New Imaging Markers in Multiple Sclerosis and Related Disorders: Smoldering Inflammation and the Central Vein Sign.

Concepts of multiple sclerosis (MS) biology continue to evolve, with observations such as "progression independent of disease activity" challenging traditional phenotypic categorization. Iron-sensitive, susceptibility-based imaging techniques are emerging as highly translatable MR imaging sequences that allow for visualization of at least 2 clinically useful biomarkers: the central vein sign and the paramagnetic rim lesion (PRL). Both biomarkers demonstrate high specificity in the discrimination of MS from other mimics and can be seen at 1.5 T and 3 T field strengths. Additionally, PRLs represent a subset of chronic active lesions engaged in "smoldering" compartmentalized inflammation behind an intact blood-brain barrier.

Super resolution using sparse sampling at portable ultra-low field MR.

Ultra-low field (ULF) magnetic resonance imaging (MRI) holds the potential to make MRI more accessible, given its cost-effectiveness, reduced power requirements, and portability. However, signal-to-noise ratio (SNR) drops with field strength, necessitating imaging with lower resolution and longer scan times. This study introduces a novel Fourier-based Super Resolution (FouSR) approach, designed to enhance the resolution of ULF MRI images with minimal increase in total scan time. FouSR combines spatial frequencies from two orthogonal ULF images of anisotropic resolution to create an isotropic T2-weighted fluid-attenuated inversion recovery (FLAIR) image. We hypothesized that FouSR could effectively recover information from under-sampled slice directions, thereby improving the delineation of multiple sclerosis (MS) lesions and other significant anatomical features. Importantly, the FouSR algorithm can be implemented on the scanner with changes to the k-space trajectory. Paired ULF (Hyperfine SWOOP, 0.064 tesla) and high field (Siemens, Skyra, 3 Tesla) FLAIR scans were collected on the same day from a phantom and a cohort of 10 participants with MS or suspected MS (6 female; mean ± SD age: 44.1 ± 4.1). ULF scans were acquired along both coronal and axial planes, featuring an in-plane resolution of 1.7 mm × 1.7 mm with a slice thickness of 5 mm. FouSR was evaluated against registered ULF coronal and axial scans, their average (ULF average) and a gold standard SR (ANTs SR). FouSR exhibited higher SNR (47.96 ± 12.6) compared to ULF coronal (36.7 ± 12.2) and higher lesion conspicuity (0.12 ± 0.06) compared to ULF axial (0.13 ± 0.07) but did not exhibit any significant differences contrast-to-noise-ratio (CNR) compared to other methods in patient scans. However, FouSR demonstrated superior image sharpness (0.025 ± 0.0040) compared to all other techniques (ULF coronal 0.021 ± 0.0037, q = 5.9, p-adj. = 0.011; ULF axial 0.018 ± 0.0026, q = 11.1, p-adj. = 0.0001; ULF average 0.019 ± 0.0034, q = 24.2, p-adj. < 0.0001) and higher lesion sharpness (-0.97 ± 0.31) when compared to the ULF average (-1.02 ± 0.37, t(543) = -10.174, p = <0.0001). Average blinded qualitative assessment by three experienced MS neurologists showed no significant difference in WML and sulci or gyri visualization between FouSR and other methods. FouSR can, in principle, be implemented on the scanner to produce clinically useful FLAIR images at higher resolution on the fly, providing a valuable tool for visualizing lesions and other anatomical structures in MS.

Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis.

Cortical lesions are common in multiple sclerosis and are associated with disability and progressive disease. We asked whether cortical lesions continue to form in people with stable white matter lesions and whether the association of cortical lesions with worsening disability relates to pre-existing or new cortical lesions. Fifty adults with multiple sclerosis and no new white matter lesions in the year prior to enrolment (33 relapsing-remitting and 17 progressive) and a comparison group of nine adults who had formed at least one new white matter lesion in the year prior to enrolment (active relapsing-remitting) were evaluated annually with 7 tesla (T) brain MRI and 3T brain and spine MRI for 2 years, with clinical assessments for 3 years. Cortical lesions and paramagnetic rim lesions were identified on 7T images. Seven total cortical lesions formed in 3/30 individuals in the stable relapsing-remitting group (median 0, range 0-5), four total cortical lesions formed in 4/17 individuals in the progressive group (median 0, range 0-1), and 16 cortical lesions formed in 5/9 individuals in the active relapsing-remitting group (median 1, range 0-10, stable relapsing-remitting versus progressive versus active relapsing-remitting P = 0.006). New cortical lesions were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Individuals with at least three paramagnetic rim lesions had a greater increase in cortical lesion volume over time (median 16 µl, range -61 to 215 versus median 1 µl, range -24 to 184, P = 0.007), but change in lesion volume was not associated with disability change. Baseline cortical lesion volume was higher in people with worsening disability (median 1010 µl, range 13-9888 versus median 267 µl, range 0-3539, P = 0.001, adjusted for age and sex) and in individuals with relapsing-remitting multiple sclerosis who subsequently transitioned to secondary progressive multiple sclerosis (median 2183 µl, range 270-9888 versus median 321 µl, range 0-6392 in those who remained relapsing-remitting, P = 0.01, adjusted for age and sex). Baseline white matter lesion volume was not associated with worsening disability or transition from relapsing-remitting to secondary progressive multiple sclerosis. Cortical lesion formation is rare in people with stable white matter lesions, even in those with worsening disability. Cortical but not white matter lesion burden predicts disability worsening, suggesting that disability progression is related to long-term effects of cortical lesions that form early in the disease, rather than to ongoing cortical lesion formation.

Identification of direct connections between the dura and the brain.

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.

Highly Sensitive 3-Tesla Real Inversion Recovery MRI Detects Leptomeningeal Contrast Enhancement in Chronic Active Multiple Sclerosis.

BACKGROUND: Leptomeningeal contrast enhancement (LME) on T2-weighted Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRI is a reported marker of leptomeningeal inflammation, which is known to be associated with progression of multiple sclerosis (MS). However, this MRI approach, as typically implemented on clinical 3-tesla (T) systems, detects only a few enhancing foci in ~25% of patients and has thus been criticized as poorly sensitive. PURPOSE: To compare an optimized 3D real-reconstruction inversion recovery (Real-IR) MRI sequence on a clinical 3 T scanner to T2-FLAIR for prevalence, characteristics, and clinical/radiological correlations of LME. MATERIALS AND METHODS: We obtained 3D T2-FLAIR and Real-IR scans before and after administration of standard-dose gadobutrol in 177 scans of 154 participants (98 women, 64%; mean ± SD age: 49 ± 12 years), including 124 with an MS-spectrum diagnosis, 21 with other neurological and/or inflammatory disorders, and 9 without neurological history. We calculated contrast-to-noise ratios (CNR) in 20 representative LME foci and determined association of LME with cortical lesions identified at 7 T (n = 19), paramagnetic rim lesions (PRL) at 3 T (n = 105), and clinical/demographic data. RESULTS: We observed focal LME in 73% of participants on Real-IR (70% in established MS, 33% in healthy volunteers, P < 0.0001), compared to 33% on T2-FLAIR (34% vs. 11%, P = 0.0002). Real-IR showed 3.7-fold more LME foci than T2-FLAIR ( P = 0.001), including all T2-FLAIR foci. LME CNR was 2.5-fold higher by Real-IR ( P < 0.0001). The major determinant of LME status was age. Although LME was not associated with cortical lesions, the number of PRL was associated with the number of LME foci on both T2-FLAIR ( P = 0.003) and Real-IR ( P = 0.0003) after adjusting for age, sex, and white matter lesion volume. CONCLUSIONS: Real-IR a promising tool to detect, characterize, and understand the significance of LME in MS. The association between PRL and LME highlights a possible role of the leptomeninges in sustaining chronic inflammation.

Association of Chronic Medical Conditions With Severe Outcomes Among Nonpregnant Adults 18-49 Years Old Hospitalized With Influenza, FluSurv-NET, 2011-2019.

Background: Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. Methods: We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. Results: A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). Conclusions: To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. Methods: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. Results: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. Conclusions: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making.

Pseudo-Label Assisted nnU-Net enables automatic segmentation of 7T MRI from a single acquisition.

Introduction: Automatic whole brain and lesion segmentation at 7T presents challenges, primarily from bias fields, susceptibility artifacts including distortions, and registration errors. Here, we sought to use deep learning algorithms (D/L) to do both skull stripping and whole brain segmentation on multiple imaging contrasts generated in a single Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) acquisition on participants clinically diagnosed with multiple sclerosis (MS), bypassing registration errors. Methods: Brain scans Segmentation from 3T and 7T scanners were analyzed with software packages such as FreeSurfer, Classification using Derivative-based Features (C-DEF), nnU-net, and a novel 3T-to-7T transfer learning method, Pseudo-Label Assisted nnU-Net (PLAn). 3T and 7T MRIs acquired within 9 months from 25 study participants with MS (Cohort 1) were used for training and optimizing. Eight MS patients (Cohort 2) scanned only at 7T, but with expert annotated lesion segmentation, was used to further validate the algorithm on a completely unseen dataset. Segmentation results were rated visually by experts in a blinded fashion and quantitatively using Dice Similarity Coefficient (DSC). Results: Of the methods explored here, nnU-Net and PLAn produced the best tissue segmentation at 7T for all tissue classes. In both quantitative and qualitative analysis, PLAn significantly outperformed nnU-Net (and other methods) in lesion detection in both cohorts. PLAn's lesion DSC improved by 16% compared to nnU-Net. Discussion: Limited availability of labeled data makes transfer learning an attractive option, and pre-training a nnUNet model using readily obtained 3T pseudo-labels was shown to boost lesion detection capabilities at 7T.

Estrategias de afrontamiento centradas en las emociones de enfermeros de un hospital de Corrientes en el año 2022 / Coping strategies focused on emotions in nurses from a hospital in Corrientes in the year 2022

Introducción: el personal de enfermería enfrenta a diario jornadas extendidas de trabajo, tiene muchos pacientes a su cargo, dificultades en las relaciones interpersonales, que podrían desencadenar en estrés, para lo cual el individuo desarrolla un proceso de adaptación o desequilibrio y es por esta razón la importancia de contar con estrategias para afrontar las situaciones. Objetivos: el objetivo de este estudio fue analizar las estrategias de afrontamiento ante situaciones de estrés utilizadas por los profesionales de enfermería de un Hospital Público de la ciudad de Corrientes capital, así como su asociación con variables socio demográficas. Metodología: estudio de tipo cuantitativo, descriptivo, transversal y observacional. La población incluyó enfermeros de un hospital público de la ciudad de Corrientes en el período 2022. Se consideró como criterios de inclusión personal de enfermería que cumpla funciones asistenciales y su tiempo de labor fuera de 1 año o más; como criterios de exclusión, personal que tuviera dos o más puestos de trabajo y de criterios de eliminación aquellos enfermeros que no se encuentren presentes al momento de la encuesta. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste 120 profesionales de enfermería. Para la recolección de datos, se aplicó una encuesta adaptada del cuestionario Ways of Coping Questionnaire de Lazarus y Folkman. Resultados: se evidenció que la estrategia de afrontamiento más utilizada por los enfermeros fue la reinterpretación positiva. Conclusión: a través de este estudio se logró reconocer las estrategias de afrontamiento que el personal de enfermería utilizó al momento de enfrentar situaciones o experiencias estresantes[AU]

Introduction: nursing staff face extended work days daily, have many patients under their care, difficulties in interpersonal relationships, which could trigger stress, for which the individual develops a process of adaptation or imbalance and it is for this reason the importance of having strategies to deal with situations. Objectives: the objective of this study was to analyze coping strategies in stressful situations used by nursing professionals from a Public Hospital in the capital city of Corrientes, as well as their association with sociodemographic variables. Methodology: quantitative, descriptive, cross-sectional and observational study. The population included nurses from a public hospital in the city of Corrientes in the period 2022. Inclusion criteria were considered nursing personnel who perform care functions and their time of work was 1 year or more; as exclusion criteria, personnel who had two or more jobs and as elimination criteria those nurses who were not present at the time of the survey. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in 120 nursing professionals. For data collection, a survey adapted from the Ways of Coping Questionnaire by Lazarus and Folkman was applied. Results: it was evidenced that the coping strategy most used by nurses was positive reinterpretation. Conclusion: through this study, it was possible to recognize the coping strategies that the nursing staff used when facing stressful situations or experiences[AU]

Introdução: a equipe de enfermagem enfrenta diariamente jorna-das de trabalho extensas, tem muitos pacientes sob seus cuidados, dificuldades no relacionamento interpessoal, podendo desenca-dear estresse, para o qual o indivíduo desenvolve um processo de adaptação ou desequilíbrio e por isso a importância de se ter estra-tégias para lidar com as situações. Objetivos: o objetivo deste estudo foi analisar as estratégias de enfrentamento em situações estressan-tes utilizadas por profissionais de enfermagem de um Hospital Pú-blico da capital Corrientes, bem como sua associação com variáveis sociodemográficas. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A população incluiu enfermeiros de um hospital público da cidade de Corrientes no período de 2022. Os critérios de inclusão foram considerados pessoal de enfermagem que desempenha funções assistenciais e seu tempo de trabalho foi de 1 ano ou mais; como critérios de exclusão, pessoal que exercesse dois ou mais vínculos empregatícios e como critérios de eliminação os enfermeiros que não estivessem presentes no momento da pes-quisa. O cálculo do tamanho da amostra foi realizado pelo método probabilístico aleatório simples, resultando em 120 profissionais de enfermagem. Para a coleta de dados, foi aplicado um questionário adaptado do Questionário de Modos de Enfrentamento de Lazarus e Folkman. Resultados: evidenciou-se que a estratégia de enfrenta-mento mais utilizada pelos enfermeiros foi a reinterpretação posi-tiva. Conclusão: Por meio deste estudo, foi possível reconhecer as estratégias de enfrentamento que a equipe de enfermagem utiliza diante de situações ou experiências estressantes[AU]

Cortical lesions uniquely predict motor disability accrual and form rarely in the absence of new white matter lesions in multiple sclerosis.

Background and objectives: Cortical lesions (CL) are common in multiple sclerosis (MS) and associate with disability and progressive disease. We asked whether CL continue to form in people with stable white matter lesions (WML) and whether the association of CL with worsening disability relates to pre-existing or new CL. Methods: A cohort of adults with MS were evaluated annually with 7 tesla (T) brain magnetic resonance imaging (MRI) and 3T brain and spine MRI for 2 years, and clinical assessments for 3 years. CL were identified on 7T images at each timepoint. WML and brain tissue segmentation were performed using 3T images at baseline and year 2. Results: 59 adults with MS had ≥1 7T follow-up visit (mean follow-up time 2±0.5 years). 9 had "active" relapsing-remitting MS (RRMS), defined as new WML in the year prior to enrollment. Of the remaining 50, 33 had "stable" RRMS, 14 secondary progressive MS (SPMS), and 3 primary progressive MS. 16 total new CL formed in the active RRMS group (median 1, range 0-10), 7 in the stable RRMS group (median 0, range 0-5), and 4 in the progressive MS group (median 0, range 0-1) (p=0.006, stable RR vs PMS p=0.88). New CL were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Baseline CL volume was higher in people with worsening disability (median 1010µl, range 13-9888 vs median 267µl, range 0-3539, p=0.001, adjusted for age and sex) and in individuals with RRMS who subsequently transitioned to SPMS (median 2183µl, range 270-9888 vs median 321µl, range 0-6392 in those who remained RRMS, p=0.01, adjusted for age and sex). Baseline WML volume was not associated with worsening disability or transition from RRMS to SPMS. Discussion: CL formation is rare in people with stable WML, even in those with worsening disability. CL but not WML burden predicts future worsening of disability, suggesting that the relationship between CL and disability progression is related to long-term effects of lesions that form in the earlier stages of disease, rather than to ongoing lesion formation.

In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis.

Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents.

Performance of McDonald 2017 multiple sclerosis diagnostic criteria and evaluation of genetic ancestry in patients with a first demyelinating event in Argentina.

BACKGROUND: Information on performance of multiple sclerosis (MS) diagnostic criteria is scarce for populations from Latin America, Asia, or the Caribbean. OBJECTIVE: To assess performance of revised 2017 McDonald criteria as well as evaluate genetic ancestry in a group of MS patients from Argentina experiencing a debut demyelinating event. METHODS: Demographic and clinical characteristics, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) findings and new T2 lesions were recorded at baseline and during relapses. Diagnostic accuracy in predicting conversion to clinically defined MS (CDMS) based on initial imaging applying revised 2017 criteria was evaluated and genetic ancestry-informative markers analyzed. RESULTS: Of 201 patients experiencing their first demyelinating event (median follow-up 60 months), CDMS was confirmed in 67. We found 2017 diagnostic criteria were more sensitive (84% vs 67%) and less specific (14% vs 33%) than 2010 criteria, especially in a group of patients revised separately, presenting positive oligoclonal bands (88% vs 8%). Genetic testing performed in 128 cases showed 72% of patients were of European ancestry and 27% presented genetic admixture. CONCLUSION: 2017 McDonald criteria showed higher sensitivity and lower specificity compared with 2010 criteria, shortening both time-to-diagnosis and time-to-treatment implementation.

Influenza Antiviral Use in Patients Hospitalized With Laboratory-Confirmed Influenza in the United States, FluSurv-NET, 2015-2019.

From surveillance data of patients hospitalized with laboratory-confirmed influenza in the United States during the 2015-2016 through 2018-2019 seasons, initiation of antiviral treatment increased from 86% to 94%, with increases seen across all age groups. However, 62% started therapy ≥3 days after illness onset, driven by late presentation to care.

Drug use and severe outcomes among adults hospitalized with influenza, 2016-2019.

BACKGROUND: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. METHODS: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who use drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. RESULTS: Among 48,430 eligible hospitalized influenza cases, 2019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD; however, these findings were not statistically significant after adjustment. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. CONCLUSION: These results support targeted initiatives to prevent influenza in this population, including influenza vaccination, which remains one of the most important tools to prevent influenza infection and associated severe outcomes.

Disease activity after discontinuation of disease-modifying therapies in patients with multiple sclerosis in Argentina: data from the nationwide registry RelevarEM.

INTRODUCTION: The discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is commonly seen in real-world settings due to several factors. AREA COVER: The aim of this study is to describe the frequency of disease activity after discontinuation of DMTs in MS patients included in the Argentinean MS and NMOSD registry. DISCUSION: Patients with relapsing remitting MS (RRMS) and active secondary progressive MS (SPMS) were included based on the following criteria: they discontinued treatment for more than 6 months, they had been treated with a DMT for ≥2 years, and they had at least 6 months of follow-up in the registry after discontinuation. Demographic and clinical data were collected. Disease activity during follow-up was defined as the presence of a clinical relapse or a new magnetic resonance (MRI) lesion (either new lesions on T2-weighted sequence and/or contrast enhancement). Bivariate analysis was applied to identify clinical and demographic factors related to disease activity. CONCLUSION: We included 377 patients (75.5% RRMS, 22.5% SPMS) who had discontinued DMTs. The mean (SD) follow-up after discontinuation was 15.7 (7.9) months. After discontinuation, the presence of relapse was detected in 18.8% and 3.5% in RRMS and SPMS, respectively; and new MRI activity in 22% and 3.5%, respectively. We found that higher risk of relapse and MRI activity was associated with younger age (p < 0.001), shorter disease duration (p < 0.001), and RRMS phenotype (p = 0.006). Males showed higher MRI activity (p 0.011). This study provides real-world data that can guide physicians when considering discontinuation of DMTs.

Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza - United States, 2021-22 Influenza Season.

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.

Confirming a Historical Diagnosis of Multiple Sclerosis: Challenges and Recommendations.

Patients with a historical diagnosis of multiple sclerosis (MS)-a patient presenting with a diagnosis of MS made previously and by a different clinician-present specific diagnostic and therapeutic challenges in clinical practice. Application of the McDonald criteria is most straightforward when applied contemporaneously with a syndrome typical of an MS attack or relapse; however, retrospective application of the criteria in some patients with a historical diagnosis of MS can be problematic. Limited patient recollection of symptoms and evolution of neurologic examination and MRI findings complicate confirmation of an earlier MS diagnosis and assessment of subsequent disease activity or clinical progression. Adequate records for review of prior clinical examinations, laboratory results, and/or MRI scans obtained at the time of diagnosis or during ensuing care may be inadequate or unavailable. This article provides recommendations for a clinical approach to the evaluation of patients with a historical diagnosis of MS to aid diagnostic confirmation, avoid misdiagnosis, and inform therapeutic decision making.

Rebound activity after fingolimod cessation: A case - control study.

BACKGROUND: There has been an increase in the number of reports of multiple sclerosis (MS) rebound activity (RA), which is usually defined as a severe disease reactivation after natalizumab or fingolimod withdrawal that exceeds pre-treatment baseline inflammatory activity. The frequency and risk factors that could predict RA remain unknown. Fingolimod is currently the most frequently prescribed disease modifying therapy for MS in Argentina, so that there is a need to determine possible predictors of RA. OBJECTIVES: To identify risk factors for developing RA after fingolimod cessation; to describe RA characteristics, management and evolution. METHODS: The study was a multicenter, retrospective, case-control study of patients with MS who had discontinued fingolimod and were followed up to nine months after discontinuation. Demographic, clinical and paraclinical data was extracted, including age, gender, MS phenotype, reason for discontinuation, number of relapses during the year prior to suspension, time treated with fingolimod, EDSS before, during and after rebound, MRI findings. RESULTS: 26 cases of RA were matched 1:1 with patients without RA. The median time elapsed to RA was 50 days. 68% showed worsening of the EDSS in the evaluation at 3 months of RA. When compared with the control group, no difference was found in terms of age, gender, phenotype, EDSS at the moment of suspension, reason for discontinuation, number of relapses in the previous year, and time on therapy. CONCLUSION: In this case-controlled study, no risk factors could be identified to predict RA after fingolimod cessation. Further controlled, prospective, better powered studies are needed to confirm these findings.

The central vein sign is present in most infratentorial multiple sclerosis plaques.

BACKGROUND AND PURPOSE: There is growing evidence supporting the presence of the central vein sign (CVS) in the supratentorial brain as an imaging biomarker for multiple sclerosis (MS) diagnosis. Recently, using optimized susceptibility-weighted angiography (SWAN-venule), we detected CVS in 86% of supratentorial white matter lesions (WMLs) in the clinical setting on images obtained in a 3T MRI scanner. Despite the relevance of the infratentorial compartment, CVS prevalence in infratentorial MS plaques has not been investigated in detail. Our objective was to determine the proportion of MS infratentorial lesions showing CVS positivity. MATERIALS AND METHODS: We included subjects with MS and other brain diseases showing at least one infratentorial lesion larger than 3 mm on 3D-FLAIR. Patients were scanned in a 3T MRI scanner (GE Medical Systems, discovery-MR750), applying a comprehensive protocol including post-contrast 3D-FLAIR and SWAN-venule sequences. CVS presence was confirmed by two trained raters. RESULTS: Thirty MRIs of subjects with MS were analyzed. One hundred and one infratentorial lesions were detected on FLAIR, and 86% were centered by a vein. Fifteen MRIs from the non-MS group were analyzed, 19 lesions were visible ion FLAIR and 16% were positive for the CVS. CONCLUSIONS: SWAN-venule detects infratentorial lesions and highlights the central vein in MS plaques at 3T MRI. As occurs in the supratentorial brain, most infratentorial lesions are perivenular.

The frequency and characteristics of multiple sclerosis misdiagnosis in Latin America: A referral center study in Buenos Aires, Argentina.

OBJECTIVE: Most contemporary data concerning the frequency and causes of multiple sclerosis (MS) misdiagnosis are from North America and Europe with different healthcare system structure and resources than countries in Latin America. We sought to determine the frequency, and potential contributors to MS misdiagnosis in patients evaluated at an MS referral center in Argentina. METHODS: The study was a retrospective medical record review. We included patients evaluated at the MS Clinic at Fleni between April 2013 and March 2021. Diagnoses prior to consultation, final diagnoses after consultation, demographic, clinical and paraclinical data, and treatment were extracted and classified. RESULTS: Seven hundred thirty-six patients were identified. Five hundred seventy-two presented with an established diagnosis of MS and after evaluation, misdiagnosis was identified in 89 (16%). Women were at 83% greater risk of misdiagnosis (p = 0.034). The most frequent alternative diagnoses were cerebrovascular disease, radiological isolated syndrome (RIS), and headache. Seventy-four (83%) of misdiagnosed patients presented with a syndrome atypical for demyelination, 62 (70%) had an atypical brain magnetic resonance imaging (MRI), and 54 (61%) were prescribed disease-modifying therapy. CONCLUSION: Sixteen percent of patients with established MS were subsequently found to have been misdiagnosed. Women were at higher risk for misdiagnosis. Expert application of the McDonald criteria may prevent misdiagnosis and its associated morbidity and healthcare system cost.