Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.

Background: In recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores. Methods: The present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships. Results: A significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045). Conclusions: These findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations.

This survey of anaesthetists in Australia and New Zealand aimed to investigate their attitudes and practice relating to the management of neuromuscular blockade monitoring. All medical practitioner members (3188) of the Australian and New Zealand Societies of Anaesthetists were invited to complete an anonymous survey, which was available online for two months. A total of 678 survey questionnaires were completed (response rate 21%). Most respondents (71.4%) underestimated the incidence of residual neuromuscular blockade and 63.2% believed this to be a significant clinical problem. Objective monitoring of neuromuscular function was used routinely only by 17% of respondents, although 70% believed routine monitoring would reduce the incidence of residual neuromuscular blockade. Only 25% of respondents correctly indicated that quantitative train-of-four counts of greater than 90% were the accepted criteria for safe extubation, with 52% using clinical judgement only. Only 29% of respondents believed neuromuscular function monitors should be part of minimum monitoring standards; quantitative neuromuscular function monitors were not available in 42% of the hospitals in which the respondents practiced. Despite the low response rate, the large sample size and heterogeneity of respondents make the findings of this survey concerning. There is a need for more education, availability of appropriate monitoring equipment and evidence-based guidelines for management of neuromuscular blockade in Australia and New Zealand.

To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F₂-isoprostanes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma, Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01). These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.