眼肌无力的诊断及依据

重症肌无力是乙酰胆碱受体抗体介导的,细胞免疫依赖及补体参与的神经-肌肉接头处（NMJ）传递障碍的自身免疫性疾病。眼肌症状是最为多见的首发症状,表现为上眼睑下垂、复视、斜视等,尤以眼睑下垂最多。通过典型的临床表现及临床实验即可诊断、腾喜龙试验、血清抗体检测、电子诊断可以进一步确诊。     

Saccadic eye movements analysis in the early diagnosis of myasthenia gravis

Saccadic eye movements were examined by electro-oculography in 21 patients with suspected myasthenia gravis. The presence of dissociated nystagmus and quiver eye movements was also assessed. The aim of the study was to assess the diagnostic value of saccadic abnormalities in the early stage of the disease. Pathological oculographic findings consisted of intra and post saccadic disorders and intersaccadic variability. A fatigue test was useful in detecting latent disorders in most patients. A Tensilon test was positive in 11 out of 16 patients with oculographic abnormalities. Diagnostic problems, apparently paradoxical findings and differential involvement of extraocular muscle fibers are discussed.

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Sommario In ventuno pazienti con sospetta miastenia gravis sono stati studiati, mediante elettro-oculografia, i movimenti oculari saccadici. è stata anche valutata la presenza di nistagmo dissociato e di movimenti oculari “vivaci”. Scopo del lavoro è stato la valutazione dell'importanza diagnostica dell'analisi dei movimenti oculari saccadici nelle fasi precoci della malattia. I disturbi della motilità oculare consistevano in deficit intra e post saccadici e nella variabilità intersaccadica. Il test di affaticamento oculare si è dimostrato utile nell'evidenziare deficit subclinici nella maggioranza dei pazienti. Dei 16 pazienti con anormalità dei movimenti oculari saccadici, solo 11 hanno mostrato una positività del test al Tensilon. Sono stati presi in considerazione problemi diagnostici, risultati apparentemente paradossali e interessamento differenziato delle fibre della muscolatura oculare estrinseca.

     

Clinical differences of early and late-onset myasthenia gravis in 985 patients

Objective: The clinical differences of early-onset myasthenia gravis (EOMG) and late-onset MG (LOMG) have not been elucidated in China. In order to clarify this, a retrospective study was conducted in 985 MG patients, whose disease duration was longer than 3 years.

Methods: These patients were separated into EOMG and LOMG according to the onset age of 50 years. The clinical differences including demographics, clinical features, thymus abnormalities and comorbidities of EOMG and LOMG patients were analyzed.

Results: Results indicated that 485 were males and 500 were females, 714 were EOMG and 271 were LOMG. Female was more common in EOMG and male was more common in LOMG (p = 0.003). The peak onset age was 0–4 years in EOMG and 55–59 years in LOMG. Ocular MG (OMG) was more common in EOMG and generalized MG (GMG) was more common in LOMG (p = 0.004). The transformation rate of OMG to GMG was higher in LOMG (p = 0.002). The positive incidence of repetitive nerve stimulation (RNS) was higher in EOMG (p = 0.026). Thymoma was more frequent in LOMG (p = 0.017) and thymic hyperplasia was more frequent in EOMG (p < 0.001). Hyperthyroidism was more common in EOMG (p = 0.017) and diabetes was more common in LOMG (p < 0.001).

Conclusion: These results have potential significance for the recognition of clinical features and the determination of management strategies in EOMG and LOMG.     

Fiberoptic endoscopic evaluation of swallowing with simultaneous tensilon application in diagnosis and therapy of myasthenia gravis

Background Dysphagia is a common symptom in myasthenia gravis (MG). Clinical examination alone fails to detect and grade myasthenic dysphagia sufficiently. For a more precise examination of swallowing function in myasthenia gravis additional technical tools are necessary. Objective To investigate the diagnostic and therapeutic impact of fiberoptic endoscopic evaluation of swallowing with simultaneous Tensilon application (FEES-Tensilon Test) in myasthenia gravis. Methods FEES-Tensilon Test was performed following a standardized protocol. Four severely affected patients with dysphagia as their leading symptom were examined. Dysphagia was characterized by five salient endoscopic findings: leakage, delayed swallowing reflex, penetration, aspiration and residues. If a normalisation or at least an improvement of swallowing function occurred shortly after Tensilon administration the FEES-Tensilon Test was rated as being positive. Results In three patients the FEES-Tensilon Test successfully detected MG-related dysphagia. In one patient with dysphagia caused by oculopharyngeal muscular dystrophy the FEES-Tensilon Test was truly negative. Beside an early diagnosis of MG-related dysphagia, the FEES-Tensilon Test was useful in the differentiation between myasthenic and cholinergic crisis and in guiding treatment decisions. In all patients the FEES-Tensilon Test was superior to clinical evaluation of dysphagia. No severe side effect occurred while performing the FEES-Tensilon Test. Conclusion The FEES-Tensilon Test is a suitable tool in the diagnosis and therapy of myasthenia gravis with pharyngeal muscles weakness.     

The effect of prednisone on the progression from ocular to generalized myasthenia gravis

Fifty percent of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia, 90% within 3 years from the onset of ocular symptoms. This study was performed to determine whether treatment with oral prednisone initiated and completed within 2 years from the onset of ocular symptoms would affect the progression of ocular myasthenia to generalized myasthenia gravis (GMG). Fifty-six patients were included in this review, with 27 patients in the prednisone-treated group and 29 patients in the untreated group. The treated group was initiated on 60 mg of prednisone daily with a slow taper over 3-6 months. At 2 years, significantly fewer patients in the treated group (3 of 27) progressed to generalized myasthenia when compared to the untreated group (10 of 29) (chi(2), p=0.04). Our results suggest that the early use of steroids may decrease progression of ocular to generalized myasthenia gravis. The decision to use steroids should be considered early in the course of patients diagnosed with ocular myasthenia gravis. This study should be considered preliminary and a prospective trial is warranted to confirm our observations.     

眼肌型重症肌无力患者发生眼外肌以外肌群受累的相关因素研究

目的探讨眼肌型重症肌无力患者发生眼外肌以外肌群受累的相关因素研究。方法回顾性分析在本院就诊的眼肌型重症肌无力患者440例,根据临床分型将随访患者分为转化组和未转化组,并对2组患者的基本资料做单因素分析,经单因素分析确定相关影响因素,对相关影响因素做多因素线性回归分析,确定独立影响因素。结果眼肌型重症肌无力患者发生肌外群受累的相关影响因素为年龄的分布,RNS异常(面部神经异常,尺神经异常,副神经异常),胸腺瘤异常,甲状腺异常以及激素治疗,多因素分析结果显示,面神经,尺神经,胸腺瘤及激素治疗为眼肌型重症肌无力患者发生肌外群受累的独立影响因素。结论面神经、尺神经,胸腺瘤以及激素治疗为眼肌型重症肌无力患者发生肌外群受累的独立影响因素,在临床治疗的过程中要对以上检测指标异常的患者提起高度的重视,可有效提高该类患者的生存质量。     

Benefits of FK 506 for refractory eye symptoms in a young child with ocular myasthenia gravis

Recently, there have been many reports on the efficacy and safety of tacrolimus (FK506) treatment for adult patients with intractable generalized myasthenia gravis (MG). There have also been a few reports of successful FK506 therapy in patients with severe childhood-onset generalized MG involving a myasthenic crisis. Herein, we report the efficacy of FK 506 for refractory ocular symptoms in a 3-year-old girl with ocular type MG. Ptosis and alternating strabismus had appeared at 10 months of age. No bulbar signs, respiratory failure or generalized muscle weakness had been seen during her course. Her ocular symptoms had persisted despite repeated steroid pulse therapy, high dose oral prednisolone and thymectomy. Adverse effects of steroids, including obesity, growth retardation, osteoporosis, cataracts and hyperlipidemia, gradually worsened. After obtaining written informed consent from her parents, we started oral tacrolimus at a dose of 0.5 mg/day and her symptoms resolved completely within 3 weeks at a maximum dose of 2.5 mg/day. No adverse effects, such as renal failure or glucose intolerance, were seen. FK506 treatment allowed the steroid dose to be reduced, eliminating its adverse effects. In patients with intractable childhood-onset MG with ocular manifestations, FK506 is an alternative to steroid therapy or thymectomy.     

糖皮质激素冲击治疗后重症肌无力早期一过性加重的机制研究

目的 探讨糖皮质激素冲击(GI)治疗后重症肌无力(MG)早期一过性加重的机制.方法 选取2012年1月～2013年6月诊治的125例MG患者,并给予GI治疗,统计分析并进行治疗前后临床评分和血清抗胆碱受体抗体滴度(AchR-Ab)、免疫球蛋白IgG和补体C3水平、肌电图检测.结果 GI治疗MG后,7天有效率为57.78％,28天有效率为75.56％,其中肌无力一过性加重发生率为36.0％;肌无力加重后患者临床绝对评分明显高于加重前,差异具有统计学意义(P＜0.05);桡神经和腋神经低频重复电刺激波幅递减程度明显高于加重前,差异具有统计学意义(P＜0.05);加重前后患者血清AchR-Ab、IgG和C3水平差异均无统计学意义(P＞0.05).结论 GI治疗MG后,具有早期一过性加重发生的风险,这可能与激素抑制神经递质的传递有关,但与体内抗体、补体水平变化无关.     

The best and worst of times in therapy development for myasthenia gravis

Within the last 5 years, the US Food and Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN) inhibitors for treatment of generalized myasthenia gravis, and several other therapies are in late-stage clinical trials or under regulatory review. However, questions about which patients are most likely to benefit from which therapies, and the relative effectiveness of these very expensive drugs, has resulted in uncertainty around the place that they should occupy in the existing therapeutic armamentarium. MGNet (a Rare Diseases Clinical Research Consortium funded by the National Institute of Neurological Diseases and Stroke) held two meetings during the 14th International Conference of the Myasthenia Gravis Foundation of America to discuss the most critical needs for clinical trial readiness and biomarker development in the context of therapy development for myasthenia gravis. Herein we provide a summary of these discussions, but not a consensus opinion, and offer a series of recommendations to guide focused research in the most critical areas. We welcome ongoing discussion through comments on this work.     

Evaluation and validation of sustained upgaze combined with the ice-pack test for ocular myasthenia gravis in Asians

The accuracy of the ice-pack test for diagnosing myasthenia gravis (MG) has been reported to be excellent, however, the sensitivity is low in patients with mild ptosis which is common in Asians who have absent or low double eyelid folds. Herein, we performed the ice-pack test after sustained upgaze and tested its validity for diagnosing MG. The study included 30 newly diagnosed MG patients with ptosis (median age 47 years, range 2–87 years) and 30 controls with ptosis other than MG (median age 58 years, range 5–83 years). All MG patients initially presented with ptosis and/or diplopia; 26 patients had purely ocular MG while 4 patients progressed to generalized MG. All patients performed the new ice-pack test after sustained upgaze for 2 min. The ice-pack test was judged positive if there was an improvement of at least 2?mm of margin reflex distance compared to the level of ptosis before (conventional ice-pack test) or after (new ice-pack test) sustained upgaze. Subgroup analysis was performed according to the level of ptosis. The conventional test showed 43.3% sensitivity and 100% specificity for diagnosing MG, while the new ice-pack test achieved 73.3% sensitivity and 96.7% specificity, respectively. In patients with mild ptosis, the sensitivity and specificity for diagnosing MG were 27.8% and 100% by the conventional test, and 72.2% and 96.7% by the new ice-pack test, respectively. The new ice-pack test combined with sustained upgaze was more sensitive for diagnosing MG, particularly in patients with mild ptosis which is common in Asians.     

Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis

Introduction: Several studies have reported high diagnostic sensitivity and specificity for the ice test in myasthenia gravis. All of the studies employed a case–control design, in which the diagnosis was already known at the time of the test for both patients and controls, leading to case selection bias. This suggests that the available literature substantially overestimates the diagnostic utility of these tests. Methods: A retrospective cohort study without selection bias was performed to examine the sensitivity and specificity of the ice test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ice test were determined by means of a 2 × 2 table. Results: The ice test has a sensitivity of 0.92 (95% CI 0.62–1.00), specificity of 0.79 (95% CI 0.56–1.00), PPV of 0.73 (95% CI 0.48–0.90), and NPV of 0.94 (95% CI 0.70–1.00). Conclusions: Due to its high negative predictive value the ice test is still a reliable and useful bed‐side test. Muscle Nerve 48 : 902–904, 2013     

HLA-DQ基因多态性对重症肌无力遗传易患性的相关研究

目的：探讨HLA－DQ基因多态性与重症无力（MG）易患性的相关性。方法：运用聚合酶链反应－限制片段长度多态性（PC－RFLP）法对60例MG病人进行HLA－DQA1、DQB1基因分型。结果：DQA1位点：病人按不同胸腺组织,不同发病年龄及性别分组,与对照组比较,都有DQA1＊0301频率的明显增高,差异有显著性;DQB1位点;MG病人组（包括亚组）与对照组比较,都有DQB1＊0303频率明显增高,DQB1＊0601和DQB1＊0602频率明显降低,差异都有显著性意义,结论：DQA1＊0301与胸腺增生型和≤30岁发病的男性MG病人易患者有关,DQB1＊0303与MG的易患性有关,而DQB1＊0601和DQB1＊0602是保护基因。     

Anti AChR antibody: Relevance to diagnosis and clinical aspects of myasthenia gravis

227 sera from myasthenic patients were tested for the presence of anti-AChR antibodies (anti-AChR Abs) by mean of a fetal calf receptor (Fc-AChR); 73.5% of cases proved positive with this method. Significant correlations were found between presence of anti-Fc-AChr Abs and various clinical aspects such as: clinical stage and duration of disease; moreover significantly higher than the median titers were found among younger patients (i.e. age <40 yrs). This work was partially supported by the National Research Council (CNR) — Progetto Finalizzato “Medicina Preventiva e Riabilitativa” n^o 85.00513.56     

Repetitive ocular vestibular evoked myogenic potential stimulation for the diagnosis of myasthenia gravis: Optimization of stimulation parameters

ObjectiveTo determine the most effective stimulation parameters for the diagnosis of ocular myasthenia gravis (MG) using repetitive ocular vestibular evoked myogenic potentials (oVEMP) for quantification of the extraocular muscle response decrement.MethodsRepetitive bone-conducted oVEMPs were elicited in 18 MG patients and 20 healthy subjects. We compared four different stimulus repetition rates (20 Hz, 30 Hz, 40 Hz, 50 Hz) and 100 Hz continuous stimulation, as well as recordings from the inferior oblique muscles and the lateral rectus muscles to determine the most sensitive and specific oVEMP parameters for decrement detection.ResultsRepetitive stimulation at all tested repetition rates with recordings from inferior oblique muscles allowed for effective differentiation between MG patients and healthy subjects. Among all repetition rates, 30 Hz showed a trend towards superiority, with a sensitivity of 71% and a specificity of 94% (area under the curve (AUC) 0.88) when using the smaller decrement of the two eyes and −10% as cutoff. Considering the larger decrement for analysis (−9% as cutoff), sensitivity increased to 82%, but specificity decreased to 78% (AUC 0.81).ConclusionsOur study demonstrates, that repetitive oVEMP stimulation elicits a robust decrement in the inferior oblique muscles of MG patients at repetition rates between 20 Hz and 50 Hz, with a probable optimum at 30 Hz.SignificanceRepetitive inferior oblique oVEMP stimulation with optimal stimulus parameters facilitates early and accurate diagnosis of ocular MG.     

Ocular myastyenia gravis: The diagnostic yield of repetitive nerve stimulation and stimulated single fiber EMG of orbicularis oculi muscle and infrared reflection oculography

For the diagnosis of ocular myasthenia gravis (ocular MG), testing of the muscles close to the affected ones may be important. The relative importance of several methods: stimulated single fiber EMG (stimulated SFEMG), repetitive nerve stimulation test (RNS) of orbicularis oculi muscle, and infrared reflection oculography (IROG) was investigated. Thirty-two patients in whom a diagnosis of ocular MG was considered on clinical grounds were admitted to the study. Based on the results of the three neurophysiological tests, the patients could be divided in three groups: a first group with an abnormal stimulated SFEMG, and an abnormal RNS and/or abnormal IROG; a second group with only a slightly abnormal stimulated SFEMG; and a third group with normal tests in all three tests. The clinical diagnosis of ocular MG was made in all 11 patients of the first group; in 86% (6 of 7) of the patients of the second group; and in 7% (1 of 14) of the patients of the third groups. This study demonstrates that the orbicularis oculi muscle is a suitable muscle for stimulated SFEMG in patients with ocular MG, and that the results obtained with this technique showed a better relation with the clinical diagnosis than those of the two other techniques. We also demonstrate that there is no additional value in studying the jitter with different stimulation rates in patients with suspected ocular MG. © 1993 John Wiley & Sons, Inc.     

重症肌无力血清乙酰胆碱受体抗体的阳性率及其影响因素

采用ABC-ELISA法检测162例重症肌无力患者的224份血清标本,100例正常人和78例其他疾病病人的血清中AchRab。重症肌无力病人的抗体阳性率为80.2％,其中单纯眼肌型63.1％,脊髓肌型90.0％,延髓肌型93.8％和全身肌型91.5％。合并胸腺瘤的阳性率为83.3％,与全组阳性率无显著性差异。激素和血浆交换治疗均未影响抗体阳性结果。随访观察表明,重症肌无力病人的AchRab阳性率与疾病严重程度不成线性相关。我们认为,AchRab滴度虽然与临床状况不相关,但在重症肌无力的诊断和自身免疫病因的研究中,仍是一项重要参数。     

伴胸腺异常重症肌无力患者对糖皮质激素治疗的反应性

目的探讨不伴其他自身免疫性疾病的重症肌无力(MG)患者胸腺异常对糖皮质激素治疗的反应性及其临床意义。方法回顾性分析2000-01—2014-12长海医院神经内科确诊并使用糖皮质激素治疗的86例MG不伴免疫性疾病患者的临床与生化检查结果资料,根据激素治疗后患者临床症状改善状况,将患者分为激素治疗敏感组与不敏感组,并比较两组间的临床及生化检查结果特征;根据是否伴有胸腺异常分为无胸腺异常组与伴胸腺异常组,比较两组间激素治疗的反应性;分析MG患者胸腺异常与激素治疗反应的相关性。结果激素治疗敏感组与不敏感组间患者性别、年龄50岁、病程3年、起病方式、上呼吸道感染、肠道泌尿道感染、累及肌群、血糖异常比例以及白细胞、C反应蛋白、红细胞沉降率水平比较差异无统计学意义(P0.05),两组间胸腺异常、血脂异常患者比例比较有统计学差异(P0.05);伴胸腺异常组与无胸腺异常组间激素治疗敏感者比例比较有统计学差异(χ~2=5.01,P=0.03);胸腺异常与激素治疗不敏感发生率呈正相关(r=0.237,P=0.03)。结论胸腺异常降低MG不伴免疫性疾病患者对激素治疗的疗效,认识两者之间的关系有助于MG患者的临床治疗评估及预后判断。