Antecedent infections and anti-ganglioside antibodies in Guillain-Barré syndrome : their role in pathogenesis and heterogeneity

The Guillain-Barre syndrome (GBS) is the most common form of acute neuromuscular paralysis in developed countries, but the pathogenesis is still largely unknown. The major clinical features of the syndrome were first united by J-B.O. Landry in 1859 (1). The syndrome was named after G. Guillain and J.A. Barre, two French army neurologists, who in 1916 described, togethe

Incidence and Prevalence of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Systematic Review and Meta-Analysis

Abstract Background: Prevalence and incidence rates of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are required to determine the impact of CIDP on society. We aimed to estimate the prevalence and incidence of CIDP worldwide and to determine the effect of diagnostic criteria on prevalence and incidence. Method: A systematic review was conducted for all published incidence and prevalence studies on CIDP until May 18, 2017. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. We performed a random effect meta-analysis to estimate pooled prevalence and incidence rates. Results: Of the 907 studies, 11 were included in the systematic review, 5 in the meta-analysis of incidence (818 cases; 220,513,514 person-years) and 9 in the meta-analysis of prevalence (3,160 cases; 160,765,325 population). These studies had a moderate quality. The pooled crude incidence rate was 0.33 per 100,000 person-years (95% CI 0.21–0.53; I2 = 95.7%) and the pooled prevalence rate was 2.81 per 100,000 (95% CI 1.58–4.39; I 2 = 99.1%). Substantial heterogeneity in incidence and prevalence across studies seems to be partly explained by using different diagnostic criteria. Conclusion: These findings provide a starting point to estimate the social burden of CIDP and demonstrate the need to reach consensus on diagnostic criteria for CIDP

Hospital admissions, transfers and costs of guillain-Barré syndrome

Background Guillain-Barré syndrome (GBS) has a highly variable clinical course, leading to frequent transfers within and between hospitals and high associated costs. We defined the current admissions, transfers and costs in relation to disease severity of GBS. Methods Dutch neurologists were requested to report patients diagnosed with GBS between November 2009 and November 2010. Information regarding clinical course and transfers was obtained via neurologists and general practitioners. Results 87 GBS patients were included with maximal GBS disability score of 1 or 2 (28%), 3 or 4 (53%), 5 (18%) and 6 (1%). Four mildly affected GBS patients were not hospital admitted. Of the 83 hospitalized patients 68 (82%) were initially admitted at a neurology department, 4 (5%) at an ICU, 4 (5%) at pediatrics, 4 (5%) at pediatrics neurology and 3 (4%) at internal medicine. Median hospital stay was 17 days (IQR 11-26 days, absolute range 1-133 days). Transfers between departments or hospitals occurred in 33 (40%) patients and 25 (30%) were transferred 2 times or more. From a cost-effectiveness perspective 21 (25%) of the admissions was suboptimal. Median costs for hospital admission of GBS patients were 15,060 Euro (IQR 11,226-23,683). Maximal GBS disability score was significantly correlated with total length of stay, number of transfers, ICU admission and costs. Conclusions Hospital admissions for GBS patients are highly heterogeneous, with frequent transfers and higher costs for those with mo

Guillain-Barré syndrome following varicella-zoster virus infection

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4 weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4 weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40 years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1 year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh

Diagnosis of Guillain–Barré syndrome in children and validation of the Brighton criteria

To describe the key diagnostic features of pediatric Guillain–Barré syndrome (GBS) and validate the Brighton criteria. Retrospective cohort study of all children (<18 years) diagnosed with GBS between 1987 and 2013 at Sophia Children’s Hospital, Erasmus MC, Rotterdam. Clinical information was collected and the sensitivity of the Brighton criteria was calculated. 67 children (35 boys) were included, with a median age of 5.0 years [interquartile range (IQR) 3.0–10.0 years]. Bilateral limb weakness was present at hospital admission in 93% of children, and at nadir in all patients. Children presented with tetraparesis in 70% or with paraparesis in 23%. Reduced reflexes in paretic limbs were observed at hospital admission in 82% and during follow-up in all children. The progressive phase lasted median 6 days (IQR 3–8 days) and less than 4 weeks in all children. A monophasic disease course was seen in 97%, including 5 children with a treatment-related fluctuation. Two children had a later relapse at 9 weeks and 19 weeks after onset. 77% of the children showed an elevated protein level in CSF. Nerve conduction studies showed evidence for a poly(radiculo)neuropathy in 91% of the children. 46 children had a complete data set, the sensitivity of the Brighton criteria level 1 was 72% (95% CI 57–84) and 96% (95% CI 85–99) for level 2 and 98% (95% CI 88–100) for level 3. The majority of the pediatric GBS patients presented in this cohort fulfilled the current diagnostic criteria

Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS

Treatment of Guillain-Barré syndrome with a standard course of high-dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc-receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc-receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain-Barré syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome

Diagnosis and treatment of Guillain-Barré syndrome during the Zika virus epidemic in Brazil: A national survey study

The Zika virus (ZIKV) epidemic in Brazil in 2015-2016 was followed by an increase in the incidence of patients with Guillain-Barré syndrome (GBS). With this national survey study, we aimed to gain a better understanding of how neurologists in Brazil are currently diagnosing and treating patients with GBS, and how this increase in incidence has impacted the management of the disease. The questionnaire consisted of 52 questions covering: personal profile of the neurologist, practice of managing GBS during and outside of the ZIKV epidemic, and limitations in managing GBS. All 3264 neurologists that were member of the Brazilian Academy of Neurology at the time of the study were invited to participate. The questionnaire was fully answered by 171 (5%) neurologists. Sixty-one percent of neurologists noticed an increase in patients with GBS during the ZIKV epidemic, and 30% experienced an increase in problems in managing GBS during this time. The most important limitations in the diagnosis and management of GBS included the availability of nerve conduction studies (NCS), beds in the Intensive Care Unit (ICU) and referral to rehabilitation centers. Most neurologists did not use a protocol for treating patients with GBS and the treatment practice varied. Increasing availability of NCS and beds in the ICU and rehabilitation centers, and the implementation of (inter)national guidelines, are critical in supporting Brazilian neurologist in their management of GBS, an

Microarray screening of Guillain-Barré syndrome sera for antibodies to glycolipid complexes

__Objective:__ To characterize the patterns of autoantibodies to glycolipid complexes in a large cohort of Guillain-Barré syndrome (GBS) and control samples collected in Bangladesh using a newly developed microarray technique. __Methods:__ Twelve commonly studied glycolipids and lipids, plus their 66 possible heteromeric complexes, totaling 78 antigens, were applied to polyvinylidene fluoride-coated slides using a microarray printer. Arrays were probed with 266 GBS and 579 control sera (2 mL per serum, diluted 1/50) and bound immunoglobulin G detected with secondary antibody. Scanned arrays were subjected to statistical analyses. __Results:__ Measuring antibodies to single targets was 9% less sensitive than to heteromeric complex targets (49.2% vs 58.3%) without significantly affecting specificity (83.9% 85.0%). The optimal screening protocol for GBS sera comprised a panel of 10 glycolipids (4 single glycolipids GM1, GA1, GD1a, GQ1b, and their 6 heteromeric complexes), resulting in an overall assay sensitivity of 64.3% and specificity of 77.1%. Notable heteromeric targets were GM1:GD1a, GM1:GQ1b, and GA1:GD1a, in which exclusive binding to the complex was observed. __Conclusions:__ Rationalizing the screening protocol to capture the enormous diversity of glycolipid complexes can be achieved by miniaturizing the screening platform to a microarray platform, and applying simple bioinformatics to determine optimal sensitivity and specificity of the targets. Glycolipid complexes are an important category of glycolipid antigens in autoimmune neuropathy cases that require specific analytical and bioinformatics methods for optimal detection