RESUMO
Leukoaraiosis is a neuroimaging marker of small-vessel disease that is characterized by high signal intensity on fluid-attenuated inversion recovery MRI. There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities that characterize leukoaraiosis are actually present within regions of normal-appearing white matter, and that the underlying pathophysiology of white matter damage related to small-vessel disease involves blood-brain barrier damage. In this study, we aim to verify whether leukoaraiosis is associated with elevated signal intensity on fluid-attenuated inversion recovery imaging, a marker of brain tissue free-water accumulation, in normal-appearing white matter. We performed a cross-sectional study of adult patients admitted to our hospital with a diagnosis of acute ischaemic stroke or transient ischaemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, normal-appearing white matter was further segmented based on voxel distance from leukoaraiosis borders, resulting in five normal-appearing white matter strata at increasing voxel distances from leukoaraiosis. The relationship between mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter and leukoaraiosis volume was studied in a multivariable statistical analysis using linear mixed modelling, having normal-appearing white matter strata as a clustering variable. One hundred consecutive patients meeting inclusion and exclusion criteria were selected for analysis (53% female, mean age 68 years). Mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. In a multivariable analysis, the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter was positively associated with leukoaraiosis volume and age (B = 0.025 for each leukoaraiosis quartile increase; 95% confidence interval 0.019-0.030). This association was found similarly across normal-appearing white matter strata. Voxel maps of the mean normalized fluid-attenuated inversion recovery signal intensity on normal-appearing white matter showed an increase in signal intensity that was not adjacent to leukoaraiosis regions. Our results show that normal-appearing white matter exhibits subtle signal intensity changes on fluid-attenuated inversion recovery imaging that are related to leukoaraiosis burden. These results suggest that diffuse free-water accumulation is likely related to the aetiopathogenic processes underlying the development of white matter damage related to small-vessel disease.
RESUMO
INTRODUCTION: Among vascular risk factors we hypothesized that an increased prevalence of diabetes in Hispanics would be associated with greater white matter hyperintensity (WMH) volume, which may contribute to cognitive decline. METHODS: A total of 1318 participants (60% female; 49% Hispanic, 51% non-Hispanic White; age 66.2 ± 8.9 years) underwent clinical evaluation and brain magnetic resonance imaging (MRI). WMH volume associations were assessed with age, sex, and ethnicity and then with vascular risk factors in a selective regression model. RESULTS: WMH volume was greater with older age (P < .0001), Hispanic ethnicity (P = .02), and female sex (P = .049). WMH volume was best predicted by age, diastolic blood pressure, hypertension history, hemoglobin A1c (HbA1c), white blood cell count, and hematocrit (P < .01 for all). Elevated HbA1c was associated with greater WMH volume among Hispanics (parameter estimate 0.08 ± 0.02, P < .0001) but not non-Hispanic Whites (parameter estimate 0.02 ± 0.04, P = .5). DISCUSSION: WMH volume was greater in Hispanics, which may be partly explained by increased WMH volume related to elevated HbA1c among Hispanics but not non-Hispanic Whites.
RESUMO
The extensive white matter of the brain, which comprises about one half of its volume, is constituted by an intricate and interwoven assemble of nerve fibers. The WMH (leukoaraiosis) represent the most frequent ischemic type of lesion of SVD, affecting the white matter. These lesions may be apparent or normal appearing on neuroimaging. In both cases such lesions may interrupt the affected white matter fibers, with consequent disconnection syndromes, and atrophy of the denervated grey matter structures. These conditions affect the structural neural networks (connectome), with functional repercussion on the cognitive and behavioral domains.
A extensa substância branca do cérebro, que compreende cerca da metade do seu volume, é constituída por um intricado e entrelaçado conjunto de fibras nervosas. As HSB (hiperintensidades da substância branca) (leucoaraiose) representam o mais frequente tipo de lesão isquêmica da DPV (doença dos pequenos vasos) que afeta a substância branca. Essas lesões podem ser aparentes ou de aparência normal na neuroimagem. Em ambos os casos tais lesões podem interromper essas fibras da substância branca, com consequente síndromes por desconexão e atrofia de estruturas de substância cinzenta desnervadas. Essas condições afetam as redes neurais estruturais (conectoma), com repercussão funcional nos domínios cognitivo e do comportamento.
Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Substância Branca/fisiopatologia , Substância Branca/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Denervação , Leucoaraiose/patologiaRESUMO
OBJECTIVES: Leukoaraiosis is described as white matter lesions that are associated with cognitive dysfunction, neurodegenerative disorders, etc. Myelin depletion is a salient pathological feature of, and the loss of oligodendrocytes is one of the most robust alterations evident in, white matter degeneration. Recent studies have revealed that claudin proteins are aberrantly expressed in leukoaraiosis and regulate oligodendrocyte activity. However, the roles of claudin-1 and claudin-3 in oligodendrocytes and leukoaraiosis are still not well-defined. METHODS: Quantitative polymerase chain reaction was used to measure the expression of claudin-1 (CLDN1), claudin-3 (CLDN3), and myelinogenesis-related genes such as myelin basic protein (MBP), proteolipid protein (PLP), oligodendrocyte transcription factor 2 (OLIG2), and SRY-box transcription factor 10 (SOX10) in leukoaraiosis patients (n=122) and healthy controls (n=122). The expression of claudin-1 and claudin-3 was either ectopically silenced or augmented in Oli-neu oligodendrocytes, and colony formation, apoptosis, and migration assays were performed. Finally, the expression of myelin proteins was evaluated by western blotting. RESULTS: Our results revealed that in addition to SOX10, the expression levels of claudin-1, claudin-3, and myelinogenesis-related proteins were prominently downregulated in leukoaraiosis patients, compared to those in healthy controls. Furthermore, the growth and migration of Oli-neu cells were downregulated upon silencing claudin-1 or claudin-3. However, the overexpression of claudin-1 or claudin-3 resulted in the reduction of the degree of apoptosis in Oli-neu cells. In addition, claudin-1 and claudin-3 promoted the expression of MBP, OLIG2, PLP, and SOX10 at the translational level. CONCLUSION: Our data has demonstrated that the abnormal expression of claudin-1 and claudin-3 regulates the pathological progression of leukoaraiosis by governing the viability and myelination of oligodendrocytes. These findings provide novel insights into the regulatory mechanisms underlying the roles of claudin-1 and claudin-3 in leukoaraiosis.
Assuntos
Humanos , Leucoaraiose , Oligodendroglia , Claudina-1 , Claudina-3/genética , Bainha de MielinaRESUMO
BACKGROUND: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A). METHODS: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques. RESULTS: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one. CONCLUSION: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment.
Assuntos
Atividades Cotidianas , Cognição , Leucoaraiose/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Efeitos Psicossociais da Doença , Estudos Transversais , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Leucoaraiose/epidemiologia , Leucoaraiose/fisiopatologia , Leucoaraiose/psicologia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Fatores de TempoRESUMO
Introducción: El concepto de Leucoaraiosis, entidad relacionada con la enfermedad de pequeños vasos, hipertensión arterial y envejecimiento poblacional, surge a raíz de la introducción de nuevas modalidades de diagnóstico por imagen como la Tomografía Computarizada y la imagen por Resonancia Magnética. Objetivos: Describir los aspectos fisiopatológicos más importantes de la Leucoaraiosis y la importancia de las técnicas de imagen como la imagen por Resonancia Magnética en su diagnóstico. Material y Métodos: Se realizó una búsqueda bibliográfica automatizada en bases de datos MEDLINE (motor de búsqueda PubMed) a través de las palabras clave: Leucoaraiosis, enfermedad cerebral de pequeños vasos e imagen por Resonancia Magnética, basándonos en la selección y análisis crítico de publicaciones preferentemente emitidas en los últimos 5 años. Desarrollo: La Leucoaraiosis está caracterizada por cambios de la sustancia blanca. Múltiples han sido las hipótesis que sustentan la fisiopatología de la Leucoaraiosis: causa isquémica (la más defendida), disfunción endotelial, ruptura de la barrera hematoencefálica o combinación de ellas. No obstante, los cambios fisiopatológicos asociados a la Leucoaraiosis permanecen inciertos. Por otro lado, técnicas de imagen como la Resonancia Magnética logran profundizar en los diferentes hallazgos que caracterizan a la condición. Conclusiones: El envejecimiento poblacional asociado a la alta prevalencia de Leucoaraiosis unido a la mayor disponibilidad de técnicas de imagen neurodiagnóstica condiciona un mejor entendimiento de sus aspectos fisiopatológicos, los cuales aún son controvertidos.
Introduction: Leukoaraiosis is related to the small cerebral vessel disease and mainly associated with the aging of population and the high prevalence of hypertension. Computed tomography and magnetic resonance imaging pave the way to its apparition. Objectives: To describe the most importance physiopathologic aspects of leukoaraiosis and the relevance of imaging techniques as magnetic resonance imaging to diagnose it. Material and Methods: It was made a review through automatized data base MEDLINE (PubMed as search engine) using leukoaraiosis, cerebral small vessel disease and magnetic resonance imaging as descriptors. The review was based on the selection and critical analysis of publications, most appearing in the last five years. Development: Leukoaraiosis is characterized by changes in the periventricular white matter. The associated physiopathologic changes remain doubtful and not completely explained being the hypothesis centred in the chronic ischemia, bloodbrain barrier breakdown and endothelial damage or in their combination. On the other hand, new neuroradiologic techniques as magnetic resonance imaging appear to allow to deeply analyze the different imaging findings that support the diagnosis of the leukoaraiosis. Conclusions: Aging associated to high prevalence of leukoaraiosis as well as the availability of improved brain imaging techniques permit a better understanding of its physiopathologic aspects which are even controversial.
RESUMO
OBJECTIVE: Silent brain infarctions are the silent cerebrovascular events that are distinguished from symptomatic lacunar infarctions by their 'silence'; the origin of these infarctions is still unclear. This study analyzed the characteristics of silent and symptomatic lacunar infarctions and sought to explore the mechanism of this 'silence'. METHODS: In total, 156 patients with only silent brain infarctions, 90 with only symptomatic lacunar infarctions, 160 with both silent and symptomatic lacunar infarctions, and 115 without any infarctions were recruited. Vascular risk factors, leukoaraiosis, and vascular assessment results were compared. The National Institutes of Health Stroke Scale scores were compared between patients with only symptomatic lacunar infarctions and patients with two types of infarctions. The locations of all of the infarctions were evaluated. The evolution of the two types of infarctions was retrospectively studied by comparing the infarcts on the magnetic resonance images of 63 patients obtained at different times. RESULTS: The main risk factors for silent brain infarctions were hypertension, age, and advanced leukoaraiosis; the main factors for symptomatic lacunar infarctions were hypertension, atrial fibrillation, and atherosclerosis of relevant arteries. The neurological deficits of patients with only symptomatic lacunar infarctions were more severe than those of patients with both types of infarctions. More silent brain infarctions were located in the corona radiata and basal ganglia; these locations were different from those of the symptomatic lacunar infarctions. The initial sizes of the symptomatic lacunar infarctions were larger than the silent brain infarctions, whereas the final sizes were almost equal between the two groups. CONCLUSIONS: Chronic ischemic preconditioning and nonstrategic locations may be the main reasons for the 'silence' of silent brain infarctions.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto Encefálico/etiologia , Isquemia Encefálica/complicações , Acidente Vascular Cerebral Lacunar/etiologia , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Estudos de Casos e Controles , Doença Crônica , Angiografia por Ressonância Magnética , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral Lacunar/patologia , Acidente Vascular Cerebral Lacunar/fisiopatologiaRESUMO
OBJECTIVE: To study the integrity of the white matter in Binswanger's disease (BD) patients with quantitative fractional anisotropy (DTI-FA). METHOD: Controls (12) and patients with BD (12) were included. Scans performed with MR (GE Signa Horizon/1.5T). Fazekas's score=6 with white matter hyperintensities extension >75 percent assessed on FLAIR scans. Standard parameters for DTI-FA were used. ROIs placed in symmetrical regions on two axial planes, data pooled in anterior (frontal) and posterior (temporo-parieto-occipital) regions. Analysis with Functool. Statistics for anterior and posterior regions comparison. RESULTS: DTI-FA showed reduction of anisotropy, reflecting axonal damage and demyelination of fibers, more prominent in anterior in relation to posterior region, in BD patients in comparison to controls. CONCLUSION: Loss of integrity of fiber tracts reflects interruption of neural networks that subserve cognitive, behavioral, and motor integration. The more severely affected frontal region is related to executive dysfunction, a characteristic feature of Binswanger's disease.
OBJETIVO: Estudar a integridade da substância branca em pacientes com doença de Binswanger (DB) com anisotropia fracionada quantitativa (DTI-FA). MÉTODO: Incluídos controles (12) e pacientes com DB (12). Obtidas imagens de RM (GE Signa Horizon/1,5T). Escore=6 de Fazekas com hiperintensidades da substância branca com extensão >75 por cento avaliados em imagens em FLAIR. Utilizados parâmetros padrão para DTI-FA. ROIs colocados em regiões simétricas de dois planos axiais, dados das regiões anterior (frontal) e posterior (têmporo-parieto-occipital) reunidos. Análise com Functool. Estatística para comparar regiões anteriores e posteriores. RESULTADOS: DTI-FA mostrou redução da anisotropia, refletindo lesão axonal e desmielinazação de fibras, com predomínio na região anterior em relação à posterior, nos pacientes com DB em comparação aos controles. CONCLUSÃO: Perda da integridade de feixes de fibras reflete interrupção de redes neurais subjacentes à integração cognitiva, comportamental e motora. A região frontal, mais gravemente atingida, está relacionada à disfunção executiva, aspecto característico da doença de Binswanger.
Assuntos
Idoso , Feminino , Humanos , Masculino , Encéfalo/patologia , Demência Vascular/patologia , Anisotropia , Estudos de Casos e Controles , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: To evaluate the prevalence of leukoaraiosis (LA) and its correlation with vascular risk factors and the cognitive performance of elderly patients. METHOD: 78 patients were randomly selected and submitted to clinic-laboratorial evaluation for vascular risk factors. Two cognitive tests were performed. All patients were submitted to cranial computerized tomography (CT), which was analyzed in two situations: the spontaneous and the directed way. RESULTS: There was no statistically significant difference between the prevalence of spontaneous and the directed diagnoses of LA (20.5 and 18 percent, respectively). The presence of LA was not significantly correlated with cognitive impairment. Only age was positively associated with LA. CONCLUSION: Cranial CT is a trustworthy method for the diagnosis of LA. Only age showed a positive association. No clinical implications were found, concerning the cognitive performance of the patients.
OBJETIVO: Avaliar a prevalência da leucoaraiose (LA) em idosos e correlacioná-los com fatores de risco vasculares e seu desempenho cognitivo. MÉTODO: 78 pacientes foram selecionados aleatoriamente e submetidos a avaliação clinico-laboratorial para fatores de risco vascular. Dois testes cognitivos foram realizados. Todos os pacientes foram submetidos a tomografia computadorizada (TC) de crânio, que foi analisada em duas situações: de forma espontânea e dirigida. RESULTADOS: Não houve diferença estatisticamente significativa entre as formas de diagnóstico espontâneo e dirigido da LA (20,5 and 18 por cento, respectivamente). Com relação ao desempenho cognitivo, a presença da LA não determinou prejuízo significativo. Somente a idade mostrou associação positiva com a LA. CONCLUSÃO: A TC de crânio é um método confiável para o diagnóstico de LA. A idade foi o único fator de risco que mostrou associação positiva. Não houve prejuízo quanto ao desempenho cognitivo.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Cognitivos , Leucoaraiose , Brasil/epidemiologia , Doença Crônica , Escolaridade , Leucoaraiose/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
La introducción de técnicas para el monitoreo ambulatorio de la presión arterial ha permitido obtener información acerca de las variaciones diurnas de la presión arterial. El patrón de dipper acentuado que equivale a hipotensión nocturna pudiera tener una relación causal específica con enfermedad cerebrovascular silente y lesión de la sustancia blanca mediada por hipoperfusión cerebral. Se presentó un caso con lesiones de la sustancia blanca cerebral sin factores de riesgo vascular convencionales, en el que el monitoreo ambulatorio de la presión arterial demostró una hipertensión ligera con un patrón de dipper acentuado, una condición fisiopatológica susceptible de ser modificada. En el futuro, esta técnica, al parecer, tendrá un uso más extendido en la enfermedad cerebrovascular, especialmente en los ictus lacunares y hemodinámicos, así como en las lesiones vasculares crónicas de la sustancia blanca cerebral.
The introduction of the techniques for the ambulatory monitoring of arterial pressure has allowed to obtain information about the day variations of arterial pressure. The pattern of accentuated Dipper may have a specific causal relation to silent cerebrovascular disease and lesion of the white matter mediated by brain hypoperfusion. A case with lesions of the cerebral white matter without conventional vascular risk factors, was presented. The ambulatory monitoring of the arterial pressure showed a mild hypertension with an accentuated Dipper pattern, a physiopathological condition susceptible to be modified. In the future, it seems that this technique will have a wider use in the cerebrovascular disease, specially in the lacunar and hemodynamic ictus, as well as in the chronic vascular lesions of the cerebral white matter.