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1.
Adv Exp Med Biol ; 1175: 199-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583590

RESUMO

Leukodystrophies are genetically determined disorders affecting the white matter of the central nervous system. The combination of MRI pattern recognition and next-generation sequencing for the definition of novel disease entities has recently demonstrated that many leukodystrophies are due to the primary involvement and/or mutations in genes selectively expressed by cell types other than the oligodendrocytes, the myelin-forming cells in the brain. This has led to a new definition of leukodystrophies as genetic white matter disorders resulting from the involvement of any white matter structural component. As a result, the research has shifted its main focus from oligodendrocytes to other types of neuroglia. Astrocytes are the housekeeping cells of the nervous system, responsible for maintaining homeostasis and normal brain physiology and to orchestrate repair upon injury. Several lines of evidence show that astrocytic interactions with the other white matter cellular constituents play a primary pathophysiologic role in many leukodystrophies. These are thus now classified as astrocytopathies. This chapter addresses how the crosstalk between astrocytes, other glial cells, axons and non-neural cells are essential for the integrity and maintenance of the white matter in health. It also addresses the current knowledge of the cellular pathomechanisms of astrocytic leukodystrophies, and specifically Alexander disease, vanishing white matter, megalencephalic leukoencephalopathy with subcortical cysts and Aicardi-Goutière Syndrome.


Assuntos
Astrócitos/patologia , Doenças Desmielinizantes/fisiopatologia , Leucoencefalopatias/fisiopatologia , Substância Branca/patologia , Humanos
2.
JAMA ; 322(6): 524-534, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408137

RESUMO

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]). Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.


Assuntos
Anti-Hipertensivos/uso terapêutico , Encéfalo/fisiologia , Hipertensão/tratamento farmacológico , Substância Branca/patologia , Idoso , Pressão Sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de Risco
3.
J Biol Regul Homeost Agents ; 33(4): 1073-1084, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389227

RESUMO

This study used Sprague Dawley (SD) rats with stroke-prone renovascular hypertension (RHRSP) to establish an animal model of hypertensive white matter lesions (WML), so as to explore the brain functions and unusual ß-amyloid (Aß) accumulation in WML. Hypertensive WML and brain dysfunctions were evaluated by measuring the caudal arterial pressure of model rats, and by observing the histomorphological deformations o f the prefrontal lobe, temporal lobe, hippocampus and corpus callosum, as well as by counting of the number of neurons using Hematoxylin and Eosin (H and E) staining, and by evaluating the changes in rat brain functions, including memory and the ability of visual space learning, using the Morris Water Maze Test. In addition, the study discussed the correlation between Aß accumulation and hypertensive WML cognitive impairment by adopting an enzyme-linked immunosorbent assay (ELISA) to detect the level of Aß 1-42, and by detecting the expression of amyloid precursor protein (APP) and Beta-secretase 1 (BACE1) using Western blot. Results of the study showed that at 4 weeks, 8 weeks, 12 weeks and 16 weeks after operation, the blood pressure and brain Aß expression in the rats of the model group notably increased (P less than 0.01), along with deformed and degenerated brain tissues, confirming that the unusual Aß accumulation may participate in the occurrence and development of hypertensive WML as well as the induction of cerebral cognitive decreases.


Assuntos
Peptídeos beta-Amiloides/análise , Encéfalo/fisiopatologia , Hipertensão/patologia , Substância Branca/patologia , Secretases da Proteína Precursora do Amiloide/análise , Precursor de Proteína beta-Amiloide/análise , Animais , Ácido Aspártico Endopeptidases/análise , Ratos , Ratos Sprague-Dawley
4.
Medicine (Baltimore) ; 98(34): e16920, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441874

RESUMO

RATIONALE: Vascular cognitive impairment (VCI) is a common cause of dementia. Research suggests that hereditary factors (gene mutations) play an important role in the pathogenesis of VCI, and a mutation of the NOTCH3 locus is frequently identified in affected patients. Herein, we report the case of a patient with confirmed VCI associated with a NOTCH3 exon 33 gene mutation and review the relevant VCI literature. PATIENT CONCERNS: A 48-year-old man presented to our neurology clinic with gradually progressive cognitive impairment. DIAGNOSES: Brain magnetic resonance imaging revealed multiple punctate hyperintensities in the patient's periventricular white matter. Genetic analysis showed a c.6744C > T, p. Ala2223Val substitution in exon 33 of the NOTCH3 gene. We diagnosed thepatient with VCI secondary to a NOTCH3 gene mutation. INTERVENTIONS: Donepezil (5 mg) and memantine (5 mg) daily. OUTCOMES: The patient showed symptom improvement at his 3-month and 6-month follow-up appointments. LESSONS: This patient may have a new type of mutation that is different from the one seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, although it involves a NOTCH3 defect. We propose that the entire NOTCH3 gene should be sequenced in patients with suspected hereditary VCI. This practice could facilitate the discovery of newpathogenic mutations and diseases.


Assuntos
Demência Vascular/genética , Receptor Notch3 , Disfunção Cognitiva/etiologia , Demência Vascular/complicações , Demência Vascular/tratamento farmacológico , Donepezila/administração & dosagem , Humanos , Masculino , Memantina/administração & dosagem , Pessoa de Meia-Idade , Mutação , Nootrópicos/administração & dosagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
5.
Cancer Radiother ; 23(5): 370-377, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331843

RESUMO

PUPOSE: Medulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16-25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. PATIENTS AND METHODS: Participants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n=16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. RESULTS: The mean standard score Full-Scale Intelligence Quotient (FSIQ) (M=63, SD=12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M=67.7, SD=13.1), perceptual reasoning (M=63.5, SD=13.8) and processing speed (M=62.7, SD=15.5) were all found to be in the extremely low range, while xorking memory (M=75.5, SD=10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P=0.001 and P<0.001 respectively. CONCLUSION: Our study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.


Assuntos
Neoplasias Cerebelares/radioterapia , Irradiação Craniana/efeitos adversos , Meduloblastoma/radioterapia , Transtornos Neurocognitivos/etiologia , Fatores Etários , Antineoplásicos/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Criança , Pré-Escolar , Terapia Combinada , Seguimentos , Substância Cinzenta/lesões , Substância Cinzenta/patologia , Hipocampo/lesões , Hipocampo/patologia , Humanos , Meduloblastoma/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Transtornos Neurocognitivos/patologia , Tamanho do Órgão , Modelos de Riscos Proporcionais , Escalas de Wechsler , Substância Branca/lesões , Substância Branca/patologia
6.
Yonsei Med J ; 60(8): 774-781, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347333

RESUMO

PURPOSE: Cerebral small vessel disease (SVD) is known to be associated with ischemic stroke, intracerebral hemorrhage (ICH), and cognitive impairment. In this retrospective observational study, we explored SVD markers on MRI relevant to spontaneous ICH. MATERIALS AND METHODS: The ICH group consisted of 150 consecutive patients with a first primary parenchymal ICH, and the control group consisted of 271 age- and sex-matched individuals who underwent brain MRI in a health care center. We compared cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular space (EPVS), and lacunae in the ICH and control groups. RESULTS: A total of 1278 CMB lesions were identified in 121 of the 150 patients in the ICH group (80.6%), while 77 CMB lesions were found in 32 of the 271 individuals in the control group (11.8%). WMH and EPVS were more severe and lacunae were more frequent in the ICH patients than in the control group. When receiver operating characteristic (ROC) curves were plotted, number of CMBs most significantly predicted ICH. All imaging markers were significantly associated with ICH in every age group. The location of CMBs coincided with the location of ICH, and ICH volume correlated with CMB count. CONCLUSION: All MRI markers for SVD were worse in ICH patients than in healthy controls, and these markers were prominent even in young ICH patients. Lacunae, WMH, EPVS, and CMB should be considered as factors related with spontaneous ICH.


Assuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imagem por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
7.
Eur J Radiol ; 116: 152-159, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153558

RESUMO

BACKGROUND AND PURPOSE: Periventricular pseudocysts (PVPCs) are cystic cavities originating from the germinal matrix. The effects of PVPCs on the development of white matter (WM) in neonates remain unclear. This study aimed to characterise WM microstructural variations in neonates with PVPCs with and without additional abnormities on MRI. MATERIALS AND METHODS: Neonates with PVPCs and controls with no MRI abnormalities were retrospectively enrolled. Test subjects were divided into groups 1 (isolated PVPCs) and 2 (PVPCs with additional MRI abnormalities). The PVPC MRI features collected included lateralisation, locularity, anatomic location, and the maximum anteroposterior diameter. Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were compared between the PVPC and control groups using tract-based spatial statistics. RESULTS: Thirty-eight neonates with PVPCs and 60 controls were enrolled. Groups 1 and 2 contained 15 and 23 subjects, respectively. The additional MRI findings in group 2 included intracranial haemorrhage, punctate WM lesions, hypoxic-ischaemic encephalopathy, and acute cerebral infarction. No significant differences were found in PVPC MRI features between the 2 test groups. Compared to controls, no significant changes in DTI metrics were observed in group 1 neonates; whereas extensive WM regions with decreased FA, increased RD, and unchanged/increased AD were found in group 2. CONCLUSIONS: Isolated PVPCs are not independently correlated with WM microstructural variations in neonates. This result provides further evidence for supporting the benign outcome of fetuses with isolated PVPCs.


Assuntos
Encefalopatias/patologia , Cistos/patologia , Substância Branca/patologia , Anisotropia , Encefalopatias/congênito , Estudos de Casos e Controles , Cistos/congênito , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
8.
Forensic Sci Int ; 301: e49-e54, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230858

RESUMO

Gunshot wounds (GSW) are one of the most common causes of penetrating spinal injury, however few data are available regarding GSW causing an indirect fatal nervous tissue injury, such as that induced by the concussive force secondary to the bullet penetration. This report describes a rare case of a death following a GSW spine injury at the level of C2 vertebral body, without direct contact with the spinal cord, as seen with computed tomography scan performed soon after the death. At autopsy, vertebral canal and dura mater, as well as spinal cord and medulla oblongata, appeared devoid of pathologies and/or lesions, major viscera were unaltered. The cause of death was attributed to a cardiorespiratory arrest subsequent to the GSW injury of the C2 vertebral bone. Histopathological analysis of spinal cord and medulla oblongata was performed by means of conventional stainings, and glial fibrillary acidic protein (GFAP) and Neurofilaments 200kD (NF) immunohistochemistry. Histological alterations stood out against a tissue with no other evident sign of neuropathology, and could be observed from the caudalmost part of the medulla oblongata to the level of the inferior olivary nucleus. Main structural changes were found in the white matter, involving often the adjacent gray matter, where they appeared as multiple scattered areas of degeneration, lacking the usual staining affinity, and showing a disrupted fibrillary pattern as evidenced by myelin staining, and GFAP- and NF-immunolabelling. The shock wave secondary to the impact on the C2 vertebral bone is likely to have been the cause of a widespread neuronal-axonal histopathological damage at the spinal-medullary junction and caudal medulla oblongata that is compatible with a severe fatal respiratory dysfunction and dysregulation of the autonomic pathways subserving the control of blood pressure and cardiac activity.


Assuntos
Vértebras Cervicais/lesões , Vértebras Cervicais/patologia , Morte Súbita/etiologia , Bulbo/patologia , Ferimentos por Arma de Fogo/patologia , Axônios/patologia , Vértebras Cervicais/diagnóstico por imagem , Patologia Legal , Parada Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Tomografia Computadorizada por Raios X , Substância Branca/patologia , Ferimentos por Arma de Fogo/diagnóstico por imagem
9.
Artigo em Russo | MEDLINE | ID: mdl-31089095

RESUMO

AIM: To analyze specific changes in brain tissue of patients with idiopathic normal pressure hydrocephalus at cellular and subcellular levels. MATERIAL AND METHODS: Brain biopsies from 32 patients with idiopathic normal pressure hydrocephalus were investigated by light and electron microscopy. Biopsies were made in 3 points (the cortex, subcortical and periventricular white matter during ventricular catheter positioning). RESULTS: A number of pathological features of idiopathic normal pressure hydrocephalus were identified. Most frequent were the exhaustion of brain tissue, enlargement of perivascular spaces, aseptic necrosis, and amyloid and Lewy body's formation. CONCLUSION: The changes in brain tissue of patients with idiopathic normal pressure hydrocephalus transform our views on its mechanisms. It becomes clear that idiopathic normal pressure hydrocephalus is part of common neurodegenerative process that has characteristic features affecting clinical manifestations of the disease.


Assuntos
Hidrocefalia de Pressão Normal , Hidrocefalia , Substância Branca , Biópsia , Encéfalo , Humanos , Hidrocefalia de Pressão Normal/patologia , Substância Branca/patologia
10.
Nat Neurosci ; 22(6): 992-999, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086316

RESUMO

The transition from adolescence to adulthood is a period when ongoing brain development coincides with a substantially increased risk of psychiatric disorders. The developmental brain changes accounting for this emergent psychiatric symptomatology remain obscure. Capitalizing on a unique longitudinal dataset that includes in vivo myelin-sensitive magnetization transfer (MT) MRI scans, we show that this developmental period is characterized by brain-wide growth in MT trajectories within both gray matter and adjacent juxtacortical white matter. In this healthy population, the expression of common developmental traits, namely compulsivity and impulsivity, is tied to a reduced growth of these MT trajectories in frontostriatal regions. This reduction is most marked in dorsomedial and dorsolateral prefrontal regions for compulsivity and in lateral and medial prefrontal regions for impulsivity. These findings highlight that psychiatric traits of compulsivity and impulsivity are linked to regionally specific reductions in myelin-related growth in late adolescent brain development.


Assuntos
Comportamento Compulsivo/patologia , Comportamento Impulsivo/fisiologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/patologia , Substância Branca/crescimento & desenvolvimento , Adolescente , Feminino , Humanos , Masculino , Substância Branca/patologia , Adulto Jovem
11.
J Clin Neurosci ; 65: 6-10, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31072738

RESUMO

Aim of this paper is to investigate the presence of White Matter Lesions (WMLs) in subjects affected by Sudden Sensorineural Hearing Loss (SSNHL) and possibly to evaluate the significance of WMLs in SSNHL patients. A total of 64 patients (cases) affected by SSNHL were included in this case-control study. Hearing tests were performed at SSNHL onset, after 7 days and after 30 days. Cerebral MRI sequences were performed to rule out retrocochlear pathology, and WMLs were evaluated if present. MRI control group included 32 subjects, without hearing loss, affected by pituitary adenoma, who underwent cerebral MRI of follow-up. WML presence in those affected by SSNHL resulted having a similar distribution to that of the control group; however, we observed complete hearing recovery in 42,9% of patients without WML and in 11,6% of patients with WML >1 (p = 0,017*). The incidence of WML in patients with SSNHL was not different compared to that of the control group; however, MRI could have a prognostic role for SSNHL patients, as the presence of WMLs can been linked to a poorer hearing recovery rate.


Assuntos
Encéfalo/patologia , Perda Auditiva Neurossensorial/patologia , Substância Branca/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Orelha/inervação , Orelha/patologia , Feminino , Perda Auditiva Neurossensorial/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
12.
Nat Neurosci ; 22(5): 709-718, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30988524

RESUMO

Disruption of the blood-brain barrier (BBB) is critical to initiation and perpetuation of disease in multiple sclerosis (MS). We report an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent demyelinating injury. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in certain active MS lesions, representing an inability to properly detach from vessels following perivascular migration. Perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates their dysfunctional vascular detachment and also leads to OPC secretion of Wif1, which interferes with Wnt ligand function on endothelial tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB.


Assuntos
Barreira Hematoencefálica/fisiopatologia , Encefalite/fisiopatologia , Esclerose Múltipla/fisiopatologia , Células Precursoras de Oligodendrócitos/fisiologia , Animais , Astrócitos/patologia , Astrócitos/fisiologia , Barreira Hematoencefálica/patologia , Movimento Celular , Células Cultivadas , Encefalite/patologia , Proteínas da Matriz Extracelular/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Esclerose Múltipla/patologia , Células Precursoras de Oligodendrócitos/patologia , Junções Íntimas/metabolismo , Substância Branca/patologia
14.
N Engl J Med ; 380(17): 1597-1605, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30969503

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti-JC virus immune activity in patients with PML was unknown. METHODS: We administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses. RESULTS: Pembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cerebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti-JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement. CONCLUSIONS: Our findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treatment of PML is warranted. (Funded by the National Institutes of Health.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores Imunológicos/uso terapêutico , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Líquido Cefalorraquidiano/virologia , Regulação para Baixo , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/imunologia , Contagem de Linfócitos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Carga Viral , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
16.
Personal Ment Health ; 13(2): 96-106, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30989833

RESUMO

BACKGROUND: Borderline personality disorder (BPD) is a psychiatric condition associated with the impairment of the frontolimbic network. However, a growing body of studies suggests that brain dysfunction underling BPD could involve other brain areas. We explored the whole-brain white matter (WM) organization in BPD patients to clarify the structural pattern underlying the disease and its relationship with clinical features. METHODS: Fourteen BPD patients and 14 healthy controls underwent a multidimensional clinical assessment and diffusion tensor imaging acquisition. Measures of fractional anisotropy (FA) and mean, axial and radial (RD) diffusivity were collected, and alterations in the WM were assessed using the voxelwise approach, including substance and alcohol abuse as covariates. Voxelwise regression analysis was performed to identify associations between microstructural changes and clinical feature in BPD. RESULTS: Group comparisons showed alterations only for FA and RD: FA decreased in the right posterior hemisphere, while RD increased bilaterally and widespread in anterior and posterior areas (p < 0.05, threshold-free cluster enhancement corrected). Moreover, WM alterations of the corpus callosum were related to anxiety in BPD group. DISCUSSION: Our data support the idea that structural alterations underling BPD also involve cortico-cortical pathways, corticothalamic and corticostriatal tracts, suggesting that the frontolimbic model should be reinterpreted. © 2019 John Wiley & Sons, Ltd.


Assuntos
Transtorno da Personalidade Borderline/patologia , Córtex Cerebral/patologia , Substância Branca/patologia , Adulto , Transtorno da Personalidade Borderline/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Substância Branca/diagnóstico por imagem
17.
J Med Syst ; 43(5): 131, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30937597

RESUMO

In order to study the application of multi-modal magnetic resonance imaging (MRI) fusion technology in schizophrenia, a 4-way multi-modal fusion method based on mCCA+jICA is used to fuse the local consistency and functional network connection of resting-state functional MRI, gray matter volume of structural MRI, and partial anisotropy of diffusion MRI four characteristics of large sample of schizophrenic patients in multi-site China, trying to find out the common characteristics of function and structure of significant differences between schizophrenia and healthy controls. It is found that compared with normal people, schizophrenic patients show higher local consistency, lower gray matter volume, lower functional network connectivity and decreased white matter integrity in the anterior thalamic radiation, upper bundle and other bundles in brain areas such as basal ganglia network, hippocampus and prominence network. There is a significant correlation between a thalamocortical perceptual loop and auditory hallucination in schizophrenia, and there is a high degree of spatial consistency and commonality among the three MRI features. The higher the volume of gray matter in the dorsolateral and medial prefrontal cortex is, the higher the integrity of white matter fibers such as corticospinal tract, superior longitudinal tract and anterior thalamic radiation is, the higher the digital backward score is, and the better the working memory ability of the subjects is.


Assuntos
Encéfalo/patologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Esquizofrenia/patologia , Adolescente , Adulto , Anisotropia , Encéfalo/diagnóstico por imagem , China , Imagem de Difusão por Ressonância Magnética , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Alucinações , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
18.
J Clin Neurosci ; 65: 59-65, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30940453

RESUMO

Using time-variant of blood oxygenation level dependent (BOLD) signal to investigate the temporal changes in functional connectivity (FC) between key nodes may shed light on the dynamic characteristics of network. Twenty-two relapsing-remitting multiple sclerosis (RRMS) and 22 well-matched healthy control subjects (HCs) participated in this study. Previously validated key nodes of attention network seeds were defined as spherical regions of interests (ROIs); then, we captured the pattern of dFC using sliding window correlation of ROIs in the RRMS and HCs during rest. Furthermore, correlation analysis between altered dFC of paired-ROIs with clinical measures in RRMS were performed. Compared with the HCs, the RRMS showed: a certain specificity transient pattern of FC of attention network at time window levels, including decreased dFC within dorsal attention network [connections of left intraparietal sulcus (LIPS)-right intraparietal sulcus (RIPS), LIPS-right frontal eye field (RFEF) and left frontal eye field (LFEF)-RIPS] and ventral attention network [connection of right ventral frontal cortex (RVFC)-right temporal parietal junction (RTPJ)], increased dFC between dorsal and ventral attention network (connections of LIPS-RTPJ and LIPS-RVFC). Secondary analysis indicated that the dFC coefficients of the connections of LIPS-RIPS (r = -0.467, P = 0.023) and RVFC-RTPJ (r = -0.452, P = 0.043) were significant negative correlated with the total white matter lesion load. In conclusion, we found that the instantaneous configuration pattern of FC in attention network of RRMS are relate to lesions loads.


Assuntos
Atenção/fisiologia , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Substância Branca/patologia , Adulto , Encéfalo/patologia , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Lobo Frontal/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Parietal/patologia , Descanso/fisiologia
19.
J Clin Neurosci ; 64: 206-213, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31023573

RESUMO

Stroke induced white matter injury can induce marked neurological deficits even after relatively small infarcts, due to the tightly packed nature of white matter tracts especially in certain areas in the brain. Many drugs which were successful in the pre-clinical trials failed in clinical trials, which was attributed in part to the focus on grey matter injury completely and ignoring their effect on white matter. In this work we selected two known neuroprotective drugs (minocycline and progesterone) and examined their effect on white matter injury after focal cerebral ischemia/reperfusion injury in rats. Focal cerebral ischemia was induced in male Wistar rats (one-hour ischemia followed by reperfusion). Progesterone and minocycline were administered immediately after reperfusion onset. Infarct size, microglial activation and white matter injury were assessed and compared between the treatment and no-treatment groups and Sham operated animals. Our data showed that both progesterone and minocycline reduced infarct size, microglial activation and white matter injury. This work shows a new neuroprotective mechanism of both drugs, via white matter injury reduction, that can be exploited for stroke management. While the utility of either drugs as a sole agent in the management of stroke is questionable, there is a value of using either drugs as an adjuvant therapy to traditional stroke therapy, making use of the white matter protective effect that would improve outcome and facilitate healing after stroke.


Assuntos
Minociclina/farmacologia , Fármacos Neuroprotetores/farmacologia , Progesterona/farmacologia , Acidente Vascular Cerebral/patologia , Substância Branca/efeitos dos fármacos , Animais , Isquemia Encefálica/patologia , Feminino , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Substância Branca/patologia
20.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999680

RESUMO

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (ß = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (ß = -0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.


Assuntos
Apatia , Inflamação/patologia , Substância Branca/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Vida Independente , Inflamação/complicações , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Pessoa de Meia-Idade
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