Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

White matter volume is decreased in bipolar disorder at early and late stages / O volume da substância branca está reduzido tanto nos estágios iniciais quanto nos estágios avançados do transtorno bipolar

Abstract Introduction: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. Objective: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Methods: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). Results: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Conclusion: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Resumo Introdução: O transtorno do humor bipolar (THB) é uma condição debilitante que afeta aproximadamente 1,3% das pessoas em todo o mundo, embora alguns estudos relatem uma prevalência acumulada de até 3,9% e de 4-6% em adultos quando os critérios diagnósticos mais abrangentes são aplicados. Objetivo: Comparar as diferenças nos volumes totais de substância branca (SB), corpo caloso (CC) e volume total de substância cinzenta (SC) em pacientes com THB tipo I em estágios iniciais e tardios em comparação com controles. Métodos: Cinquenta e cinco sujeitos foram incluídos neste protocolo de estudo. O desenho de caso com duplo controle incluiu 14 pacientes com THB em estágio inicial; 15 pacientes com THB em fase tardia; e seus respectivos controles correspondentes (14 e 12 sujeitos). Resultados: Os volumes do CC e total de SB foram significativamente menores nos pacientes com THB nos estágios iniciais e tardios vs. controles. Não houve diferença para o volume total de SC no grupo em estágio inicial, mas em pacientes em fase tardia o volume total de SC foi significativamente menor do que nos controles. A redução do volume total de SC em pacientes em fase tardia está de acordo com a teoria da neuroprogressão do THB. A redução dos volumes de SB em SB total e no CC em fases precoces e tardias suporta a possibilidade de que um processo de desmielinização precoce poderia ocorrer subjacente à manifestação clínica de THB. Conclusão: Nossos achados podem direcionar a investigação de anormalidades da SB em populações de alto risco para o desenvolvimento de THB, talvez como biomarcadores precoces antes da síndrome aberta.

Dementia and behavioral disorders in progressive multifocal leukoencephalopathy (PML) ­ case report / Demência e alterações comportamentais na leucoencefalopatia multifocal progressive (LEMP) ­ relato de caso

Psychiatric disturbances in Progressive Multifocal Leukoencephalopathy (PML) are rarely adressed and its study can offer insights into the neurobiology of psychosis. The authors report a case of male patient, 42 years old, HIV positive, with PML and psychotic symptoms. The present case shows the need for regular neurological and neuropsychological evaluations of HIV positive patients and the importance of studying diseases that cause lesions in the white matter,such as PML, to elucidate the neurobiology of psychosis.(AU)

Os distúrbios psiquiátricos na Leucoencefalopatia Multifocal Progressiva (LEMP) raramente são abordados e seu estudo pode oferecer insights sobre a neurobiologia da psicose. Os autores relatam caso de paciente do sexo masculino, 42 anos, HIV positivo, com LEMP e sintomas psicóticos. O caso apresentado evidencia a necessidade de realização regular de avaliações neurológicas e neuropsicológicas de pacientes HIV positivos e a importância de se estudar doenças que causam lesões na substância branca, como a LEMP, para elucidar a neurobiologia da psicose.(AU)

Integrity of white matter structure is related to episodic memory performance in the low-educated elderly / Memória e integridade da substância branca em idosos de baixa escolaridade

ABSTRACT The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. Methods: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. Results: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. Conclusions: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

RESUMO Idosos de baixo nível educacional representam uma população vulnerável em que o estudo do papel da integridade da substância branca na memória pode revelar como essa declina no envelhecimento. Métodos: Trinta e um indivíduos (22 mulheres), sendo 23 cognitivamente saudáveis, oito com comprometimento cognitivo não demência, 80,4 ± 3,8 anos de idade e 2,2 ± 1,9 anos de escolaridade, foram submetidos à RM com imagem de tensor de difusão, cujos parâmetros foram correlacionados com a Bateria Cognitiva Breve (BCSB) e o Teste Auditivo Verbal de Rey (RAVLT). Resultados: A evocação tardia da BCSB correlacionou-se com fascículos de conexão frontotemporoparietal, fascículo longitudinal superior direito e cíngulo parte hipocampal bilateral, sendo que esse último também correlacionou com o RAVLT (aprendizado e evocação tardia). Conclusão: Apesar de preliminar, nosso estudo sugere que a integridade da substância branca parece ser importante para a memória em idosos de baixa escolaridade, achado que revela alvo potencial na prevenção do seu declínio em populações vulneráveis.

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile / Utilidad del tensor de difusión en esclerosis lateral amiotrofica: potencial biomarcador y asociación con el perfil cognitivo

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

RESUMEN El objetivo del presente estudio preliminar fue correlacionar alteraciones del Tensor de Difusión (TD) con el perfil cognitivo de pacientes con Esclerosis Lateral Amiotrofica (ELA). Metodos Se realizó estudio casos-controles entre el 1 de Diciembre del 2012 hasta el 1 de Diciembre del 2014. Se registraron datos clínicos y demográficos. Se utilizó batería de tests neuropsicológicos adaptada a ELA. Se realizó RMN de cerebro con TD en todos los pacientes, la Fracción de Anisotropía (FA) se analizó en sustancia blanca, utilizando el programa Tract Based Spatial Statistics. Resultados Se incluyeron 24 pacientes con ELA (15 mujeres, edad media 66.9 + -2.3) y 13 controles sanos (4 mujeres, edad media 66.9 +-2). El TD mostró daño en sustancia blanca en los pacientes con ELA vs controles (p < 0.001). Discusión En nuestro estudio preliminar las alteraciones de sustancia blanca en TD se asociaron significativamente con alteraciones cognitivas en pacientes con ELA.

Comparison of Regional Gray Matter Atrophy, White Matter Alteration, and Glucose Metabolism as a Predictor of the Conversion to Alzheimer's Disease in Mild Cognitive Impairment

We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimer's disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period.

Gray and White Matter Degenerations in Subjective Memory Impairment: Comparisons with Normal Controls and Mild Cognitive Impairment

Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes.