外源性神经节苷脂相关性吉兰-巴雷综合征的临床特征及肌电图表现(附3例报道)

目的 探讨外源性神经节苷脂相关性吉兰-巴雷综合征(GBS)的临床特点、发病机制及治疗措施。方法 回顾性分析3例外源性神经节苷脂相关性GBS患者临床资料。结果 3例男性老年患者自开始用药后7～14 d起病,临床表现以进行性加重的四肢无力为主要表现,四肢软瘫,腱反射消失,无感觉障碍,肌电图(EMG)检查提示轴索损害为主,符合外源性神经节苷脂相关性GBS诊断;治疗上以尽早停用外源性神经节苷脂并以迅速经静脉注射人血免疫球蛋白或行血浆置换治疗为主。结论 外源性神经节苷脂可能与GBS的发生与进展有关,通常患者预后不良。     

以呼吸困难为首发症状的神经节苷脂相关性急性运动轴索性神经病2例及文献复习

正急性运动轴索性神经病(Acute motor axonal neuropathy,AMAN)是吉兰-巴雷综合征(Guillain-Barre’syndrome,GBS)中的一种主要分型,以脊神经前根和运动神经纤维轴索变性损害为主,属自身免疫病范畴。单唾液酸四己糖神经节苷脂钠注射液长久以来作为神经营养药物广泛应用于神经系统疾病,该药在改善脑细胞功能,促进受损神经细胞恢复方面疗效显著,但近年来,其临床不良副反应逐渐显露,国内外陆续报道多例外源性神经节苷脂所致GBS病例。现报道2例因呼吸困难入住我院重症监护室的神经节苷脂相关性GBS患者,运动神经纤维轴索病变为其主要特点,旨在深化临床对药物性GBS的认识。     

单唾液酸四己糖神经节苷脂相关性吉兰-巴雷综合征:三例报告并文献复习

研究背景单唾液酸四己糖神经节苷脂钠(神经节苷脂)注射液系从猪脑中提取获得的神经细胞功能物质,参与多种细胞病理生理过程,在神经组织发生、生长、分化过程中发挥重要作用。神经节苷脂对血管源性脑损伤、创伤性脑脊髓损伤神经元的恢复具有促进和保护作用,可改善帕金森病行为障碍。但随着临床的广泛应用,其不良反应逐渐被发现,其中注射神经节苷脂后并发的类似吉兰巴雷综合征表现的病例较为少见,其临床特点和机制尚需进一步总结和探讨。方法分析3例神经节苷脂治疗后发生吉兰巴雷综合征患者的临床、神经电生理及脑脊液特征。结果患者均为39～65岁男性,分别于静脉注射神经节苷脂后9～14d出现四肢瘫痪、肌张力减退及腱反射消失等肌肉病症状与体征,可伴呼吸困难(1例)或脑脊液蛋白细胞分离现象(1例)或周围神经轴索变性(1例)等表现,符合神经节苷脂相关性吉兰巴雷综合征诊断。结论单唾液酸四己糖神经节苷脂静脉注射后可诱发吉兰巴雷综合征,多发生于静脉注射后9～14d,患者预后不良。其可能机制与外源性神经节苷脂通过诱导免疫机制导致神经轴索变性有关。     

吉兰-巴雷综合征

吉兰-巴雷综合征(GBS)是一种相对少见, 但可危及患者性命的累及周围神经和神经根的免疫介导性疾病, 常由感染诱发。其临床特征为急性起病的对称性迟缓性瘫痪, 部分患者可出现呼吸衰竭, 很多伴有自主神经功能损害。通常可根据临床症状作出诊断, 腰椎穿刺和电生理检查可协助诊断, 并帮助进行亚型分类。目前较公认的关于GBS的发病机制为分子模拟学说, 即病原微生物诱导产生针对神经节苷脂的交叉抗体。GBS的治疗方案为静脉注射免疫球蛋白或血浆置换以及一般的临床治疗。多数患者预后良好, 数周至数月基本恢复, 少数患者遗留持久神经功能障碍甚至死亡。     

神经节苷脂在SD大鼠周围神经中分布的实验研究

目的了解神经节苷脂在大鼠的运动和感觉神经中的分布情况,为阐明与神经节苷脂抗体有关的周围神经疾病的发病机制提供实验依据。方法应用免疫组化技术对正常SD大鼠的脊髓前根和后根进行免疫组化染色,并对两者进行比较。结果神经节苷脂存在于大鼠周围神经的轴索中,运动和感觉神经比较无明显差异。结论SD大鼠运动和感觉神经中神经节苷脂的分布无差异,神经节苷脂成分并非急性运动性轴索型神经病等周围神经疾病中运动轴索选择性受累的主要原因。     

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。     

脑外伤后并发吉兰-巴雷综合征一例并文献复习

目的探讨脑外伤后并发吉兰-巴雷综合征(GBS)的临床特点、发病机制、诊断、治疗及预后。方法报道1例作者医院收治的脑外伤并发GBS患者的临床资料,并结合文献进行复习。结果检索9篇文献共11例患者,结合本文1例共12例,其中男11例,女1例,脑外伤至发病时间间隔为6～24 d,中位数为12 d,多集中于7～14 d内发病。临床症状以运动障碍为主,主要表现为四肢无力,呈对称性,合并呼吸困难2例,合并感觉障碍1例。发病前有呼吸道感染1例,腹泻1例(可疑空肠弯曲菌感染),无接种疫苗病史。发病后明确使用神经节苷脂药物有3例。9例行脑脊液检查均出现蛋白-细胞分离现象。11例患者行肌电图检查提示均有异常表现,表现为波幅或传导速度的改变。4例进行血清自身免疫抗体谱检测,其中3例阳性,其中抗GD1a(+)2例、抗GD1b(+)2例、抗GM1(+)2例,1例阴性;本例进行脑脊液自身抗体谱检测发现抗Sulfatide(+)。影像学检查显示脑挫裂伤6例,脑挫裂伤及出血部位累及额叶6例,颞叶3例,枕叶1例,弥漫性轴索损伤1例,合并创伤性蛛网膜下腔出血6例,硬膜下血肿6例。GBS分型为急性运动性轴索神经病(AMAN)6例,急性炎症性脱髓鞘性多发性神经根神经病(AIDP)5例,急性运动感觉轴索型(AMSAN)1例。6例患者单用大剂量丙种球蛋白(IVIGs)治疗,IVIGs联合糖皮质激素治疗3例,IVIGs联合血浆置换治疗1例。随访10例患者,1例无自主呼吸,3例卧床及生活不能自理,2例患者需辅助行走,4例患者恢复至可独立行走。结论脑外伤后非手术治疗患者并发GBS综合征在临床上少见,发病时间多在脑外伤后7～14 d,需与危重病相关性多发性神经病和肌病相鉴别,早期诊断并规范治疗,有助于改善预后。     

GBS与空肠弯曲菌感染

吉兰巴雷综合征(GuillainBarr啨syndrome,GBS)表现为一种由前驱细菌或病毒感染所触发的自限性自身免疫疾病,其中空肠弯曲菌(Campylobacterjejuni,CJ)是最常见的前驱感染病原,研究提示血清型O(Penner)O:1,O:2,O:4,O:10,O:19,O:23,O:36,O:41等CJ菌株的脂多糖(lipopolysaccharide,LPS)在分子结构上与人类神经节苷脂表位之间具有分子模拟现象,从而导致机体对二者的交叉反应产生抗神经节苷脂自身抗体可能是GBS的发病机理。抗神经节苷脂抗体在不同类型的GBS患者中具有一定的特异性,这个特点在急性周围神经病中可用于临床诊断和估计预后。     

大剂量免疫球蛋白治疗轴索型GBS临床观察

近年来,利用大剂量免疫球蛋白治疗格林巴利综合征(Guillain-barresyndrome,GBS)越来越受到人们的重视,尤其对轴索型GBS的治疗效果较好。我们使用大剂量免疫球蛋白治疗6例轴索型GBS,现报告如下。1　临床资料1.1　一般资料　本组男4例,女2例,年龄16～20岁,平均年龄17.33岁。4例病前有腹泻、2例病前有上感病史。均为急性或亚急性起病,四肢对称性软瘫,腱反射减弱或消失。4例出现双侧周围型面神经瘫,感觉均正常。电生理学检查:本组患者运动神经传导速度正常,运动诱发电位波幅明显降低,F波潜伏期正常,感觉传导速度及波幅均正常。1.2　治疗方…     

神经节苷脂相关吉兰-巴雷综合征14例报告及文献复习

正吉兰-巴雷综合征(Guillain-Barre,GBS)是一类免疫介导的周围神经病,以对称性肢体瘫痪、腱反射减弱或消失为临床特点,是脊髓灰质炎基本被消灭后急性迟缓性瘫痪最主要的原因。全球年发病率为0.81~1.89/10万人。GBS的预后相对较好,且随着呼吸机在临床的应用,该病的死亡率明显下降,但仍有大约20%的患者遗留严重的肢体功能障碍。发病原因考虑与感染性病原微生物有关,也有研究报道神经节苷脂可能诱发GBS,且此类患者病情较重、预后差。本研     

Axonal conduction block at intermediate nerve segments in pure motor Guillain-Barré syndrome

The pathophysiology of axonal Guillain-Barré syndrome (GBS) is not simple axonal degeneration, but includes reversible conduction failure. Acute motor axonal neuropathy (AMAN) and acute motor conduction block (CB) neuropathy are the two subtypes of pure motor axonal GBS, but their nosologic boundary is still in debate. We investigated clinical and electrophysiological features of 21 consecutive patients with GBS in Korea. Analysis was focused on the presence of CB at intermediate nerve segments (iCB) in pure motor GBS, and its serial changes during the acute phase of disease. Pure motor GBS was common (81%), and iCB was observed in 12 patients with pure motor GBS. Clinical features of pure motor GBS with iCB were distinct from sensorimotor GBS, but similar to pure motor GBS without iCB, characterized by frequent preceding diarrhea, uncommon cranial nerve palsy, and fast recovery. The iCB was not restricted to common entrapment sites, and the distal segments were also commonly involved in the nerves with iCB. The temporal course of iCB was marked by a rapid and often disproportionate increase of proximal and distal amplitudes without remyelinating slow components. Clinical and electrophysiological features of pure motor GBS in patients with iCB suggest that acute motor CB neuropathy may constitute a spectrum of axonal GBS, sharing a common pathomechanism with AMAN.     

Guillain-Barré syndrome: An update

Guillain-Barré syndrome (GBS) is an acute polyneuropathy consisting of different subtypes. Acute inflammatory demyelinating polyradiculoneuropathy, the classic demyelinating form of GBS, accounts for 90% of all GBS cases in the Western world. Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are axonal forms of GBS that are more prevalent in Asia, South and Central America, often preceded by infection by Campylobacter jejuni. AMAN and AMSAN may be mediated by specific anti-ganglioside antibodies that inhibit transient sodium ion (Na⁺) channels. The efficacy of plasmapheresis and intravenous immunoglobulin has been established in large international randomised trials, with corticosteroids proven ineffective. Although axonal demyelination is an established pathophysiological process in GBS, the rapid improvement of clinical deficits with treatment is consistent with Na⁺ channel blockade by antibodies or other circulating factors, such as cytokines. This review provides an update on the epidemiology, clinical features, diagnosis, pathogenesis and treatment of GBS.     

Outcome of axonal and demyelinating forms of Guillain-Barré syndrome in children

Previous reports have suggested that outcome is worse in the axonal compared with the demyelinating form of Guillain-Barré syndrome (GBS). We performed a retrospective study of 23 children with electrophysiologically confirmed cases of predominant subtypes of GBS to investigate this issue. The patients were classified based on the electrodiagnostic features: Ten (44%) had acute inflammatory demyelinating polyradiculoneuropathy, eight (35%) had acute motor axonal neuropathy, and five (21%) had acute motor-sensory axonal neuropathy. All patients received a standard intravenous immunoglobulin therapy (0.4 g /kg /day for 5 consecutive days). In the acute phase of the disease, patients with the axonal forms of GBS were more disabled than were those with the demyelinating GBS, as measured by GBS scores. Mechanical ventilation was required in five (38%) patients in the axonal group compared with one (10%) patient in the demyelinating group. There was no significant difference at 6 months in GBS scores between demyelinating and axonal forms of GBS. All 20 survivors recovered completely by 12 months. After standard intravenous immunoglobulin therapy, children with axonal forms of GBS recover more slowly than those with the demyelinating form, but outcome at 12 months appears to be equally favorable in two groups.     

Treatment of immune-mediated, dysimmune neuropathies

This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B-cell surface-membrane-marker CD20.     

Ganglioside mimicry and peripheral nerve disease

Four criteria must be satisfied to conclude that a given microorganism causes Guillain-Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry.     

Acute Motor Axonal Neuropathy Associated with Pandemic H1N1 Influenza A Infection

Background  

Guillain–Barre syndrome (GBS) is a well known entity that has many infectious agents reported as antecedent events. The spectrum of GBS includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), and some other variants like Miller-Fisher syndrome (MFS).     

Clinical features and prognosis with Guillain-Barr�� syndrome

Background:

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy commonly characterized by rapidly progressive, symmetric weakness and areflexia.

Materials and Methods:

We retrospectively assessed the clinical manifestations, results of electrodiagnostic tests, functional status and prognosis of 36 children diagnosed with GBS.

Results:

Based on clinical and electrophysiological findings, the patients were classified as having acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (n = 25), acute motor axonal neuropathy (AMAN) (n = 10) and acute motor-sensory axonal neuropathy (AMSAN) (n = 1). Twenty (55.5%) patients were males and 16 (44.5%) patients were females. The mean age of the 36 patients was 68.1 ± 45.01 months (range, 6–180 months). Five (13.8%) patients were younger than 2 years. The most common initial symptoms were limb weakness, which was documented in 34 (94.4%) patients. In our study, 18 patients (51.4%) showed albuminocytological dissociation (raised protein concentration without pleocytosis) on cerebrospinal fluid (CSF) examination. Three patients (8.3%) required mechanical ventilation therapy during hospitalization. Unfortunately, three (8.3%) patients died; one patient had AIDP and two patients had axonal involvement (one case was AMAN and another case was AMSAN). When we compared the cases of residual sequel/dead and cases of complete recovery for neural involvement type including AIDP, AMAN and AMSAN, we did not find a statistically significant difference between the groups (P > 0.05).

Conclusion:

Our findings showed that cases of GBS was not uncommon in children younger than 2 years of age, and CSF protein level might be found high in the first week of the disease in about one half of the patients, with a higher rate of morbidity and mortality in patients with axonal involvement than in those with AIDP.     

Clinical characteristics of Guillain-Barré syndrome in a tropical country: a Brazilian experience

Dourado ME, Félix RH, da Silva WKA, Queiroz JW, Jeronimo SMB. Clinical characteristics of Guillain–Barré syndrome in a tropical country: a Brazilian experience.
Acta Neurol Scand: 2012: 125: 47–53.
© 2011 John Wiley & Sons A/S. Objective – To analyze the clinical variants, outcomes, and prognosis of Guillain–Barré syndrome (GBS) in a Brazilian population. Materials and methods – Clinical and laboratory data of 149 cases of GBS diagnosed from 1994 to 2007 were analyzed. Results – Acute inflammatory demyelinating polyneuropathy (AIDP) was the most frequent variant (81.8%) of GBS, followed by acute motor axonal neuropathy (AMAN) (14.7%) and acute motor and sensory axonal neuropathy (AMSAN) (3.3%). The incidence of GBS was 0.3/100,000 for the state of Rio Grande do Norte and cases occurred at a younger age. GBS was preceded by infections, with the axonal variant associated with episodes of diarrheas (P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP (P < 0.0001), 84.6% of cases with the axonal variant had nadir in <10 days. Individuals with the axonal variant took longer to recover deambulation (P < 0.0001). The mortality of GBS was 5.3%. Conclusion – A predominance of the AIDP variant was seen, and the incidence of the disease decreased with age. As expected, the distribution of weakness correlated with the clinical variants, and individuals with the axonal variant had a poorer prognosis.     

IL-10 and IFN-gamma in Guillain-Barré syndrome. Network Members of the Swedish Epidemiological Study Group

Guillain-Barré syndrome (GBS) is an acute inflammatory disease affecting myelin and axons of the peripheral nervous system (PNS). GBS is considered to be caused by breakdown of tolerance to autoantigens of the PNS. The involvement of cytokines in GBS and in relation to treatment with high dose intravenous immunoglobulin (IvIg) is incompletely known. We studied the temporal profiles of IL-10 and IFN-gamma-secreting blood mononuclear cells (MNC) over the course of GBS, using enzyme-linked immunospot (ELISPOT) assays. Pretreatment levels of blood MNC spontaneously secreting IL-10 were higher in the acute phase of GBS than in control patients with aseptic meningitis, other neurological diseases, diabetic neuropathy and healthy subjects. Levels of IFN-gamma-secreting blood MNC were not increased over the course of GBS. Patients treated with IvIg had lower numbers of IL-10-secreting MNC compared to untreated patients. High levels of IL-10-secreting MNC correlated with serum anti-ganglioside IgM antibody levels, and with neurophysiological signs of axonal damage. The present data suggests that IFN-gamma is not involved in GBS pathogenesis, and IL-10 being up-regulated in the early phase of GBS and associated with axonal damage, may have a pathogenetic role in GBS.     

Axolemmal nanoruptures arising from paranodal membrane injury induce secondary axon degeneration in murine Guillain-Barré syndrome

The major determinant of poor outcome in Guillain-Barré syndrome (GBS) is axonal degeneration. Pathways leading to primary axonal injury in the motor axonal variant are well established, whereas mechanisms of secondary axonal injury in acute inflammatory demyelinating polyneuropathy (AIDP) are unknown. We recently developed an autoantibody-and complement-mediated model of murine AIDP, in which prominent injury to glial membranes at the node of Ranvier results in severe disruption to paranodal components. Acutely, axonal integrity was maintained, but over time secondary axonal degeneration occurred. Herein, we describe the differential mechanisms underlying acute glial membrane injury and secondary axonal injury in this model. Ex vivo nerve-muscle explants were injured for either acute or extended periods with an autoantibody-and complement-mediated injury to glial paranodal membranes. This model was used to test several possible mechanisms of axon degeneration including calpain activation, and to monitor live axonal calcium signalling. Glial calpains induced acute disruption of paranodal membrane proteins in the absence of discernible axonal injury. Over time, we observed progressive axonal degeneration which was markedly attenuated by axon-specific calpain inhibition. Injury was unaffected by all other tested methods of protection. Trans-axolemmal diffusion of fluorescent proteins  and live calcium imaging studies indirectly demonstrated the presence of nanoruptures in the axon membrane. This study outlines one mechanism by which secondary axonal degeneration arises in the AIDP variant of GBS where acute paranodal loop injury is prominent. The data also support the development of calpain inhibitors to attenuate both primary and secondary axonal degeneration in GBS.