Modeling functional network topology following stroke through graph theory: functional reorganization and motor recovery prediction

The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain's functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain's FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.

NAA and NAAG variation in neuronal activation during visual stimulation

N-acetyl-aspartyl-glutamate (NAAG) and its hydrolysis product N-acetyl-L-aspartate (NAA) are among the most important brain metabolites. NAA is a marker of neuron integrity and viability, while NAAG modulates glutamate release and may have a role in neuroprotection and synaptic plasticity. Investigating on a quantitative basis the role of these metabolites in brain metabolism in vivo by magnetic resonance spectroscopy (MRS) is a major challenge since the main signals of NAA and NAAG largely overlap. This is a preliminary study in which we evaluated NAA and NAAG changes during a visual stimulation experiment using functional MRS. The paradigm used consisted of a rest period (5 min and 20 s), followed by a stimulation period (10 min and 40 s) and another rest period (10 min and 40 s). MRS from 17 healthy subjects were acquired at 3T with TR/TE = 2000/288 ms. Spectra were averaged over subjects and quantified with LCModel. The main outcomes were that NAA concentration decreased by about 20% with the stimulus, while the concentration of NAAG concomitantly increased by about 200%. Such variations fall into models for the energy metabolism underlying neuronal activation that point to NAAG as being responsible for the hyperemic vascular response that causes the BOLD signal. They also agree with the fact that NAAG and NAA are present in the brain at a ratio of about 1:10, and with the fact that the only known metabolic pathway for NAAG synthesis is from NAA and glutamate.

Depression and anxiety in a community sample with epilepsy in Brazil / Depressão e ansiedade na epilepsia: uma amostra da comunidade no Brasil

OBJECTIVE: To estimate the frequency of depression/anxiety and to establish the social, epilepsy and psychiatric characteristics in individuals with epilepsy. METHOD: A cross-sectional study was employed to evaluate 153 subjects with epilepsy who were identified in a previous community-based survey. First, a structured interview was conducted, followed by a psychiatric evaluation. Subjects with depression were compared to those without, and subjects with anxiety were compared to those without. RESULTS: The prevalence of anxiety and depression was 39.4 and 24.4 percent, respectively. Both were associated with low schooling (OR 3.8, 95 percent CI 1.6 to 9.0 and OR 2.8, 95 percent CI 1.2 to 6.5 for depression and anxiety, respectively), lifetime suicidal thoughts (OR 4.4, 95 percent CI 1.9 to 10.3 and OR 3.6, 95 percent CI 1.7 to 7.7) and lifetime suicide attempts (OR 9.3, 95 percent CI 2.6 to 32.8 and OR 6.9, 95 percent CI 1.8 to 26.4). CONCLUSION: The high rates of depression and anxiety reinforced the need for recognition and treatment of mental disorders in epilepsy.

OBJETIVO: Estimar a frequência de depressão/ansiedade em pessoas com epilepsia e estabelecer as características sociais, da epilepsia e psiquiátricas associadas. MÉTODO: Foi feito um estudo transversal para avaliar 153 sujeitos com epilepsia identificados em um levantamento prévio feito na comunidade. Primeiramente foi realizada uma entrevista estruturada, seguida de uma avaliação psiquiátrica. Os sujeitos deprimidos foram comparados com aqueles sem depressão e os sujeitos com ansiedade foram comparados com aqueles sem ela. RESULTADOS: A prevalência de ansiedade e depressão foi de 39,4 por cento e 24,4 por cento, respectivamente. Ambas foram associadas a baixa escolaridade (OR 3,8; IC95 por cento 1,6-9,0 e OR 2,8, IC95 por cento 1,2- 6,5 para depressão e ansiedade, respectivamente), ideação suicida (OR 4,4; IC95 por cento 1,9-10,3 e OR 3,6; IC95 por cento 1,7-7,7) e tentativa de suicídio (OR 9,3; IC95 por cento 2,6-32,8 e OR 6,9; IC95 por cento 1,8-26,4). CONCLUSÃO: As altas taxas de depressão e ansiedade reforçam a necessidade de reconhecimento e tratamento dos transtornos mentais na epilepsia.

Texture analysis of computed tomography images of acute ischemic stroke patients

Computed tomography (CT) images are routinely used to assess ischemic brain stroke in the acute phase. They can provide important clues about whether to treat the patient by thrombolysis with tissue plasminogen activator. However, in the acute phase, the lesions may be difficult to detect in the images using standard visual analysis. The objective of the present study was to determine if texture analysis techniques applied to CT images of stroke patients could differentiate between normal tissue and affected areas that usually go unperceived under visual analysis. We performed a pilot study in which texture analysis, based on the gray level co-occurrence matrix, was applied to the CT brain images of 5 patients and of 5 control subjects and the results were compared by discriminant analysis. Thirteen regions of interest, regarding areas that may be potentially affected by ischemic stroke, were selected for calculation of texture parameters. All regions of interest for all subjects were classified as lesional or non-lesional tissue by an expert neuroradiologist. Visual assessment of the discriminant analysis graphs showed differences in the values of texture parameters between patients and controls, and also between texture parameters for lesional and non-lesional tissue of the patients. This suggests that texture analysis can indeed be a useful tool to help neurologists in the early assessment of ischemic stroke and quantification of the extent of the affected areas.

Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.

The importance of accurate anatomic assessment for the volumetric analysis of the amygdala

There is a wide range of values reported in volumetric studies of the amygdala. The use of single plane thick magnetic resonance imaging (MRI) may prevent the correct visualization of anatomic landmarks and yield imprecise results. To assess whether there is a difference between volumetric analysis of the amygdala performed with single plane MRI 3-mm slices and with multiplanar analysis of MRI 1-mm slices, we studied healthy subjects and patients with temporal lobe epilepsy. We performed manual delineation of the amygdala on T1-weighted inversion recovery, 3-mm coronal slices and manual delineation of the amygdala on three-dimensional volumetric T1-weighted images with 1-mm slice thickness. The data were compared using a dependent t-test. There was a significant difference between the volumes obtained by the coronal plane-based measurements and the volumes obtained by three-dimensional analysis (P < 0.001). An incorrect estimate of the amygdala volume may preclude a correct analysis of the biological effects of alterations in amygdala volume. Three-dimensional analysis is preferred because it is based on more extensive anatomical assessment and the results are similar to those obtained in post-mortem studies.

Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE), we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic) with FMTLE. We used NIH-Image© for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52 percent of all individuals: 54 percent of affected subjects and 48 percent of asymptomatic subjects. T1 hippocampal signal changes were found in 34 percent of all individuals: 42.5 percent of affected subjects and 15 percent of asymptomatic subjects. Analysis of the hippocampal head (first three slices) revealed T2 abnormalities in 73 percent of all individuals (74 percent of affected subjects and 72 percent of asymptomatic subjects) and T1 abnormalities in 59 percent (67 percent of affected subjects and 41 percent of asymptomatic subjects). Affected individuals had smaller volumes than controls (P < 0.0001). There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39 percent of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals) had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.

Purificación y caracterización parcial de una enzima dextranasa a partir de una cepa del hongo del género Penicillium / Purification and partial characterization of a destranase enzyme from a fungal strain of the genero Penicillium

Una fracción dextranasa (EC 3.2.1.11) excretada por un hongo del género Penicillium, fue purificada después de cinco días de inducción de la enzima en cultivo sumergido en agitación a 28-C. El crudo enzimático fue precipitado con 80 % de sulfato de amonio, resuspendido en tampóm acetato y aplicado en cromatografía sucesivas de filtración por el gel e intercambio iónico. La fracción homogénea de dextrabasa está formada por dos bandas de proteinas superpuestas con un peso molecular aproximado de 67 000 Da, un nivel de glicosidación entre 15-18 % y un punto isoeléctrico a pH 3,88. La actividad específica osciló entre 1 500 y 2 000 U/mg de proteína con un máximo de actividad a pH 5