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Abstracts / Neuromuscular Disorders 24 (2014) 791–924

role in protein degradation and of several chaperones including BiP and calreticulin, two proteins that are involved in unfolded protein response and SR stress, and components of a chaperone complex that was not described in the context of sIBM so far. Our proteomic approach also revealed an over-representation of proteins that play a role in inflammatory pathways, e.g. interferon-induced proteins and proteins involved in T-cell activation. In conclusion, our proteomic data provide essential new insights into the composition of rimmed vacuoles in sIBM. The application of a combined laser microdissection and mass spectrometry approach enabled the identification of more than 200 proteins that accumulate in RV areas. The results not only confirm previous findings but expand our knowledge about proteins and pathways that seem to be relevant in pathogenesis of sIBM. http://dx.doi:10.1016/j.nmd.2014.06.078

G.P.65 Obstructive sleep apnoea and subclinical impairment of respiratory function are common in sporadic inclusion body myositis P.M. Rodriguez Cruz 1, M. Needham 1, P. Hollingsworth 2, F.L. Mastaglia 1, D.R. Hillman 3 1 Western Australian Neuroscience Research Institute, Perth, Australia; 2 Queen Elizabeth II Medical Centre, Perth, Australia; 3 West Australian Sleep Disorders Research Institute, Perth, Australia To examine the occurrence of respiratory dysfunction in sporadic inclusion body myositis (IBM) and its relationship to peripheral muscle strength and ventilation during sleep. Anthropometric, muscle strength, dyspnoea, daytime sleepiness and dysphagia data were collected. Spirometry, respiratory muscle strength and arterial blood gas tensions were measured. Ventilation during sleep was assessed by dual channel (oximetry, nasal pressure) home monitoring. Sixteen patients with biopsy-proven IBM were studied (10 males, 6 females; age 68.1 ± 9.9 years; disease duration 11.9 ± 5.0 years; body mass index 28.5 ± 4.0 kg/m2). Four patients reported excessive daytime sleepiness (Epworth Sleepiness Scale P10); 8 had at least mild dysphagia (Dysphagia Outcome Severity Scale 65); forced vital capacity was <80% of the predicted normal in 7; sniff nasal inspiratory pressure was reduced (<60 cm H2O) in 3; daytime hypoxemia (PaO2 < 80 mmHg) was present in 10 and hypercapnia (PaCO2 > 45 mmHg) in one. Sleep study was performed in 15 patients and revealed sleep hypoxemia (P2% of total sleep time at or below a saturation <90% (TST 6 90)) in 10 and obstructive sleep apnoea (respiratory disturbance index 23.4 ± 12.8 (range 7–50.3) events/h) in all 15. Daytime PaO2 was related to TST 6 90 (r = 0.55, p = 0.04). Asymptomatic impairment of wakeful respiratory function was common and obstructive sleep apnoea was observed in all patients tested, irrespective of daytime respiratory function. This high occurrence probably reflects the combined effects of pharyngeal muscle weakness and sleep-related reduction in muscle activation and ventilatory drive. These findings suggest that tests of respiratory function, including an overnight sleep study, should be performed routinely in IBM patients, irrespective of peripheral muscle function or other non-respiratory disease severity parameters. http://dx.doi:10.1016/j.nmd.2014.06.079

G.P.66 Real-time MRI for the evaluation of dysphagia in inclusion body myositis (IBM) P.O. Carstens 1, S. Zhang 2, A. Olthoff 3, E. Bremen 4, J. Lotz 4, J. Frahm 2, J. Schmidt 1 1 Clinic for Neurology, University Medical Centre Go¨ttingen, Go¨ttingen,

Germany; 2 Biomedizinische NMR Forschungs GmbH at the Max Planck Institute for Biophysical Chemistry, Go¨ttingen, Germany; 3 Clinic for Otorhinolaryngology, Phoniatrics and Pedaudiology, University Medical Centre Go¨ttingen, Go¨ttingen, Germany; 4 Department of Radiology, University Medical Centre Go¨ttingen, Go¨ttingen, Germany Inclusion body myositis (IBM) is the most common acquired myopathy in patients over 50 years and is characterized by a progressive muscle weakness and dysphagia. The aim of this study was to compare a novel real-time MRI technique with the standard assessments for dysphagia. The evaluation of symptoms of dysphagia and of the swallowing quality of life was performed by a standardized questionnaire (SWAL-QoL) in 20 non-selected, consecutive patients with IBM. Technical testing included flexible endoscopic evaluation of swallowing (FEES), videofluoroscopy (VF) and real-time MRI. The clinical parameters included the IBM-functional rating score (IBM-FRS), a patient reported functional assessment (sIFA) and the strength of different muscles (MRC-score). Dysphagia was noted in SWAL-QoL in 72% of the patients and it revealed a higher frequency of dysphagia and a poorer swallowing quality of life in IBM patients compared to reference values of healthy elderly. The SWAL-QoL significantly correlated with the IBM-FRS and the MRC score. Swallowing in a supine position during MRI was well tolerated by all patients and no aspiration occurred. In some patients, during swallowing a muscle propulsion in the area of the cricopharygeal muscle was seen on MRI and VF. The MRI showed a significant increase of the oral and pharyngeal transit times and the esophageal opening time in patients compared to healthy controls from a prior published study. The pharyngeal transit time significantly correlated to the eating duration per SWAL-QoL. Symptoms of dysphagia were found in the majority of IBM patients. Dynamic real-time MRI is highly suitable for the assessment of dysphagia in IBM. Besides avoiding exposure to X-rays, MRI advantages are additional information such as morphology and time lapse, which are not provided by standard methods. Improved diagnostic tools for evaluating swallowing in IBM may help to prevent aspiration and subsequent pneumonia. http://dx.doi:10.1016/j.nmd.2014.06.080

G.P.67 Myositis with invasion of endomysial cell infiltrate but without rimmed vacuoles: Separate phenotype or variant of sporadic inclusion body myositis? M. de Visser 1, J. van de Vlekkert 1, J.E. Hoogendijk 2 1 Academic Medical Center, Amsterdam, Netherlands; 2 University Medical Center, Utrechts, Netherlands To investigate the hypothesis that patients with inclusion body myositis (IBM) are underdiagnosed if strict histopathological and/or clinical criteria are applied. Muscle biopsies and clinical data of all adult patients diagnosed with an inflammatory myopathy during the years 1979–2006 in two tertiary neuromuscular referral centers were re-evaluated. Patients with endomysial inflammation with invasion of healthy looking muscle fibres were divided into three groups: (1) patients whose biopsies showed rimmed vacuoles; (2) patients whose biopsies showed no vacuoles but fulfilled clinical criteria for IBM, and (3) patients with no vacuoles, and also did not fulfill clinical criteria (unclassified). These groups were compared as regards gender, disease course including response to immunosuppressive treatment and clinical features at follow up. There were 81 patients (40 women). Rimmed vacuoles were found in 49 patients (60%; significantly more often in men (61%) than in women (39%; p = 0.018), 14 (17%) fulfilled clinical criteria for IBM and 18 (22%, 78% women) were unclassified. At follow up (mean duration 9 years, SD 5 years) three women remained unclassified (4 %) and 96 % were classified as IBM. All patients showed

Abstracts / Neuromuscular Disorders 24 (2014) 791–924 stable or progressive disease and none experienced sustained improvement. There were no differences in disease course or effect of treatment between the three groups. At onset there were more unclassified women (p = 0,018), but not at follow up because then they fulfilled clinical criteria for IBM. Women more often had a concomitant autoimmune disease (p = 0,012). Men and women did not differ with respect to age at presentation, time to biopsy, or duration of follow up. (1) Endomysial mononuclear cell infiltrates with invasion of non-necrotic fibres indicates a diagnosis of IBM even if clinical criteria are not fulfilled. (2) There are gender differences at onset, and especially women with IBM are at risk for underdiagnosis. http://dx.doi:10.1016/j.nmd.2014.06.081

G.P.68 The utility of anti-cN1A autoantibody for the diagnosis of sporadic inclusion body myositis H. Nihimura 1, S. Suzuki 2, S. Noguchi 1, A. Uruha 1, S. Mitsuhashi 1, Y.K. Hayashi 3, I. Nonaka 1, I. Nishino 1 1 National Center of Neurology and Psychiatry, Kodaira, Japan; 2 Keio University School of Medicine, Tokyo, Japan; 3 Tokyo Medical University, Tokyo, Japan Sporadic inclusion body myositis (sIBM) is diagnosed by its clinical and pathological features. sIBM is clinically characterized by asymmetric weakness of finger flexors with slow progression and resistance to immunosuppressive therapy. Pathologically, sIBM shows an inflammatory feature, namely T-lymphocyte infiltration into endomysium, and degenerative features, by presence of rimmed vacuoles (RV) and aggregated proteins like amyloid, p62, TDP-43 and others in myofibers. Although sIBM has been diagnosed clinically and pathologically, it is quite difficult to make a correct diagnosis for sIBM only by pathological evaluation without any clinical information, if pathological hallmarks such as RV and amyloid inclusions, are absent in muscle biopsy. Serological biomarkers for sIBM had not been found for a long time, however recently the autoantibody to cytosolic 50 -nucleotidase 1A (cN1A) was reported as a highly specific marker to sIBM. In this study, we tested the diagnostic utility of this anti-cN1A autoantibody in plasma of sIBM patients. We measured a titer of anti-cN1A autoantibody by ELISA in plasma samples of 315 patients who were suspected to have inflammatory myopathy. Among them, the antibody was positive in 12 of 34 sIBM patients, 5 of 18 polymyositis, 0 of 22 dermatomyositis, 7 of 37 SRP myopathy, and 9 of 204 others (total 33 of 315). Anti-cN1A autoantibody found out more than one-third of sIBM patients as previously reported but also found polymyositis (28%) and SRP myopathy (19%). The presence of anti-cN1A autoantibody in some patients with polymyositis may raise a possibility that those patients may in fact have had sIBM. In fact, previous studies also reported similar results. However, increased titer in SRP myopathy has never been reported. Considering that SRP myopathy has markedly different clinical and pathological features from sIBM, SRP myopathy may have a different mechanism to produce anti-cN1A autoantibody although further studies are necessary. http://dx.doi:10.1016/j.nmd.2014.06.082

G.P.69 Th2-M2 immunity in granulomas of neuromuscular sarcoidosis and macrophagic myofasciitis C. Preuße 1, H. Goebel 1, D. Pehl 1, J.L. Rinnenthal 1, Y. Allenbach 1, F.L. Heppner 1, R.A. Kley 2, M. Vorgerd 2, F.J. Authier 3,4, R. Gherardi 3,4, W. Stenzel 1

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Charite´ - Universita¨tsmedizin, Berlin, Germany; 2 Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, Ruhr-Universita¨t Bochum, Bochum, Germany; 3 Henri Mondor Hospital, Creteil, France; 4 INSERM U955, Faculty of Medicine, Paris, France Granulomatous inflammation of skeletal muscle is the hallmark of neuromuscular sarcoidosis (NMS) and macrophagic myofasciitis (MMF). We have recently described an M2-polarized immune response in neuromuscular sarcoidosis. Now, the intrinsic immune signature of granulomas from both entities, and the adjacent non-inflamed muscle tissue was analysed. Granulomas and contiguous muscle from ten patients with NMS and ten patients with MMF were cut out by laser microdissection. Mediators of the T helper cell 1 – classical macrophage activation and Th2 – alternatively activated macrophage immune response as well as molecules involved in development of fibrosis and giant cells were assessed by immunohistochemistry and real-time PCR. STAT6-induced Th2 immunity leads to up-regulated expression of CD206, SOCS1 and TGF-b in granulomas, in comparison to adjacent tissue. DAP12 and TREM2, molecules regulating giant cell formation, are more strongly expressed in granulomas of NMS patients than in those of MMF, while RAC1 is not up-regulated in both entities. TGF-b co-localizes with CD206 + macrophages in NMS but not in MMF. Conversely, Th1 immunity with STAT1-induced IFN-c and CXCR3 expression in granulomas and the surrounding tissue was elevated, without statistically significant differences. While Th1-mediated immunity is up-regulated in the entire inflamed muscle specimen, Th2-M2 markers are expressed at significantly higher levels in granulomas. These results indicate that muscle tissue per se may provide a permissive environment for M2 polarization in NMS and MMF. Further, DAP12/TREM2-induced giant cell formation and expression of TGF-b in M2 macrophages are hallmarks of NMS and share common activation signalling. http://dx.doi:10.1016/j.nmd.2014.06.083

G.P.70 Classification of perspectives Y. Allenbach 1, W. Stenzel 3 1 Charite, Berlin, France; 3 Charite

inflammatory myopathies- new avenues and future O. Benveniste 2, C. Preusse 3, D. Pehl 3, H. Goebel 3, Germany; 2 Universite´ Pierre et Marie Curie, Paris, – Universita¨tsmedizin, Berlin, Germany

The principal classification of inflammatory myopathies is based on a diagnostic approach combining evaluation of a certain clinical syndrome, laboratory results, electromyography and myoimaging with results of a muscle biopsy analysis. Clinical syndromes have been linked to defined entities, and biopsy results have also been recognized as being characteristic for these entities. Numerous studies have evaluated the impact of certain pathomechanisms like a CD8-mediated, MHC-class I-restricted immune response, deposition of complement or distribution of atrophic fibers. Recently a number of muscle-related auto-antibodies (so called MSAs) have been identified and implicated in disease pathogenicity. However, the spectrum of clinical features in one given disease entity is broad and shows numerous variations, the disease-defining clinical features are not well described. Along that line, the morphological spectrum and associated morphological phenomena of one entity (e.g. dermatomyositis) may also be surprisingly large. Morphology is a crucial diagnostic procedure and includes a number of different steps and techniques, however, we believe that all diagnostic possibilities in daily routine have not yet been fully explored. In most publications, authors promote a small number of described patterns like e.g. perifascicular atrophy, MHC class I expression, C5b9 deposition, immune attack of CD8 + T cells, myofiber necrosis etc. Although