The Insula and Its Epilepsies

Insular seizures are great mimickers of seizures originating elsewhere in the brain. The insula is a highly connected brain structure. Seizures may only become clinically evident after ictal activity propagates out of the insula with semiology that reflects the propagation pattern. Insular seizures with perisylvian spread, for example, manifest first as throat constriction, followed next by perioral and hemisensory symptoms, and then by unilateral motor symptoms. On the other hand, insular seizures may spread instead to the temporal and frontal lobes and present like seizures originating from these regions. Due to the location of the insula deep in the brain, interictal and ictal scalp electroencephalogram (EEG) changes can be variable and misleading. Magnetic reso- nance imaging, magnetic resonance spectroscopy, magnetoencephalography, positron emission tomography, and single-photon computed tomography imaging may assist in establishing a diagnosis of insular epilepsy. Intracranial EEG recordings from within the insula, using stereo-EEG or depth electrode techniques, can prove insular seizure origin. Seizure onset, most commonly seen as low-voltage, fast gamma activity, however, can be highly localized and easily missed if the insula is only sparsely sampled. Moreover, seizure spread to the contralateral insula and other brain regions may occur rapidly. Extensive sampling of the insula with multiple electrode trajectories is necessary to avoid these pitfalls. Understanding the functional organization of the insula is helpful when interpreting the semiology produced by insular seizures. Electrical stimulation mapping around the central sulcus of the insula results in paresthesias, while stimulation of the posterior insula typically produces painful sensations. Visceral sensations are the next most common result of insular stimulation. Treatment of insular epilepsy is evolving, but poses challenges. Surgical resections of the insula are effective but risk significant morbidity if not carefully planned. Neurostimulation is an emerging option for treatment, especially for seizures with onset in the posterior insula. The close association of the insula with marked autonomic changes has led to interest in the role of the insula in sudden unexpected death in epilepsy and warrants additional study with larger patient cohorts

Genetic characterization of a VanG-type vancomycin-resistant Enterococcus faecium clinical isolate

International audienceObjectives: To characterize, phenotypically and genotypically, the first Enterococcus faecium clinical isolate harbouring a vanG operon.Methods: The antibiotic resistance profile of E. faecium 16-346 was determined and its whole genome sequenced using PacBio technology. Attempts to transfer vancomycin resistance by filter mating were performed and the inducibility of expression of the vanG operon was studied by reverse-transcription quantitative PCR (RT-qPCR) in the presence or absence of subinhibitory concentrations of vancomycin.Results: E. faecium 16-346 was resistant to rifampicin (MIC >4 mg/L), erythromycin (MIC >4 mg/L), tetracycline (MIC >16 mg/L) and vancomycin (MIC 8 mg/L), but susceptible to teicoplanin (MIC 0.5 mg/L). The strain harboured the vanG operon in its chromosome, integrated in a 45.5 kb putative mobile genetic element, similar to that of Enterococcus faecalis BM4518. We were unable to transfer vancomycin resistance from E. faecium 16-346 to E. faecium BM4107 and E. faecalis JH2-2. Lastly, transcription of the vanG gene was inducible by vancomycin.Conclusions: This is, to the best of our knowledge, the first report of a VanG-type vancomycin-resistant strain of E. faecium. Despite the alarm pulled because of the therapeutic problems caused by VRE, our work shows that new resistant loci can still be found in E. faecium

Long-term tolerance and efficacy of siltuximab (anti-IL-6) in a young adult with idiopathic multicentric Castleman disease during COVID-19

Background: Castleman disease (CD) is a rare lymphoproliferative disorder with various subtypes, including the HHV-8-negative/idiopathic multicentric CD (iMCD). The diagnosis of iMCD remains challenging due to its non-specific presentation, in the form of generalised lymphadenopathies and inflammation. Two clinical presentations have been recently defined: a severe form iMCD-TAFRO and a milder form of iMCD not otherwise specified (iMCD-NOS). identification of interleukin-6 (IL-6) as a major culprit of inflammatory symptoms led to the development of anti-IL-6 therapies, with siltuximab being the approved first-line treatment. Case description: A 16-year-old male presented with recurrent fever, night sweats and several other non-specific symptoms. After extensive evaluations, an excisional lymph node biopsy confirmed the iMCD-NOS diagnosis. The patient received high-dose steroid therapy followed by siltuximab for four years. This treatment was well tolerated with only mild neutropenia not leading to dose adjustment. On siltuximab, the patient developed two mild COVID-19 episodes. His response to siltuximab remained effective throughout four years. Discussion: The absence of biomarker or causal agent identification poses a diagnostic challenge requiring lymph node histopathology for a definitive diagnosis of iMCD. Anti-IL 6 (siltuximab) is the recommended frontline therapy, suppressing inflammation and halting disease progression. Intravenous administration every 3 to 6 weeks can impact patient quality of life, prompting further research for alternative treatments. High-dose steroids, rituximab, cyclosporine, tacrolimus, lenalidomide or combined chemotherapy such as rituximab-bortezomib-dexamethasone are among the considered options according to disease severity. Conclusion: Overall, long-term siltuximab effectively controlled iMCD symptoms and was well tolerated by this young adult, who endured two mild COVID-19 episodes

064 Temporal trends in prescription rates of recommended treatments in chronic heart failure outpatients: a comparison of three French surveys IMPACT RECO I, II & III

BackgroundRecent registries have shown that recommended drugs for the treatment of congestive heart failure (CHF) remain under-prescribed in daily practice.AimsTo compare prescription rates of CHF drugs in three French surveys Impact Reco I, II and III.MethodsWe included outpatients followed by private cardiologists: 1947 in Impact Reco I (2005), 1974 in Impact Reco II (2005/2006) and 1574 in Impact Reco III (2007), with NYHA class II-IV heart failure and a left ventricular ejection fraction < 40%, and we compared treatment modalities. Recommended treatments and target doses were defined according to ESC guidelines.ResultsThere was an improvement in both the rate of prescription, and in the proportion of patients reaching target dose or 50% of target dose of ACE I, ARBs and beta blockers (see table).ConclusionWe observed an improvement with time in the management of CHF outpatients with an increase in prescription rates of recommended CHF drugs, as well as in the dosage used for ACE-I, ARB and beta-blockers,PrescriptionIMPACT I 2005IMPACT II 2005/2006IMPACT III 2007Global population191719741574ACE INumber patients with prescriptionN (%)1361 (71.0)1349 (68.3)1099 (70.2)Target dose%48.757.3*52.3•50% Target dose%80.484.5*88.4†,•ARBsNumber patients with prescriptionN (%)395 (20.6)592 (30.0)*516 (33.3)†,•Target dose%9.17.420.7†,•50% Target dose%52.949.768.6†,•BetablockersNumber patients with prescriptionN (%)1245 (65.2)1382 (70.0)*1229 (78.3)†,•Target dose%18.423.4*25.7†50% Target dose%47.353.5*59.9†•*: p<0.05 Impact II vs I•: p<0.05 Impact III vs II†: p<0.05 Impact III vs Ialthough there is still room for improvement particularly for beta blockers. These encouraging findings suggest a better awareness and implementation of ESC guidelines by French private cardiologists

Circulating LPS and (1→3)-β-D-Glucan: A Folie à Deux Contributing to HIV-Associated Immune Activation

Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into systemic circulation. Bacteria and fungi are the two most abundant populations of the gut microbiome. Circulating lipopolysaccharide (LPS) and (1→3)-β-D-Glucan (βDG), major components of bacterial and fungal cell walls respectively, are measured as markers of microbial translocation in the context of compromised gut barriers. While LPS is a well-known inducer of innate immune activation, βDG is emerging as a significant source of monocyte and NK cell activation that contributes to immune dysfunction. Herein, we critically evaluated recent literature to untangle the respective roles of LPS and βDG in HIV-associated immune dysfunction. Furthermore, we appraised the relevance of LPS and βDG as biomarkers of disease progression and immune activation on ART. Understanding the consequences of elevated LPS and βDG on immune activation will provide insight into novel therapeutic strategies against the occurrence of AIDS and non-AIDS events

Un dépôt de crémation du Bronze final aux Ardelières, Brézins (Isère)

À l’occasion d’un diagnostic réalisé par l’Inrap en 2013 sur la commune de Brézins en Isère, un dépôt secondaire de crémation en fosse a été mis au jour. La parcelle n’ayant pas fait l’objet d’une prescription de fouille, la fosse a été prélevée et fouillée à l’occasion de la Fête de la science en 2014 au musée de Saint-Romain-en-Gal. Les résultats présentent l’analyse de ce dépôt incomplet, daté du Bronze final IIIb, accompagné d’un matériel de qualité comprenant notamment la présence d’un fragment de rasoir en alliage cuivreux et d’un gobelet décoré à l’étain.During an archaeological diagnosis carried out by Inrap in 2013 in the commune of Brézins in Isère, a cremation deposit was discovered. As the plot was not subject to an excavation order, the deposit was removed and excavated on the occasion of the Science Festival in 2014 at the Saint-Romain-en-Gal Museum. The results present the analysis of a secondary burial site dated from the final bronze IIIb. It was accompanied by quality artefacts including a copper alloy razor and a tin-decorated cup

LILAC pilot study : effects of metformin on mTOR activation and HIV reservoir persistence during antiretroviral therapy

Background: Chronic inflammation and residual HIV transcription persist in people living with HIV (PLWH) receiving antiretroviral therapy (ART), thus increasing the risk of developing non-AIDS co-morbidities. The mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism and HIV transcription, and therefore represents an interesting novel therapeutic target. Methods: The LILAC pilot clinical trial, performed on non-diabetic ART-treated PLWH with CD4+ /CD8+ T-cell ratios <0.8, evaluated the effects of metformin (12 weeks oral administration; 500-850 mg twice daily), an indirect mTOR inhibitor, on the dynamics of immunological/virological markers and changes in mTOR activation/phosphorylation in blood collected at Baseline, Week 12, and 12 weeks after metformin discontinuation (Week 24) and sigmoid colon biopsies (SCB) collected at Baseline and Week 12. Findings: CD4+ T-cell counts, CD4+ /CD8+ T-cell ratios, plasma markers of inflammation/gut damage, as well as levels of cell-associated integrated HIV-DNA and HIV-RNA, and transcriptionally-inducible HIV reservoirs, underwent minor variations in the blood in response to metformin. The highest levels of mTOR activation/ phosphorylation were observed in SCB at Baseline. Consistently, metformin significantly decreased CD4+ Tcell infiltration in the colon, as well as mTOR activation/phosphorylation, especially in CD4+ T-cells expressing the Th17 marker CCR6. Also, metformin decreased the HIV-RNA/HIV-DNA ratios, a surrogate marker of viral transcription, in colon-infiltrating CD4+ T-cells of 8/13 participants