Cortical and Subcortical Alterations and Clinical Correlates after Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) often results in persistent cognitive impairment and psychiatric symptoms, while lesion location and severity are not consistent with its clinical complaints. Previous studies found cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however, the location and extent of contusions often cannot fully explain the patient's impairments. Thus, we try to find the structural changes of gray matter (GM) and white matter (WM), clarify their correlation with psychiatric symptoms and memory following TBI, and determine the brain regions that primary correlate with clinical measurements. Methods: Overall, 32 TBI individuals and 23 healthy controls were recruited in the study. Cognitive impairment and psychiatric symptoms were examined by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), and Wechsler Memory Scale-Chinese Revision (WMS-CR). All MRI data were scanned using a Siemens Prisma 3.0 Tesla MRI system. T1 MRI data and diffusion tensor imaging (DTI) data were processed to analyze GM volume and WM microstructure separately. Results: In the present study, TBI patients underwent widespread decrease of GM volume in both cortical and subcortical regions. Among these regions, four brain areas including the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and anterior cingulate cortex (ACC) were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints. TBI patients also underwent changes of WM microstructure, involving decreased fractional anisotropy (FA) value in widespread WM tracts and increased mean diffusivity (MD) value in the forceps minor. The changes of WM microstructure were significantly correlated with the decrease of GM volume. Conclusions: TBI causes widespread cortical and subcortical alterations including a reduction in GM volume and change in WM microstructure related to clinical manifestation. Lesions in temporal lobe may lead to more serious cognitive and emotional dysfunction, which should attract our high clinical attention.

Structural and Functional Alterations of Substantia Nigra and Associations With Anxiety and Depressive Symptoms Following Traumatic Brain Injury.

Backgrounds: Although there are a certain number of studies dedicated to the disturbances of the dopaminergic system induced by traumatic brain injury (TBI), the associations of abnormal dopaminergic systems with post-traumatic anxiety and depressive disorders and their underlying mechanisms have not been clarified yet. In the midbrain, dopaminergic neurons are mainly situated in the substantia nigra (SN) and the ventral tegmental area (VTA). Thus, we selected SN and VTA as regions of interest and performed a seed-based global correlation to evaluate the altered functional connectivity throughout the dopaminergic system post-TBI. Methods: Thirty-three individuals with TBI and 21 healthy controls were recruited in the study. Anxiety and depressive symptoms were examined by the Hospital Anxiety and Depression Scale. All MRI data were collected using a Siemens Prisma 3.0 Tesla MRI system. The volume of SN and the global functional connectivity of the SN and VTA were analyzed. Results: In the present study, patients with TBI reported more anxiety and depressive symptoms. More importantly, some structural and functional alterations, such as smaller SN and reduced functional connectivity in the left SN, were seen in individuals with TBI. Patients with TBI had smaller substantia nigra on both right and left sides, and the left substantia nigra was relatively small in contrast with the right one. Among these findings, functional connectivity between left SN and left angular gyrus was positively associated with post-traumatic anxiety symptoms and negatively associated with depressive symptoms. Conclusions: The TBI causes leftward lateralization of structural and functional alterations in the substantia nigra. An impaired mesocortical functional connectivity might be implicated in post-traumatic anxiety and depression.

Decreased Interhemispheric Functional Connectivity and Its Associations with Clinical Correlates following Traumatic Brain Injury.

Objective: To explore the interhemispheric functional coordination following traumatic brain injury (TBI) and its association with posttraumatic anxiety and depressive symptoms. Methods: This was a combination of a retrospective cohort study and a cross-sectional observational study. We investigated the functional coordination between hemispheres by voxel-mirrored homotopic connectivity (VMHC). Grey matter volumes were examined by voxel-based morphometry (VBM), and microstructural integrity of the corpus callosum (CC) was assessed by diffusion tension imaging (DTI). The anxiety and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale. Results: The VMHC values of the bilateral middle temporal gyrus (MTG) and orbital middle frontal gyrus (MFG) were significantly decreased in TBI patients versus the healthy controls. Weakened homotopic functional connectivity (FC) in the bilateral orbital MFG is moderate positively correlated with anxiety and depressive symptoms. The white matter integrity in the CC was extensively reduced in TBI patients. In the receiver operating characteristic analysis, the VMHC value of the orbital MFG could distinguish TBI from HC with an area under the curve of 0.939 (sensitivity of 1 and specificity of 0.867). Conclusion: TBI disrupts the interhemispheric functional and structural connection, which is correlated with posttraumatic mood disorders. These findings may serve as a clinical indicator for diagnosis.

Association of Anxiety and Depressive Symptoms with Memory Function following Traumatic Brain Injury.

INTRODUCTION: Memory impairment and mood disorders are among the most troubling sequelae following traumatic brain injury (TBI). The relationships between comorbid psychiatric disorders and memory function have not been well illustrated. The aim of the study was to explore the relationships of comorbid anxiety and depressive symptoms with memory function following TBI. METHODS: A total of 46 TBI participants across all levels of injury and 23 healthy controls were enrolled in this case-control study. Wechsler Memory Scale-Chinese Revision (WMS-CR) picture, recognition, associative learning, comprehension memory, and digit span were administered to evaluate several categories of memory capacity. The Hospital Anxiety and Depression Scale (HADS) was employed to evaluate the anxiety and depressive symptoms. Stepwise multiple linear regressions were conducted. RESULTS: Compared to healthy controls, the participants with TBI reported more anxiety and depressive symptoms. In the meanwhile, they performed more poorly on memory tests, showing 1.84 SDs, 1.07 SDs, and 0.68 SDs below healthy participants on visuospatial memory, working memory, and verbal memory, respectively. A variety of variables, including HADS depression, HADS anxiety, age, GCS, and education were associated with posttraumatic memory function in the bivariate models. The stepwise multiple linear regressions demonstrated a negative association between HADS depression and posttraumatic memory function, especially performance on visuospatial and verbal memory and a positive association between education and posttraumatic memory function. CONCLUSION: More depressive symptoms rather than anxiety symptoms and less years of education are significant predictors for posttraumatic memory dysfunction.

Exogenous insulin-like growth factor 1 attenuates acute ischemic stroke-induced spatial memory impairment via modulating inflammatory response and tau phosphorylation.

Acute ischemic stroke is one of the main causes of mortality and morbidity worldwide. The present study aimed to explore the effects of exogenous insulin-like growth factor 1 (IGF-1) on the cognitive injuries induced by acute ischemic stroke and the underlying mechanisms. Acute ischemic stroke rat model was established via transient occlusion of the left middle cerebral artery to male Sprague-Dawley rats. IGF-1 was administered intravenously every other day 24 h after surgery for 14 days. Cognitive functions were determined by Morris water maze assay. Cerebral infarction and edema were determined by riphenyltetrazolium chloride staining and cerebral water content measurement. ELISA and Western blot were performed to detect concentrations of target proteins. Ischemic stroke rats exhibited reduced plasma IGF-1 level and impaired cognitive functions. Intravenous IGF-1 delivery increased the IGF-1 levels in plasma, ischemic amygdala, hippocampus and cortex, improved the neurological dysfunction, cognitive deficits, cerebral infarction and brain edema. Furthermore, IGF-1 relieved the systemic and cerebral inflammatory response by inhibiting the secretion of pro-inflammatory cytokines, interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α), in serum and ischemic hippocampus of ischemic rats. Additionally, IGF-1 attenuated tau phosphorylation in ischemic hippocampus. In short, intravenous IGF-1 administration attenuates acute ischemic stroke-induced cognitive injuries in the experimental rat model possibly via modulating inflammatory response and tau phosphorylation, and might be of promising therapeutic value to ischemic stroke in the future.

Prognosis analysis and risk factors related to progressive intracranial haemorrhage in patients with acute traumatic brain injury.

BACKGROUND: Since progressive intracranial haemorrhage (PIH) was introduced in neurosurgical literatures, several studies have been performed. PIH has been shown to be associated with a high increase in the risk of clinical worsening and related to morbidity and mortality as well. So, early detection and prediction of PIH is practically important in a clinical situation. OBJECTIVES: To investigate the risk factors related to PIH in patients with acute traumatic brain injury (TBI) and analyse their clinical significances. METHODS: PIH was confirmed by comparing the first and repeated CT scans. Data compared included gender, age, mechanism of injury, Glasgow Coma Score (GCS) at admission, timing from injury to the first CT, the signs of the initial CT scan, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), platelet (PLT) and D-dimer (D-D) values. Logistic regression analysis was used to show the risk factors related to PIH. RESULTS: A cohort of 498 patients with TBI was evaluated, and there were 139 (27.91%) patients who suffered from PIH. The differences between PIHs and non-PIHs were significant in age, GCS at admission, the signs of the initial CT scan (fracture, subarachnoid haemorrhage, brain contusion and primary haematoma), PT, Fg and D-D values (p < 0.001). Logistic regression analysis was used to identify that CT scans (subarachnoid haemorrhage, brain contusion and primary haematoma) and plasma D-D values as the most important predictors of PIH (p < 0.001). CONCLUSIONS: For patients with the initial CT scan showing subarachnoid haemorrhage, brain contusion and primary haematoma with abnormal D-D levels, an earlier and dynamic CT scan should be performed, for the detection of PIH as early as possible and the medical intervention would be enforced in time.

Early CT signs of progressive hemorrhagic injury following acute traumatic brain injury.

INTRODUCTION: Since progressive hemorrhagic injury (PHI) was introduced in neurosurgical literatures, several studies have been performed, the results of which have influenced doctors but do not define guidelines for the best treatment of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and it has been shown to be associated with a fivefold increase in the risk of clinical worsening and is a significant cause of morbidity and mortality as well. So, early detection of PHI is practically important in a clinical situation. METHODS: To analyze the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury (TBI) and explore their clinical significances, PHI was confirmed by comparing the first and repeated CT scans. Data were analyzed and compared including times from injury to the first CT and signs of the early CT scan. Logistic regression analysis was used to show the risk factors related to PHI. RESULTS: A cohort of 630 TBI patients was evaluated, and there were 189 (30%) patients who suffered from PHI. For patients with their first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases who suffered from PHI. The differences between PHIs and non-PHIs were significant in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple hematoma as well as the times from injury to the first CT scan (P < 0.01). Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture, and brain contusion) were predictors of PHI (P < 0.01). CONCLUSION: For patients with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan should be performed promptly. If the initial CT scan shows SAH, brain contusion, and primary hematoma with brain swelling, an earlier and dynamic CT scan should be performed for detection of PHI as early as possible and the medical intervention would be enforced in time.

Prediction of motor function by diffusion tensor tractography in patients with basal ganglion haemorrhage.

INTRODUCTION: Haemorrhagic stroke is one of the leading causes of death and the most common cause of long-term adult disability. An accurate estimation of prognosis is very important for haemorrhagic stroke patients. Impairment of motor function caused by pyramidal tract injury is common in these patients. In this study, we performed MR diffusion tensor tractography (DTT) to predict the impairment of motor function in patients with basal ganglion haemorrhage and explore its clinical value. MATERIAL AND METHODS: Diffusion tensor tractography was performed in 33 patients with basal ganglia haemorrhage within 2 weeks after onset to visualize the course of pyramidal tracts (PTs), and patients were classified into four groups according to the fibre ratio of PTs, calculated by dividing the PT number of the affected hemisphere by that of the unaffected hemisphere, as follows: type A, the fibre ratio was less than 1/4; type B, less than 1/2; type C, more than 1/2; and type D, more than 3/4. The upper extremity motricity index (UMI) was used to evaluate the motor function at onset and 6 months after onset. Upper extremity motricity index scores were compared among the different groups and a Spearman analysis was performed to correlate the UMI scores with different integrity of pyramidal tracts. RESULTS: There were no differences in the UMI scores at onset among the 4 groups (p< 0.05). The UMI scores obtained at 6 months after onset were significantly unequal and were influenced by the DTT type (p < 0.05). There was a significant correlation between the integrity of the pyramidal tracts and the UMI scores 6 months after onset (r = 0.7312, p< 0.05). CONCLUSIONS: There was a positive correlation between the integrity grade of pyramidal tracts and the motor function, showing that the more seriously were the pyramidal tracts damaged, the worse was the motor function. The DTT findings of the pyramidal tract in acute cerebral haemorrhage may valuably predict the motor function outcome.