Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.
Plasmodium falciparum placental malaria is characterized by the sequestration of infected erythrocytes (IEs) in the placental intervillous space via adherence to chondroitin sulphate A (CSA), production of inflammatory molecules, and leukocytes infiltration. Previous reports suggest that the syncytiotrophoblast (ST) immunologically responds to IEs contact. This study explores the inflammatory response induced in BeWo cells by adherence of IEs and TNFstimulation.
The aim of the study was to examine longitudinal patterns of decision making based on risk and reward using a modified version of the Iowa Gambling Task (IGT) in children who had sustained traumatic brain injury (TBI) and children with orthopedic injury (OI). Participants were 135 children and adolescents with TBI (n=71) or OI (n=64) who were 7-17 years at the time of injury were enrolled and assessed prospectively at baseline and at follow-up intervals of 3, 12, 18, and 24 months after injury. Groups were similar in age, socioeconomic status, and gender. Participants chose from four decks of cards with the aim of maximizing earnings across 100 trials. Two of the decks offered relatively small rewards and relatively small losses, but were advantageous over the course of the experiment. The other two decks offered large rewards, but also introduced occasional large losses, and were considered disadvantageous over the course of the experiment. The variable of interest was the proportion of advantageous decks chosen across trials. Longitudinal analysis of the pattern of change across 2 years revealed a three-way interaction among injury group, age, and the quadratic term of interval-since-injury. In this interaction, the effect of age weakened in the TBI group across time, as compared to the OI group, which showed stronger quadratic patterns across the recovery intervals that differed by age. The OI group generally outperformed the TBI group. In addition, analyses revealed a three-way interaction among group, gender and the cubic term of post-injury interval, such that overall, males improved a great deal with time, but females showed small gains, regardless of injury group.
Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI.
The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.
A 26-year-old woman with secondary amenorrhea and turneroid stigmata was found to have a 46,X,rea(X)(qter?p11.2::q21.2?qter)/46,X,del(X)(qter?p11.2:) mosaicism in 101 G-banded metaphases (71 and 30, respectively). The mothers karyotype was normal (the father was already deceased). A fully skewed inactivation of both abnormal X-chromosomes was documented in RBG-banded metaphases and by means of the HUMARA assay. In addition, the latter revealed that the involved X-chromosome was the paternal one. The patients secondary amenorrhea and turneroid stigmata can reliably be ascribed to her nearly complete Xp deletion present in all cells. Thus, this observation is consistent with the well-known gradation of ovarian function depending on the Xp deletion size. We assume that the first event was an intrachromosome recombination during paternal meiosis between paralogous sequences at Xp11.2 and Xq21.2, which resulted in a fertilizing rea(X) spermatozoid. Early in embryogenesis, the rea(X) dissociated at the Xp11.2 junction point to originate the del(X), which in turn was healed by the de novo addition of telomeric repeats (the acentric Xq21.2?qter segment was lost in the process). The reverse sequence appears unlikely because it implies that the del(X) chromosome was healed only after it undergone a postzygotic interchromatid recombination and apposite segregation required to obtain the rea(X) clone. The present observation further expands the cytogenetic heterogeneity in Turner syndrome and may represent another instance of a terminal deletion healed by the de novo addition of telomeric repeats.
We studied social cognition in 49 children 3 months after moderate to severe traumatic brain injury (TBI) and in 39 children with orthopedic injury (OI). Children underwent diffusion tensor imaging (DTI) and a mental attribution task showing two triangles. Mental state attributions increased when one triangle reacted to intentions of the other, but less so in the TBI than the OI group. DTI identified injury to white matter microstructure in the TBI group, but the relation of DTI to mental attributions did not differ between groups. Moderate to severe TBI produces white matter disconnections that may affect social cognitive networks.
Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n=37) or moderate-to-severe TBI (n=40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p=0.003), left orbitofrontal WM (p<0.02), and left (p<0.02) and right (p<0.008) uncinate fasciculi significantly predicted EB-PM performance in the high motivation condition. We infer that the cingulum bundles, orbitofrontal WM, and uncinate fasciculi are important WM structures mediating motivation-based EB-PM responses following moderate-to-severe TBI in children.
Information regarding the remediation of event-based prospective memory (EB-PM) impairments following pediatric traumatic brain injury (TBI) is scarce. Addressing this, two levels of monetary incentives were used to improve EB-PM in children ages 7 to 16 years with orthopedic injuries (OI, n = 51), or moderate (n = 25) and severe (n = 39) TBI at approximately 3 months postinjury. The EB-PM task consisted of the child giving a specific verbal response to a verbal cue from the examiner while performing a battery of neuropsychological measures (ongoing task). Significant effects were found for age-at-test, motivation condition, period, and group. Within-group analyses indicated that OI and moderate TBI groups performed significantly better under the high- than under the low-incentive condition, but the severe TBI group demonstrated no significant improvement. These results indicate that EB-PM can be significantly improved at 3 months postinjury in children with moderate, but not severe, TBI.
Distal 15q trisomy or tetrasomy is associated with a characteristic phenotype that includes mild to moderate intellectual disability, abnormal behavior, speech impairment, overgrowth, hyperlaxity, long face, prominent nose, puffy cheeks, pointed chin, small ears, and hand anomalies (mainly arachno- and camptodactyly). We present the case of a 13-yr-old girl with the main clinical features of 15q overgrowth syndrome and a 46,XX,dup(15)(q24q26.3)/46,XX.ish dup(15)(q24q26.3) (SNPRN+,PML+,subtel++,tel++) de novo karyotype. The findings in this case are consistent with those in the previous distal 15q trisomy cases that presented with overgrowth and mental retardation. Further, the rearranged chromosome had a double set of directly oriented telomeric and subtelomeric sequences.
Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.
While event-based prospective memory (EB-PM) tasks are a familiar part of daily life for children, currently no data exists concerning the relation between EB-PM performance and brain volumetrics after traumatic brain injury (TBI). This study investigated EB-PM in children (7 to 17 years) with moderate to severe TBI or orthopedic injuries. Participants performed an EB-PM task and concurrently underwent neuroimaging at three months postinjury. Surface reconstruction and cortical thickness analysis were performed using FreeSurfer software. Cortical thickness was significantly correlated with EB-PM (adjusting for age). Significant thinning in the left (dorsolateral and inferior prefrontal cortex, anterior and posterior cingulate, temporal lobe, fusiform, and parahippocampal gyri), and right hemispheres (dorsolateral, inferior, and medial prefrontal cortex, cingulate, and temporal lobe) correlated positively and significantly with EB-PM performance; findings are comparable to those of functional neuroimaging and lesion studies of EB-PM.
Individuals with traumatic brain injury (TBI) exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically developing (TD) controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems), distraction (distractor item present or absent), and animacy (living or non-living items in the problems). We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical-behavior correlations as observed in TD individuals.
Atrophy of the corpus callosum (CC) is a documented consequence of moderate-to-severe traumatic brain injury (TBI), which has been expressed as volume loss using quantitative magnetic resonance imaging (MRI). Other advanced imaging modalities such as diffusion tensor imaging (DTI) have also detected white matter microstructural alteration following TBI in the CC. The manner and degree to which macrostructural changes such as volume and microstructural changes develop over time following pediatric TBI, and their relation to a measure of processing speed is the focus of this longitudinal investigation. As such, DTI and volumetric changes in the CC in participants with TBI and a comparison group at approximately 3 and 18 months after injury as well as their relation to processing speed were determined.
This study examined the use of diffusion tensor imaging in detecting white matter changes in the frontal lobes following pediatric traumatic brain injury. A total of 46 children (ages 8-16 years) with moderate to severe traumatic brain injury and 47 children with orthopedic injury underwent 1.5 Tesla magnetic resonance imaging (MRI) at 3 months postinjury. Conventional MRI studies were obtained along with diffusion tensor imaging. Diffusion tensor imaging metrics, including fractional anisotropy, apparent diffusion coefficient, and radial diffusivity, were compared between the groups. Significant group differences were identified, implicating frontal white matter alterations in the injury group that were predictive of later Glasgow Outcome Scale ratings; however, focal lesions were not related to the Glasgow Outcome Scale ratings. Injury severity was also significantly associated with diffusion tensor imaging metrics. Diffusion tensor imaging holds great promise as an index of white matter integrity in traumatic brain injury and as a potential biomarker reflective of outcome.
Deficits in self awareness and taking the perspective of others are often observed following traumatic brain injury (TBI). Nine adolescents (ages 12-19 years) who had sustained moderate to severe TBI after an average interval of 2.6 years and nine typically developing (TD) adolescents underwent functional MRI (fMRI) while performing a perspective taking task (DArgembeau et al., 2007). Participants made trait attributions either from their own perspective or from that of the significant other. The groups did not differ in reaction time or on a consistency criterion. When thinking of the self from a third-person perspective, adolescents with TBI demonstrated greater activation in posterior brain regions implicated in social cognition, the left lingual gyrus (BA 18) and posterior cingulate (BA 31), extending into neighboring regions not generally associated with social cognition, that is, cuneus (BA 31) and parahippocampal gyrus, relative to TD adolescents. We postulate that adolescents with moderate to severe TBI recruited alternative neural pathways during perspective-taking because traumatic axonal injury disrupted their fronto-parietal networks mediating social cognition.
There are very few studies investigating remediation of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, we used 2 levels of motivational enhancement (dollars vs. pennies) to improve EB-PM in children with moderate to severe TBI in the subacute recovery phase. Children with orthopedic injuries (OI; n = 61), moderate (n = 28), or severe (n = 30) TBI were compared. Significant effects included Group x Motivation Condition (F(2, 115) = 3.73, p < .03). The OI (p < .002) and moderate TBI (p < .03) groups performed significantly better under the high- versus low-incentive condition; however, the severe TBI group failed to demonstrate improvement (p = .38). EB-PM performance was better in adolescents compared to younger children (p < .02). These results suggest that EB-PM can be significantly improved in the subacute phase with this level of monetary incentives in children with moderate, but not severe, TBI. Other strategies to improve EB-PM in these children at a similar point in recovery remain to be identified and evaluated.
Diffusion tensor imaging (DTI) was performed in 39 right-handed children to examine structural hemispheric differences and the impact of age, socioeconomic status, and sex on these differences. Apparent diffusion coefficient (ADC) values were smaller in the left than in the right temporal, prefrontal, anterior internal capsular and the thalamic regions, and fractional anisotropy (FA) values were larger in the left than in the right internal capsule, thalamus, and cingulate. Significant region-by-sex interactions disclosed that the relation of DTI asymmetries to performance depended on sex including the relation of temporal lobes to reading comprehension and the relation of frontal lobes to solving applied mathematical problems.
The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream.
To examine initial Glasgow Coma Scale (GCS) score and its relationship with later cerebral atrophy in children with traumatic brain injury (TBI) using Quantitative Magnetic Resonance Imaging (QMRI) at 4 months post-injury. It was hypothesized that a lower GCS score would predict later generalized atrophy. As a guide in assessing paediatric TBI patients, the probability of developing chronic cerebral atrophy was determined based on the initial GCS score.
The most recognized pathogenic mechanisms of the infection with Plasmodium falciparum, during both the erythrocytic and exo-erythrocytic stages are presented. Vascular obstruction explained by the sequestration of parasitized red blood cells and erythrocyte rosetting, mediated by different endothelial ligands and receptors, in addition to the inflammatory processes induced by the presence of the parasite, are central aspects in the pathogenesis of malaria that explain the processes of damage, dysfunction and cell death in various organs. Alterations such as increased vascular permeability, hypoxia and anaerobic metabolism leading to localized lesions in organs such as brain and lung, as well as to a generalized acidotic state with multisystem failure can be explained by events such as the injury and destruction of erythrocytes, hepatocytes and endothelial cells, the loss of endothelial integrity, and the activation of cell damage and apoptosis promoters.
The objective was to examine the effects of traumatic brain injury (TBI), as compared with orthopedic injury (OI), relative to the risk for psychiatric disorder. There has only been one previous prospective study of this nature. Participants were age 7-17 years at the time of hospitalization for either TBI (complicated mild-to-severe) or OI. The study used a prospective, longitudinal, controlled design, with standardized psychiatric assessments conducted at baseline (reflecting pre-injury functioning) and 3 months post-injury. Assessments of pre-injury psychiatric, adaptive functioning, family adversity, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales. The outcome measure was the presence of a psychiatric disorder not present before the injury ("novel"), during the first 3 months after TBI. Enrolled participants (N=141) included children with TBI (N=75) and with OI (N=66). The analyses focused on 118 children (84%) (TBI: N=65; OI: N=53) who returned for follow-up assessment at 3 months. Novel psychiatric disorder (NPD) occurred significantly more frequently in the TBI (32/65; 49%) than the OI (7/53; 13%) group. This difference was not accounted for by pre-injury lifetime psychiatric status; pre-injury adaptive functioning; pre-injury family adversity, family psychiatric history, socioeconomic status, injury severity, or age at injury. Furthermore, none of these variables significantly discriminated between children with TBI who developed, versus those who did not develop, NPD. These findings suggest that children with complicated mild-to-severe TBI are at significantly higher risk than OI-controls for the development of NPD in the first 3 months after injury.
To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI).
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