International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

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, multi-centre 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 two 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 1000 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 1400 participants from 143 active centres 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 modelling, 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. ClinicalTrials.gov Identifier: NCT01582763

Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult

The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intérieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a blood–nerve interface (BNI) rather than a blood–nerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via blood–nerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cell–cell and cell–matrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders

Variations in rates of appropriate and inappropriate carotid endarterectomy for stroke prevention in 4 Canadian provinces

BACKGROUND: Carotid endarterectomy (CE), when performed on appropriate patients, reduces the incidence of stroke, yet there are marked variations in rates of this procedure. We sought to determine reasons for the variation in CE rates in 4 Canadian provinces. METHODS: We identified all CEs performed in 4 Canadian provinces between January 2000 and December 2001, inclusive. From chart review and expert assessment, we determined the proportion of these procedures that were appropriate, inappropriate or of uncertain appropriateness, using the RAND/UCLA Appropriateness Method. We sought to determine the variation in rates by province and whether the variation was due to differences in type of hospital, surgical specialty or surgical volume. RESULTS: Overall, 1656 (52.3%) of the 3167 CEs studied were performed for appropriate indications. The proportions of appropriate procedures were 78.2% (176/225) in Saskatchewan, 58.7% (481/819) in Alberta, 49.1% (350/713) in Manitoba and 46.0% (649/1410) in British Columbia (p < 0.001 across provinces). Rates of appropriate procedures per 100 000 population ranged from 44.3 in Manitoba to 16.2 in Saskatchewan (p < 0.001 across provinces). CEs were more likely to be appropriate when performed by a neurosurgeon compared with all other surgeons (74.4% v. 49.4% were appropriate; p < 0.001), when performed by surgeons doing fewer than 31 procedures over 2 years compared with surgeons doing more than 31 (70.1% v. 49.5% were appropriate; p < 0.001) and when performed in hospitals doing fewer than 135 procedures per year compared with hospitals doing more than 135 (63.4% v. 49.1% were appropriate; p < 0.001). Overall, 10.3% of procedures were done for inappropriate reasons. INTERPRETATION: Our findings suggest some overuse (for inappropriate or uncertain indications) but also some underuse (low population rates in some regions). High rates of CE are associated with lower rates of appropriateness for both surgeons and hospitals. That 1 in 10 CEs is done inappropriately suggests the need for preoperative assessment of appropriateness