Electrophysiological subtypes and prognosis of childhood Guillain-Barré syndrome in Japan

Guillain-Barré syndrome (GBS) is classified into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), but little is known about the incidence of the subtypes and the prognosis of childhood GBS. To elucidate the features and long-term prognosis, clinical and electrophysiological data for 31 Japanese GBS children were reviewed. By electrodiagnostic criteria, children were classified as having AIDP (35%) or AMAN (48%), or were unclassified (16%). The AMAN children invariably had normal sensory nerve potentials. Between the two groups, age, sex, and clinical disability did not differ significantly, but the AIDP children more frequently had cranial and sensory nerve involvement, and the AMAN children more frequently had preceding gastroenteritis. By 6 months after onset, all the AIDP and 80% of the AMAN children had regained the ability to walk; by 2 years, all but one of the AMAN children could walk. In Japanese childhood GBS, the proportion of AIDP and AMAN appears to be similar. Recovery is generally favorable in both subtypes, but some of the AMAN children experienced delayed recovery.     

Evolving pattern of Guillain-Barre syndrome in a community hospital in Israel

Objectives –  To investigate the frequency of axonal Guillain–Barre syndrome (GBS) in our ward over 6 years (1999–2005).
Materials and methods –  Clinical and electrophysiological findings of 40 patients admitted to neurology with abnormalities compatible with acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN) and acute inflammatory demyelinating polyneuropathy (AIDP) were reviewed.
Results –  Electrophysiological findings showed that 25 (63%) patients had AIDP, nine (22%) AMAN and six (15%) AMSAN. There were significant differences in disease severity. Most axonal patients (87%) were hospitalized with moderate or severe symptoms (3–4 Hughes grade score) and progressed to severe grade (4–6) in comparison with AIDP patients (64% admitted with mild forms) (1–2 Hughes grade score) and progressed to severe in 44% of cases. Cranial nerve involvement was more frequent in AIDP (56%) in comparison with the axonal type (13%). Raised cerebrospinal fluid protein at the time of hospitalization was observed in 76% of demyelinating and 33% of axonal patients.
Conclusions –  Axonal GBS occurred more frequently in Israel compared with other Western countries.     

Serial nerve conduction studies provide insight into the pathophysiology of Guillain-Barré and Fisher syndromes

The electrodiagnosis of Guillain-Barré syndrome (GBS) can be broadly divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Fisher syndrome (FS) is a variant of GBS, although the underlying neuropathy of FS has yet to be established. Serial nerve conduction studies (NCS) can provide further insight into the likely pathophysiology by further subtyping of GBS and FS. We present a patient with an initial diagnosis of AIDP in whom repeated NCS revealed the AMAN variant. This led us to investigate serial NCS in five patients with GBS, FS and FS/GBS overlap presenting over a period of a year. Three patients with AIDP showed a gradual increase in distal motor latencies during the acute phase of illness. NCS of two patients with FS and FS/GBS overlap showed no demyelinating features suggesting underlying axonal neuropathy in this group of patients. The importance of serial NCS in establishing the underlying pattern of neuropathy in GBS and FS is further emphasized in this study. Larger studies incorporating serial NCS are required to confirm the observations seen in our case series especially when pathological studies are often not justified in this group of patients.     

Guillain‐Barré syndrome: subtypes and predictors of outcome from India

There is a paucity of large studies evaluating the subtypes of Guillain‐Barré syndrome (GBS) and their outcome from Southeast Asia. We report cliniconeurophysiological subtypes of GBS and their correlation with triggering events and 3‐month outcome from northern India. Three hundred and twenty eight consecutive patients with GBS were clinically evaluated, including their triggers, severity, autonomic involvement, cranial nerve palsy, and respiratory paralysis. Nerve conduction study (NCS) was repeated at 3 weeks if the initial study was normal. They were categorized into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), inexcitable motor nerve, and equivocal. Clinically, 204 (62.2%) patients had pure motor, 106 (32.3%) motor sensory, 16 (4.9%) Miller Fisher syndrome, and 2 (0.6%) pure sensory GBS. Based on NCS, 242 (73.8%) had AIDP, 44 (13.4%) AMAN, 15 (4.6%) AMSAN, 8 (2.4%) inexcitable motor nerves, and 27 (8.2%) equivocal GBS. AIDP patients were older, more common in summer, had lesser peak disability, and better outcome compared to those with AMAN. Eleven (3.4%) patients died and 48 (14.6%) had poor outcome at 3 months. The poor outcome was related to severity, dysautonomia, and inexcitable motor nerves. AIDP is the commonest variant of GBS in our study and has better outcome compared to AMAN.     

Increased incidence of axonal Guillain‐Barré syndrome in La Spezia area of Italy: A 13‐year follow‐up study

Guillain‐Barré syndrome (GBS) is an acute immune‐mediated polyradiculoneuropathy with a worldwide incidence of 0.81‐1.89 per 100 000 person‐years. In Europe and North America only 5% of patients with GBS have axonal subtypes, which in South America and Asia account for 30%‐47% of cases. The aim of our study is to assess the annual incidence and clinical features of GBS in La Spezia area in Italy. A retrospective (from 1 January 2003 to 31 December 2011) followed by a prospective (from 1 January 2012 to 31 December 2015) analysis was carried out on patients admitted to La Spezia hospital who fulfilled the GBS diagnostic criteria. A total of 86 patients (58 men), mean age of 62.7 years (range 21‐90), were included. The mean annual incidence rate was 3/100 000 (range: 0.9/100 000‐5.37/100 000) significantly higher than the European incidence (P < 0.001). Forty‐seven percent were classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 35% as acute motor and motor‐sensory axonal neuropathy (AMAN‐AMSAN), 13% as variant forms, and 5% were not defined. AIDP was most common in “Golfo dei Poeti” (50%) and “Val di Magra” (63.2%), whereas AMAN/AMSAN prevailed in “Val di Vara” (63.6%) and “Riviera Spezzina” (62.5%) (P = 0.024). In La Spezia area GBS incidence (especially the AMAN subtype) is significantly higher than the incidence reported in Europe. AIDP predominates in the eastern area whereas AMAN/AMSAN in the western, with a significantly different incidence rate (P = 0.003). Prospective studies to assess possible predisposing environmental factors are needed.     

Electrophysiological studies in the Guillain–Barré syndrome: Distinguishing subtypes by published criteria

Guillain–Barré syndrome (GBS) is recognized clinically by the presence of acute, rapidly progressive weakness, areflexia, and albuminocytological dissociation in cerebrospinal fluid. Although GBS was initially considered to be primarily an acute inflammatory demyelinating polyneuropathy (AIDP), several other subtypes have been recognized: acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Fisher syndrome (FS). Because each of these subtypes may have an independent immunopathogenesis and, therefore, may require selective treatments in the future, recognition of these subtypes is important. When using nerve conductions to classify the subtypes, the most easily and confidently identified subtype is AIDP. Therefore, most electrodiagnostic criteria have attempted to identify demyelination in this acute setting, in which physiology is constantly changing. In a single well-defined GBS population, we compared the various published criteria for demyelination in GBS. We reviewed charts of 43 patients with GBS between 1991 and 1996. Applying six available criteria sets, the number of patients categorized as having AIDP ranged from 21% to 72%. Until investigators can agree on a single set of criteria, considerable variability will continue to exist when identifying cases of AIDP. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1275–1279, 1998.     

Electrodiagnostic criteria for Guillain-Barrè syndrome: a critical revision and the need for an update

Electrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification of the subtypes and in establishing prognosis. In the last three decades, different electrodiagnostic criteria sets have been proposed for acute inflammatory demyelinating neuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). Criteria sets for AIDP varied for the parameters indicative of demyelination considered, for the cut-off limits and the number of required abnormalities (all a priori established) showing different sensitivities. Criteria sets for AMAN and AMSAN were proposed on the initial assumption that these subtypes were pathologically characterised by simple axonal degeneration. However, some AMAN patients show transient conduction block/slowing in intermediate and distal nerve segments, mimicking demyelination but without the development of abnormal temporal dispersion, named reversible conduction failure (RCF). The lack of distinction between RCF and demyelinating conduction block leads to fallaciously classify AMAN patients with RCF as AIDP or AMAN with axonal degeneration. Serial electrophysiological studies are mandatory for proper diagnosis of GBS subtypes, identification of pathophysiological mechanisms and prognosis. More reliable electrodiagnostic criteria should be devised to distinguish axonal and demyelinating subtypes of GBS, taking into consideration the RCF pattern and focussing on temporal dispersion.     

用免疫学方法分析格林-巴利综合征与空肠弯曲菌感染关系

对不同类型格林-巴利综合征病人血清中所含抗格林-巴利综合征病人分离株空肠弯曲菌、动物来源株空肠弯曲菌、北京对照用人源性空肠弯曲菌及其脂多糖抗体进行分析,结果显示,AMAN病人血清中含有高滴度抗AMAN病人感染株空肠弯曲菌LPS的抗体,同时含有较弱的抗当地分离株空肠弯曲菌LPS的抗体,但不含有抗对照组空肠弯曲菌LPS的抗体,AIDP病人血清中不含有抗空肠弯曲菌LPS的抗体,仅含有较弱的抗空肠弯曲菌蛋白抗原的抗体,表明抗空肠弯曲菌LPS抗体的产生与AMAN的发生密切相关;若某些AIDP的发生与空肠弯曲菌感染相关,则其发生也与抗空肠弯曲菌LPS抗体的产生无明显关系。AIDP与AMAN病人在发病机理上存在明显不同,对临床GBS病人血清中抗空肠弯曲菌LPS抗体的检测,可能对AMAN与AIDP的鉴别诊断具有重要意义。     

Physiologic-pathologic correlation in Guillain-Barré syndrome in children

OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.     

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.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Unclassified subtype of Guillain-Barré syndrome is associated with quick recovery

Electrophysiological classification of Guillain-Barré syndrome (GBS) is important for predicting its clinical course; however, few reports discuss GBS patients who do not conform to the acute inflammatory demyelinating polyneuropathy (AIDP) or acute motor axonal neuropathy (AMAN) classifications. Therefore, the present study assessed the features of unclassified types of GBS and compared them to those of AIDP and AMAN. We compared clinical symptoms, nerve conduction, and laboratory data among patients with AIDP, AMAN, and unclassified subtypes of GBS, according to criteria developed by Rajabally, Hadden, and Ho. According to the Rajabally criteria, the F wave frequency in the upper and lower extremities was higher in the unclassified subgroup than in the AIDP and AMAN subgroups; however, according to the Hadden and Ho criteria, the F wave frequency in only the lower extremities was higher in the unclassified subgroup than in the other subgroups. The unclassified subgroup showed better prognosis using the Rajabally criteria. Classification with the Rajabally criteria is useful for predicting prognosis and determining treatment in patients with GBS. Moreover, unclassified patients exhibit the quickest recovery.     

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).     

急性运动轴索型神经病的预后分析

目的 研究吉兰-巴雷综合征(GBS)的临床特征,分析比较急性炎性脱髓鞘型多神经病(AIDP)和急性运动轴索型神经病(AMAN)的预后. 方法 分析卫生部北京医院神经科自2003年1月至2007年12月收治的50例GBS患者临床资料.根据电生理分型诊断标准将患者分为AIDP组(24例)与AMAN组(22例),不能分类4例,对出院时仍不能独立行走的患者至少随访6个月,分析比较两组患者的临床特征和预后. 结果 AIDP与AMAN两组患者的性别、年龄、颅神经受累情况、就诊及高峰时的病情评级、接受的治疗方法 等比较差异无统计学意义(P>0.05);治疗1个月时患者Hughes运动功能评级两组间比较差异无统计学意义(P>0.05);而AMAN组患者快速恢复、缓慢恢复的比例(63%,18%)均高于AIDP组(33%,4%),差异均有统计学意义(P<0.05). 结论 AMAN患者临床上存在快速恢复与缓慢恢复两种情况:对AMAN患者应予积极免疫治疗.以获早期恢复和较好预后.     

Use of immunoglobulin in severe childhood Guillain-Barré syndrome

OBJECTIVES: To compare the clinical results in children with Guillain-Barré syndrome (GBS) admitted to the intensive care unit. Patients treated with intravenous immunoglobulin (IVIg) were compared with patients admitted before the immunoglobulin treatment was introduced. DESIGN: Study of historical cohorts. Methods - The outcome of the children who did not receive IVIg before 1993 was compared with those children who received immunoglobulin treatment from this year until 2002. The days of ventilatory support and the time it took to reach state III on the GBS disability scale were used as measures of outcome. Age, muscular strength, cranial nerve palsy and the electrophysiological classification were the independent variables. RESULTS: In all, 48 of 96 children were classified - 18 patients as axonal motor acute neuropathy (AMAN) and 30 patients as axonal inflammatory demyelinating polyneuropathy (AIDP). For both groups the analysis showed similar results behavior when comparing the outcome of patients with or without immunoglobulin treatment. A high proportion of patients with unexcitable nerves was found in the group with immunoglobulin treatment. Quadriplegia and the presence of unexcitable motor nerves were associated with a longer period of recovery. CONCLUSION: Immunoglobulin did not change the history of the illness as far as the time of ventilatory support in AMAN and AIDP groups is concerned and the time to reach state III on the GBS disability scale.     

Elevated levels of S100B, tau and pNFH in cerebrospinal fluid are correlated with subtypes of Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is an immune-mediated inflammatory disease in the peripheral nervous system. Specific biomarkers for the two most common clinical subtypes of GBS, i.e., acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) are still missing. The distinctive pathological features of AIDP and AMAN may lead to release of such specific biomarkers including glial markers (calcium-binding astroglial protein, S100B) and axonal damage markers [axoskeletal protein, phosphorylated neurofilament heavy protein (pNFH); cytoskeletal protein, tau], etc. To explore the potentials of biochemical markers for differential diagnosis and evaluation of prognosis of clinical subtypes in GBS, we used ELISA to measure the levels of S100B, tau and pNFH in serum and cerebrospinal fluid (CSF) from the patients with AIDP, AMAN, viral encephalitis and other non-inflammatory neurological disorders (OND), respectively. The values of albumin quotient and IgG index in CSF are significantly higher in AIDP and AMAN than in OND. The levels of S100B, tau and pNFH in serum and CSF are elevated in the patients with AIDP and AMAN compared to OND. The concentrations of these proteins are all higher in CSF than in serum. Increased levels of S100B in CSF at the acute phase are positively correlated with the GBS disability scale scores (GDSs) in AIDP, whereas enhanced levels of tau and pNFH in CSF are positively correlated with the GDSs in AMAN. Increased CSF levels of S100B, tau and pNFH at the acute phase may predict a poor prognosis and evaluate the severity of AIDP or AMAN at plateau and the recovery phase. Elevated levels of pNFH in CSF may be used for differentiating between AMAN and AIDP.     

Inflammatory infiltrates in the spinal cord of patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is defined as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) of the peripheral nervous system. Reports on central nervous system involvement in patients with GBS are rare and the histopathological analysis was usually restricted to conventional staining techniques. We were able to investigate four cases with GBS at autopsy in respect to the inflammatory infiltrates and histopathological changes in the spinal cord by immunohistochemistry using a panel of antibodies recognizing lymphocytes and different macrophage-activation antigens. There were increased inflammatory cell infiltrates comprising lymphocytes and macrophages in the spinal cord of two cases. In one of these two cases, GBS predominantly affecting the motor system similar to acute motor axonal neuropathy (AMAN) developed following hepatitis B vaccination; in the second one, GBS developed rapidly 4 days after onset of intravenous purified GM1-ganglioside application affecting the motor as well as the sensory system, resembling acute motor sensory axonal neuropathy (AMSAN). Impairment of the spinal anterior horn cells with their axons was suggested to be responsible for prolonged motor symptoms and the predominantly axonal type of neuropathy at least as a late-stage feature in these two cases with fatal outcome. Insignificant cellular infiltrates in the spinal cord were noted in the other two GBS cases. Focal cellular infiltration of spinal nerve roots and meninges was similar in all cases.     

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome and its variants by the agglutination assay

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.     

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.     

The refractory period of transmission is impaired in axonal Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is classified as acute motor axonal neuropathy (AMAN) or acute inflammatory demyelinating polyneuropathy (AIDP). Motor nerve conduction block is frequently found in both subtypes of GBS. To compare patterns of conduction block and the safety factor for impulse transmission in AMAN and AIDP, pairs of supramaximal stimuli at intervals of 1-5 ms were delivered to stimulate the median nerve at the wrist. At the 2- and 3-ms intervals, compound muscle action potentials (CMAPs) to the second stimulus were significantly smaller in AMAN patients (n = 7) than in normal subjects (n = 10) and AIDP patients (n = 6). Over 4 weeks from onset, the amplitude of both conditioned and unconditioned CMAPs returned toward normal, consistent with improvement in the safety factor for impulse transmission. The refractory period of transmission is impaired in AMAN, and the site of transmission failure is likely to be the motor nerve terminals. In addition to axonal degeneration, the critically but reversibly reduced safety factor is important in the pathophysiology of AMAN, and consistent with the rapid resolution of distal conduction block often seen in AMAN patients.