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1.
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
2.
Nat Commun ; 10(1): 2945, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270332

RESUMO

Age- and sex-related alterations in gene transcription have been demonstrated, however the underlying mechanisms are unresolved. Neuroepigenetic pathways regulate gene transcription in the brain. Here, we measure in vivo expression of the epigenetic enzymes, histone deacetylases (HDACs), across healthy human aging and between sexes using [11C]Martinostat positron emission tomography (PET) neuroimaging (n = 41). Relative HDAC expression increases with age in cerebral white matter, and correlates with age-associated disruptions in white matter microstructure. A post mortem study confirmed that HDAC1 and HDAC2 paralogs are elevated in white matter tissue from elderly donors. There are also sex-specific in vivo HDAC expression differences in brain regions associated with emotion and memory, including the amygdala and hippocampus. Hippocampus and white matter HDAC expression negatively correlates with emotion regulation skills (n = 23). Age and sex are associated with HDAC expression in vivo, which could drive age- and sex-related transcriptional changes and impact human behavior.


Assuntos
Encéfalo/fisiologia , Epigênese Genética , Caracteres Sexuais , Adamantano/análogos & derivados , Adamantano/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono/farmacocinética , Emoções , Feminino , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacocinética , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
3.
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
4.
JAMA ; 322(4): 336-347, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334794

RESUMO

Importance: United States government personnel experienced potential exposures to uncharacterized directional phenomena while serving in Havana, Cuba, from late 2016 through May 2018. The underlying neuroanatomical findings have not been described. Objective: To examine potential differences in brain tissue volume, microstructure, and functional connectivity in government personnel compared with individuals not exposed to directional phenomena. Design, Setting, and Participants: Forty government personnel (patients) who were potentially exposed and experienced neurological symptoms underwent evaluation at a US academic medical center from August 21, 2017, to June 8, 2018, including advanced structural and functional magnetic resonance imaging analytics. Findings were compared with imaging findings of 48 demographically similar healthy controls. Exposures: Potential exposure to uncharacterized directional phenomena of unknown etiology, manifesting as pressure, vibration, or sound. Main Outcomes and Measures: Potential imaging-based differences between patients and controls with regard to (1) white matter and gray matter total and regional brain volumes, (2) cerebellar tissue microstructure metrics (eg, mean diffusivity), and (3) functional connectivity in the visuospatial, auditory, and executive control subnetworks. Results: Imaging studies were completed for 40 patients (mean age, 40.4 years; 23 [57.5%] men; imaging performed a median of 188 [range, 4-403] days after initial exposure) and 48 controls (mean age, 37.6 years; 33 [68.8%] men). Mean whole brain white matter volume was significantly smaller in patients compared with controls (patients: 542.22 cm3; controls: 569.61 cm3; difference, -27.39 [95% CI, -37.93 to -16.84] cm3; P < .001), with no significant difference in the whole brain gray matter volume (patients: 698.55 cm3; controls: 691.83 cm3; difference, 6.72 [95% CI, -4.83 to 18.27] cm3; P = .25). Among patients compared with controls, there were significantly greater ventral diencephalon and cerebellar gray matter volumes and significantly smaller frontal, occipital, and parietal lobe white matter volumes; significantly lower mean diffusivity in the inferior vermis of the cerebellum (patients: 7.71 × 10-4 mm2/s; controls: 8.98 × 10-4 mm2/s; difference, -1.27 × 10-4 [95% CI, -1.93 × 10-4 to -6.17 × 10-5] mm2/s; P < .001); and significantly lower mean functional connectivity in the auditory subnetwork (patients: 0.45; controls: 0.61; difference, -0.16 [95% CI, -0.26 to -0.05]; P = .003) and visuospatial subnetwork (patients: 0.30; controls: 0.40; difference, -0.10 [95% CI, -0.16 to -0.04]; P = .002) but not in the executive control subnetwork (patients: 0.24; controls: 0.25; difference: -0.016 [95% CI, -0.04 to 0.01]; P = .23). Conclusions and Relevance: Among US government personnel in Havana, Cuba, with potential exposure to directional phenomena, compared with healthy controls, advanced brain magnetic resonance imaging revealed significant differences in whole brain white matter volume, regional gray and white matter volumes, cerebellar tissue microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks but not in the executive control subnetwork. The clinical importance of these differences is uncertain and may require further study.


Assuntos
Encéfalo/patologia , Empregados do Governo , Doenças do Sistema Nervoso/diagnóstico por imagem , Adulto , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Cuba , Imagem de Difusão por Ressonância Magnética , Feminino , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Doenças do Sistema Nervoso/etiologia , Ruído/efeitos adversos , Tamanho do Órgão , Valores de Referência , Estados Unidos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem
5.
J Headache Pain ; 20(1): 78, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291903

RESUMO

BACKGROUND: Several studies have investigated white matter with diffusion tensor imaging (DTI) in those suffering from headache, but so far only in clinic based samples and with conflicting results. METHODS: In the present study, 1006 individuals (50-66 years) from the general population (Nord-Trøndelag Health Study) participated in an imaging study of the head at 1.5 T (HUNT-MRI). Hundred and ninety-six individuals were excluded because of errors in the data acquisition or brain pathology. Two hundred and forty-six of the remaining participants reported suffering from headache (69 from migraine and 76 from tension-type headache) the year prior to the scanning. DTI data were analysed with Tract-Based Spatial Statistics and automated tractography. Type of headache, frequency of attacks and evolution of headache were investigated for an association with white matter fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), radial diffusivity (RD) and tract volume. Correction for various demographical and clinical variables were performed. RESULTS: Headache sufferers had widespread higher white matter MD, AD and RD compared to headache free individuals (n = 277). The effect sizes were mostly small with the largest seen in those with middle-age onset headache, who also had lower white matter FA. There were no associations between white matter microstructure and attack frequency or type of headache. CONCLUSION: Middle-age onset headache may be related to a widespread process in the white matter leading to altered microstructure.


Assuntos
Cefaleia/diagnóstico por imagem , Cefaleia/patologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Idoso , Anisotropia , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Stroke Cerebrovasc Dis ; 28(8): 2343-2350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31208821

RESUMO

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is related to motor function disturbance. It includes several types: lacunar infarction, white matter hyperintensity, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). Transcranial magnetic stimulation (TMS) has been successfully used to evaluate the function of the pyramidal tract. Central motor conduction time (CMCT) is one of the indicators of pyramidal tract dysfunction in motor evoked potential (MEP). The aim of this study was to investigate the association between each type of CSVD and CMCT. METHODS: We enrolled 350 patients with vascular risk factors or a history of cerebrovascular events, who showed signs of CSVD in magnetic resonance imaging in the prospective registry. Among them, 138 patients agreed to the evaluation of MEP. CMCT, resting motor threshold (RMT), and silent period are indicators of the function of motor pathways in MEP. A total of 276 hemispheres were divided into 45 symptomatic hemispheres with a history of pyramidal tract dysfunction and 231 without it. Correlation between each type of CSVD and CMCT were examined in total, symptomatic, and asymptomatic hemispheres. RESULTS: The mean age was 70.5 ± 10.3 (mean ± SD) years, and 89 (65%) were men. In the symptomatic hemisphere, CMCT and RMT were significantly higher than in the asymptomatic hemisphere. In the symptomatic hemisphere, significant association was observed between the number of EPVS in the white matter and CMCT (R2 = 0.201, p < .01). CONCLUSIONS: In the symptomatic hemispheres, CMCT was associated with the number of EPVS in the white matter. The EPVS in the white matter may be involved in the motor disturbance due to CSVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Potencial Evocado Motor , Atividade Motora , Córtex Motor/fisiopatologia , Músculo Esquelético/inervação , Condução Nervosa , Tratos Piramidais/fisiopatologia , Substância Branca/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Estudos Transversais , Eletromiografia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Contração Muscular , Tratos Piramidais/diagnóstico por imagem , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estimulação Magnética Transcraniana , Substância Branca/diagnóstico por imagem
7.
J Comput Assist Tomogr ; 43(3): 460-466, 2019 May/Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31082952

RESUMO

OBJECTIVE: To evaluate the optimal virtual monochromatic energy in dual-energy computed tomography for differentiating between infarcted areas and normal brain parenchyma. METHODS: We enrolled 29 patients with middle cerebral artery acute brain infarction of who underwent examination by dual-energy computed tomography. We calculated the contrast-to-noise ratio (CNR) between white or gray matter and the infarcted area (CNR(W-I) and CNR(G-I), respectively) and normalized CNRs. From the normalized CNRs, we assessed which monochromatic energy gave the best balance between the infarcted area and normal brain parenchyma. The 70-keV images were used for comparison. RESULTS: The 99-keV images demonstrated the best balance between the infarction and normal brain parenchyma. In quantitative analysis, the 99-keV images were not inferior to the 70-keV images. (CNR(G-I), 1.92 ± 0.80 vs 2.00 ± 0.70, respectively [P = 0.16]; CNR(W-I), 0.52 ± 0.72 vs 0.40 ± 0.64, P < 0.01, respectively). CONCLUSIONS: Monochromatic 99-keV energy images may be optimal for evaluating middle cerebral artery acute brain infarction.


Assuntos
Infarto da Artéria Cerebral Média/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Infarto Cerebral/diagnóstico por imagem , Feminino , Substância Cinzenta , Humanos , Masculino , Estudos Retrospectivos , Razão Sinal-Ruído , Substância Branca/diagnóstico por imagem
8.
J Pediatr Ophthalmol Strabismus ; 56(3): 178-182, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31116866

RESUMO

PURPOSE: To report a series of patients with cyclic esotropia, their surgical outcomes, and incidental findings. METHODS: The medical records of five patients with cyclic esotropia presenting over 17 months were reviewed. Age at onset, ocular and motility examinations, brain magnetic resonance imaging (MRI), acetylcholine receptor antibodies, thyroid hormone levels and antibodies, calendars documenting phases, surgical treatments, postoperative alignment, and fusion were documented. RESULTS: Three boys and two girls presented at 3 to 4 years old in 2015-2016. Typical periodicity followed a 48-hour cycle. Duration of cycling varied from 1 to 9 weeks. Mean maximum deviation was 37 prism diopters (PD) of esotropia (range: 35 to 40 PD of esotropia). All patients had normal laboratory studies. MRIs showed an abnormal white matter signal in the frontal lobes in 2 patients and were normal in the others. Bilateral medial rectus recessions for the maximum angle were successful in 4 patients at a minimum follow-up of 13 months; the other patient required reoperation for a residual esotropia. Fusion was present in 4 patients preoperatively and all postoperatively. Stereopsis was stable or improved in all postoperatively. CONCLUSIONS: This is the first report of frontal white matter changes occurring in the setting of cyclic esotropia. MRI with attention to frontal lobe white matter might be considered in the work-up of cyclic esotropia to determine if this is a common finding. Bilateral medial rectus recessions can restore fusion in these patients. [J Pediatr Ophthalmol Strabismus. 2019;56(3):178-182.].


Assuntos
Esotropia/diagnóstico , Lobo Frontal/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Visão Binocular/fisiologia , Substância Branca/diagnóstico por imagem , Pré-Escolar , Esotropia/fisiopatologia , Esotropia/cirurgia , Movimentos Oculares/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Músculos Oculomotores/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Brain Topogr ; 32(3): 504-518, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30949863

RESUMO

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.


Assuntos
Síndrome de Asperger/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Síndrome de Asperger/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Criança , Potencial Evocado Motor/fisiologia , Exercício , Face , Lateralidade Funcional , Substância Cinzenta/diagnóstico por imagem , Mãos , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/fisiopatologia , Músculo Esquelético , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Substância Branca/diagnóstico por imagem
10.
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
11.
BMC Med Imaging ; 19(1): 26, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943911

RESUMO

BACKGROUND: Initial reports of 23Na magnetic resonance imaging (MRI) date back to the 1970s. However, methodological challenges of the technique hampered its widespread adoption for many years. Recent technical developments have overcome some of these limitations and have led to more optimal conditions for 23Na-MR imaging. In order to serve as a reliable tool for the assessment of clinical stroke or brain tumor patients, we investigated the repeatability and reproducibility of cerebral sodium (23Na) imaging in healthy subjects. METHODS: In this prospective, IRB approved study 12 consecutive healthy volunteers (8 female, age 31 ± 8.3) underwent three cerebral 23Na-MRI examinations at 3.0 T (TimTrio, Siemens Healthineers) distributed between two separate visits with an 8 day interval. For each scan a T1w MP-RAGE sequence for anatomical referencing and a 3D-density-adapted, radial GRE-sequence for 23Na-imaging were acquired using a dual-tuned (23Na/1H) head-coil. On 1 day, these scans were repeated consecutively; on the other day, the scans were performed once. 23Na-sequences were reconstructed according to the MP-RAGE sequence, allowing direct cross-referencing of ROIs. Circular ROIs were placed in predetermined anatomic regions: gray and white matter (GM, WM), head of the caudate nucleus (HCN), pons, and cerebellum. External 23Na-reference phantoms were used to calculate the tissue sodium content. RESULTS: Excellent correlation was found between repeated measurements on the same day (r2 = 0.94), as well as on a different day (r2 = 0.86). No significant differences were found based on laterality other than in the HCN (63.1 vs. 58.7 mmol/kg WW on the right (p = 0.01)). Pronounced inter-individual differences were identified in all anatomic regions. Moderate to good correlation (0.310 to 0.701) was found between the readers. CONCLUSION: Our study has shown that intra-individual 23Na-concentrations in healthy subjects do not significantly differ after repeated scans on the same day and a pre-set time interval. This confirms the repeatability and reproducibility of cerebral 23Na-imaging. However, with manual ROI placement in predetermined anatomic landmarks, fluctuations in 23Na-concentrations can be observed.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Sódio/administração & dosagem , Adulto , Núcleo Caudado/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Variações Dependentes do Observador , Imagens de Fantasmas , Ponte/diagnóstico por imagem , Estudos Prospectivos , Reprodutibilidade dos Testes , Substância Branca/diagnóstico por imagem , Adulto Jovem
12.
Neuron ; 102(1): 17-20, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946819

RESUMO

Recent research has identified a single factor accounting for broad risk to experience common forms of psychopathology. Structural alterations of cerebellar circuitry have emerged as a neural nexus of this broad risk, highlighting the cerebellum's importance for executive control.


Assuntos
Cerebelo/diagnóstico por imagem , Transtornos Mentais , Anisotropia , Cerebelo/patologia , Cerebelo/fisiopatologia , Suscetibilidade a Doenças , Neuroimagem Funcional , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Vias Neurais , Tamanho do Órgão , Ponte/diagnóstico por imagem , Ponte/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Psicopatologia , Risco , Tálamo , Substância Branca/diagnóstico por imagem , 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.
Medicine (Baltimore) ; 98(14): e15058, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946352

RESUMO

BACKGROUND: Impaired language function is frequently observed as an initial sign in people with autism spectrum disorder (ASD). However, clinically, the early stages of ASD are difficult to distinguish from those of developmental language disorder (DLD). OBJECTIVE: To evaluate the ability of diffusion tensor imaging (DTI) parameters for language-related white matter tracts (arcuate fasciculus) to differentiate ASD from DLD among toddlers. MATERIALS AND METHODS: We included 16 ASD toddlers with language delay and 18 DLD toddlers in this study. Magnetic resonance imaging sequences included T2-weighted imaging (T2WI), T1 3-dimensional magnetization-prepared rapid acquisition gradient-echo (3D MP-RAGE), and DTI. Tractography was performed using Neuro 3D in the Siemens Syngo Workstation, and fractional anisotropy (FA), average fiber length (AFL), tract volume (TV), and number of voxels (NV) were automatically calculated. Data were then analyzed using IBM SPSS Statistics 22. RESULTS: The ASD group exhibited significantly lower FA values, as well as significantly higher TV and NV values compared with the DLD group. With age as the covariate, analysis of covariance revealed different significances in TV and NV. Analysis of variance for AFL revealed no significant differences between the 2 groups. CONCLUSION: DTI parameters of arcuate fasciculus were useful for differentiating ASD with language delay from DLD among toddlers. DTI has the potential to provide an objective and effective method for aiding early diagnosis, early intervention and improving long-term outcomes of ASD.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Transtornos do Desenvolvimento da Linguagem/diagnóstico por imagem , Análise de Variância , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imagem Tridimensional , Lactente , Masculino , Testes Psicológicos , Substância Branca/diagnóstico por imagem
18.
Magn Reson Imaging ; 59: 17-30, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30817962

RESUMO

Susceptibility weighted imaging (SWI) involves post-processing of gradient echo images which are sensitive to the spatial variations in magnetic susceptibility. The aim of this study is to develop an automated filtering scheme to enhance the contrast-to-noise ratio (CNR) and blooming on SWI. Here, the high-pass filtering for SWI processing is designed by applying a weighting function to the neighboring phase differences to enhance the susceptibility-related (SuR) contrast. This is accomplished by summing the neighboring phase differences, weighted with a scaled and shifted error function of the phase difference. Besides using the filter weights of this weighted high-pass (WHP) filter to minimize the filtering artefacts using a filter scale parameter, the CNR is further increased by introduction of the neighborhood-based noise compensation weights into the filtering process. These weights are deduced from the channel phase distribution, conditioned on the channel magnitude and noise variance. Using in vivo SWI data acquired at 1.5 T (16 nos.) and 3.0 T (30 nos.), the magnitude SWI processed using the noise compensated WHP (WHPC) filter is shown to provide an average CNR improvement of 68.40% over that of a homodyne high-pass (HHP) filter. Two tailed t-tests performed separately for different field strengths, show significant differences (p < 0.001) between mean separations of phase masks generated from the WHPC and HHP filtered phase images. In conclusion, the WHPC filter, tuned by the mean separation of the phase mask, enhances the SuR contrast of magnitude SWI for evaluation of mild cognitive impairments, brain tumor and hemorrhagic stroke.


Assuntos
Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética , Adulto , Idoso , Algoritmos , Artefatos , Neoplasias Encefálicas/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Demência/diagnóstico por imagem , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Distribuição Normal , Razão Sinal-Ruído , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
19.
Turk J Med Sci ; 49(2): 604-609, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889943

RESUMO

Background/aim: In the present study we aimed to investigate whether the earlobe crease (ELC) might provide predictive information about white matter intensities (WMIs) in the brain that reflect brain aging. Materials and methods: A total of 350 individuals examined from January 2016 to July 2016 were screened. Patients with known demyelinating white matter disease, neurodegenerative disorders, cerebrovascular event history, or brain tumors were excluded from the study. Finally, 285 cases were included in the study. The four-point cerebral intensity classification system of Fazekas was used in the evaluation of the brain. The ELC was evaluated by inspection. Results: A total of 285 patients were enrolled consecutively. The incidence of WMI was significantly higher in patients with ELC than the others. Age (95% CI: 1.105­1.213, P < 0.001) and ELC (95% CI: 0.098­0.783, P = 0.015) were found as an independent determinants of abnormal WMI. ELC predicted abnormal WMIs with 89% specificity and 62% sensitivity. Conclusion: The presence of an ELC may provide predictive information in terms of detecting abnormal WMIs with prognostic impact in apparently healthy subjects.


Assuntos
Pavilhão Auricular/anormalidades , Voluntários Saudáveis , Substância Branca/anormalidades , Substância Branca/patologia , Adulto , Idoso , Aterosclerose/diagnóstico , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Valor Preditivo dos Testes , Estudos Prospectivos , Rigidez Vascular , Substância Branca/diagnóstico por imagem
20.
Proc Natl Acad Sci U S A ; 116(14): 7101-7106, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30886094

RESUMO

The development of complex cognitive functions during human evolution coincides with pronounced encephalization and expansion of white matter, the brain's infrastructure for region-to-region communication. We investigated adaptations of the human macroscale brain network by comparing human brain wiring with that of the chimpanzee, one of our closest living primate relatives. White matter connectivity networks were reconstructed using diffusion-weighted MRI in humans (n = 57) and chimpanzees (n = 20) and then analyzed using network neuroscience tools. We demonstrate higher network centrality of connections linking multimodal association areas in humans compared with chimpanzees, together with a more pronounced modular topology of the human connectome. Furthermore, connections observed in humans but not in chimpanzees particularly link multimodal areas of the temporal, lateral parietal, and inferior frontal cortices, including tracts important for language processing. Network analysis demonstrates a particularly high contribution of these connections to global network integration in the human brain. Taken together, our comparative connectome findings suggest an evolutionary shift in the human brain toward investment of neural resources in multimodal connectivity facilitating neural integration, combined with an increase in language-related connectivity supporting functional specialization.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Imagem Multimodal/métodos , Adulto , Idoso , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Cognição , Conectoma/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Linguagem , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/crescimento & desenvolvimento , Rede Nervosa/fisiologia , Pan troglodytes , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Adulto Jovem
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