuscular Disorder Patient Registry

Introduction: Neuromuscular disorders (NMDs) are a group of diseases affecting the peripheral nervous system (1). Many NMDs cause disability or even premature death (2). We aim to design and establish a robust NMD patient registry in Hong Kong. Methods: By modelling international NMD patient registries, we designed patient-professional reported questionnaires to collect the demographic, clinical c haracteristics, genetic details, family history, investigation findings and specific treatment of NMD patients. Patients were recruited through Hong Kong West Cluster (DKCH, QMH) and Kowloon Central Cluster (HKCH). We also developed self-registration online platform. p<0.05 was considered statistically significant. Findings: Since June 2019, 125 NMD patients have been enrolled in the registry with 12 participants registered online. The registry recruited 13 types of NMDs, including spinal muscular atrophy (SMA) (n=31), Duchenne muscular dystrophy (DMD) (n=19) and congenital myopathy (n=18). The age range was 7 months to 63 years old. 65.6% of those enrolled were children (<18 years old). 63.2% were male. 64.8% of the patients had genetic diagnosis. The registry has contributed to two studies. The first one is a prospective study of clinical efficiency of Nusinersen in SMA patients (n=22). 14/16 SMA patients showed improvement in at least one of motor performance (CHOP intend/RULM/HINE/HFMSE) and health-related quality of life after 1st year of treatment. The second study is the reactogenicity and immunogenicity study of the COVID-19 vaccine in DMD patients (n=4). Data will be available in October. Conclusion: Hong Kong Patient registry has contributed to ongoing and new research study to optimise medical care.

Assessing the Impact of COVID-19 in Healthcare Providers Treating Spinal Muscular Atrophy (SMA)

Objective: The purpose of the study was to examine the effects of COVID-19 on SMA patient care and clinical trial management in the United States. Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Early treatment has been shown to modify disease progression and is expected to alter phenotype. Despite strains to the healthcare system due to the ongoing COVID-19 pandemic, the diagnosis of SMA remains a medical emergency. Design/Methods: A sample of providers at known SMA treatment and clinical trial sites was invited by Cure SMA to complete an online survey that was open from November 24, 2020 through March 8, 2021. 48 complete responses were received (SMA treatment sites (Care): n=22;SMA treatment and clinical trial sites (Care & Trial): n=26). Results: 26.9% of Care & Trial Sites and 27.3% of Care Sites report clinic/facility appointment cancellation(s) or delays for SMA drug treatment during the pandemic (from March 2020 to time of survey completion);11.5% of Care & Trial Sites and 9.1% of Care Sites report similar cancellations within the month prior to survey completion. 96.2% of Care & Trial Sites and 86.4% of Care Sites report patient and/or families cancelled/delayed SMA-related appointments due to exposure concerns during the pandemic while 65.4% of Care & Trial Sites and 63.6% of Care Sites noted these cancellations within the month prior to survey completion. 26.9% of Care & Trial Sites reported having paused enrollment, and 34.6% reported notable recruitment delays. Prioritization of assessments, telemedicine, and protocol amendments were helpful strategies to maintain trial continuity. Conclusions: This research provided insight into effects of the COVID-19 pandemic on access to SMA management and clinical trials. Healthcare providers are encouraged to collaborate with SMA patients to mitigate ongoing exposure concerns while supporting improved SMA outcomes and trial participation.

Prescrire's ratings of new drugs in 2021: A brief review

Three new drugs, all based on messenger RNA or small interfering RNA technology, represented a major therapeutic advance in 2021. But the bigger picture is that most of the new authorisations that advanced patient care were adaptations of existing drugs. And that more than half of this year's new authorisations were not advances, and in fact about one-tenth represented a step backwards compared to existing options.

Management of Spinal Muscular Atrophy in the Adult Population.

Spinal muscular atrophy (SMA) is a group of neurodegenerative disorders resulting from the loss of spinal motor neurons. 95% of patients share a pathogenic mechanism of loss of survival motor neuron (SMN) 1 protein expression due to homozygous deletions or other mutations of the SMN1 gene, with the different phenotypes influenced by variable copy numbers of the SMN2 gene. Advances in supportive care, disease modifying treatment and novel gene therapies have led to an increase in the prevalence of SMA, with a third of SMA patients now represented by adults. Despite the growing number of adult patients, consensus on the management of SMA has focused primarily on the pediatric population. As the disease burden is vastly different in adult SMA, an approach to treatment must be tailored to their unique needs. This review will focus on the management of the adult SMA patient as they age and will discuss proper transition of care from a pediatric to adult center, including the need for continued monitoring for osteoporosis, scoliosis, malnutrition, and declining mobility and functioning. As in the pediatric population, multidisciplinary care remains the best approach to the management of adult SMA. Novel and emerging therapies such as nusinersen and risdiplam provide hope for these patients, though these medications are of uncertain efficacy in this population and require additional study.

'This battle, between your gut feeling and your mind. Try to find the right balance': Parental experiences of children with spinal muscular atrophy during COVID-19 pandemic.

AIMS: Parents of children with spinal muscular atrophy (SMA) often struggle with the all-consuming nature of the demands of caring for a child with substantial physical needs. Our aim was to explore experiences, challenges and needs of parents of a child with SMA in a COVID-19 pandemic situation. METHOD: Nineteen parents of 21 children (15 months to 13 years of age) with SMA types 1-3 participated in semi-structured interviews in June to July 2020. The interviews were analysed using inductive thematic analysis. RESULTS: Parents mentioned the protection of the health and well-being of the child as the central perspective and driving force during the COVID-19 pandemic. Three subthemes were identified: (1) responsibility, (2) balancing vulnerability and resilience and (3) (in)security. Some parents focused on the positive aspects during the lockdown, such as continuation of nusinersen treatment and family life. Some parents described helpful and positive cognitions to cope with the situation. In general, parents described a need for information with regard to COVID-19 and their child with SMA and a need for discussing their dilemmas and insecurities with a healthcare professional. INTERPRETATION: Parents put the health and well-being of their children first during the pandemic. From this study, we learned that parents of children with SMA need information and value direct contact with a healthcare professional to share their dilemmas and insecurities. The dialogue can help to empower parents in the conflicts and decisions they have to make during a pandemic.

Buccal swab testing with the AmplideX PCR/CE SMN1/2 Plus Kit that assesses copy number and critical mutations for SMA

Introduction: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease that results from mutation of the survival motor neuron 1 gene (SMN1) and the most common genetic cause of infant death. Approximately 95% of SMA cases are caused by a deletion in both alleles of exon 7 in the SMN1 gene. The copy number of the highly homologous SMN2 gene is an important predictor of the severity of SMA as it has been shown to decrease disease severity in a dose-dependent manner. SMN1 and SMN2 only differ by a few nucleotides, presenting a challenge in determining copy numbers. While carriers typically have one copy of SMN1, cis duplication of SMN1 can produce “silent carrier” (2 + 0) genotypes, which are often associated with two SMN1 variants, c.*3 + 80T>G and c.*211_*212del, that can improve the overall carrier detection rate. SMA treatments SPINRAZA®,, Evrysdi™, and ZOLGENSMA® achieve profound benefits on survival and motor milestones by modifying SMN2 splicing or using gene replacement with functional SMN genes. Early detection of SMA (including SMN2 copy number status) and identification of at-risk couples through carrier screening is critical to aid in early intervention and family planning decisions. We developed an accurate and robust single-tube PCR assay and companion software (AmplideX® PCR/CE SMN1/2 Plus Kit*) that uses capillary electrophoresis (CE) to quantify SMN1 and SMN2 copy numbers (0 to ≥4) and determines the presence/absence of the two SMN1 gene duplication “silent carrier” variants, c.*3 + 80T>G and c. *211_*212del, and the SMN2 disease modifier variant c.859G>C. The SMN1/2 Plus Kit has been previously validated for use with DNA isolated from blood. Here, we verify that DNA isolated from buccal swabs can also be used to determine SMN1 and SMN2 copy number and expanded content using this kit. Materials and Methods: A total of 60 DNA samples isolated from buccal swabs, with varying SMN1/2 copies and other positive and negative variants,were tested using the SMN1/2 Plus kit at a single site (Asuragen). Samples were tested in two cohorts: an initial cohort containing 17 samples isolated from buccal swabs with column or magnetic bead-based methods, and a second cohort of 43 samples isolated from matched blood and buccal samples using column-based methods. PCR products were generated using a Veriti thermal cycler and resolved on Applied Biosystems™ 3500xL, 3130xl, 3730xl, and SeqStudio™ Genetic Analyzers. Raw electrophoresis data (.fsa) files were directly imported into an assay-specific analysis module of the AmplideX® Reporter software that automates peak detection and sizebased classification, SMN1 and SMN2 exon 7 copy number quantification, detection of gene duplication and disease modifier variants, and sample- and batch-level quality control checks. Samples were analyzed using the default (kit calibrator) and user-defined calibration (UDC) (buccal DNA) workflows as described in the protocol. Results: For the initial cohort of 17 Buccal swab samples, SMN1 copy number calls were concordant with MLPA reference results (reported as 0, 1, 2, or ≥3) for 16/17 (94.1%) of samples with default calibration and 17/17 (100%) of samples with UDC. Further, concordance for carrier samples (1 SMN1 copy) were 7/7 (100%) using both methods. SMN2 copy numbercallswere concordant with MLPA reference results for 17/17 (100%) of samples with either default calibration or UDC. For the second cohort of 43 buccal swab samples with matched blood samples, SMN1 and SMN2 copy number calls were concordant with the results from the paired whole blood for at least 95% of samples assessed across the four different CE platforms. All variant status calls were concordant between the buccal swab and whole blood results. Conclusions: Here, we demonstrate that buccal swabs are a compatible DNA source for the quantification of 0, 1, 2, 3, and ≥4 gene copies of both SMN1 and SMN2 and the status determination of three clinically significant variants using the single-tube PCR/CE SMN1/2 Plus kit. Although d fault calibration yielded high rates of agreement between copy number results from buccal swabs and reference results, analyzing samples with user-defined calibration (i.e. calibrating to a buccal swab sample) modestly improved concordance. These results suggest that DNA samples isolated from buccal swabs are compatible with this assay and has implications for more facile sample collection and handling, particularly given the strain of COVID-19 on healthcare infrastructure.

A Comprehensive Review of Neuromuscular Manifestations of COVID-19 and Management of Pre-Existing Neuromuscular Disorders in Children.

Since the emergence of SARS-CoV-2, several studies have been published describing neuromuscular manifestations of the disease, as well as management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic. These disorders include muscular dystrophies, myasthenic syndromes, peripheral nerve disorders, and spinal muscular atrophy. Such patients are a vulnerable population due to frequent complications such as scoliosis, cardiomyopathy, and restrictive lung disease that put them at risk of severe complications of COVID-19. In this review, neuromuscular manifestations of COVID-19 in children and the management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic are discussed. We also review strategies to alleviate pandemic-associated disruptions in clinical care and research, including the emerging role of telemedicine and telerehabilitation to address the continued special needs of these patients.

Psychosocial impact of risk mitigation strategies and shielding from COVID-19 in adults and children with early-onset neuromuscular disease and their families

Introduction: Patients with early-onset neuromuscular diseases (NMDs) were considered clinically vulnerable to COVID-19 due to assumptions that treatments e.g. corticosteroids, or complications e.g. pre-existing respiratory failure or cardiac disease would increase risk. In the UK, most were advised to 'shield' and strictly limit social contact, however it is poorly understood how patients and families approached and responded to this. Methods: In-depth questionnaires specifically designed to meet research aims were completed by telephone between September 17 and December 31 2020 by NMD patients or their parent. Open and closed questions enabled a) quantitative analysis and b) thematic analysis to evaluate reasoning and psychosocial impact. Results: 40 questionnaires were completed: patients were 70% male, aged 2 to 48 years with NMDs e.g. muscular dystrophies, spinal muscular atrophy. 80% (n=32) had long-term non-invasive or tracheostomy ventilation;20% (n=8) had cardiac involvement. Strict adherence to shielding was initially reported: this included temporary cessation or reduction in external care support in 68% (n=27), leading to increased parental care. Shielding measures were often relaxed due to 1) official guidance, 2) evidence of less severe outcomes in children and NMDs, and 3) unsustainability of limited social contact. Anxiety, fear and worry were the most frequently reported emotions, but level and pervasiveness fluctuated. 75% (n=30) remained “extremely” or “very” worried about risk of COVID-19 to the patient's health. Concern about hospital attendance during the pandemic and anxiety regarding perceived lack of capacity or access to Intensive care were common. Virtual healthcare access, experienced by 97.5% (n=39), was seen as positive, largely as an interim measure, but was less useful where examination or tests were required. Conclusions: Measures to reduce transmission of COVID-19 have disproportionately affected NMD patients and their families. For most, negative psychosocial impacts have and will continue to improve, particularly due to the success of the vaccination programme. Patients and carers require access to support and up-to-date information to minimise risk of infection and psychological burden.

Persistent neuromuscular junction transmission defects in adults with spinal muscular atrophy treated with nusinersen.

OBJECTIVE: Spinal muscular atrophy (SMA) is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. Prior work in models and patients has demonstrated electrophysiological and morphological defects at the neuromuscular junction (NMJ). Therapeutic development has resulted in clinically available therapies to increase SMN protein levels in patients and improve muscle function. Here we aimed to investigate the effect of SMN restoration (via nusinersen) on NMJ transmission in adults with SMA. METHODS: Participants undergoing nusinersen treatment underwent 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve to assess compound muscle action potential amplitude decrement. Maximum voluntary isometric contraction (MVICT), Revised Upper Limb Module (RULM), and 6 min walk test (6MWT) were assessed for correlations with decrement. RESULTS: Data from 13 ambulatory (7 men/6 women, mean age 40±11 years) and 11 non-ambulatory (3 men/8 women, mean age 38±12 years) participants were analysed. Cross-sectional analyses of RNS decrement were similar at 14 months of nusinersen (-14.2%±11.5%, n=17) vs baseline (-11.9%±8.3%, n=15) (unpaired t-test, p=0.5202). Longitudinal comparison of decrement in eight participants showed no change at 14 months (-13.9%±6.7%) vs baseline (-16.9%±13.4%) (paired t-test, p=0.5863). Decrement showed strong correlations with measures of MVICT, RULM and 6MWT but not age or disease duration. CONCLUSION: Adults with SMA had significant NMJ transmission defects that were not corrected with 14 months of nusinersen treatment. NMJ defects were negatively associated with physical function, and thus may represent a promising target for additive or combinatorial treatments.

Bioinformatic analysis of SMN1-ACE/ACE2 interactions hinted at a potential protective effect of spinal muscular atrophy against COVID-19-induced lung injury.

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.

COVID-19 in children with neuromuscular disorders.

OBJECTIVE: Children with neuromuscular disorders have been assumed to be a particularly vulnerable population since the beginning of COVID-19. Although this is a plausible hypothesis, there is no evidence that complications or mortality rates in neuromuscular patients are higher than in the general population. The aim of this study is to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. METHODS: A registry of children with neuromuscular conditions and laboratory-confirmed-SARS-CoV-2 infection was set up by the Neuromuscular Working Group of the Spanish Pediatric Neurology Society (SENEP). Data to be collected were focused on the characteristics and baseline status of the neuromuscular condition and the course of COVID-19. RESULTS: Severe complications were not observed in our series of 29 children with neuromuscular disorders infected by SARS-CoV-2. Eighty-nine percent of patients were clinically categorized as asymptomatic or mild cases and 10% as moderate cases. Patients with a relatively more severe course of COVID-19 had SMA type 1 and were between 1 and 3 years. CONCLUSIONS: The course of COVID-19 in children with neuromuscular disorders may not be as severe as expected. The protective role of young age seems to outweigh the risk factors that are common in neuromuscular patients, such as a decreased respiratory capacity or a weak cough. Further studies are needed to know if this finding can be generalized to children with other chronic diseases.

Pediatric neuromuscular disorders: Care considerations during the COVID-19 pandemic.

COVID-19, the respiratory and frequently systemic disease caused by the novel SARS-COV-2 virus, was first recognized in December 2019 and quickly spread to become a pandemic and world-wide public health emergency over the subsequent 3-4 months. While COVID-19 has a very low morbidity rate across approximately 80% of the population, it has a high morbidity and mortality rate in the remaining 20% of the population.1 These numbers have put a significant strain on medical systems around the world. Patients with neuromuscular diseases such as those with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), tend to be more medically fragile and have higher health care needs than the general population. Respiratory insufficiency, cardiac disease, obesity, and immunocompromised status due to chronic steroid treatments in certain patient populations with neuromuscular conditions are specific risk factors for severe COVID-19 disease. In general, the pediatric population has shown to be less severely impacted with lower infection rates and lower morbidity and mortality rates than the adult population, however, as expected, children with underlying medical conditions are at higher risk of morbidity from COVID-19 than their peers.2 Many patients with neuromuscular disease also rely heavily on caregiver support through their lifetime and thus maintaining the health of their primary caregivers is also a significant consideration in the health and well-being of the patients. This paper will address routine and emergency medical care, rehabilitation services, and other considerations for the pediatric patient with a neuromuscular condition during the COVID-19 pandemic.