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G.P.17.10 Macrophagic myofasciitis-associated cognitive dysfunction
886
Abstracts / Neuromuscular Disorders 17 (2007) 764–900 1
G.P.17.08 Expressions of FOXO in inflammatory myositis Ishii, A. 1,*; Ohkoshi, N. 2; Tamaoka, A. 1 1 University of Tsukuba, Neurology, Tsukuba, Japan; of Technology, Neurology, Tsukuba, Japan
Henri Mondor Hospital, APHP; INSERM U841, Creteil, France; Henri Mondor Hospital, APHP, Creteil, France; 3 Henri Mondor Hospital, APHP, Reference Centre for Neuromuscular Disorders, Creteil, France 2
2
Tsukuba University
Background: FOXO transcription factors are believed to be negatively regulated by IGF-1 signaling pathway and promote atrophy in skeletal muscle. Objective and hypotheses: To demonstrate that FOXO family plays an important role in muscle atrophy associated with inflammatory muscle disease. Methods: Diagnostic limb muscle biopsies of patients with inflammatory myositis (5 patients with dermatomyositis (DM), 10 patients with polymyositis (PM), and 5 patients with inclusion body myositis (IBM)) were used for immunohistochemical analysis. Results: No FOXO1 staining was found in the muscle samples from DM, PM, and IBM. FOXO3a staining in the muscle fibers was found in PM specimens. In IBM, strong FOXO3a staining was found at atrophic muscle fibers with vacuole. In DM, atrophic fibers locate in perifascicule were also stained by FOXO3a. Conclusion: Our data suggest that FOXO3a plays a critical role in the development of muscle atrophy in inflammatory myositis. doi:10.1016/j.nmd.2007.06.414
G.P.17.09 Clinical and pathological features of focal myositis Rodolico, C. 1,*; Mazzeo, A. 1; Toscano, A. 1; Gaeta, M. 2; Aguennouz, M. 1; Vita, G.L. 1; Russo, M. 1; Vita, G. 1 1 University of Messina, Neurosciences, Psychiatry and Anaesthesiology, Messina, Italy; 2 University of Messina Radiological Sciences, Messina, Italy Focal myositis (FM) is a rare and misdiagnosed muscle disorder characterised by focal muscle enlargement with histopathological features of an inflammatory myopathy and fibrosis. Progression to polymyositis (PM) has rarely been reported. To describe clinical, muscle magnetic resonance (MR) and pathological features of FM and to find pathogenic differences between FM and systemic forms of idiopathic inflammatory myopathies. We studied 12 patients with FM (19–72 yrs). Two had a dropped head due to a focal involvement of paraspinal cervical muscles, and 10 a lower limb FM. The diagnosis was based on clinical features electromyography, MR imaging and muscle biopsy. Muscle samples from 5 patients with PM, 5 patients with dermatomyositis (DM) and 5 patients with inclusion body myositis (IBM) were used as disease control. Immunohistochemistry for MHC class I antigens, immunoreactive cells and metalloproteinases (MMP) 2, 7 and 9 was performed. MR imaging showed hyperintensity of the damaged muscle. FM resolved in 8 cases after prednisone therapy, 4 patients recovered without any medication. Various morphological changes were observed. Areas of fibrosis were seen in three cases. Endomysial infiltrates constituted by a mixed population of macrophages, T-cells and sporadic B-cells were found in all patients. MHC I class molecules were expressed in FM with a pattern similar to that seen in systemic idiopathic inflammatory myopathies. MMP9 was increased in all patients, whereas MMP2 and MMP7 were not expressed only in FM. Muscle MR represents a very useful technique for the diagnosis and follow-up of patients with FM. The present study confirms cell-mediated origin of the inflammatory process in FM. doi:10.1016/j.nmd.2007.06.415
G.P.17.10 Macrophagic myofasciitis-associated cognitive dysfunction Couette, M. 1; Boisse, M. 1; Gherardi, R. 1; Brugieres, P. 2; Cesaro, P. 2; Chevalier, X. 2; Bachoud-Levi, A. 1; Authier, F. 3,*
Background: Macrophagic myofasciitis (MMF) is a rare emerging entity, characterised by specific deltoid muscle lesions assessing long-term persistence of aluminium hydroxide after intramuscular immunization. MMF patients mainly complained of chronic arthromyalgias, fatigue, and cognitive impairment. The present study aimed to characterize the MMF-associated cognitive dysfunction (MACD) and assess its genuineness. Methods: All MMF patients routinely evaluated at Henri Mondor University Hospital underwent brain MRI and a comprehensive battery of neuropsychological tests. We retrospectively analyzed data obtained from 25 consecutive unselected patients, and delineated the neuropsychological profile of MACD. Then MMF patients were compared with chronically painful controls, matched for age, educational level, pain, fatigue and depression, in order to free from non specifc factors and assess the genuineness of MACD. Findings, and Interpretation: Neuropsychological evaluation was abnormal in all MMF patients, at least one test reaching dementia threshold in 24/25 (96%). Results did not correlate with pain, fatigue, depression or brain MRI findings. Affected domains were (i) immediate/differed visual memory and short term verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) dichotic listening. When compared with diseased controls, MMF patients displayed distinctive impairment of visual memory, working memory and dichotic listening. Such pattern is suggestive of cortico– subcortical organic damages involving fronto-parieto-thalamo-striatal areas, with deep white matter alterations. Pathophysiology of MACD is unknown but its neuropsycological pattern suggests that it could originate from inflammatory or toxic processes. doi:10.1016/j.nmd.2007.06.416
G.P.17.11 Syrian hamster infected with Leishmania infantum: A new experimental model for inflammatory myopathies Paciello, O. 1,*; Gradoni, L. 2; Oliva, G. 3; Politano, L. 4; Papparella, S. 1 1 University of Naples Federico II, Department of Pathology and Animal Health, Naples, Italy; 2 Istituto Superiore di Sanita`, Rome, Italy; 3 University of Naples Federico II, Department of Veterinary Clinical Science, Naples, Italy; 4 Second University of Naples, Department of Exp Med Cardiomyology and Med. Genet, Naples, Italy Idiopathic inflammatory myopathies (IIMs) are inflammatory disorders of unknown origin. On the basis of clinical, histopathlogical and immunological features, they can be differentiated in three major and distinct subsets: dermatomyositis, polymyositis and inclusion-body myositis. The aetiology and pathogenesis of idiopathic inflammatory myopathies remain poorly understood. A few animal models for idiopathic inflammatory myopathies are currently available; however, these models lack of several characteristic aspects of IIMs. Aim of our study was to examine skeletal muscle involvement in an experimental animal model of visceral leishmaniasis and to compare the pattern of inflammation with that of human idiopathic inflammatory myopathies. To this goal Syrian hamsters, infected intraperitoneally with 107 amastigotes of Leishmania infantum – a protozoan parasite causing myositis in naturally-infected dogs (Paciello et al. 2006) -, were sacrificed at 3 or 4 months postinfection and the skeletal muscles were studied. The serum values of CK, LDH, and AST enzymes were highly increased. In muscle specimens, focal inflammation was predominantly observed in the endomysium and, to a lesser extent, in perivascular areas. Degenerating muscle fibers were also found, as well as myonecrosis. Immunofluorescence with confocal laser scanning microscopy was used to characterize the phenotype of inflammatory infiltrates and the distribution of MHC class I and MHC class II. The infiltrating
Abstracts / Neuromuscular Disorders 17 (2007) 764–900 1
G.P.17.08 Expressions of FOXO in inflammatory myositis Ishii, A. 1,*; Ohkoshi, N. 2; Tamaoka, A. 1 1 University of Tsukuba, Neurology, Tsukuba, Japan; of Technology, Neurology, Tsukuba, Japan
Henri Mondor Hospital, APHP; INSERM U841, Creteil, France; Henri Mondor Hospital, APHP, Creteil, France; 3 Henri Mondor Hospital, APHP, Reference Centre for Neuromuscular Disorders, Creteil, France 2
2
Tsukuba University
Background: FOXO transcription factors are believed to be negatively regulated by IGF-1 signaling pathway and promote atrophy in skeletal muscle. Objective and hypotheses: To demonstrate that FOXO family plays an important role in muscle atrophy associated with inflammatory muscle disease. Methods: Diagnostic limb muscle biopsies of patients with inflammatory myositis (5 patients with dermatomyositis (DM), 10 patients with polymyositis (PM), and 5 patients with inclusion body myositis (IBM)) were used for immunohistochemical analysis. Results: No FOXO1 staining was found in the muscle samples from DM, PM, and IBM. FOXO3a staining in the muscle fibers was found in PM specimens. In IBM, strong FOXO3a staining was found at atrophic muscle fibers with vacuole. In DM, atrophic fibers locate in perifascicule were also stained by FOXO3a. Conclusion: Our data suggest that FOXO3a plays a critical role in the development of muscle atrophy in inflammatory myositis. doi:10.1016/j.nmd.2007.06.414
G.P.17.09 Clinical and pathological features of focal myositis Rodolico, C. 1,*; Mazzeo, A. 1; Toscano, A. 1; Gaeta, M. 2; Aguennouz, M. 1; Vita, G.L. 1; Russo, M. 1; Vita, G. 1 1 University of Messina, Neurosciences, Psychiatry and Anaesthesiology, Messina, Italy; 2 University of Messina Radiological Sciences, Messina, Italy Focal myositis (FM) is a rare and misdiagnosed muscle disorder characterised by focal muscle enlargement with histopathological features of an inflammatory myopathy and fibrosis. Progression to polymyositis (PM) has rarely been reported. To describe clinical, muscle magnetic resonance (MR) and pathological features of FM and to find pathogenic differences between FM and systemic forms of idiopathic inflammatory myopathies. We studied 12 patients with FM (19–72 yrs). Two had a dropped head due to a focal involvement of paraspinal cervical muscles, and 10 a lower limb FM. The diagnosis was based on clinical features electromyography, MR imaging and muscle biopsy. Muscle samples from 5 patients with PM, 5 patients with dermatomyositis (DM) and 5 patients with inclusion body myositis (IBM) were used as disease control. Immunohistochemistry for MHC class I antigens, immunoreactive cells and metalloproteinases (MMP) 2, 7 and 9 was performed. MR imaging showed hyperintensity of the damaged muscle. FM resolved in 8 cases after prednisone therapy, 4 patients recovered without any medication. Various morphological changes were observed. Areas of fibrosis were seen in three cases. Endomysial infiltrates constituted by a mixed population of macrophages, T-cells and sporadic B-cells were found in all patients. MHC I class molecules were expressed in FM with a pattern similar to that seen in systemic idiopathic inflammatory myopathies. MMP9 was increased in all patients, whereas MMP2 and MMP7 were not expressed only in FM. Muscle MR represents a very useful technique for the diagnosis and follow-up of patients with FM. The present study confirms cell-mediated origin of the inflammatory process in FM. doi:10.1016/j.nmd.2007.06.415
G.P.17.10 Macrophagic myofasciitis-associated cognitive dysfunction Couette, M. 1; Boisse, M. 1; Gherardi, R. 1; Brugieres, P. 2; Cesaro, P. 2; Chevalier, X. 2; Bachoud-Levi, A. 1; Authier, F. 3,*
Background: Macrophagic myofasciitis (MMF) is a rare emerging entity, characterised by specific deltoid muscle lesions assessing long-term persistence of aluminium hydroxide after intramuscular immunization. MMF patients mainly complained of chronic arthromyalgias, fatigue, and cognitive impairment. The present study aimed to characterize the MMF-associated cognitive dysfunction (MACD) and assess its genuineness. Methods: All MMF patients routinely evaluated at Henri Mondor University Hospital underwent brain MRI and a comprehensive battery of neuropsychological tests. We retrospectively analyzed data obtained from 25 consecutive unselected patients, and delineated the neuropsychological profile of MACD. Then MMF patients were compared with chronically painful controls, matched for age, educational level, pain, fatigue and depression, in order to free from non specifc factors and assess the genuineness of MACD. Findings, and Interpretation: Neuropsychological evaluation was abnormal in all MMF patients, at least one test reaching dementia threshold in 24/25 (96%). Results did not correlate with pain, fatigue, depression or brain MRI findings. Affected domains were (i) immediate/differed visual memory and short term verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) dichotic listening. When compared with diseased controls, MMF patients displayed distinctive impairment of visual memory, working memory and dichotic listening. Such pattern is suggestive of cortico– subcortical organic damages involving fronto-parieto-thalamo-striatal areas, with deep white matter alterations. Pathophysiology of MACD is unknown but its neuropsycological pattern suggests that it could originate from inflammatory or toxic processes. doi:10.1016/j.nmd.2007.06.416
G.P.17.11 Syrian hamster infected with Leishmania infantum: A new experimental model for inflammatory myopathies Paciello, O. 1,*; Gradoni, L. 2; Oliva, G. 3; Politano, L. 4; Papparella, S. 1 1 University of Naples Federico II, Department of Pathology and Animal Health, Naples, Italy; 2 Istituto Superiore di Sanita`, Rome, Italy; 3 University of Naples Federico II, Department of Veterinary Clinical Science, Naples, Italy; 4 Second University of Naples, Department of Exp Med Cardiomyology and Med. Genet, Naples, Italy Idiopathic inflammatory myopathies (IIMs) are inflammatory disorders of unknown origin. On the basis of clinical, histopathlogical and immunological features, they can be differentiated in three major and distinct subsets: dermatomyositis, polymyositis and inclusion-body myositis. The aetiology and pathogenesis of idiopathic inflammatory myopathies remain poorly understood. A few animal models for idiopathic inflammatory myopathies are currently available; however, these models lack of several characteristic aspects of IIMs. Aim of our study was to examine skeletal muscle involvement in an experimental animal model of visceral leishmaniasis and to compare the pattern of inflammation with that of human idiopathic inflammatory myopathies. To this goal Syrian hamsters, infected intraperitoneally with 107 amastigotes of Leishmania infantum – a protozoan parasite causing myositis in naturally-infected dogs (Paciello et al. 2006) -, were sacrificed at 3 or 4 months postinfection and the skeletal muscles were studied. The serum values of CK, LDH, and AST enzymes were highly increased. In muscle specimens, focal inflammation was predominantly observed in the endomysium and, to a lesser extent, in perivascular areas. Degenerating muscle fibers were also found, as well as myonecrosis. Immunofluorescence with confocal laser scanning microscopy was used to characterize the phenotype of inflammatory infiltrates and the distribution of MHC class I and MHC class II. The infiltrating