Imaging swallowing function and the mechanisms driving dysphagia in inclusion body myositis.

Sporadic inclusion body myositis (IBM) is a progressive condition which commonly affects patients aged above 40. IBM does not respond to immunosuppression and no proven treatments are available. Up to 80% of patients develop some degree of swallowing impairment during the disease course. Dysphagia is a source of marked morbidity in IBM and predisposes patients to life-threatening complications such as aspiration pneumonia. The pathophysiology behind dysphagia in IBM is not fully understood. Evidence from imaging demonstrates that impaired swallowing is predominantly underpinned by oropharyngeal deficits. Changes in cricopharyngeal physiology is thought to be an important factor influencing dysphagia in IBM. However, it is unclear whether this is secondary to structural changes within the cricopharyngeus itself or driven by impairment of the muscles promoting pharyngeal clearance. The approach to dysphagia in IBM patients is limited by a lack of validated instruments to reliably assess swallowing function and an absence of effective therapeutic interventions derived from controlled trials targeting dysphagia. Imaging modalities such as the video fluoroscopic swallowing study (VFSS) are commonly used to evaluate dysphagia in IBM. Whilst VFSS is a commonly used technique in clinical practice; cumulative radiation exposure with repeated testing can be a limitation. Alternative imaging techniques could be developed further as outcome measures for assessing swallowing.In this review, we provide an overview of imaging techniques used to assess swallowing and the insight provided from such investigations into the mechanisms behind dysphagia in IBM. We suggest future directions for evaluation and outcome measurement of dysphagia in this population.

Bilateral Facial Palsy: A Rare Presenting Symptom for Inclusion Body Myositis.

Inclusion body myositis is a common type of inflammatory myopathy among populations over the age of 50 years, classically presenting with weakness and atrophy of the forearms and quadriceps. While a third of patients may eventually present with mild facial weakness, findings of ptosis, facial palsy, or involvement of extraocular muscles are rarely, if ever, seen. The authors describe a unique case of inclusion body myositis in which a patient initially presented with bilateral severe facial palsy and exposure keratitis but minimal limb weakness. While midface weakness, unilateral lagophthalmos, and ptosis have been documented in one reported case, key presenting symptoms of bilateral facial palsy and symmetric paralytic lagophthalmos with corneal exposure have not been presented before. Therefore, this case serves as an important reminder to consider the inclusion body myositis in the differential diagnosis of bilateral facial palsy.

Diagnosing and managing dysphagia in inclusion body myositis: a systematic review.

OBJECTIVES: Dysphagia is a common debilitating clinical feature of IBM. However, the impact of dysphagia in IBM has been historically overlooked. This study aimed to identify, evaluate and summarize the evidence regarding the assessment and management of dysphagia in persons with IBM undergoing treatment. METHODS: A systematic review was conducted using a multiengine search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies had to employ an intervention for persons with IBM, report a swallowing outcome and be published in English. Quality assessments of the eligible studies were performed. RESULTS: Of 239 studies found, 19 met the inclusion criteria. One study was rated as 'fair' and the rest as 'poor' quality, particularly due to the lack of published and validated swallowing assessment procedures and outcome measures. Cricopharyngeal (CP) dysfunction (12/19) was the most commonly reported swallowing abnormality. Interventions for disease management included pharmacological agents (10/19), followed by surgical (3/19), behavioral (1/19) and combined approaches (5/19). Interventions with immunosuppressants, botulinum toxin injection, balloon dilation and/or CP myotomy led to mixed and transient benefits. Few studies examining statins or behavioral therapies (primarily focused on respiratory function) showed no effects for dysphagia. CONCLUSION: Various interventions have been reported to temporarily improve dysphagia in persons with IBM. However, these findings are based on limited and overall low-quality evidence. This study cautions against the generalization of these findings and emphasizes the need for further systematic research to improve the diagnosis and management of dysphagia in IBM.

Macroglossia in rapidly progressive inclusion body myositis.

Inclusion body myositis (IBM) is a refractory muscle disease characterized by inflammatory and degenerative features in myofibers. Macroglossia is common in systemic amyloid light chain amyloidosis; however, no reports have been published on patients with IBM. We encountered a female patient with clinicopathologically defined IBM who exhibited relatively rapid progression of dysphagia, gait disturbance, and macroglossia. Muscle biopsy demonstrated endomysial mononuclear inflammatory infiltrates, fiber necrosis and regeneration with rimmed vacuoles, and sarcoplasmic inclusions of p62. Tongue biopsy demonstrated fiber degeneration with fatty replacement and fibrosis, nonnecrotic fibers surrounded and invaded by mononuclear cells, and sarcoplasmic dotlike inclusions of p62. Based on the parotid gland, lip, and muscle biopsy, she was diagnosed as having IBM with Sjögren's syndrome. She was treated with steroid pulse and intravenous immunoglobulin therapy followed by oral administration of prednisolone, which resulted in temporary clinical improvement. Macroglossia might be an indicator of immunotherapy effectiveness.

Evidence of nerve hypertrophy in patients with inclusion body myositis on lower limb MRI.

INTRODUCTION/AIMS: Inclusion body myositis (IBM) is a myopathic condition but in some patients has been associated with an axonal length-dependent polyneuropathy. In this study, we quantified the cross-sectional area of the sciatic and tibial nerves in patients with IBM comparing with Charcot-Marie-Tooth disease type 1A (CMT1A) and healthy controls using magnetic resonance neurography (MRN). METHODS: MRN of the sciatic and tibial nerves was performed at 3T using MPRAGE and Dixon acquisitions. Nerve cross-sectional area (CSA) was measured at the mid-thigh and upper third calf regions by an observer blinded to the diagnosis. Correlations were performed between these measurements and clinical data. RESULTS: A total of 20 patients with IBM, 20 CMT1A and 29 healthy controls (age- and sex-matched) were studied. Sciatic nerve CSA was significantly enlarged in patients with IBM and CMT1A compared to controls (sciatic nerve mean CSA 62.3 ± 22.9 mm2 (IBM) vs. 35.5 ± 9.9 mm2 (controls), p < 0.001; and 96.9 ± 35.5 mm2 (CMT1A) vs. 35.5 ± 9.9 mm2 (controls); p < 0.001). Tibial nerve CSA was also enlarged in IBM and CMT1 patients compared to controls. DISCUSSION: MRN reveals significant hypertrophy of the sciatic and tibial nerves in patients with IBM and CMT1A compared to controls. Further studies are needed to correlate with neurophysiological measures and assess whether this finding is useful diagnostically.

Sirolimus leads to rapid and sustained clinical improvement of motor deficits in a patient with inclusion body myositis.

BACKGROUND AND PURPOSE: To provide further evidence for sirolimus, a mammalian target of rapamycin inhibitor, as a treatment strategy for patients with inclusion body myositis (IBM). METHODS: We acquired longitudinal clinical data and immunological assessments of CD8+ T-cell subsets in peripheral blood for evaluation of potential anti-inflammatory treatment effects of sirolimus. RESULTS: Therapy with sirolimus 2 mg/day by mouth led to rapid and sustained clinical improvement of motor symptoms for an observation period of more than 1 year. Treatment was well tolerated, with no occurrence of adverse effects. We did not observe a meaningful alteration of CD8+ T-cell subsets in our patient after 9 and 12 months compared to baseline. CONCLUSIONS: The significant and persistent clinical improvement highlights the use of sirolimus as a potential treatment option in patients with IBM. In light of the lack of immunological treatment effects observed for cytotoxic CD8+ T cells, further studies should investigate the potential myoprotective effects of sirolimus.

Interstitial amyloidosis in sporadic inclusion body myositis.

INTRODUCTION/AIMS: Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis. METHODS: We reviewed the muscle biopsy database (1998-2020) to identify sIBM patients with extracellular amyloid deposits. Clinical and laboratory data were reviewed. RESULTS: We identified five sIBM patients (three clinicopathologically defined and two clinically defined) with extracellular amyloid deposits in muscle. Mean age at diagnosis was 74.8 y (range, 68-84 y). All patients had a typical sIBM pattern of weakness without associated sensory or autonomic symptoms. None had electrophysiological evidence of peripheral neuropathy. Only one patient had a monoclonal gammopathy (immunoglobulin M-lambda, IgM-λ) with normal bone marrow biopsy. This patient with monoclonal gammopathy and three other patients underwent abdominal fat pad aspirate and were negative for amyloid. Cardiac evaluation was unrevealing in the four patients tested. Three patients without monoclonal gammopathy had normal transthyretin gene sequencing and inconclusive mass spectrometry-based analysis. The patient with monoclonal gammopathy died of pneumosepsis 5 y after diagnosis and autopsy revealed multi-organ transthyretin amyloidosis. DISCUSSION: Detection of extracellular amyloid deposition in muscle should trigger an aggressive search for systemic amyloidosis independently from other associated myopathological abnormalities. Amyloid subtyping is crucial for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt a search for non-hematological causes of systemic amyloidosis.

Temporomandibular Disorders and Oral Features in Idiopathic Inflammatory Myopathies (IIMs) Patients: An Observational Study.

Aim: Inflammatory idiopathic myopathies (IIMs) are inflammatory processes affecting skeletal musculature and extramuscular organs. Temporomandibular disorders (TMD) involve jaw muscles and temporomandibular joint. The aim of this observational study was to investigate the prevalence of the main TMD symptoms and signs as well as oral implications in IIM patients. Methods: The study group included 54 patients (42 women and 12 men), 22 of whom affected by dermatomyositis (DM), 29 by polymyositis (PM) and 3 by inclusion body myositis (IBM). A group of 54 patients not affected by this disease, served as CG. Oral and TMD signs and symptoms were evaluated by means of a questionnaire and through clinical examination. Results: About oral symptoms, the study group complained more frequently dysgeusia, with loss of taste or unpleasant taste (p<0.0001) and feeling of burning mouth (9.4% versus 0 controls). Xerostomia was more prevalent in the study group respect to the CG (p<0.0001). Dysphagia was reported by 48.1% of IIM patients while was absent in CG (p<0.0001). About oral signs, cheilitis (p<0.05) and oral ulcers (p<0.05) were significantly more frequent in CG. As regard to TMD symptoms, arthralgia and tinnitus didn't showed significant differences between the two groups, while neck/shoulders and masticatory muscle pain was significantly more referred in IIM patients than in the CG (p<0.05). About TMJ signs, sounds were overlapping in the two groups: click=11.1% in both IIM patients and CG (p>0.05), crepitation in 11.1% of IIM and 9.3% of controls (p>0.05). No significant difference was detected about deflection (9.3%, p>0.05), while deviation was wider in CG (p<0.05). Active opening and lateralities showed no significant differences, while endfeel was significantly increased in IIM group for a higher presence of muscular contracture. Bruxism was present only in CG. Conclusion: The data collected from this observational study seem to support the existence of a relationship between the prevalence of TMD symptoms and signs as well as oral features in patients with myositis. A remarkable reduction of salivary flow and dysphagia were more frequent and severe in IIM patients, as well as muscle contracture and myofacial pain evoked by palpation, this result being highly significant.

Inclusion body myositis in patients with spinocerebellar ataxia types 3 and 6.

OBJECTIVES: To describe the combination of spinocerebellar ataxia (SCA) types 3 and 6 and sporadic inclusion body myositis (IBM). METHODS: A description of five patients with SCA type 3 and 6 who were diagnosed with IBM. We explore possible mechanisms explaining the coexistence of both diseases. RESULTS: The patients with SCA-3 (n=4) and SCA-6 (n=1) developed asymmetric muscle weakness in a pattern suggestive of IBM in the course of their disease. Based on findings of neurological examination and additional investigations (muscle ultrasound, muscle biopsy), the diagnosis of IBM was made in all patients. CONCLUSION: We report on five patients with concomitant SCA and IBM. Our cases may merely illustrate coincidental co-occurrence of IBM and SCA-3/SCA-6. However, the presence of SCA mutations could predispose to the development of IBM in some SCA patients, or, the presence of toxic aggregates and malfunctioning of cellular quality control processes in both diseases could indicate a convergence of disease mechanisms.

Myopathies featuring early or prominent dysphagia.

BACKGROUND: Limited data exist regarding myopathies with early or prominent dysphagia. METHODS: A retrospective study was performed (January 2003 to August 2019) to identify myopathy patients in whom dysphagia was the initial symptom or was disproportionately severe compared with limb weakness. RESULTS: Thirty-two patients were identified. The median age at diagnosis was 65 y (range, 36-80 y). Inclusion body myositis (IBM) (n = 15), immune-mediated necrotizing myopathy (IMNM) (n = 5), and oculopharyngeal muscular dystrophy (n = 4), were the most common diagnoses. In 4 patients (3 IMNM and 1 nonspecific myositis) dysphagia evolved rapidly. At evaluation, 21 patients required diet alterations, 5 required feeding tubes, and 8 had aspiration pneumonia. Follow-up data were available for 20 patients (median, 24 mo). Eight patients received immunosuppressive therapies with improvement in 7, including 3 of 4 with rapidly progressive dysphagia. CONCLUSIONS: IBM and IMNM accounted for approximately two-thirds of patients with early or prominent dysphagia at our institution. Rapidly progressive dysphagia may predict immunotherapy responsiveness.

Inclusion-body myositis and primary Sjögren syndrome: mechanisms for shared etiologies.

Herein we report a case of sporadic inclusion-body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti-cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T-cell large granular lymphocyte leukemia (T-LGLL). Further evaluation of this patient did in fact reveal underlying T-LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8-positive T cells in sIBM, and, although sIBM is traditionally considered treatment-refractory, we report a significant response to the anti-CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated.

A Patient with Sjogren's Syndrome and Subsequent Diagnosis of Inclusion Body Myositis and Light-Chain Amyloidosis.

We discuss a challenging case of a 58-year-old Vietnamese-American woman who presented to her new primary care provider with an 8-year history of slowly progressive dysphagia, hoarseness, muscle weakness with associated frequent falls, and weight loss. She eventually reported dry eyes and dry mouth, and she was diagnosed with Sjogren's syndrome. Subsequently, she was additionally diagnosed with inclusion body myositis and gastric light-chain (AL) amyloidosis. Although inclusion body myositis has been previously associated with Sjogren's syndrome, inclusion body myositis is rare in non-Caucasians, and the trio of Sjogren's syndrome, inclusion body myositis, and AL amyloidosis has not been previously reported. Sjogren's syndrome is a systemic autoimmune condition characterized by ocular and oral dryness. It is one of the most common rheumatologic disorders in the USA and worldwide. Early diagnosis of Sjogren's is particularly important given the frequency and variety of associated autoimmune diseases and extraglandular manifestations. Furthermore, although inclusion body myositis has a low prevalence, it is the most common inflammatory myopathy in older adults and is unfortunately associated with long delays in diagnosis, so knowledge of this disorder is also crucial for practicing internists.

[Inclusion Body Myopathy, Paget's Disease, and Fronto-temporal Dementia: a VCP-related Multi-systemic Proteinopathy]. / Einschlusskörpermyopathie, Paget-Krankheit und frontotemporale Demenz: eine VCP-bedingte, multisystemische Proteinopathie.

Mutations of the human VCP gene, which encodes the V: alosin C: ontaining P: rotein (synonyms: p97, TER ATPase), are associated with various multi-systemic protein aggregation diseases. We report on a patient with progressive myopathy and incipient cognitive deficits. A diagnostic muscle biopsy revealed an inclusion body myopathy with protein aggregates. Magnetic resonance imaging and F18-positron-emission-tomography disclosed a fronto-temporal atrophy and glucose hypometabolism of the frontal and temporal lobes, respectively. Based on the clinical findings, a genetic analysis was performed which revealed a heterozygous c.277C>T (p.Arg93Cys) mutation of the VCP gene, thus confirming the diagnosis of IBMPFD (I: nclusion B: ody M: yopathie with P: aget Disease of the Bones and F: ronto-temporal D: ementia).

Association of inclusion body myositis with T cell large granular lymphocytic leukaemia.

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present on follow-up testing in 15 patients a median of 350 days later. T cell aberrant loss of CD5 or gain of expression of CD16 and CD94 were common (19/42, 45%). In comparison, 2/15 (14%) age-matched patients with dermatomyositis, polymyositis, or necrotizing myopathy, and 0/20 (0%) age-matched healthy subjects had large granular lymphocyte expansions, with none of these patients having T cell aberrant expression of CD5, CD16 or CD94. Reduced blood CD4/CD8 ratio, increased blood CD8 count, and lymphocytosis were additional biomarkers highly correlated with flow cytometry-measured large granular lymphocyte expansions. Cross-sectional data suggested more aggressive disease in patients with such expansions than without. Muscle immunohistochemistry demonstrated invasion of large granular lymphocytes into muscle in 15/15 inclusion body myositis patients but in only 1/28 patients with dermatomyositis or polymyositis. The extent of CD8+ and CD57+ cells in inclusion body myositis muscle correlated with the size of blood large granular lymphocyte populations. Myofibre-invading cells expressed CD57, a marker of persistent T cell exposure to antigen and T cell aggressiveness. In many patients with inclusion body myositis, the autoimmune T cell expansion has evolved into a neoplastic-like or overtly neoplastic disorder, perhaps contributing to its relative refractoriness to immune-directed therapies previously reported.

Lagophthalmos and Ptosis in Inclusion Body Myositis.

Sporadic inclusion body myositis is the most commonly acquired type of idiopathic inflammatory myopathy in people aged 50 and above. There is early weakness and atrophy of forearms and quadriceps and a third of patients also have mild facial weakness. Extraocular muscles are not affected and ptosis is rarely seen. The authors describe a unique case in which inclusion body myositis presented with early mid face weakness and atrophy resulting in unilateral lagophthalmus, and ptosis, which have not been documented before. This case is not only unique in its presentation but also emphasizes the importance of considering differential diagnoses and conservative measures before contemplating surgery.

Concomitant occurrence of FXTAS and clinically defined sporadic inclusion body myositis: report of two cases.

This report describes unique presentations of inclusion body myositis (IBM) in two unrelated patients, one male and one female, with genetically and histologically confirmed fragile X-associated tremor/ataxia syndrome (FXTAS). We summarize overlapping symptoms between two disorders, clinical course, and histopathological analyses of the two patients with FXTAS and sporadic IBM, clinically defined per diagnostic criteria of the European Neuromuscular Centre. In case 1, a post-mortem analysis of available brain and muscle tissues is also described. Histopathological features (rimmed vacuoles) consistent with clinically defined IBM were detected in both presented cases. Postmortem testing in case 1 revealed the presence of an FMR1 premutation allele of 60 CGG repeats in both brain and skeletal muscle samples. Case 2 was a premutation carrier with 71 CGG repeats who had a son with FXS. Given that FXTAS is associated with immune-mediated disorders among premutation carriers, it is likely that the pathogeneses of IBM and FXTAS are linked. This is, to our knowledge, the first report of these two conditions presenting together, which expands our understanding of clinical symptoms and unusual presentations in patients with FXTAS. Following detection of a premutation allele of the FMR1 gene, FXTAS patients with severe muscle pain should be assessed for IBM.

Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement.

OBJECTIVES: To explore phenotypic differences between individuals with sporadic inclusion body myositis (sIBM) who are seropositive for the NT5c1A antibody compared with those who are seronegative. METHODS: Cross-sectional clinical, serological and functional analysis in 25 consecutive participants with sIBM. RESULTS: All participants met criteria for clinically defined or probable sIBM. 18 of 25 participants with sIBM (72%) were seropositive for the NT5c1A antibody. No differences between median age and duration of illness between the two groups were seen. Females have higher odds of being seropositive (OR=2.30). Participants with seropositive sIBM took significantly longer to get up and stand (p=0.012). There were no significant differences between the two groups in terms of distance covered on a 6 min walk. Seropositive participants were more likely to require assistive devices such as a walker or wheelchair for mobility (OR=23.00; p=0.007). A number of secondary (exploratory) outcomes were assessed. NT5c1A seropositive sIBM cases had lower total Medical Research Council (MRC) sum score and MRC sum score on the right (p=0.03 and 0.02, respectively). Participants with the NT5c1A antibody were significantly more likely to have symptoms of dysphagia (OR=10.67; p=0.03) and reduced forced vital capacity (p=0.005). Facial weakness occurred in 50% of seropositive participants while it was only seen in 14% of seronegative participants. CONCLUSIONS: Even though the small sample size limits definite conclusions, our cross-sectional study showed seropositivity to the NT5c1A antibody is associated with greater motor and functional disability in sIBM. The study also suggests more prominent bulbar, facial and respiratory involvement in individuals positive for NT5c1A antibodies.

Interventions for dysphagia in long-term, progressive muscle disease.

BACKGROUND: Normal swallowing function is divided into oral, pharyngeal, and oesophageal phases. The anatomy and physiology of the oral cavity facilitates an oral preparatory phase of swallowing, in which food and liquid are pushed towards the pharynx by the tongue. During pharyngeal and oesophageal phases of swallowing, food and liquid are moved from the pharynx to the stomach via the oesophagus. Our understanding of swallowing function in health and disease has informed our understanding of how muscle weakness can disrupt swallowing in people with muscle disease. As a common complication of long-term, progressive muscle disease, there is a clear need to evaluate the current interventions for managing swallowing difficulties (dysphagia). This is an update of a review first published in 2004. OBJECTIVES: To assess the effects of interventions for dysphagia in people with long-term, progressive muscle disease. SEARCH METHODS: On 11 January 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, LILACS, and CINAHL. We checked references in the identified trials for additional randomised and quasi-randomised controlled trials. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform on 12 January 2016 for ongoing or completed but unpublished clinical trials. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials that assessed the effect of interventions for managing dysphagia in adults and children with long-term, progressive muscle disease, compared to other interventions, placebo, no intervention, or standard care. Quasi-randomised controlled trials are trials that used a quasi-random method of allocation, such as date of birth, alternation, or case record number. Review authors previously excluded trials involving people with muscle conditions of a known inflammatory or toxic aetiology. In this review update, we decided to include trials of people with sporadic inclusion body myositis (IBM) on the basis that it presents as a long-term, progressive muscle disease with uncertain degenerative and inflammatory aetiology and is typically refractory to treatment. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodological procedures. MAIN RESULTS: There were no randomised controlled trials (RCTs) that reported results in terms of the review's primary outcome of interest, weight gain or maintenance. However, we identified one RCT that assessed the effect of intravenous immunoglobulin on swallowing function in people with IBM. The trial authors did not specify the number of study participants who had dysphagia. There was also incomplete reporting of findings from videofluoroscopic investigations, which was one of the review's secondary outcome measures. The study did report reductions in the time taken to swallow, as measured using ultrasound. No serious adverse events occurred during the study, although data for the follow-up period were lacking. It was also unclear whether the non-serious adverse events reported occurred in the treatment group or the placebo group. We assessed this study as having a high risk of bias and uncertain confidence intervals for the review outcomes, which limited the overall quality of the evidence. Using GRADE criteria, we downgraded the quality of the evidence from this RCT to 'low' for efficacy in treating dysphagia, due to limitations in study design and implementation, and indirectness in terms of the population and outcome measures. Similarly, we assessed the quality of the evidence for adverse events as 'low'. From our search for RCTs, we identified two other non-randomised studies, which reported the effects of long-term intravenous immunoglobulin therapy in adults with IBM and lip-strengthening exercises in children with myotonic dystrophy type 1. Headaches affected two participants treated with long-term intravenous immunoglobulin therapy, who received a tailored dose reduction; there were no adverse events associated with lip-strengthening exercises. Both non-randomised studies identified improved outcomes for some participants following the intervention, but neither study specified the number of participants with dysphagia or demonstrated any group-level treatment effect for swallowing function using the outcomes prespecified in this review. AUTHORS' CONCLUSIONS: There is insufficient and low-quality RCT evidence to determine the effect of interventions for dysphagia in long-term, progressive muscle disease. Clinically relevant effects of intravenous immunoglobulin for dysphagia in inclusion body myositis can neither be confirmed or excluded using the evidence presented in this review. Standardised, validated, and reliable outcome measures are needed to assess dysphagia and any possible treatment effect. Clinically meaningful outcomes for dysphagia may require a shift in focus from measures of impairment to disability associated with oral feeding difficulties.

Demographic and clinical features of inclusion body myositis in North America.

INTRODUCTION: Few studies of the demographics, natural history, and clinical management of inclusion body myositis (IBM) have been performed in a large patient population. To more accurately define these characteristics, we developed and distributed a questionnaire to patients with IBM. METHODS: A cross-sectional, self-reporting survey was conducted. RESULTS: The mean age of the 916 participants was 70.4 years, the male-to-female ratio was 2:1, and the majority reported difficulty with ambulation and activities of daily living. The earliest symptoms included impaired use and weakness of arms and legs. The mean time from first symptoms to diagnosis was 4.7 years. Half reported that IBM was their initial diagnosis. A composite functional index negatively associated with age and disease duration, and positively associated with participation in exercise. CONCLUSIONS: These data are valuable for informing patients how IBM manifestations are expected to impair daily living and indicate that self-reporting could be used to establish outcome measures in clinical trials.