What's new in Guillain‐Barré syndrome in 2007–2008?*

The years 2007 and early 2008 have been an exciting time for Guillain‐Barré syndrome (GBS) research. Epidemiological studies have shown that the incidence of GBS remains stable at about 2/100,000 per year but that there have been changes in hospitalization use, likely due to the widespread availability of IVIg. Research into mechanisms has shown the importance of single amino acids in Campylobacter jejuni and the importance of ganglioside conformation. In a murine model of anti‐ganglioside antibody‐mediated neuropathy, Eculizumab was effective in reversing clinical disease and preventing pathology. This suggests trials of Eculizumab in GBS should be considered. Unfortunately, there are no new randomized controlled trials in GBS to report although the unmet need is great.     

Paraparetic Guillain‐Barré syndrome: Nondemyelinating reversible conduction failure restricted to the lower limbs

Introduction: Paraparetic Guillain‐Barré 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     

Update on Guillain‐Barré syndrome

Understanding of Guillain‐Barré syndrome (GBS) has progressed substantially since the seminal 1916 report by Guillain et al. Although Guillain, Barré, and Strohl summarised the syndrome based on observations of two French infantrymen, 2012 saw the beginning of an ambitious collaborative study designed to collect detailed data from at least 1,000 patients worldwide (IGOS, www.gbsstudies.org/about‐igos ). Progress has been made in many areas even since GBS was last reviewed in this journal in 2009. GBS subsequently received prominent attention in light of concerns regarding H1N1 influenza vaccinations, and several large‐scale surveillance studies resulted. Despite these developments, and promising pre‐clinical studies, disease‐modifying therapies for GBS have not substantially altered since intravenous immunoglobulin was introduced over 20 years ago. In other areas, management has improved. Antibiotic prophylaxis in ventilated patients reduces respiratory tract infection, thromboprophylaxis has reduced the risk of venous thromboembolism, and there is increasing awareness of the benefit of high‐intensity rehabilitation. This article highlights some of the interesting and thought‐provoking developments of the last 3 years, and is based on a plenary lecture given at the 2012 Peripheral Nerve Society (PNS) meeting.     

Acute bulbar,neck and limb weakness with monospecific anti‐GT1a antibody: A rare localized subtype of Guillain‐Barré sydnrome

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‐Barré 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 53 : 143–146, 2016     

Guillain‐Barré syndrome in the elderly

The aim of the study was to analyze specific features of Guillain‐Barré syndrome (GBS) in old people. The study included 403 GBS patients (62% young [<60 years], 35% young‐old [60–80 years], and 3% old‐old [>80 years]). Diagnosis of GBS was made according to the National Institute of Neurological Disorders and Stroke (NINDS criteria). Severe disability (GBS disability score of >3) at nadir was more common in old compared with young patients (p = 0.0001) as was mortality (9% vs. 2%, respectively). Acute motor and sensory axonal neuropathy and hyponatremia were more common in old compared with young patients (12% vs. 6% and 27% vs. 18%, respectively, p = 0.04). A positive history for malignancy was more than three times more common in old than young patients (11% vs. 3%, respectively, p = 0.01). Disability on nadir was similar in young‐old and old‐old subjects with disability on discharge being more severe in old‐old (p = 0.04) suggesting slower recovery in this subgroup. Bulbar symptoms were more common in old‐old compared with young‐old (50% vs. 19%, respectively, p = 0.01). Comorbidities were present in virtually all old‐old patients compared with 66% of young‐old patients (p = 0.04). In conclusion, Elderly patients, and especially old‐old patients, with GBS have more severe disease with slower recovery than do younger patients.     

Pathogenesis of axonal Guillain–Barré syndrome: Hypothesis

Pathologic studies of acute motor axonal neuropathy show strong evidence of the presence of primary axonal Guillain–Barré syndrome (GBS). The pathogenesis of axonaf GBS is speculated to be as follows: (1) Infection by an organism induces the high production of a crossreactive antibody between an infectious agent and the motor nerve axon in patients with a particular immunogenetic background. (2) The antineural antibody binds to the motor nerve terminals, thereby inhibiting motoneuron excitability and causing muscular weakness. (3) Binding of the antineural antibody, or subsequent functional impairment of the motoneurons, causes the motor axon to degenerate from the terminals. (4) In severe cases, extensive axonal loss and central chromatolysis of the motoneurons occur. These inhibit recovery and lead to a poor functional prognosis. © 1994 John Wiley & Sons, Inc.     

Complete recovery of an aged patient with Guillain–Barré syndrome associated with multiple IgM anti‐ganglioside antibodies

In this report we describe a 72‐year‐old woman who had cytomegalovirus infection–related Guillain–Barré syndrome (GBS) associated with multiple immunoglobulin M (IgM) anti‐ganglioside antibodies. She became tetraplegic with respiratory failure, but recovered completely after intravenous immunoglobulin therapy and plasmapheresis. The serum contained high‐titer IgM antibody activities to several gangliosides with disialosyl residues (GD1b, GD3, GT1b, GQ1b, and GT1a) and GD1a. These antibodies are often found in sera from patients with chronic sensory ataxic neuropathy, but they occur rarely in GBS. Muscle Nerve 38: 1630–1633, 2008     

Motor nerve excitability after childhood Guillain‐Barré syndrome

Residual motor nerve dysfunction after pediatric Guillain‐Barré syndrome (GBS) was determined in an observational cross‐sectional cohort study in patients who previously developed GBS during childhood (<18 years). Ulnar motor nerve dysfunction was defined by compound motor action potential (CMAP) scan in patients after a follow up of at least 1 year compared with age‐matched healthy controls, in relation to clinical course and outcome. A total of 37 persons previously diagnosed with GBS in childhood were included with a mean age at current examination of 20.6 years (4–39 years). The median time between diagnosis and follow‐up was 11 years (range: 1–22 years). CMAP scanning indicated ulnar motor nerve dysfunction in 25 (68%) participants. The most frequent abnormality was a reduction in nerve excitability observed both in those with residual limb weakness and in the majority of those with complete recovery. CMAP scan characteristics were not related to prognostic factors or outcome. In conclusion, GBS in childhood results in residual motor nerve excitability disturbances, even in those completely recovered, probably reflecting altered physiology of regenerated peripheral nerves.     

Incidence of Guillain‐Barré syndrome in Chile: a population‐based study

The Guillain‐Barré syndrome (GBS) incidence rate (IR) varies between 0.16 and 3.00 cases per 100,000 inhabitants. Little data exist on the epidemiology of GBS in Latin American countries. Our objective was to describe GBS epidemiology based on a national database in a Latin American country and to contribute to the global map of GBS epidemiology. This was a retrospective study that included all reported GBS cases in Chile between 2001 and 2012. Gender, age, seasonal occurrence, and geographical distribution were analyzed. A total of 4,158 GBS cases were identified from 19,513,655 registries. The mean age was 37 ± 24 years, and 59% of patients were male (male to female ratio of 1.5 : 1). Gender IR was 2.53/100,000 for males and 1.68/100,000 for females. The overall standardized IR was 2.1/100,000, although this varied between 1.61/100,000 (2001) and 2.35/100,000 (2010). The seasonal distribution was as follows: autumn 22%; winter 25%; spring 27%; and summer 26%. The geographical IR were as follows: far North 1.49/100,000; North 1.94/100,000; Central 1.97/100,000; South 3.18/100,000; and far South 2.78/100,000. The reported IR of GBS in Chile was similar to other studies based on national databases. In Chile, IR was greater in men and in the south.     

Markers for Guillain‐Barré syndrome with poor prognosis: a multi‐center study

Guillain‐Barré syndrome (GBS) is an acute monophasic neuropathy. Prognostic tools include the modified Erasmus GBS outcome score (mEGOS), Erasmus GBS respiratory insufficiency score (EGRIS), and the increase in serum IgG levels (ΔIgG) 2 weeks after intravenous immunoglobulin (IVIg) treatment. Given that proportions of GBS subtypes differ between Western countries and Japan, the usefulness of these tools in Japan or other countries remains unknown. We enrolled 177 Japanese patients with GBS from 15 university hospitals and retrospectively obtained mEGOS and EGRIS for all and ΔIgG status for 79 of them. High mEGOS scores on admission or on day 7 were significantly associated with poorer outcomes (unable to walk independently at 6 months). High EGRIS scores (≥5 points) were associated with an increased risk for mechanical ventilation. Patients with ΔIgG <1,108 mg/dl had significantly poorer outcomes. We suggest that mEGOS, EGRIS, and ΔIgG in GBS are clinically relevant in Japan.     

Long‐term outcome of Guillain‐Barré syndrome in children

The objective of this study is to determine the long‐term outcome and consequences of Guillain‐Barré syndrome (GBS) in children. This is an observational cross‐sectional cohort study of children diagnosed with GBS (0–18 years old) at the Sophia Children's Hospital in Rotterdam from 1987 to 2009. All patients were invited for a structured interview, questionnaires, and full neurologic exam to record their current clinical condition focused on complaints and symptoms, neurological deficits, disabilities, behavior, and quality of life. Thirty‐seven patients participated, 23 were now adults, with a median age of 20 years (range 4–39 years) and a median follow‐up time of 11 years (range 1–22 years). Residual complaints were reported by 24 (65%) patients, including paresthesias (38%), unsteadiness of gait in the dark (37%), painful hands or feet (24%), and severe fatigue (22%). Four patients had severe neurological deficits, including facial diplegia and limb weakness. Two patients had had a recurrence of GBS. In 10 patients (26%), GBS had a negative impact on their school career. Questionnaires identified a wide range of behavioral problems. Quality of life was below normal on the subscale vitality, and above normal on the subscales social functioning and positive emotions in the adult group. Most children show good recovery of neurological deficits after GBS, but many have persisting long‐term residual complaints and symptoms that may lead to psychosocial problems interfering with participation in daily life.     

High mortality from Guillain‐Barré syndrome in Bangladesh

Although Guillain‐Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6–30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1–16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02–5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1–3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05–3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5–19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves.     

Association of antibodies to ganglioside complexes and conduction blocks in axonal Guillain‐Barré syndrome presenting as acute motor conduction block neuropathy

A close relationship between acute motor conduction block neuropathy and antibodies against the complex of GM1 and GalNAc‐GD1a has been reported. This study investigates the hypothesis that conduction block at the early phase of axonal Guillain‐Barré syndrome (GBS) is also associated with such ganglioside complexes. Sera were obtained from seven French patients with initial evidence of isolated conduction blocks that resolved or progressed to acute motor axonal neuropathy. Serum IgG to asialo‐GM1 and gangliosides of LM1, GM1, GM1b, GD1a, GalNAc‐GD1a, GD1b, GT1a, GT1b, and GQ1b as well as their complexes were measured. Five of seven patients progressed within the first month of disease to AMAN. One patient had IgG antibodies against the complex of asialo‐GM1 and each of the other ganglioside antigens. Another patient carried IgG antibodies against GM1 complex with GM1b, GD1a, and GT1a as well as asialo‐GM1 complex with GD1a and GT1a. None had IgG antibodies against GM1/GalNAc‐GD1a complex. Six patients had IgG against single antigens GM1, GD1a, GalNAc‐GD1a, GD1b, and asialo‐GM1. In three patients, a reduced reaction against GM1/GalNAc‐GD1a complex was observed. The presence of conduction block in axonal GBS is not always associated with anti‐GM1/GalNAc‐GD1a complex antibodies.     

The long‐term functional status in patients with Guillain‐Barré syndrome

Background and purpose: The purpose of this study was to analyse the long‐term impact of Guillain‐Barré syndrome (GBS) on quality of life, and the relationship between clinical variables at disease onset and symptoms at follow‐up to general health status. Methods: Forty‐two GBS patients were examined at median 6 years after disease onset and were compared with 50 healthy controls. The fatigue severity scale (FSS), visual analogue scale (VAS) for pain, disability rating index (DRI) and medical outcome study 36‐item short‐form health status scale (SF‐36) were applied. Variables at onset and symptoms at follow‐up were correlated with outcome measurements in GBS. Results: VAS [2.9 (SD 3.3) vs. 1.5 (SD 1.9); P = 0.01] and DRI [2.5 (SD 2.1) vs. 1.0 (SD 1.5); P < 0.001] were significantly higher in patients with GBS, compared with healthy controls. Decreased physical functioning and general health were found on SF‐36. Differences between GBS patients with shorter (<6 years) and longer (≥6 years) follow‐up after onset were not found. Conclusions: Relatively independent from various variables at onset, patients with GBS seem to have a reduced quality of life and functioning, and the distress seems to have become persistent after the first few years with improvement following the acute disease.     

Health‐related quality of life in Guillain‐Barré syndrome patients: a systematic review

Guillain‐Barré syndrome (GBS) encompasses a broad spectrum of health‐related quality of life (HRQL) determinants, including mobility, fatigue, pain, and depression. We systematically reviewed the literature on functional outcome domains in which GBS patients experience limitations in the short and long terms and evaluated determinants of HRQL in GBS patients. MEDLINE and EMBASE were systematically searched by two independent reviewers for articles covering HRQL data of GBS patients. Of 730 abstracts screened, 17 articles covering data of 14 studies matched the selection criteria. The included articles showed that many GBS patients experienced physical limitations, even years after the acute phase of the disease, while results were inconsistent for perceived levels of pain, fatigue, and general mental well‐being. Only three papers covered HRQL assessments at more than one time point, generally showing large improvements in HRQL in the first year after GBS onset, but not thereafter. We appraised the methodological quality of included studies using a 13‐item checklist; none of the articles fulfilled all items and only seven articles presented data on correlations between HRQL and determinants. In conclusion, the majority of studies on HRQL in GBS patients are cross‐sectional and of low methodological quality. This paper provides guidance for much needed high‐quality studies on patterns of patient‐perceived recovery after GBS onset.