Advances in treatments of patients with classical and emergent neurological toxicities of anticancer agents.

The neurotoxicity associated to the anticancer treatments has received a growing body of interest in the recent years. The development of innovating therapies over the last 20years has led to the emergence of new toxicities. Their diagnosis and management can be challenging in the clinical practice and further research is warranted to improve the understanding of their pathogenic mechanisms. Conventional treatments as radiation therapy and chemotherapy are associated to well-known and under exploration emerging central nervous system (CNS) and peripheral nervous system (PNS) toxicities. The identification of the risk factors and a better understanding of their pathogeny through a "bench to bedside and back again" approach, are the first steps towards the development of toxicity mitigation strategies. New imaging techniques and biological explorations are invaluable for their diagnosis. Immunotherapies have changed the cancer treatment paradigm from tumor cell centered to immune modulation towards an efficient anticancer immune response. The use of the immune checkpoints inhibitors (ICI) and CAR-T cells (chimeric antigen receptor) lead to an increase in the incidence of immune-mediated toxicities and new challenges in the neurological patient's management. The neurological ICI related adverse events (n-irAE) are rare but potentially severe and may present with both CNS and PNS involvement. The most frequent and well characterized, from a clinical and biological standpoint, are the PNS phenotypes: myositis and polyradiculoneuropathy, but the knowledge on CNS phenotypes and their treatments is expanding. The n-irAE management requires a good balance between dampening the autoimmune toxicity without impairing the anticancer immunity. The adoptive cell therapies as CAR-T cells, a promising anticancer strategy, trigger cellular activation and massive production of proinflammatory cytokines inducing frequent and sometime severe toxicity known as cytokine release syndrome and immune effector cell-associated neurologic syndrome. Their management requires a close partnership between oncologist-hematologists, neurologists, and intensivists. The oncological patient's management requires a multidisciplinary clinical team (oncologist, neurologist and paramedical) as well as a research team leading towards a better understanding and a better management of the neurological toxicities.

Autoimmune cerebellar hypermetabolism: Report of three cases and literature overview.

We report three cases of vermian cerebellar hypermetabolism in patients with autoimmune encephalitis. One of our patients was positive for anti-Ma2 antibodies and one for anti-Zic4 antibodies while the remaining patient did not present any known antibodies. The seronegative patient deteriorated after immune checkpoint inhibitor treatment for a pulmonary adenocarcinoma and improved with immunosuppressive drugs, which is in favour of an underlying autoimmune mechanism. They all presented with subacute neurological symptoms. Brain magnetic resonance imaging was normal except in one patient, where hyperintensities were present on FLAIR sequence around the third ventricle and the cerebral aqueduct. 18F-FDG brain positron emission tomography with computed tomography (18F-FDG PET-CT) demonstrated an unusual vermian cerebellar hypermetabolism in the three cases. While cerebellar hypermetabolism on 18F-FDG PET-CT has been described in various neurological diseases, such vermian - and more broadly cerebellar - hypermetabolism was seldom described in previous studies on autoimmune encephalitis. When differential diagnoses have been ruled out, this pattern may be of interest for the positive diagnosis of autoimmune encephalitis in difficult diagnostic cases.

Environmental risk factors of primary brain tumors: A review.

Adult primary tumors of the central nervous system are rare, but the incidence is increased in some European countries. Several environmental exposures have been investigated as potential risk factors, but for most, scientific evidence is still lacking. Here we review studies of environmental factors potentially involved in the carcinogenesis of brain tumors: the potential association between primary central nervous system tumors and ionizing radiation, some toxic agents (N-nitroso compounds, pesticides), air pollution, and radiofrequency electromagnetic waves. Brain-ionizing irradiation, especially during childhood, constitutes a well-established risk factor for brain tumors. Exposure to environmental toxins has been poorly explored and data give inconsistent clues about N-nitroso compounds or pesticides as risk factors of brain tumors even for prenatal exposure. For out-door pollution and risk of brain tumour, results of large prospective studies are contradictory. The effect of mobile phones on the risk of developing brain tumors has not been established for glioma and meningioma in adults, but the link with acoustic neurinoma is becoming robust. The effect of mobile phones has still not been explored in children.

Unusual presentation of leptospirosis in the late stage of pregnancy.

Here we report a case of leptospirosis without fever during the late stage of pregnancy in which the initial clinical presentation was more suggestive of a pregnancy-related liver dysfunction rather than an infectious disease. A 32-year-old primipara at 37 week of gestation was hospitalised with a 10-day history of nausea, vomiting, and abdominal pain without fever. Initial routine blood tests showed hyperbilirubinemia, a moderate increase in transaminase levels, severe coagulopathy and an increased creatinine level. On clinical suspicion of pregnancy-related liver dysfunction such as HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) or acute fatty liver of pregnancy (AFLP), emergency caesarean section was performed and a healthy baby was delivered. Postoperatively, the patient was stable, but 5 days later she developed clouding of consciousness, severe jaundice and respiratory failure. At this time, an infectious disease was considered and leptospirosis was confirmed by serological tests. In conjunction with intensive care management, antibiotic therapy was given; the patient was discharged in good condition and her baby did not develop signs of active leptospirosis. While leptospirosis is rare in pregnancy, this is the first report of acute infection without fever mimicking the clinical pattern of HELLP syndrome or AFLP

Anesthesiologic preoperative evaluation of drug addicted patient.

Even if there are few scientific data about preoperative management of drug addict patients, a careful anesthesiology evaluation facilitates the prevention of interactions between drugs and anaesthetics and avoids intraoperative and postoperative complications. Moreover it is important to earn the confidence of patient in order to know the abuse substances consumed and the frequency of consumption. This knowledge is necessary to the anaesthetist in order to manage possible withdrawal syndromes or overdose, which are the two greatest dangers for a drug addict patient during the hospital stay.

NIV treatment for acute exacerbation in COPD patients.

The authors review the clinical applications of non invasive ventilation (NIV) in patients with chronic obstructive pulmonary disease (COPD), mostly focusing on NIV issues and possible solutions. After briefly reviewing the respiratory mechanics modification during an episode of COPD exacerbation, the authors describe the two crucial technical aspects (choice of the interface and leaks control) that are mostly involved in patient-ventilator interaction. Finally, they briefly review the most important clinical trials on NIV.

[Double mitral valve orifice. Apropos of a case discovered by echocardiography]. / Orifice mitral double. A propos d'un cas de découverte échocardiographique.

The authors report a case of isolated double orifice mitral valve in a 20-year old pregnant woman. This exceptional and seldom isolated anomaly is usually discovered at autopsy or surgery. In this particular case it was diagnosed by pulsed doppler ultrasound combined with echocardiography. Data from the literature are reviewed on that occasion, and the echocardiographic images of the malformation are described. Despite its rarity, double orifice mitral valve deserves to be known and its presence should be looked for by echocardiography, notably in patients with complete or partial atrioventricular canal.

[Prognosis of ventricular tachycardia]. / Pronostic des tachycardies ventriculaires.

The prognosis of monomorphous, sustained, non-iatrogenic ventricular tachycardia was studied in 86 patients followed up for a mean period of 42.8 months. The patients were divided into three groups as follows: group I, 46 patients with myocardial infarction beyond the acute phase; group II, 30 patients with non-ischaemic heart disease; group III, 10 patients without heart disease detectable at angiography and/or echotomography. Fifty patients died during the follow-up period. Forty (80 p. cent) of these deaths (26 in group I, 14 in group II) were due to cardiac causes: heart failure in 24 cases, sudden death in 15 cases, recurrent myocardial infarction in 1 case. The percentage of cardiac death was higher in patients with left ventricular dysfunction (66 p. 100 versus 15.2 p. 100) and when the ejection fraction was below 0.40 (52.9 p. 100 versus 11.8 p. 100). The proportion of sudden death was 66.7 p. 100 when Lown's grade IV ectopic rhythm persisted under treatment, and only 7.7 p. 100 when this was not the case (p less than 0.001). These results confirm that: ventricular tachycardia has a high mortality rate in patients with heart disease; ventricular tachycardia on a "healthy" heart is of good prognosis; left ventricular dysfunction and persistence of repetitive forms under treatment have a high predictive value for cardiac death.

[Coronary occlusion immediately following a successful coronary angioplasty. Treatment by repeat angioplasty]. / Occlusion coronarienne au décours immédiat d'un succès d'angioplastie coronarienne. Traitement par nouvelle angioplastie.

The authors report the case of a 52 year old patient with a significant stenosis of the medial portion of the left anterior descending artery (LAD) with excellent left ventricular function. Transluminal coronary angioplasty (TCA) was indicated following a positive exercise stress test. This was initially performed successfully. Fifteen minutes after the end of the procedure, a total obstruction occurred at the site of dilatation immediately eliciting significant precordial chest pain and massive elevation of the ST segment. Isosorbide dinitrate (ISDN) at a dose of 2 mg was injected into the artery 3 times without success as was an attempt to pass through the obstruction with a guide wire. Another TCA was then attempted without administration of the thrombolytic agent. The dilating catheter passed easily by the obstruction permitting several dilatations which restored rapid coronary artery flow, relieved completely the chest pain, and normalized electrocardiographic abnormalities. This procedure represents a new therapeutic approach to obstruction, an often unpredictable and serious complication of coronary angioplasty in the absence of collateral circulation, thereby preventing the development of a myocardial infarction and an emergency aortocoronary bypass operation.

[Toxic effects of nitrosamines with respect to marine organisms]. / Etude des effets toxiques de composés nitrosoaminés vis-à-vis d'organismes marins.

Nitrosamins present in the aquatic medium are considered as carcinogenic substances to the laboratory animals. This experimentation has for object to precise toxicity effects of the nitroso-compounds: nitrosodimethyllamine (NDMA) on two phytoplankton cultures, and on the common mussels. The addition of NDMA to the seawater of aquarium, in particular experimental conditions induces toxicity effects on the growth and behavior of phytoplanktonic cultures and of the common mussels: Mytilus edulis (tissus modification, and attack of some organs).