Assessing robustness and generalization of a deep neural network for brain MS lesion segmentation on real-world data.

OBJECTIVES: Evaluate the performance of a deep learning (DL)-based model for multiple sclerosis (MS) lesion segmentation and compare it to other DL and non-DL algorithms. METHODS: This ambispective, multicenter study assessed the performance of a DL-based model for MS lesion segmentation and compared it to alternative DL- and non-DL-based methods. Models were tested on internal (n = 20) and external (n = 18) datasets from Latin America, and on an external dataset from Europe (n = 49). We also examined robustness by rescanning six patients (n = 6) from our MS clinical cohort. Moreover, we studied inter-human annotator agreement and discussed our findings in light of these results. Performance and robustness were assessed using intraclass correlation coefficient (ICC), Dice coefficient (DC), and coefficient of variation (CV). RESULTS: Inter-human ICC ranged from 0.89 to 0.95, while spatial agreement among annotators showed a median DC of 0.63. Using expert manual segmentations as ground truth, our DL model achieved a median DC of 0.73 on the internal, 0.66 on the external, and 0.70 on the challenge datasets. The performance of our DL model exceeded that of the alternative algorithms on all datasets. In the robustness experiment, our DL model also achieved higher DC (ranging from 0.82 to 0.90) and lower CV (ranging from 0.7 to 7.9%) when compared to the alternative methods. CONCLUSION: Our DL-based model outperformed alternative methods for brain MS lesion segmentation. The model also proved to generalize well on unseen data and has a robust performance and low processing times both on real-world and challenge-based data. CLINICAL RELEVANCE STATEMENT: Our DL-based model demonstrated superior performance in accurately segmenting brain MS lesions compared to alternative methods, indicating its potential for clinical application with improved accuracy, robustness, and efficiency. KEY POINTS: • Automated lesion load quantification in MS patients is valuable; however, more accurate methods are still necessary. • A novel deep learning model outperformed alternative MS lesion segmentation methods on multisite datasets. • Deep learning models are particularly suitable for MS lesion segmentation in clinical scenarios.

Latin American consensus recommendations on the risk of infections in people with multiple sclerosis treated with disease modifying drugs.

INTRODUCTION: The emergence of several therapeutic options in multiple sclerosis (MS), which significantly modify the immune system functioning, has led to the need for the consideration of additional factors, such as risk of infections, in the decision-making process. The aim of these consensus recommendations was to discuss and perform a practical guide to Latin American neurologists on the risk of infections at diagnosis, follow-up and prior to initiation of DMDs. METHODS: A panel of Latin American neurologists, experts in demyelinating diseases and dedicated to management and care of MS patients, gathered during 2021 and 2022 to make consensus recommendations on the risk of infections in PwMS treated with DMDs in Latin America. The RAND/UCLA methodology was developed to synthesize the scientific evidence and expert opinions on health care topics and was used for reaching a formal agreement. RESULTS: Recommendations were established based on relevant published evidence and expert opinion, focusing on: 1- baseline infection disease and vaccination status; 2- opportunistic infections; 3- progressive multifocal leukoencephalopathy; 4- genitourinary system infections; 5- respiratory tract infections; 6- digestive system infections, 7-others local infections and 8- COVID-19. CONCLUSION: The recommendations of this consensus seek to optimize the care, management and treatment of PwMS in Latin America. The standardized evidence-based care of pwMS infections will allow better outcomes.

ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. OBJECTIVE: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND AND PURPOSE: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Alteration of Fatty Acid Profile in Fragile X Syndrome.

Fragile X Syndrome (FXS) is the most prevalent monogenic cause of Autism Spectrum Disorders (ASDs). Despite a common genetic etiology, the affected individuals display heterogenous metabolic abnormalities including hypocholesterolemia. Although changes in the metabolism of fatty acids (FAs) have been reported in various neuropsychiatric disorders, it has not been explored in humans with FXS. In this study, we investigated the FA profiles of two different groups: (1) an Argentinian group, including FXS individuals and age- and sex-matched controls, and (2) a French-Canadian group, including FXS individuals and their age- and sex-matched controls. Since phospholipid FAs are an indicator of medium-term diet and endogenous metabolism, we quantified the FA profile in plasma phospholipids using gas chromatography. Our results showed significantly lower levels in various plasma FAs including saturated, monosaturated, ω-6 polyunsaturated, and ω-3 polyunsaturated FAs in FXS individuals compared to the controls. A decrease in the EPA/ALA (eicosapentaenoic acid/alpha linoleic acid) ratio and an increase in the DPA/EPA (docosapentaenoic acid/eicosapentaenoic acid) ratio suggest an alteration associated with desaturase and elongase activity, respectively. We conclude that FXS individuals present an abnormal profile of FAs, specifically FAs belonging to the ω-3 family, that might open new avenues of treatment to improve core symptoms of the disorder.

Towards imaging criteria that best differentiate MS from NMOSD and MOGAD: Large multi-ethnic population and different clinical scenarios.

BACKGROUND: The "1/3″ brain magnetic resonance imaging (MRI) criteria including 1) a lesion adjacent to the lateral ventricle and in the inferior temporal lobe, or 2) a juxtacortical lesion, or 3) a Dawson finger-type lesion were shown to distinguish multiple sclerosis (MS) from antibody-mediated conditions. In this large multicentre study, we aimed to assess how the criteria perform 1) in different onset phenotypes, 2) distinct ethnic groups, 3) when the absence of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD)-typical fluffy infratentorial (FIT) lesions and longitudinally extensive transverse myelitis (LETM) lesions are added as features ("2/4″ and 3/5″ criteria, respectively). METHODS: 577 patients with MS (n = 332), aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD) (n = 196) and MOGAD (n = 49) were recruited from 6 international centres (Buenos Aires, Sao Paolo, Maracaibo, Goyang, Oxford and Milan). Imaging scans were obtained at disease onset or relapse. RESULTS: Adding the absence of FIT lesions increased the specificity of the "1/3″ criteria vs. AQP4-Ab NMOSD from 84.7% to 87.2% and vs. MOGAD from 85.7% to 93.9% without compromising their sensitivity (86%). In particular, for those presenting with brain/brainstem attacks "2/4″ had significantly higher specificity than "1/3″ (85% vs. 80% against AQP4-Ab NMOSD, 88.9% vs. 72.2% against MOGAD). Positive predictive values of the "1/3″ criteria for MS were lowest for Asian patients (84.8 vs. 99.1% for White) but were significantly increased by adding further criteria (94.1% for "3/5″). CONCLUSION: The "1/3″ criteria perform well in discriminating MS from NMOSD and MOGAD regardless of ethnic background and clinical scenario. Adding the absence of FIT lesions increases the specificity in those presenting with brain/brainstem symptoms.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

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.

The Immune Response in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS is characterized by immune dysregulation, which results in the infiltration of the CNS by immune cells, triggering demyelination, axonal damage, and neurodegeneration. Although the exact causes of MS are not fully understood, genetic and environmental factors are thought to control MS onset and progression. In this article, we review the main immunological mechanisms involved in MS pathogenesis.

Theory of mind, emotion recognition and emotional reactivity factors in early multiple sclerosis: Results from a South American cohort.

OBJECTIVES: To study different components of social cognition and quality of life in patients with early multiple sclerosis and low Expanded Disability Status Scale and to test the influence of cognitive performance, fatigue and neuropsychiatric symptoms on social cognition performance. METHODS: Thirty-four patients with relapsing-remitting MS, with ≤2 years of disease duration and scores ≤2 on the EDSS and 30 healthy controls underwent neuropsychological assessment with the Brief Repeatable Neuropsychological Test Battery. Components of social cognition, such as emotion recognition, theory of mind, empathy, and emotional reactivity, were assessed with the Reading the Mind in the Eyes test, the Faux Pas task, the International Affective Imagery System, and the Empathy Quotient. Anxiety, depression, fatigue and quality of life were measured. RESULTS: Patients showed significant differences in verbal memory, executive functions and social cognition, especially emotion recognition and ToM. Regarding emotional reactivity, patients showed a positive bias in the interpretation of the valence of neutral images. CONCLUSIONS: Patients with early MS showed impairments in several components of social cognition independent of cognitive performance, neuropsychiatric symptoms and fatigue. Social cognition deficits may be present in MS even in the early stages.

Obesity and the risk of Multiple Sclerosis. The role of Leptin.

OBJECTIVE: To investigate the effects of leptin on different T-cell populations, in order to gain more insight into the link between leptin and obesity. METHODS: Three hundred and nine RRMS patients and 322 controls participated in a cross-sectional survey, to confirm whether excess weight/obesity in adolescence or early adulthood increased the risk of MS. Serum leptin levels were determined by ELISA. MBP83-102 , and MOG63-87 peptide-specific T cells lines were expanded from peripheral blood mononuclear cells. Leptin receptor expression was measured by RT-PCR and flow cytometry. Bcl-2, p-STAT3, pERK1/2, and p27kip1 expression were assayed using ELISA, and apoptosis induction was determined by Annexin V detection. Cytokines were assessed by ELISPOT and ELISA, and regulatory T cells (Tregs) by flow cytometry. RESULTS: Logistic regression analysis, showed excess weight at age 15, and obesity at 20 years of age increased MS risk (OR = 2.16, P = 0.01 and OR = 3.9, P = 0.01). Leptin levels correlated with BMI in both groups. The addition of Leptin increased autoreactive T-cell proliferation, reduced apoptosis induction, and promoted proinflammatory cytokine secretion. Obese patients produced more proinflammatory cytokines compared to overweight/normal/underweight subjects. Inverse correlation was found between leptin levels and circulating Treg cells (r = -0.97, P < 0.0001). Leptin inhibited Treg proliferation. Effects of leptin on CD4+ CD25- effector T cells were mediated by increased STAT3 and ERK1/2 phosphorylation, and down modulation of the cell cycle inhibitor P27kip1 . In contrast, leptin effects on Tregs resulted from decreased phosphorylation of ERK1/2 and upregulation of p27kip1 . INTERPRETATION: Leptin promotes autoreactive T-cell proliferation and proinflammatory cytokine secretion, but inhibits Treg-cell proliferation.

Brain volumes quantification from MRI in healthy controls: Assessing correlation, agreement and robustness of a convolutional neural network-based software against FreeSurfer, CAT12 and FSL.

BACKGROUND AND PURPOSE: There are instances in which an estimate of the brain volume should be obtained from MRI in clinical practice. Our objective is to calculate cross-sectional robustness of a convolutional neural network (CNN) based software (Entelai Pic) for brain volume estimation and compare it to traditional software such as FreeSurfer, CAT12 and FSL in healthy controls (HC). MATERIALS AND METHODS: Sixteen HC were scanned four times, two different days on two different MRI scanners (1.5 T and 3 T). Volumetric T1-weighted images were acquired and post-processed with FreeSurfer v6.0.0, Entelai Pic v2, CAT12 v12.5 and FSL v5.0.9. Whole-brain, grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) volumes were calculated. Correlation and agreement between methods was assessed using intraclass correlation coefficient (ICC) and Bland Altman plots. Robustness was assessed using the coefficient of variation (CV). RESULTS: Whole-brain volume estimation had better correlation between FreeSurfer and Entelai Pic (ICC (95% CI) 0.96 (0.94-0.97)) than FreeSurfer and CAT12 (0.92 (0.88-0.96)) and FSL (0.87 (0.79-0.91)). WM, GM and CSF showed a similar trend. Compared to FreeSurfer, Entelai Pic provided similarly robust segmentations of brain volumes both on same-scanner (mean CV 1.07, range 0.20-3.13% vs. mean CV 1.05, range 0.21-3.20%, p = 0.86) and on different-scanner variables (mean CV 3.84, range 2.49-5.91% vs. mean CV 3.84, range 2.62-5.13%, p = 0.96). Mean post-processing times were 480, 5, 40 and 5 min for FreeSurfer, Entelai Pic, CAT12 and FSL respectively. CONCLUSION: Based on robustness and processing times, our CNN-based model is suitable for cross-sectional volumetry on clinical practice.

Lesiones medulares catastróficas en el rugby argentino. Impacto de las medidas implementadas y su reducción relativa en el tiempo / Catastrophic spinal cord injuries in argentine rugby. Impact of the measures implemented and their relative reduction in time

Introducción: Se entiende por lesión catastrófica a cualquier trauma grave que comprometa la cabeza, el cerebro, la columna vertebral o la médula espinal, que pone en riesgo la vida o puede dejar una discapacidad permanente o semipermanente. En la Argentina, la incidencia de lesionados en el ámbito del rugby es alta comparada con la de otros países. En los últimos años, se han implementado múltiples medidas de prevención y se han modificado normas con el objetivo de evitar las lesiones catastróficas. materiales y métodos: Se analizaron datos obtenidos de una encuesta telefónica realizada en el marco de colaboración entre la Unión Argentina de Rugby y la Fundación para la Lucha de Enfermedades Neurológicas de la Infancia (Fleni). Se realizó un análisis descriptivo de los datos. Se recopilaron los cambios en las normativas del deporte, que pudieran tener impacto en las futuras lesiones. Resultados: Se observa que el número de lesiones se mantiene estable año tras año. Al asociar este dato con un aumento sostenido de la cantidad de jugadores por año, impresiona haber una disminución relativa del riesgo de lesionarse. Conclusiones: Las lesiones catastróficas generan un gran impacto en la calidad de vida del jugador y de su entorno. Deben considerarse inadmisibles y se deben incrementar los esfuerzos para lograr eliminar los riesgos de lesionarse. El esfuerzo de las entidades reguladoras impresiona tener un impacto positivo al haberse logrado una reducción relativa de las lesiones en relación con el aumento de jugadores año tras año. Nivel de Evidencia: IV

Introduction: A catastrophic injury is defined as any serious trauma that involves the head, brain, spine, or spinal cord. They are life-threatening or may leave a permanent or semi-permanent disability. In Argentina, there is a high incidence of injuries. materials and methods: Data obtained from a t elephone survey carried out in the collaborative framework between the Union Argentina de Rugby and the Fundación para la Lucha de Enfermedades Neurológicas de la Infancia (Fleni, by its acronym) were analyzed. We carried out a qualitative analysis of the data and their relationship to progressive changes in sports regulations. Results: It was observed that the number of injuries remained stable year after year. When associating this fact with a sustained increase in the number of players per year, we can see a relative decrease in the risk of injury. Conclusion: Catastrophic injuries have a gr eat impact on the quality of life of the player and his environment. They must be considered inadmissible and the efforts must be increased to achieve zero risk. In recent years, multiple preventive measures have been implemented and regulations have been modified in order to avoid catastrophic injuries. Level of Evidence: IV

COVID-19 pneumonia accurately detected on chest radiographs with artificial intelligence.

PURPOSE: To investigate the diagnostic performance of an Artificial Intelligence (AI) system for detection of COVID-19 in chest radiographs (CXR), and compare results to those of physicians working alone, or with AI support. MATERIALS AND METHODS: An AI system was fine-tuned to discriminate confirmed COVID-19 pneumonia, from other viral and bacterial pneumonia and non-pneumonia patients and used to review 302 CXR images from adult patients retrospectively sourced from nine different databases. Fifty-four physicians blind to diagnosis, were invited to interpret images under identical conditions in a test set, and randomly assigned either to receive or not receive support from the AI system. Comparisons were then made between diagnostic performance of physicians working with and without AI support. AI system performance was evaluated using the area under the receiver operating characteristic (AUROC), and sensitivity and specificity of physician performance compared to that of the AI system. RESULTS: Discrimination by the AI system of COVID-19 pneumonia showed an AUROC curve of 0.96 in the validation and 0.83 in the external test set, respectively. The AI system outperformed physicians in the AUROC overall (70% increase in sensitivity and 1% increase in specificity, p < 0.0001). When working with AI support, physicians increased their diagnostic sensitivity from 47% to 61% (p < 0.001), although specificity decreased from 79% to 75% (p = 0.007). CONCLUSIONS: Our results suggest interpreting chest radiographs (CXR) supported by AI, increases physician diagnostic sensitivity for COVID-19 detection. This approach involving a human-machine partnership may help expedite triaging efforts and improve resource allocation in the current crisis.

Intravenous Chlorpromazine as Potentially Useful Treatment for Chronic Headache Disorders.

OBJECTIVE: The aim of this study was to describe a group of patients with chronic headache disorders (CH) and medication overuse headache (MOH) treated with intravenous chlorpromazine (IVC). We hypothesized that IVC is an effective and safe addition to well-known treatment strategies for CH and MOH management. INTRODUCTION: Up to 4% of the general population could experience CH. Most cases occur in women, in association with MOH. To date, evidence to support different treatment strategies is lacking. Although IVC is frequently used in the emergency room (ER), documentation on its use as supportive treatment for CH and for withdrawal management of MOH is poor. METHODS: A retrospective cohort of patients hospitalized to receive treatment for CH in a specialized neurological center in Argentina was analyzed. RESULTS: A total of 35 CH patients were included. Of the 35 patients, 33 (94%) patients also presented MOH. Patients reported only minor side effects to IVC administration (mainly drowsiness and symptomatic hypotension). Three months after inpatient treatment, the number of ER visits made by these patients decreased from an average of 2.8 in the 3 months prior to hospitalization to 0.7 after it (72%, P = .009). Headache frequency decreased in 20/34 (59%) patients during the same time period. Pain levels had dropped from a mean of 8 points at admission (in the scale of 1-10) to 2 points at discharge. In the first 3 months of follow-up, the average number of days per month in which patients experienced headache decreased from 28.9 to 15.4 days (53.3%, P < .0001). CONCLUSION: In this particular group of inpatients, there were no significant safety issues with IVC administration and the study might suggest that the efficacy of IVC as an add-on treatment for CH and MOH.

Diagnosis of Rapidly Progressive Dementia in a Referral Center in Argentina.

INTRODUCTION: Rapidly progressive dementia (RPD) is a broadly defined clinical syndrome. Our aim was to describe clinical and ancillary study findings in patients with RPD and evaluate their diagnostic performance for the identification of nonchronic neurodegenerative rapidly progressive dementia (ncnRPD). METHODS: We reviewed clinical records and ancillary methods of patients evaluated for RPD at our institution in Buenos Aires, Argentina from 2011 to 2017. We compared findings between chronic neurodegenerative RPD and ncnRPD and evaluated the diagnostic metrics using receiver operating characteristic curves. RESULTS: We included 104 patients with RPD, 29 of whom were chronic neurodegenerative RPD and 75 of whom were ncnRPD. The 6-month time to dementia cutpoint had a sensitivity of 89% and specificity of 100% for ncnRPD, with an area under the receiver operating characteristic curve of 0.965 (95% confidence interval=0.935-0.99; P<0.001). A decision tree that included time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis identified ncnRPD patients with a sensitivity of 100%, specificity of 79%, positive predictive value of 93%, and negative predictive value of 100% overall. DISCUSSION: RPD is a clinical syndrome that comprises different diagnoses, many of them for treatable diseases. Using the time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis when triaging these patients could help identify those diseases that need to be studied more aggressively.

Mucosal-Associated Invariant T Cell Features and TCR Repertoire Characteristics During the Course of Multiple Sclerosis.

Objective: To investigate the frequency, phenotype, function, and longitudinal repertoire of mucosal-associated invariant T (MAIT) cells in relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) patients. Methods: Forty-five RRMS patients in remission, 20 RRMS patients experiencing exacerbations, 15 PPMS patients, and 30 healthy controls (HCs) were included in the study. MAIT cells were identified phenotypically as CD3+ TCRγδ- Vα7.2 + CD161high. In 15 patients, MAIT cell number and MRI lesions were evaluated every 6 months, for 36 months. MAIT cell TCRVß repertoire was defined using single-cell cloning and mRNA sequencing. Results: Circulating MAIT cells were significantly reduced in both RRMS and PPMS patients, particularly during exacerbations, compared to healthy subjects. This decrease was accompanied by pro-inflammatory cytokine production (TNF-α, IFN-γ, IL-17, and GM-CSF). Three months post-exacerbation, peripheral blood MAIT cell percentages increased significantly along with clinical recovery. Likewise, we observed inverse correlation between MRI lesions and peripheral blood MAIT cell numbers. In paired samples, MAIT cell percentage was significantly higher in CSF than in peripheral blood, suggesting MAIT cell migration through the blood-brain barrier. Finally, MAIT cells showed limited TCRVß repertoires, in both CSF and peripheral blood, which remained stable over time. Conclusions: MAIT cell levels correlated with MS course both clinically and radiologically, showing marked and sustained oligoclonality. These findings may contribute to a better understanding of pathophysiological phenomena underlying the course of MS, and discovery of MAIT cell inhibitors could pave the way for the development of new therapeutic strategies.

Driving and Alzheimer's disease: A neuropsychological screening battery for the elderly.

As life expectancy increases, there is a marked increase in the elderly population eager to continue driving. A large proportion of these elderly drive safely, however, patients with mild dementia are high-risk drivers. OBJECTIVE: to identify the cognitive tests that best predict driving ability in subjects with mild dementia. METHODS: 28 drivers with mild dementia and 28 healthy elderly subjects underwent an extensive cognitive assessment (NACC Uniform Data Set Neuropsychological Battery), completed an adapted On Road Driving Test (ORDT) and a Driving Simulator assessment. RESULTS: drivers with mild dementia made more mistakes on the ORDT and had slower responses in the simulator tasks. Cognitive tests correlated strongly with on road and simulator driving performance. Age, the Digit Symbol Modalities Test and Boston Naming Test scores were the variables that best predicted performance on the ORDT and were included in a logistic regression model. CONCLUSION: the strong correlation between driving performance and performance on specific cognitive tests supports the importance of cognitive assessment as a useful tool for deciding whether patients with mild dementia can drive safely. The algorithm including these three variables could be used as a screening tool for the detection of unsafe driving in elderly subjects with cognitive decline.

À medida que aumenta a expectativa de vida, há um crescimento notável da população idosa ansiosa por continuar dirigindo. Uma grande proporção deles dirige com segurança, mas, pacientes com demência leve são condutores de alto risco. OBJETIVO: identificar os testes cognitivos que melhor predizem a capacidade de dirigir em indivíduos com demência leve. MÉTODOS: 28 motoristas com demência leve e 28 idosos saudáveis foram submetidos a uma extensa avaliação cognitiva (Bateria Neuropsicológica de Conjunto de Dados Uniformes NACC), completaram um teste de condução real adaptado (TCRA) e uma avaliação do Simulador de Condução. RESULTADOS: motoristas com demência leve cometeram mais erros no TCRA e tiveram respostas mais lentas nas tarefas do simulador. Os testes cognitivos correlacionaram-se fortemente com a condução na estrada e no simulador. A idade, o Teste de Modalidades do Símbolo Digit e o Teste de Nomeação de Boston foram as variáveis que melhor predisseram o desempenho no ORDT e foram incluídos em um modelo de regressão logística. CONCLUSÃO: a forte correlação entre o desempenho na direção e os testes cognitivos específicos apoia a importância da avaliação cognitiva como uma ferramenta útil para decidir se os pacientes com demência leve podem dirigir com segurança. O algoritmo que inclui essas três variáveis poderia ser usado como uma ferramenta de triagem para a detecção de condução de risco em idosos com declínio cognitivo.

Driving and Alzheimer's disease: A neuropsychological screening battery for the elderly / Condução e doença de alzheimer: uma bateria de triagem neuropsicológica para idosos

ABSTRACT As life expectancy increases, there is a marked increase in the elderly population eager to continue driving. A large proportion of these elderly drive safely, however, patients with mild dementia are high-risk drivers. Objective: to identify the cognitive tests that best predict driving ability in subjects with mild dementia. Methods: 28 drivers with mild dementia and 28 healthy elderly subjects underwent an extensive cognitive assessment (NACC Uniform Data Set Neuropsychological Battery), completed an adapted On Road Driving Test (ORDT) and a Driving Simulator assessment. Results: drivers with mild dementia made more mistakes on the ORDT and had slower responses in the simulator tasks. Cognitive tests correlated strongly with on road and simulator driving performance. Age, the Digit Symbol Modalities Test and Boston Naming Test scores were the variables that best predicted performance on the ORDT and were included in a logistic regression model. Conclusion: the strong correlation between driving performance and performance on specific cognitive tests supports the importance of cognitive assessment as a useful tool for deciding whether patients with mild dementia can drive safely. The algorithm including these three variables could be used as a screening tool for the detection of unsafe driving in elderly subjects with cognitive decline.

RESUMO À medida que aumenta a expectativa de vida, há um crescimento notável da população idosa ansiosa por continuar dirigindo. Uma grande proporção deles dirige com segurança, mas, pacientes com demência leve são condutores de alto risco. Objetivo: identificar os testes cognitivos que melhor predizem a capacidade de dirigir em indivíduos com demência leve. Métodos: 28 motoristas com demência leve e 28 idosos saudáveis foram submetidos a uma extensa avaliação cognitiva (Bateria Neuropsicológica de Conjunto de Dados Uniformes NACC), completaram um teste de condução real adaptado (TCRA) e uma avaliação do Simulador de Condução. Resultados: motoristas com demência leve cometeram mais erros no TCRA e tiveram respostas mais lentas nas tarefas do simulador. Os testes cognitivos correlacionaram-se fortemente com a condução na estrada e no simulador. A idade, o Teste de Modalidades do Símbolo Digit e o Teste de Nomeação de Boston foram as variáveis que melhor predisseram o desempenho no ORDT e foram incluídos em um modelo de regressão logística. Conclusão: a forte correlação entre o desempenho na direção e os testes cognitivos específicos apoia a importância da avaliação cognitiva como uma ferramenta útil para decidir se os pacientes com demência leve podem dirigir com segurança. O algoritmo que inclui essas três variáveis poderia ser usado como uma ferramenta de triagem para a detecção de condução de risco em idosos com declínio cognitivo.

Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 2002 American Academy of Neurology (AAN) guideline regarding immunization and multiple sclerosis (MS). METHODS: The panel performed a systematic review and classified articles using the AAN system. Recommendations were based on evidence, related evidence, principles of care, and inferences according to the AAN 2011 process manual, as amended. MAJOR RECOMMENDATIONS LEVEL B EXCEPT WHERE INDICATED: Clinicians should discuss the evidence regarding immunizations in MS with their patients and explore patients' opinions, preferences, and questions. Clinicians should recommend that patients with MS follow all local vaccine standards, unless there are specific contraindications and weigh local vaccine-preventable disease risks when counseling patients. Clinicians should recommend that patients with MS receive the influenza vaccination annually. Clinicians should counsel patients with MS about infection risks associated with specific immunosuppressive/immunomodulating (ISIM) medications and treatment-specific vaccination guidance according to prescribing information (PI) and vaccinate patients with MS as needed at least 4-6 weeks before initiating patients' ISIM therapy. Clinicians must screen for infections according to PI before initiating ISIM medications (Level A) and should treat patients testing positive for latent infections. In high-risk populations, clinicians must screen for latent infections before starting ISIM therapy even when not specifically mentioned in PI (Level A) and should consult specialists regarding treating patients who screen positive for latent infection. Clinicians should recommend against using live-attenuated vaccines in people with MS receiving ISIM therapies. Clinicians should delay vaccinating people with MS who are experiencing a relapse.