'It becomes the new everyday life' - experiences of chronic pain in everyday life of people with limb-girdle muscular dystrophy.

PURPOSE: To investigate experiences and reflections on challenges in everyday life of people living with limb-girdle muscular dystrophy (LGMD) and chronic pain in order to improve rehabilitation services. MATERIALS AND METHODS: The design for this study was qualitative using the Interpretive Description methodology and the salutogenic theory of Sense of Coherence as the theoretical framework. Four semi-structured focus group interviews were conducted with 19 adults with LGMD from April to May 2021. The interviews were conducted online due to COVID-19. RESULTS: Living with chronic pain and LGMD affected everyday life in terms of the participants' overall Sense of Coherence. Beneficial or unfavorable coping strategies were identified within four interrelated categorical themes: pain management, normality comprehension, affected emotional sentiment and altered identity. CONCLUSION: Healthcare professionals should acknowledge possible chronic pain secondary to LGMD. Chronic pain appears to be a prevalent problem in people with LGMD with negative impact on everyday life, yet patients with LGMD did not receive sufficient information and necessary tools from health professionals to cope with chronic pain. Thus, adequate pain management appeared to be a difficult and self-taught process. Educating health professionals on how to support patients with LGMD and chronic pain is needed.IMPLICATIONS FOR REHABILITATIONHealth professionals should acknowledge and address the possibility of chronic pain secondary to limb-girdle muscular dystrophy (LGMD) and educate patients in pain management.Physiotherapy, energy management and engagement in meaningful activities may help patients gain some control of pain and limit the consequences of pain on everyday life.Supporting patients to accept pain and to shift focus towards their current capabilities may potentially improve pain management.Educating health professionals on how to support patients with LGMD and chronic pain is needed.

Assessing Dysferlinopathy Patients Over Three Years With a New Motor Scale.

OBJECTIVE: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. METHODS: We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. RESULTS: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline. INTERPRETATION: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967-978.

Psychological parameters impact health-related quality of life in mental and physical domains in adults with muscular dystrophy.

The impacts of potentially treatable psychological parameters on quality of life are relatively unreported in adults with Facioscapulohumeral, Becker and Limb-girdle muscular dystrophy. The purpose of this study was to compare quality of life, psychological parameters, and physical function between adults with muscular dystrophy and controls, and to examine relationships among these parameters in muscular dystrophy. Twenty-one adults with muscular dystrophy (n = 7 Becker, n = 8 Facioscapulohumeral, n = 6 Limb-girdle) and ten age-matched controls participated. Outcome measures were health-related quality of life, depressive symptoms, trait anxiety, self-esteem, physical self-worth and six-minute walk distance. Quality of life scores were lower in the muscular dystrophy groups than the control (p < .05). Depressive symptoms had the greatest association with quality of life in the Mental Health domain (r= -0.89, p < .001). Depressive symptoms also had the most associations with quality of life (7 of 10 domains), followed by trait anxiety (6 of 10 domains), physical self-worth (5 of 10 domains), self-esteem (4 of 10 domains) and six-minute walk distance (3 of 10 domains). Psychological parameters and, to a lesser extent, physical function impact quality of life in muscular dystrophy. This study provides a rationale to include psychological assessment and treatment within muscular dystrophy healthcare.

The correlation of clinical evaluation with life quality and mental status in a Chinese cohort with dysferlinopathy.

INTRODUCTION: Impaired mood and quality of life was common in muscular dystrophies and play an important role in long-term management. Previous studies in dysferlinopathies mainly focused on the genotype-phenotypes correlations. Currently there are very few reports regarding the mental status, life quality and the correlated factors. METHODS: A total of 22 patients with dysferlinopathy was recruited and evaluated by 6-minute walking test (6MWT) and adapted-North Star Ambulatory Assessment (a-NSAA). Chinese version of SF-36, PHQ-9, and GAD-7 scale were used to evaluate the Quality of Life (QoL), depression and anxiety. Statistical analysis was applied to investigate the correlation between clinical variables and life quality or mental status. RESULTS: SF-36 evaluation revealed multiple dimensional impairment in dysferlinopathy patients. Declined score in body pain (78.00 vs. 91.23, p = 0.0129) and mental health (56.00 vs.72.88, p = 0.0493) were of note in female patients. Some patients suffered from depression (23%) and anxiety (23%) with a high score in PHQ-9/GAD-7. The 6MWT was well-correlated with the severity of depression and most scores in QoL except Body Pain and Role emotion. CONCLUSION: The cross-sectional study revealed impaired mental status and life quality in dysferlinopathy, particularly in female patients. The life quality impairment is correlated with the clinical severity.

Limb-girdle muscular dystrophy: A perspective from adult patients on what matters most.

INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) consists of over 30 genetic conditions with varying clinical phenotypes primarily affecting pelvic girdle, shoulder girdle, and other proximal limb muscles. Studies focusing on the physical, mental, and social effects of this disease from the patient's perspective are limited. METHODS: Adults with LGMD were interviewed and asked to identify issues that have the greatest impact on their quality of life. Each interview was recorded, transcribed, coded, and analyzed. RESULTS: Participants provided 1385 direct quotes. One hundred sixty-five potential symptoms of importance were identified and grouped into 15 larger themes. The most frequently reported themes included limitations with mobility, difficulty performing activities, social role limitations, and emotional distress. DISCUSSION: There are multiple symptoms that alter the lives of adults with LGMD. These affect their physical, emotional, and social health, and may be amenable to medical intervention.

Perceptions of the transition from receiving the diagnosis recessive limb-girdle muscular dystrophy to becoming in need of human support and using a wheelchair: an interview study.

Purpose: To describe perceptions of the transition from receiving the diagnosis recessive limb-girdle muscular dystrophy to becoming in need of human support to manage daily life and using a wheelchair for ambulation, from the affected young adults' and their parents' perspectives. Method: A qualitative and descriptive study design was used. Semi-structured interviews were held with 14 young adults diagnosed with recessive limb-girdle muscular dystrophy and 19 parents. Phenomenography was used for data analysis. Results: The diagnosis was described as being a shock and difficult to comprehend but also as a relief and a tool for information. Beginning to use a wheelchair was perceived to be mentally difficult but it also provided freedom. New ways of living involved physical, emotional, practical, and social difficulties as well as experiences of learning to adapt to the disease. The transition was overshadowed by concern about disease progression and influenced by facilitating factors, which were young adult being seen as a person; supportive family and friends; mobilized internal resources; meaningful daily activities; adapted environment; and professional support. Conclusions: The different perceptions expressed in this study highlight the importance of identifying personal perceptions and needs in order to optimize support provided by healthcare professionals. Implications for Rehabilitation The different perceptions described in this study emphasize the need for person-centered care for young adults living with recessive limb-girdle muscular dystrophy and their parents. Regular controls and professional support to cope with the disease and its consequences should be offered, not only at the time of diagnosis but also throughout disease progression. Beginning to use a wheelchair can be a psychologically distressing process, which has to be acknowledged by healthcare professionals when introducing it. Healthcare professionals should not only recognize the importance of having social relations and activities that are meaningful but also be a link to authorities in society and to interest organizations that can help to facilitate the person's management of the disease.

Quality of life in adult patients with limb-girdle muscular dystrophies.

Although limb-girdle muscular dystrophies (LGMD) can cause permanent disability, to date there are no studies that examined quality of life (QoL) in these patients. Our aim was to evaluate QoL in patients with LGMD, and to identify the most significant predictors of QoL. The study comprised 46 patients with diagnosis of limb-girdle muscular weakness. QoL in patients was evaluated using two scales-SF-36 questionnaire and the Individualized Neuromuscular Quality of Life questionnaire (INQoL). Following scales were also applied: Epworth Sleepiness Scale (ESS), Hamilton Scale for Depression (HamD), and Krupp's Fatigue Severity Scale (FSS). Mean SF-36 score was 52.4 ± 23.5, and physical composite score was worse than mental. Total INQoL score was 46.1 ± 20.4, with worst results obtained for weakness, fatigue and independence, while social relationships and emotions showed better results. Significant predictors of worse SF-36 score in LGMD patients were higher fatigue level (ß = - 0.470, p < 0.01) and use of assistive device (ß = - 0.245, p < 0.05). Significant predictors of worse INQoL score were higher fatigue level (ß = 0.514, p < 0.01) and presence of cardiomyopathy (ß = - 0.385, p < 0.01). It is of special interest that some of the identified factors that correlated with worse QoL in LGMD patients were amenable to treatment.

Experiences of being parents of young adults living with recessive limb-girdle muscular dystrophy from a salutogenic perspective.

Recessive limb-girdle muscular dystrophies (LGMD2) involve progressive muscle weakness. Parental support is important for young adults living with LGMD2, but no study has been identified focusing on the parents' experiences. The salutogenic perspective concentrates on how daily life is comprehended, managed and found meaningful, i.e. the person's sense of coherence. The aim of this study was to describe, from a salutogenic perspective, experiences of being parents of young adults living with LGMD2. Nineteen participants were included. Data were collected by semi-structured interviews and the self-administrated 13-item sense of coherence questionnaire. Interview data were analysed with content analysis and related to self-rated sense of coherence. The result shows experiences of being influenced, not only by thoughts and emotions connected to the disease but also by caregiving duties and the young adults' well-being. Simultaneously, difficulty in fully grasping the disease was expressed and uncertainty about progression created worries about future management. Trying their best to support their young adults to experience well-being and to live fulfilled lives, the importance of having a social network, support from concerned professionals and eventually access to personal assistance was emphasized. The need to have meaningful pursuits of one's own was also described. The median sense of coherence score was 68 (range 53-86). Those who scored high (≥68) described satisfaction with social network, external support provided, work and leisure activities to a greater extent than those who scored low (<68). The result shows that the young adults' disease has a major impact on the parents' lives. Assessment of how the parents comprehend, manage and find meaning in everyday life may highlight support needed to promote their health.

Health perceptions of young adults living with recessive limb-girdle muscular dystrophy.

AIM: The aim of this study was to describe health perceptions related to sense of coherence among young adults living with recessive limb-girdle muscular dystrophy. BACKGROUND: Limb-girdle muscular dystrophy refers to a group of progressive muscular disorders that may manifest in physical disability. The focus in health care is to optimize health, which requires knowledge about the content of health as described by the individual. DESIGN: A descriptive study design with qualitative and quantitative data were used. METHOD: Interviews were conducted between June 2012-November 2013 with 14 participants aged 20-30 years. The participants also answered the 13-item sense of coherence questionnaire. Qualitative data were analysed with content analysis and related to self-rated sense of coherence. FINDINGS: Health was viewed as intertwined physical and mental well-being. As the disease progressed, well-being was perceived to be influenced not only by physical impairment and mental strain caused by the disease but also by external factors, such as accessibility to support and attitudes in society. Factors perceived to promote health were having a balanced lifestyle, social relations and meaningful daily activities. Self-rated sense of coherence varied. The median score was 56 (range 37-77). Those who scored ≥56 described to a greater extent satisfaction regarding support received, daily pursuits and social life compared with those who scored <56. CONCLUSION: Care should be person-centred. Caregivers, with their knowledge, should strive to assess how the person comprehends, manages and finds meaning in daily life. Through dialogue, not only physical, psychological and social needs but also health-promoting solutions can be highlighted.

Young adults' experiences of living with recessive limb-girdle muscular dystrophy from a salutogenic orientation: an interview study.

PURPOSE: To describe young adults' experiences of living with recessive limb-girdle muscular dystrophy (LGMD2) from a salutogenic orientation. METHODS: A qualitative explorative interview study, including 14 participants aged 20-30 years, was performed focusing on comprehensibility, manageability and meaningfulness in daily life. Content analysis was used for data analysis. RESULT: Living with LGMD2 not only implies learning to live with the disease and the variations between good and bad periods but also means trying to make sense of a progressive disease that brings uncertainty about future health, by striving to make the best of the situation. Disease progression involves practical and mental struggle, trying to maintain control over one's life despite vanished physical functions that require continual adjustments to the body. Restrictions in a double sense were described, not only due to the disease but also due to poor comprehension of the disease in society. Lack of knowledge about LGMD2 among professionals often results in having to fight for the support needed. CONCLUSION: In order to manage daily life, it is important to be seen and understood as an individual in contacts with professionals and in society in general, to have informal social support and meaningful activities as well as access to personal assistance if necessary. IMPLICATIONS FOR REHABILITATION: Recessive limb-girdle muscular dystrophy (LGMD2) is a group of progressive disorders, which manifest in physical and psychological consequences for the individual. According to the salutogenic orientation, people need to find life comprehensible, manageable and meaningful, i.e. to achieve a sense of coherence (SOC), but living with LGMD2 may recurrently challenge the individual's SOC. Through the holistic view of the individual's situation that the salutogenic orientation provides, professionals may support the individual to strengthen SOC and thereby facilitate the movement towards health.

Neuronal-specific overexpression of a mutant valosin-containing protein associated with IBMPFD promotes aberrant ubiquitin and TDP-43 accumulation and cognitive dysfunction in transgenic mice.

Mutations in valosin-containing protein (VCP) cause a rare, autosomal dominant disease called inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD). One-third of patients with IBMPFD develop frontotemporal dementia, characterized by an extensive neurodegeneration in the frontal and temporal lobes. Neuropathologic hallmarks include nuclear and cytosolic inclusions positive to ubiquitin and transactive response DNA-binding protein 43 (TDP-43) in neurons and glial activation in affected regions. However, the pathogenic mechanisms by which mutant VCP triggers neurodegeneration remain unknown. Herein, we generated a mouse model selectively overexpressing a human mutant VCP in neurons to study pathogenic mechanisms of mutant VCP-mediated neurodegeneration and cognitive impairment. The overexpression of VCPA232E mutation in forebrain regions produced significant progressive impairments of cognitive function, including deficits in spatial memory, object recognition, and fear conditioning. Although overexpressed or endogenous VCP did not seem to focally aggregate inside neurons, TDP-43 and ubiquitin accumulated with age in transgenic mouse brains. TDP-43 was also found to co-localize with stress granules in the cytosolic compartment. Together with the appearance of high-molecular-weight TDP-43 in cytosolic fractions, these findings demonstrate the mislocalization and accumulation of abnormal TDP-43 in the cytosol of transgenic mice, which likely lead to an increase in cellular stress and cognitive impairment. Taken together, these results highlight an important pathologic link between VCP and cognition.

Cognitive profile and MRI findings in limb-girdle muscular dystrophy 2I.

Limb-girdle muscular dystrophy 2I (LGMD2I) is a neuromuscular disorder with a heterogeneous phenotype. It is caused by mutations in the Fukutin Related Protein (FKRP) gene, which is ubiquitously expressed in human tissues. FKRP functions in CNS are largely unknown. To investigate possible cognitive impairment in LGMD2I and to describe brain MRI features. Ten LGMD2I patients (four males and six females, mean age 44 years, age range 19-69 years) were assessed with an extensive neuropsychological battery, psychopathological tests and neuromuscular specific quality-of-life questionnaire. Adults were compared with ten matched healthy controls. All patients underwent complete neurological examination, and nine underwent brain MRI scanning. Patients showed a fairly specific cognitive profile with mild impairment in executive functions and visuo-spatial planning without substantial impairment in global and logic IQ. MRI findings were heterogeneous: four patients showed non-specific white matter abnormalities; two patients showed moderate ventriculomegaly; three patients showed mild enlargement of subarachnoid spaces, without a specific pattern. Cerebellar atrophy was marked in one patient. Abnormal glycosylation of α-dystroglycan in LGMD2I may interfere with brain development and cognitive performances involving the frontal and posterior parietal regions, but does not result in specific brain MRI abnormalities.

Limb girdle muscular dystrophy: an interval study of weakness and functional impairment.

OBJECTIVE: Prospective studies of the natural history of a myopathy are effective means of measuring the status and progression of disease. This 10-year interval study of progressive weakness and functional decline was aimed to document the natural course of clinically well-characterized limb girdle muscular dystrophy in South Africa. METHODS: The manual muscle test (MMT) was used to evaluate limb strength; global strength was measured by the average muscle score (AMS). A nonlinear functional grading system was used to measure impairment of the arms and legs. An activities of daily living (ADL) scale was used to assess disability across multiple functional domains in a home environment. RESULTS: The mean AMS deteriorated from 5.9 to 4.9 (on a 10-point scale) and was unrelated to patient age and disease duration. Most (78%) patients lost arm function. All patients maintained useful hand function. Two thirds of patients lost leg function. Half of the patients were wheelchair bound, and they reached this level of function around the end of their fourth decade of life. Every patient showed functional deterioration on the ADL scale. The mean score worsened from 65.6 to 77.2 (out of 156 points). The disability change was most pronounced in patients who became wheelchair bound. CONCLUSION: This interval analysis showed a significant decline of limb strength that was independent of patient age or duration of disease and was more rapid in stronger patients. A functional grading system detected decline and was a useful measure of deterioration when applied to patients over intervals. An ADL assessment ascertained a significant functional decline across multiple functional domains in a home environment and allowed us to advise patients on compensatory strategies to limit dependence.

Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant.

BACKGROUND: Mutations in protein-O-mannose-beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) have been found in muscle-eye-brain disease, a congenital muscular dystrophy with structural eye and brain defects and severe mental retardation. OBJECTIVE: To investigate whether mutations in POMGnT1 could be responsible for milder allelic variants of muscular dystrophy. DESIGN: Screening for mutations in POMGnT1. SETTING: Tertiary neuromuscular unit. PATIENT: A patient with limb-girdle muscular dystrophy phenotype, with onset at 12 years of age, severe myopia, normal intellect, and decreased alpha-dystroglycan immunolabeling in skeletal muscle. RESULTS: A homozygous POMGnT1 missense mutation (c.1666G>A, p.Asp556Asn) was identified. Enzyme studies of the patient's fibroblasts showed an altered kinetic profile, less marked than in patients with muscle-eye-brain disease and in keeping with the relatively mild phenotype in our patient. CONCLUSIONS: Our findings widen the spectrum of disorders known to result from mutations in POMGnT1 to include limb-girdle muscular dystrophy with no mental retardation. We propose that this condition be known as LGMD2M. The enzyme assay used to diagnose muscle-eye-brain disease may not detect subtle abnormalities of POMGnT1 function, and additional kinetic studies must be carried out in such cases.