Future Directions for Respiratory Muscle Training in Neuromuscular Disorders: A Scoping Review.

BACKGROUND: Respiratory muscle training (RMT) aims to improve inspiratory and/or expiratory muscle function in neuromuscular disorders (NMDs). A comprehensive overview of the available literature is lacking. This scoping review explores methodological characteristics, (adverse) effects, and adherence of RMT studies in NMDs. Moreover, it identifies limitations and research gaps in the literature and provides future research directions. SUMMARY: Eligible studies were identified using MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases. Three reviewers independently selected articles. Inclusion criteria were English language, original research articles on RMT using a device, patients with an NMD, and pulmonary function tests or respiratory muscle strength as outcome measures. We included NMDs with slow, intermediate and fast progression. Exclusion criteria were critically ill patients, weaning from mechanical ventilation, other neurological disorders, and RMT combined with non-respiratory interventions. One reviewer extracted the data on patients' characteristics, methodological characteristics, results of outcome measures, adverse events, and patient adherence. Forty-five studies were identified. We found a large diversity in study designs and training protocols. The effects of RMT on respiratory muscle strength and/or endurance are variable. Patient adherence was high and no serious adverse events were reported. KEY MESSAGES: The diversity in studies across the available literature precludes definitive conclusions regarding the effects of RMT on respiratory muscle function and clinically relevant outcomes in NMDs. Therefore, well-powered and -designed studies that focus on clinically relevant outcomes and assess whether RMT can improve or offset deterioration of respiratory muscle weakness in NMDs are needed.

Effectiveness of an outpatient rehabilitation programme in patients with neuralgic amyotrophy and scapular dyskinesia: a randomised controlled trial.

BACKGROUND: Neuralgic amyotrophy (NA) is an acute inflammation of nerves within the brachial plexus territory leading to severe pain and multifocal paresis resulting in >60% of patients having residual complaints and functional limitations correlated with scapular dyskinesia. Our primary aim was to compare the effects of multidisciplinary rehabilitation (MR), focused on motor relearning to improve scapular dyskinesia and self-management strategies for reducing pain and fatigue, with usual care (UC) on shoulder, arm and hand functional capability in patients with NA. METHODS: In a non-blinded randomised controlled trial (RCT), patients with NA (aged≥18 years, scapular dyskinesia, >8 weeks after onset) were randomised to either an MR or an UC group. MR consisted of a diagnostic multidisciplinary consultation and eight sessions of physical and occupational therapy. Primary outcome was functional capability of the shoulder, arm and hand assessed with the Shoulder Rating Questionnaire-Dutch Language Version (SRQ-DLV). RESULTS: We included 47 patients with NA; due to drop-out, there were 22 participants in MR and 15 in UC for primary analysis. The mean group difference adjusted for sex, age and SRQ-DLV baseline score was 8.60 (95%CI: 0.26 to 16.94, p=0.044). The proportion attaining a minimal clinically relevant SRQ-DLV improvement (≥12) was larger for the MR group (59%) than the UC group (33%) with a number needed to treat of 4. CONCLUSION: This RCT shows that an MR programme focused on motor relearning to improve scapular dyskinesia, combined with self-management strategies for reducing pain and fatigue, shows more beneficial effects on shoulder, arm and hand functional capability than UC in patients with NA. TRIAL REGISTRATION NUMBER: NCT03441347.

Feasible and clinical relevant outcome measures for adults with mitochondrial disease.

There is no consensus on clinical outcome measures that reflect function, activities and participation which are suitable for adults with mitochondrial diseases (MD). The aim of this study was to determine feasible and clinically relevant outcome measures for patients with MD . In 156 adult patients with MD, endurance, balance, strength and mobility tests were evaluated. All tests showed a negative deviation to healthy reference values. Balance tests were feasible and significantly correlated with clinical severity. The Åstrand cycle test was not feasible in 55%, whereas the feasibility of the 6 min walking test is unclear in patients with MD.

Reachable workspace analysis is a potential measurement for impairment of the upper extremity in neuralgic amyotrophy.

INTRODUCTION/AIMS: Neuralgic amyotrophy (NA) is a multifocal neuropathy involving the nerves of the upper extremity, limiting functional capability and reducing range of motion. The reachable workspace (RWS) is a computerized three-dimensinal analysis system that evaluates the relative surface area (RSA) of an individual's arm reachability and has shown utility in several neuromuscular disorders. The aims of this study were to examine the ability of the RWS to quantitatively detect limitations in upper extremity active range of motion in patients with NA, and correlate these with other upper extremity functional outcome measures. METHODS: Forty-seven patients with NA and 25 healthy age- and sex-matched controls were measured with the RWS. Study participants' RSAs were correlated with scores on the Shoulder Rating Questionnaire (SRQ), the Disabilities of Arm Shoulder and Hand (DASH) questionnaire, and upper extremity strength measurements using hand-held dynamometry. RESULTS: Patients with NA showed significantly lower values in the affected arm for all quadrants (except for the ipsilateral lower quadrant) and total RSA compared with controls (P < 0.001). We found moderate correlations between the reachable workspace, the DASH questionnaire result (r = -0.415), and serratus anterior muscle strength (r = 0.414). DISCUSSION: RWS is able to detect limitations in active range of motion of the affected arm in patients with NA, and is moderately correlated with upper extremity functional measures. RWS can demonstrate impairment of the affected upper extremity in NA and it has potential as a clinical outcome measure.

Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study.

BACKGROUND: SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. METHODS: LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient's age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. DISCUSSION: Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. CONCLUSION: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. TRIAL REGISTRATION: This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).

Validity and reliability of serratus anterior hand held dynamometry.

BACKGROUND: Strength testing of the serratus anterior muscle with hand held dynamometry (HDD) in supine subjects has low reproducibility, and is influenced by compensatory activity of other muscles like the pectoralis major and upper trapezius. Previously, two manual maximum voluntary isometric contraction tests of the serratus anterior muscle were reported that recruited optimal surface electromyography (sEMG) activity in a sitting position. We adapted three manual muscle tests to make them suitable for HHD and investigated their validity and reliability. METHODS: Twenty-one healthy adults were examined by two assessors in one supine and two seated positions. Each test was repeated twice. Construct validity was determined by evaluating force production (assessed with HHD) in relation to sEMG of the serratus anterior, upper trapezius and pectoralis major muscles, comparing the three test positions. Intra- and interrater reliability were determined by calculating intra-class correlation coefficients (ICC) smallest detectable change (SDC) and standard error of measurement (SEM). RESULTS: Serratus anterior muscle sEMG activity was most isolated in a seated position with the humerus in 90° anteflexion in the scapular plane. This resulted in the lowest measured force levels in this position with a mean force of 296 N (SEM 15.8 N). Intrarater reliability yielded an ICC of 0.658 (95% CI 0.325; 0.846) and an interrater reliability of 0.277 (95% CI -0.089;0.605). SDC was 127 Newton, SEM 45.8 Newton. CONCLUSION: The results indicate that validity for strength testing of the serratus anterior muscle is optimal with subjects in a seated position and the shoulder flexed at 90° in the scapular plane. Intrarater reliability is moderate and interrater reliability of this procedure is poor. However the high SDC values make it difficult to use the measurement in repeated measurements.

Correction to: Validity and reliability of serratus anterior hand held dynamometry.

Following publication of the original article [1], the authors reported that the headers in Table 2 in their paper were omitted.

Neuralgic amyotrophy: An update on diagnosis, pathophysiology, and treatment.

In this review we provide a current overview of the clinical features, pathophysiology, epidemiology, and diagnostic and therapeutic strategies in neuralgic amyotrophy (NA). The disorder has several phenotypic variations, with a classic form in 70% of the patients. It is not rare, with an incidence of 1 per 1,000 individuals, but it is still often missed. Recurrences are common, yet the proposed multifactorial etiology, which includes genetic, biomechanical, and immunologic factors, limits our capacity to predict or prevent them. NA is a clinical diagnosis, and ancillary studies serve to exclude infectious or malignant causes or to assess a differential diagnosis. If patients are seen early and are still in pain, a short trial of high-dose oral corticosteroids is advised, and adequate analgesia may require opioids and non-steroidal anti-inflammatory drugs. Persistent complaints are common, and a multidisciplinary rehabilitation approach focusing on scapular coordination, energy distribution strategies, and self-management is indicated.

Effectiveness and cost-effectiveness of a self-management group program to improve social participation in patients with neuromuscular disease and chronic fatigue: protocol of the Energetic study.

BACKGROUND: Chronic fatigue is present in more than 60% of the patients with a neuromuscular disease and can be their most disabling symptom. In combination with other impairments, fatigue often results in low levels of physical activity and decreased social participation, leading to high societal costs. 'Energetic' is a self-management group program aimed at improving social participation, physical endurance and alleviating fatigue in these patients. The primary aim of this study is to evaluate the effectiveness and cost-effectiveness of the Energetic program. METHODS/DESIGN: A multicentered, assessor-blinded, two-armed randomized controlled trial is conducted with evaluations at inclusion and four, seven and fifteen months later. The study includes patients with a neuromuscular disease and chronic fatigue and, when present, their caregivers. The participants are randomized (ratio 1:1) to either an intervention group, receiving the Energetic program, or a control group, receiving usual care (i.e., no specific intervention). The Energetic program covers four months and includes four modules: 1) individually tailored aerobic exercise training; 2) education about aerobic exercise; 3) self-management training in applying energy conservation strategies; and 4) implementation and relapse prevention in daily life. Two months after cessation of the program a booster session is provided. The primary outcome is the perceived performance score of the Canadian Occupational Performance Measure (COPM). Secondary outcomes include the COPM-satisfaction score, and measures of fatigue, physical endurance, activity engagement, mood, and self-efficacy. Caregiver burden is also evaluated as a secondary outcome. Health-related quality of life and medical and societal costs are assessed to estimate cost-effectiveness of the program. DISCUSSION: The Energetic study is the first randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical and self-management group training program for improving social participation, physical endurance and alleviating fatigue in patients with neuromuscular diseases. It will generate new insights in (cost-)effective rehabilitation strategies for these incurable conditions. TRIAL REGISTRATION: Clinicaltrials.gov NCT02208687 .

The capability approach in rehabilitation: developing capability care.

PURPOSE: To develop a multidisciplinary outpatient rehabilitation intervention for people with neuromuscular diseases (NMD) based on the capability approach: capability care for persons with NMD. MATERIALS AND METHODS: The development process is described using a framework of actions for intervention development. It has been an iterative process consisting of a design phase based on theoretical insights and project group discussions, and a refine phase involving input from relevant stakeholders. RESULTS: Multidisciplinary efforts have resulted in the development of capability care for rehabilitation of persons with NMD. It can focus both on facilitating and achieving functionings (beings and doings), as well as looking for alternative functionings that fulfil the same underlying value, thereby contributing to the persons' well-being. To facilitate a conversation on broader aspects that impact on well-being, persons with NMD receive a preparation letter and healthcare professionals are provided with guiding questions and practical tools to use. CONCLUSIONS: We have shown that it is possible to develop a healthcare intervention based on the capability approach. We hope that rehabilitation professionals will be encouraged to use capability care and that other medical professionals will be inspired to develop capability care in their respective fields. REGISTRATION: Registered at trialregister.nl NL8946.

The capability approach can be used for development of healthcare interventions.Capability care in rehabilitation focuses on realising what is of real value to the person.The capability approach and the ICF are complementary and can both be used in rehabilitation.

Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study.

INTRODUCTION: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) are rare neuromuscular diseases with respiratory impairment from a young age. Prospective natural history studies are needed for prevalence estimations, respiratory characterization, optimizing clinical care and selecting outcome measures for trial readiness. METHODS: Our prospective 1.5-year natural history study included spirometry (forced vital capacity (FVC); difference between upright and supine vital capacity (dVC)), respiratory muscle strength tests (sniff nasal inspiratory pressure (SNIP)) (age≥5 years), and diaphragm ultrasound (thickness; thickening; echogenicity; all ages). RESULTS: Twenty-six LAMA2-MD patients (M = 8, median 21 [9; 31] years) and 11 SELENON-RM patients (M = 8, 20 [10; 33] years) were included. At baseline, 17 (85 %) LAMA2-MD (FVC%: 59 % [33; 68]) and all SELENON-RM patients (FVC%: 34 % [31; 46]) had an impaired respiratory function (FVC%<80 %). Nine (35 %) LAMA2-MD and eight (73 %) SELENON-RM patients received mechanical ventilation at baseline, and two additional SELENON-RM patients started during follow-up. Contrarily to LAMA2-MD, SELENON-RM patients had severe diaphragm atrophy (diaphragm thickness z-score: 2.5 [-3.1; -2.1]) and dysfunction (diaphragm thickness ratio: 1.2 [1.0; 1.7]; dVC: 30 % [7.7; 41]). SNIP was low in both neuromuscular diseases and correlated with motor function. In SELENON-RM, respiratory function decreased during follow-up. CONCLUSION: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials. CLINICAL TRIAL NUMBER: NCT04478981.

Bone quality in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a one-year prospective natural history study.

Fragility fractures are frequently reported in neuromuscular diseases and negatively influence functional prognosis, quality of life and survival. In LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) cross-sectional and prospective natural history studies on bone quality and fragility long bone fractures (LBFs) are lacking. We therefore aim to systematically assess bone quality and provide recommendations for clinical care. We performed a one-year prospective natural history study in 21 LAMA2-MD and 10 SELENON-RM patients including a standardized fracture history and bone quality assessment through dual energy Xray absorptiometry scan (DEXA-scan) and/or bone health index (BHI). Ninety percent of the LAMA2-MD and SELENON-RM patients showed low bone quality. Eight (38%) LAMA2-MD and five (50%) SELENON-RM patients had a history of fragility LBFs. During the one-year follow-up period, one LAMA2-MD patient (female, 3 years) experienced a fragility LBF of the right humerus. We found no difference in bone mineral density between baseline and one-year follow-up. Based on general international guidelines for osteoporosis, we advise adequate vitamin D and calcium intake, and standardized clinical follow-up through a DEXA-scan or BHI in all LAMA2-MD and SELENON-RM patients. On indication, patients should be referred to the pediatrics or internal medicine for consideration of additional treatments.

Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.

Background: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking. Objective: The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care. Methods: In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction. Results: 21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients. Conclusion: ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.

Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

BACKGROUND: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance. OBJECTIVE: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance. METHODS: An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5. RESULTS: One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources. CONCLUSION: Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.

Treatment Approaches for Altered Facial Expression: A Systematic Review in Facioscapulohumeral Muscular Dystrophy and Other Neurological Diseases.

Background: Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities. Objective: We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD. Methods: A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning. Results: Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures. Conclusions: Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.

A cross-sectional study in 18 patients with typical and mild forms of nemaline myopathy in the Netherlands.

Nemaline myopathy (NM) is a congenital myopathy with generalised muscle weakness, most pronounced in neck flexor, bulbar and respiratory muscles. The aim of this cross-sectional study was to assess the Dutch NM patient cohort. We assessed medical history, physical examination, quality of life (QoL), fatigue severity, motor function (MFM), and respiratory muscle function. We included 18 of the 28 identified patients (13 females (11-67 years old); five males (31-74 years old)) with typical or mild NM and eight different genotypes. Nine patients (50 %) used a wheelchair, eight patients (44 %) used mechanical ventilation, and four patients (22 %) were on tube feeding. Spinal deformities were found in 14 patients (78 %). The median Medical Research Council (MRC) sum score was 38/60 [interquartile range 32-51] in typical and 48/60 [44-50] in mild NM. The experienced QoL was lower and fatigue severity was higher than reference values of the healthy population. The total MFM score was 55 % [49-94] in typical and 88 % [72-93] in mild NM. Most of the patients who performed spirometry had a restrictive lung function pattern (11/15). This identification and characterisation of the Dutch NM patient cohort is important for international collaboration and can guide the design of future clinical trials.

Complete absence of evening melatonin increase in tetraplegics.

Individuals with a spinal cord injury (SCI), especially with tetraplegia, experience poor sleep quality, and this may be related to impaired control of circadian rhythmicity. Here, we examined the evening onset of melatonin secretion, an important hormone for the initiation of sleep, in people with a complete cervical (tetraplegia) and thoracic (paraplegia) SCI, and age- and sex-matched able-bodied control participants. Multiple samples of salivary melatonin were obtained during the evening hours and analyzed by ELISA methods in 10 control partcipants, 9 individuals with paraplegia, and 6 individuals with tetraplegia. Sleep quality was assessed using questionnaires. Interactive effects of group and time were found for melatonin levels (P=0.022). In the control and paraplegia groups, the mean melatonin level increased significantly from 2.59 ± 1.04 and 4.28 ± 3.28 pg/ml at 7 PM to 10.62 ± 4.59 and 13.10 ± 7.39 pg/ml at 11 PM, respectively (P<0.001). In the tetraplegia group, melatonin level was 5.25 ± 3.72 at 7 PM but only 2.41 ± 1.25 pg/ml at 11 PM (P>0.05). Decreased sleep quality was more prevalent in individuals with tetraplegia (83%) and paraplegia (75%) compared with controls (20%; P=0.02). Unlike in the control and paraplegia groups, the evening increase in melatonin concentration was completely absent in the tetraplegia group. This provides biological insight into sleep regulation in humans and provides better understanding of the poor sleep quality in people with tetraplegia.

Indications for Tube Feeding in Adults with Muscular Disorders: A Scoping Review.

BACKGROUND: Eating an adequate diet and maintaining a healthy body weight can be challenging for patients with muscular disorders (MD). Starting tube feeding can have a positive impact on nutritional status, functioning and quality of life. Guidelines on when to start tube feeding in adults with MD are lacking. OBJECTIVE: We aim to review the scientific literature on indications to start tube feeding in adults with facioscapulohumeral dystrophy (FSHD), inclusion body myositis (IBM), muscular dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD) and congenital myopathies. METHODS: This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Relevant studies were identified in Pubmed, Embase and Cinahl (April 2022). The medical subject headings (MeSH) and text words used were related to FSHD, IBM, DM1, OPMD or congenital myopathies and dysphagia, enteral nutrition or malnutrition. RESULTS: Of 1046 unique articles, 9 case reports and 2 retrospective case series were included. Indications to start tube feeding were dysphagia, malnutrition/weight loss and respiratory infections (due to aspiration). Percutaneous endoscopic gastrostomy (PEG) tubes were used most often and complications were respiratory failure, problems with the tube itself, accidental tube removal, cutaneous symptoms, digestive symptoms, and peritonitis. CONCLUSION: Data on tube feeding in MD is scarce. Indications to start tube feeding were similar across the various MD. We call for more research in this field and suggest to include screening for dysphagia, aspiration and malnutrition in for the treatment of various MD.

Psychosocial functioning in patients with altered facial expression: a scoping review in five neurological diseases.

PURPOSE: To perform a scoping review to investigate the psychosocial impact of having an altered facial expression in five neurological diseases. METHODS: A systematic literature search was performed. Studies were on Bell's palsy, facioscapulohumeral muscular dystrophy (FSHD), Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease patients; had a focus on altered facial expression; and had any form of psychosocial outcome measure. Data extraction focused on psychosocial outcomes. RESULTS: Bell's palsy, myotonic dystrophy type 1, and Parkinson's disease patients more often experienced some degree of psychosocial distress than healthy controls. In FSHD, facial weakness negatively influenced communication and was experienced as a burden. The psychosocial distress applied especially to women (Bell's palsy and Parkinson's disease), and patients with more severely altered facial expression (Bell's palsy), but not for Moebius syndrome patients. Furthermore, Parkinson's disease patients with more pronounced hypomimia were perceived more negatively by observers. Various strategies were reported to compensate for altered facial expression. CONCLUSIONS: This review showed that patients with altered facial expression in four of five included neurological diseases had reduced psychosocial functioning. Future research recommendations include studies on observers' judgements of patients during social interactions and on the effectiveness of compensation strategies in enhancing psychosocial functioning.

Negative effects of altered facial expression on psychosocial functioning are common and more abundant in women and in more severely affected patients with various neurological disorders.Health care professionals should be alert to psychosocial distress in patients with altered facial expression.Learning of compensatory strategies could be a beneficial therapy for patients with psychosocial distress due to an altered facial expression.

Development and validation of the patient-reported "Facial Function Scale" for facioscapulohumeral muscular dystrophy.

PURPOSE: Facial weakness and its functional consequences are an often underappreciated clinical feature of facioscapulohumeral muscular dystrophy (FSHD) by healthcare professionals and researchers. This is at least in part due to the fact that there are few adequate clinical outcome measures available. METHODS: We developed the Facial Function Scale, a Rasch-built questionnaire on the functional disabilities relating to facial weakness in FSHD. A preliminary 33-item questionnaire was created based on semi-structured interviews with 16 FSHD patients and completed by 119 patients. For reliability studies, 73 patients completed it again after a two-week interval. Data were subjected to semi-automated Rasch analysis to select the most appropriate item set to fit model expectations. RESULTS: This resulted in a 25-item unidimensional, linear-weighted questionnaire with high internal consistency (person separation index = 0.92) and test-retest reliability (patients' locations ICC = 0.98 and items' locations ICC = 0.99). Good external construct validity scores were obtained through correlation with the Communicative Participation Item Bank questionnaire, examiner-reported Facial Weakness Score and facial weakness subscale of the FSHD evaluation score (respectively r = 0.733, r = -0.566, and r = 0.441, all p < 0.001). CONCLUSIONS: This study provides a linear-weighted, clinimetrically sound, patient-reported outcome measure on the functional disabilities relating to facial weakness in FSHD, to enable further research on this relevant topic.Implications for rehabilitationFacial weakness and its functional consequences are an often underappreciated clinical feature of facioscapulohumeral muscular dystrophy (FSHD), both in symptomatic treatment and in research.To enable the development and testing of therapeutic symptomatic interventions for facial weakness, clinical outcome measures are required.This study provides a linear-weighted, clinimetrically sound, patient-reported outcome measure on the functional disabilities relating to facial weakness in FSHD patients.