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Treatment of myasthenia gravis 重症肌无力的治疗
Pub Date : 2007-11-07 DOI: 10.4414/sanp.2007.01882
K. V. Toyka, R. Gold, K. V. Toyka
Myasthenia gravis is a prototypic antibody-mediated neurological autoimmune disorder. Its pathogenesis is much better understood than that of multiple sclerosis or immune neuropathies. Currently two targets in the endplate membrane are considered as autoantigens, the acetylcholine receptor (in up to 90%) and the muscle-specific kinase (MuSK, in about 5%). Fortunately, substantial therapeutic progress has been made even before the era of molecular and translational medicine. In this review we characterise modern treatment algorithms that are adapted to disease severity and introduce the principle of escalating treatment strategies for myasthenia gravis. In mild cases and ocular forms of myasthenia gravis treatment with acetylcholine esterase inhibitors may be sufficient, at least temporarily. In generalised myasthenia gravis a wide array of immunosuppressive treatments have been established but most have never been tested in a full-size prospective randomised trial. Up to 10% of patients with myasthenia gravis are associated with a thymoma, i.e. of paraneoplastic origin, and this has to be looked for by CAT scan or MRI. In non-thymoma patients younger than about 50 years of age and with generalised weakness a complete early (but not urgent) thymectomy is considered as state of the art based on circumstantial evidence and expert opinion; the best type of procedure is still under debate. Usually, pretreatment with immunosuppressive medication or plasma-pheresis is recommended. Myasthenic crisis is best treated by plasma-pheresis, mostly combined with immunoadsorption techniques. Intravenous immunoglobulins are a reasonable therapeutic alternative, but a shortage in supply and high prices limit its use. With regard to immunosuppression azathioprine is still the standard base-line treatment, often combined with initial corticosteroids. In rare patients with inborn hepatic enzyme deficiency of thiomethylation azathioprine it is not well tolerated and may be substituted by mycophenolate mofetil. Severe cases may profit from combined immunosuppression with corticosteroids, cyclosporine A and even moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation. All such combination therapies need to be supervised by an experienced academic neuroimmunological centre. Serial measurements of anti-acetylcholine receptor antibodies, once these are elevated, or MuSK antibodies are a useful adjunct for monitoring treatment success. In escalating therapy for very severe cases one may employ monoclonal anti-CD 20 antibodies (rituximab). In highly refractory cases also immunoablation via high-dose cyclophosphamide, followed by trophic factors such as G-CSF has been suggested.
重症肌无力是一种典型的抗体介导的神经自身免疫性疾病。其发病机制比多发性硬化症或免疫神经病变更容易理解。目前,终板膜上的两个靶点被认为是自身抗原,乙酰胆碱受体(高达90%)和肌肉特异性激酶(MuSK,约5%)。幸运的是,甚至在分子医学和转化医学时代之前,就已经取得了实质性的治疗进展。在这篇综述中,我们描述了适应疾病严重程度的现代治疗算法,并介绍了重症肌无力的升级治疗策略原则。在轻度病例和眼部形式的重症肌无力,用乙酰胆碱酯酶抑制剂治疗可能是足够的,至少暂时的。在广泛性重症肌无力中,已经建立了广泛的免疫抑制治疗方法,但大多数从未在全尺寸前瞻性随机试验中进行过测试。高达10%的重症肌无力患者伴有胸腺瘤,即副肿瘤起源,这必须通过CAT扫描或MRI来寻找。在年龄小于50岁且全身虚弱的非胸腺瘤患者中,基于间接证据和专家意见,早期(但不紧急)完全胸腺切除术被认为是最先进的;最好的手术类型仍在争论中。通常,建议使用免疫抑制药物或血浆采血进行预处理。肌无力危象最好的治疗方法是血浆置换,通常与免疫吸附技术相结合。静脉注射免疫球蛋白是一种合理的治疗选择,但供应短缺和高昂的价格限制了它的使用。关于免疫抑制,硫唑嘌呤仍然是标准的基线治疗,通常与初始皮质类固醇联合使用。在罕见的先天性肝酶缺乏症患者中,硫甲基硫唑嘌呤耐受性不佳,可由霉酚酸酯代替。重症患者可联合使用皮质类固醇、环孢素A、甚至中等剂量的甲氨蝶呤或环磷酰胺进行免疫抑制治疗。他克莫司正在接受调查。所有这些联合疗法都需要由经验丰富的学术神经免疫学中心进行监督。连续测量抗乙酰胆碱受体抗体,一旦这些抗体升高,或MuSK抗体是监测治疗成功的有用辅助手段。在升级治疗非常严重的情况下,可以使用单克隆抗cd20抗体(利妥昔单抗)。在高度难治性病例中,建议采用高剂量环磷酰胺免疫消融术,然后使用G-CSF等营养因子。
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引用次数: 7
[Differentiation of anxiety and depression--terminology, clinical and psychological aspects]. [焦虑和抑郁的区分——术语、临床和心理学方面]。
A Schulze

Conceptual, symptomatological, nosological, biological, and anthropological aspects of anxiety and depression are juxtaposed and surveyed. Qualitative and quantitative distinctions, and conditions governing the rise of the syndromes are discussed.

焦虑和抑郁的概念、症状学、疾病学、生物学和人类学方面被并列和调查。定性和定量的区别,和条件控制的上升综合症进行了讨论。
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引用次数: 0
[Pathology of inflammatory diseases of the central nervous system--an autopsy analysis 1967-1988]. [中枢神经系统炎症性疾病的病理学——1967-1988年的尸检分析]。
N Grunow, R Goertchen, D Modelmog, E Goertchen

This paper deals with investigations of CNS-inflammations based on 23,338 autopsies in the period from 1967 to 1988. Inflammatory CNS-findings were observed in 210 cases (0.9 per cent). Their etiology was caused bacterially in 66 per cent and viral infections were found in 20 per cent. Additionally multiple sclerosis appeared in 14 per cent of all CNS-inflammations. The meningitis dominated among the bacterial infections and the leukencephalitis and nekrotizing polioencephalitis of Herpes type among the viral inflammations. The histological classification of the nonbacterial inflammations was difficult or impossible in 9 per cent. A clinical diagnosis was established only in 70 per cent of all cases. Especially babies and patients at the age about 60 or 70 were involved.

本文对1967年至1988年23338例尸体解剖的中枢神经系统炎症进行了研究。210例(0.9%)出现炎性中枢神经系统。它们的病因是细菌引起的占66%,病毒感染占20%。此外,多发性硬化症出现在所有中枢神经系统炎症的14%。细菌性感染以脑膜炎为主,病毒性感染以疱疹型白脑炎和病毒性脊髓灰质炎脑炎为主。9%的非细菌性炎症难以或不可能进行组织学分类。只有70%的病例进行了临床诊断。尤其是六七十岁的婴儿和病人。
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引用次数: 0
[Endogenous psychoses in relation to absent phenylalanine hydroxylase activity in thrombocytes]. [血小板中苯丙氨酸羟化酶活性缺失与内源性精神病的关系]。
E Umann, L Franke

Out of 100 psychotic patients who underwent neurobiochemical examination, in 24 cases activity of phenylalanine hydroxylase in the thrombocytes was found to be absent. 38% of these cases were susceptible to stimulation in vitro by means of folic acid derivative, without actually reaching a normal level of activity. The patients are presented first as a homgeneous group, then in the two major diagnostic divisions, and divided according to the biochemical data. An account is given of early experiences in the treatment of the more intractable cases.

在100例接受神经生化检查的精神病患者中,有24例发现血栓细胞中苯丙氨酸羟化酶活性缺失。这些病例中有38%的人对叶酸衍生物的体外刺激敏感,但实际上没有达到正常的活性水平。患者首先呈现为一个同质组,然后在两个主要的诊断部门,并根据生化数据进行划分。叙述了早期治疗较为棘手的病例的经验。
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引用次数: 0
[Clinical multiplicity of cerebrovascular disorders in childhood]. [儿童脑血管疾病的临床多样性]。
I Georgiev, V Bojinova, R Jotova, L Belopitova

A group of 107 children with vascular diseases of the nervous system aged 3-14 years have been studied. In 100 children of the study group acute disturbances of the brain blood circulation have been found, out of which 37 children were with transitory ischemic attacks; 29 were found to be with brain ischaemia; 22-with haemorrhages (7 cases with subarchnoidal, 9 cases with intracerebral and 6 cases with subarachnoidal-parenchimatose); 5 children had wenous thromboses; 7 children were with spinal strokes. In other 7 children we found the presence of Sturge-Weber syndrome. Congenital vascular malformations have been found in 32 children (30%), out of which 16 children (15%) with loops and stenosis of the extracranial segments of the internal carotid artery, and another 16 children (15%) with AV-malformations. Congenital and acquired heart diseases are found to be primary cause for the strokes in 12 children (11%). Considerable is the rate of the epileptic seizures in the acute stage of the strokes as well as of the residual epileptic syndromes.

本文对107名3-14岁的神经系统血管性疾病儿童进行了研究。在研究组100例患儿中发现急性脑血液循环紊乱,其中37例患儿为短暂性脑缺血发作;脑缺血29例;22例出血(蛛网膜下腔出血7例,颅内出血9例,蛛网膜下腔-脑实质出血6例);静脉血栓5例;脊髓性中风7例。在其他7个孩子中我们发现了斯特奇-韦伯综合症。先天性血管畸形32例(30%),其中颈内动脉颅外段袢狭窄16例(15%),av -畸形16例(15%)。先天性和后天性心脏病是12名儿童中风的主要原因(11%)。相当大的是癫痫发作的比率,在中风的急性阶段,以及残余的癫痫综合征。
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引用次数: 0
[Symptomatic myasthenia as a paraneoplastic syndrome in mixed-cell myelosis?]. [症状性肌无力作为混合细胞骨髓病的副肿瘤综合征?]。
C Hackebeil, H J Matschke
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引用次数: 0
[Action and reaction elements as performance-modifying components of computer use in clinical psychology]. [行为和反应因素作为临床心理学中计算机使用的性能改变因素]。
P Weber, A Krause, O Forgbert, H Leo

Application of computerized equipment in psychodiagnosis and cognitive training entails novel methodical aspects which relate to design of operator and response controls as well as to the test configuration. Some of these aspects are discussed.

计算机设备在心理诊断和认知训练中的应用需要新的系统方面,涉及到操作员和反应控制的设计以及测试配置。本文讨论了其中的一些方面。
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引用次数: 0
[Comments on psychosomatic manifestations in ophthalmology]. [关于眼科心身表现的评论]。
J Salfield
{"title":"[Comments on psychosomatic manifestations in ophthalmology].","authors":"J Salfield","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76385,"journal":{"name":"Psychiatrie, Neurologie, und medizinische Psychologie","volume":"42 12","pages":"764-5"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13249171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Sacro-coccygeal meningocele--a case report on differential diagnosis of urinary incontinence in adulthood]. 【骶尾骨脑膜膨出——成人尿失禁鉴别诊断1例报告】。
E Banzhaf, T Hagemeier, K Herrmann

The case of a 38-year-old woman is reported who developed manifest incontinence of urine following spontaneous parturition on two occasions. An extensive sacrococcygeal meningocele was identified. The paper refers to special features of such clinical after-manifestations.

病例38岁的妇女报告谁发展明显尿失禁后自然分娩两次。发现广泛的骶尾骨脑膜膨出。本文对此类临床后表现的特点进行了探讨。
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引用次数: 0
[The EMBU project--a multinational study of the importance of parental child rearing behavior for the development of psychopathologic phenomena]. [EMBU项目——一项关于父母养育子女行为对精神病理现象发展重要性的多国研究]。
J Richter, M Eisemann, C Perris

The influence of childhood experience on psychological development is discussed from various scientific viewpoints. Against this background, the origin of the cross-cultural, multinational EMBU Project on the relationship between upbringing in the family and psychopathology is described. It becomes obvious that a systematic, cross-cultural, and theory-orientated approach can bring significant material for the development of psychiatric theory.

从不同的科学观点探讨了童年经历对心理发展的影响。在此背景下,本文描述了跨文化、跨国的EMBU项目的起源,该项目研究家庭教养与精神病理学之间的关系。很明显,一个系统的、跨文化的、以理论为导向的方法可以为精神病学理论的发展带来重要的材料。
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引用次数: 0
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Psychiatrie, Neurologie, und medizinische Psychologie
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