Anaesthetic management of people with multiple sclerosis.

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles.

Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease.

BACKGROUND: Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses. RESULTS: Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; Anelloviridae (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1). CONCLUSIONS: Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection. Video abstract.

Correlation of clinical symptoms and signs with conjunctival gene expression in primary Sjögren syndrome dry eye patients.

PURPOSE: The aim of this study was to characterize the expression of inflammation-related genes on the ocular surface of Sjögren syndrome (SS) patients and to evaluate their correlations with clinical symptoms and signs. METHODS: The study enrolled 30 patients with SS dry eye and 15 healthy controls. Symptoms were evaluated using OSDI questionnaire. The clinical signs were investigated using corneal fluorescein staining (CFS), tear breakup time (TBUT), Schirmer test and tear osmolarity measurement. Conjunctival superficial cells were collected using conjunctival impression cytology and total RNAs were extracted for analysis using the NanoString® nCounter technology. The Mann-Whitney nonparametric statistical test and Spearman correlations were used to explore the correlations between the up/downregulated genes and the clinical signs and symptoms. RESULTS: Twenty-seven genes were upregulated and 13 were downregulated with statistically significant fold changes ranging from 1.5 to 16.7 and 0.3 to 0.8, respectively. OSDI and CFS were the most significantly correlated parameters with 21 and 19 inflammatory genes, respectively. Among all the upregulated genes, 14 were positively correlated with both OSDI and CFS. Two downregulated genes (GNGT1, HSPB2) were negatively correlated with OSDI and CFS. IL1RN was the only gene positively correlated with the Schirmer test. CONCLUSIONS: These results highlight the differentially expressed genes in primary Sjögren syndrome and their relationships between the inflammatory genes expressed and the patient symptom score and corneal damage. The inflammatory genes implicated in SS-associated dry eye could be important tools to determine the pathophysiological profiles of SS and potentially useable as specific signatures.

Human pegivirus persistence in human blood virome after allogeneic haematopoietic stem-cell transplantation.

OBJECTIVES: Because commensal viruses are defined by the immunologic tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem-cell transplantation, may shift the demarcation between innocuous viral resident and disease-causing pathogen. METHODS: We analysed by deep-sequencing the plasma virome of 40 allogeneic haematopoietic stem-cell transplantation patients 1 month after transplantation. Because human pegivirus (HPgV) was highly prevalent, we performed a 1-year screening of 122 plasma samples by specific real-time reverse transcription PCR assay. We used the log-rank test and the Gray test to assess association with outcomes, and the Mann-Whitney test and multivariable linear regression model to assess association with T-cell reconstitution. RESULTS: Polyomaviruses (PyV) (20/40 patients), anelloviruses (16/40), pegiviruses (14/40) and herpesviruses (14/40) were most frequently identified, including ten cytomegalovirus; three Epstein-Barr virus; two herpes simplex virus type 1; one human herpesvirus 6b and one human herpesvirus 7; 18 Merkel cell-PyV; two BK-PyV; three PyV-6; and one JC-PyV. Papillomavirus and adenovirus were identified in 11 and two patients, respectively. The HPgV specific real-time reverse transcription PCR screening identified 51 of 122 positive samples, high virus loads and persistent infections up to 1 year after transplantation. Comparison between patients with or without HPgV infection at time of transplantation did not reveal a significant difference in infections, engraftment, survival, graft vs. host disease, relapse or immune reconstitution. CONCLUSIONS: The blood virome after allogeneic haematopoietic stem-cell transplantation includes several DNA viruses, notably herpesviruses and PyV. Among RNA viruses, HPgV is highly prevalent and persists for several months, and it thus may deserve special attention in further research on immune reconstitution.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology.

Toscana virus meningitis case in Switzerland: an example of the ezVIR bioinformatics pipeline utility for the identification of emerging viruses.

Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses.

Glioblastoma surgery with and without intraoperative MRI at 3.0T.

BACKGROUND: Gross total or near total resection (GTR/NTR; resection ≥95%) of glioblastoma (GBM) seems correlated with a longer survival. Intraoperative MRI (ioMRI) is one method to evaluate the extent of resection (EOR) in order to improve it during the same anesthesia. We compared GBM resections using a 3.0T ioMRI and then without considering the EOR, safety, survival and discussed the indications for using this expensive modality. METHODS: Between March 2006 and November 2011, 56 GBM resections were performed using an ioMRI, and 38 without (control group). The only criterion in order to have access to the ioMRI was its availability. We compared the variables EOR, Karnofsky Performance Scale scores and survival in both groups. RESULTS: In the ioMRI group, 15 patients (26.8%) underwent an immediate second resection increasing the GTR rate of 10.7% and the GTR/NTR rate of 8.9%. There was a significant difference between the use of an ioMRI and the control group in reaching a larger EOR (P=0.049, Fisher's exact test). The effect of using the ioMRI or not on the overall survival, with EOR as covariate, was not significant (P=0.147, Likelihood ratio test). However, the EOR alone had a significant effect on survival (P=0.049, Wald test), with a shorter survival for the patients with a partial resection (PR) than a GTR/NTR (Hazard ratio=1.6, 95% CI HR: 1.00-2.69), with a median overall survival of 15.26 months (95% CI: 12.34-19.08) for the GTR/NTR subgroup versus 10.26 months (95% CI: 6.64-15.82) for the PR subgroup. Multivariate regression analysis also identified age, sex and adjuvant chemotherapy as factors significantly associated with overall survival. CONCLUSIONS: A 3.0T ioMRI improved the quality of resection by 17.8% and increased the GTR/NTR rate by 8.9% up to 73.2% without additional morbidity. A GTR/NTR improves survival duration by about 50%. Thus, it remains reasonable to increase the EOR to reach GTR/NTR using an intraoperative control. However, ioMRI should be limited to the cases for which a GTR/NTR seems preoperatively possible.

[Indications and surgical treatments for failed coiled aneurysms]. / Indications et traitement chirurgical des anévrismes intracrâniens après recanalisation ou embolisation incomplète.

The possibility of treating intra-cranial aneurysms (ICA) through an endovascular approach is a great progress. But, as any technique, it has its own limitations. Multidisciplinary neurovascular teams are regularly confronted with ICA where embolization is a poor option or even failed (a residue of more than 5% at six months follow-up or after recanalization). Another potential failure is a coil extrusion into the parent vessel with thrombo-embolic risks. Our team and others in the world developed strategies to manage these complex cases. After a brief review of the literature, we describe our experience and present a modified Gurian classification. This classification allows a better identification of the various failed coiled aneurysms types and their potential surgical treatments.

Two cases of isolated unilateral paralysis of hypoglossal nerve after uncomplicated orotracheal intubation.

We report two cases of postoperative unilateral hypoglossal nerve palsy following uncomplicated orotracheal intubation for plastic surgery. Both patients underwent a long procedure and were installed in a non physiological position. These two factors might have played an important role in the mechanism of nerve damage. Furthermore, other etiologies of neurological injury like a difficult airway or anatomical anomalies were not present. The aim of these two case reports is to sensitize the anesthetists to hypoglossal nerve palsy and to highlight a potential clinical problem of positioning during plastic surgery.

Purinergic activation of a leak potassium current in freshly dissociated myocytes from mouse thoracic aorta.

AIM: Exogenous ATP elicits a delayed calcium-independent K(+) current on freshly isolated mouse thoracic aorta myocytes. We investigated the receptor, the intracellular pathway and the nature of this current. METHODS: The patch-clamp technique was used to record ATP-elicited delayed K(+) current in freshly dissociated myocytes. RESULTS: ATP-elicited delayed K(+) current was not inhibited by a 'cocktail' of K(+) channel blockers (4-AP, TEA, apamin, charybdotoxin, glibenclamide). The amplitude of the delayed K(+) current decreased after the reduction of extracellular pH from 7.4 to 6.5. These two characteristics suggest that this current could be carried by the TASK subfamily of 'twin-pore potassium channels' (K2P). Purinergic agonists including dATP, but not ADP, activated the delayed K(+) current, indicating that P2Y(11) is the likely receptor involved in its activation. The PKC activator phorbol ester 12,13-didecanoate stimulated this current. In addition, the PKC inhibitor Gö 6850 partially inhibited it. Real-time quantitative PCR showed that the genes encoding TASK-1 and TASK-2 are expressed. CONCLUSION: Our results indicate that blocker cocktail-insensitive delayed K(+) current in freshly dissociated aortic myocytes is probably carried by the TASK subfamily of twin-pore channels.

Neurosurgical management of inadequately embolized intracranial aneurysms: a series of 17 consecutive cases.

OBJECTIVE: Inadequately embolized aneurysms (IEA) are coiled aneurysms with a significant remnant (>5%), initially or after recanalisation, or with a coil extrusion deemed too thrombogenic or threatening the blood flow in the parent vessel. Our objective is to report our experience with the surgical clipping (SC) of a consecutive series of 17 IEA considered as not appropriate for an additional endovascular procedure. METHODS: Between February 1996 and April 2006, we evaluated 523 ICA in 380 patients of whom 192 underwent coil embolisation (CE), 117 with complete occlusion (61%), 47 with near complete occlusion (> or = 95%), 9 with partial occlusion (<95%), and 19 without any coil delivery (attempted embolisation). Of the 173 ICA embolized one or two times, at their radiological follow-up 15 (8.6%) were considered as IEA and not appropriate for an additional CE. Two IEA treated endovascularly before February 1996 were added to this series. The female/male ratio was 0.47 with an average age of 54 years (range, 37-65). All cases were located on the anterior circulation except the last one. The 17 IEA were treated by SC either because of an aneurysm remnant deemed not accessible to a further CE and large enough for direct clipping or because the risks of a thromboembolic event related to extruded coils was too high. RESULTS: SC was complete in all 17 cases, confirmed angiographically. Postoperatively, the clinical status of two patients deteriorated slightly but transiently. Our surgical experience with this series led us to classify IEA into five types, in three groups: group A (with one type: type A) was the most important group (n = 11) with IEA characterized by an aneurysm residue allowing direct SC, as assessed preoperatively; group B (n = 4) comprised aneurysms with a residue smaller than predicted and showing parent vessel stenosis when a clip was applied to the neck residue requiring the fundus full of coils to be removed followed by either clip application to the neck residue (type B1, n = 3) or suture if the remnant was too small (type B2, n = 1); and group C (n = 2) grouping cases requiring coil extraction through the parent vessel (type C2, n = 1) or through the fundus (type C2, n = 1). CONCLUSIONS: With this series of IEA, we observed that open surgery of type A and C aneurysms can be a straightforward procedure. Our experience with type B IEA encourages us to wait for a sufficient aneurysm residue before performing SC because of the potential difficulties that may be encountered by the surgeon, particularly in type B2. SC of IEA was very effective with complete occlusion and no permanent morbidity in all 17 cases.

Microsurgical results with large vestibular schwannomas with preservation of facial and cochlear nerve function as the primary aim.

OBJECTIVE: To evaluate our microsurgical results in dealing with vestibular schwannomas (VS) greater than or equal to 30 mm when preservation of cranial nerve function was considered more important than total tumour removal. METHODS: Sixteen consecutive cases were operated on by the same neurosurgeon according to a prospective protocol using intraoperative neuro-monitoring (IONM) based on electromyographic and brain stem auditory evoked potential recordings. Facial nerve function was evaluated on the House-Brackmann Scale and cochlear nerve function on the Gardner-Robertson Scale. Someone not involved in the clinical management of our patients collected all data. RESULTS: Fifteen patients showed facial nerve (FN) function of House-Brackmann grade (HBG) I or II at one year postoperatively and one kept the HBG IV she had preoperatively. Two patients of four maintained a cochlear nerve function of Gardner-Robertson grade (GRG) II. The tumour excision rates were: total, 68.7%; near total, 6.3%; subtotal, 18.7%, and partial, 6.3%. The average follow-up was 55 months (1-106). Three patients underwent radiotherapy later with growth stabilisation and no additional morbidity. CONCLUSION: When dealing with VS greater than or equal to 30 mm, microsurgery guided by IONM, with a rate of total or near-total tumour excision of about 75%, can retain socially acceptable facial nerve function (HBG I or II) in all cases and serviceable hearing (GRG I or II) in two cases out of four. Maintaining serviceable cranial nerve function should take precedence over total tumour excision.

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia.

BACKGROUND: Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. METHODS: The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg(-1)) naloxone, i.v. (10 mg kg(-1)) and i.t. (50, 100 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor). RESULTS: Sufentanil 0.005 micro g kg(-1) min(-1) significantly increased MACbar (3.2 (sd 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 micro g], i.t. meloxicam [150 micro g]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg(-1)], i.v. MK-801 [0.5, 1 mg kg(-1)], i.v. ketorolac [10 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]). CONCLUSIONS: We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

[Anesthesia in a child presenting a anhydrotic ectodermic dysplasia associated with a multiminicore myopathy]. / Anesthésie d'une enfant presentant une dysplasie anhydrotique ectodermique associée à une myopathie multiminicore.

PURPOSE: To report the perioperative management of anesthesia and analgesia in a child presenting with the association of multiminicore myopathy (MMM) and anhydrotic ectodermic dysplasia (AED). CLINICAL FEATURES: An eight-year-old girl was admitted for elective orthopedic surgery of the lower limbs. AED is a congenital dermatosis characterized by the absence of sweating and subsequent problems with thermoregulation; in addition, maxillary hypoplasia and abnormal teeth can render intubation difficult. MMM is a rare congenital myopathy characterized by proximal muscle weakness, stable in time or with a slow and progressive evolution. It can involve respiratory muscles and be associated with severe cardiomyopathy. Moreover, MMM shares some characteristics with Central Core Disease which is known to be associated with malignant hyperthermia. Since depolarizing muscle relaxants and halogenated agents could not be used, a combined propofol-based intravenous anesthesia with lumbar epidural analgesia was chosen. This combination provided stable anesthesia, smooth recovery and excellent analgesia during and after the operation, without complications. Temperature was monitored closely during surgery and in the postoperative period. CONCLUSIONS: The association of MMM and AED requires rapid distinction between hyperthermia secondary to anhydrosis and malignant hyperthermia. The management should provide a "trigger-free" anesthetic and optimal postoperative analgesia without sedation. If appropriate for the surgical procedure, a combination of general with regional anesthesia is particularly attractive in achieving these objectives.

The maternal effect mutation sésame affects the formation of the male pronucleus in Drosophila melanogaster.

After entering the oocyte and before the formation of the diploid zygote, the sperm nucleus is transformed into a male pronucleus, a process that involves a series of conserved steps in sexually reproducing animals. Notably, a major modification of the male gamete lies in the decondensation of the highly compact sperm chromatin. We present here the phenotype of sésame (ssm), a maternal effect mutation which affects the formation of the male pronucleus in Drosophila melanogaster. Homozygous ssm(185b) females produce haploid embryos which develop with only the maternally derived chromosomes. These haploid embryos die at the end of embryogenesis. Cytological analyses of the fertilization in eggs laid by ssm(185b) mutant females showed that both pronuclear migration and pronuclear apposition occurred normally. However, a dramatic alteration of the male pronucleus by which its chromatin failed to fully decondense was systematically observed. Consequently, the affected male pronucleus does not enter the first mitotic spindle, which is organized around only the maternally derived chromosomes. Immunodetection of lamina antigens indicates that a male pronuclear envelope is able to form around the partially decondensed paternal chromatin. This suggests that the maternally provided sésame(+) function is required for a late stage of sperm chromatin remodeling.

Germ-line expression of a functional LINE from Drosophila melanogaster: fine characterization allows for potential investigations of trans-regulators.

The I factor (IF) is a functional non-viral retrotransposon, or LINE, from Drosophila melanogaster. It is mobilized in the germ-line of dysgenic SF females during I-R hybrid dysgenesis. In previous papers (Lachaume et al., Development 115: 729-735, 1992; Lachaume and Pinon, Mol. Gen. Gen. 240: 277-285, 1993) we used a transgenic fusion between the 5' part of the IF and the lacZ gene to characterize IF expression and its regulation. This I-lacZ transgenic fusion expresses beta-galactosidase activity during oogenesis. We established a Drosophila line bearing four transgenic insertions (the 4I-lacZ line) and got new insights about IF expression: (1) I-lacZ expression is proportional to the copy number of transgenes present in the genome, (2) the expression occurs just before or when meiosis begins, (3) this expression seems to be subjected to a variegation effect within the germ-line cells, (4) the transgenic activity is mainly directed toward the decondensed chromatin of nurse cells. The close relationship between I factor expression and oogenesis led us to investigate the role played by genes expressed during oogenesis on I factor expression. We present recent data indicating that mutants which interfere with oogenesis can also affect I factor expression. From this data we propose an original screen using the 41-lacZline to detect identified mutations which also affect I factor expression.