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BACKGROUND: Multiple sclerosis (MS) is an irreversible progressive CNS pathology characterized by the loss of myelin (i.e. demyelination). The lack of myelin is followed by a progressive neurodegeneration triggering symptoms as diverse as fatigue, motor, locomotor and sensory impairments and/or bladder, cardiac and respiratory dysfunction. Even though there are more than fourteen approved treatments for reducing MS progression, there are still no cure for the disease. Thus, MS research is a very active field and therefore we count with different experimental animal models for studying mechanisms of demyelination and myelin repair, however, we still lack a preclinical MS model assembling demyelination mechanisms with relevant clinical-like signs. RESULTS: Here, by inducing the simultaneous demyelination of both callosal and cerebellar white matter fibers by the double-site injection of lysolecithin (LPC), we were able to reproduce CNS demyelination, astrocyte recruitment and increases levels of proinflammatory cytokines levels along with motor, locomotor and urinary impairment, as well as cardiac and respiratory dysfunction, in the same animal model. Single site LPC-injections either in corpus callosum or cerebellum only, fails in to reproduce such a complete range of MS-like signs. CONCLUSION: We here report that the double-site LPC injections treatment evoke a complex MS-like mice model. We hope that this experimental approach will help to deepen our knowledge about the mechanisms of demyelinated diseases such as MS.

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Introduction: Multiple sclerosis significantly affects the quality of life of those suffering from this specific condition. Objective: To assess the quality of life of people with multiple sclerosis and analyse the correlation between the disease and its associated effects and different sociodemographic, clinical, and functional variables. Materials and Methods: An observational, cross-sectional, descriptive-correlational and quantitative study conducted using a non-probabilistic convenience sample composed of 70 patients suffering from multiple sclerosis registered with the Multiple Sclerosis Association of the Central Region of Portugal. The data collection protocol included sociodemographic and clinical questions, the Family Apgar Scale, and the Barthel Index. Descriptive and inferential statistics were used to process the data. Data collection took place between April and July 2021. Results: The majority of participants reported a moderate overall quality of life (M=51,78 ± 24,09). Higher scores were observed in the social relationships and environmental health domains, while lower scores were recorded for the physical domain. Better quality of life was found to be positively associated with being under 45 years old, having higher educational qualifications, living in functional families, and experiencing greater functional independence in activities of daily living. Discussion: The variables with the strongest association were those capable of influencing the physical and social domains. Those variables explained 59.00% and 53.00% of the variability. Conclusions: These results indicate that people with multiple sclerosis have a compromised quality of life, highlighting the need for new strategies focusing on early diagnosis and effective preventive interventions meant to improve quality of life across all its domains.

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INTRODUCTION: Predicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data. METHOD: The ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model. RESULTS: Nine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes. CONCLUSION: The model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.

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Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by damage to the myelin sheaths of oligodendrocytes. Currently, there is no specific biomarker to identify the disease; however, a diagnostic criterion has been established based on patient's clinical, laboratory, and imaging characteristics, which assists in identifying this condition. The primary method for diagnosing MS is the McDonald criteria, first described in 2001 and revised in the years 2005, 2012, and 2017. These criteria have been continuously reviewed to enhance specificity and sensitivity in the diagnosis of MS, thereby reducing errors in its differential diagnosis. An important differential diagnosis that shares overlapping features with MS, mainly the progressive forms, are leukodystrophies with demyelination as underlying pathology. Leukodystrophies comprise a rare group of genetically determined disorders that lead to either demyelination or hypomyelination of the central nervous system that can result neuroimaging changes as well as clinical findings similar to those observed in MS. Thus, systematic evaluation encompassing clinical presentation, neuroimaging findings, and laboratory metrics proves indispensable for a differential diagnosis. As such, this study aimed to establish, clearly and objectively, the similarities and differences between MS and the main demyelinating leukodystrophies. The study analyzed the parameters of the McDonald criteria, including clinical, laboratory, and magnetic resonance imaging aspects, as found in patients with leukodystrophies through scoping literature review. The data were compared with the determinations of the revised 2017 McDonald criteria to facilitate the differential diagnosis of these diseases in clinical practice.

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El manejo y el pronóstico de la Esclerosis Múltiple (EM) ha cambiado sustancialmente en los últimos años, a ser una enfermedad muy reconocida por los Neurólogos; el conocimiento de los aspectos epidemiológicos, clínicos, diagnósticos y terapéutico han conllevado a un mejor diagnóstico y pronóstico para los pacientes permitiendo al clínico establecer una terapia individualizada para los pacientes según el fenotipo de la enfermedad que presenten. Con la expansión del arsenal terapéuticos, estos fármacos ejercen su eficacia modulando o suprimiendo la respuesta inmunológica. Este documento proporciona la clasificación de la enfermedad, manifestaciones clínicas, diagnóstico y tratamiento individualizado (Terapias Modificadoras de la enfermedad-TMD) para la toma de decisiones en el manejo de pacientes. El presente protocolo está elaborado con evidencia clínica luego de una exhaustiva búsqueda de literatura actualizada; con el fin de brindar opciones de manejo terapéutico para profesionales de la Neurología, que deberán tomar decisiones individualizadas en el manejo integral de los pacientes con EM...(AU)

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BACKGROUND: Osmotic demyelination syndrome (ODS) with cerebral cortical involvement is a rare complication of severe hyponatremia correction. Careful management of hyponatremia is crucial, particularly in patients with risk factors, such as alcohol use disorder and diabetes insipidus. CASE: A patient in his 40s with a history of alcohol use disorder and central diabetes insipidus developed ODS after a 24 mEq/L osmolar increase during the treatment of hyponatremia. The patient's condition progressed into locked-in syndrome and then improved to spastic tetraparesis after cortical basal ganglia ODS improved. DISCUSSION: The differential diagnosis of cortical demyelination includes laminar cortical necrosis, being the interpretation of Apparent Diffusion Coefficient (ADC) MRI sequence is a useful tool.This case underscores the need to investigate and improve diagnosis and treatment strategies in patients with ODS. It also emphasises the significance of careful hyponatremia correction and frequent monitoring, particularly in patients with known risk factors for ODS.

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BACKGROUND: Rapid correction of hyponatremia, especially when severe and chronic, can result in osmotic demyelination. The latest guideline for diagnosis and treatment of hyponatremia (2014) recommends a correction limit of 10 mEq/L/day. Our aim was to summarize published cases of osmotic demyelination to assess the adequacy of this recommendation. METHOD: Systematic review of case reports of osmotic demyelination. We included cases confirmed by imaging or pathology exam, in people over 18 years of age, published between 1997 and 2019, in English or Portuguese. RESULTS: We evaluated 96 cases of osmotic demyelination, 58.3% female, with a mean age of 48.2 ± 12.9 years. Median admission serum sodium was 105 mEq/L and > 90% of patients had severe hyponatremia (<120 mEq/L). Reports of gastrointestinal tract disorders (38.5%), alcoholism (31.3%) and use of diuretics (27%) were common. Correction of hyponatremia was performed mainly with isotonic (46.9%) or hypertonic (33.7%) saline solution. Correction of associated hypokalemia occurred in 18.8%. In 66.6% of cases there was correction of natremia above 10 mEq/L on the first day of hospitalization; the rate was not reported in 22.9% and in only 10.4% was it less than 10 mEq/L/day. CONCLUSION: The development of osmotic demyelination was predominant in women under 50 years of age, with severe hyponatremia and rapid correction. In 10.4% of cases, there was demyelination even with correction <10 mEq/L/day. These data reinforce the need for conservative targets for high-risk patients, such as 4-6 mEq/L/day, not exceeding the limit of 8 mEq/L/day.

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Extracellular vesicles (EVs) are involved in diverse cellular functions, playing a significant role in cell-to-cell communication in both physiological conditions and pathological scenarios. Therefore, EVs represent a promising therapeutic strategy. Oligodendrocytes (OLs) are myelinating glial cells developed from oligodendrocyte progenitor cells (OPCs) and damaged in chronic demyelinating diseases such as multiple sclerosis (MS). Glycoprotein transferrin (Tf) plays a critical role in iron homeostasis and has pro-differentiating effects on OLs in vivo and in vitro. In the current work, we evaluated the use of EVs as transporters of Tf to the central nervous system (CNS) through the intranasal (IN) route. For the in vitro mechanistic studies, we used rat plasma EVs. Our results show that EVTf enter OPCs through clathrin-caveolae and cholesterol-rich lipid raft endocytic pathways, releasing the cargo and exerting a pro-maturation effect on OPCs. These effects were also observed in vivo using the animal model of demyelination induced by cuprizone (CPZ). In this model, IN administered Tf-loaded EVs isolated from mouse plasma reached the brain parenchyma, internalizing into OPCs, promoting their differentiation, and accelerating remyelination. Furthermore, in vivo experiments demonstrated that EVs protected the Tf cargo and significantly reduced the amount of Tf required to induce remyelination as compared to soluble Tf. Collectively, these findings unveil EVs as functional nanocarriers of Tf to induce remyelination.

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Introducción: La alucinosis peduncular (AP) hace referencia a alucinaciones autodiscriminadas, cuyo origen son lesiones en el mesencéfalo y en el puente. Presentación del caso: Paciente 27 años, femenina, con alucinaciones visuales, auditivas autodiscriminadas por ella misma, sin antecedentes previos de importancia y con lesiones en resonancia magnética cerebral y cervical en el pedúnculo cerebeloso superior, tegmento pontino, y en columna cervical con bandas oligoclonales patrón 2, que cumplían criterios de Mc Donalds para esclerosis múltiple. Discusión: La alucinosis peduncular hace referencia a la presencia de alucinaciones visuales, criticadas por el paciente, con la consecuencia de lesiones de las vías inhibitorias por deaferentación y desinhibición mesencéfalotalámicas, y retinogenículo calcarina, descritas como manifestación de múltiples patologías neurológicas como trauma, afectación vascular, tumores y pocos casos de enfermedad desmielinizante, entre otras. Conclusión: La alucinosis peduncular es una forma atípica de presentación de lesiones pontomesencefálicas descritas en varias patologías; se debe tener en cuenta en la localización de la lesión neurológica; se han reportado pocos casos como síntoma de la enfermedad desmielinizante.

Introduction: Peduncular hallucinosis (PA) refers to self-discriminating hallucinations, these are caused by lesions in the midbrain and pons. Presentation of the case: 27-year-old right handed female patient with visual and auditory hallucinations self-discriminated by the patient, with no prior history of importance and with lesions in cerebral and cervical Magnetic Resonance in the superior cerebellar peduncle, pontine tegmentum, and in the cervical spine with pattern 2 oligo clonal bands, which met Mc Donald's criteria for multiple sclerosis. Discussion: Peduncular hallucinosis refers to the presence of visual hallucinations criticized by the patient, consequence of lesions in the inhibitory pathways with deafferentation and disinhibition of the midbrain-thalamic and retinogeniculus-calcarine pathways. Described as a manifestation of multiple neurological pathologies such as trauma, vascular, tumor and few cases of demyelinating among others. Conclusion: Peduncular hallucinosis is an atypical form of presentation of pontomesencephalic lesions described in several pathologies, it must be taken into account when locating the neurological lesion, few cases have been reported as symptom of the demyelinating disease.

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BACKGROUND: Clinically Isolated Syndrome (CIS) is the first clinical episode suggestive of Clinical Definite Multiple Sclerosis (CDMS). There are no reports on possible predictors of conversion to CDMS in Mexican mestizo patients. AIM OF THE STUDY: To investigate immunological markers, clinical and paraclinical findings, and the presence of herpesvirus DNA to predict the transition from CIS to CDMS in Mexican patients. METHODS: A single-center prospective cohort study was conducted with newly diagnosed patients with CIS in Mexico between 2006 and 2010. Clinical information, immunophenotype, serum cytokines, anti-myelin protein immunoglobulins, and herpes viral DNA were determined at the time of diagnosis. RESULTS: 273 patients diagnosed with CIS met the enrolment criteria; after 10 years of follow-up, 46% met the 2010 McDonald criteria for CDMS. Baseline parameters associated with conversion to CDMS were motor symptoms, multifocal syndromes, and alterations of somatosensory evoked potentials. The presence of at least one lesion on magnetic resonance imaging was the main factor associated with an increased risk of conversion to CDMS (RR 15.52, 95% CI 3.96-60.79, p = 0.000). Patients who converted to CDMS showed a significantly lower percentage of circulating regulatory T cells, cytotoxic T cells, and B cells, and the conversion to CDMS was associated with the presence of varicella-zoster virus and herpes simplex virus 1 DNA in cerebrospinal fluid and blood. CONCLUSION: There is scarce evidence in Mexico regarding the demographic and clinical aspects of CIS and CDMS. This study shows several predictors of conversion to CDMS to be considered in Mexican patients with CIS.

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