Months-long seismicity transients preceding the 2023 MW 7.8 Kahramanmaras earthquake, Türkiye.

Short term prediction of earthquake magnitude, time, and location is currently not possible. In some cases, however, documented observations have been retrospectively considered as precursory. Here we present seismicity transients starting approx. 8 months before the 2023 MW 7.8 Kahramanmaras earthquake on the East Anatolian Fault Zone. Seismicity is composed of isolated spatio-temporal clusters within 65 km of future epicentre, displaying non-Poissonian inter-event time statistics, magnitude correlations and low Gutenberg-Richter b-values. Local comparable seismic transients have not been observed, at least since 2014. Close to epicentre and during the weeks prior to its rupture, only scarce seismic activity was observed. The trends of seismic preparatory attributes for this earthquake follow those previously documented in both laboratory stick-slip tests and numerical models of heterogeneous earthquake rupture affecting multiple fault segments. More comprehensive earthquake monitoring together with long-term seismic records may facilitate recognizing earthquake preparation processes from other regional deformation transients.

Protein binding investigation of first-line and second-line antituberculosis drugs.

Data on protein binding are incomplete for first-line antituberculosis drugs, and lacking for second-line antituberculosis drugs that are used extensively for multi-drug-resistant tuberculosis (levofloxacin, linezolid and moxifloxacin). Thus, the main purposes of this study were to investigate: (i) the relationship between carrier protein concentration and drug binding; and (ii) the feasibility of predicting free drug concentration using in-vitro and in-vivo results. In-vitro experiments were performed on spiked plasma mimicking real-case samples (drug combinations from clinical practice). Median in-vivo protein binding was 1.5% for ethambutol, 9.7% for isoniazid, 0.7% for pyrazinamide and 88.2% for rifampicin; and median in-vitro protein binding was 26.2% for levofloxacin, 12.8% for linezolid and 46.3% for moxifloxacin. Albumin concentration (<30 g/L) had a moderate impact on moxifloxacin binding and a strong impact on levofloxacin, linezolid and rifampicin binding. Determination of the free drug concentration seems to be of little value for ethambutol, isoniazid, moxifloxacin and pyrazinamide; limited value for linezolid because of its low binding; and major value for rifampicin in hypoalbuminaemic patients with tuberculosis, and levofloxacin because total concentration was an inaccurate reflection of free concentration. The free concentration predicted by the mathematical model was suitable for levofloxacin and linezolid, whereas the real free concentration should be measured for rifampicin. Further investigations should be carried out to investigate the benefit of using free concentration for levofloxacin, linezolid and rifampicin, particularly in the critical period of active tuberculosis associated with hypoalbuminaemia.

Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI.

INTRODUCTION: White matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. OBJECTIVE: To analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. METHODS: Through a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians' subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants' completion. RESULTS: In total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). CONCLUSION: Our results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

Intraoperative cerebral blood flow monitoring in neurosurgery: A review of contemporary technologies and emerging perspectives.

Intraoperative monitoring of cerebral blood flow (CBF) has become an invaluable adjunct to vascular and oncological neurosurgery, reducing the risk of postoperative morbidity and mortality. Several technologies have been developed during the last two decades, including laser-based techniques, videomicroscopy, intraoperative MRI, indocyanine green angiography, and thermography. Although these technologies have been thoroughly studied and clinically applied outside the operative room, current practice lacks an optimal technology that perfectly fits the workflow within the neurosurgical operative room. The different available technologies have specific strengths but suffer several drawbacks, mainly including limited spatial and/or temporal resolution. An optimal CBF monitoring technology should meet particular criteria for intraoperative use: excellent spatial and temporal resolution, integration in the operative workflow, real-time quantitative monitoring, ease of use, and non-contact technique. We here review the main contemporary technologies for intraoperative CBF monitoring and their current and potential future applications in neurosurgery.

Simultaneous determination of 8 beta-lactams and linezolid by an ultra-performance liquid chromatography method with UV detection and cross-validation with a commercial immunoassay for the quantification of linezolid.

Linezolid and beta-lactams are anti-infective drugs frequently used in intensive care unit patients. Critical illness could induce alterations of pharmacokinetic parameters due to changes in the distribution, the metabolism and the elimination process. Therapeutic drug monitoring (TDM) is therefore recommended to prevent mainly under-dosing of beta-lactams or hematological and neurological toxicities of linezolid. In Multi-or Extensively-Drugs Resistant-Tuberculosis Bacteria, the regimen could include linezolid with meropenem and amoxicillin/clavulanate justifying the development of a method allowing their simultaneous quantification. The aim of this work was to develop an in-house ultra-performance liquid chromatography method with UV detection (UHPLC-PDA) allowing the simultaneous determination of 8 beta-lactams (amoxicillin, aztreonam, cefepime, ceftazidime, ceftriaxone, cefuroxime, meropenem and piperacillin) and linezolid and to cross-validate the linezolid quantification with a new commercial immunoassay (ARK kit) tested on a Cobas analyzer. The main advantages of the immunoassay are a 24/24 h random access assay which is fully automated and results provided within 2 h. The interference due to potential co-administrated drugs was evaluated on both methods. The preanalytical factors (type of matrix, stability) for linezolid were also investigated. The influence of hemolysis, icteria or lipemia on the spectroscopic detection of the immunoassay was assessed. The analytical performances were evaluated using the accuracy profiles approach with acceptance limits fixed at ±30%. Seventy patient samples were measured using both methods. No cross-reaction with the tested anti-infective drugs as well as no influence of hemolysis, lipemia, icteria were observed. The linezolid concentration could be measured on heparinized plasma or serum without a significant difference and remained stable for at least 72h at 4°C.The UHPLC-PDA method performed well in the analytical range investigated (0.25-50 mg/L for meropenem, 0.75-50 mg/L for linezolid and 1-200 mg/L for other beta-lactams) with an intermediate precision and a relative bias below 7.6 and 7.7%, respectively. The analytical range of the immunoassay was narrower, from 0.85 to 18.5 mg/L. The precision and relative bias were lower than 8.1% and 4.2%, respectively. Results obtained on clinical samples showed an acceptable difference between methods with a mean bias of -1.8% [95% confidence interval: -5.2% - 1.6%]. To conclude, both methods showed acceptable performance to perform TDM of linezolid considering the therapeutic through target of 2-8 mg/L. The choice of the method should be made according to the degree of emergency of the response required and the field of application justifying or not the simultaneous quantification of beta-lactams and linezolid.

MRI characteristics of MOG-Ab associated disease in adults: An update.

Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.

Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

PURPOSE: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data. MATERIALS AND METHODS: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges. The training dataset consisted of 971 multiple sclerosis patients from the "Observatoire français de la sclérose en plaques" (OFSEP) cohort with initial FLAIR MRI and corresponding EDSS score at two years. A test dataset (475 subjects) was provided without an EDSS score. Ten percent of the training dataset was used for validation. RESULTS: Our algorithm predicted EDSS score in patients with multiple sclerosis and achieved a MSE=2.2 with the validation dataset and a MSE=3 (mean EDSS error=1.7) with the test dataset. CONCLUSION: Our method predicts two-year clinical disability in patients with multiple sclerosis with a mean EDSS score error of 1.7, using FLAIR sequence and basic patient demographics. This supports the use of our model to predict EDSS score progression. These promising results should be further validated on an external validation cohort.

Advanced multiparametric magnetic resonance imaging of multinodular and vacuolating neuronal tumor.

BACKGROUND AND PURPOSE: Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare brain lesion with suggestive imaging features. The aim of our study was to report the largest series of MVNTs so far and to evaluate the utility of advanced multiparametric magnetic resonance (MR) techniques. METHODS: This multicenter retrospective study was approved by our institutional research ethics board. From July 2014 to May 2019, two radiologists read in consensus the MR examinations of patients presenting with a lesion suggestive of an MVNT. They analyzed the lesions' MR characteristics on structural images and advanced multiparametric MR imaging. RESULTS: A total of 64 patients (29 women and 35 men, mean age 44.2 ± 15.1 years) from 25 centers were included. Lesions were all hyperintense on fluid-attenuated inversion recovery and T2-weighted imaging without post-contrast enhancement. The median relative apparent diffusion coefficient on diffusion-weighted imaging was 1.13 [interquartile range (IQR), 0.2]. Perfusion-weighted imaging showed no increase in perfusion, with a relative cerebral blood volume of 1.02 (IQR, 0.05) and a relative cerebral blood flow of 1.01 (IQR, 0.08). MR spectroscopy showed no abnormal peaks. Median follow-up was 2 (IQR, 1.2) years, without any changes in size. CONCLUSIONS: A comprehensive characterization protocol including advanced multiparametric magnetic resonance imaging sequences showed no imaging patterns suggestive of malignancy in MVNTs. It might be useful to better characterize MVNTs.

Three artificial intelligence data challenges based on CT and MRI.

PURPOSE: The second edition of the artificial intelligence (AI) data challenge was organized by the French Society of Radiology with the aim to: (i), work on relevant public health issues; (ii), build large, multicentre, high quality databases; and (iii), include three-dimensional (3D) information and prognostic questions. MATERIALS AND METHODS: Relevant clinical questions were proposed by French subspecialty colleges of radiology. Their feasibility was assessed by experts in the field of AI. A dedicated platform was set up for inclusion centers to safely upload their anonymized examinations in compliance with general data protection regulation. The quality of the database was checked by experts weekly with annotations performed by radiologists. Multidisciplinary teams competed between September 11th and October 13th 2019. RESULTS: Three questions were selected using different imaging and evaluation modalities, including: pulmonary nodule detection and classification from 3D computed tomography (CT), prediction of expanded disability status scale in multiple sclerosis using 3D magnetic resonance imaging (MRI) and segmentation of muscular surface for sarcopenia estimation from two-dimensional CT. A total of 4347 examinations were gathered of which only 6% were excluded. Three independent databases from 24 individual centers were created. A total of 143 participants were split into 20 multidisciplinary teams. CONCLUSION: Three data challenges with over 1200 general data protection regulation compliant CT or MRI examinations each were organized. Future challenges should be made with more complex situations combining histopathological or genetic information to resemble real life situations faced by radiologists in routine practice.

[White matter hyperintensities in ageing: Pathophysiology, associated cognitive disorders and prevention]. / Hypersignaux de la substance blanche chez la personne âgée : physiopathologie, troubles cognitifs associés et pistes de prévention.

White matter hyperintensities (WMH), also known as leukoaraïosis are very common neuroradiological manifestations in the elderly. The main risk factors for WMH are age and high blood pressure. The vascular origin of these lesions is classically accepted and WMH are considered as one feature of the small vessel disease. WMH may be associated with clinical symptoms, depending notably on their importance according to age. They are associated with increased mortality, strokes and changes in cognition with a higher risk of dementia (vascular dementia or Alzheimer's disease). Modification of vascular risk factors could have a beneficial effect, but few evidences from controlled trials are available.

Multinodular and Vacuolating Posterior Fossa Lesions of Unknown Significance.

Multinodular and vacuolating neuronal tumor of the cerebrum is a rare supratentorial brain tumor described for the first time in 2013. Here, we report 11 cases of infratentorial lesions showing similar striking imaging features consisting of a cluster of low T1-weighted imaging and high T2-FLAIR signal intensity nodules, which we referred to as multinodular and vacuolating posterior fossa lesions of unknown significance. No relationship was found between the location of the lesion and clinical symptoms. A T2-FLAIR hypointense central dot sign was present in images of 9/11 (82%) patients. Cortical involvement was present in 2/11 (18%) of patients. Only 1 nodule of 1 multinodular and vacuolating posterior fossa lesion of unknown significance showed enhancement on postcontrast T1WI. DWI, SWI, MRS, and PWI showed no malignant pattern. Lesions did not change in size or signal during a median follow-up of 3 years, suggesting that multinodular and vacuolating posterior fossa lesions of unknown significance are benign malformative lesions that do not require surgical intervention or removal.

Investigation of unbound colistin A and B in clinical samples using a mass spectrometry method.

Colistin, used as a last-resort drug, has a narrow therapeutic range that justifies therapeutic drug monitoring. Few data are available in the literature regarding the in vivo unbound fraction of colistin. The objectives of this study were to develop a method to isolate unbound colistin in clinical samples by ultrafiltration and to quantify it. The association between unbound colistin and biological parameters (total protein, albumin, alpha-1-acid glycoprotein and creatinine) was investigated. The measured ranges were 0.036-7.160 mg/L for colistin A and 0.064-9.630 mg/L for colistin B. The process of isolation and determination of unbound colistin was applied to clinical samples (n = 30) within 40 min and no non-specific binding was observed during the ultracentrifugation step. The median unbound fractions of colistin measured were 34.3% (12.8-51.0%) and 53.4% (27.0-77.8%) for colistin A and B, respectively. High interindividual biological variation of binding was observed for colistin A and B that was not explained by the biochemical parameters studied. The method developed could be useful to improve outcomes for patients.

Main inherited neurodegenerative cerebellar ataxias, how to recognize them using magnetic resonance imaging?

Ataxia is a neurodegenerative disease resulting from brainstem, cerebellar, and/or spinocerebellar tracts impairments. Symptoms onset could vary widely from childhood to late-adulthood. Autosomal cerebellar ataxias are considered as one of the most complex group in neurogenetics. In addition to their genetic heterogeneity, there is an important phenotypic variability in the expression of cerebellar impairment, complicating the genetic mutation research. A pattern recognition approach using brain MRI measures of atrophy, hyperintensities and iron-induced hypointensity of the dentate nuclei, could be therefore helpful in guiding genetic research. This review will discuss a pattern recognition approach that, associated with the age at disease onset, and clinical manifestations, may help neuroradiologists differentiate the most frequent profiles of ataxia.

[Diagnosis and treatment of nephrolithiasis and prevention of recurrences]. / Mise au point et traitement des lithiases rénales et prévention des récidives.

INTRODUCTION: despite fluctuations, the prevalence of nephrolithiasis has significantly increased during the last decades in industrialized nations worldwide (1 to 15 %), which has a significant impact on the cost of healthcare. This increased prevalence is mainly explained by diet modifications. Environmental, metabolic and genetic factors may also influence the formation of kidney stones. As a consequence, the medical management of this disease is preferentially multidisciplinary and involves urologists, nephrologists, radiologists, biologists and dietitians. Urological management : may be mandatory during any acute and/or remote phase of an episode of renal colic, in case of residual stones. Several techniques are available: insertion of double J stent, extracorporeal shock wave lithotripsy, ureteroscopy (flexible or rigid), percutaneous nephrolithotomy and more occasionally, open surgery. Nephrological management: is justified in the course of the acute episode and aims to identify the causal factor(s) of kidney stones formation. The diagnostic approach involves a thorough interrogation (personal medical and surgical history, details of the kidney stone disease and family medical history) as well as a metabolic assessment. Moreover, given the high rate of recurrence (about 50 % within 5 to 10 years), individualized secondary prevention measures are necessary. The recommendations should take into account the identified risk factors and any metabolic abnormalities.

INTRODUCTION: la néphrolithiase est une affection dont la prévalence (1 à 15 %) a beaucoup augmenté ces dernières décennies dans les pays industrialisés et a, de ce fait, un impact sur les dépenses en soins de santé. Cette augmentation de prévalence s'explique essentiellement par une modification des habitudes alimentaires. La survenue d'une néphrolithiase peut en outre, être influencée par des facteurs environnementaux, métaboliques voire génétiques. La prise en charge de cette affection est le plus souvent pluridisciplinaire, impliquant urologues, néphrologues, radiologues, biologistes et diététiciens. La prise en charge urologique peut être nécessaire en phase aiguë et/ou à distance de l'épisode de colique néphrétique, pour l'élimination éventuelle de calculs résiduels. Plusieurs techniques sont disponibles : la mise en place de sondes double J, la lithotritie extracorporelle, l'urétéroscopie (souple ou rigide) voire la néphrolithotomie percutanée et plus rarement la chirurgie ouverte. La prise en charge néphrologique est justifiée au décours de l'épisode aigu et vise à identifier la ou les cause(s) ayant conduit à la formation de calculs. La démarche diagnostique comporte un interrogatoire approfondi (antécédents personnels médicaux et chirurgicaux, histoire de la maladie lithiasique et antécédents familiaux) et un bilan métabolique. Par ailleurs, compte-tenu du taux élevé de récidive (environ 50 % dans les 5 à 10 ans), la mise en place de mesures individualisées de prévention secondaire est nécessaire. Ces recommandations doivent tenir compte des facteurs de risque identifiés et des éventuelles anomalies du bilan métabolique.

Gray Matter-White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence.

BACKGROUND: Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. METHODS: In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. RESULTS: At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21 at the basal ganglia level was identified, below which brain death systematically occurred. CONCLUSIONS: GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system.

A rare case of SPG11 mutation with multiple sclerosis.

We describe a patient with SPG11 hereditary spastic paraplegia (HSP), who developed walking disorder in childhood. He presented three episodes of subacute gait disorders worsening between the age of 20 and 22 years. Brain and spinal MRI revealed multiple T2 hypersignal lesions, consistent with inflammatory lesions. Surprisingly, CSF analysis showed neither oligoclonal bands nor increased IgG index. He was dramatically improved by intravenous methylprednisolone. A relapsing-remitting multiple sclerosis (MS) was suspected. This is the first description of SPG11 HSP associated with MS.

[Recurrent episodes of brushite nephrolithiasis revealing primary hyperparathyroidism]. / Néphrolithiases récurrentes de brushite révélant une hyperparathyroïdie primaire.

INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.

OFSEP, a nationwide cohort of people with multiple sclerosis: Consensus minimal MRI protocol.

Multiple sclerosis (MS) is most generally considered as a severe disease with high physical and mental risks of disability. Since the end of the 1990s, several high cost long-term disease-modifying treatments provided some clinical efficiency. However, patient's follow-up was needed for the detection and the assessment of their side-effects. The "Observatoire français de la sclérose en plaques" (OFSEP) project aims to improve the clinical, biological and imaging systematic longitudinal follow-up of patients. It should increase the quality, efficiency and safety of patients' care, with a unique opportunity of large scale, about 41,000 patients followed in 62 French centers using the European Database for Multiple Sclerosis (EDMUS) software. OFSEP is divided into three working groups (clinical, biological and imaging). The imaging working group defines standards for routine MRI follow-up in the whole cohort and contains three subgroups: acquisition, workflow, and data processing. A common and feasible brain and spinal cord acquisition protocol has been defined by the acquisition group, and accepted by the OFSEP steering and scientific committees. This protocol can be implemented in all French MRI centers. The major MRI manufacturers have agreed to provide the dedicated collection of sequences as an "OFSEP box" with every software upgrade or new MRI machine. The new OFSEP protocol will provide a unique opportunity to study a population-based collection of data from people with MS.