COVID-19 and myositis - unique challenges for patients.

OBJECTIVE: The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM). METHODS: An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population. RESULTS: Of the 608 participants (81.1% female, median (s.d.) age 57 (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic. CONCLUSION: This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.

Physical function and muscle strength in sporadic inclusion body myositis.

INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). RESULTS: TUG performance was the strongest predictor of self-reported physical function (r2 = 0.56, P < 0.05). Knee extension strength and between-limb strength asymmetry were the strongest multi-regression indicators of TUG performance (r2 = 0.51, P < 0.05). Strength asymmetry showed the strongest single-factor (negative) association with 2MWT performance (r2 = 0.49, P < 0.05). DISCUSSION: TUG assessment appears to sensitively predict self-perceived physical function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve 56: E50-E58, 2017.

Psychological Impact of Predictive Genetic Testing in VCP Inclusion Body Myopathy, Paget Disease of Bone and Frontotemporal Dementia.

Inclusion Body Myopathy associated with Paget's disease of bone and Fronto-temporal Dementia, also known as multisystem proteinopathy is an autosomal dominant, late onset neurodegenerative disorder caused by mutations in Valosin containing protein (VCP) gene. This study aimed to assess uptake and decision making for predictive genetic testing and the impact on psychological well-being. Individuals who had participated in the gene discovery study with a 50 % a priori risk of inheriting VCP disease were sent a letter of invitation offering genetic counseling and testing and were also invited to participate in this psychosocial study. A total of 102 individuals received an invitation and 33 individuals participated in genetic counseling and testing (32.3 %) with 29 completing baseline questionnaires. Twenty completed the follow-up post-test Hospital Anxiety and Depression Scale questionnaire including 13 of the 18 who had tested positive. Mean risk perception at baseline was 50.1 %. Reasons for testing included planning for the future, relieving uncertainty, informing children and satisfying curiosity. At baseline, one quarter of the participants had high levels of anxiety. However, scores were normal one year following testing. In this small cohort, one third of individuals at 50 % risk chose pre-symptomatic testing. Although one quarter of those choosing testing had high anxiety at baseline, this was not evident at follow-up.

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.

What determines quality of life in inclusion body myositis?

BACKGROUND: Quality of life (QoL) assessment allows healthcare professionals to appreciate the patient perspective of their disease. This can help us make a better choice from among the various ways we currently measure the severity of a muscle disease such as inclusion body myositis (IBM). However, we cannot assume that QoL in IBM is just related to disease severity as psychosocial factors may play an important role in determining QoL. METHODS: Sixty subjects with IBM had assessments of disease severity and concurrent assessment of mood and QoL using the Short-Form 36 (SF-36). RESULTS: There were significant reductions in Physical functioning, Role physical, General health and Social functioning domains of the SF-36. Functional disability was more indicative of the broader effects of IBM on SF-36 than was the muscle strength sum score. Mood was relatively independent of disease severity and had a different profile of effects on SF-36 domains. Up to 14% of the effect of functional disability on some aspects of QoL was mediated through mood. CONCLUSIONS: The functional disability caused by IBM reduces QoL, but psychosocial factors such as mood affect QoL directly and by influencing the degree to which disease severity reduces QoL. Further study should follow the effects of IBM on QoL over time and look at the influence of other psychosocial factors. Such studies may point to psychosocial interventions that may help improve QoL in IBM even if the disease itself cannot be treated.

Challenges in diagnosis and treatment of sporadic inclusion-body myositis.

Sporadic inclusion body myositis (sIBM) is a rare yet increasingly prevalent disease and the most common cause of inflammatory myopathy in people over the age of 50. The exact cause of the disorder is unknown. In sIBM 2 processes, first autoimmune and the other degenerative, parallelly occur in the muscle cells. The inflammation aspect is characterized by the cloning of T cells that appear to be driven by specific antigens to invade muscle fibers. The degeneration aspect is characterized by the appearance of holes in the muscle cell vacuoles, deposits of abnormal proteins within the cells and in filamentous inclusions. The disease has a major impact on patients' motor functionality and their quality of life. The treatment of sIBM still remains a major challenge. Early diagnosis of sIBM (already at the histopathology stage), when one still cannot observe fully developed clinical symptoms, may stop help to the progression of the disease.

Inclusion Body Myositis: What Most Impacts Patients' Lives.

OBJECTIVE: Inclusion body myositis (IBM) is the most common form of idiopathic inflammatory myopathy in adults older than 50 years. Few studies have focused on the functional, physical, and social limitations of this disease. This study identifies pertinent symptoms that impact the health and daily function of patients with IBM. METHODS: We used semistructured interviews with 10 biopsy-confirmed adults with IBM to identify the psychological, physical, and functional limitations that have the greatest impact on the lives of patients with IBM. RESULTS: Participants with IBM provided 644 direct quotes identifying issues that have the greatest effect on their lives. Two hundred nine individual symptoms and 17 symptomatic themes were identified by patients as having a significant impact on their lives. The symptomatic themes mentioned most frequently involved mobility and ambulation, emotional distress, and activity impairment. CONCLUSIONS: Identifying critical issues to patients with IBM is potentially useful for clinicians whose aim is to provide optimal care to patients with IBM.