人体免疫球蛋白治疗多灶性运动神经病

运动神经元病、脊髓性肌萎缩、背髓灰质炎后肌萎缩、氨基已糖苷酯酶A缺乏、铅中毒及多灶性运动神经病(MMN)均以无感觉障碍的进行性肢体无力及肌萎缩为主要临床表现,但只有MMN是可以治疗的疾病,其诊断依据包括进行性非对称性的下运动神经元瘫痪,电生理检查提示多灶性运动纤维脱鞘伴部分运动传导阻滞,感觉诱发电位正常,血清抗糖脂抗体(antiglycolipid antibodies)滴度升高。血清抗糖脂抗体的出现、免疫抑制剂治疗有效及诸多与CIDP相同的电生理特点提示MMN的发病机制与免疫介导有关、强地松和血浆交换未取得满意疗效。环磷酰胺(cyclophosphamide,CTX)是目前报道的唯一可改善MMN症状的免疫抑制剂,但常有严重的副作用。本文作者应用人体免疫球蛋白(HIG)治疗了9例MMN,取得较好疗效。     

多灶性运动神经病

多灶性运动神经病(MMN)是一种近年来新被认识的神经疾病，临床特征为：不对称的的肌无力，肌萎缩，伴束颤和痉挛，常见于上肢。诊断依据是：神经传导有持续性，多灶性、部分运动传导阻滞(PMCBs)，局限于运动神经，病理学检查发现传导阻滞(CB)部们有慢性脱髓鞘改变。血清抗GMI抗体等常有升高，环磷酰胺及大剂量免疫球蛋白治疗取得临床进步，这一切提示本病与免疫机制有关。     

多灶性运动神经病研究动态

多灶性运动神经病(multifocal motor neuropathy,MMN)是一种由免疫介导的多灶性周围神经病,主要表现为缓慢进展的非对称性肢体无力,以上肢远端为主,一般不累及或很少累及感觉神经;电生理特点为持续性节段性运动神经传导阻滞(couduction block,CB);部分患者神经节苷脂GM1抗体滴度升高;对免疫球蛋白及环磷酰胺治疗有效,对激素无效.下面就近几年对MMN各方面的研究进行综述.     

多灶性运动神经病的研究进展(综述)

多灶性运动神经病(multifocal motor neuropathy，MMN)是近年来新被认识的一种神经疾病。表现为进行性、非对称性肢体运动无力，以远端为重，免疫学检查部分患者抗一神经节苷脂(GM1)抗体滴度升高。电生理检查以持续性、节段性运动神经传导阻滞(PMCBs)为特征。病理学检查发现传导阻滞部位有慢性脱髓鞘改变。激素治疗无效，环磷酰胺及大剂量免疫球蛋白等治疗有效。     

多灶性运动神经病临床及神经电生理特点2例分析

多灶性运动神经病（muhifocal motor neuropathy，MMN）是一种由免疫介导的，主要累及运动纤维的多灶性运动神经病。主要表现为缓慢进展的、非对称性的肢体无力，以上肢受累多见，且远端重于近端。神经电生理表现为持续性节段性运动神经传导阻滞（conduction block，CB）；病理表现以脱髓鞘为主，少数可伴有轻微的轴索损害，不伴有炎性细胞浸润及水肿；免疫学检查部分患者抗神经节苷脂抗体（GMI）滴度升高；同时，对免疫球蛋白及环磷酰胺等治疗有效。现报告2例MMN患者的临床及神经电生理检测结果如下。     

多灶性运动神经病的研究进展

198 2年 L ewis描述了一种慢性、不对称 ,主要累及前臂的感觉运动周围神经病 ,Roth G于 1986年首次报道此类单纯累及运动神经的周围神经病——多灶性运动神经病(MMN) ,此类病又称 L ewis- Summ er综合征。其具有慢性进行性 ,多不对称累及肢体远端 ;运动传导阻滞或部分阻滞 ,肌力减弱而感觉正常 ,病理检查可见阻滞区域有多灶性部分性脱髓鞘特点。本病发病机理不明 ,由于常伴有血清抗 GM1 抗体滴度升高 ,考虑为免疫介导性疾病。现分别从临床表现、电生理、病理、鉴别诊断及治疗进行综述。1　临床表现MMN好发于 2 0～ 75岁 ,据 Alan Pest…     

多灶性运动神经病的研究进展

<正> 多灶性运动神经病(multifocal motor neuropathy,MMN)亦称为多灶性脱鞘性运动神经病,为一周围神经受累的疾病。临床表现为非对称性肢体运动无力,缓慢进展;电生理检查以运动神经传导阻滞(conduction block,CB)或部分阻滞为特点;常伴有血抗神经节苷酯GM_1抗体升高。临床易误诊为慢性炎性脱鞘性多神经根神经病(chronic inflammatory demyelinating polyneuropathy,CIDP)、运动神经元病及急性运动轴索神经病(acute motor axonal neuropathy,AMAN)。     

多灶性运动神经病1例分析及文献复习

多灶性运动神经病（multifocalmotorneuropathy,MMN）是一种少见的周围神经病,病因不清,多认为与自身免疫机制有关。临床以周围运动神经受累为主,表现为慢性、非对称性远端肢体无力、感觉正常、肌电图示运动传导阻滞或部分阻滞,常伴有血清抗神经节苷脂（GM1）抗体滴度     

IVIg治疗抗GM_1抗体阳性的运动神经元综合征

作者通过一项双盲对照交叉研究对运动神经元综合征病人静注免疫球蛋白(IVIg)进行了疗效观察。12例运动神经元综合征病人均伴有高滴定度抗GM_1抗体,平均年龄42.1岁(19～63岁)。根据运动 神经元紊乱情况,将病人分为多发性运动神经病(MMN)组及下运动神经元综合征(LMNS)组。所有病人均进行了肌电图检查,由酶联免疫吸附试验测定血清抗GM_1抗体滴度。根据双盲交叉设计,分别给予病人IVIg(0.4g/kg/d;连续5天)或生理盐水,在第一阶段治疗8周后进行第二阶段治疗。在试验前3个月及试验期间病人均未用过免疫抑制剂,给药前和给药后第5、28和56天分别测定下列四项:(1)肌力,(2)病人劳动力丧失程度,(3)运动神经传导速度,(4)免疫参数:抗GM_1抗体、免疫复合物及CD_2、CD_4、CD_8淋巴细胞。     

多灶性运动神经病7例分析

目的 探讨多灶性运动神经病MMN的临床特点、神经电生理及病理变化的特异性.方法 结合文献分析7例MMN的临床资料、肌电图、病理特征及治疗结果.结果 MMN的临床表现为慢性、非对称性远端肢体无力;电生理检查以运动神经传导阻滞或部分阻滞为特点;病理学特征为运动神经局灶性脱髓鞘性改变.结论 MMN应与运动神经元病和慢性炎性脱髓鞘性多发性神经根神经病鉴别.可采用免疫球蛋白治疗.     

Long-term follow-up of multifocal motor neuropathy with conduction block under intravenous immunoglobulin

INTRODUCTION: Multifocal motor neuropathy with conduction block is an immune-mediated motor neuropathy, which usually responds to intravenous immunoglobulin. However, efficacy of long-term intravenous immunoglobulin is controversial. Our aim was to establish the long-term effects of intravenous immunoglobulin therapy on clinical and neurophysiological outcome measures and to determine the criteria predicting a good response to long-term intravenous immunoglobulin treatment. METHODS: We retrospectively included all multifocal motor neuropathy with conduction blocks patients followed for at least 4 years who received intravenous immunoglobulin therapy. We compared clinical data, MRC sumscores and electrophysiological data between the first and the last examination in the department. RESULTS: Seventeen patients were followed for an average of 8 years (range 4 to 18 years). At last examination, weakness remained asymmetric, predominant in the upper limbs, with a peripheral nerve distribution. At last examination, 3 patterns of evolution was seen: 6/17 patients had muscle strength improvement and need no more intravenous immunoglobulin therapy, 6/17 had initial improvement but became intravenous immunoglobulin dependent and 5/17 did not respond to intravenous immunoglobulin. MRC sumscores, number of conduction blocks and distal compound muscle action potential amplitudes were comparable between the first and the last examination (p>0.05). Improvement of MRC sumscores was not correlated with the clinical, biological and electrophysiological data that we analysed: age, gender, duration of disease, time from onset to intravenous immunoglobulin therapy, number of involved nerves, number of affected limbs, presence of muscle atrophy, MRC sumscores at diagnosis, number of conduction blocks, mean amplitude of the motor evoked potentials, presence of anti-GM1 antibodies, titers and IgM or IgG type of anti-GM1 antibodies. CONCLUSIONS: In this study, one third of multifocal motor neuropathy with conduction blocks patients have clinical improvement at last examination and need no more treatment, one third are intravenous immunoglobulin dependent and one third have never responded to intravenous immunoglobulin. Electrophysiological data are comparable between the first and the last examination. No predictive factor has been disclosed for long-term response to intravenous immunoglobulin.     

Chronic motor axonal neuropathy associated with antibodies monospecific for N-acetylgalactosaminyl GD1a

We report on three patients with chronic motor neuropathy who had elevated titers of immunoglobulin (Ig)G antibodies against N-acetylgalactosaminyl GD1a (GalNAc-GD1a) and normal titers of antibodies against other gangliosides. Presenting with progressive muscular atrophy, fasciculations, and no sensory deficits, the patients had been diagnosed to have motor neuron disease. Electrodiagnostic features were predominantly axonal. Two patients clinically improved after intravenous Ig infusion and cyclophosphamide therapy. Increased titers of IgM antibodies to GalNAc-GD1a were also found in two of 15 patients with multifocal motor neuropathy with conduction block but were associated with concomitant rise of anti-GM1 antibodies. These three cases represent a chronic motor axonal neuropathy in which antibody testing for a minor ganglioside was helpful for instituting therapy.     

多灶性运动神经病的临床表现及肌电图特征

目的 探讨多灶性运动神经病(multifocal motor neuropathy,MMN)的临床表现及肌电图(electromyography,EMG)特征.方法 选择2016 年6 月至2019 年12 月南京医科大学附属南京医院(南京市第一医院)收治的7 例MMN 患者,对其临床资料及神经电生理检查结果进行回顾性...     

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.     

Clinical features and response to treatment in Guillain-Barré syndrome associated with antibodies to GM1b ganglioside

GM1b is a minor ganglioside in human peripheral nerves. Serum anti-GM1b antibodies frequently are present in patients with Guillain-Barré syndrome (GBS). In this collaborative study, we investigated the antecedent infections, clinical features, and response to treatment of GBS patients with anti-GM1b antibodies. Of 132 GBS patients who participated in the Dutch GBS trial that compared the effect of intravenous immunoglobulins and plasma exchange, 25 (19%) patients had anti-GM1b antibodies. IgM antibodies were present in 14, IgG antibodies in 15, and both isotypes in 4 patients. The 25 patients with anti-GM1b antibodies had a clinical pattern distinct from that of the other 107 GBS patients. They more often had an episode of gastrointestinal illness and frequently showed serological evidence of recent infection by Campylobacter jejuni. The anti-GM1b-positive subgroup was marked by more rapidly progressive, more severe, and predominantly distal weakness. Cranial nerve involvement and sensory deficits were less common in the patients with anti-GM1b antibodies. The presence of anti-GM1b antibodies was associated with slower recovery. The clinical manifestations predominantly were associated with anti-GM1b antibodies of the IgG isotype. Fourteen (56%) of the 25 patients with anti-GM1b antibodies also had anti-GM1 antibodies. The group of patients with both antibodies was clinically more homogeneous and had a more rapidly progressive, pure motor neuropathy. The subgroup of anti-GM1b-positive GBS patients responded well to treatment with immunoglobulins but not to plasmapheresis. The distinctive clinical features of the patients with anti-GM1b antibodies show that acute motor neuropathy represents a specific subgroup within GBS and that recognizing these patients may have consequences as to the choice of therapy.     

Use of human intravenous immunoglobulin in lower motor neuron syndromes

OBJECTIVE: To determine whether patients with the clinical phenotype of multifocal motor neuropathy but without the electrophysiological criteria for conduction block would respond to intravenous immunoglobulin (IVIg). METHODS: Ten patients were selected with a slowly progressive, asymmetric, lower motor neuron disorder, and were treated prospectively with IVIg at a dose of 2g/kg over 5 days. All subjects had neurophysiological testing to look for evidence of conduction block before treatment. Muscle strength was assessed by MRC grades and hand held myometry, measuring pinch and grip strength. A 20% increase in both pinch and grip myometry was considered a positive response. RESULTS: In no patient was conduction block detected. Four of the 10 patients showed a positive response to IVIg, with the best response occurring in two patients who presented with weakness but without severe muscle wasting. Three of the four responders have continued to receive IVIg for a mean period of 17 months (range 15-24 months), with continued effect. The response to IVIg was not related to the presence of anti-GM1 antiganglioside antibodies, but responders had a selective pattern of muscle weakness and normal (>90% predicted) vital capacity. CONCLUSION: The findings suggest that a course of IVIg should be considered in patients with the clinical phenotype of multifocal motor neuropathy but without neurophysiological evidence of conduction block.     

Chronic relapsing multifocal sensory-motor neuropathy with conduction block

A 47 years old man had 13 episodes of relapsing and remitting sensory-motor neuropathy involving the upper limbs over the last 20 years. All but the last episode resolved spontaneously within 2 months. Neurophysiology revealed multifocal motor and sensory conduction block in the upper limbs with normal terminal latencies. CSF analysis was normal and anti-GM1 antibodies were not detected. There was a dramatic clinical improvement after intravenous immunoglobulin treatment. This case represents an unusual multifocal variant of chronic inflammatory demyelinating neuropathy.     

Multifocal motor neuropathy with conduction block: current issues in diagnosis and treatment

Multifocal motor neuropathy (MMN) with conduction block is an acquired, autoimmune-mediated neuropathy that is responsive to treatment. The clinical history is one of slowly, progressive distal weakness, which more commonly involves the upper extremities, and it affects mainly young adults. Physical examination reveals weakness without sensory loss in the distribution of individual nerves. Atrophy may be present, but hyperreflexia and spasticity are not seen. Electrophysiological studies reveal motor conduction blocks at sites not prone to compression with normal sensory responses. Immunoglobulin M anti-GM1 titers may be elevated. Treatment with human immunoglobulin or cyclophosphamide has been shown to improve strength in the majority of patients with MMN in the short term. However, motor strength and function may gradually decline over years in spite of long-term therapy.     

Anti-GM1 antibodies in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg)

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and with a chronic polyneuropathy (non-CIDP) were studied for the presence of anti-GM1 antibodies. In pretreatment sera of CIDP patients, we found IgG anti-GM1 antibodies in 23%, IgM in 7%, and IgA in 14%. Predominantly motor involvement was associated with IgG and IgM anti-GM1 antibodies in CIDP patients (P = 0.002). Improvement after intravenous immunoglobulin (IVIg) therapy was not associated with anti-GM1 antibody titer before or after treatment. Anti-GM1 antibody titers before onset of treatment was not related to poor clinical outcome, although large clinical improvements after IVIg therapy were observed less often (P = 0.057) in patients with high titer anti-GM1 antibodies before treatment.     

A patient of sensorimotor neuropathy with small cell lung carcinoma and anti-GM1 antibody]

We reported a 62-year-old woman had sensorimotor neuropathy with small cell lung carcinoma (SCLC) and anti-GM1 antibody. She was admitted with several months history of progressive numbness, walking disturbance and anorexia. Neurologic examination revealed severe numbness and deep sensory disturbance of extremities and body, and mild weakness of distal extremities. Deep tendon reflexes were absent. Her limbs were ataxic. Nerve conduction studies showed no sensory evoked responses. CSF protein was elevated. Sural nerve biopsy revealed severe loss of myelinated fibers and perivascular mononuclear cells surrounding the perineurial vessel. Vasculitic neuropathy was diagnosed, and prednisolone was started, with no benefit. In the clinical course, she developed cough attacks and was found the lymphnode swelling in the mediastinum and supraclavicular fossa, which was diagnosed SCLC. Although anti-Hu antibody were not detected, anti-GM1 antibody was positive. She was treated with intravenous immunoglobulin, with transient improvement. The rare case of the paraneoplastic peripheral neuropathy with SCLC and anti-GM1 antibody was reported.