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.

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.

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.

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.

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.

Written production in a case of locked-in syndrome with bilateral corticopontic degeneration.

Patients in locked-in syndrome show normal or near normal mental abilities that contrast with the limited motor capacity that hinders voluntary communication. However, eye movements and blinking are usually preserved and can be used to establish a communication system. We report an exceptional case of locked-in syndrome. The aetiology was basilar thrombosis consecutive to a cervical manipulation. In addition, brain MRI performed 23 years later showed a ventral pontine stroke with bilateral corticopontic degeneration. In this study the patient was able to produce written output using a chin-controlled Morse system decoded by a computer. A detailed linguistic analysis of text written over 20 years by the patient was carried out. The data demonstrate that improvements in language performance can be observed even in patients with brain lesions in areas associated with high-level cognitive processes. The data show a decrease of typing, grammatical and lexical errors over time, use of less frequent words, and an increase of more complex linguistic structures. This paper adds to previous findings confirming the value of daily practice and rehabilitation to enhance quality of life in this group of patients.

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.

[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.

Manipulating magnetism: Ru25⁺ paddlewheels devoid of axial interactions.

Variable-temperature magnetic and structural data of two pairs of diruthenium isomers, one pair having an axial ligand and the formula Ru2(DArF)4Cl (where DArF is the anion of a diarylformamidine isomer and Ar = p-anisyl or m-anisyl) and the other one being essentially identical but devoid of axial ligands and having the formula [Ru2(DArF)4]BF4, show that the axial ligand has a significant effect on the electronic structure of the diruthenium unit. Variable temperature crystallographic and magnetic data as well as density functional theory calculations unequivocally demonstrate the occurrence of π interactions between the p orbitals of the chlorine ligand and the π* orbitals in the Ru2(5+) units. The magnetic and structural data are consistent with the existence of combined ligand σ/metal σ and ligand pπ/metal-dπ interactions. Electron paramagnetic resonance data show unambiguously that the unpaired electrons are in metal-based molecular orbitals.

A strong metal-to-metal interaction in an edge-sharing bioctahedral compound that leads to a very short tungsten-tungsten double bond.

An ionic edge-sharing bioctahedral (ESBO) species has been prepared having a tetramethylated bicyclic guanidinate with two fused six-membered rings characterized by a fairly flat N-C(N)-N skeleton and abbreviated as TMhpp. The anion has two W(IV) atoms bridged by two oxo groups; the metal atoms are also spanned by two bridging guanidinate ligands, and each has two monodentate chlorine atoms. The complex formulated as (H2TMhpp)2[W(µ-O)(µ-TMhpp)Cl2]2 has the shortest W-W distance (2.3318(8) Å) of any species with a σ(2)π(2) electronic configuration. The anion and cations are connected by hydrogen bonds. To unambiguously ascertain the existence of the double-bonded W2(µ-O)2 entity, density functional theory calculations and natural bond orbital analyses were done on an analogous but hypothetical species with a W2(µ-OH)2 core having trivalent tungsten atoms and a possible σ(2)π(2)δ(2) electronic configuration. The calculations decidedly support the presence of tungsten-oxo instead of tungsten-hydroxo groups and thus the existence of the double-bonded W2(µ-O)2 core. The strong bonding interaction between metal atoms is a clear indication that under certain circumstances the two octahedra in ESBO species do not behave as the sum of two mononuclear compounds.

Lesions of the ovary with T1-hypersignal.

Pelvic magnetic resonance imaging (MRI) has been used successfully to diagnose ovarian masses that cannot be adequately evaluated using pelvic ultrasound. T1 hyperintensity is a common finding in an ovarian mass and has important diagnostic implications. The aims of this review are to list the substances that may produce high signal intensity on T1-weighted MRI, to explain the physical basis for causes of the high T1 signal intensity, and to describe common and uncommon T1 hyperintense ovarian lesions. The morphological findings, the imaging features of the additional sequences, and clinical variables can help in the differential diagnosis, and in some cases, enable a specific diagnosis, leading to appropriate management of the patient.

[Nosology and etiologies of acute longitudinally extensive transverse myelitis]. / Cadre nosologique et stratégie diagnostique de la myélite aiguë transverse longitudinalement étendue.

Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment.

[Contribution of clinical biology in the etiological exploration and follow-up of urolithiasis]. / Apport de la biologie clinique dans l'exploration étiologique et le suivi de l'urolithiase.

Urolithiasis is a frequent pathology with a constantly increasing prevalence in industrial countries. The relapse frequency is around 50 % with a risk of complications. The laboratory input is essential in the determination of the etiology and in the therapeutic monitoring. The morphoconstitutional analysis of the stone is the most important element. It comprises the examination of the stone with binocular loupes and the simultaneous analysis of its crystalline composition. This can be done by different techniques but infrared spectrophotometry is the most powerful. The chemical analysis should be definitely proscribed. The analysis of crystalluria includes the search, the identification and the counting of crystals in fresh morning urines. It is useful for the diagnosis and for the patient follow-up. Finally, the biochemical analyses in urine and serum, in first line or on the basis of the stone composition, are an important part of the etiological exploration and therapeutic monitoring.

Solubilizing the most easily ionized molecules and generating powerful reducing agents.

Two very soluble compounds having W2(bicyclic guanidinate)4 paddlewheel structures show record low ionization energies (onsets at 3.4 to 3.5 eV) and very negative oxidation potentials in THF (-1.84 to -1.90 V vs Ag/AgCl). DFT computations show the correlation from the gas-phase ionization energies to the solution redox potentials and chemical behavior. These compounds are thermally stable and easy to synthesize in high yields and good purity. They are very reactive and potentially useful stoichiometric reducing agents in nonpolar, nonprotonated solvents.

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.

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.

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

Direct evidence from electron paramagnetic resonance for additional configurations in uncommon paddlewheel Re2(7+) units surrounded by an unsymmetrical bicyclic guanidinate.

Three rare compounds have been synthesized and structurally characterized; these species have paddlewheel structures and Re(2)(7+) cores surrounded by four bicyclic guanidinates and two axial ligands along the Re-Re axis. Each possesses a formal bond order of 3.5 and a σ(2)π(4)δ(1) electronic configuration that entails the presence of one unpaired electron for each compound. The guanidinate ligands characterized by having CH(2) entities and a central C(N)(3) unit that joins two cyclic units--one having two fused 6-membered rings (hpp) and the other having a 5- and a 6-membered ring fused together (tbn)--allowed the isolation of [Re(2)(tbn)(4)Cl(2)]PF(6), 1, [Re(2)(tbn)(4)Cl(2)]Cl, 2, and [Re(2)(hpp)(4)(O(3)SCF(3))(2)](O(3)SCF(3)), 3. Because of the larger bite angle of the tbn relative to the hpp ligand, the Re-Re bond distances in 1 and 2 (2.2691(14) and 2.2589(14) Å, respectively) are much longer than that in 3 (2.1804(8) Å). Importantly, electron paramagnetic resonance (EPR) studies at both X-band (~9.4 GHz) and W-band (112 GHz) in the solid and in frozen solution show unusually low g-values (~1.75) and the absence of zero-field splitting, providing direct evidence for the presence of one metal-based unpaired electron for both 1 and 3. These spectroscopic data suggest that the unsymmetrical 5-/6-membered ligand leads to the formation of isomers, as shown by significantly broader EPR signals for 1 than for 3, even though both compounds possess what appears to be similar ideal crystallographic axial symmetry on the X-ray time scale.