GM-CSF is a marker of compartmentalised intrathecal inflammation in multiple sclerosis.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays. OBJECTIVE: To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS. METHODS: We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood-CSF-barrier integrity. RESULTS: GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin - a measure of blood-CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS. CONCLUSION: GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood-CSF-barrier.

Improving the quality of systematic reviews of neurological conditions: an assessment of current practice and the development and validation of six new search strategies.

BACKGROUND AND PURPOSE: Our aim was to study the quality of the literature search strategies used in recent systematic reviews and to develop and assess the diagnostic accuracy of six new search strategies (i.e. hedges). METHODS: Six neurological conditions were studied: migraine, stroke, dementia, epileptic seizures, Parkinson's disease and multiple sclerosis. Two reviewers independently assessed the quality of the search strategies used in systematic reviews published in 2015-2016. Complex hedges pertaining to the six conditions for use in Ovid MEDLINE were developed. Their diagnostic accuracy was compared to simple, single-term keyword searches. RESULTS: Almost 60% of quality criteria for the overall literature search strategy used in 182 systematic reviews were not respected. Over 30% of search strategies relied on a single keyword to identify the neurological condition. The sensitivities of our complex hedges amongst 10 311 articles were between 83% and 95%, significantly higher than the simple keyword searches (as low as 48%). The specificities were greater than 97%. CONCLUSIONS: There is great room for improvement in the search strategies used in systematic reviews of neurological conditions. Complex hedges were developed and validated to improve the accuracy of such searches. It is expected that this will lead to higher quality systematic reviews and meta-analyses.

Multiclinic evaluation of the antihypertensive effect of a methyldopa, hydrochlorothiazine, and amiloride combination.

A multiclinic, double-blind, randomized study in 361 patients with essential hypertension compared Aldoretic, (Merck & Co., Inc., New Jersey), a combination of methyldopa, hydrochlorothiazide, and amiloride with the combination of hydrochlorothiazide and amiloride and with methyldopa alone. At the end of week 12, the proportion of patients who were classified as normotensive (diastolic less than or equal to 90 mm Hg) was 61% in the group treated with Aldoretic, which was statistically significantly greater than the 48% in the hydrochlorothiazide/amiloride group and the 35% in the methyldopa group.