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Interventions for promoting physical activity in people with neuromuscular disease.
Jones, K, Hawke, F, Newman, J, Miller, JA, Burns, J, Jakovljevic, DG, Gorman, G, Turnbull, DM, Ramdharry, G
The Cochrane database of systematic reviews. 2021;(5):CD013544
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Abstract
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.
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Nutritional practices in pediatric patients with neuromuscular disorders.
Chou, E, Lindeback, R, Sampaio, H, Farrar, MA
Nutrition reviews. 2020;(10):857-865
Abstract
Children with neuromuscular disorders (NMDs) may experience a spectrum of nutritional issues with adverse health consequences. This review summarizes the current understanding of nutritional care in pediatric NMDs, recognizing disease-specific aspects of nutrition alongside the challenges and needs in dietetic care. General or disease-related nutritional issues for children with NMDs include being underweight, overweight, or obese and having swallowing difficulty, gastroesophageal reflux, diarrhea, and/or constipation. Specific challenges in NMD nutritional assessment include alterations in body composition and energy requirements and difficulties in measuring anthropometry. Multidisciplinary dietetic intervention focuses on optimizing nutrient intakes to avert growth failure or obesity and managing feeding difficulties and gastrointestinal problems. Care guidelines are disease specific and vary in approach and detail. To promote best clinical practice across diverse settings, a standardized approach to assessing growth and nutrition across all pediatric NMDs is needed to direct optimal care centered on individual requirements. Future studies should focus on determining the prevalence of specific nutritional issues and the effectiveness of specific interventions among various pediatric NMD populations.
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Electrolyte Disorders and the Nervous System.
Jacoby, N
Continuum (Minneapolis, Minn.). 2020;(3):632-658
Abstract
PURPOSE OF REVIEW This article provides an overview of the major electrolyte disorders and discusses in detail the homeostasis, etiologies, neurologic manifestations, and treatment of these disorders. RECENT FINDINGS The diagnosis and management of hyponatremia continue to evolve. Diagnostic accuracy is improved by assessing serum and urine osmolality as well as urinary sodium. Avoiding overcorrection of hyponatremia is crucial to avoid osmotic demyelination syndrome, although even careful correction can cause osmotic demyelination syndrome in patients who have other risk factors. The clinical presentation of osmotic demyelination syndrome has expanded, with many patients presenting with extrapontine myelinolysis in addition to central pontine myelinolysis. SUMMARY Electrolyte disorders often present with neurologic manifestations. Whereas disorders of some electrolytes, such as sodium, preferentially affect the central nervous system, disorders of others, such as potassium and calcium, have significant neuromuscular manifestations. An understanding of the pathophysiology of these disorders and recognition of these manifestations are crucial for the practicing neurologist as the symptoms are reversible with correct management.
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Neuromuscular presentations in patients with COVID-19.
Paliwal, VK, Garg, RK, Gupta, A, Tejan, N
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2020;(11):3039-3056
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Abstract
COVID-19 is caused by the coronavirus SARS-CoV-2 that has an affinity for neural tissue. There are reports of encephalitis, encephalopathy, cranial neuropathy, Guillain-Barrè syndrome, and myositis/rhabdomyolysis in patients with COVID-19. In this review, we focused on the neuromuscular manifestations of SARS-CoV-2 infection. We analyzed all published reports on SARS-CoV-2-related peripheral nerve, neuromuscular junction, muscle, and cranial nerve disorders. Olfactory and gustatory dysfunction is now accepted as an early manifestation of COVID-19 infection. Inflammation, edema, and axonal damage of olfactory bulb have been shown in autopsy of patients who died of COVID-19. Olfactory pathway is suggested as a portal of entry of SARS-CoV-2 in the brain. Similar to involvement of olfactory bulb, isolated oculomotor, trochlear and facial nerve has been described. Increasing reports Guillain-Barrè syndrome secondary to COVID-19 are being published. Unlike typical GBS, most of COVID-19-related GBS were elderly, had concomitant pneumonia or ARDS, more prevalent demyelinating neuropathy, and relatively poor outcome. Myalgia is described among the common symptoms of COVID-19 after fever, cough, and sore throat. Duration of myalgia may be related to the severity of COVID-19 disease. Few patients had muscle weakness and elevated creatine kinase along with elevated levels of acute-phase reactants. All these patients with myositis/rhabdomyolysis had severe respiratory complications related to COVID-19. A handful of patients with myasthenia gravis showed exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids.
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Prevalence, pathological mechanisms, and genetic basis of limb-girdle muscular dystrophies: A review.
Taghizadeh, E, Rezaee, M, Barreto, GE, Sahebkar, A
Journal of cellular physiology. 2019;(6):7874-7884
Abstract
Limb-girdle muscular dystrophies (LGMDs) are a highly heterogeneous group of neuromuscular disorders that are associated with weakness and wasting of muscles in legs and arms. Signs and symptoms may begin at any age and usually worsen by time. LGMDs are autosomal disorders with different types and their prevalence is not the same in different areas. New technologies such as next-generation sequencing can accelerate their diagnosis. Several important pathological mechanisms that are involved in the pathology of the LGMD include abnormalities in dystrophin-glycoprotein complex, the sarcomere, glycosylation of dystroglycan, vesicle and molecular trafficking, signal transduction pathways, and nuclear functions. Here, we provide a comprehensive review that integrates LGMD clinical manifestations, prevalence, and some pathological mechanisms involved in LGMDs.
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Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies.
Lang, B, Makuch, M, Moloney, T, Dettmann, I, Mindorf, S, Probst, C, Stoecker, W, Buckley, C, Newton, CR, Leite, MI, et al
Journal of neurology, neurosurgery, and psychiatry. 2017;(4):353-361
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Abstract
OBJECTIVES Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. METHODS Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125I-αDTX and 125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. RESULTS VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical-serological correlations and a limited immunotherapy response. CONCLUSIONS Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies.
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The importance of de novo mutations for pediatric neurological disease--It is not all in utero or birth trauma.
Erickson, RP
Mutation research. Reviews in mutation research. 2016;:42-58
Abstract
The advent of next generation sequencing (NGS, which consists of massively parallel sequencing to perform TGS (total genome sequencing) or WES (whole exome sequencing)) has abundantly discovered many causative mutations in patients with pediatric neurological disease. A surprisingly high number of these are de novo mutations which have not been inherited from either parent. For epilepsy, autism spectrum disorders, and neuromotor disorders, including cerebral palsy, initial estimates put the frequency of causative de novo mutations at about 15% and about 10% of these are somatic. There are some shared mutated genes between these three classes of disease. Studies of copy number variation by comparative genomic hybridization (CGH) proceded the NGS approaches but they also detect de novo variation which is especially important for ASDs. There are interesting differences between the mutated genes detected by CGS and NGS. In summary, de novo mutations cause a very significant proportion of pediatric neurological disease.
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Increasing Role of Titin Mutations in Neuromuscular Disorders.
Savarese, M, Sarparanta, J, Vihola, A, Udd, B, Hackman, P
Journal of neuromuscular diseases. 2016;(3):293-308
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Abstract
The TTN gene with 363 coding exons encodes titin, a giant muscle protein spanning from the Z-disk to the M-band within the sarcomere. Mutations in the TTN gene have been associated with different genetic disorders, including hypertrophic and dilated cardiomyopathy and several skeletal muscle diseases.Before the introduction of next generation sequencing (NGS) methods, the molecular analysis of TTN has been laborious, expensive and not widely used, resulting in a limited number of mutations identified. Recent studies however, based on the use of NGS strategies, give evidence of an increasing number of rare and unique TTN variants. The interpretation of these rare variants of uncertain significance (VOUS) represents a challenge for clinicians and researchers.The main aim of this review is to describe the wide spectrum of muscle diseases caused by TTN mutations so far determined, summarizing the molecular findings as well as the clinical data, and to highlight the importance of joint efforts to respond to the challenges arising from the use of NGS. An international collaboration through a clinical and research consortium and the development of a single accessible database listing variants in the TTN gene, identified by high throughput approaches, may be the key to a better assessment of titinopathies and to systematic genotype- phenotype correlation studies.
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Common complications of pediatric neuromuscular disorders.
Skalsky, AJ, Dalal, PB
Physical medicine and rehabilitation clinics of North America. 2015;(1):21-8
Abstract
Children with pediatric neuromuscular disorders experience common complications, primarily due to immobility and weakness. Musculoskeletal complications include hip dysplasia with associated hip subluxation or dislocation, neuromuscular scoliosis, and osteoporosis and resulting fractures. Constipation, gastroesophageal reflux, and obesity and malnutrition are commonly experienced gastrointestinal complications. Disordered sleep also is frequently observed, which affects both patients and caregivers.
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Fatigue in healthy and diseased individuals.
Finsterer, J, Mahjoub, SZ
The American journal of hospice & palliative care. 2014;(5):562-75
Abstract
OBJECTIVES Although fatigue is experienced by everyone, its definition and classification remains under debate. METHODS A review of the previously published data on fatigue. RESULTS Fatigue is influenced by age, gender, physical condition, type of food, latency to last meal, mental status, psychological conditions, personality type, life experience, and the health status of an individual. Fatigue may not only be a symptom but also a measurable and quantifiable dimension, also known as fatigability. Additionally, it may be classified as a condition occurring at rest or under exercise or stress, as physiologic reaction or pathologic condition, as spontaneous phenomenon or triggerable state, as resistant or irresistant to preconditioning, training, or attitude, as prominent or collateral experience, and as accessible or inaccessible to any type of treatment or intervention. Fatigue may be the sole symptom of a disease or one among others. It may be also classified as acute or chronic. Quantification of fatigability is achievable by fatigue scores, force measurement, electromyography, or other means. Fatigue and fatigability need to be delineated from conditions such as sleepiness, apathy, exhaustion, exercise intolerance, lack of vigor, weakness, inertia, or tiredness. Among neurological disorders, the prevalence of fatigue is particularly increased in multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, traumatic brain injury, stroke, and bleeding and also in neuromuscular disorders. Fatigue may be influenced by training, mental preconditioning, or drugs. CONCLUSIONS Fatigue needs to be recognized as an important condition that is not only a symptom but may also be quantified and can be modified by various measures depending on the underlying cause.