Does inspiratory muscle training improve lung function and quality of life in people with inclusion body myositis? A pilot study.

Inclusion body myositis is the most common acquired myositis in adults, predominantly weakening forearm flexor and knee extensor muscles. Subclinical respiratory muscle weakness has recently been recognised in people with inclusion body myositis, increasing their risk of respiratory complications. Inspiratory muscle training, a technique which demonstrates efficacy and safety in improving respiratory function in people with neuromuscular disorders, has never been explored in those with inclusion body myositis. In this pilot study, six adults with inclusion body myositis (age range 53 to 81 years) completed eight weeks of inspiratory muscle training. Measures of respiratory function, quality of life, sleep quality and a two-minute walk test were performed pre and post-intervention. All participants improved their respiratory function, with maximal inspiratory pressure, sniff nasal inspiratory pressure and forced vital capacity increasing by an average of 50 % (p = .002), 43 % (p = .018) and 13 % (p = .003) respectively. No significant change was observed in quality of life, sleep quality or two-minute walk test performance. No complications occurred due to inspiratory muscle training This pilot study provides the first evidence that inspiratory muscle training may be safe and effective in people with Inclusion Body Myositis, potentially mitigating the complications of poor respiratory function.

Inclusion body myositis-health-related quality of life and care situation during phases of the "patience journey" in Germany: results from a qualitative study.

BACKGROUND: To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease. METHODS: An exploratory qualitative study was performed via in-depth semi-structured interviews. Seven patients (males n = 5) with 2011 European Neuromuscular Centre (ENMC) IBM criteria from the German IBM patient registry were interviewed for this study. The dynamic network approach of resilience and the throughput-model of health services research were used to structure the qualitative analysis. RESULTS: Our results suggest that IBM patients experience the holistic HRQoL and care situation typically in four phases: (1) uncertainty about physical vulnerability until diagnosis, (2) promising treatment approaches, (3) self-management and dyadic coping, (4) weak body, busy mind and caregiver burden. The homophonous in-vivo code "patience journey" describes the frequently reported emotional perspective of the patient journey. Although the overarching theme of perceived social support varied throughout these phases, a reliable patient-partner-dyad may lead to improved HRQoL in the long-term. CONCLUSIONS: New hypotheses for future quantitative research were generated to better understand the IBM patients' burden in the long term. The identified relevance of social support emphasizes the patients' need to handle IBM as manageable in medical settings. During exhausting phases of IBM progression, more effective care elements for patients and their partners could disclose varying needs. Strengthening multi-professional healthcare services via individualised informational, practical, or emotional support could improve HRQoL, especially since there is no curative treatment available so far.

Development of a standard of care for patients with valosin-containing protein associated multisystem proteinopathy.

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group's conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally.

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5.

Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.

Role of noninvasive ventilation in perioperative patients with neuromuscular disease: a clinical case / Papel da ventilação não invasiva no período perioperatório de doentes com patologia neuromuscular: caso clínico

The inclusion body myositis is an inflammatory myopathy that leads to chronic muscle inflammation associated with muscle weakness. It is characterized by a restrictive ventilatory syndrome requiring ventilatory support under non-invasive ventilation. The authors describe a clinical case and the anaesthetic management of a patient with inclusion body myopathy candidate for vertebroplasty, which highlights the importance of locoregional anaesthesia and of noninvasive ventilation and includes assisted cough techniques, maintained throughout the perioperative period.

A miosite por corpos de inclusão é uma miopatia inflamatória que cursa com inflamação crônica muscular associada à fraqueza muscular. Caracteriza-se por uma síndrome ventilatória restritiva com necessidade de suporte ventilatório sob ventilação não invasiva. Os autores descrevem caso clínico e respectivo manuseio anestésico de paciente com miopatia por corpos de inclusão proposta para vertebroplastia que realça a importância da anestesia locorregional e da ventilação não invasiva e inclui as técnicas de tosse assistida, mantidas durante todo o período perioperatório.

Role of noninvasive ventilation in perioperative patients with neuromuscular disease: a clinical case.

The inclusion body myositis is an inflammatory myopathy that leads to chronic muscle inflammation associated with muscle weakness. It is characterized by a restrictive ventilatory syndrome requiring ventilatory support under non-invasive ventilation. The authors describe a clinical case and the anaesthetic management of a patient with inclusion body myopathy candidate for vertebroplasty, which highlights the importance of locoregional anaesthesia and of noninvasive ventilation and includes assisted cough techniques, maintained throughout the perioperative period.

Therapeutic effect of hyperbaric oxygen on inclusion body myositis.

An inflammatory myopathy, inclusion body myositis (IBM) presents with progressive muscle weakness against a background of elevated creatine kinase and diffuse endomysial damage. Typically occurring in patients greater than 50 years of age, it is commonly misdiagnosed as polymyositis or other rheumatological disease and is often ineffectively treated with steroids [1]. The approach to IBM is frequently a clinical challenge due to its unique and often aberrant response to common treatment modalities. Here we report an apparent improvement in the clinical course of and associated laboratory findings in a patient with co-existing IBM following the use of hyperbaric oxygen therapy as an adjunct for managing ischemic colitis.

QTc prolongation and family history of sudden death in a patient with desmin cardiomyopathy.

This case report describes a pregnant female patient who presented with new-onset congestive heart failure symptoms and prolonged QTc, with strong family history of sudden death. Endomyocardial biopsy and genetic testing revealed myocardial desmin accumulation and a previously described mutation in the DES (desmin) gene, as well as variants in two LQT genes, SCN5A and KCNH2. The case highlights the phenotypic variability for a particular desmin genotype, and the possible interaction of desminopathy with LQT variants not independently associated with large differences in current properties or QT prolongation from wild type.

Rehabilitación de un paciente con miositis por cuerpos de inclusión / Rehabilitation of patient with inclusion bodies

La miositis por cuerpos de inclusión (MCI) es una de las miopatías inflamatorias idiopáticas menos frecuente y más desconocida. Se presenta el caso de un varón de 36 años con tetraparesia secundaria a MCI trasladado a nuestro hospital para tratamiento rehabilitador consistente en: tratamiento postural, cinesiterapia, electroestimulación, ortesis, terapia ocupacional y ayudas técnicas. El enfermo era dependiente para las actividades de la vida diaria (AVD), presentaba amiotrofia, no realizaba sedestación y se le diagnosticó además de polineuropatía del enfermo crítico en miembros inferiores. Al alta, era independiente para AVD básicas e instrumentales y realizaba marcha con una ortesis antiequina y una ayuda externa contralateral. Nuestra experiencia no coincide con la creencia generalizada de que no se puede realizar cinesiterapia activa en estos pacientes, mientras existan alteraciones de los parámetros de inflamación o de las enzimas musculares

Inclusion body myositis (IBM) is one of the less frequent and most unknown idiopathic inflammatory myopathies. The case of a 36 year old male is presented. He had tetraparesis secondary to IBM and was transferred to our hospital for rehabilitation treatment consisting in: postural treatment, kinesitherapy, electrostimulation, orthesis, occupational therapy and technical help. The patient was dependent for daily life activities (DLA), had amyotrophy, did not sit up and was also diagnosed of polyneuropathy of critical patient in lower limbs. On discharge, he was independent for basic and instrumental DLA and could walk with an anti-equine orthesis and external contralateral help. Our experience does not coincide with the generalized belief that active kinesitherapy cannot be done in these patients while there are alterations of the inflammation or muscular enzyme parameters

Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease.

We report a patient with late-onset celiac disease and neurological manifestations including myopathy, polyneuropathy, and ataxia. Laboratory investigations showed anti-gliadin antibodies and severe vitamin E deficiency. Muscle biopsy revealed inflammatory infiltrates and rimmed vacuoles, similar to those found in inclusion-body myositis. A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer present. This case illustrates the spectrum of neurological complications of celiac disease and documents the occurrence of reversible pathology resembling inclusion-body myopathy in the muscle.

Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects on cytochrome oxidase activity in skeletal muscle and brain.

In order to furnish a combined model of relevance to human inclusion-body myopathy and Alzheimer's disease, transgenic mice expressing human betaAPP-C99 in skeletal muscle and brain under the control of the cytomegalovirus/beta-actin promoter were produced (Tg13592). These transgenic mice develop Abeta deposits in muscles but not in brain. Cell metabolic activity was analyzed in brain regions and muscle by cytochrome oxidase (CO) histochemistry, the terminal enzyme of the electron transport chain. By comparison to age-matched controls of the C57BL/6 strain, CO activity was selectively increased in dark skeletal muscle fibers of Tg13592 mice. In addition, only increases in CO activity were obtained in those brain regions where a significant difference appeared. The CO activity of Tg13592 mice was elevated in several thalamic nuclei, including laterodorsal, ventromedial, and midline as well as submedial, intralaminar, and reticular. In contrast, the groups did not differ in most cortical regions, except for prefrontal, secondary motor, and auditory cortices, and in most brainstem regions, except for cerebellar (fastigial and interpositus) nuclei and related areas (red and lateral vestibular nuclei). No variation in cell density and surface area appeared in conjunction with these enzymatic alterations. The overproduction of betaAPP-C99 fragments in brain without (amyloidosis did not appear to affect the metabolic activity of structures particularly vulnerable in Alzheimer's disease.

High-dose vitamin C therapy for inclusion body myositis.

OBJECTIVES: The efficiency of high-dose vitamin C therapy for inclusion body myositis (IBM) was assessed. SUBJECTS & METHODS: The subjects were five patients with IBM confirmed pathologically. After the intravenous administration of 40 mg/kg vitamin C five times/week for four weeks, muscle weakness was found to improve in three cases. The average muscle score improved from 8.1 to 8.8, from 7.0 to 8.1 and from 6.2 to 6.8. Magnetic resonance imaging (MRI) demonstrated a reduction in the size of T2 high lesions and gadolinium enhancement in the thigh muscles in one case. Based on our findings, high-dose vitamin C therapy is considered to be effective in some cases of IBM.

Beta-amyloid peptide expression is sufficient for myotube death: implications for human inclusion body myopathy.

Inclusion body myositis (sIBM) is the most common disorder of skeletal muscle in aged humans. It shares biochemical features with Alzheimer's disease, including congophilic deposits, which are immunoreactive for beta-amyloid peptide (Abeta) and C'-terminal betaAPP epitopes. However, the etiology of myofiber loss and the role of intracellular Abeta in IBM is unknown. Here we report correlative evidence for apoptotic cell death in myofibers of IBM patients that exhibit pronounced Abeta deposition. HSV-1-mediated gene transfer of Abeta(42) into cultured C2C12 myotubes resulted in a 12.6-fold increase in dUTP-labeled and condensed nuclei over nonexpressing myotubes (P < 0.05). The C'-terminal betaAPP domain C99 also induced myotube apoptosis, but to a significantly lesser extent than Abeta. Apoptosis specific to Abeta-expressing myotubes was also demonstrated through DNA fragmentation, decreased mitochondrial function and the loss of membrane phospholipid polarity. Myotubes laden with Abeta(42), but not other transgene products, developed cytoplasmic inclusions consisting of fibrillar material. Furthermore, injection of normal mouse gastrocnemius muscle with HSV-encoding Abeta cDNA resulted in TUNEL-positive myofibers with pyknotic nuclei. We conclude that Abeta is sufficient to induce apoptosis in myofibers both in vivo and in vitro and suggest it may contribute to myofiber loss and muscle dysfunction in patients with IBM.

Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body myositis assessed by 31P-magnetic resonance spectroscopy.

Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patients with definite s-IBM. Eleven patients showed multiple mitochondrial DNA deletions in skeletal muscle and 67% showed ragged red fibres and/or cytochrome c oxidase-negative fibres. T1-weighted MR images showed increased signal intensity in the calf muscle of all patients except one. The involvement of calf muscle was confirmed by 31P magnetic resonance spectroscopy of resting muscle, which disclosed abnormalities in metabolite ratios in all patients. However, muscle oxidative metabolism assessed during recovery from exercise was normal in patients with s-IBM, as maximum rates of mitochondrial ATP production and post-exercise ADP recovery rates were within the normal range in all cases. We conclude that muscle mitochondrial abnormalities are a secondary process and unlikely to play a significant role in the pathogenesis of s-IBM.