Axonal variants of Guillain–Barré syndrome: an update

Journal of Neurology - Axonal variants of Guillain–Barré syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and...     

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.     

CYBA allelic variants are associated with severity and recovery in Guillain–Barré syndrome

Background and Aims

Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22^phox) on acute severity, axonal damage, and recovery in adult GBS patients.

Methods

Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years.

Results

CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/ G and rs4673/ A , were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS.

Interpretation

These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.     

Nationwide survey of childhood Guillain-Barré syndrome,Fisher syndrome,and Bickerstaff brainstem encephalitis in Japan

ObjectiveGuillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan.MethodsWe sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis.ResultsFive-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year.ConclusionThe prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange.     

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.     

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.     

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.     

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.     

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.     

Antiganglioside antibodies in Guillain-Barré syndrome and its related conditions

Guillain-Barré syndrome (GBS) is typically classified into two major subtypes: acute inflammatory demyelinating neuropathy and acute motor axonal neuropathy. Its most recognizable variant is Fisher syndrome. The last two decades have seen considerable advances in our understanding of GBS. Of note, various autoantibodies against ganglioside antigens have been identified and found to have significant associations with the axonal forms of GBS and Fisher syndrome. In this article, we discuss the different clinical presentations in GBS and the role of antiganglioside antibodies in their underlying pathogenesis. We also discuss the impact that antiganglioside antibodies have had in the development of experimental models and treatment modalities in GBS.     

Clinical and electrophysiological features of Guillain–Barré syndrome in Iran

We evaluated the clinical and electrophysiological characteristics of 121 consecutive patients admitted with Guillain–Barré syndrome (GBS) to a tertiary referral hospital in Tehran, Iran, from 1997 to 2007. The mean age of patients was 38.9 (standard deviation 19.7) years. The predominant subtype of GBS was the demyelinating form. Miller Fisher syndrome was present in 3.3% of patients. There was no significant seasonal clustering among the three subtypes, but axonal variants tend to occur in summer. In contrast with other subtypes, the majority of patients with acute motor-sensory axonal neuropathy (AMSAN) were female (72.3%). AMSAN patients also had significantly longer hospitalization time (p = 0.002) and intensive care unit (ICU) admission (p = 0.017), while none of the acute motor axonal neuropathy patients needed ICU admission. Involvement of cranial nerves and symmetry of signs were significantly detected in the demyelinating variant (p = 0.021 and p = 0.040, respectively). The overall mortality was 3.3%.     

Cerebellar ataxia and acute motor axonal neuropathy associated with Anti GD1b and Anti GM1 antibodies.

The anti-GD1b antibody is known to bind to the cerebellar granular layer or spinocerebellar Ia fibers. A few cases of anti-GD1b positive acute inflammatory demyelinating polyneuropathy with prominent cerebellar ataxia were reported. Recently, we encountered a middle-aged woman with Guillain Barré syndrome (GBS) with severe cerebellar ataxia and relatively mild motor weakness. Anti-GD1b Ig G antibody and anti-GM1 Ig G antibody titers were markedly elevated in her serum. She was diagnosed with acute motor axonal neuropathy (AMAN) with prominent cerebellar ataxia based on the results of the serial nerve conduction study suggesting axonal neuropathy. This case presents the clinico-pathogenic role of autoantibodies to the GD1b and the GM1 in acute inflammatory neuropathy.     

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.     

Two sets of nerve conduction studies may suffice in reaching a reliable electrodiagnosis in Guillain–Barré syndrome

ObjectiveRecent studies have advocated the use of serial nerve conduction studies (NCS) in the electrodiagnosis of Guillain–Barré syndrome (GBS). The current study aims to elucidate when and how frequent NCS can be performed to reflect the disease pathophysiology.MethodsA prospective study of GBS patients documenting the initial and final electrodiagnoses following serial NCS performed at three time intervals: 1–2 weeks, 3–8 weeks and 8–12 weeks.ResultsTwenty-one patients were recruited over a period of 2 years. Electrodiagnosis within 2 weeks revealed 17 acute inflammatory demyelinating polyneuropathy; two acute motor axonal neuropathy and two unclassified. After 12 weeks the final diagnoses were: 12 acute inflammatory demyelinating polyneuropathy; seven acute motor axonal neuropathy and two unclassified. NCS performed within the 3–8 week period reflected the true electrodiagnosis. Patients with acute inflammatory demyelinating polyneuropathy had persistent demyelination features at the 8–12 week NCS.ConclusionTwo sets of NCS performed within the first 2 weeks and between 3–8 weeks of disease onset is likely to suffice in elucidating the true electrodiagnosis of GBS.SignificanceThese findings can be incorporated into a much-needed revision of the existing GBS electrodiagnostic criteria.     

吉兰-巴雷综合征发病机制研究进展

吉兰-巴雷综合征是临床常见的急性炎性周围神经病,在我国发病率较高。主要分为急性炎性脱髓鞘性多发神经根神经病、急性运动轴索性神经病、急性运动感觉轴索性神经病及Miller Fisher综合征等亚型。近年对吉兰-巴雷综合征主要亚型的发病机制已有更深入的研究。     

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.     

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.     

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barré Syndrome in Korea: A Nationwide Multicenter Study

Background and Purpose

No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barré syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance.

Methods

Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody.

Results

Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study.

Conclusions

Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.     

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.     

Association between acute motor axonal neuropathy and ophthalmoplegia during pregnancy

Different subtypes producing the clinical picture of Guillain-Barré syndrome (GBS) and overlapping forms of GBS subtypes have been described. GBS as a complication in pregnancy has been reported rarely. The present report describes the clinical, electrophysiological and prognostic features of a pregnant woman with overlapping forms of GBS subtypes, acute motor axonal neuropathy and ophthalmoplegia.