Alucinosis peduncular en esclerosis múltiple, síntoma poco común en la expresión de enfermedad desmielinizante / Peduncular hallucinosis in multiple sclerosis, a rare symptom in demyelinating disease

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.

Impacto de la pandemia COVID-19 en pacientes con enfermedades desmielinizantes / IMPACT OF THE COVID-19 PANDEMIC ON PATIENTS WITH DEMYELINIZING DISEASES

Introducción: A más de un año del inicio de la pandemia, el seguimiento y la atención presencial de pacientes con enfermedades desmielinizantes se ha visto modificado. Según la evidencia, pacientes con diagnóstico de esclerosis múltiple (EM), síndrome desmielinizante aislado (SDA), Síndrome Radiológico Aislado (SRA) o enfermedades del espectro de neuromielitis óptica (NMO) no parecen ser un grupo de riesgo para COVID19 por el hecho de tener la enfermedad. La presencia de ciertas condiciones puede hacerlos susceptibles de cursar infección severa. Se ha descripto una asociación de curso grave con drogas anti CD20, faltan datos sobre la respuesta a vacunas COVID19 en esta población. Objetivos: Establecer características clínico-epidemiológicas de pacientes con enfermedades desmielinizantes que han padecido COVID-19 y describir su evolución. Caracterizar población vacunada, evaluar acceso al seguimiento médico/ terapéutico durante la pandemia. Materiales y métodos: Estudio observacional descriptivo. Se revisaron las historias clínicas de 168 pacientes con EM, SDA y SRA y 33 pacientes con NMO correspondientes al Hospital de Clínicas José de San Martin. Mediante encuesta telefónica se evaluó adherencia al tratamiento, evolución clínica, infección COVID-19, vacunación y acceso durante la pandemia. Resultados: Se encontraron 49 pacientes que desarrollaron COVID-19 en el grupo de pacientes con EM, y 7 en el grupo de NMO. Del primer grupo ninguno requirió internación, mientras que en el segundo, 2 fueron hospitalizados y uno de ellos falleció. La complicación post-COVID más frecuente fue: astenia prolongada y 3 pacientes presentaron un brote de la enfermedad de base en los 3 meses posteriores. Cerca del 90% de nuestra población ya contaba con al menos 1 dosis de vacuna para SARS-CoV2. Se interrogó sobre el acceso a la consulta neurológica y casi el 70% de los pacientes otorgó máximo puntaje al acceso a consultas virtuales. Conclusión: Los pacientes con enfermedades desmielinizantes que cursaron COVID-19 no tuvieron complicaciones severas por la infección, con solamente 2 pacientes cursando un brote en los 3 meses posteriores. No observamos reacciones adversas severas post vaccinales, ni infección posterior, sólo 2 pacientes presentaron un brote en el período post aplicación. Gran cantidad de pacientes percibieron acceso fluido a sus neurólogos de manera virtual, lo que podría relacionarse con alta tasa de adherencia a sus tratamientos a pesar de la limitación a la consulta presencial.

Introduction: More than a year after the start of the pandemic, the follow-up and face-to-face care of patients with demyelinating diseases has been modified. According to the evidence, patients with a diagnosis of multiple sclerosis (MS), isolated demyelinating syndrome (ADS), Isolated Radiological Syndrome (RAS) or neuromyelitis optica (NMO) spectrum diseases do not seem to be a risk group for COVID19 due to the fact that they have the disease. The presence of certain conditions can make them susceptible to severe infection. A severe course association with anti-CD20 drugs has been described, data on the response to COVID19 vaccines in this population are lacking. Objectives: To establish clinical-epidemiological characteristics of patients with demyelinating diseases who have suffered from COVID-19 and describe their evolution. Characterize the vaccinated population, evaluate access to medical/therapeutic follow-up during the pandemic. Materials and methods: Descriptive observational study. The medical records of 168 patients with MS, ADS and ARS and 33 patients with NMO corresponding to the Hospital de Clínicas José de San Martin were reviewed. Through a telephone survey, adherence to treatment, clinical evolution, COVID-19 infection, vaccination, and access during the pandemic were evaluated. Results: 49 patients who developed COVID-19 were found in the MS patient group, and 7 in the NMO group. Of the first group, none required hospitalization, unlike in the second, 2 were hospitalized and one of them died. The most frequent post-COVID complication was: prolonged asthenia and 3 patients presented an outbreak of the underlying disease in the following 3 months. Close to 90% of our population already had at least 1 dose of SARS-CoV2 vaccine. Access to the neurological consultation was questioned and almost 70% of the patients gave the highest score to access to virtual consultations. Conclusion: Patients with demyelinating diseases who had COVID-19 did not have severe complications from the infection, with only 2 patients having an outbreak in the subsequent 3 months. We did not observe severe post-vaccinal adverse reactions, nor subsequent infection, only 2 patients presented an outbreak in the post-application period. A large number of patients perceived fluid access to their neurologists virtually, which could be related to a high rate of adherence to their treatments despite the limitation to face-to-face consultation

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Vitamin D3 mediates spatial memory improvement through nitric oxide mechanism in demyelinated hippocampus of rat

Abstract Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3.

Research advances in the clinical genetics of leukodystrophy in children / 中国当代儿科杂志

Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.

Experiencia en la unidad de enfermedades desmielinizantes a 2 años / Experience in the demyelinating diseases unit after 2 years

La esclerosis múltiple es una enfermedad desmielinizante crónica que produce discapacidad progresiva, por lo que el tratamiento se centra en retrasar la progresión, prevenir recaídas y disminuir los síntomas de manera efectiva. Realizamos un estudio observacional, descriptivo, longitudinal, de un solo centro, con los pacientes admitidos en la unidad de enfermedades desmielinizantes, desde diciembre 2017 hasta febrero 2020. Del total de pacientes, 62.5% recibieron tratamiento con ocrelizumab y completaron seguimiento por 12 meses, sin progresión de la enfermedad. Con este estudio, resaltamos la importancia y la efectividad de los tratamientos modificadores de la enfermedad.

Multiple sclerosis is a chronic demyelinating disease that causes progressive disability, so treatment focuses on slowing progression, preventing relapses, and effectively reducing symptoms. We conducted an observational, descriptive, longitudinal, single-center study with patients admitted to the demyelinating diseases unit from December 2017 to February 2020. Of the total number of patients, 62.5% received treatment with ocrelizumab and completed 12-month follow-up, without disease progression. With this study, we highlight the importance and effectiveness of disease-modifying treatments

Serum YKL-40 levels in patients with multiple sclerosis / Níveis séricos de YKL-40 em pacientes com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. The YKL-40 protein, which is secreted from various cells that contribute to inflammation and infection, plays a role in immune regulation. Objective: This study investigated the serum YKL-40 levels of patients with clinically isolated syndrome (CIS) and MS. Methods: The participants was divided into three groups: 1) patients with CIS (n = 20); 2) patients with relapsing-remitting MS (RRMS; n = 39); and 3) healthy individuals (n = 35). The YKL-40 levels in serum samples obtained from the participants were measured using enzyme-linked immunoassays. Results: The median serum YKL-40 level was 20.2 ng/mL (range 9.8-75.9 ng/mL) in the patients with CIS, 22.7 ng/mL (range 13.4-57.9 ng/mL) in the patients with RRMS and 11.0 ng/mL (range 10.0-17.3 ng/mL) in the control group (p < 0.001). The serum YKL-40 levels in the patients with RRMS were correlated with the patients' expanded disability status scale scores and ages (p < 0.05). No relationships were determined between the serum YKL-40 levels and the other variables (p > 0.05). The serum YKL-40 levels were higher in the CIS group than in the MS group. These findings show that the serum YKL-40 levels were high even at the beginning of the disease. The serum YKL-40 levels were also not involved in the progression to clinically definite MS. Conclusions: The findings from this study suggested that YKL-40 may be a useful marker for the inflammatory process of MS.

RESUMO Contexto: A Esclerose Múltipla (EM) é uma doença inflamatória crônica que afeta o sistema nervoso central. A proteína UKL-40, secretada de várias células que participam de processos inflamatórios e infecciosos, desempenha um importante papel na regulação imunológica. Objetivo: Este estudo investigou níveis séricos de YKL-40 em pacientes com Síndrome Clinicamente Isolada (SCI) e EM. Métodos: Os participantes foram divididos em três grupos: 1) pacientes com SCI (n = 20); 2) pacientes com EM recorrente-remitente (EMRR; n = 39); e 3) indivíduos saudáveis (n = 35). Os níveis de YKL-40 em amostras séricas obtidas dos participantes foram medidos usando-se imunoensaios ligados a enzimas. Resultados: O nível sérico médio de YKL-40 foi 20.2 ng/mL (range 9.8-75.9 ng/mL) em pacientes com CIS, 22.7 ng/mL (intervalo entre 13.4-57.9 ng/mL) em pacientes com EMRR e 11.0 ng/mL (intervalo entre 10.0-17.3 ng/mL) no grupo controle (p < 0.001). Os níveis séricos de YKL-40 em pacientes com EMRR estavam correlacionados às pontuações e idades dos pacientes na EDSS (p < 0.05). Não foram determinadas relações entre os níveis séricos de YKL-40 e outras variáveis (p > 0.05). Os níveis séricos de YKL-40 no grupo SCI estavam mais elevados do que no grupo EM. Estes resultados demonstram que os níveis séricos de YKL-40 estavam mais elevados até mesmo no início da doença. Os níveis séricos de YKL-40 também não estavam associados à progressão da EM clinicamente definida. Conclusões: A partir deste estudo, os resultados sugeriram que a proteína YKL-40 pode ser um indicador útil no processo inflamatório da EM.

Caracterización epidemiológica, clínica e imagenológica de pacientes con esclerosis múltiple / Epidemiological, clinical and imaging characterization of patients with multiple sclerosis

RESUMEN Introducción: la esclerosis múltiple es una enfermedad desmielinizante, degenerativa, crónica, autoinmune e inflamatoria, que afecta al sistema nervioso central. Esta afección constituye la primera causa de invalidez neurológica en adultos jóvenes. Objetivo: caracterizar a los pacientes con diagnóstico de esclerosis múltiple ingresados en el servicio de Neurología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro¼. Métodos: se realizó un estudio descriptivo y transversal con los pacientes con diagnóstico de esclerosis múltiple ingresados en el servicio de Neurología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro¼, Santa Clara, Villa Clara, durante el período de enero 2018 - diciembre 2019; la población de estudio quedó constituida por 30 pacientes. Resultados: el promedio de edad de debut fue de 38,7 años. La relación entre pacientes con color de piel blanca y no blanca fue 9:1, y la de mujeres y hombres de 14:1. La esclerosis múltiple recidivante-remitente representó el 70 %, y el grado mínimo de discapacidad el 60 %. El 48,27 %, 41,37 % y 37,93 % de los pacientes presentaron lesiones supratentoriales, infratentoriales y en número de dos a cuatro, respectivamente. Conclusiones: predominó el sexo femenino con edad de debut entre los 20 a 29 años. Los síntomas más comunes fueron: las alteraciones motoras, sensitivas y cerebelosas. La forma clínica de presentación predominante fue la esclerosis múltiple recidivante-remitente y el grado de discapacidad mínimo. Las lesiones supratentoriales e infratentoriales y la cantidad de lesiones en número dos a cuatro fueron las más frecuentes; la mayoría de los casos presentó cambio de intensidad del cuerpo calloso.

ABSTRACT Introduction: multiple sclerosis is a demyelinating, degenerative, chronic, autoimmune and inflammatory disease that affects the central nervous system. This condition is the leading cause of neurological disability in young adults. Objective: to characterize patients with a diagnosis of multiple sclerosis admitted to the Neurology service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital. Methods: a descriptive and cross-sectional study was carried out in patients with a diagnosis of multiple sclerosis admitted to the Neurology Service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital, Santa Clara, Villa Clara, from January 2018 to December 2019; the study population consisted of 30 patients. Results: the average age at debut was 38.7 years. The ratio between patients with white and non-white skin color was 9: 1, and that of women and men was 14: 1. Relapsing-remitting multiple sclerosis accounted for 70%, and the minimum degree of disability for 60%. The 48.27%, 41.37% and 37.93% of the patients had supratentorial and infratentorial lesions and two to four in number, respectively. Conclusions: female gender predominated with the age at debut between 20 to 29 years. Motor, sensory and cerebellar alterations were the most common symptoms. Relapsing-remitting multiple sclerosis was the predominant clinical presentation and minimal degree of disability. Supratentorial and infratentorial lesions and the number of lesions in number two to four were the most frequent; most of the cases had a change in intensity of the corpus callosum.

Eficacia de la movilización de células madre en pacientes con Polineuropatía Desmielinizante Inflamatoria Crónica refractaria / Efficacy of mobilization of stem cells in patients with Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Introducción: La polineuropatía desmielinizante inflamatoria crónica (CIDP) es una enfermedad desmielinizante e inflamatoria de mediación autoinmune. El tratamiento convencional es basado en la inmunomodulación e inmunosupresión. El uso de células madre es una terapia novedosa en los trastornos autoinmune, siendo incluida como terapia. Objetivo: Determinar la eficacia de la movilización de células madre mediante la aplicación del factor estimulador de colonias granulocíticas (F-ECG) en pacientes con CIDP que han recibido otras líneas de tratamiento. Material y Métodos: Se realizó un estudio aleatorizado, doble ciego sobre una cohorte de 45 pacientes con CIDP, donde se administró el (F-ECG) en 25 pacientes y 20 continuaron con el tratamiento habitual, tratados anteriormente con otras variantes terapéuticas por más de tres años, sin respuesta satisfactoria. Resultados: Predominio de los hombres para 64,4 por ciento, la Diabetes Mellitus tuvo mayor asociación y la medicación más usada fueron los esteroides. Los síntomas y signos clínicos mejoraron significativamente tras el tratamiento. Los valores de la puntuación del TCSS al mes y 3 meses después del tratamiento disminuyeron significativamente; pero este decremento no se mantuvo al final del estudio. La velocidad de conducción y el potencial de acción de los nervios sensoriales y motores mejoraron considerablemente después del tratamiento. Conclusiones: La efectividad de la aplicación del (F-ECG) para la mejoría de los síntomas clínicos y resultados de estudios neurofisiológicos evolutivamente son mayores que otras variantes terapéuticas en los primeros meses, con buena seguridad y tolerabilidad, por lo que se puede incluir en la terapéutica convencional para la CIDP(AU)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune demyelinating disease. Conventional treatment is based on immunomodulation and immunosuppression. The use of stem cells is a novel therapy in autoimmune disorders, so it is included as therapy. Objective: To determine the efficacy of mobilization of stem cells by applying granulocyte colony-stimulating factor (G-CSF) in patients with CIDP who have followed other lines of treatment. Material and Methods: A randomized, double-blind study was carried out on a cohort of 45 patients with CIDP. G-CSF was administered to 25 patients and 20 of them continued with the usual treatment. These patients were previously treated with other therapeutic variants for more than three years without satisfactory response. Results: There was a prevalence of men (64.4 percent), Diabetes Mellitus had a greater association, and the most used medications were steroids. Clinical symptoms and signs improved significantly after treatment. TCSS scores significantly decreased at one and three months after treatment, but this decrease was not maintained at the end of the study. The conduction velocity and action potential of sensory and motor nerves improved considerably after treatment. Conclusions: The effectiveness of the use of G-CSF shows an improvement of clinical symptoms. The results of neurophysiological studies have a better course than other therapeutic variants during the first months, with good safety and tolerability, so it can be included in the conventional therapy for the CIDP(AU)

Medicamentos modificadores en esclerosis múltiple: esquemas terapéuticos actuales / Disease-Modifying drugs in multiple sclerosis: current therapeutic schemes

La esclerosis múltiple (EM) es una enfermedad crónica, autoinmune y neurodegenerativa; que tiene como principal característica la desmielinización de los axones en el sistema nervioso. Los medicamentos modificadores de la enfermedad (MME) logran retrasar la aparición de los síntomas y modificar parcialmente el progreso de la desmielinización y daño neuronal, resultando cada vez más complejo determinar un esquema terapéutico estandarizado según la condición particular de cada paciente. En este artículo se presenta una revisión actualizada de la evidencia clínica que ha llevado al uso de los esquemas terapéuticos en EM. La mayoría de los medicamentos aprobados actualmente son utilizados para la EM remitente-recurrente y se pueden dividir de acuerdo a la eficacia y seguridad. Los medicamentos de primera línea han mostrado una baja o moderada eficacia y alta seguridad; después de usar estos fármacos sin lograr una buena respuesta o ante una enfermedad avanzada se usan medicamentos de segunda y tercera línea que tienen una alta eficacia, pero son menos seguros, presentando mayores efectos secundarios y riesgos asociados para los pacientes. El ocrelizumab es el único fármaco aceptado para la EM primaria progresiva y el siponimod fue aprobado como una alternativa para la EM secundaria progresiva. El desarrollo de nuevos medicamentos y el seguimiento clínico de los ya aprobados permitirá establecer un mejor abordaje terapéutico logrando así mejorar la calidad de vida de cada paciente.

Multiple sclerosis (MS) is a chronic, autoimmune and neurodegenerative disease; whose main characteristic is the demyelination of axons in the nervous system. Disease-modifying drugs (DMD) can delay the onset of symptoms and partially modify the progression of demyelination and neuronal damage, making it increasingly complex to determine a standardized therapeutic scheme that is individualized to each patient. This article presents an updated review on the clinical evidence that has led to the use of current therapeutic schemes in MS with focus on DMD. Current medications in treating relapsing-remitting MS can be divided according to efficacy and safety. First-line drugs have shown low or moderate efficacy and high safety. Second- and third-line drugs are used after a poor response or in cases of advanced disease. These drugs are highly effective, but less safe, presenting greater side effects and associated risks for patients. Ocrelizumab is the only accepted drug for primary progressive MS and siponimod is accepted as an alternative for secondary progressive MS. The development of new medications and the clinical follow-up of those already approved will allow establishing a better therapeutic approach, thus improving the quality of life of each patient.

Eficacia de la rehabilitación cognitiva en un paciente con esclerosis múltiple progresiva primaria / Efficacy of cognitive rehabilitation in a patient with primary progressive multiple sclerosis

La esclerosis múltiple (EM) es una enfermedad inflamatoria crónica que cursa con la desmielinización y la neurodegeneración a nivel del sistema nervioso central. Existen tres tipos de EM en función de la progresión de la enfermedad, pero la mayor parte de los pacientes tienden a presentar déficits cognitivos. Por lo tanto, resulta imprescindible el desarrollo de programas de entrenamiento cognitivos dirigidos a la mejora de estos déficits y, en definitiva, a la mejora de la calidad de vida de estos pacientes. En este sentido, el objetivo principal de este estudio fue la puesta en marcha de un programa de entrenamiento cognitivo dirigido a un paciente con esclerosis múltiple progresiva primaria (EMPP) a lo largo de un año. Los resultados pusieron de manifiesto que algunos de los déficits cognitivos que presentó inicialmente el paciente mejoraron tras varios meses de intervención. En este sentido, el paciente presentó notables mejoras en el control inhibitorio y la flexibilidad cognitiva. No obstante, los déficits en la velocidad de procesamiento se mantuvieron constantes a lo largo de toda la intervención. Asimismo, aparecieron otros déficits a lo largo de la intervención que remitieron tras la adecuación de los objetivos de intervención. Por todo ello, nuestro estudio reforzó la importancia de la puesta en marcha de los programas de rehabilitación cognitiva dirigidos a pacientes con enfermedades desmielinizantes para paliar las secuelas cognitivas derivadas de las mismas. Además, es importante que estos programas de entrenamiento cognitivo sean revisados periódicamente para adecuar los objetivos del tratamiento.

Multiple sclerosis (MS) is a chronic inflammatory disease that involves demyelination and neurodegeneration at the level of the central nervous system. Despite the different characteristics of each of the three types of MS, most patients with this disease present significant cognitive deficits. Therefore, it is essential to develop cognitive training programs to improve these deficits and, ultimately, increase the quality of life of these patients. Thus, the main objective of this study was to implement a one-year cognitive training program with a patient with progressive primary multiple sclerosis (PPMS). The results showed that some of the cognitive deficits the patient initially presented improved after several months of intervention. In this regard, the patient presented noteworthy improvements in inhibitory control and cognitive flexibility. However, deficits in processing speed remained constant throughout the intervention. Likewise, other deficits appeared during the intervention that remitted after adapting the intervention objectives to the patient's needs. Therefore, our study reinforces the importance of implementing cognitive rehabilitation programs for patients with demyelinating diseases to alleviate the cognitive sequelae they produce. In addition, it is important to evaluate these cognitive training programs periodically in order to adapt the objectives and improve the patient's functionality.

Demyelination in experimental intraventricular neurocysticercosis / Desmielinização na neurocisticercose intraventricular experimental

Abstract Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Resumo A neurocisticercose (NCC) é classificada como uma doença tropical negligenciada que afeta principalmente a América Latina e a África, apesar de alguns relatos na América do Norte e na Europa. A NCC é responsável por cerca de 30% dos casos de epilepsia em países endêmicos. Estas lesões parecem ter estreita relação com o estádio de desenvolvimento, com a localização e o número de parasitas, bem como a resposta imune do hospedeiro. O presente estudo objetivou caracterizar a resposta de células inflamatórias e as lesões teciduais pela análise da desmielinização periventricular e parenquimatosa ao longo da infecção experimental de NCC intraventricular. Para tanto, camundongos BALB/c foram submetidos a NCC experimental através da inoculação de cisticercos de Taenia crassiceps. O encéfalo foi retirado aos 7, 30, 60 e 90 dias após inoculação (DAI) e analisado após coloração por Hematoxilina e Eosina (HE), Luxol Fast Blue e Nissl. Observou-se ventriculomegalia, processo de infiltração inflamatório composto por células polimorfonucleares, mononucleares e macrófagos espumosos. A presença de células inflamatórias foi associada com neurodegeneração, observada pelas áreas de desmielinização que foram inicialmente periventricular e mais tardiamente no parênquima. Em conclusão, observa-se que a presença dos cisticercos e a inflamação foram capazes de promover desmielinização periventricular inicial e parenquimatosa conforme houve progressão tardia da infecção.

Les troubles cognitifs dans les syndromes cliniquement isolés: Etude cas-témoins / Cognitive impairment in clinically isolated syndromes: A control-case study

ntroduction - L'atteinte cognitive est fréquente dans la Sclérose en Plaques (SEP) mais son diagnostic se fait souvent tardivement, au stade de désinsertion sociale et professionnelle. Les études portant sur les aspects cognitifs dans les formes pré-coces de la SEP tels que les syndromes cliniquement isolés (SCI) et les syndromes radiologiquement isolés (SRI) sont rares.Objectifs - Analyserles fonctions cognitives d'un premier événement démyélinisant et identifier les domainesqui seraient les plus précocement atteints.Patients et méthodes - Le profil cognitif d'une populationhomogène de 13 patients présentant unSCI a été évalué, eta été comparé à 15 témoins sains appareillés en fonction de l'âge, du sexe et du niveau d'éducation. Une batterie de tests neu-ropsychologiques(BCCogSEP, batterie courte d'évaluation cognitive de la SEP),vali-dée dans la SEP, a été utilisée. Ses composants explorent les capacités mnésiques et verbales, l'attention, la vitesse de traitement de l'information (VTI) et les fonctions exécutives.Résultats - Lesperformances cognitives globales étaient amoindries dans le groupe SCI, comparativement au groupe témoin. Sur les 13 patients atteints de SCI, cinq (38%) présentaient une altération cognitive globale qui a été objectivée par l'at-teinte d'au moins deux ou trois tests de la batterie. La PASAT (Paced Auditory Serial Addition Test)était le test le plus altéré (84,6% d'atteinte). La VTI et la mémoire de travail étaient les fonctions les plus atteintes chez les patients.Conclusion - Les dysfonctions cognitives peuvent se voir très précocement et peuvent grever lourdement le pronostic de la SEP.

Introduction - Cognitive impairment is common in multiple sclerosis (MS) but its diagnosis is often made late, at the stage of social and professional disinsertion. Studies of the cognitive aspects in early forms of MS such as clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) are rare. Objectives - To analysis the cognitive functions of a first demyelinating event and identify the areas that would be most affected early. Patients and methods - The cognitive profile of a homogeneous population of 13 patients with a CIS was evaluated, and compared with 15 healthy controls, matched according to age, sex and level of education. A battery of neuropsychological tests (BCCogSEP, Short battery for cognitive assessment of MS) validated in MS,was used. Its components explore memory and verbal skills, attention, information processing speed (IPS) and executive functions. Results - The overall cognitive performance was reduced in the CIS group,compared to control group. Five out of thirteen CIS patients (38%) had an overall cognitive impairment, demonstrated by the achievement of at least two or three battery tests. The Paced Auditory Serial Addition Test (PASAT) was the most altered test (84.6% impairment). IPS and working memory were the most affected functions in the patients. Conclusion - Cognitive dysfunctions can be seen very early and can severely affect the prognosis of MS.

Isolamento e diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais / Isolation and differentiation of canine dental pulp stem cells in neural progenitor cells

O objetivo deste estudo foi verificar a capacidade de diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais bem como quantificar obtenção e viabilidade celular, durante três passagens em cultura. As células foram extraídas da polpa dentária de dois cadáveres caninos, com aproximadamente dez meses de idade, que foram a óbito em decorrência de traumatismo automotivo. Após três subculturas, realizou-se avaliação da viabilidade celular por quantificação em câmara de Neubauer. A partir disso, induziu-se diferenciação neural em meio de cultura neurobasal (Gibco™), com células aderidas ao plástico ou suspensas em placas tratadas com agarose. Após sete e 14 dias em cultivo indutor, observou-se morfologia e perfil imunofenotípico utilizando citometria de fluxo e imunocitoquímica fluorescente. Aos 14 dias as células apresentaram alto grau de expressão para marcadores anti-nestina e anti-glial fibrillary acidic protein (anti-GFAP). Anteriormente, obteve-se ao 25º dia, média de 18x106 células viáveis indiferenciadas oriundas do tecido pulpar. Sugere-se que as células-tronco indiferenciadas da polpa dentária canina apresentem índices satisfatórios de diferenciação em células progenitoras neurais, aderidas ou suspensas em cultura. A polpa dentária dos dentes decíduos caninos, fornece células indiferenciadas viáveis em quantidade adequada.(AU)

The objective of this study was to verify the differentiation capacity of canine tooth pulp stem cells in neural progenitor cells as well as to quantify the attainment and viability during three culture passages. The cells were extracted from the dental pulp of two canine cadavers, with approximately ten months of age, which died due to automotive trauma. After three subcultures, cell viability evaluation was performed by Neubauer chamber quantification. Neural differentiation was induced in neurobasal culture medium (Gibco ™), with cells adhered to the plastic or suspended in agarose-treated plates. After seven and 14 days in inducer culture, morphology and immunophenotypic profile were observed using flow cytometry and fluorescent immunocytochemistry. At 14 days the cells had a high degree of expression for anti-nestin and anti-glial fibrillary acidic (anti-GFAP) markers. Previously, an average of 18x106 undifferentiated viable cells from the pulp tissue were obtained on the 25th day. It is suggested that the undifferentiated canine pulp stem cells present satisfactory differentiation indices in neural progenitor cells, adhered or suspended in culture. The dental pulp of deciduous canine teeth provides viable undifferentiated cells in adequate quantity.(AU)

The effect of intermittent fasting diet on the hippocampus of adult male mouse after inducing demyelination by ethidium bromide injection / Efecto de la dieta de ayuno intermitente en el hipocampo de ratón macho adulto después de inducir la desmielinización por inyección de bromuro de etidio

Intermittent fasting diet (IF) as a restrictive regimen prevents neural degeneration and stimulates overexpression of various neurotropic factors in the hippocampus of animal models. This study evaluates the potential effect of the IF in the prevention of learning and memory dysfunction and improving the alterations in the number and volume of neurons in an ethidium bromide (EB) induced mouse model of demyelination.Mice were randomly assigned into N group (Normal Diet and normal saline injection), F group (IF and normal saline injection), EBN group (Normal Diet and EB injection), EBF group (IF and EB injection). The hidden platform test was carried out based on path length, escape latency and swim speeds of mice. Stereological studies were determined by the Cavalieri and the Optical Dissector technique. Maintenance of mice on the IF results in significantly decreased the body weight and biochemical parameters, increased total number of neurons and volume of the hippocampus, and improved learning and memory parameters of adult male mice. However, IF in EBF group did not show as excellently as F group. The EBF group displayed significantly spatial memory improvement than that in EBN group. There were no statistically significant differences between EBF and EBN groups in stereological and learning parameters, though the EBF group displayed faster escape latencies, and swam faster and shorter path lengths than the EBN group in these parameters. Therefore as a conclusion, The IF fairly improved some adverse effects of EB in experimental demyelination models.

La dieta de ayuno intermitente (AI) como régimen restrictivo, previene la degeneración neural y la estimación de la presencia de diversos factores neurotrópicos en el hipocampo de modelos animales. Este estudio evalúa el efecto potencial de la AI en la prevención del aprendizaje y la disfunción de la memoria y mejora las alteraciones en el número y el volumen de las neuronas en un modelo de desmielinización, en ratón, inducido con bromuro de etidio (BE). Los ratones se asignaron al azar en el grupo N (dieta normal e inyección salina normal), Grupo A (AI e inyección salina normal), Grupo BEN (dieta normal e inyección BE), Grupo EBF (inyección AI y BE). La prueba de la plataforma oculta se llevó a cabo en función de la longitud del trayecto, la latencia de escape y la velocidad de nado de los ratones. Los estudios estereológicos fueron determinados por la técnica de Cavalieri y la técnica del disector óptico. En el grupo AI disminuyeron significativamente el peso corporal de los ratones, los parámetros bioquímicos, el número total de neuronas y el volumen del hipocampo, y los parámetros de aprendizaje y la memoria de los ratones machos adultos. Sin embargo, el grupo AI en BEF no se mostró tan bien como el grupo A. El grupo EBF mostró una mejora en la memoria espacial significativamente mayor que la del grupo BEN. No hubo diferencias estadísticamente significativas entre los grupos A, BE y BEN en los parámetros estereológicos y de aprendizaje, aunque el grupo EBF mostró latencias de escape más rápidas, y nado en las rutas más rápidas y más cortas que el grupo BEN en estos parámetros. Por lo tanto, como conclusión, el grupo AI mejoró bastante algunos efectos adversos de la BE en los modelos de desmielinización experimental.