眼肌型重症肌无力研究进展及临床问题

在重症肌无力(MG)患者中眼肌型重症肌无力(ocular myasthenia gravis,OMG)是最常见的临床类型,在我国OMG发病率较高。OMG患者表现的眼外肌无力(如上睑下垂)可以直观地显示MG患者的表征特点,以及表现为晨轻暮重或活动     

单纤维肌电图在甲亢伴眼肌型重症肌无力和Graves眼病鉴别诊断中的价值

目的探讨单纤维EMG(SFEMG)技术在甲亢伴眼肌型重症肌无力(OMG)与Graves眼病鉴别诊断中的价值。方法对32例甲亢伴OMG、35例Graves眼病患者进行眼轮匝肌SFEMG测定,分析两组间SFEMG改变的特点。结果在2组患者中,平均颤抖(jitter)值分别为(96. 2±23. 7)、(42. 8±12. 6)μs,jitter 55μs的百分比M50分别为92%、5%,阻滞所占百分比M50分别为25%、0,纤维密度分别为(1. 9±0. 4)、(1. 7±0. 5)。两组比较,甲亢伴OMG患者各SFEMG参数均明显高于Graves眼病患者组(分别t=15. 56,Z=9. 26,Z=7. 35,均P 0. 01)。结论甲亢伴OMG患者的眼轮匝肌SFEMG均表现为jitter明显增宽,可伴有阻滞,与Graves眼病患者明显不同。眼轮匝肌SFEMG测定有助于甲亢伴OMG和Graves眼病的鉴别诊断。     

眼肌型重症肌无力辅助诊断方法对比研究

目的比较冰试验、新斯的明试验、单纤维肌电图(SFEMG)诊断眼肌型重症肌无力的敏感性和特异性,以期建立益于临床开展的诊断流程。方法共116例新发眼睑下垂和(或)复视患者,进行冰试验、新斯的明试验和SFEMG,经随访6个月观察病情变化和试验性治疗效果而最终明确诊断。结果剔除最终诊断不明、失访和随访期间进展为全身型重症肌无力的患者,最终纳入81例患者[包括眼肌型重症肌无力21例和其他疾病引起的眼睑下垂和(或)复视60例],冰试验诊断眼肌型重症肌无力的灵敏度为95.24%(20/21)、特异度为98.33%(59/60),新斯的明试验分别为90.48%(19/21)和85%(51/60),SFEMG分别为95.24%(20/21)和80%(48/60),3种诊断方法仅特异性差异有统计学意义(χ2=5.232,P=0.022),且冰试验的特异度高于新斯的明试验(χ2=5.707,P=0.017)和SFEMG(χ2=6.023,P=0.014)。结论冰试验诊断眼肌型重症肌无力的敏感性和特异性均较高,结合新斯的明试验和SFEMG对眼肌型重症肌无力的早期诊断具有重要临床意义。     

单纤维肌电图在眼肌型重症肌无力中的应用(附80例报告)

目的　研究眼肌型重症肌无力 ( OMG)患者的单纤维肌电图 ( SFEMG)及与其他辅助检查的关系 ,期望对临床诊断提供帮助。方法　对 80例 (男 39例 ,女 4 1例 ) OMG患者低频和高频重复神经电刺激 ( RNS)、伸指总肌 (部分额肌 ) SFEMG和血中乙酰胆碱受体抗体 ( ACh RAb)进行测定。结果　伸指总肌 SFEMG示 ,5 0例( 6 2 .5 % )异常 ,表现为颤抖增宽和阻滞。平均颤抖为 ( 4 5 .2± 2 1 .0 )μs,颤抖 >5 5μs所占百分比为 ( 1 8.2± 2 6 .5 ) ,阻滞所占百分比为 ( 8.7± 1 5 .3)。额肌 SFEMG示 ,8例 ( 80 % )异常 ,平均颤抖为 ( 6 6 .3± 2 6 .8)μs,颤抖 >5 5μs所占百分比为 ( 32 .7± 2 8.5 ) ,阻滞所占百分比为 ( 2 8.0± 2 4 .3) ,明显高于正常对照组 ( P<0 .0 0 1 )。 RNS异常率为 2 8.8% ( 2 3/80 )。 ACh RAb滴度增高占 38.8% ( 2 6 /6 7)。 SFEMG的颤抖和阻滞与 RNS递减的程度呈明显的负相关性。 RNS和 ACh RAb异常组平均颤抖明显高于正常组 ( P<0 .0 0 1 )。但 SFEMG正常组仍有 1 3.3% ( 4 /30 ) RNS异常和 2 6 .7% ( 8/30 ) ACh RAb异常。结论　SFEMG在 OMG患者的辅助检查中阳性率最高 ,与 RNS和 ACh RAb具有互补作用 ,三者结合可有助于 OMG的诊断。     

眼轮匝肌刺激型单纤维肌电图在眼肌型重症肌无力的应用

目的建立眼轮匝肌刺激型单纤维肌电图(SFEMG)正常对照组的颤抖参考值, 并探索其应用于重复神经刺激(RNS)阴性眼肌型重症肌无力(OMG)患者的敏感度及其与各临床指标的关系。方法 2019年1—12月于中山大学附属第一医院神经科肌电图室招募健康志愿者32名, 以建立正常对照组的参考值。收集2019年12月至2023年1月中山大学附属第一医院RNS阴性的OMG患者36例。对患者进行定量MG评分(QMGS), 记录其新斯的明试验、抗体及胸腺CT结果。使用一次性同心圆针电极对一侧眼轮匝肌进行刺激型SFEMG检测, 计算平均连续波间期差(MCD), 与正常对照组的MCD平均值及单个值上限对比以评估颤抖是否异常。将均值异常的MCD值分别与QMGS和抗体滴度进行Spearman相关分析。结果 32名健康人中男性13名, 女性19名, 年龄(46.8±18.7)岁, MCD为(19.0±4.4)μs。所得MCD的参考值上限为平均27.7 μs, 单个37.4 μs, 超过平均值上限或单个值超过上限者占比超过10%为异常。36例OMG患者中男性20例, 女性16例, 年龄(37.2±17.0)岁, ...     

辅助检查方法对新发病重症肌无力的诊断价值

目的 观察辅助检查方法对尚未经免疫治疗的新发病重症肌无力(MG)患者的诊断价值.方法 回顾性分析156例诊断明确的新发病MG患者初诊时的临床电生理检查[主要包括重复电刺激(RNS)和单肌纤维肌电图(SFEMG)]、新斯的明试验、乙酰胆碱受体抗体(AChRAb)等资料.结果 156例新发病MG患者(无Ⅰ型患者)新斯的明试验以及SFEMG、RNS和AChRAb检查阳性者分别为135(86.5%)、129(82.7%)、108(69.2%)和99(63.5%)例.新斯的明试验和SFEMG阳性检出率差异无统计学意义(P>0.05),但均明显高于RNS和AChRAb阳性检出率(P<0.05).结论 MG的诊断需要进行临床综合判断,各项辅助检查不可相互替代.对新发病MG患者规范化的新斯的明实验和SFEMG检查敏感性高.     

Charcot-Marie-Tooth合并重症肌无力两例

<正>1 病例报告病例1:患者男,22岁,货运司机。以"疲劳后双睑下垂18年"于2015年7月就诊。患者3岁无明显诱因出现右侧眼睑下垂,症状呈波动性,晨轻暮重,就诊于当地医院,查血清乙酰胆碱受体抗体增高(资料不详),新斯的明试验阳性,当地诊断为"重症肌无力(MG)",口服溴吡斯的明(用量不详)症状可改善。8岁时于当地医院行胸腺手术后眼睑下垂逐渐缓解。2013年复发至此次就诊期间,疲劳后双侧眼睑下垂,偶有双影,晨轻暮重,重体力劳动后     

欧洲神经病学联盟发表眼肌型重症肌无力治疗指南

<正>2014年初,欧洲神经病学联盟(EFNS)发表了眼肌型重症肌无力(OMG)的治疗指南[1]。指南对OMG的定义为无力局限于眼外肌和提上睑肌的重症肌无力(MG)。实际上,OMG是一个动态的概念,研究发现大约80%的OMG将发展到全身受累,因此OMG治疗指南围绕改善眼肌症状和阻止向全身型发展这两个主题进行指导。现将主要证据类别、推荐级别和相关问题做一摘要介绍。1胆碱酯酶抑制剂尚无相关随机对照试验(RCT),但病例系列研究和临床经验均显示胆碱酯酶抑制剂有明确的疗     

慢性进行性眼外肌瘫痪1例报告

慢性进行性眼外肌瘫痪(CPEO)是线粒体肌病的一种,临床少见,现报告1例如下. 1 病例女,51岁.因"双眼睑下垂28年,加重伴双下肢无力2年"于2008年6月23日入院.患者28年前无明显诱因渐起双眼睑下垂,并逐渐加重以至双睑完全不能上提,无晨轻暮重、复视及视力下降;27年前在当地医院行双侧上睑重塑手术后双上睑能正常上提及闭合.     

重症肌无力患者眼轮匝肌单纤维肌电图检测

目的 探讨重症肌无力患者眼轮匝肌单纤维肌电网(SFEMG)检查的临床应用价值.方法 40例重症肌无力患者(眼肌型27例,全身型13例)分别接受眼轮匝肌单纤维肌电图[以平均颤抖值>正常值上限、>10%单个肌纤维对颤抖增宽(>55μs)、伴或小伴阻滞作为异常颤抖判断标准]和面神经重复神经电刺激(RNS)检查(以复合肌肉动作电位衰减>15%作为异常动作电位判断标准),比较两种电生理学检查方法的阳性检出率、敏感性和特异性,以及SFEMG测值与重症肌无力分型之间的关系.结果 重症肌无力患者眼轮匝肌平均颤抖值为(76.42±24.59)μs,颤抖增宽电位对比例(69.01±26.66)%,阻滞电位对比例(46.62±27.41)%,与对照组比较差异具有统计学意义(均P<0.05).SFEMG阳性检出率为82.50%(33/40),高于RNS(35%,14/40),差异具有统计学意义(P<0.05).SFEMG检查敏感度分别为82.50%和77.50%,特异度均为100%;RNS检查敏感度分别为27.50%和22.00%,特异度均为0.结论 眼轮匝肌单纤维肌电图是诊断重症肌无力较为敏感的电生理学检查方法,应用于临床时尚需与其他肌肉单纤维肌电图检查、重复神经电刺激检查及乙酰胆碱受体抗体试验相结合.     

眼肌型重症肌无力干预后状态

目的 评估溴吡斯的明、激素、胸腺切除、胸腺切除-激素联合4种治疗对于以眼肌型重症肌无力(OMG)起病的患者干预后状态的差异.方法 对180例OMG患者进行回顾加前瞻性临床研究,患者起病年龄≥15岁,根据患者接受的治疗非随机性入组,分为手术组60例、激素组39例、联合组31例、对症组50例.按照美国重症肌无力基金会标准以干预后状态仅余"轻微异常"为理想状态.结果 ①激素组治疗后3～6个月,睑下垂、眼肌麻痹、总体理想状态率相对高于其他3组,其中,42.1%(16/38)的患者治疗3个月睑下垂达到理想状态,高于对症组(7/48,14.6%,×2=8.200,P=0.004).②联合组、手术组从治疗后1年起,各项理想状态率呈上升趋势,以联合组略高于手术组;观察期终末21.7%(13/60)手术组患者达到完全缓解;纵向配对比较,手术组治疗2年后睑下垂(22/40,55.0%)、眼肌麻痹(16/27,59.3%)和总体效果(20/40,50.0%)达理想状态率均显著高于治疗3个月后[11/59,18.6%;11/44,25.0%;9/60,15.0%;P=0.002、0.031、0.000(此处无统计值,仅有P值)].③选择对症治疗的患者平均起病年龄(51.9±18.0)岁,高于其他3组(F=10.563,P=0.000).④伴有眼肌麻痹的OMG患者更倾向于选择激素或联合治疗,联合组眼肌麻痹率高于对症、手术2组(×2=12.939、14.380,均P=0.000),激素组眼肌麻痹率高于手术组(×2=8.017,P=0.005).结论 对于以OMG起病的青中年患者,激素治疗起效快,胸腺切除、联合治疗长期疗效好,激素甚或联合治疗可能是伴有眼肌麻痹者较好的选择.     

The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis

The eye movements of 100 patients with multiple sclerosis were examined clinically, including a saccade test. Thirty-four cases of internuclear ophthalmoplegia were found, of which 14 were bilateral and 20 were unilateral. Only three patients had full restriction of adduction, whereas 16 had no restriction at all. A continuous dissociated nystagmus was present in one patient only, while in 15 just a few beats of the abducting eye could be observed. In ten cases both restriction of adduction and dissociated nystagmus were lacking, and the diagnosis could only be made with the saccade test, which in all 34 patients showed a clearly visible disjunction of horizontal saccades. In 15 cases, infrared oculography was performed, which in all cases confirmed the clinical findings, and which in some cases disclosed an additional subclinical internuclear ophthalmoplegia on the opposite side.     

Painful ophthalmoplegia: the Tolosa-Hunt syndrome and orbital pseudotumor syndrome

We experienced 9 patients with "painful ophthalmoplegia", which included 7 cases of the Tolosa-Hunt syndrome (2 males and 5 females, with ages ranging from 36 to 65 years) and 2 cases of the orbital pseudotumor syndrome (2 females aged 42 and 68). The diagnosis of these syndromes was based upon Hunt's criteria and the presence of the intraorbital mass on the brain CT scan. Main manifestations of both syndromes were periorbital pain and ipsilateral oculomotor nerve palsies. Out of 9 cases, 1 patient with Tolosa-Hunt syndrome and 1 patient with the orbital pseudotumor syndrome had bilateral retro-orbital pain and ophthalmoplegia. Pain preceded the ophthalmoplegia except in one patient with Tolosa-Hunt syndrome. Total paralysis of the extraocular muscles supplied by the oculomotor nerve was noted in all the nine patients, and mydriasis was observed on the affected side in 4 of 7 patients with Tolosa-Hunt syndrome and 2 patients with the orbital pseudotumor syndrome. Neurological involvement was not only the oculomotor nerve but also the other cranial nerves; the optic nerve (in 4 cases with Tolosa-Hunt syndrome and 2 cases with the orbital pseudotumor syndrome), the abducens nerve (in 3 cases with Tolosa-Hunt syndrome and 1 case with the orbital pseudotumor syndrome), and the first division of the trigeminal nerve (in 2 cases with Tolosa-Hunt syndrome). Six patients with Tolosa-Hunt syndrome and 2 patients with the orbital pseudotumor syndrome had palpebral edema. Visual disturbance and palpebral edema were severer in the patients with the orbital pseudotumor syndrome. After corticosteroid hormone was administered, there was diminution of the pain within 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-Ri-Antibody-Associated Paraneoplastic Syndrome in a Man with Breast Cancer Showing a Reversible Pontine Lesion on MRI

Background

Paraneoplastic neurological disorders associated with anti-Ri-antibodies, which are typically present with opsoclonus-myoclonus-ataxia. Most cases with anti-Ri-antibodyassociated paraneoplastic syndrome due to breast cancer occur in women - its occurrence in men is extremely rare.

Case Report

We present herein the case of a male patient with breast cancer who had atypical anti-Ri-antibody-associated paraneoplastic syndrome presenting as complete horizontal ophthalmoplegia, left trigeminal sensory symptoms, and truncal ataxia. Following the diagnosis of paraneoplastic syndrome, chemotherapy and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri-antibodies 14 weeks later, his symptoms persisted.

Conclusions

To our knowledge, this is the first case report of ophthalmoplegia without opsoclonus-myoclonus in a male anti-Ri-antibody-positive patient with breast cancer.     

Vergence disorders in patients with spinocerebellar ataxia 3/Machado-Joseph disease: a synoptophore study

Diplopia, a common symptom in spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) cases, is not always due to asymmetric ophthalmoplegia. We found a Japanese SCA3/MJD family, in which three patients clearly had an impairment of divergence eye movement. We thus quantitatively examined the vergence ranges in eight Japanese SCA3/MJD cases using the synoptophore test. An impairment of the vergence eye movements was found in all patients, and the vergence impairment pattern, but not the ophthalmoplegia pattern, was found to be compatible with the diplopia pattern. The diplopia in SCA3/MJD cases is, therefore, attributed, at least in part, to the impairment of the vergence eye movements.     

Abduction nystagmus in internuclear ophthalmoplegia

We tested the hypothesis that abnormalities of the abducting eye in internuclear ophthalmoplegia reflect an adaptive process that helps overcome the adduction weakness of the opposite eye. This response operates under the constraints of Hering's law of equal innervation: any attempt to increase the innervation to a weak muscle in one eye must be accompanied by a commensurate increase in innervation to the yoke muscle in the other eye. In 4 patients with internuclear ophthalmoplegia, we patched one eye for 1 to 5 days to allow time for the central nervous system to optimize innervation for the habitually viewing eye. We predicted that there would be a conjugate adjustment of innervation that would diminish the abduction overshoot and backward postsaccadic drift made by the habitually viewing eye. This was the case in 3 of our 4 patients. Our findings show that the abduction nystagmus is a manifestation of a normal adaptive response in some patients with INO.     

The one-and-a-half syndrome--a unilateral disorder of the pontine tegmentum: a study of 20 cases and review of the literature

The one-and-a-half syndrome is a clinical disorder of extraocular movements characterized by a conjugate horizontal gaze palsy in one direction plus an internuclear ophthalmoplegia in the other. The syndrome is usually due to a single unilateral lesion of the paramedian pontine reticular formation or the abducens nucleus on one side (causing the conjugate gaze palsy), with interruption of internuclear fibers of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral abducens nucleus (causing failure of adduction of the ipsilateral eye). Twenty cases are reported; 14 had multiple sclerosis.     

慢性进行性眼外肌麻痹的临床、病理及诊断（附6例报道）

目的:探讨慢性进行性眼外肌麻痹(CPEO)的临床、病理及诊断。方法:对6例CPEO患者的临床表现、病理特点进行分析并与另5组CPEO比较。结果:6例患者中男3例,女3例,平均起病年龄13岁。2例为同胞兄弟。6例均有进行性加重的双睑下垂和眼球活动障碍,其中1例起病不对称。除眼外肌麻痹外,3例闭目肌力减退、1例轻度吞咽困难、1例轻度肢体无力。3例伴内分泌功能异常。肌活检破碎红纤维(RRF)阳性肌纤维数和细胞色素氧化酶(cytochromeoxidase,COX)阴性肌纤维数均明显>2%。结论:CPEO的主要临床表现为进行性发展的眼外肌麻痹,可伴肢体肌无力、视网膜色素变性、听力障碍、心脏传导异常、内分泌异常等。诊断主要依赖临床和肌肉活检中发现>2%的RRF 肌纤维、COX-肌纤维。     

Total ocular akinesis: Miller Fisher or Guillain-Barré syndrome?

Total, bilateral ophthalmoplegia is very rare. More than 50% of cases are Miller Fisher (MFS) and Guillain-Barré (GBS) syndromes. There is a correlation of MFS with anti-GQ1b antibodies. High levels of GQ1b gangliosides are found in myelin sheathes of cranial nerves supplying the extraocular muscles. This may explain the association of anti-GQ1b antibodies with ophthalmoplegia. Anti-GQ1b were also found in cases of GBS accompanied by ophthalmoplegia, atypical MFS (MFS without ataxia), MFS/GBS overlap syndromes and Bickerstaff brainstem encephalitis. This has led some authors to classify them as 'anti-GQ1b syndromes'. In this article we describe a diagnostically difficult case of a patient with a very rare, total bilateral paralysis of all ocular muscles, accompanied by bilateral ptosis, diminished tendon reflexes of upper extremities, paresis and hypoesthesia of the left upper extremity.     

A case of anti-GQ1b-positive atypical Fisher syndrome with internal ophthalmoplegia but without external ophthalmoplegia]

We report a 21-year-old man who developed an atypical form of Fisher syndrome. One week after having a common cold, he was admitted to our hospital because of a gait disturbance. Neurological examination revealed a somnolent state, cerebellar ataxia, areflexia, limb muscle weakness, and numbness in a glove and stocking like distribution. The patient had internal ophthalmoplegia but did not have external ophthalmoplegia. Brain MRI showed no abnormality in the orbital and the pretegmental brain regions. The protein level in the cerebrospinal fluid was 57 mg/dl and the cell count was 5 mononuclear cells/mm3. His serum titer of anti-GQ1b IgG antibody was markedly elevated. There have been only two previous reports of isolated internal ophthalmoplegia with elevated anti-GQ1b antibody. The present case suggests that anti-GQ1b antibody play an important role in the pathogenesis of patients who present with internal ophthalmoplegia but without external ophthalmoplegia.