Regional variation of Guillain-Barré syndrome Doets, Alex Y; Verboon, Christine; van den Berg, Bianca ...
Brain (London, England : 1878),
10/2018, Letnik:
141, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Reports from single countries suggest regional differences in Guillain-Barré syndrome (GBS), but no comparative studies have been conducted. Doets et al. present the first results from the ...International GBS Outcome Study, and show that factors related to geography strongly influence clinical phenotype, disease severity, electrophysiological subtype and outcome.
Abstract
Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: 'Europe/Americas', 'Asia' (without Bangladesh), and 'Bangladesh'. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome.
The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the ...NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuTAa and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.
International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg ...treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone.
An international, randomised, double-blind, placebo-controlled trial, in adults with 'probable' or 'definite' CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3-5 days) followed by 6 courses of IVIg 1/g/kg (over 1-2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety.
In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed.
ISRCTN registry ISRCTN15893334 . Prospectively registered on 12 February 2018.
Operating reconfigurable quantum circuits with single photon sources is a key goal of photonic quantum information science and technology. We use an integrated waveguide device containing directional ...couplers and a reconfigurable thermal phase controller to manipulate single photons emitted from a chromium related color center in diamond. Observation of both a wavelike interference pattern and particlelike sub-Poissionian autocorrelation functions demonstrates coherent manipulation of single photons emitted from the chromium related center and verifies wave particle duality.
A method to accurately understand the processes controlling the burning behavior of porous wildland fuels is presented using numerical simulations and laboratory experiments. A multiphase approach ...has been implemented in OpenFOAM, which is based on the FireFOAM solver for large eddy simulations (LES). Conservation equations are averaged in a control volume containing a gas and a solid phase. Drying, pyrolysis, and char oxidation are described by interaction between the two phases. Numerical simulations are compared to laboratory experiments carried out with porous pine needle beds in the FM Global Fire Propagation Apparatus (FPA). These experiments are used to support the use and the development of submodels that represent heat transfer, pyrolysis, gas-phase combustion, and smoldering processes. The model is tested for different bulk densities, two distinct species and two different radiative heat fluxes used to heat up the samples. It has been possible to reproduce mass loss rates, heat release rates, and temperatures that agree with experimental observations, and to highlight the current limitations of the model.
Particulate emissions from biomass burning can both alter the atmosphere's radiative balance and cause significant harm to human health. However, due to the large effect on emissions caused by even ...small alterations to the way in which a fuel burns, it is difficult to study particulate production of biomass combustion mechanistically and in a repeatable manner. In order to address this gap, in this study, small wood samples sourced from Côte D'Ivoire in West Africa were burned in a highly controlled laboratory environment. The shape and mass of samples, available airflow and surrounding thermal environment were carefully regulated. Organic aerosol and refractory black carbon emissions were measured in real time using an Aerosol Mass Spectrometer and a Single Particle Soot Photometer, respectively. This methodology produced remarkably repeatable results, allowing aerosol emissions to be mapped directly onto different phases of combustion. Emissions from pyrolysis were visible as a distinct phase before flaming was established. After flaming combustion was initiated, a black-carbon-dominant flame was observed during which very little organic aerosol was produced, followed by a period that was dominated by organic-carbon-producing smouldering combustion, despite the presence of residual flaming. During pyrolysis and smouldering, the two phases producing organic aerosol, distinct mass spectral signatures that correspond to previously reported variations in biofuel emissions measured in the atmosphere are found. Organic aerosol emission factors averaged over an entire combustion event were found to be representative of the time spent in the pyrolysis and smouldering phases, rather than reflecting a coupling between emissions and the mass loss of the sample. Further exploration of aerosol yields from similarly carefully controlled fires and a careful comparison with data from macroscopic fires and real-world emissions will help to deliver greater constraints on the variability of particulate emissions in atmospheric systems.
To define the current treatment practice of Guillain-Barré syndrome (GBS).
The study was based on prospective observational data from the first 1,300 patients included in the International GBS ...Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.
We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.
In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.
Guillain‐Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly ...understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow‐up of 1–3 years. Data are collected via a web‐based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long‐term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.
The rat transporter rCNT1 is the archetype of a family of concentrative nucleoside transporters (CNTs) found both in eukaryotes
and in prokaryotes. In the present study we have used antibodies to ...investigate the subcellular distribution and membrane
topology of this protein. rCNT1 was found to be expressed predominantly in the brush-border membranes of the polarized epithelial
cells of rat jejunum and renal cortical tubules and in the bile canalicular membranes of liver parenchymal cells, consistent
with roles in the absorption of dietary nucleosides, of nucleosides in the glomerular filtrate, or of nucleosides arising
from the action of extracellular nucleotidases, respectively. The effect of endoglycosidase F treatment on wild-type and mutant
rCNT1 expressed in Xenopus oocytes revealed that the recombinant transporter could be glycosylated at either or both of Asn 605 and Asn 643 , indicating that its C terminus is extracellular. In contrast, potential N -glycosylation sites introduced near the N terminus, or between putative transmembrane (TM) helices 4 and 5, were not glycosylated.
The deduced orientation of the N terminus in the cytoplasm was confirmed by immunocytochemistry on intact and saponin-permeabilized
Chinese hamster ovary cells expressing recombinant rCNT1. These results, in conjunction with extensive analyses of CNT family
protein sequences using predictive algorithms, lead us to propose a revised topological model, in which rCNT1 possesses 13
TM helices with the hydrophilic N-terminal and C-terminal domains on the cytoplasmic and extracellular sides of the membrane,
respectively. Furthermore, we show that the first three TM helices, which are absent from prokaryote CNTs, are not essential
for transporter function; truncated proteins lacking these helices, derived either from rCNT1 or from its human homolog hCNT1,
were found to retain significant sodium-dependent uridine transport activity when expressed in oocytes.
Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European ...Journal of Neurology and Journal of the Peripheral Nervous System.
Objectives: To revise these guidelines.
Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.
Recommendations: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).
Click here for the corresponding questions to this CME article.
PDF
