INTRODUCTION/AIMS:The value of electrodiagnostic subtyping of Guillain-Barré syndrome (GBS) is still debated. This study aimed to determine the diagnostic yield, timing, and changes of the electrodiagnostic subtyping in patients with GBS in serial nerve conduction studies (NCS). METHODS:Data were extracted from the International GBS Outcome Study (IGOS) database. Serial NCS were available for 469 patients. For the serial NCS analysis, the intervals between the first and second study were defined as ≥ 7 and ≤ 42 days after onset of weakness. All NCS were classified according to the electrodiagnostic criteria sets of Hadden et al. and Rajabally et al. RESULTS:In NCS conducted within 3 days of onset of weakness, an axonal or demyelinating subtype could be demonstrated in 58.4% (Hadden) and 52.1% (Rajabally). NCS performed at a later timepoint demonstrated a similar yield of axonal and demyelinating subtypes. In patients with motor-sensory and motor GBS, the electrodiagnostic subtype changed on serial NCS in 37.8% (Hadden) and 44.7% (Rajabally). As the subtypes changed in multiple and opposite directions, the total proportion of axonal and demyelinating subtypes remained stable across time points. In patients with motor GBS, both axonal and demyelinating subtypes were found. DISCUSSION:This study demonstrates the highly dynamic disease course of GBS. The role of NCS remains to support the clinical diagnosis of GBS and should be performed as quickly as possible after onset of weakness. If these early NCS are non-diagnostic, repeating the study should be considered. Electrodiagnostic subtyping offers no additional value.

Guillain–Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence‐based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence‐to‐Decision (EtD) frameworks. For the six intervention PICOs, evidence‐based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti‐ganglioside antibodies is of limited clinical value in most patients with typical motor‐sensory GBS, but anti‐GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal–paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute‐onset chronic inflammatory demyelinating polyradiculoneuropathy (A‐CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2–4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12–15 L in four to five exchanges over 1–2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission.

BACKGROUND AND PURPOSE:The aim of this study was to determine the frequency of over- and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls. METHODS:We conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups. RESULTS:A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level. CONCLUSION:Over- and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy.

This special commentary refers to ‘Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome’ by Keddie et al. (doi:10.1093/brain/awaa433).

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

The most common subtypes of Guillain‐Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes.

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are acute autoimmune neuropathies, often preceded by an infection. Antiglycolipid antibody titres are frequently elevated in sera from the acute-phase patients. Particularly, IgG anti-GQ1b antibodies are positive in as high as 90% of FS cases and thus useful for diagnosis. The development of animal models of antiglycolipid antibody-mediated neuropathies proved that some of these antibodies are directly involved in the pathogenetic mechanisms by binding to the regions where the respective target glycolipid is specifically localised. Discovery of the presence of the antibodies that specifically recognise a new conformational epitope formed by two different gangliosides (ganglioside complex) in the acute-phase sera of some patients with GBS suggested the carbohydrate–carbohydrate interaction between glycolipids. This finding indicated the need for further research in basic glycobiological science. Antiglycolipid antibodies, in particular antigangliosides antibodies, are mostly detected in acute motor axonal neuropathy type of GBS and in FS, and less frequently in the acute inflammatory demyelinating polyneuropathy (AIDP) type of GBS or in central nervous system (CNS) diseases. In the future, the search for the putative antibodies in AIDP and those that might be present in CNS diseases should continue. In addition, more efficient standardisation of antiglycolipid antibody detection methods and use as biomarkers in daily clinical practice in neurology is needed.

A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7–16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous immune-mediated disorder with extensive variation in clinical presentation, electrophysiological phenotype, treatment response and long-term outcome. This heterogeneity may reflect the existence of distinct subtypes of CIDP with a different pathogenesis that require personalized treatment. The International CIDP Outcome Study (ICOS) is a prospective, observational, multicenter cohort study that aims to describe this variation and to define clinical and biological determinants and predictors of these subtypes, disease activity, treatment response and outcome. All patients fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society 2010 diagnostic criteria for CIDP can participate, independent of age, duration and severity of the disease or treatment. We collect data on the clinical presentation, diagnostics, validated clinical outcome measures, (response to) treatment, and we collect biomaterials (DNA, cerebrospinal fluid and serial serum samples). We aim to include at least 1000 CIDP patients with a follow-up of at least 2 years. ICOS started in November 2015 in three academic medical centers in The Netherlands and by October 2018 169 patients are included: 69 new and 100 prevalent cases. ICOS is based on the format of the International Guillain-Barré syndrome (GBS) Outcome Study (IGOS). Dutch centers are invited to participate in ICOS that will continue as an independent national registry. International centers will be able to collect data and biomaterials according to the ICOS protocol by using the optional ICOS module within the INCbase infrastructure. ICOS will help to standardize the collection of data and biosamples for future research in CIDP.

Purpose of review The clinical presentation of Guillain–Barré syndrome (GBS) is highly variable, which can make the diagnosis challenging. Intravenous immunoglobulin (IVIg) and plasma exchange are the cornerstones of treatment since decades. But despite these treatments, 25% initially progress in muscle weakness, 25% require artificial ventilation, 20% is still not able to walk independently after 6 months, and 2–5% die, emphasizing the need for better treatment. We summarize new developments regarding the diagnosis, prognosis, and management of GBS. Recent findings GBS is a clinical diagnosis that can be supported by cerebrospinal fluid examination and nerve conduction studies. Nerve ultrasound and MRI are potentially useful techniques to diagnose inflammatory neuropathies. Several novel infections have recently been associated to GBS. Evidence from experimental studies and recent phase 2 clinical trials suggests that complement inhibition combined with IVIg might improve outcome in GBS, but further studies are warranted. Prognostic models could guide the selection of patients with a relatively poor prognosis that might benefit most from additional IVIg or otherwise intensified treatment. Summary New diagnostic tools may help to have early and accurate diagnosis in difficult GBS cases. Increased knowledge on the pathophysiology of GBS forms the basis for development of new, targeted, and personalized treatments that hopefully improve outcome.

Dear Editor, We thank Drs Rodríguez and Anaya for their interest in our publication.1 We agree that the situation in Bangladesh2 seems to differ from the context of the ZIKV outbreaks in the Pacific Islands and Latin America.3 The introduction of ZIKV did not cause an apparent epidemic or increase the incidence of acute flaccid paralysis GBS in Bangladesh. The only PCR-confirmed ZIKV infection in Bangladesh was reported in 2014.4 We provided the first data on the seroprevalence of ZIKV-neutralizing antibodies in Bangladesh (0–13.2%). Although our study was conducted during the period when ZIKV spread from Asia and Africa to the Pacific islands and Latin America, no ZIKV-related disease outbreaks were reported in Bangladesh. Thus, it appears that the introduction and circulation of ZIKV is not necessarily followed by an increase in GBS. The determinants driving the emergence of ZIKV-related GBS are yet unknown. Previous infections are implicated in the immune defense alterations and pathogenesis of ZIKV-related diseases. Co-infections may influence the risk of GBS after ZIKV infection, though there is currently no evidence to support this hypothesis. Conceivably, in patients with two recent infections, only one microorganism or virus may have triggered GBS; this is most likely in areas with epidemic infections. Therefore, it is important to assess known GBS-associated infections before attributing a case to a specific novel infection like ZIKV. We therefore investigated the antibody responses to Campylobacter jejuni, the predominant preceding infection in GBS worldwide.5 GBS following C. jejuni is predominantly axonal, while GBS after ZIKV is usually demyelinating (except in a report from French-Polynesia6). Strikingly, all patients in our study with positive serology for both recent C. jejuni and ZIKV infections developed the axonal subtype. These findings emphasize the importance of differentiating ZIKV with other infections related to GBS, including C. jejuni, Mycoplasma pneumoniae and other related (viral) infections. C. jejuni infections are associated with specific clinical subtypes of GBS, including pure motor forms. Also in this study, we found an association between C. jejuni and pure motor GBS. In contrast, patients with ZIKV infection and no evidence of C. jejuni infection more frequently presented with concomitant sensory and autonomic dysfunction, though the groups were too small to make strong conclusions. Extensive large-cohort studies are required to establish the clinical variants of ZIKV-associated GBS; such studies will improve our understanding of pathogenesis and assist clinical decision-making. Given the rarity of ZIKV-associated GBS, these questions will require international collaboration. No conflicts of interest.

Hepatitis E virus (HEV) infections are not limited to the liver but may also affect other organs. Several diseases, including Guillain-Barre syndrome, neuralgic amyotrophy, glomerulonephritis, cryoglobulinemia, pancreatitis, lymphoma, thrombopenia, meningitis, thyroiditis and myocarditis have been observed in the context of hepatitis E. To date, the definite pathophysiological links between HEV and extrahepatic manifestations are not yet established. However, it is suggested that HEV infection might be causative based on serological studies, case series, in vitro data and animal models. In particular, neuronal and renal diseases as well as pancreatitis seem to be caused by HEV, while a causative relationship between HEV and other diseases is more doubtful.Either direct cytopathic tissue damage by extrahepatic replication, or immunological processes induced by an overwhelming host immune response, are possible origins of HEV-associated extrahepatic manifestations.Hepatologists should be aware of the possibility that acute or chronically HEV-infected patients could develop extrahepatic manifestations. Neurologists, nephrologists, rheumatologists and other groups of physicians should consider HEV infection as a potential differential diagnosis when observing one of the diseases described in this review.Ribavirin and steroids have been used in small groups of patients with extrahepatic manifestations of HEV, but the efficacy of these drugs still needs to be verified by large, multicenter studies.This article comprehensively reviews the published literature regarding HEV and extrahepatic manifestations. We discuss the probability of specific extrahepatic diseases being caused by previous or ongoing HEV infection, and summarize the published knowledge about antiviral treatment in extrahepatic disorders. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Eight currently ongoing international CIDP registries were compared to assess infrastructure and collected clinical data, diagnostic data and biomaterials to enhance future research and improve standards of care in CIDP.

In December 2016, a 69-year-old man with a history of hypertension, hypercholesterolaemia and knee operations developed an erythematous pruritic rash on his trunk, cold shivers and swollen hands and feet with paraesthesias and numbness while on holiday in Curacao. Eight days later he developed pain in his right leg and back, provoked by walking and stretching. This pain slowly increased over the next 5 weeks to the point that it became difficult to walk. He was admitted to the neurology ward of a regional hospital in The Netherlands, and neurological examination showed an antalgic gait, hypaesthesia of fingertips and feet and normal muscle strength and tendon reflexes. MRI of the cervical, thoracic and lumbar spine without gadolinium was normal. Eight days after admission he developed a progressive weakness of the legs starting in the right leg. Neurological examination showed a proximal and distal flaccid paraparesis with absent reflexes of the legs and normal reflexes of the arms. Cerebrospinal fluid (CSF) examination 3 days after admission showed a leucocyte count of 1/10 E6/L and a protein level of 620 mg/L. Electrolytes, liver and kidney function and inflammatory parameters were normal. Nerve conduction studies (NCS) 5 days after admission showed slightly prolonged distal motor latencies of the peroneal and tibial nerves, mildly prolonged F-wave latencies of the ulnar and tibial …