The impact of multiple sclerosis on the size and morphology of corpus callosum: an MRI-based retrospective study / Impacto de la esclerosis múltiple en el tamaño y la morfología del cuerpo calloso: un estudio retrospectivo basado en resonancia magnética

SUMMARY: The corpus callosum (CC) includes the majority of fibers linking the two brain hemispheres. Several cross sectional studies showed an association between callosal atrophy and malfunction and neurodegenerative diseases, which may play a role in their pathological manifestations. As a result, the accurate quantification of the corpus callosum is important to have normative values according to sex, age and ethnicity. The purpose of this study is to determine the size of CC in patients suffering from multiple sclerosis, and compare it to CC size in healthyindividuals. Midsagittal size of CC were recorded prospectively from 404 routine MR brain examinations in normal individuals. The internal skull surface was measured to calculate CC/ internal skull surface ratio. Two groups of patients were studied: 200 (100 male /100 female) healthy individuals and 204 (101 males/103 females) with multiple sclerosis (MS). Mean surface area of CC in controls was 6.58±1.04 cm2 and there was no significant difference between males and females (P< 0.627). CC/ internal skull surface ratio was 4.44±0.77 %. MS patients showed a significant decrease in CC size compared to normal controls. Using MR imaging, we measured the mean sizes of the various portions of the CC in normal individuals, in addition to MS patients; these values may provide a useful basis to determine changes occurring in CC structures.

El cuerpo calloso (CC) incluye la mayoría de las fibras que unen los dos hemisferios cerebrales. Varios estudios transversales mostraron una asociación entre la atrofia y el mal funcionamiento calloso y las enfermedades neurodegenerativas, lo que puede desempeñar un papel en sus manifestaciones patológicas. En consecuencia, la cuantificación precisa del cuerpo calloso es importante para tener valores normativos según sexo, edad y etnia. El propósito de este estudio fue determinar el tamaño de CC en pacientes que padecen esclerosis múltiple y compararlo con el tamaño de CC en individuos sanos. El tamaño sagital medio del CC se registró prospectivamente a partir de 404 exámenes cerebrales de RM de rutina en individuos normales. Se midió la superficie interna del cráneo para calcular la relación CC/superficie interna del cráneo. Se estudiaron dos grupos de pacientes: 200 (100 hombres/100 mujeres) sanos y 204 (101 hombres/103 mujeres) con esclerosis múltiple (EM). El área superficial media de CC en los controles fue de 6,58±1,04 cm2 y no hubo diferencia significativa entre hombres y mujeres (P< 0,627). La relación CC/superficie interna del cráneo fue de 4,44±0,77 %. Los pacientes con EM mostraron una disminución significativa en el tamaño de CC en comparación con los controles normales. Usando imágenes de RM, medimos los tamaños medios de las diversas porciones del CC en individuos normales, además de pacientes con EM; estos valores pueden proporcionar una base útil para determinar los cambios que ocurren en las estructuras CC.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Regional brain atrophy is related to social cognition impairment in multiple sclerosis / La atrofia cerebral regional se relaciona con el deterioro de la cognición social en sclerosis múltiple

ABSTRACT Background: Multiple sclerosis exhibits specific neuropathological phenomena driving to both global and regional brain atrophy. At the clinical level, the disease is related to functional decline in cognitive domains as the working memory, processing speed, and verbal fluency. However, the compromise of social-cognitive abilities has concentrated some interest in recent years despite the available evidence suggesting the risk of disorganization in social life. Recent studies have used the MiniSEA test to assess the compromise of social cognition and have found relevant relationships with memory and executive functions, as well as with the level of global and regional brain atrophy. Objective: The present article aimed to identify structural changes related to socio-cognitive performance in a sample of patients with relapsing-remitting multiple sclerosis. Methods: 68 relapsing-remitting multiple sclerosis Chilean patients and 50 healthy control subjects underwent MRI scans and neuropsychological evaluation including social-cognition tasks. Total brain, white matter, and gray matter volumes were estimated. Also, voxel-based morphometry was applied to evaluate regional structural changes. Results: Patients exhibited lower scores in all neuropsychological tests. Social cognition exhibited a significant decrease in this group mostly related to the declining social perception. Normalized brain volume and white matter volume were significantly decreased when compared to healthy subjects. The regional brain atrophy analysis showed that changes in the insular cortex and medial frontal cortices are significantly related to the variability of social-cognitive performance among patients. Conclusions: In the present study, social cognition was only correlated with the deterioration of verbal fluency, despite the fact that previous studies have reported its link with memory and executive functions. The identification of specific structural correlates supports the comprehension of this phenomenon as an independent source of cognitive disability in these patients.

RESUMEN Antecedentes: La esclerosis múltiple presenta fenómenos neuropatológicos específicos que conducen a la atrofia cerebral global y regional. A nivel clínico, la enfermedad está relacionada con el deterioro funcional de los dominios cognitivos como la memoria de trabajo, la velocidad de procesamiento y la fluidez verbal. Sin embargo, el compromiso de las habilidades socio-cognitivas ha concentrado cierto interés en los últimos años debido a la evidencia disponible que sugiere el riesgo de desorganización en la vida social. Estudios recientes han utilizado la prueba MiniSEA para evaluar el compromiso de la cognición social y han encontrado relaciones relevantes con la memoria y funciones ejecutiva, así como con el nivel de atrofia cerebral global y regional. Objetivo: El presente artículo tiene como objetivo identificar cambios estructurales relacionados con el rendimiento sociocognitivo en una muestra de pacientes con esclerosis múltiple recurrente-remitente. Métodos: 68 pacientes Chilenos con esclerosis múltiple recurrente-remitente y 50 sujetos de control sanos se sometieron a resonancias magnéticas y evaluación neuropsicológica, incluidas las tareas de cognición social. Se estimaron los volúmenes cerebrales totales, de materia blanca y materia gris. Además, se aplicó la morfometría basada en vóxel para evaluar los cambios estructurales regionales. Resultados: Los pacientes muestran puntuaciones más bajas en todas las pruebas neuropsicológicas. La cognición social exhibe una disminución significativa en este grupo principalmente relacionada con la disminución de la percepción social. El volumen normalizado del cerebro y el volumen de la materia blanca disminuyeron significativamente en comparación con los sujetos sanos. El análisis regional de atrofia cerebral mostró que los cambios en la corteza insular y la corteza frontal medial están significativamente relacionados con la variabilidad del rendimiento sociocognitivo entre los pacientes. Conclusiones: En el presente estudio, la cognición social sólo se correlacionó con el deterioro de la fluencia verbal, a pesar de que estudios previos han reportado su vinculación con la memoria y funciones ejecutivas. La identificación de correlatos estructurales específicos apoya la comprensión de este fenómeno como una fuente independiente de discapacidad cognitiva en estos pacientes.

Prevalência do diagnóstico de enfermagem Mobilidade Física Prejudicada em pessoas com esclerose múltipla / Prevalence of nursing diagnosis Impaired Physical Mobility in people with multiple sclerosis / Prevalencia del diagnóstico de enfermería Movilidad Física Deteriorada en personas con esclerosis múltiple

Objetivo: identificar a prevalência do diagnóstico de enfermagem Mobilidade Física Prejudicada, suas características definidoras e fatores relacionados em pessoas com Esclerose múltipla e verificar a associação entre ambos e suas razões de prevalência. Métodos: estudo transversal com 113 pacientes em um hospital da região Nordeste do Brasil. Para a análise dos dados utilizou-se os testes de qui-quadrado de Pearson e exato de Fisher, sendo calculadas também as razões de prevalência. Resultados: o diagnóstico esteve presente em 89% da amostra e as características e fatores que apresentaram associação foram: alterações na marcha; instabilidade postural; movimentos descoordenados; redução nas habilidades motoras finas e grossas; depressão; força muscular diminuída e prejuízo músculo esquelético. Conclusão: o diagnóstico apresentou-se com elevada frequência na amostra, o que permite identificar as necessidades de intervenções que diz respeito à capacidade funcional do indivíduo, potencializando seu rendimento funcional e pessoal, através do planejamento do cuidado e da assistência qualificada

Objective: to identify the prevalence of the nursing diagnosis Impaired Physical Mobility, its defining characteristics and related factors in people with multiple sclerosis, and to verify the association between both and their prevalence ratios. Methods: cross-sectional study, with 113 patients in a hospital in the Northeast region of Brazil. Pearson's chi-square test and Fisher's exact test were used to perform data analysis, and the prevalence ratios were calculated. Results: the diagnosis was present in 89% of the sample and the characteristics and factors that presented association were: changes in gait; postural instability; uncoordinated movements; reduction in fine and gross motor skills; depression; decreased muscle strength and skeletal muscle injury. Conclusion: the diagnosis was presented with high frequency in the sample, which allows identifying the needs of interventions that relate to the functional capacity of the individual, enhancing their functional and personal income through the planning of care and qualified care.

Objetivo: identificar la prevalencia del diagnóstico de enfermería Movilidad Física Deteriorada, sus características definitorias y factores relacionados en personas con esclerosis múltiple, y verificar la asociación entre ambos y sus razones de prevalencia. Métodos: estudio transversal, con 113 pacientes en un hospital de la región noreste de Brasil. La prueba de chi-cuadrado de Pearson y la prueba exacta de Fisher se usaron para realizar el análisis de datos, y se calcularon las razones de prevalencia. Resultados: el diagnóstico estuvo presente en el 89% de la muestra y las características y factores que presentaron asociación fueron: cambios en la marcha; inestabilidad postural; movimientos descoordinados; reducción de las habilidades motoras fina y gruesa; depresión; disminución de la fuerza muscular y lesión del esqueleto muscular. Conclusión: el diagnóstico se presentó con alta frecuencia en la muestra, lo que permite identificar las necesidades de las intervenciones que se relacionan con la capacidad funcional del individuo, mejorando sus ingresos funcionales y personales a través de la planificación de la atención y la atención calificada.

Critical analysis on the present methods for brain volume measurements in multiple sclerosis / Análise crítica dos métodos atuais para medidas de volume cerebral em esclerose múltipla

ABSTRACT Objective The treatment of multiple sclerosis (MS) has quickly evolved from a time when controlling clinical relapses would suffice, to the present day, when complete disease control is expected. Measurement of brain volume is still at an early stage to be indicative of therapeutic decisions in MS. Methods This paper provides a critical review of potential biases and artifacts in brain measurement in the follow-up of patients with MS. Results Clinical conditions (such as hydration or ovulation), time of the day, type of magnetic resonance machine (manufacturer and potency), brain volume artifacts and different platforms for volumetric assessment of the brain can induce variations that exceed the acceptable physiological rate of annual loss of brain volume. Conclusion Although potentially extremely valuable, brain volume measurement still has to be regarded with caution in MS.

RESUMO Objetivo O tratamento da esclerose múltipla (EM) evoluiu rapidamente de um tempo onde o controle clínico dos surtos era suficiente para o momento atual, quando se almeja o completo controle da doença. Medidas de volume cerebral ainda estão em fases iniciais para utilização nas decisões terapêuticas na EM. Métodos Este artigo fornece uma revisão crítica de potenciais vieses e artefatos na volumetria cerebral utilizada no seguimento de pacientes com EM. Resultados Condições clínicas (como hidratação ou ovulação), hora do dia, tipo de máquina de ressonância magnética (fabricante e força do campo) artefatos de volume e diferentes plataformas de avaliação volumétrica cerebral podem induzir variações que excedem a taxa aceitável de perda anual fisiológica do volume cerebral. Conclusão Embora seja potencialmente de grande valor, a medida de volume cerebral ainda deve ser vista com cautela na EM.

Benign multiple sclerosis: aspects of cognition and neuroimaging / A esclerose múltipla benigna: aspectos cognitivos e de neuroimagem

ABSTRACT The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment, despite the apparent preservation of motor function. The objective of this study was to review and analyze a number of publications that discuss the general aspects of this disease form, such as the definition criteria, prevalence, and clinical and neuroimaging markers. A systematic review of published data on BMS up to October 2015 was performed. Thirty-one published articles were analyzed. The estimated frequency of BMS varied between 6% and 73%. Cognitive impairment was recognized as affecting 17% to 47% of the subjects and presented significant correlation with neuroimaging, such as brain atrophy, increased lesion volume in T2 magnetic resonance assay, and regional grey matter atrophy. The current criteria overestimated the frequency of BMS and, for that reason, this highlights the importance of validating the diagnostic methods practiced.

RESUMO A existência real de uma forma benigna da esclerose múltipla (EMB) é um tema controverso. Ampliar o número de publicações que abordam os aspectos gerais do subtipo da doença, tais como os critérios de definição utilizados, análise de prevalência e da presença de marcadores clínicos e de neuroimagem. Foi realizada uma revisão sistemática dos dados publicados até outubro de 2015, relativa à EMB. Os dados encontrados foram dicotomizados em gráficos e, posteriormente, analisados. Foram analisados 31 artigos publicados. A frequência estimada EMB oscila entre 6% a 73%. O comprometimento cognitivo foi reconhecido em 17–47% dos sujeitos, apresentando correlação significativa com os aspectos de neuroimagem, como a atrofia cerebral global, aumento do volume lesional em T2 e atrofia regional da substância cinzenta. Os critérios atualmente utilizados superestimam a freqüência de EMB, e, por essa razão, destaca-se a importância da validação dos métodos de diagnóstico praticados.

Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy

Multiple sclerosis [MS] is a chronic inflammatory disease characterized by central nervous system [CNS] lesions that can lead to severe physical or cognitive disability as well as neurological defects. Although the etiology and pathogenesis of MS remains unclear, the present documents illustrate that the cause of MS is multifactorial and include genetic predisposition together with environmental factors such as exposure to infectious agents, vitamin deficiencies, and smoking. These agents are able to trigger a cascade of events in the immune system which lead to neuronal cell death accompanied by nerve demyelination and neuronal dysfunction. Conventional therapies for MS are based on the use of anti-inflammatory and immunomodulatory drugs, but these treatments are not able to stop the destruction of nerve tissue. Thus, other strategies such as stem cell transplantation have been proposed for the treatment of MS. Overall, it is important that neurologists be aware of current information regarding the pathogenesis, etiology, diagnostic criteria, and treatment of MS. Thus, this issue has been discussed according to recent available information

Evaluación de la intensidad de señal en núcleo dentado, puente, globus pallidus y tálamo en pacientes con esclerosis múltiple: valoración de la retención de gadolinio / Evaluation of signal intensity in dentate nucleus, pons, globus pallidus and thalamus in patients with multiple sclerosis: assessment of gadolinium retention

Introduction: Recently, some studies have reported accumulation of gadolinium in the brain of patients with multiple administrations of gadolinium-based contrast. Patients with multiple sclerosis are subjected to multiple contrasting resonances and could become a population at risk. Objective: To determine whether repeated intravenous exposure to gadolinium is associated with more intensity in the thalamus, dentate nucleus, pons and the globus pallidus. Methods: A retrospective study of 60 patients with MS who had undergone two or more contrasted MRs between 2007 and 2015, was performed. The ratios calculated were: dentate nuclei-to-pons (DNP), thalamus-to-pons (TP), caudate nuclei-to-pons (CNP), globus pallidus-to-thalamus (GPT), globus pallidus-to-pons (GPP), by reviewing simple T1 axial sequences. Relative changes were calculated and compared with the number of contrasted MRs. The concordance between observers and the intraclass correlation coefficient was evaluated. Results: There was no evidence of increased signal intensity in T1 sequences (DNP 0.524, GPT 0.466, GPP 0.684, TP 0.771, CNP 0.352). As there were no differences, the Spearman coefficient showed no correlation between relative changes and the number of resonances performed. Inter-observer agreement was almost perfect (0.982) for all structures. Conclusion: Our study did not find a statistically significant increase in the T1 signal intensity in patients with multiple sclerosis. However, there are factors to consider, such as the type of gadolinium and the time lapse between administrations.

Introducción: Recientemente, algunos estudios han informado acumulación de gadolinio en el cerebro de los pacientes con múltiples administraciones de contraste basado en gadolinio. Los pacientes con esclerosis múltiple son sometidos a múltiples resonancias contrastadas y podrían convertirse en una población de riesgo. Objetivo: Determinar si la exposición repetida por vía intravenosa a gadolino se asocia con mayor intensidad en el tálamo, el dentado, el puente y el globo pálido. Métodos: Se realizó un estudio retrospectivo núcleo de 60 pacientes con EM que habían sido sometidos a dos o más RM contrastadas entre 2007 - 2015. Se calcularon las razones núcleo dentado - puente (DNP), tálamo-puente (TP), núcleo caudado- puente (CNP), globus pallidus - tálamo (GPT), globus pallidos - puente (GPP), revisando secuencias T1 axiales simples. Se calcularon los cambios relativos y se compararon con el número de RM contrastadas. Se evaluó la concordancia entre observadores con el coeficiente de correlación intraclase. Resultados: No hubo evidencia de aumento de la intensidad de la señal en secuencias T1 (DNP 0,524, 0,446 GPT, GPP 0,684, 0,771 PT, CNP 0.352). Al no existir diferencias, el coeficiente de Spearman no mostró correlación entre los cambios relativos y el número de resonancias realizadas. La concordancia interobservador fue casi perfecta (0.982) para todas las estructuras. Conclusión: Nuestro estudio no encontró un aumento estadísticamente significativo en la intensidad de la señal T1 en pacientes con esclerosis múltiple. Sin embargo, hay factores a considerar, tales como el tipo de gadolinio y el lapso de tiempo entre las administraciones.

Balo's concentric lesions with concurrent features of Schilder's disease in relapsing multiple sclerosis: neuropathological findings

Atypical inflammatory demyelinating syndromes are rare neurological diseases that differ from multiple sclerosis (MS), owing to unusual clinicoradiological and pathological findings, and poor responses to treatment. The distinction between them and the criteria for their diagnoses are poorly defined due to the lack of advanced research studies. Balo's concentric sclerosis (BCS) and Schilder's disease (SD) are two of these syndromes and can present as monophasic or in association with chronic MS. Both variants are difficult to distinguish when they present in acute stages. We describe an autopsy case of middle-aged female with a chronic history of MS newly relapsed with atypical demyelinating lesions, which showed concurrent features of BCS and SD. We also describe the neuropathological findings, and discuss the overlapping features between these two variants.

Disability and progression in Afro-descendant patients with multiple sclerosis / Incapacidade e progressão em pacientes afrodescendentes com esclerose múltipla

ABSTRACT Multiple sclerosis (MS) prevalence is higher in Caucasian (CA) populations, narrowing the analysis of the impact of Afro-descendant (AD) populations in disease outcomes. Even so, recent studies observed that AD patients have a more severe course. The main objective of this study is to confirm and discuss, through a systematic review, that being AD is a risk factor for disability accumulation and/or severe progression in patients with MS. A systematic review of published data in the last eleven years was performed, which evaluated clinical aspects and long term disability in patients with MS. Fourteen studies were included. Of these fourteen articles, thirteen observed a relationship between ancestry and poorer outcome of MS. African ancestry is a condition inherent in the patient and should be considered as an initial clinical characteristic affecting prognosis, and influencing which therapeutic decision to make in initial phases.

RESUMO A prevalência da esclerose múltipla (EM) é maior em populações caucasianas (CA), o que limita a análise do impacto da Afrodescendencia (AD) nos desfechos da doença. Apesar disto, estudos recentes observaram que a AD determina um curso clínico mais severo. O principal objetivo deste estudo é confirmar e discutir, por meio de uma revisão sistemática, que a afrodescendência é um fator de risco para acúmulo de incapacidade e/ou progressão mais severa em pacientes com EM. Foi realizada uma revisão sistemática de trabalhos publicados nos últimos onze anos que avaliaram aspectos clínicos e incapacidade a longo prazo em pacientes com EM. Quatorze artigos foram incluídos. Entre eles, treze observaram uma relação entre AD e pior prognóstico da EM. AD é uma condição inerente ao paciente e deveria ser considerada, assim como as características clínicas relacionadas ao prognóstico, influenciando a decisão terapêutica a ser tomada nas fases iniciais da doença.

Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact / Atrofia cerebral en esclerosis múltiple: impacto clínico, cognitivo y terapéutico

ABSTRACT Multiple sclerosis (MS) was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

RESUMEN La esclerosis múltiple (EM) fue considerada históricamente como una enfermedad inflamatoria de la sustancia blanca. Hoy en día hay mucha evidencia que apoya, además, el compromiso de la sustancia gris y los mecanismos neurodegenerativos, que son al menos parcialmente independientes de la inflamación. La atrofia de la sustancia gris se desarrolla más rápido que la atrofia de la sustancia blanca y predomina en las etapas iniciales de la enfermedad. El mecanismo neurodegenerativo, crea un daño permanente y se correlacionaría con la discapacidad física y cognitiva del paciente. En esta revisión, se describe la evidencia disponible actual con respecto a la atrofia cerebral y su consecuencia en los pacientes con EM.

Diffusion tensor magnetic resonance imaging may show abnormalities in the normal-appearing cervical spinal cord from patients with multiple sclerosis / Exames de imagem por tensor de difusao podem mostrar alteracoes na coluna cervical aparentemente normal em pacientes com esclerose multipla

Objective This study aims to evaluate “in vivo” the integrity of the normal-appearing spinal cord (NASC) in patients with multiple sclerosis (MS) compared to controls, using diffusion tensor MR imaging. Methods We studied 32 patients with MS and 17 without any neurologic disorder. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were calculated within regions of interest at C2 and C7 levels in the four columns of the spinal cord. Results At C2, FA value was decreased in MS patients. Besides, RD value was higher in MS than in controls. At C7, MD values were increased in MS. Conclusion The NASC in the right column of the cervical spinal cord showed abnormal FA, RD and MD values, which is possibly related to demyelination, since the FA abnormality was related to the RD and not to the AD. .

Objetivo Este estudo avalia “in vivo” a integridade da medula espinhal cervical aparentemente normal (MEAN) em pacientes com esclerose múltipla (EM) comparados aos controles, usando a imagem por tensor de difusão. Métodos Foram selecionados 32 pacientes com EM e 17 controles. Foram calculadas fração anisotrópica (FA), difusão axial (DA), difusão radial (DR) e difusibilidade média (DM) dentro das regiões de interesse nos níveis C2 e C7 nas quatro colunas da medula espinhal. Resultados Em C2, o valor de FA foi reduzido em pacientes com EM. Além disso, o valor da DR se mostrou mais elevado na EM do que nos controles. Em C7, os valores de MD foram maiores na EM. Conclusão A MEAN na coluna direita da medula cervical mostrou valores alterados de FA, RD e MD, possivelmente relacionados à desmielinização, uma vez que a alteração de FA está relacionada à DR e não à DA. .

Uso de volumetría y carga lesional en el seguimiento de pacientes con esclerosis múltiple: experiencia local y revisión de la literatura / Use of lesion volumes and loads for monitoring patients with multiple sclerosis: local experience and literature review

Multiple sclerosis (MS) is a common demyelinating disease that involves the central nervous system causing focal lesions in the brain and spinal cord causing diverse neurological development deficits, many of them severe and irreversible, affecting and invaliding a large percentage of young productive-aged patients. MRI exams have improved diagnostic capability compared to computed tomography, but in this decade the development of new magnets, coils and software have allowed the development of quantitative neuroradiology which achieves the evaluation of parameters such as total brain volume, of each of its structures, as well as semi-automated or automated counting of the lesion load, allowing better monitoring of each individual patient in relation to a particular event such as a new neurological deficit in an outbreak of the disease, a previously undetected cognitive impairment or in related to a given treatment. We will show our local experience using the FreeSurfer software in our habitual practice, as well as other post-processing software, this being the first experience of its use in multiple sclerosis published in our country.

La esclerosis múltiple (EM) es una frecuente enfermedad desmielinizante que afecta el sistema nervioso central produciendo lesiones focales a nivel cerebral y medular que condicionan diversos déficit neurológicos evolutivos, muchos de ellos severos e irreversibles, afectando e invalidando un gran porcentaje de pacientes jóvenes en edad productiva. El estudio con resonancia magnética mejoró la capacidad diagnóstica respecto a la tomografía computada, pero en esta década el desarrollo de nuevos magnetos, bobinas y software han permitido desarrollar la neurorradiología cuantitativa que logra evaluar parámetros como el volumen cerebral global, de cada una de sus estructuras así como el recuento semi o automatizado de la carga lesional, lo que permite el mejor seguimiento de cada paciente individual en relación a un evento determinado como un nuevo déficit neurológico dentro de un brote de la enfermedad, un deterioro cognitivo no detectado previamente o en relación a un tratamiento determinado. Mostraremos nuestra experiencia local utilizando el software freesurfer en nuestra práctica habitual, así como otro software de postproceso, siendo la primera experiencia de su uso en esclerosis múltiple publicada en nuestro país.

O legado dos exames post-mortem para o estudo da relação entre forma clínica e substrato patológico na esclerose múltipla. Uma revisão sobre a anatomopatologia da doença / The legacy of post-mortem examination for the study of the relation between the clinical form and the pathological substrate in multiple sclerosis. A review on the anatomopathology of the disease

Após a dissecção de cérebro de uma paciente em 1868, Charcot definiu uma evidência histopatológica mais assertiva para a esclerose múltipla (EM): "sclerose en plaque". Entretanto, mais de um século depois, poucos estudos examinando o substrato patológico específico de fenótipos clínicos diferentes da EM são encontrados na literatura. O objetivo deste estudo é uma revisão da literatura sobre achados post-mortem (autopsia, exame histopatológico e técnicas imuno-histoquímicas) em pacientes com EM. Utilizando os termos "autopsy", "necropsy", "pathology", "post-mortem" e "multiple sclerosis", a pesquisa foi desenvolvida sobre a literatura e recursos presentes no MEDLINE no período janeiro 1990 a agosto 2012. Artigos relevantes baseados em análise macro/microscópica das lesões da EM e o uso de técnicas imuno-histoquímicas (marcadores imunológicos e neurobiológicos) foram revistos. Tratados de patologia cirúrgica e neuropatologia em suas últimas edições foram também consultados. Além dos estudos no início dos anos 2000 que identificaram padrões diferentes de desmielinização em casos de autópsia, considerando a perda de mielina, a geografia e extensão das lesões, a destruição dos oligodendrócitos e a evidência do dano imunopatológico, estudos mais detalhados e baseados em aspectos anatomopatológicos e implicações patogênicas são raros. A maioria destes poucos e específicos estudos reportam que as lesões da EM tipicamente aparecem na substância branca, mas são também abundantes na substância cinza, heterogeneidade de lesões inter-paciente e homogeneidade intra-paciente, graus diferentes para perda de mielina e estágios de atividade, foco de atividade inflamatória que origina gliose fibrilar, distrofia de oligodendrócitos e densidade axonal central diminuída. Desmielinização é um importante indicador de progressão clínica e a remielinização pode ser incompleta ou decresce com a cronicidade da doença. A importância das lesões na substância branca de aparência normal e na substância cinzenta tem sido cada vez mais reconhecida em recentes estudos com técnicas imuno-histoquímicas. Não há ainda um consenso se as diferenças entre as formas clínicas são fundamentalmente quantitativas ou qualitativas em relação ao substrato patológico e mais estudos sobre autopsias utilizando exame histopatológico e técnicas modernas de imuno-histoquímica são necessários para dirimir esta questão. Um melhor entendimento sobre a heterogeneidade das lesões da esclerose múltipla proporcionará o desenvolvimento de métodos terapêuticos mais direcionados e eficazes.

After dissection of a female brain in 1868, Charcot outlined a more assertive histopathological evidence of Multiple Sclerosis: "sclerose en plaque". However, more than a century later, very few studies examining the specific underlying pathology of a defined MS clinical phenotype are found in literature. The purpose of this study is to provide a literature review of post-mortem findings (histopathology and immunohistochemical techniques) in MS patients. The literature in MEDLINE was searched from January 1990 to August 2012 using the terms "autopsy", "necropsy", "pathology", "postmortem" and "multiple sclerosis". Relevant papers based on macroscopic/microscopic analysis of the MS lesions and the use of broad spectrum of immunological and neurobiological markers (immunohistochemistry) were reviewed. Textbooks of Surgical Pathology and Neuropathology in latest editions were also consulted.Besides the studies in the early 2000s that identified different patterns of demyelination in autopsy cases, consider the myelin impairment, the geography and extension of lesions, the oligodendrocyte destruction and the evidence of immunopathological damage, more detailed studies based on anatomopathological aspects and pathogenic implications are rare. Most of these few specific studies reported that MS lesions typically appear in the white matter, but are also abundant in grey matter, inter-patient lesions heterogeneity with intra-patient homogeneity, different degree of myelin loss and stage of activity, focus of inflammatory activity that gives way to fibrillary gliosis, oligodendrocyte dystrophy and decreased central axonal density. Demyelination is an important pathological correlate of clinical progression and remyelination could be incomplete or decreases with disease chronicity. The importance of healthy-appearing white matter damage and grey matter demyelination has been increasingly recognized in recent studies using immunohistochemical techniques. There is still no consensus on whether the differences between the clinical forms of MS are fundamentally quantitative or qualitative in relation to the pathological substrate, and more detailed studies with data on autopsies is required to resolve this issue. A better understanding of the pathogenetic heterogeneity of MS lesions will lead the development of more effective treatment methods.

Tratamiento de la esclerosis múltipple: la era del natalizumab / Treatment of Multiple Sclerosis: the era of Natalizumab

La esclerosis múltiple es una enfermedad inflamatoria crónica y autoinmune del sistema nervioso central. Produce un variado abanico de síntomas que suelen llevar a la incapacidad del paciente que la padece. Para su tratamiento se ha empleado una amplia gama de drogas, todas destinadas a contrarrestar la respuesta inflamatoria. Entre ellas se destacan los corticoides, acetato de glatiramer, interferón beta, entre otras. Ninguna de ellas trata la causa primaria de la enfermedad pero pueden aminorar su progresión y retrasar la aparición de nuevos síntomas. Sin embargo, no son capaces de lograr el control de la enfermedad sin que sus efectos adversos o sus pautas y formas de administración se interpongan en la terpéutica. La introducción del natalizumab en el tratmiento de la esclerosis múltiple constituye un avance sin precedentes. Esta droga controla el progreso de la enfermedad como ninguna de sus antecesoras con una muy baja frecuencia de administración y una gran aceptación del tratamiento por parte de los pacientes. Sin embargo, el riesgo de aparición de leucoencefalopatía multifocal progresiva durante el tratamiento con natalizumab hace que su terapéutica requiera un enfoque multidisciplinario de profesionales de la salud

Multple Sclerosis is a chronic, inflammatory and autoimmune disease of the central nervous system. It causes a wide range of symptoms which may lead to the impairment of the patient that suffers from it. Numerous drugs have been used for its treatment to counteract the inflammatory response. Among these drugs are corticosteriods, glatiramer acetate and Interferon beta. Although none of them treat the primary cause of the disease, they may slow down its progression and delay the appearance of new symptoms. In addition, they are not capable of achieving the control of the disease without their adverse effects, guidelines, or ways of administration interposing in the therapeutic treatment. The introduction of natalizumab in the treatment of multiple sclerosis is an unprecedented advance. This drug controls the progression of the disease in a way which none of the former drugs has achieved, with a very low frequency of administration and a high treatment acceptance by the patients. However, the risk of developing progressive multifocal leukoencephalopathy during treatmente with natalizumab makes its therapeutic treatment require a multidisciplinary approach on the part of healthcare professionals