Analyse des céphalées post- ponction de la dure-mère en obstétrique à la Maternité du CHUV

Contexte : L'analgésie péridurale lors d'un accouchement est très fréquente et peut notamment se compliquer d'une brèche de la dure-mère pouvant se manifester par des céphalées post-ponction. Le but de ce travail est de calculer l'incidence des perforations involontaires, d'analyser les facteurs de risque ainsi que les modalités de traitement des céphalées post-ponction durale, et ainsi améliorer le contrôle de Qualité. Méthode : Nous avons utilisé les données de contrôle de Qualité récoltées prospectivement à la Maternité du CHUV entre 2011 et 2014, que nous avons saisies dans une base de données et analysées statistiquement, puis comparées à la littérature. Résultats : Dans notre population, l'incidence des brèches de la dure-mère est de 1.3%, dont 83% sont devenues symptomatiques. La nuit, la fin de service d'un anesthésiste, ainsi que les jours non- ouvrables, ne sont statistiquement pas des facteurs de risque. L'analyse des différents volumes des blood patchs ne montre pas statistiquement d'avantages d'un certain volume sur un autre. Les taux de réussite des blood patchs sont de 67.6% après un blood patch et de 83.8% après deux blood patchs. Nos résultats sont comparables à la littérature récente. Conclusions : Il serait intéressant de pouvoir regrouper des données de plusieurs hôpitaux suisses ainsi que continuer le contrôle de Qualité adapté et standardisé sur une plus longue durée pour permettre de meilleures analyses statistiques. Il faudrait mettre en place un essai clinique pour permettre d'identifier la meilleure prise en charge par blood patch qui reste encore peu evidence- based medicine mais empirique

Decreased hippocampal cell proliferation in mice with experimental antiphospholipid syndrome

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, which may trigger vascular thrombosis with consecutive infarcts. However, cognitive dysfunctions representing one of the most commonest neuropsychiatric symptoms are frequently present despite the absence of any ischemic brain lesions. Data on the structural and functional basis of the neuropsychiatric symptoms are sparse. To examine the effect of APS on hippocampal neurogenesis and on white matter, we induced experimental APS (eAPS) in adult female Balb/C mice by immunization with β2-glycoprotein 1. To investigate cell proliferation in the dentate gyrus granular cell layer (DG GCL), eAPS and control mice (n = 5, each) were injected with 5-bromo-2′-deoxyuridine (BrdU) once a day for 10 subsequent days. Sixteen weeks after immunization, eAPS resulted in a significant reduction of BrdU-positive cells in the DG GCL compared to control animals. However, double staining with doublecortin and NeuN revealed a largely preserved neurogenesis. Ultrastructural analysis of corpus callosum (CC) axons in eAPS (n = 6) and control mice (n = 7) revealed no significant changes in CC axon diameter or g-ratio. In conclusion, decreased cellular proliferation in the hippocampus of eAPS mice indicates a limited regenerative potential and may represent one neuropathological substrate of cognitive changes in APS while evidence for alterations of white matter integrity is lacking. Keywords Antiphospholipid syndrome Corpus callosum g-ratio BrdU Neurogenesi

Memory B cells activate brain-homing, autoreactive CD4(+) T cells in multiple sclerosis

Multiple sclerosis is an autoimmune disease that is caused by the interplay of genetic, particularly the HLA-DR15 haplotype, and environmental risk factors. How these etiologic factors contribute to generating an autoreactive CD4+ T cell repertoire is not clear. Here, we demonstrate that self-reactivity, defined as “autoproliferation” of peripheral Th1 cells, is elevated in patients carrying the HLA-DR15 haplotype. Autoproliferation is mediated by memory B cells in a HLA-DR-dependent manner. Depletion of B cells in vitro and therapeutically in vivo by anti-CD20 effectively reduces T cell autoproliferation. T cell receptor deep sequencing showed that in vitro autoproliferating T cells are enriched for brain-homing T cells. Using an unbiased epitope discovery approach, we identified RASGRP2 as target autoantigen that is expressed in the brain and B cells. These findings will be instrumental to address important questions regarding pathogenic B-T cell interactions in multiple sclerosis and possibly also to develop novel therapies

Low- versus high-dose intraoperative opioids: A systematic review with meta-analyses and trial sequential analyses.

Opioid-induced hyperalgesia is a state of nociceptive sensitisation secondary to opioid administration. The objective of this meta-analysis was to test the hypothesis that high-dose intraoperative opioids contribute to increased post-operative pain and hyperalgesia when compared with a low-dose regimen in patients under general anaesthesia. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and rated the certainty of evidence with the Grading of Recommendations, Assessment, Development and Evaluation system. Only trials investigating pain outcomes and comparing two different dosages of the same intraoperative opioid in patients under general anaesthesia were included. The primary outcome was pain score (analogue scale, 0-10) at 24 post-operative hours. Secondary outcomes included pain score and cumulative intravenous morphine equivalents (mg) consumed at 2 post-operative hours, together with mechanical pain threshold (g·mm <sup>-2</sup> ). Twenty-seven randomised controlled trials, including 1630 patients, were identified. Pain score at rest at 24 post-operative hours was increased in the high-dose group (mean difference [95% CI]: -0.2 [-0.4, -0.1]; trial sequential analysis-adjusted CI: -0.4, -0.02; low certainty of evidence). Similarly, at 2 post-operative hours, both pain score (mean difference [95% CI]: -0.4 [-0.6, -0.2]; low certainty of evidence) and cumulative intravenous morphine equivalents consumed (mean difference [95% CI]: -1.6 mg [-2.6, -0.7]; low certainty of evidence) were significantly higher in the high-dose group. Finally, the threshold for mechanical pain was significantly lower in the high-dose group (mean difference to pressure [95% CI]: 3.8 g·mm <sup>-2</sup> [1.8, 5.8]; low certainty of evidence). There is low certainty of evidence that high-dose intraoperative opioid administration increases pain scores in the post-operative period, when compared with a low-dose regimen

Intra‐operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta‐analysis with trial sequential analysis

Intra-operative remifentanil is associated with increased postoperative analgesic requirements and opioid consumption. Dexmedetomidine has characteristics suggesting it may substitute for intra-operative remifentanil during general anaesthesia, but existing literature has reported conflicting results. We undertook this meta-analysis to investigate whether general anaesthesia including dexmedetomidine would result in less postoperative pain than general anaesthesia including remifentanil. The MEDLINE and PubMed electronic databases were searched up to October 2018. Only randomised trials including patients receiving general anaesthesia and comparing dexmedetomidine with remifentanil administration were included. Meta-analyses were performed mostly employing a random effects model. The primary outcome was pain score at rest (visual analogue scale, 0-10) at two postoperative hours. The secondary outcomes included: pain score at rest at 24 postoperative hours; opioid consumption at 2 and 24 postoperative hours; and rates of hypotension, bradycardia, shivering and postoperative nausea and vomiting. Twenty-one randomised trials, including 1309 patients, were identified. Pain scores at rest at two postoperative hours were lower in the dexmedetomidine group, with a mean difference (95%CI) of -0.7 (-1.2 to -0.2), I <sup>2</sup>  = 85%, p = 0.004, and a moderate quality of evidence. Secondary pain outcomes were also significantly better in the dexmedetomidine group. Rates of hypotension, shivering and postoperative nausea and vomiting were at least twice as frequent in patients who received remifentanil. Time to analgesia request was longer, and use of postoperative morphine and rescue analgesia were less, with dexmedetomidine, whereas episodes of bradycardia were similar between groups. There is moderate evidence that intra-operative dexmedetomidine during general anaesthesia improves pain outcomes during the first 24 postoperative hours, when compared with remifentanil, with fewer side effects

Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia: a systematic review and meta-analysis.

Opioids are administered peri-operatively for postoperative analgesia, and intra-operatively to control the sympathetic response to surgical stimuli, frequently as a surrogate for presumed pain. However, opioid use during surgery is a matter of dispute in contemporary practice and carries the risk of side-effects such as postoperative nausea and vomiting. This meta-analysis investigated whether opioid-inclusive, compared with opioid-free anaesthesia, would reduce postoperative pain, without increasing the rate of postoperative nausea and vomiting. The electronic databases Medline and PubMed were searched until June 2018. We included trials investigating pain outcomes and comparing any type of intra-operative opioid administration with placebo injection or no intra-operative opioid. Most meta-analyses were performed using a random effects model. We rated the quality of evidence for each outcome. The primary outcome was pain score at rest (analogue scale, 0-10) at two postoperative hours. Our secondary outcomes included the rate of postoperative nausea and vomiting within the first 24 postoperative hours and length of stay in the recovery area. Twenty-three randomised controlled trials, including 1304 patients, were identified. Pain scores at rest at two postoperative hours were equivalent in the opioid-inclusive and opioid-free groups with a mean difference (95%CI) of 0.2 (-0.2 to 0.5), I <sup>2</sup> = 83%, p = 0.38 and a high quality of evidence. Similarly, there was high-quality evidence that the rate of postoperative nausea and vomiting was reduced in the opioid-free group, with a risk ratio (95%CI) of 0.77 (0.61-0.97), I <sup>2</sup> = 16%, p = 0.03 and high-quality evidence for a similar length of stay in the recovery area, the mean difference (95%CI) being 0.6 (-8.2 to 9.3), min, I <sup>2</sup> = 60%, p = 0.90. As there is strong evidence that opioid-inclusive anaesthesia does not reduce postoperative pain, but is associated with more postoperative nausea and vomiting, when compared with opioid-free anaesthesia, we suggest that anaesthetists should reconsider their intra-operative opioid choices on a case-by-case basis

Neurological Impairment in Experimental Antiphospholipid Syndrome is Associated with increased Ligand Binding to Serotonergic 5-HT1A Receptors

Coneley's Gallopers - G109 - pulling down circa 1957

A neuroprotective role for microglia in prion diseases

Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34(−/−)) mice again resulted in significantly augmented proteinase K–resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis