Biomarkers of Brain Dysfunction in Perinatal Iron Deficiency.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

Chronic glucocorticoid management in neuromuscular disease: A survey of neuromuscular neurologists.

INTRODUCTION/AIMS: Glucocorticoids (GC) are first-line therapy for many neuromuscular diseases. There is a lack of guidelines regarding the prevention and management of GC complications in the context of neuromuscular disease, introducing the potential for practice variation, that may compromise quality of care. Our aim was to evaluate the practice patterns among Canadian adult neuromuscular neurologists on the screening, management, and treatment of GC-related complications and to identify variances in practice. METHODS: A web-based anonymous questionnaire was disseminated to 99 Canadian adult neuromuscular neurologists. Questions addressed patterns of screening, prevention, monitoring, and treatment of GC-induced adverse events, including infection prophylaxis, vaccination, bone health, hyperglycemia, and other complications. RESULTS: Seventy-one percent completed the survey. Of those, 52% perform screening blood work prior to initiating GC, 56% screen for infections, and 18% for osteoporosis. The majority monitor glycemic control and blood pressure (>85%). Thirty-two (46%) reported that they do not primarily monitor GC complications, but rather provide recommendations to the primary care physician. Pneumocystis jiroveci pneumonia prophylaxis was never used by 29%, and 29% recommend vaccinations prior to GC initiation. Calcium supplementation was recommended by 80% to prevent osteoporosis. Only 36% were aware of any existing guidelines for preventing GC complications, and 91% endorsed a need for neurology-specific guidelines. DISCUSSION: There is substantial variability in the management of GC adverse effects among neuromuscular neurologists, often not corresponding to limited published literature. Our results support the need for improved education and neurology-specific guidelines to help standardize practice and improve and prevent complications.

Use of Complementary and Alternative Medicine in Children with Neuromuscular Disorders Followed at Penn State Health Pediatric Muscular Dystrophy Association Care Center Clinic.

The exact prevalence of complementary and alternative medicine (CAM) use is not known in pediatric patients with neuromuscular diseases followed by any of the 150 Muscular Dystrophy Association (MDA) Care Center Clinics nationwide. This study describes the prevalence and variety of CAM usage in this population, while also assessing the prevalence of caregiver disclosure of CAM use and caregiver perception of provider support for CAM. Fifty-two caregivers of pediatric patients seen at Penn State Health's Pediatric MDA Care Center Clinic completed our online survey. Overall, 19.2% of caregivers reported CAM use by their child. Less than half of caregivers reported discussing CAM use with their child's neurologist (41.5%); however, a majority of respondents reported interest in using CAM for their child in the future (52.8%). Understanding the prevalence of CAM usage and disclosure in pediatric MDA clinics may facilitate safer use of CAM in this community.

Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis.

AIM: The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS: In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS: Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION: The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.

Respiratory muscle training in neuromuscular disease: a systematic review and meta-analysis.

BACKGROUND: Neuromuscular disease causes a progressive decline in ventilatory function which respiratory muscle training may address. Previous systematic reviews have focussed on single diseases, whereas this study systematically reviewed the collective evidence for respiratory muscle training in children and adults with any neuromuscular disease. METHODS: Seven databases were searched for randomised controlled trials. Three reviewers independently reviewed eligibility, extracted characteristics, results, determined risk of bias and combined results using narrative synthesis and meta-analysis. RESULTS: 37 studies (40 publications from 1986-2021, n=951 participants) were included. Respiratory muscle training improved forced vital capacity (standardised mean difference (SMD) 0.40 (95% confidence interval 0.12-0.69)), maximal inspiratory (SMD 0.53 (0.21-0.85)) and maximal expiratory pressure (SMD 0.70 (0.35-1.04)) compared to control (usual care, sham or alternative treatment). No impact on cough, dyspnoea, voice, physical capacity or quality of life was detected. There was high degree of variability between studies. DISCUSSION: Study heterogeneity (children and adults, different diseases, interventions, dosage and comparators) suggests that the results should be interpreted with caution. Including all neuromuscular diseases increased the evidence pool and tested the intervention overall. CONCLUSIONS: Respiratory muscle training improves lung volumes and respiratory muscle strength in neuromuscular disease, but confidence is tempered by limitations in the underlying research.

A scoping review of the contralateral effects of unilateral peripheral stimulation on neuromuscular function.

It is known that resistance exercise using one limb can affect motor function of both the exercised limb and the unexercised contralateral limb, a phenomenon termed cross-education. It has been suggested that cross-education has clinical implications, e.g. in rehabilitation for orthopaedic conditions or post-stroke paresis. Much of the research on the contralateral effect of unilateral intervention on motor output is based on voluntary exercise. This scoping review aimed to map the characteristics of current literature on the cross-education caused by three most frequently utilised peripheral neuromuscular stimulation modalities in this context: electrical stimulation, mechanical vibration and percutaneous needling, that may direct future research and translate to clinical practice. A systematic search of relevant databases (Ebsco, ProQuest, PubMed, Scopus, Web of Science) through to the end of 2020 was conducted following the PRISMA Extension for Scoping Review. Empirical studies on human participants that applied a unilateral peripheral neuromuscular stimulation and assessed neuromuscular function of the stimulated and/or the unstimulated side were selected. By reading the full text, the demographic characteristics, context, design, methods and major findings of the studies were synthesised. The results found that 83 studies were eligible for the review, with the majority (53) utilised electrical stimulation whilst those applied vibration (18) or needling (12) were emerging. Although the contralateral effects appeared to be robust, only 31 studies claimed to be in the context of cross-education, and 25 investigated on clinical patients. The underlying mechanism for the contralateral effects induced by unilateral peripheral stimulation remains unclear. The findings suggest a need to enhance the awareness of cross-education caused by peripheral stimulation, to help improve the translation of theoretical concepts to clinical practice, and aid in developing well-designed clinical trials to determine the efficacy of cross-education therapies.

Aquatic Therapy for Persons with Neuromuscular Diseases - A Scoping Review.

BACKGROUND: Aquatic exercise is among the most common physical activity modalities performed by people with disabilities. OBJECTIVE: The present paper reviews currently-available research on aquatic therapy (AT) for persons with neuromuscular diseases (NMD). METHODS: A scoping review of the existing literature was conducted on PubMed, Embase, Medline, Scopus, Web of Science, SPORTdiscus, CINAHL and Lilacs from the earliest date available until October 2020. It follows the methodological framework for conducting a scoping review proposed by the Joanna Briggs Institute. RESULTS: A total of 28 articles were analyzed and the study parameters grouped by the topography of NMD; most of the studies (n = 16) addressed myopathies. A considerable increase in the number of studies was found over time, and heterogeneity was identified across and within AT interventions for persons with NMD; hence, to allow more effective interpretation of study results, there is a need to standardize the fundamental parameters and procedures for AT. CONCLUSIONS: This scoping review provides a comprehensive outline of available literature; the findings could serve as a starting point for clinical studies on the effects of AT on persons with NMD, and encourage a more coherent approach to their design.

Mimicking human riboflavin responsive neuromuscular disorders by silencing flad-1 gene in C. elegans: Alteration of vitamin transport and cholinergic transmission.

Riboflavin (Rf), or vitamin B2, is the precursor of FMN and FAD, redox cofactors of several dehydrogenases involved in energy metabolism, redox balance and other cell regulatory processes. FAD synthase, coded by FLAD1 gene in humans, is the last enzyme in the pathway converting Rf into FAD. Mutations in FLAD1 gene are responsible for neuromuscular disorders, in some cases treatable with Rf. In order to mimic these disorders, the Caenorhabditis elegans (C. elegans) gene orthologue of FLAD1 (flad-1) was silenced in a model strain hypersensitive to RNA interference in nervous system. Silencing flad-1 resulted in a significant decrease in total flavin content, paralleled by a decrease in the level of the FAD-dependent ETFDH protein and by a secondary transcriptional down-regulation of the Rf transporter 1 (rft-1) possibly responsible for the total flavin content decrease. Conversely an increased ETFDH mRNA content was found. These biochemical changes were accompanied by significant phenotypical changes, including impairments of fertility and locomotion due to altered cholinergic transmission, as indicated by the increased sensitivity to aldicarb. A proposal is made that neuronal acetylcholine production/release is affected by alteration of Rf homeostasis. Rf supplementation restored flavin content, increased rft-1 transcript levels and eliminated locomotion defects. In this aspect, C. elegans could provide a low-cost animal model to elucidate the molecular rationale for Rf therapy in human Rf responsive neuromuscular disorders and to screen other molecules with therapeutic potential.

Intermittent Abdominal Pressure Ventilation: An Alternative for Respiratory Support.

Intermittent abdominal pressure ventilation is a positive pressure ventilation technique that works with abdominal compressions. It has been known since 1938; however, for many years, it was out of production. In recent years, a new device has been produced that has captured the attention to this old respiratory support technique. We considered eight patients with respiratory failure secondary to a neuromuscular disease (congenital myopathy, Duchenne dystrophy, and amyotrophic lateral sclerosis) intolerant to daytime noninvasive ventilation (NIV). IAPV was proposed as an alternative to NIV. We performed baseline and post-IAPV respiratory function assessment. All patients, two years later, are still using intermittent abdominal ventilation. Intermittent positive abdominal mechanical ventilation can be a valid alternative to noninvasive mechanical ventilation with a nasal or face mask. It improves gas exchange, symptoms, and quality of life, decreases the incidence of pneumonia, and can avert the need for intubation and tracheotomy.

Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases.

Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life.

Interventions for promoting physical activity in people with neuromuscular disease.

BACKGROUND: The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health conditions, international guidance advises being as physically active as possible. Evidence from community interventions of physical activity indicate that people living with medical conditions are sometimes excluded from participation in studies. In this review, we considered the effects of activity-promoting interventions on physical activity and well-being in studies, as well as any adverse events experienced by participants living with inherited or acquired neuromuscular diseases (NMDs).  OBJECTIVES: To assess the effects of interventions designed to promote physical activity in people with NMD compared with no intervention or alternative interventions. SEARCH METHODS: On 30 April 2020, we searched Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, and ClinicalTrials.Gov. WHO ICTRP was not accessible at the time. SELECTION CRITERIA: We considered randomised or quasi-randomised trials, including cross-over trials, of interventions designed to promote physical activity in people with NMD compared to no intervention or alternative interventions. We specifically included studies that reported physical activity as an outcome measure. Our main focus was studies in which promoting physical activity was a stated aim but we also included studies in which physical activity was assessed as a secondary or exploratory outcome. DATA COLLECTION AND ANALYSIS: We used standard Cochrane procedures. MAIN RESULTS: The review included 13 studies (795 randomised participants from 12 studies; number of participants unclear in one study) of different interventions to promote physical activity. Most studies randomised a minority of invited participants. No study involved children or adolescents and nine studies reported minimal entry criteria for walking. Participants had one of nine inherited or acquired NMDs. Types of intervention included structured physical activity support, exercise support (as a specific form of physical activity), and behaviour change support that included physical activity or exercise. Only one included study clearly reported that the aim of intervention was to increase physical activity. Other studies reported or planned to analyse the effects of intervention on physical activity as a secondary or exploratory outcome measure. Six studies did not report results for physical activity outcomes, or the data were not usable. We judged 10 of the 13 included studies at high or unclear risk of bias from incomplete physical activity outcome reporting. We did not perform a meta-analysis for any comparison because of differences in interventions and in usual care. We also found considerable variation in how studies reported physical activity as an outcome measure. The studies that reported physical activity measurement did not always clearly report intention-to-treat (ITT) analysis or whether final assessments occurred during or after intervention. Based on prespecified measures, we included three comparisons in our summary of findings. A physical activity programme (weight-bearing) compared to no physical activity programme One study involved adults with diabetic peripheral neuropathy (DPN) and reported weekly duration of walking during and at the end of a one-year intervention using a StepWatch ankle accelerometer. Based on the point estimate and low-certainty evidence, intervention may have led to an important increase in physical activity per week; however, the 95% confidence interval (CI) included the possibility of no difference or an effect in either direction at three months (mean difference (MD) 34 minutes per week, 95% CI -92.19 to 160.19; 69 participants), six months (MD 68 minutes per week, 95% CI -55.35 to 191.35; 74 participants), and 12 months (MD 49 minutes per week, 95% CI -75.73 to 173.73; 70 participants). Study-reported effect estimates for foot lesions and full-thickness ulcers also included the possibility of no difference, a higher, or lower risk with intervention. A sensor-based, interactive exercise programme compared to no sensor-based, interactive exercise programme One study involved adults with DPN and reported duration of walking over 48 hours at the end of four weeks' intervention using a t-shirt embedded PAMSys sensor. It was not possible to draw conclusions about the effectiveness of the intervention from the very low-certainty evidence (MD -0.64 hours per 48 hours, 95% CI -2.42 to 1.13; 25 participants). We were also unable to draw conclusions about impact on the Physical Component Score (PCS) for quality of life (MD 0.24 points, 95% CI -5.98 to 6.46; 35 participants; very low-certainty evidence), although intervention may have made little or no difference to the Mental Component Score (MCS) for quality of life (MD 5.10 points, 95% CI -0.58 to 10.78; 35 participants; low-certainty evidence). A functional exercise programme compared to a stretching exercise programme One study involved adults with spinal and bulbar muscular atrophy and reported a daily physical activity count at the end of 12 weeks' intervention using an Actical accelerometer. It was not possible to draw conclusions about the effectiveness of either intervention (requiring compliance) due to low-certainty evidence and unconfirmed measurement units (MD -8701, 95% CI -38,293.30 to 20,891.30; 43 participants). Functional exercise may have made little or no difference to quality of life compared to stretching (PCS: MD -1.10 points, 95% CI -5.22 to 3.02; MCS: MD -1.10 points, 95% CI -6.79 to 4.59; 49 participants; low-certainty evidence). Although studies reported adverse events incompletely, we found no evidence of supported activity increasing the risk of serious adverse events. AUTHORS' CONCLUSIONS: We found a lack of evidence relating to children, adolescents, and non-ambulant people of any age. Many people living with NMD did not meet randomised controlled trial eligibility criteria. There was variation in the components of supported activity intervention and usual care, such as physical therapy provision. We identified variation among studies in how physical activity was monitored, analysed, and reported. We remain uncertain of the effectiveness of promotional intervention for physical activity and its impact on quality of life and adverse events. More information is needed on the ITT population, as well as more complete reporting of outcomes. While there may be no single objective measure of physical activity, the study of qualitative and dichotomous change in self-reported overall physical activity might offer a pragmatic approach to capturing important change at an individual and population level.

Does respiratory muscle training improve respiratory function compared to sham training, no training, standard treatment or breathing exercises in children and adults with neuromuscular disease? A Cochrane Review summary with commentary.

BACKGROUND: Progressive muscle weakness is a feature of neuromuscular diseases (NMDs), a heterogeneous group of conditions with variable onset, presentation and prognosis that affect both children and adults. Respiratory muscle weakness compromises respiratory function and may lead to respiratory failure. OBJECTIVE: To assess the effects of respiratory muscle training (RMT) in adults and children with NMD. METHODS: A Cochrane Review by Silva et al. was summarized with comments. RESULTS: Eleven studies involving 250 randomized participants with NMD were included. While the studies showed that RMT may lead to improvements in lung function and respiratory muscle strength in people with ALS and DMD, this was not a consistent finding. The evidence from all the included trials was of low or very low certainty. CONCLUSIONS: There may be some improvement in lung capacity and respiratory muscle strength following RMT in some NMD. There appears to be no clinically meaningful effect of RMT on physical functioning and quality of life in ALS. The low certainty of the evidence means that the results need to be interpreted with caution.

Growth and nutrition in pediatric neuromuscular disorders.

BACKGROUND & AIMS: Little is currently known about the nutrition and growth outcomes in children with neuromuscular disorders (NMDs), and these are likely disease dependent. The aim of this study was to describe the range of nutritional issues in pediatric NMDs and identify similarities and differences in growth outcomes and nutritional needs in children with a variety of NMDs at different ages, with the goal of informing future services. METHODS: In this cross-sectional study we collected data on growth, dietetic interventions and nutrition-related issues in 160 children who attended a multidisciplinary clinic in a tertiary children's hospital, from February to December 2019. Children with significant weakness affecting mobility before the age of 3 years were clinically grouped into 'early-onset NMDs'. RESULTS: Across our clinic, 42.5% children had a history of chronic gastrointestinal issues, and 34.4% received dietetic care on the day of clinical visit. Children with early-onset NMDs had significantly higher prevalence of swallowing issues, gastroesophageal reflux, and vomiting, as well as higher frequency of dietetic consultations, high energy diet, swallowing assessment and tube-feeding, compared to later-onset NMDs (p < 0.05). In total, 49.2% children with NMDs had an abnormal weight, in which the prevalence of underweight (n = 24, 19.2%) was significantly higher compared to normal Australian children (8.2%) (p < 0.05). In Duchenne muscular dystrophy, over 50% children were overweight/obese. CONCLUSION: Among children with NMDs, there were many disease-specific nutrition-related symptoms, growth issues, and dietetic practices that were tailored to individual needs. Future studies should focus on measuring the impact of specific dietetic practices on growth and nutritional outcomes, as well as developing a precision medicine approach tailored to the individual nutritional needs of children with NMDs.

Development and evaluation of a novel music-based therapeutic device for upper extremity movement training: A pre-clinical, single-arm trial.

Restoration of upper limb motor function and patient functional independence are crucial treatment targets in neurological rehabilitation. Growing evidence indicates that music-based intervention is a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions such as cerebral palsy, stroke, and Parkinson's Disease. In this context, music technology may be particularly useful to increase the availability and accessibility of music-based therapy and assist therapists in the implementation and assessment of targeted therapeutic goals. In the present study, we conducted a pre-clinical, single-arm trial to evaluate a novel music-based therapeutic device (SONATA) for upper limb extremity movement training. The device consists of a graphical user interface generated by a single-board computer displayed on a 32" touchscreen with built-in speakers controlled wirelessly by a computer tablet. The system includes two operational modes that allow users to play musical melodies on a virtual keyboard or draw figures/shapes whereby every action input results in controllable sensory feedback. Four motor tasks involving hand/finger movement were performed with 21 healthy individuals (13 males, aged 26.4 ± 3.5 years) to evaluate the device's operational modes and main features. The results of the functional tests suggest that the device is a reliable system to present pre-defined sequences of audiovisual stimuli and shapes and to record response and movement data. This preliminary study also suggests that the device is feasible and adequate for use with healthy individuals. These findings open new avenues for future clinical research to further investigate the feasibility and usability of the SONATA as a tool for upper extremity motor function training in neurological rehabilitation. Directions for future clinical research are discussed.

Novel CAPN3 variant associated with an autosomal dominant calpainopathy.

AIMS: The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. The exclusively recessive inheritance of this disorder has been recently challenged by the description of the recurrent variants, c.643_663del21 [p.(Ser215_Gly221del)] and c.598_612del15 [p.(Phe200_Leu204del)], associated with autosomal dominant inheritance. Our objective was to confirm the existence of autosomal dominant calpainopathies. METHODS: Through our activity as one of the reference centres for genetic diagnosis of calpainopathies in France and the resulting collaborations through the French National Network for Rare Neuromuscular Diseases (FILNEMUS), we identified four families harbouring the same CAPN3 heterozygous variant with supposedly autosomal dominant inheritance. RESULTS: We identified a novel dominantly inherited CAPN3 variant, c.1333G>A [p.(Gly445Arg)] in 14 affected patients from four unrelated families. The complementary phenotypic, functional and genetic findings correlate with an autosomal dominant inheritance in these families, emphasizing the existence of this novel transmission mode for calpainopathies. The mild phenotype associated with these autosomal dominant cases widens the phenotypic spectrum of calpainopathies and should therefore be considered in clinical practice. CONCLUSIONS: We confirm the existence of autosomal dominant calpainopathies as an entity beyond the cases related to the in-frame deletions c.643_663del21 and c.598_612del15, with the identification of a novel dominantly inherited and well-documented CAPN3 missense variant, c.1333G>A [p.(Gly445Arg)]. In addition to the consequences for genetic counselling, the confirmation of an autosomal dominant transmission mode for calpainopathies underlines the importance of re-assessing other myopathies for which the inheritance is considered as strictly autosomal recessive.

Psychosocial impact of sport activity in neuromuscular disorders.

Previous studies demonstrated the benefits of motor exercise and physical activity in neuromuscular disorders. However, very few papers assessed the effects of sport practise. The aim of this multicentre study was to assess the impact of sport activity on self-esteem and emotional regulation in a cohort of athletes with neuromuscular disorders. The 38 patients with Duchenne, Becker or other types of muscular dystrophy or spinal muscular atrophy practising sport (aged 13-49 years) and 39 age-, gender-, disability- and disease-matched patients not practising sport were enrolled. Testing procedures to assess self-esteem, anxiety and depression disorder, personality trait and quality of life (QoL) were used. Patients practising sport had a significantly higher self-esteem, lower level of depression, greater social own identity and adherence and QoL. Frequency of sport activity may represent a complementary therapy in neuromuscular disorders to improve mental and social well-being.

Taste disorder in facial onset sensory and motor neuronopathy: a case report.

BACKGROUND: Taste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom. CASE PRESENTATION: A 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support. CONCLUSION: Taste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus.

Agility Training to Integratively Promote Neuromuscular, Cognitive, Cardiovascular and Psychosocial Function in Healthy Older Adults: A Study Protocol of a One-Year Randomized-Controlled Trial.

Exercise training effectively mitigates aging-induced health and fitness impairments. Traditional training recommendations for the elderly focus separately on relevant physiological fitness domains, such as balance, flexibility, strength and endurance. Thus, a more holistic and functional training framework is needed. The proposed agility training concept integratively tackles spatial orientation, stop and go, balance and strength. The presented protocol aims at introducing a two-armed, one-year randomized controlled trial, evaluating the effects of this concept on neuromuscular, cardiovascular, cognitive and psychosocial health outcomes in healthy older adults. Eighty-five participants were enrolled in this ongoing trial. Seventy-nine participants completed baseline testing and were block-randomized to the agility training group or the inactive control group. All participants undergo pre- and post-testing with interim assessment after six months. The intervention group currently receives supervised, group-based agility training twice a week over one year, with progressively demanding perceptual, cognitive and physical exercises. Knee extension strength, reactive balance, dual task gait speed and the Agility Challenge for the Elderly (ACE) serve as primary endpoints and neuromuscular, cognitive, cardiovascular, and psychosocial meassures serve as surrogate secondary outcomes. Our protocol promotes a comprehensive exercise training concept for older adults, that might facilitate stakeholders in health and exercise to stimulate relevant health outcomes without relying on excessively time-consuming physical activity recommendations.

Soporte ventilatorio no invasivo en insuficiencia ventilatoria aguda severa en adolescentes con enfermedad neuromuscular y obesidad: estudio de casos / Non-invasive ventilatory support in severe acute ventilatory failure in adolescents with neuromuscular disease and obesity: study of cases

Noninvasive ventilatory support (NIVS) combined with mechanical cough assist (MI-E) is an effective tool to treat patients with acute ventilatory failure due to neuromuscular disorders (NMD). Airway respiratory infection could be lethal or with risk of endotraqueal intubation, especially when vital capacity (VC) is less than 15 ml/k. We report 2 obese adolescents, aged 11 and 14 years old, with myasthenic crisis (MC) and Duchenne muscular dystrophy (DMD). The last one with a severe cifoescoliosis treated with nocturnal noninvasive ventilation at home. MC girl has been treated with pyridostigmine, prednisolone and mycophenolate. They were admitted for thymectomy and spinal surgery arthrodesis respectively. After admission they developed airway respiratory infection triggering by Methaneumovirus and were treated with oxygen therapy, non-invasive ventilation with low-pressure support and EV immunoglobulin for the MC girl. After 48 h both patients developed severe respiratory failure, Sa/FiO2 < 200, atelectasis of lower lobes and difficulty to swallow, a peak cough flow (PFT)

El soporte ventilatorio no invasivo (SVNI) y la rehabilitación respiratoria con apilamiento de aire más tos asistida manual o mecánica, son efectivas para tratar la insuficiencia ventilatoria aguda en pacientes con enfermedades neuromusculares (ENM) y deterioro progresivo de la bomba respiratoria. Las agudizaciones gatilladas por infecciones respiratorias causan insuficiencia ventilatoria aguda potencialmente mortal y con alto riesgo de intubación, en especial cuando la capacidad vital (CV) es < de 15ml/k. Se reportan 2 adolescentes obesos con ENM de 11 y 14 años con miastenia gravis y distrofia muscular de Duchenne (DMD) con asistencia ventilatoria no invasiva nocturna con baja presión de soporte (AVNI), ingresados para timectomía y artrodesis de columna respectivamente. Una vez ingresados evolucionan con insuficiencia ventilatoria aguda secundaria a una infección respiratoria por Metaneumovirus. Inicialmente fueron manejados con oxigenoterapia, AVNI y gamaglobulina endovenosa en el caso de la paciente con crisis miasténica (CM). A las 48h presentan dificultad respiratoria severa, Sa/FiO2 < 200, atelectasias bibasales y disfagia, CV de 800ml (11ml/k) en el paciente con CM y de 200 ml (2,5ml/k) en el paciente con DMD y un pico flujo tosido (PFT) < 100 l/m. Se cambia a SVNI con equipo Trilogy® y BipapA40®, en modalidad S/T (espontáneo/tiempo) y AVAPS (volumen promedio asegurado en presión de soporte) con altos parámetros ventilatorios; suspendiendo rápidamente la oxigenoterapia, al combinar tos mecánicamente asistida con in-exsufflator (MI-E) en forma intensiva. Ambos pacientes presentan mejoría clínica sostenida, de la CV, PFT y pico flujo exuflado máximo con MI-E (PFE-MI-E). El SVNI más la aplicación sistemática del MI-E hasta lograr SaO2 de al menos 95% con oxígeno ambiental evita la intubación endotraqueal en ENM, a diferencia del agravamiento producido por AVNI y oxigenoterapia con criterios clásicos.

Health and Economic Outcomes of Posterior Spinal Fusion for Children With Neuromuscular Scoliosis.

OBJECTIVES: Neuromuscular scoliosis (NMS) can result in severe disability. Nonoperative management minimally slows scoliosis progression, but operative management with posterior spinal fusion (PSF) carries high risks of morbidity and mortality. In this study, we compare health and economic outcomes of PSF to nonoperative management for children with NMS to identify opportunities to improve care. METHODS: We performed a cost-effectiveness analysis. Our decision analytic model included patients aged 5 to 20 years with NMS and a Cobb angle ≥50°, with a base case of 15-year-old patients. We estimated costs, life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness from published literature and conducted sensitivity analyses on all model inputs. RESULTS: We estimated that PSF resulted in modestly decreased discounted life expectancy (10.8 years) but longer quality-adjusted life expectancy (4.84 QALYs) than nonoperative management (11.2 years; 3.21 QALYs). PSF costs $75 400 per patient. Under base-case assumptions, PSF costs $50 100 per QALY gained. Our findings were sensitive to quality of life (QoL) and life expectancy, with PSF favored if it significantly increased QoL. CONCLUSIONS: In patients with NMS, whether PSF is cost-effective depends strongly on the degree to which QoL improved, with larger improvements when NMS is the primary cause of debility, but limited data on QoL and life expectancy preclude a definitive assessment. Improved patient-centered outcome assessments are essential to understanding the effectiveness of NMS treatment alternatives. Because the degree to which PSF influences QoL substantially impacts health outcomes and varies by patient, clinicians should consider shared decision-making during PSF-related consultations.