多发性肌炎的动物模型及雷公藤多甙对其疗效的研究

目的　寻找一种多发性肌炎的良好动物模型及其有效的治疗药物。　　方法　给动物注射同种大鼠的肌匀浆 ,观察其活动状态 ;通过肌肉组织染色及ELISA法 ,研究肌肉的病理学变化 ,同时给动物喂服雷公藤多甙观察药物疗效。　　结果　部分动物表现肌无力和肌萎缩 ,大多数肌肉组织学检查示肌纤维炎性变 ;免疫组化检查可见肌膜、肌内膜和肌束膜中有IgG沉积。动物服雷公藤多甙后肌肉病变明显减轻 ,其疗效与强的松相似。　　结论　用同种大鼠肌匀浆免疫动物可诱导出多发性肌炎的动物模型 ;雷公藤多甙能有效地治疗多发性肌炎。     

Pathogenesis of neuroimmunologic diseases

Animal models of autoimmune diseases have greatly improved our current understanding of the pathogenesis of human autoimmunity and have provided the potential for therapies based on manipulation of the immune system. In our laboratory, we have investigated the immunopathogenesis of autoimmune diseases of the nervous system and muscle. We have developed immune-based approaches for the suppression of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), and experimental autoimmune neuritis (EAN), a model for the Guillain-Barré syndrome (GBS). These approaches included induction of peripheral tolerance, immunotoxin targeting of activated T cells, and cytokine manipulations. In addition, we identified the antigen and characterized immunopathologically an autoimmune inflammatory disease of skeletal muscle, experimental autoimmune myositis (EAM), a model for the human inflammatory muscle disease polymyositis.     

West Nile virus encephalitis with myositis and orchitis

This report documents the hospital course and autopsy findings of a 43-year-old man with a renal allograft who died of West Nile virus (WNV) encephalitis. Central nervous system (CNS) findings were those of severe necrotizing and hemorrhagic encephalitis affecting gray matter regions limited to the diencepahlon, rhombencephalon, spinal cord, and limbic system. The bilateral process exhibited preferential involvement of motor neurons. Brain imaging obtained 6 days before death demonstrated an unusual pattern of involvement corresponding with the autopsy findings, confirming that imaging may be a specific diagnostic guide in WNV encephalitis. Extra-CNS findings include myositis with T-lymphocyte infiltration of nerve fibers, suggesting that the virus may reach the CNS via peripheral nerves. Orchitis with dense T-lymphocyte infiltration and syncytial cell formation thought to be due to WNV were also noted.     

Expression of growth associated protein 43 and neural cell adhesion molecule in congenital fibre type disproportion with interstitial myositis

We report on the expression of growth associated protein (GAP)43 and neural cell adhesion molecule (NCAM) in congenital fibre type disproportion (CFTD) with myopathological additional signs of interstitial myositis. We assume that sarcolemmal GAP43 in developmental disordered myocytes plays a role in maintenance of growth morphology. In muscular dystrophy light microscopical evaluation reveals no GAP43 immunoreactivity in regenerating fibres. The expression of GAP43 seems to be a characteristic feature of CFTD. The expression of NCAM, particularly in the sarcolemma of small muscle fibres of CFTD, indicates a functional state of permanent partial denervation. Whether the steroid-responsive interstitial myositis is pathogenetically related to CFTD or a coincidental inflammation is not known. Because of the clinical and myopathological data the differential diagnosis of Emery-Dreifuss muscular dystrophy is considered.     

CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

The prion protein in human neuromuscular diseases

The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC-PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress-response effect in various neuromuscular disorders.     

Inflammatory and non-inflammatory inclusion body myositis

Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.     

Localized nodular myositis and the diagnosis of the localized muscle mass

Localized nodular myositis (LNM) is a rare variant of polymyositis beginning with inflammatory nodules within muscles. Only seven cases have so far been reported in the literature. We describe a probable further case of LNM in a 67-year-old man with ischemic claudication of the left leg for three years who presented with painful nodules in the left gastrocnemius muscle and signs of systemic disease; a complete follow-up was not possible, because the patient died after only two months and autopsy was not performed. Muscle biopsy showed localized areas of necrotic and inflammatory pleomorphic changes, in keeping with the features of the other known cases. The ultrastructural findings (not previously reported in this disease) were characterized by marked changes of endomysial capillaries, with fibroblastic metamorphosis of the endothelial cells, and by the presence of filamentous inclusions in the myonuclei. The differential diagnosis of LNM from other localized muscle masses, chiefly from muscle infarct, is discussed.

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Sommario La miosite nodulare localizzata è una rara variante della polimiosite caratterizzata all'esordio da noduli infiammatori circoscritti nell'ambito delle masse muscolari, di cui sono stati sinora descritti solo sette casi. Viene qui riportata un'ulteriore osservazione in un uomo di 67 anni, sofferente di claudicatio ischemica alla gamba sinistra da 3 anni, che aveva presentato noduli dolorosi al muscolo gastrocnemio sinistro e segni di malattia sistemica; il paziente morí dopo 2 mesi, e non fu possibile eseguire autopsia. La biopsia muscolare mostrò aspetti localizzati di necrosi e infiltrazione pleiomorfa, in accordo con le precedenti osservazioni. L'indagine ultrastrutturale (mai descritta finora in quest a malattia) mostrò gravi alterazioni dei capillari endomisiali con metamorfosi fibroblastica delle cellule endoteliali, e presenza di inclusioni filamentose nei mionuclei. La diagnosi di miosite nodulare localizzata viene discussa nell'ambito delle varie forme di tumefazioni circostritte dei muscoli, con particolare riguardo all'infarto muscolare.

     

Hybrid Assistive Limb® for sporadic inclusion body myositis: A case series

We evaluated the efficacy of rehabilitation therapy with Hybrid Assistive Limb® (HAL; hereafter HAL therapy) in three patients diagnosed with sporadic inclusion body myositis (sIBM) who were hospitalized to undergo HAL therapy. Among them, one patient participated in eight courses and the other two in two courses of HAL therapy between 2017 and 2020. We determined the mean rate of improvement in two-minute walking distance and 6 m walking speed at the time of hospital discharge. After HAL therapy, we confirmed the patients’ desire to continue the use of HAL. In one patient, we observed improvements of 146.0% and 120.0% in two-minute walk and 6 m walking speed, respectively, after the first course of HAL therapy; these values are 133.7% and 130% after the eighth course of HAL therapy. These values exceeded 90% in the other two patients after the second course of HAL therapy. HAL therapy maintained both quantity and quality of ambulation and showed positive psychological effects on patient conditions because it reduces exercise load and facilitates safety. While HAL therapy might be effective in maintaining and improving ambulation in patients with sIBM, we should consider to discontinue HAL therapy as it increased risk of falling.     

A Child with Benign Acute Childhood Myositis After Influenza

Background: Benign acute childhood myositis (BACM) is a rare transient muscle syndrome classically occurring in children after a viral upper respiratory infection (URI). BACM causes difficulty walking due to severe bilateral calf pain. The incidence of this well-described phenomenon is uncertain but infrequent, and it is typically appreciated during times of large influenza outbreaks and epidemics. The URI symptoms that precede BACM are consistent with an uncomplicated viral influenza infection and include fever, malaise, cough, sore throat, headache, and rhinitis. Objectives: Little is written in the Emergency Medicine literature regarding this clinical entity. In this report, a brief review of BACM from the current literature is provided, as well as tools to aid in differentiating it from more severe but similar disorders such as rhabdomyolysis and Guillain-Barré syndrome. Case Report: We present a case of BACM in a 7-year-old boy who presented to the emergency department after a resolving URI with the acute onset of calf pain causing alarming difficulty in his ability to walk. His presentation was typical for BACM and his condition improved with supportive treatment. Conclusions: Although quite alarming and potentially puzzling to the physician who is not familiar with BACM, this syndrome is self limited and spontaneously resolves with no specific intervention. Recognition of this rare but distinct clinical entity by the emergency physician can spare a patient from potentially unneeded invasive testing and hospital admission.