Volumetric muscle composition analysis in sporadic inclusion body myositis using fat-referenced magnetic resonance imaging: Disease pattern, repeatability, and natural progression.

INTRODUCTION/AIMS: Fat-referenced magnetic resonance imaging (MRI) has emerged as a promising volumetric technique for measuring muscular volume and fat in neuromuscular disorders, but the experience in inflammatory myopathies remains limited. Therefore, this work aimed at describing how sporadic inclusion body myositis (sIBM) manifests on standardized volumetric fat-referenced MRI muscle measurements, including within-scanner repeatability, natural progression rate, and relationship to clinical parameters. METHODS: Ten sIBM patients underwent whole-leg Dixon MRI at baseline (test-retest) and after 12 months. The lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) of the quadriceps, hamstrings, adductors, medial gastrocnemius, and tibialis anterior were computed. Clinical assessments of IBM Functional Rating Scale (IBMFRS) and knee extension strength were also performed. The baseline test-retest MRI measurements were used to estimate the within-subject standard deviation (sw). 12-month changes were derived for all parameters. RESULTS: The MRI measurements showed high repeatability in all muscles; sw ranged from 2.7 to 18.0 mL for LMV, 0.7-1.3 percentage points (pp) for MFF, and 0.2-0.7 pp for MFI. Over 12 months, average LMV decreased by 7.4% while MFF and MFI increased by 3.8 pp and 1.8 pp, respectively. Mean IBMFRS decreased by 2.4 and mean knee extension strength decreased by 32.8 N. DISCUSSION: The MRI measurements showed high repeatability and 12-month changes consistent with muscle atrophy and fat replacement as well as a decrease in both muscle strength and IBMFRS. Our findings suggest that fat-referenced MRI measurements are suitable for assessing disease progression and treatment response in inflammatory myopathies.

Impact of sex, age at onset, and anti-cN1A antibodies on sporadic inclusion body myositis.

BACKGROUND: Inclusion body myositis (IBM) is a progressive myopathy occurring in patients over 45 years of age, with heterogeneous and variable clinical features. This study aimed to determine the influence of autoantibodies, gender, and age of onset on the clinical features of IBM. METHODS: Medical records and muscle histology findings of 570 participants with suspected IBM were reviewed. Various characteristics of patients who met the 2011 ENMC IBM diagnostic criteria were compared based on the presence of anti-cytosolic 5'-nucleotidase 1 A (cN1A) autoantibodies, gender, age of onset, and disease duration. RESULTS: Of the 353 patients who met the criteria, 41.6% were female. The mean age at onset was 64.6 ± 9.3 years, and the mean duration from onset to diagnosis was 5.7 ± 4.7 years. 196 of the 353 patients (55.5%) were positive for anti-cN1A autoantibodies and 157 were negative. Logistic regression showed that patients with anti-cN1A autoantibodies had a higher frequency of finger flexion weakness. Multiple regression showed that patients with later age of onset had shorter disease duration, lower BMI, and lower serum CK levels. Male patients had a higher frequency of onset with finger weakness and female patients had a lower BMI. CONCLUSION: Autoantibodies, gender, age of onset, and disease duration may influence the clinical presentation of IBM, highlighting the need for a precision medicine approach that considers these factors along with the underlying mechanisms of the disease.

Quantitative muscle MRI in sporadic inclusion body myositis (sIBM): A prospective cohort study.

Background: Sporadic inclusion body myositis (sIBM) is the predominant idiopathic inflammatory myopathy (IIM) in older people. Limitations of classical clinical assessments have been discussed as possible explanations for failed clinical trials, underlining the need for more sensitive outcome measures. Quantitative muscle MRI (qMRI) is a promising candidate for evaluating and monitoring sIBM. Objective: Longitudinal assessment of qMRI in sIBM patients. Methods: We evaluated fifteen lower extremity muscles of 12 sIBM patients (5 females, mean age 69.6, BMI 27.8) and 12 healthy age- and gender-matched controls. Seven patients and matched controls underwent a follow-up evaluation after one year. Clinical assessment included testing for muscle strength with Quick Motor Function Measure (QMFM), IBM functional rating scale (IBM-FRS), and gait analysis (6-minute walking distance). 3T-MRI scans of the lower extremities were performed, including a Dixon-based sequence, T2 mapping and Diffusion Tensor Imaging. The qMRI-values fat-fraction (FF), water T2 relaxation time (wT2), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (RD) were analysed. Results: Compared to healthy controls, significant differences for all qMRI parameters averaged over all muscles were found in sIBM using a MANOVA (p < 0.001). In low-fat muscles (FF < 10%), a significant increase of wT2 and FA with an accompanying decrease of MD, λ1, and RD was observed (p≤0.020). The highest correlation with clinical assessments was found for wT2 values in thigh muscles (r≤-0.634). Significant changes of FF (+3.0%), wT2 (+0.6 ms), MD (-0.04 10-3mm2/s), λ1 (-0.05 10-3mm2/s), and RD (-0.03 10-3mm2/s) were observed in the longitudinal evaluation of sIBM patients (p≤0.001). FA showed no significant change (p = 0.242). Conclusion: qMRI metrics correlate with clinical findings and can reflect different ongoing pathophysiological mechanisms. While wT2 is an emerging marker of disease activity, the role of diffusion metrics, possibly reflecting changes in fibre size and intracellular deposits, remains subject to further investigations.

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging.

Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting the quadriceps, deep finger flexors, and foot extensors. At present, there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathological phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and the accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis, including environmental factors, autoimmunity, abnormalities of protein transcription and processing, the accumulation of several toxic proteins, the impairment of autophagy and the ubiquitin-proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has also been proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.

Efficacy of endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope in patients with sporadic inclusion body myositis: four retrospective case reviews.

Sporadic inclusion body myositis (s-IBM) is an acquired degenerative inflammatory myopathy that leads to slowly progressive muscle weakness and atrophy of the limbs, face, and pharynx. Owing to the slow progression of the disease, the indications for surgical intervention remain unclear. Herein, we retrospectively reviewed the records of four patients with s-IBM who had undergone cricopharyngeal myotomy for severe dysphagia at our institution between 2016 and 2021. Among these, one patient underwent transcervical cricopharyngeal myotomy and laryngeal suspension, as videofluoroscopic examination of swallowing revealed poor laryngeal elevation. The remaining three patients underwent endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope. Preoperatively, the mean Hyodo score was 8 points (range: 6-10) using a flexible endoscope. The mean surgical duration was 104 min, and no severe complications were observed. Postoperatively, all patients achieved improvement in swallowing function and food intake. Moreover, swallowing function was maintained in all four patients even 6-12 months postoperatively. Cricopharyngeal myotomy may be a safe surgical procedure with the potential to improve swallowing function, and a Hyodo score of 6 may be considered a surgical indication for cricopharyngeal myotomy in patients with s-IBM.

Retrospective Study Shows That Serum Levels of Chemokine CXCL10 and Cytokine GDF15 Support a Diagnosis of Sporadic Inclusion Body Myositis and Immune-Mediated Necrotizing Myopathy.

The implementation of novel blood-based biomarkers is desired to reduce the diagnostic delay and burden for myositis patients. In this retrospective study, the potential of C-X-C motif chemokine ligand 10 (CXCL10) and growth differentiation factor 15 (GDF15) was explored in an established patient cohort diagnosed with immune-mediated necrotizing myopathy (IMNM; n = 21), sporadic inclusion body myositis (IBM; n = 18), overlap myositis (OM; n = 3), dermatomyositis (DM; n = 2), and anti-synthetase syndrome (ASS; n = 1), comparing these results with healthy controls (n = 10) and patients with a hereditary neuromuscular disorder (n = 14). CXCL10 and GDF15 were quantified in sera with enzyme-linked immunosorbent assays and immunolocalized in skeletal muscle tissue. In myositis patients, serum CXCL10 levels were significantly increased 9.6-fold compared to healthy controls and 4.2-fold compared to disease controls. Mean levels of CXCL10 were 929 ± 658 pg/mL of serum in IBM and 425 ± 324 pg/mL of serum in IMNM. With the threshold set to 180 pg/mL of CXCL10, myositis patients could be differentiated from healthy and disease controls with a sensitivity of 0.80 and a specificity of 0.71. Incorporating a threshold of 300 pg/mL for GDF15 reduced false negatives to two IMNM patients only. Subsets of muscle-infiltrating immune cells expressed CXCL10, and serum levels correlated with muscle inflammation grade. We propose adding circulating CXCL10 and GDF15 to the blood-based diagnostic toolkit for myositis as a valuable patient-friendly approach.

Myositis with prominent B cell aggregates may meet classification criteria for sporadic inclusion body myositis.

The objective of this study was to report the clinical, serological and pathological features of patients with autoimmune myositis other than dermatomyositis, who displayed both muscle weakness on physical examination and prominent B cell aggregates on muscle pathology, defined as ≥ 30 CD20+ cells/aggregate. Specifically, the presence of a brachio-cervical inflammatory myopathies or a sporadic inclusion body myositis (sIBM) phenotype was recorded. Over a three-year period, eight patients were identified from two university neuropathology referral centers. Seven of 8 (88%) patients had an associated connective tissue disease (CTD): rheumatoid arthritis (n=3), systemic sclerosis (n=2), Sjögren's syndrome (n=1) and systemic lupus erythematosus (n=1), while one patient died on initial presentation without a complete serological and cancer investigation. A brachio-cervical phenotype, i.e. neck weakness, proximal weakness more than distal and shoulder abduction weakness greater than hip flexors, was seen in two patients (25%), while one patient had both proximal and diaphragmatic weakness. In contrast, an IBM-like clinical phenotype was seen in the last five patients (63%), who either had finger flexor weakness and/or quadriceps weakness ≤ 4 on the manual muscle testing MRC-5 scale. Although these 5 patients met at least one set of classification criteria for sIBM, an integrated clinico-sero-pathological approach argued against a diagnosis of sIBM. In summary, in a weak patient with myositis plus an associated CTD and lymphoid aggregates at muscle pathology, B cell predominant aggregates may represent a morphological biomarker against a diagnosis of sIBM.

Inclusion body myositis: from genetics to clinical trials.

Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies and is characterized by a slowly progressive disease course with asymmetric muscle weakness of predominantly the finger flexors and knee extensors. The disease leads to severe disability and most patients lose ambulation due to lack of curative or disease-modifying treatment options. Despite some genes reported to be associated with hereditary IBM (a distinct group of conditions), data on the genetic susceptibility of sporadic IBM are very limited. This review gives an overview of the disease and focuses on the current genetic knowledge and potential therapeutic implications.

Aging Muscles, Myositis, Pain, and Peripheral Neuropathies: PET Manifestations in the Elderly.

Advancing age significantly affects the structural and functional characteristics of organs and tissues, including the peripheral nervous system (PNS) and musculoskeletal system. PET molecular imaging systems offer the ability to assess the metabolic and quantitative effects due to nerve and muscle injuries, which has the potential to impact clinical management of aged subjects. Here, we aim to describe some features of molecular imaging PET systems using different tracers and methods of imaging in musculoskeletal disorders and peripheral neuropathies commonly seen in elderly patients.

Clinical characteristics of dysphagic inclusion body myositis.

This study aimed to characterize dysphagic patients with inclusion body myositis (IBM) with cricopharyngeal bar (CPB) (n = 17; IBM-CPB(+)) by comparing their swallowing function and muscle magnetic resonance imaging data with IBM patients without CPB (n = 28; IBM-CPB(-)). IBM-CPB(+) patients were older at diagnosis and had more frequent obstruction-related dysphagia and stronger knee extension than IBM-CPB(-) patients. IBM-CPB(+) patients also had less intramuscular fatty infiltration than IBM-CPB(-) patients on T1-weighted magnetic resonance images of the rectus femoris (2.6% versus 10.3%, p < 0.05), vastus lateralis (27.8% versus 57.1%, p < 0.01), vastus intermedius (17.6% versus 43.5%, p < 0.01), vastus medialis (14.1% versus 39.1%, p < 0.01), deltoid (5.5% versus 18.7%, p < 0.05), biceps (6.6% versus 21.1%, p < 0.001), and triceps (12.9% versus 33.0%, p < 0.05). These findings suggest that IBM-CPB(+) patients were older, frequently exhibited obstruction-related dysphagia, had stronger knee extension, and had less fatty infiltration of the limb muscles compared to IBM-CPB(-) patients, and provide valuable information on the clinical subset of IBM-CBP(+) patients in order to expand the knowledge of the clinical heterogeneity in IBM.

COVID-19-Induced Sporadic Inclusion Body Myositis.

Sporadic inclusion body myositis (sIBM) is an autoimmune condition that is characterized by progressive weakness and muscular atrophy in the extremities. The pathophysiology is not exactly clear; however, some studies have postulated an involvement of cytotoxic T cells (CD8+), causing an autoimmune response. While the implications of COVID-19 infection are an evolving topic, myositis has been previously implicated in other viral etiologies. We discuss a case of sIBM secondary to COVID-19 in a patient with chronic myalgias bringing to light a rare implication of COVID-19 to educate the medical community.

Clinical implication of denervation in sporadic inclusion body myositis.

INTRODUCTION: Sporadic inclusion body myositis (sIBM) is often accompanied by signs suggestive of denervation on electromyography (EMG), which mimics neurogenic disorders. Hence, the current study aimed to assess reinnervation after denervation in sIBM and its clinical impllcation. METHODS: We retrospectively examined consecutive muscle biopsy specimens collected from 109 sIBM patients who were referred to our institution for diagnostic muscle biopsy from 2001 to 2018. Reinnervation after denervation in sIBM patients was assessed via muscle biopsy and EMG. The levels of acetylcholine receptor subunit γ (Chrng) and muscle-specific kinase (MuSK) mRNA, which are markers of denervation, were examined using real-time polymerase chain reaction. Response to treatment was defined as an increase of grade 1 or higher in two or more muscle groups as assessed using the Medical Research Council scale. RESULTS: In total, 93 (85.3%) of 109 sIBM patients had reinnervation after denervation on histological examination and/or EMG. The mean disease duration before biopsy was significantly longer in patients with reinnervation after denervation than in those without (p < 0.00001). Patients with denervation had significantly higher levels of Chrng and MuSK mRNA than those without. The proportion of patients who responded to immunosuppressive therapies was smaller in the patients with denervation than those without (p < 0.05). However, there was no significant difference regarding time from onset to using a walking aid between the two groups. DISCUSSION: Reinnervation after denervation is associated with disease duration and short-term response to therapy in individuals with sIBM.

An exploratory study of circulating cytokines and chemokines in patients with muscle disorders proposes CD40L and CCL5 represent general disease markers while CXCL10 differentiates between patients with an autoimmune myositis.

Discriminating an autoimmune myositis from other disorders and subtyping of patient groups within this heterogeneous group of conditions remain diagnostic challenges. In our study we explored the potential of cytokine and chemokine typing in patient sera as an addition to the expanding set of blood-accessible diagnostic biomarkers available today. We selected sets of ten patients within well-characterized disease groups representing healthy controls, and patients with hereditary muscular dystrophies, immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis (IBM). Prescreening using proteome arrays singled out three biomarker candidates, being the cytokine CD40L, and chemokines CXCL10 and CCL5. Enzyme-linked immunosorbent assays showed all three markers to be elevated in muscle disease irrespective of patient subgroup. CXCL10 levels on the other hand were higher in autoimmune myositis only, and levels were significantly higher in IBM compared to IMNM. The strong CXCL10 expression observed in the auto-aggressive inflammatory cells within IBM muscle tissues possibly represents a major source of circulating CXCL10. We conclude that CXCL10 levels could represent a convenient marker for autoimmune myositis indicative of patient subgroups.

Growth differentiation factor-15 as an emerging biomarker for identifying myositis.

INTRODUCTION: The autoimmune disorders of the skeletal muscle tissue termed myositis are a rare yet diverse group of diseases with distinct clinical and pathological features and with different prognoses and treatment responses. Subtyping of patients is necessary for appropriate disease management, and requires specialized expertise and elaborate diagnostic testing of clinico-pathological disease features. AREAS COVERED: Current clinical practice and diagnostic criteria for subtyping patients are searched on medical online platforms including PubMed and Web of Science. Recent publications on growth differentiation factor-15 (GDF-15) and muscle disorders are summarized and analyzed, and comparisons are made of data published in studies describing disease cohorts as well as individual patients. Influence of age and physical activity on GFD-15 levels and potential as a diagnostic criterion are discussed. This review contains supportive evidence of the elevated levels of GDF-15 in the blood of myositis patients, a feature which distinguishes these autoimmune muscle disorders from muscular dystrophy with secondary inflammation. EXPERT OPINION: GDF-15 represents a novel and promising serological biomarker for diagnosing myositis, yet more studies are needed to assay its sensitivity and specificity. Increased diagnostic power is expected by combining GDF-15 levels with other blood-derived biomarkers.

Effects of blood-flow restricted resistance training on mechanical muscle function and thigh lean mass in sIBM patients.

Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory muscle disease associated with skeletal muscle inflammation and a parallel progressive decline in muscle strength and physical function. Eventually, most sIBM patients require use of wheelchair after about 10 years of diagnosis and assistance to perform activities of daily living. This study presents data from a randomized controlled intervention trial (NCT02317094) that examined the effect of 12 weeks low-load blood-flow restricted (BFR) resistance training on maximal muscle strength, power, rate of force development (RFD), thigh lean mass (TLM), and voluntary muscle activation (VA) in sIBM patients. A time-by-group interaction in knee extensor strength was observed in the stronger leg (p ≤ 0.033) but not the weaker leg. Within-group changes were observed with BFR training (BFR) manifested by increased knee extensor strength in the strongest leg (+13.7%, p = 0.049), whereas non-exercising patients (CON) showed reduced knee extensor strength (-7.7%, p = 0.018). Maximal leg extensor power obtained for the stronger leg remained unchanged following BFR training (+9.5%, p = 0.37) while decreasing in CON (-11.1%, p = 0.05). No changes in TLM were observed. VA declined post-training (p = 0.037) in both BFR (-6.3% points) and CON (-7.5% points). The present data indicate that BFR resistance training can attenuate the rate of decline in mechanical muscle function typically experienced by sIBM patients. The preservation of muscle mass and mechanical muscle function with BFR resistance training may be considered of high clinical importance in sIBM patients to countermeasure the disease-related decline in physical function.

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders affecting primarily muscles, but other organs can be involved. This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS). The diagnostic approach has been updated recently based on the discovery of circulating autoantibodies, which has enhanced the management of patients. Currently, validated classification criteria for IIMs allow clinical studies with well-defined sets of patients but diagnostic criteria to guide the care of individual patients in routine clinical practice are still missing. This review analyzes the clinical manifestations and laboratory findings of IIMs, discusses the efficiency of modern and standard methods employed in their workup, and delineates optimal practice for clinical care. Α multidisciplinary diagnostic approach that combines clinical, neurologic and rheumatologic examination, evaluation of electrophysiologic and morphologic muscle characteristics, and assessment of autoantibody immunoassays has been determined to be the preferred approach for effective management of patients with suspected IIMs.

A rare case of sporadic inclusion body myositis and rheumatoid arthritis exhibiting ectopic lymphoid follicle-like structures: a case report and literature review.

Sporadic inclusion body myositis (sIBM) is a degenerative, intractable, inflammatory myopathy with an immune pathomechanism. We report on a case of a 44-year-old Japanese man who began developing progressive muscle weakness at age 40. Rheumatoid arthritis symptoms manifested at 43 with strongly positive anti-cyclic citrullinated peptide antibodies. Along with typical sIBM pathology, a muscle biopsy revealed dramatic inflammation with prominent perivascular B-cell infiltration forming ectopic lymphoid follicle-like structures (ELFLSs). Exome sequencing identified no causative variants of hereditary myopathy or immune disorders. A combination of immunotherapy slowed the progression of the muscular symptoms. This unusual form of sIBM, including earlier age at onset, a partial response to immunotherapy, and a histopathology presenting B-cell infiltrate with ectopic lymphoid follicle-like structures, indicates a possible association of rheumatoid arthritis and heterogeneity with the autoimmune involvement of sIBM. We review the clinical and pathological features of patients with rheumatoid arthritis associated sIBM in the literature.

Blocking the activin IIB receptor with bimagrumab (BYM338) increases walking performance: A meta-analysis.

AIM: Diseases and bed rest may result in decreased muscle size and function. While exercise is recommended as a countermeasure, there are times when diseases or injuries make it difficult for the patient to partake in an exercise intervention. Pharmaceutical interventions using a myostatin inhibitor, BYM338, have been investigated as a way to increase or maintain muscle function. Of interest in the present analysis was the 6-min walk test. The 6-min walk test was selected, as there is an association between walking ability and the ease of performing activities of daily living. Thus, our aim was to investigate the effects of BYM338 on walking performance relative to a placebo. METHODS: A meta-analysis using a random effects model was conducted in April 2021. RESULTS: Four studies were included with a total sample size of 244 participants receiving BYM338 and 114 participants receiving a placebo. The average age of the participants included was 68 years. The main analysis produced a weighted mean effect size of 10 m (SE 5) (P = 0.05) for BYM338 over a placebo. Excluding the lowest dosage (1 mg/kg) provided similar results (12 m [SE 5], P = 0.033). Of note, the weighted mean effect with or without the lowest dosage is surrounded by a large degree of uncertainty. CONCLUSIONS: Our results suggest that BYM338 is a viable drug for improving 6-min walk test in populations associated with impaired function. Geriatr Gerontol Int 2021; 21: 939-943.

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.

Sporadic Inclusion Body Myositis: A Clinicopathological Study.

BACKGROUND: Sporadic inclusion body myositis (s-IBM) is rare in India. AIM: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011. MATERIALS AND METHODS: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed. RESULTS: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1-5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57-2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies. CONCLUSIONS: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.