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Background and purpose This study aimed to investigate geographical differences in the clinical features of Guillain-Barre syndrome (GBS) between patients from our region in Eastern China and patients from other areas. Methods A total of 595 patients fulfilling the diagnostic criteria ​for GBS or its variants were included from two large hospitals located in Eastern China. Data collection included demographics, antecedent events, clinical presentation and signs, electrophysiological subtypes, treatment, complications during hospitalization, clinical severity at nadir, and outcome at 12 months, and these data were compared to data from a study conducted in Southern China and the Europe/Americas section of the International GBS Outcome Study. Results The median (interquartile range) age of patients was 50 (36-61) years, the ratio of men to women was 1.2, and 49% of patients had antecedent events. Patients in our region of Eastern China had pure motor predominant GBS (158/340, 46%) and 30% (103/340) had complications during hospitalization. Patients aged over 60 years had a lower frequency of antecedent infections and single, axonal subtypes, but higher disability scores at entry, nadir, and 12 months. When compared with the Europe/Americas data, our patients had a lower frequency of antecedent infection (46% vs. 63%), cranial nerve involvement (43% vs. 49%), sensory deficits (45% vs. 69%), pain (19% vs. 57%) and mechanical ventilation (11% vs. 17%), but a higher frequency of axonal subtype (35% vs. 6%). There was a higher frequency of patients with antecedent gastroenteritis (16% vs. 8%), mechanical ventilation (11% vs. 8%) and axonal subtypes (35% vs. 19%) in our region in Eastern China than in Southern China. Conclusions Patients with GBS in Eastern China showed significant clinical heterogeneity and differences when compared to other geographic areas.

Introduction We present a painful small-fiber neuropathy variant of Guillain-Barre syndrome characterized by antecedent infectious symptoms, hyporeflexia, and albuminocytologic dissociation. Methods Two patients received intravenous immunoglobulin, one corticosteroids. Results The patients subsequently improved. Immunoglobulin G (IgG) antibodies in their acute phase sera strongly bound to murine small nerve fibers, and the binding disappeared during the convalescent phase. Serum transfer to a murine nociceptive model induced transient alteration in thermal pain responses. Discussion Our case series suggest that an acute transient immune response can be directed against small nerve fibers, and that patients so affected can exhibit features of Guillain-Barre syndrome. Muscle Nerve 57: 320-324, 2018.

IgG autoantibodies against gangliosides show the highest titers at the disease onset of axonal Guillain-Barré syndrome (GBS), in which there are no IgM anti-ganglioside antibodies. We hypothesized that memory B cells take part in the development of producing IgG autoantibodies. In this study, we analyzed the memory B cells in patients with GBS using flow cytometry. There was significantly higher percentage of memory B cells in patients with GBS than the healthy controls. The Spearman correlation analysis demonstrated that increased percentage of memory B cells was positively correlated with the clinical severity of the patients with GBS. Our study provides the evidences that memory B cells may be involved in mechanism of GBS.

Introduction: Paraparetic Guillain-Barre syndrome (GBS) is a rare subtype of GBS characterized by leg weakness and areflexia in the absence of neurological involvement of the arms, cranial nerves, or respiratory muscles. Onset is characterized by lower back, buttock, or leg pain, followed by development of symmetric flaccid limb weakness in the absence of sensory disturbance. Methods: We describe an elderly woman who developed postinfectious symmetric flaccid leg weakness in the absence of sensory disturbance. Serial nerve conduction studies were carried out over 5 months. Results: Antecedent infection, a monophasic disease course, and the presence of cerebrospinal fluid albuminocytological dissociation suggested a diagnosis of paraparetic GBS. Serial nerve conduction studies demonstrated nondemyelinating reversible conduction failure, which was restricted to the legs. Axonal neuropathy was supported by the presence of anti-GM1 IgG antibodies. Conclusions: These findings suggest that patients with paraparetic GBS have axonal neuropathy, which is restricted to the lower limbs. Muscle Nerve 55: 281–285, 2017

Objective Guillain–Barre syndrome (GBS), Miller Fisher syndrome (MFS), and Bickerstaff brainstem encephalitis (BBE) are usually monophasic, but some patients experience recurrences after long asymptomatic intervals. We aimed to investigate clinical features of recurrent GBS, MFS, and BBE at a single hospital. Methods Records from 97 consecutive patients with GBS, MFS or BBE who were admitted to a tertiary hospital between 2001 and 2013 were reviewed. Clinical and laboratory features of patients with recurrent GBS, MFS, or BBE were investigated. Results Patients included 55 (32 males) with GBS, 34 (22 males) with MFS, and 8 (6 males) with BBE. Recurrent cases occurred in 2 (4%) of the 55 patients with GBS, 4 (12%) of the 34 patients with MFS, and 2 (25%) of the 8 patients with BBE. Patients with recurrent MFS had a tendency to be younger at the first episode than patients with non-recurrent MFS (median, 22 versus 37 years old). Symptoms and signs were less severe during relapses than during the initial episode in recurrent patients. Conclusions Recurrences occurred more frequently in patients with MFS or BBE compared with those with GBS. Patients with recurrent MFS might be younger than those with non-recurrent MFS.

Background and purpose Fisher syndrome (FS) may overlap with Guillain–Barre syndrome (GBS), in particular the pharyngeal–cervical–brachial variant form (PCB-GBS), or Bickerstaff brainstem encephalitis (BBE). Our aim was to elucidate the frequency of this overlap and the patterns of clinical progression in patients with FS. Methods Sixty consecutive patients with FS were studied. FS/PCB-GBS was diagnosed when the patients developed pharyngeal, cervical and/or brachial weakness. Patients with flaccid tetraparesis were diagnosed as having FS/conventional GBS. FS/BBE was defined as the development of consciousness disturbances. Results All 60 patients initially developed the FS clinical triad alone (pure FS). Of these, 30 (50%) patients had pure FS throughout their course, whereas the remaining 50% of patients showed an overlap: PCB-GBS in 14 (23%) patients, conventional GBS in nine (15%) patients and BBE in seven (12%) patients. The median (range) durations from FS onset to progression to FS/PCB-GBS, FS/GBS or FS/BBE were 5 (1–7), 3 (1–4) and 3 (1–5) days, respectively. Patients with overlap syndromes more frequently received immune-modulating treatment, and the outcomes were generally favourable. The frequencies of positivity for anti-GQ1b, GT1a, GD1a, GD1b, GalNAc-GD1a and GM1 antibodies were not significantly different amongst the four groups. Conclusions Of the patients with pure FS, 50% later developed an overlap with PCB-GBS, conventional GBS or BBE. The overlap occurred within 7 days of FS onset; thus, physicians should pay attention to the possible development of this overlap during the first week after FS onset.

A 17-year-old male with no medical history noticed weakness of his limbs with imbalance and subsequent finger tremors. Physical examination revealed features of polyneuropathy, including diffuse weakness, distal symmetrical numbness with impaired deep sensation and areflexia in all limbs. Postural tremor was present in fingers. Ataxia was apparent in both lower limbs, causing a wide-based gait with a positive Romberg sign. Cerebrospinal fluid contained elevated total protein without pleocytosis. A nerve conduction study disclosed demyelinating features with prolonged terminal latencies, slow velocities with delayed F-wave latencies, and prominent temporal dispersion. These findings led to diagnosis of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with notable feature of postural finger tremor and ataxia of unknown cause. These atypical features prompted us to examine neurofascin-155 (NF155) antibodies, which were positive. No significant improvement occurred after initial administration of intravenous immunoglobulin and subsequent plasma exchange. However, corticosteroids with intravenous pulse therapy followed by oral prednisolone significantly improved the symptoms. Patients with CIDP with anti-NF155 antibodies may have similar clinical features and constitute a CIDP subgroup. In such patients, corticosteroids may be more effective than intravenous immunoglobulin. Further studies are needed to define the features of this subgroup and determine effective therapy for CIDP.

Objective The “sural-sparing pattern” of Guillain–Barre syndrome (GBS) is believed to reflect demyelinating pathology. We asked if it is present in non-demyelinating GBS-subtypes, namely acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN) and Miller Fisher syndrome (MFS), in addition to acute inflammatory demyelinating polyneuropathy (AIDP). Methods We studied the occurrence of sural-sparing pattern in clinically defined GBS and MFS patients. Using serial electrodiagnostic studies, GBS patients were divided into AIDP, according to appearance of demyelination–remyelination and AMAN/AMSAN, if there were signs of reversible conduction failure or Wallerian-like degeneration. Equivocal cases were left unclassified. We defined sural-sparing as a greater decrease in median and or ulnar sensory nerve action potential than that of the sural, compared to age and height-matched normal controls. Results Twelve of 30 GBS and 7 of 20 MFS patients had sural-sparing. This pattern was seen in 4 of 8 AIDP, 5 of 13 AMAN/AMSAN and 3 of 9 unclassified cases. Sequential studies uncovered sural-sparing, initially covert, in additional 1 MFS, 1 unclassified, 1 AIDP and 1 AMAN/AMSAN patient. Conclusions Sural-sparing occurs in axonal and demyelinating GBS subtypes. Significance The sural-sparing pattern reflects a pathological process common to axonal and demyelinating GBS-subtypes alike.

Introduction: Acute bulbar, neck, and limb weakness carries several potential differential diagnoses. Although a diagnosis can often be established clinically, investigations such as electrodiagnostic and antibody testing can provide support for the clinical diagnosis and may aid in understanding the pathogenesis. A 65-year-old woman presented with acute bulbar, neck, and rapidly progressive bilateral upper limb weakness. Methods: Clinical evaluation, electrophysiological, and serological studies were undertaken. Results: Neurophysiology demonstrated proximal conduction block. A clinical diagnosis of pharyngeal-cervical-brachial weakness, a localized variant of Guillain-Barre syndrome, was made. The patient received treatment with intravenous immunoglobulin and made a remarkable recovery over the next month. She was found to have serum monospecific anti-GT1a antibodies. Conclusions: We report a case of pharyngeal-cervical-brachial weakness with monospecific anti-GT1a antibodies and discuss the differential diagnosis of acute bulbar, neck, and limb weakness. Muscle Nerve, 2015

The present review aims at discussing the recent advances in pathogenesis, diagnosis, and treatment of major subtypes of autoimmune inflammatory neuropathies.Concerning pathogenesis, further evidence has proved that antibodies to nodal proteins are pathogenic in inflammatory neuropathies. The presence of these antibodies is related to distinctive clinical features. Disruption of blood-nerve barrier mediated by cytokines and chemokines also plays an important role in the pathogenesis. The new terminology of 'nodopathies' describes immune-mediated attack beginning and limited to the nodal region, and this phenomenon can be found in both acute and chronic inflammatory neuropathies. Recent trials comparing intravenous and subcutaneous immunoglobulin confirm that subcutaneous immunoglobulin is not only cost-effective, but also improves patients' satisfaction and quality of life compared to intravenous immunoglobulin. Although immunotherapies are effective in most of the inflammatory neuropathies, accurate predictors and biomarkers of treatment response are lacking. Moreover, some patients do not respond to current immunotherapies and continue to relapse after discontinuation of treatment.More studies are required to understand the exact antigenic targets and mechanism in inflammatory neuropathies, so as to develop more novel immunotherapies.

Bifacial weakness with paresthesias (BFP) is a subtype of Guillain-Barre syndrome defined by rapidly progressive bilateral facial weakness in the absence of other cranial neuropathies, ataxia, or limb weakness. Many patients also complain of distal limb paresthesias and display diminished or absent deep tendon reflexes. BFP is a localized form of Guillain-Barre syndrome and is thought to be caused exclusively by demyelinating- rather than axonal-type neuropathy. Patients with BFP do not display anti-ganglioside IgG antibodies. Since it is rare, many physicians are unfamiliar with BFP, as bilateral facial weakness is more commonly associated with sarcoidosis, Lyme disease, or meningeal pathology. Many patients diagnosed with bilateral Bell palsy may instead have BFP. In this review, we highlight the clinical features of BFP and outline diagnostic criteria.

Background and purpose Anti-GQ1b antibodies have been found in patients with Miller Fisher syndrome as well as its related conditions. Our aim was to identify the mechanism by which autoantibodies produce various clinical presentations in ‘anti-GQ1b antibody syndrome’. Methods Immunoglobulin G antibodies to ganglioside complex (GSC) of GQ1b or GT1a with GM1, GD1a, GD1b or GT1b were tested in sera from patients with anti-GQ1b (n = 708) or anti-GT1a (n = 696) IgG antibodies. Optical densities of the single anti-GQ1b or anti-GT1a antibodies were used as reference (100%), and those of anti-GSC antibodies were expressed in percentages to reference. The relationships between anti-GSC antibody reactivity and the corresponding clinical features were assessed by multivariate logistic regression analysis. Results Ophthalmoplegia and hypersomnolence were significantly associated with complex-attenuated anti-GQ1b and anti-GT1a antibodies. Ataxia was associated with GD1b- and GT1b-enhanced anti-GQ1b antibodies or GM1-enhanced anti-GT1a antibodies. Bulbar palsy was associated with GT1b-enhanced anti-GQ1b antibodies. Neck weakness was associated with GD1a-enhanced anti-GQ1b antibodies. Arm weakness was associated with GD1b-enhanced anti-GQ1b and GD1a-enhanced anti-GT1a antibodies. Leg weakness was associated with GD1a-enhanced anti-GQ1b and anti-GT1a antibodies. Conclusions Differences in fine specificity of anti-GQ1b antibodies are associated with clinical features, possibly due to the different expression of gangliosides in different parts of the nervous system.

Introduction: Conduction block (CB) has been included in the Rajabally criteria for axonal Guillain–Barre syndrome (GBS). Because the nerve roots may be affected early in GBS, detection of proximal CB by the triple stimulation technique (TST) can be useful. Methods: We describe TST findings in 2 patients who presented with the pharyngeal–cervical–brachial (PCB) variant of axonal GBS. Results: In the first patient, although conventional nerve conduction studies (NCS) did not fit electrodiagnostic criteria for axonal GBS, the TST detected proximal CB in the median and ulnar nerves. In the second patient, NCS fulfilled criteria for axonal GBS, and the TST detected proximal CB in the median nerve. After plasmapheresis, NCS and TST findings were normalized, suggesting reversible conduction failure rather than demyelinating CB. Conclusion: The TST may be useful for diagnosis of PCB when NCS remain inconclusive. The technique provides additional clues for classifying PCB into the acute nodo-paranodopathies. Muscle Nerve, 2015

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS.

Introduction: Guillain–Barre syndrome is the most common acute flaccid paralysis worldwide. Advances in pathogenesis and diagnosis over recent years have enhanced our understanding of the disease.Areas covered: Literature in PubMed and Cochrane Library with keywords of ‘Guillain-Barre syndrome’, ‘acute motor axonal neuropathy’, ‘diagnosis’ and ‘pathogenesis’ were searched. Papers up to January 2015 were included and the emphasis is mainly put on those published in the past 3 years.Expert opinion: Significant advances have been made in the diagnosis and pathogenesis of Guillain–Barre syndrome and improvement has been made in the understanding of the disease as well as management of patients. However, more studies involving large multicenter cohorts are required as there are still unanswered questions in this field.

To evaluate the use of intravenous immunoglobulin (IVIG) in preventing relapses in patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSDs).Six NMO/NMOSD patients who were treated with IVIG induction dose followed by 2- to 3- monthly infusions were retrospectively identified. Annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) pre- and post-IVIG were recorded.Median number of relapses and median ARR significantly reduced from 8.0 to 1.0 and 0.75 to 0.15 (p0.05) respectively. Median EDSS of 6.5 remained the same. Median duration of treatment was 4.0 years.IVIG may be used to reduce the relapse frequency in patients with NMO/NMOSD.

Cerebrospinal fluid (CSF) protein level, cell count, and its relationship to the timing of lumbar puncture were collected from patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) from various Asian centers. A total of 507 patients with GBS were studied. Overall, 56% had elevated CSF protein level. This was significantly lower than that reported in a recent Dutch study (56% vs 64%). Cytoalbuminologic dissociation was also lower in the Asian cohort (55% vs 64%), with a significantly higher proportion of patients with mild pleocytosis (26% vs 15%). A lower proportion of the 164 patients with MFS had elevated CSF protein level (38% vs 56%), mild pleocytosis (11% vs 26%), and cytoalbuminologic dissociation (41% vs 55%) compared to patients with GBS. In both conditions, cytoalbuminologic dissociation was linked to the timing of lumbar puncture. Cytoalbuminologic dissociation was only observed in half of the Asian patients with GBS and MFS, and it is strongly dependent on the timing of the lumbar puncture.

Introduction: Dr. C. Miller Fisher described the appearance of unilateral facial palsy after resolution of ataxia in a patient with the eponymic Miller Fisher syndrome (MFS). However, there have been very few reports of delayed appearance of facial weakness in Guillain-Barre syndrome (GBS) and MFS when the other neurological signs reached nadir or started improving. Methods: In this study we reviewed the clinical and laboratory findings of consecutive patients with GBS (n = 195) and MFS (n = 68). Results: Delayed facial weakness occurred in 12 (6%) GBS and 4 (6%) MFS patients and was unilateral in 5 (42%) GBS and 2 (50%) MFS patients. In those patients with delayed facial weakness, neither limb weakness nor ataxia progressed, and facial weakness disappeared without immunotherapy. Conclusions: Because facial weakness can lead to further morbidity, it would be prudent for clinicians to warn patients of this possibility, although additional immunotherapy is usually not required. Muscle Nerve 51: 811–814, 2015

Guillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features of acute motor axonal neuropathy are reduced amplitude or absence of distal compound muscle action potentials indicating axonal degeneration. In contrast, autopsy study results show early nodal changes in acute motor axonal neuropathy that may produce motor nerve conduction block. Because the presence of conduction block in acute motor axonal neuropathy has yet to be fully recognized, we reviewed how often conduction block occurred and how frequently it either reversed or was followed by axonal degeneration. Based on Ho's criteria, acute motor axonal neuropathy was electrodiagnosed in 18 patients, and repeated motor nerve conduction studies were carried out on their median and ulnar nerves. Forearm segments of these nerves and the across-elbow segments of the ulnar nerve were examined to evaluate conduction block based on the consensus criteria of the American Association of Electrodiagnostic Medicine. Twelve (67%) of the 18 patients with acute motor axonal neuropathy had definite (n = 7) or probable (n = 5) conduction blocks. Definite conduction block was detected for one patient (6%) in the forearm segments of both nerves and probable conduction block was detected for five patients (28%). Definite conduction block was present across the elbow segment of the ulnar nerve in seven patients (39%) and probable conduction block in two patients (11%). Conduction block was reversible in seven of 12 patients and was followed by axonal degeneration in six. All conduction blocks had disappeared or begun to resolve within three weeks with no electrophysiological evidence of remyelination. One patient showed both reversible conduction block and conduction block followed by axonal degeneration. Clinical features and anti-ganglioside antibody profiles were similar in the patients with (n = 12) and without (n = 6) conduction block as well as in those with (n = 7) and without (n = 5) reversible conduction block, indicating that both conditions form a continuum; a pathophysiological spectrum ranging from reversible conduction failure to axonal degeneration, possibly mediated by antibody attack on gangliosides at the axolemma of the nodes of Ranvier, indicating that reversible conduction block and conduction block followed by axonal degeneration and axonal degeneration without conduction block constitute continuous electrophysiological conditions in acute motor axonal neuropathy

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.

Autoantibodies to nodal/paranodal proteins have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). To determine the frequency of anti-paranodal antibodies in our cohort of CIDP patients and to validate the presence anti-nodal antibodies in MMN, sera were screened for IgG against human neurofascin 155, contactin-1, neurofascin 186 and gliomedin using ELISA. In CIDP patients, 7% were anti-NF155 IgG4 positive and 7% were anti-CNTN1 IgG4 positive. Positive results were confirmed using cell based assays and indirect immunofluorescence on teased nerve fibres. We did not detect IgG autoantibodies against these nodal/paranodal antigens in MMN patients.

Autoimmunity is an important cause of disease both in the central and peripheral nervous systems. Aetiologies and clinical manifestations are complex and heterogeneous. Inappropriate control of complement activation at inappropriate sites has been recognized as a major determinant in several neurological conditions, including Guillain-Barré syndrome and neuromyelitis optica. In each case pathogenesis is thought to be associated with generation of autoantibodies which upon binding guide activation of the complement system to self-tissue. Areas covered: Modulation of the complement system activation at such sites may represent a novel therapeutic approach for treatment of immune-mediated inflammatory conditions. In this review we focus on the therapeutic effects of complement inhibitors in Guillain-Barré syndrome and neuromyelitis optica and highlight recent developments within the field. Expert Commentary: Conventional first line treatment strategies in GBS and NMO have the potential disadvantage of causing widespread immunosuppressive effects. A more targeted approach may therefore be more effective and less disruptive to the immune system, especially in the case of NMO, which requires long term immunosuppression. Modulation of the complement system may hold the key and has already been shown to be of clinical benefit in other non-neurological conditions, including paroxysmal nocturnal hemoglobinuria and hereditary angioedema.

Guillain–Barre syndrome and chronic inflammatory demyelinating polyneuropathy are autoimmune disorders of the peripheral nervous system in which autoantibodies are implicated in the disease pathogenesis. Recent work has focused on the nodal regions of the myelinated axon as potential autoantibody targets. Here we screened patient sera for autoantibodies to neurofascin and assessed the pathophysiological relevance of anti-neurofascin antibodies in vivo . Levels of anti-neurofascin antibodies were higher in sera from patients with Guillain–Barre syndrome and chronic inflammatory demyelinating polyneuropathy when compared with those of controls. Anti-neurofascin antibodies exacerbated and prolonged adoptive transfer experimental autoimmune neuritis and caused conduction defects when injected intraneurally.

A 72-year-old man presented with sudden onset of right-sided facial muscle weakness and slurred speech and a 3-day history of fevers, myalgia and sore throat. There was no hyperacusis, change in taste or lacrimation. His history included untreated hepatitis C diagnosed 10 years before, but quiescent at his annual liver review 8 weeks before presentation. He smoked cannabis intermittently but there was no recent alcohol or other drug abuse. There was a history of promiscuity with female partners. On examination, he was alert and orientated. His blood pressure was elevated at 159/86 mm Hg but other vital signs and general examination were normal. Neurological examination showed a severe right-sided lower motor facial weakness with Bell's phenomenon (see online supplementary video). The remaining cranial nerve examination was normal, including eye movements, pupillary responses, facial sensation, hearing, taste and otoscopy. There was mild left hip flexion weakness but preserved deep tendon reflexes. There was reduced sensation to temperature in a glove-and-stocking pattern; joint-position sense, light touch and pain sensation were intact. There was mild gait instability on walking tandem. His condition progressed rapidly and on day 2 of admission he developed left-sided facial weakness (figure 1) with bilateral, proximal lower limb weakness. His paraesthesias were more painful. His lower limb deep tendon reflexes were no longer present (see online supplementary video). Spirometry remained normal. He was transferred to a high dependency unit for ongoing monitoring. Figure 1 Bifacial lower motor neurone weakness (see online supplementary video). ### Question 1 What is the differential diagnosis and what are the most appropriate investigations? Lower motor neurone facial weakness and (to a lesser extent) the absence of deep tendon reflexes are highly localising signs. The lesion explaining the facial and the limb weakness can be …

A few studies have reported the association of autoantibodies to GM1 or GQ1bα with Alzheimer's disease (AD) or vascular dementia. Here we investigated whether patients with AD or vascular dementia had high titers of the anti-ganglioside antibodies. Sera were obtained from patients with AD (n = 22), vascular dementia (n = 14), Guillain-Barré syndrome, and multifocal motor neuropathy as well as normal controls. Enzyme-linked immunosorbent assay showed titers of IgG and IgM anti-GM1, anti-GQ1bα, and anti-GT1aα antibodies did not differ among AD, vascular dementia, and normal controls, and being remarkably lower than those in Guillain-Barré syndrome and multifocal motor neuropathy. The anti-ganglioside antibodies are not biological markers of AD.

Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.

Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS) have several subtypes, together forming a continuous spectrum of discrete and overlapping syndromes. Such is the heterogeneity within this spectrum that many physicians may be surprised to learn that these disorders are related pathophysiologically, and therefore share certain clinical features. These include history of antecedent infection, monophasic disease course and symmetrical cranial or limb weakness. The presence of cerebrospinal fluid albuminocytological dissociation (raised protein, normal cell count), antiganglioside antibodies and neurophysiological evidence of axonal or demyelinating neuropathy also support a diagnosis in many cases, but should not be relied upon. Mimics of GBS and MFS can broadly be divided into those presenting with symmetrical limb weakness and those presenting with brainstem signs. MFS and the pharyngeal-cervical-brachial variant of GBS are frequently mistaken for brainstem stroke, botulism or myasthenia gravis, whereas Bickerstaff's brainstem encephalitis is often diagnosed as Wernicke's encephalopathy. Chameleons or atypical presentations of GBS-related disorders include: paraparetic GBS, bifacial weakness with paraesthesias, acute ataxic neuropathy, acute ophthalmoparesis, acute ptosis and acute mydriasis. Many neurologists may also not be aware that deep tendon reflexes remain present or may even appear brisk in up to 10% of patients with GBS. Correct diagnosis of GBS-related disorders helps to avoid unnecessary investigations and allows early immunotherapy if appropriate.

Objective: To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barre syndrome subtypes and clinical features. Methods: In acute sera from 199 patients with Guillain-Barre syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside complexes were tested using ELISA against individual antigens from single glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from the combination of 2 different glycolipids. Based on serial nerve conduction studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85 axonal subtypes, and 45 unclassified. Results: Significant associations were detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1, GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or complex of LM1/GA1. No significant association was demonstrated between acute inflammatory demyelinating polyneuropathy and any of the glycolipids or ganglioside complexes. Anti-ganglioside complex antibodies alone were detected in 7 patients (5 axonal subtype). Conclusions: The current study demonstrates that antibodies to single glycolipids and ganglioside complexes are associated with acute motor axonal neuropathy or acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Classification of evidence: This study provides Class II evidence that antibodies to glycolipids are increased in patients with acute motor axonal neuropathy and acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy.

Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.

Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

Acute ataxic neuropathies with disialosyl antibodies include Fisher syndrome, ataxic Guillain-Barre syndrome (GBS), and acute sensory ataxic neuropathy. Fisher syndrome and ataxic GBS are more strongly associated with IgG anti-GQ1b and anti-GT1a than with anti-GD1b antibodies, whereas the association is reversed in the case of acute sensory ataxic neuropathy. Chronic ataxic neuropathy with disialosyl antibodies is associated with IgM paraprotein to GD1b and GQ1b, which occasionally reacts with GT1a. The clinical, electrophysiological, and pathological features, along with experimental findings, suggest that acute and chronic ataxic neuropathies with disialosyl antibodies form a continuous clinical and pathophysiological spectrum characterized by a complement-mediated disruption at the nodal region and are better classified in the new category of nodo-paranodopathies.

Introduction: Differing patterns of neurophysiological abnormalities have been reported in patients with Fisher syndrome. Fisher syndrome is rare, and few series have incorporated prospective serial studies to define the natural history of nerve conduction studies in Guillain–Barre syndrome. Methods: In an ongoing prospective study of Guillain–Barre syndrome patients, patients who presented with Fisher syndrome and its spectrum of illness were assessed through serial neurological examinations, nerve conduction studies, and serological testing of IgG against gangliosides and ganglioside complexes. Results: Of the 36 Guillain–Barre syndrome patients identified within 2 years, 17 had features of Fisher syndrome. Serial nerve conduction studies detected significant abnormalities in sensory nerve action potential amplitude in 94% of patients associated with 2 patterns of recovery—non-demyelinating reversible distal conduction failure and axonal regeneration. Similar changes were seen in motor nerves of 5 patients. Conclusions: Patients with the Fisher syndrome spectrum of illness have significant sensory involvement, which may only be evident with serial neurophysiological studies. Muscle Nerve 49:558–563, 2014

Results from the PATH study indicate that subcutaneous immunoglobulin is efficacious and well tolerated for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). This finding represents an important step in the management of patients with immunoglobulin-responsive CIDP, with considerable implications for the cost of treatment and, most importantly, for these patients' quality of life.

Over the past 20 years, the most notable advance in understanding Guillain–Barre syndrome (GBS) has been the identification of an axonal variant. This advance arose chiefly through studies undertaken in East Asian countries and comprised two major aspects: first, the immunopathogenesis of axonal GBS related to anti-ganglioside antibodies and molecular mimicry of Campylobacter jejuni ; and second, the observation that distinct electrophysiological patterns of axonal GBS existed, reflecting reversible conduction failure (RCF). As a consequence, the pathophysiology of acute motor axonal neuropathy (AMAN) has perhaps become better understood than acute inflammatory demyelinating polyneuropathy. Despite these more recent advances, a critical issue remains largely unresolved: whether axonal GBS is more common in Asia than in Europe or North America. If it is more common in Asia, then causative factors must be more critically considered, including geographical differences, issues of genetic susceptibility, the role of antecedent infections and other potential triggering factors. It has become apparent that the optimal diagnosis of AMAN requires serial electrophysiological testing, to better delineate RCF, combined with assessment for the presence of anti-ganglioside antibodies. Recent collaborative approaches between Europe and Asia have suggested that both the electrophysiological pattern of AMAN and the seropositivity for anti-ganglioside antibodies develop similarly. Separately, however, current electrodiagnostic criteria for AMAN limited to a single assessment appear inadequate to identify the majority of cases. As such, diagnostic criteria will need to be revised to improve the diagnostic sensitivity for AMAN.

Summary Acute motor axonal neuropathy (AMAN) is a pure motor axonal subtype of Guillain-Barre syndrome (GBS) that was identified in the late 1990s. In Asia and Central and South America, it is the major subtype of GBS, seen in 30–65% of patients. AMAN progresses more rapidly and has an earlier peak than demyelinating GBS; tendon reflexes are relatively preserved or even exaggerated, and autonomic dysfunction is rare. One of the main causes is molecular mimicry of human gangliosides by Campylobacter jejuni lipo-oligosaccharides. In addition to axonal degeneration, electrophysiology shows rapidly reversible nerve conduction blockade or slowing, presumably due to pathological changes at the nodes or paranodes. Autoantibodies that bind to GM1 or GD1a gangliosides at the nodes of Ranvier activate complement and disrupt sodium-channel clusters and axoglial junctions, which leads to nerve conduction failure and muscle weakness. Improved understanding of the disease mechanism and pathophysiology might lead to new treatment options and improve the outlook for patients with AMAN.

In some anti-ganglioside antibody-mediated neuropathies, human and experimental data suggest a common pathogenic mechanism of dysfunction/disruption at the node of Ranvier resulting in a pathophysiologic continuum from transitory nerve conduction failure to axonal degeneration. The traditional classification of polyneuropathies into demyelinating or axonal may generate some confusion in the electrophysiological diagnosis of Guillain-Barré syndrome subtypes associated with anti-ganglioside antibodies. The axonal forms show, besides axonal degeneration, promptly reversible nerve conduction failure. This may be interpreted, by a single electrophysiological study, as demyelinating conduction block or distal axonal degeneration leading to errors in classification and in establishing prognosis. Moreover the term axonal may be misleading as it is commonly associated to axonal degeneration and not to a transitory, promptly reversible, dysfunction of the excitable axolemma. To focus on the site of nerve injury and overcome the classification difficulties, we propose the new category of nodo-paranodopathy which seems appropriate to various acute and chronic neuropathies associated with anti-ganglioside antibodies and we think better systematizes the neuropathies characterized by an autoimmune attack targeting the nodal region.

Objective The exclusive association of Campylobacter jejuni infection with the axonal variant of Guillain–Barre syndrome (GBS) is debatable. The current study aims to elucidate the GBS subtypes of patients with an antecedent C. jejuni infection. Methods Nerve conduction study results of 73 patients with GBS were reviewed. Patients were defined as having a recent C. jejuni infection when there was a positive stool culture or serological evidence of C. jejuni in the presence of preceding diarrhea. Results A total of 23 patients had evidence of a recent C. jejuni infection. At the early stage, patients were classified as AMAN ( n =9; 39%), AIDP ( n =3; 13%) or equivocal ( n =9) using existing electrophysiological criteria. Prolonged distal latencies and conduction slowing that were seen in 11 patients rapidly normalized within 3weeks in seven, whereas four had minor abnormalities throughout the course. Subsequently, all patients showed either acute motor axonal neuropathy pattern or reversible conduction failure. Conclusion Serial neurophysiology suggests that C. jejuni infections are exclusive to axonal GBS. Significance Our findings suggest that AMAN can demonstrate the full complement of demyelinating features at the early stages of disease.

Guillain-Barré syndrome (GBS) is the commonest cause of acquired flaccid paralysis in the world and regarded by many as the prototype for postinfectious autoimmunity. Here the authors consider both infectious and noninfectious triggers of GBS and determine where possible what immunological mechanisms may account for this association. In approximately two-thirds of cases, an infectious trigger is reported in the weeks that lead up to disease onset, indicating that the host's response to infection must play an important role in disease pathogenesis. The most frequently identified bacteria, Campylobacter jejuni, through a process known as molecular mimicry, has been shown to induce cross-reactive anti-ganglioside antibodies, which can lead to the development of axonal-type GBS in some patients. Whether this paradigm can be extended to other infectious organisms or vaccines remains an important area of research and has public health implications. GBS has also been reported rarely in patients with underlying systemic diseases and immunocompromised states and although the exact mechanism is yet to be established, increased susceptibility to known infectious triggers should be considered most likely.

Background: Optimal dose and timing of repeated intravenous immunoglobulin therapy (IVIg) for intractable chronic inflammatory demyelinating polyneuropathy (CIDP) patients have not been determined. The aim of this study was to optimize dose and timing of IVIg for CIDP patients who need frequent IVIg using daily grip strength measurement. Methods: Repeated IVIg were administered for two intractable CIDP patients. Grip strength was recorded at home every day to access the clinical change in symptoms, and dose and timing of IVIg were optimized based on the results. Results: The decrement on grip strength was a sensitive indicator of symptom exacerbation. 100 g of IVIg had a limited effect for each patient. In one patient, symptoms maintained after monthly 60 g of IVIg. In another, 100 g of IVIg every 7 weeks resulted in a marked improvement. After receiving 20 g of IVIg weekly, each patient showed further improvement. Conclusion: Optimal dose and timing possibly vary in each individual patient. Dose titration of IVIg is necessary to avoid over- and undertreatment. The daily self-monitoring of grip strength is a helpful tool for clinical assessment in CIDP.

A 52-year-old man presented with acute onset of weakness and paresthesias involving all 4 extremities in 2008 preceded by an episode of viral catarrh 3 weeks prior. Examination revealed symmetrical upper and lower extremity weakness (Medical Research Council [MRC] 3/5) and absent deep tendon reflexes. Sensory and cranial nerve examination was normal. CSF showed albumino-cytologic dissociation with leukocyte count of 3 and protein of 110 mg/dL. Acute demyelinating polyneuropathy (AIDP) was diagnosed based on electrodiagnostic studies (table), and IV immunoglobulin (IVIg) was commenced. Recovery was slow, taking 1 year. In 2014, he was admitted with similar symptoms. Examination revealed normal power of the upper extremities and grade 4/5 power of the lower extremities. There was loss of vibration and proprioception over his toes. Deep tendon reflexes were absent. There was facial diplegia. Considering the clinical presentation and electrodiagnostic studies, he was diagnosed with recurrent AIDP and treated with IVIg. He continued to deteriorate and by the third week, his power was MRC grade 3/5 in his upper and lower extremities. There was no bulbar involvement.

International audience; Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have recently been associated with subsets of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Contactin-1 and Nfasc155 are cell adhesion molecules that constitute the septate-like junctions observed by electron microscopy in the paranodes of myelinated axons. Antibodies to Contactin-1 have been shown to affect the localization of paranodal proteins both in patient nerve biopsies and in animal models after passive transfer. However, it is unclear whether these antibodies alter the paranodal ultrastructure. We examined by electron microscopy sural nerve biopsies from two patients presenting with anti-Nfasc155 antibodies, and also four patients lacking antibodies, three normal controls, and five patients with other neuropathies. We found that patients with anti-Nfasc155 antibodies presented a selective loss of the septate-like junctions at all paranodes examined. Further, cellular processes penetrated into the expanded spaces between the paranodal myelin loops and the axolemma in these patients. These patients presented with important nerve conduction slowing and demyelination. Also, the reactivity of anti-Nfasc155 antibodies from these patients was abolished in neurofascin-deficient mice, confirming that the antibodies specifically target paranodal proteins. Our data indicate that anti-Nfasc155 destabilizes the paranodal axo-glial junctions and may participate in conduction deterioration.

The pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome is defined by rapidly progressive oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs. Serial nerve conduction studies suggest that PCB represents a localised subtype of Guillain-Barré syndrome characterised by axonal rather than demyelinating neuropathy. Many neurologists are unfamiliar with PCB, which is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism. The presence of additional ophthalmoplegia and ataxia indicates overlap with Fisher syndrome. Half of patients with PCB carry IgG anti-GT1a antibodies which often cross-react with GQ1b, whereas most patients with Fisher syndrome carry IgG anti-GQ1b antibodies which always cross-react with GT1a. Significant overlap between the clinical and serological profiles of these patients supports the view that PCB and Fisher syndrome form a continuous spectrum. In this review, we highlight the clinical features of PCB and outline new diagnostic criteria.

International audience; OBJECTIVE: We report the clinical and serologic features of Japanese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) displaying anti-neurofascin-155 (NF155) immunoglobulin G4 (IgG4) antibodies.ăMETHODS: In sera from 533 patients with CIDP, anti-NF155 IgG4 antibodies were detected by ELISA. Binding of IgG antibodies to central and peripheral nerves was tested.ăRESULTS: Anti-NF155 IgG4 antibodies were identified in 38 patients (7%) with CIDP, but not in disease controls or normal participants. These patients were younger at onset as compared to 100 anti-NF155-negative patients with CIDP. Twenty-eight patients (74%) presented with sensory ataxia, 16 (42%) showed tremor, 5 (13%) presented with cerebellar ataxia associated with nystagmus, 3 (8%) had demyelinating lesions in the CNS, and 20 of 25 (80%) had poor response to IV immunoglobulin. The clinical features of the antibody-positive patients were statistically more frequent as compared to negative patients with CIDP (n = 100). Anti-NF155 IgG antibodies targeted similarly central and peripheral paranodes.ăCONCLUSION: Anti-NF155 IgG4 antibodies were associated with a subgroup of patients with CIDP showing a younger age at onset, ataxia, tremor, CNS demyelination, and a poor response to IV immunoglobulin. The autoantibodies may serve as a biomarker to improve patients' diagnosis and guide treatments.

Guillain-Barre syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti-ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes.

Guillain–Barre syndrome is an immune-mediated neuropathy that accounts for one of the most common acute neuromuscular paralysis worldwide. Characteristic to its history is an antecedent illness and this includes Campylobacter jejuni enteritis. The pathogenesis of C. jejuni-related Guillain–Barre syndrome has been extensively studied, and there is good evidence to support molecular mimicry between self and microbial components as the mechanism of disease. Self-antigens in the form of gangliosides which are predominantly cell-surface glycolipids highly expressed in nervous tissue share similar characteristics as lipo-oligosaccharides of C. jejuni outer membrane. Molecular mimicry has been demonstrated between GM1 ganglioside and lipo-oligosaccharide of C. jejuni isolated from Guillain–Barre syndrome patients. This includes the establishment of disease models by sensitisation of rabbits with GM1 and C. jejuni lipo-oligosaccharide. This chapter discusses the current understanding of Guillain–Barre syndrome following C. jejuni enteritis.

Intravenous immunoglobulin (IVIG), consisting of IgG, is the first-line treatment for Guillain-Barré syndrome and multifocal motor neuropathy. IgG, but neither IgM nor IgA, has been demonstrated in vitro to inhibit complement deposition mediated by anti-ganglioside autoantibodies in sera from patients with both conditions. The objective of this study is to investigate the in vitro effectiveness of IgM and IgA in inhibiting complement deposition to ganglioside/anti-ganglioside antibody complexes. Serum samples were obtained from patients with multifocal motor neuropathy associated with anti-GM1 IgM antibodies, Guillain-Barré syndrome associated with anti-GM1 IgG antibodies and Miller Fisher syndrome associated with anti-GQ1b IgG antibodies. Inhibition of complement deposition using different immunoglobulin preparations was measured by enzyme-linked immunosorbent assay. IgM/A-enriched IVIG and immunoglobulin isotypes (polyclonal IgM and IgA) showed higher potential in inhibiting complement deposition than standard IVIG. Although the safety concerns about the use of IgM and IgA for an immunotherapy still remain, IgM and IgA may serve as an alternative immunotherapy in those anti-ganglioside antibody-mediated neuropathies.

Pathophysiologically, Guillain-Barré syndrome is divided into demyelinating and axonal subtypes. Recent studies have shown that serial nerve conduction studies (NCSs) are required to differentiate a demyelination-remyelination pathophysiology from one with axonal nodal reversible conduction failure. Cases with an overlap of pharyngeal-cervical-brachial weakness and Fisher syndrome (PCB/FS) are uncommon; the NCS findings of such cases have not been well described and the evolution of the NCS findings has not been previously studied. We describe the clinical features and serial NCS findings of a patient with PCB/FS. The evolution of abnormalities in NCS reflected a clinical pattern of weakness that progressed from the top of the body and descended toward the legs, and terminated before reaching the legs. The amplitudes of motor and sensory potentials were decreased, as is consistent with acute motor-sensory axonal neuropathy. However, the amplitudes recovered without the appearance of dispersed potentials seen in remyelination, implicating the pathophysiology of nodal reversible conduction failure. Together with the electrophysiological evidence of the pathophysiology of nodal reversible conduction failure in previously reported PCB patients and FS patients, our case suggests that PCB, FS and PCB/FS fall in a continuous spectrum with axonal GBS subtypes.

In the 1950s, Bickerstaff and Fisher independently described cases with a unique presentation of ophthalmoplegia and ataxia. The neurological features were typically preceded by an antecedent infection and the majority of patients made a spontaneous recovery. In the cases with Bickerstaff brainstem encephalitis, there was associated altered consciousness and in some, hyperreflexia, in support of a central pathology whereas in Fisher syndrome, patients were areflexic in keeping with a peripheral aetiology. However, both authors recognised certain similarities to Guillain-Barré syndrome such as the presence of peripheral neuropathy and cerebrospinal fluid albuminocytological dissociation. The discovery of immunoglobulin G anti-GQ1b antibodies in patients with Fisher syndrome and later in Bickerstaff brainstem encephalitis was crucial in providing the necessary evidence to conclude that both conditions were in fact part of the same spectrum of disease by virtue of their common clinical and immunological profiles. Following this, other neurological presentations that share anti-GQ1b antibodies emerged in the literature. These include acute ophthalmoparesis and acute ataxic neuropathy, which represent the less extensive spectrum of the disease whereas pharyngeal-cervical-brachial weakness and Fisher syndrome overlap with Guillain-Barré syndrome represent the more extensive end of the spectrum. The conditions can be referred to as the 'anti-GQ1b antibody syndrome'. In this review, we look back at the historical descriptions and describe how our understanding of Fisher syndrome and Bickerstaff brainstem encephalitis has evolved from their initial descriptions more than half a century ago.