重症肌无力患者红细胞免疫功能的变化

为了探讨重症肌无力（ＭＧ）患者红细胞免疫功能的变化，我们测定了２０１例ＭＧ患者外周血ＲＢＣ－Ｃ３ｂ受体花环率（ＲＢＣ－Ｃ３ｂＲＲ）和ＲＢＣ－ＩＣ花环率（ＲＢＣ－ＩＣＲ）和５０名正常人进行对照。结果为ＭＧ患者的ＲＢＣ－Ｃ３ｂＲＲ（７．５８±３．４％）明显低于正常对照组（１２．８７±５．０７％）（Ｐ＜０．０１），ＲＢＣ－ＩＣＲ（５．８３±４．６２％）稍高于正常对照组（５．０３±３．８４％）（Ｐ＞０．０５），ＭＧ全身型组ＲＢＣ－Ｃ３ｂＲＲ（５．２５±１．８５％）明显低于眼肌型组（８．５９±３．１９％）（Ｐ＜０．０１），强的松治疗前组（７．９８±４．０１％）与治疗后组（１１．６４±４．３５％）有明显差异（Ｐ＜０．０１），强的松治疗前后ＲＢＣ－ＩＣＲ的变化无统计学意义。上述结果表明ＭＧ患者红细胞免疫粘附功能低下与ＭＧ发病有一定的相关性。ＭＧ的发病不仅有体液免疫功能障碍，还可能有红细胞免疫功能障碍，我们的资料为ＭＧ免疫病原学发病机理提供了一项新的实验依据，也可为免疫治疗ＭＧ评定疗效提供客观辅助指标。     

Mitochondrial function in myasthenia gravis

We determined the respiration rate, respiratory control and ADP/O ratios, with different substrates in mitochondria isolated from 2 patients with myasthenia gravis and compared them with normal human muscle. In all cases studied, a severe alteration of the respiratory control with variable derangement of oxidative phosphorylation was found. This abnormality of mitochondrial metabolism was referred to by Luft as 'loosely coupled' and was reported in other neuromuscular diseases. In our opinion this defective oxidative metabolism is nonspecific.     

Lymphocyte function in myasthenia gravis.

Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia.     

Ⅰ型重症肌无力患者呼吸功能状况评估

目的研究Ⅰ型重症肌无力(MG)患者的呼吸功能状况与健康人的差异,并对比研究应用抗胆碱酯酶药后患者肺功能状况的改变.方法46例MG患人和50例健康人,分别行肺功能(肺活量、第1秒用力呼气量、用力肺活量、1秒率、吸气量、最大呼吸流量容积曲线、最大通气量、残气容积)、和血气分析(pH、PaCO2、PaO2)和血氧饱和度(SaO2)检测.MG患者在检测肺功能之后平静休息30 min以上,肌注抗胆碱酯酶药(新斯的明1 mg)后30 min再次检测肺功能.结果(1)MG患者肺功能状况显著低于健康人,但其动脉血气水平和SaO2与健康人比较无显著性差异;(2)MG患者在应用新斯的明之后肺功能状况有明显的改善.结论MG患者尽管平静状态下无呼吸困难,但呼吸功能状况已有潜在性损害,当有肺部感染、需要麻醉手术治疗等情况时,应密切注意其肺功能状况.     

重症肌无力对执行功能的影响

目的 研究重症肌无力(MG)对执行功能的影响.方法 采用数字符号转换测验(SDMT)、连线测验(TMT)、Stroop色词测验(SCWT)、言语流畅性测验(VFT)等执行功能认知测验,对36例全身型MG患者(全身型组)、33例眼肌型MG患者(眼肌型组)及36名健康体检者(正常对照组)进行执行功能检查.结果 与正常对照组比较,全身型组SDMT评分明显降低(P＜0.01),TMT-1计时、TMT-2计时和错误提醒次数的评分均明显增高(均P＜0.01),SCWT(A、B、C)说错个数和SCWT(C)计时的评分均明显增高(均P＜0.01),VFT动物及家中用品计时的评分明显增高,正确个数的评分明显降低(均P＜0.01);眼肌型组VFT动物计时的评分明显增高,家中用品正确个数的评分明显降低(均P＜0.01).与眼肌型组比较,全身型组SCWT(B、C)说错个数的评分均明显增高(均P＜0.01).结论 MG患者存在执行功能障碍,提示MG可能存在中枢神经系统额叶的损害.     

Left ventricular long-axis function in myasthenia gravis

Abstract   Myasthenia gravis (MG) primarily affects skeletal muscles, but influence on cardiac function has been suggested. The aim of this study was to assess left ventricular long-axis function in MG patients compared to healthy controls, and to examine whether any MG-related heart involvement was influenced by the acetylcholine-esterase inhibitor pyridostigmine. We found that early diastolic atrioventricular-plane velocity and tissue Doppler peak systolic strain was lower in MG patients than in controls before pyridostigmine. The differences disappeared following administration of pyridostigmine. Also, tissue velocities at systole and early diastole tended to be lower in patients before pyridostigmine. In multivariate analyses adjusting for between-group differences in blood pressure, MG was no longer associated with lower longaxis function. Conventional echocardiographic measures of left ventricular diastolic and systolic function did not differ between groups. In conclusion, this study, using modern tissue Doppler imaging as well as conventional echocardiography, could not demonstrate definite MG-related cardiac involvement in a group of MG patients without known cardiac disease, but indicates that pyridostigmine-responsive MG-related alterations in cardiac muscle function exist in MG patients.     

Prednisone-induced worsening of neuromuscular function in myasthenia gravis

In patients with myasthenia gravis who received single doses of prednisone orally (40 to 100 mg), we found acute inhibition of neuromuscular function as manifest by increased decremental responses to repetitive nerve stimulation, reduced twitch tension, and lowered maximum voluntary contraction strength. The time course of these changes correlated with plasma methylprednisolone levels, implying direct drug effects on neuromuscular function.     

Detection and characterization of MuSK antibodies in seronegative myasthenia gravis

Antibodies to rat muscle specific kinase, MuSK, have recently been identified in some generalized "seronegative" myasthenia gravis (SNMG) patients, who are often females with marked bulbar symptoms. Using immunoprecipitation of (125)I-labelled-human MuSK, 27 of 66 (41%) seronegative patients were positive, but 18 ocular SNMG patients, 105 AChR antibody positive MG patients, and 108 controls were negative. The antibodies are of high affinity (Kds around 100 pM) with titers between 1 and 200 nM. They bind to the extracellular Ig-like domains of soluble or native MuSK. Surprisingly they are predominantly in the IgG4 subclass. MuSK-antibody associated MG may be different in etiological and pathological mechanisms.     

Assessment of esophageal function in patients with myasthenia gravis

Background: Myasthenia gravis (MG) is an autoimmune disease in which impairment of neuromuscular transmission results in a pathological fatigability of striated muscles. Dysphagia is a common symptom in MG. It is caused by a weakness of the striated muscles in the pharynx and esophagus. The purpose of our study was to evaluate the role of esophageal scintigraphy in the assessment of esophageal function in MG. Methods: In 15 patients with clinically proven MG (oculopharyngeal manifestation in 6/15 patients, generalized weakness in 9/15 patients) esophageal transit was investigated scintigraphically with a multiple swallow test protocol. 10/15 patients had a history of dysphagia. Patients were studied twice: under baseline conditions, and immediately after pharmacological stimulation with 10 mg of edrophonium chloride (EC), a short-acting acetylcholinesterase inhibitor. Results: Under baseline conditions all patients showed an impaired esophageal function (emptying [%]= 58 % ± 21; normal range > 85 %). In 14/15 individuals esophageal transit improved after administration of EC (emptying [%]= 75 % ± 18; p < 0.01), reaching the normal range in 6 patients. One patient showed no effect attributable to EC. Conclusions: Esophageal transit is often compromised in MG. Functional abnormalities may be also present in patients without a history of dysphagia. Inhibition of cholinesterase positively affects striated muscles in the pharynx and upper esophagus, thus improving esophageal transit. Esophageal scintigraphy may be considered as a simple, non-invasive method for diagnosing impairment of esophageal function in MG and to monitor the changes under pharmacological stimulation. Received: 20 August 2002, Received in revised form: 11 December 2002, Accepted: 18 December 2002 Correspondence to Rainer Linke, MD     

Pulmonary function tests and blood gases in worsening myasthenia gravis

The aim of this study was to determine whether pulmonary function tests have a role in predicting the need for ventilation support in myasthenia gravis. Medical records were reviewed for 42 patients with severe myasthenia gravis who required 55 admissions to the intensive care unit. Patients with a vital capacity of more than 20 ml/kg, a maximal expiratory pressure more than 40 cm H(2)O, or a maximal inspiratory pressure more negative than -40 cm H(2)O are unlikely to require mechanical ventilation. A decline of 30% or more in maximal inspiratory pressure predicted a group at higher risk of requiring mechanical or noninvasive ventilation. Hypercapnia was frequent and was more common in patients who required mechanical ventilation. Worsening of these pulmonary function and blood gas values in patients with myasthenia gravis may guide decisions about intubation and ventilatory support.     

T suppressor cell function in patients with myasthenia gravis

The activities of Con A-induced Suppressor Cells (Con-ASC) were determined in 50 patients with myasthenia gravis (MG) and 24 healthy controls. The ConA-SC activity of the patients with MG was significantly decreased as compared with that of the controls (10.06%) versus 25.28%, (P less than 0.01). Furthermore, the patients with generalized myasthenia gravis (GMG) had a lower ConA-SC activity than those with extraocular muscle myasthenia gravis (EMMG) (9.37% versus 12.13%, P less than 0.05), but their serum anti-acetylcholine receptor antibody titer was higher than that of patients with EMMG (20.55 x 10(-9) M versus 2.4 x 10(-9) M, P less than 0.01). No correlation found between the ConA-SC activity and the sex or duration of disease of the MG patients. And no effects of prednisone and thymectomy were found on the ConA-SC activity of MG patients. The results of the study suggested that the decreased function of suppressor T lymphocytes might play an important role in the pathogenesis of MG.     

Central acetylcholine receptor function in patients with myasthenia gravis

There are some reports on central nervous system involvements in patients with myasthenia gravis, such as abnormal EEG, and memory disturbance. Myasthenia gravis is considered to be an autoimmune disease with antibodies against the skeletal nicotinic acetylcholine receptor (n-AChR). ACh is a neurotransmitter in osmoregulation. Neuronal n-AChR plays an important role in this regulation. In order to investigate the function of neuronal n-AChR in patients with myasthenia gravis, we performed a 5% hypertonic saline infusion test on 9 patients and 9 healthy volunteers. We also carried out an orthostatic stress test (50 degree passive head-up tilt) on 6 patients with myasthenia gravis and 5 healthy controls to evaluate arginine-vasopressin (AVP) release via baroreceptors. Three of the 9 MG patients showed exaggerated plasma AVP secretion, and one revealed a blunt response to hypertonic stimulation. Both patients and controls did not differ significantly in terms of plasma AVP response to orthostatic stress. To conclude, we suggest the possibility that function of neuronal n-AChR in the central nervous system is impaired in patients with myasthenia gravis.     

Detection of immune complexes in the sera and around the muscle fibers in a case of myasthenia gravis and polymyositis

A case of myasthenia gravis accompanied with polymyositis and malignant thymoma, detected immune complexes in the sera and around the muscle fibers, was described. A 37-year-old woman was admitted to Shinshu University Hospital in September, 1987 because of dyspnea, dysphagia and muscle weakness. She first noticed her right blepharoptosis 3 weeks before admission. Weakness of all four limbs and myalgia of lower extremities were noticed one week later. These symptoms got worse and nocturnal dyspnea, dysphagia and easy fatigability at mastication appeared. On admission, she looked ill and neurological examination revealed left blepharoptosis, bilateral facial weakness, weakness of all four limbs, more prominent in proximal muscles and tenderness of lower extremities. Edrophonium test was positive, improving her muscle weakness. Laboratory examination revealed the elevated serum levels of CK, the increased titre of circulating immune complexes and high titres of acetylcholine receptor antibodies and anti-skeletal muscle antibodies. Electromyographic study showed myogenic pattern and Harvey-Masland test revealed waning at low frequency stimulation. Muscle biopsy showed marked perivascular infiltration of lymphocytes, accompanied by phagocytosis and interstitial fibrosis. IgG deposits were shown around the muscle fibers exclusively around the infiltrates of mononuclear cells. Granular deposits of C3 were also shown specifically around the muscle fibers exclusively around the infiltrates of mononuclear cells. Thymectomy was performed on September 21, 1987. Invasion of thymoma, predominantly lymphocytic type, to right lung and pericardium was observed histologically. After thymectomy, she got better. Immunological data and immunohistochemical examination of the present case suggest that in the case of myasthenia gravis accompanied with polymyositis and malignant thymoma, immune complexes may play a primary role on the pathogenesis of myositis.     

Morphologic and immunologic studies in experimental autoimmune myasthenia gravis and myasthenia gravis.

An indirect immunoperoxidase technique was used to study by light microscopy the binding of serum from experimental autoimmune myasthenia gravis (EAMG) rabbits to junctionally and extrajunctionally located acetylcholine receptors (AChRs) in human and rat muscles. Binding was restricted to junctional AChR. Alpha bungarotoxin (a-BGT) partially blocked the binding of EAMG serum, while myasthenia gravis serum, carbamylcholine, decamethonium, and tubocurarine did not. A radioimmunoassay showed significant binding of antibodies in EAMG sera to 125l AChR. This binding was not inhibited by a-BGT, nor by carbamylcholine, decamethonium, or tubocurarine. Sera from 10 myasthenia gravis patients did not contain antibodies binding to the 125l AChR. We suggest that EAMG in rabbits induced by Torpedo AChR differs serologically from myasthenia gravis in patients, probably owing to antigenic differences between Torpedo and human AChR, and that antigenic differences also exist between junctional and extrajunctional receptors.     

Videofluoroscopic assessment of swallowing function in patients with myasthenia gravis

Swallowing function in myasthenia gravis (MG) was investigated by videofluoroscopy (VF). A total of 23 VF examinations were performed on 11 MG patients at various time points over the exacerbation and remission stages of disease. The assessment parameters on VF examination are set as follows: bolus transport from the mouth to the pharynx, bolus holding in the oral cavity, velopharyngeal seal, tongue base movement, pharyngeal constriction, laryngeal elevation, upper esophageal sphincter (UES) opening, and bolus stasis at the pyriform sinus (PS). Aspiration was also assessed on VF examination. Aspiration was seen in 34.8%, and half of these cases involved silent aspiration. Three of four cases that showed silent aspiration went on to experience aspiration pneumonia during the follow-up term. By Spearman's rank correlation, disturbance of laryngeal elevation was significantly correlated with aspiration (p=0.001), and incomplete UES opening was not significantly, but tended to be, correlated with aspiration (p=0.067). Although other parameters in the oral and pharyngeal phase on VF examination, such as bolus transport from the oral cavity to the pharynx, pharyngeal constriction, or stasis at the PS, were remarkably disturbed (in more than 50% of the examinations), those parameters were not good indicators for aspiration. When a disturbance of laryngeal elevation is found at a bedside clinical test, we recommend performing precise swallowing evaluation, such as VF, Fiberoptic Endoscopic Evaluation of Swallowing (FEES), and/or scintigraphic assessment of swallowing, for MG patients, to detect silent aspiration.