Multiplexed Quantitative Proteomics Reveals Proteomic Alterations in Two Rodent Traumatic Brain Injury Models.

In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.

An exploratory study on functional connectivity after mild traumatic brain injury: Preserved global but altered local organization.

INTRODUCTION: This study aimed to investigate alterations in whole-brain functional connectivity after a concussion using graph-theory analysis from global and local perspectives and explore the association between changes in the functional network properties and cognitive performance. METHODS: Individuals with mild traumatic brain injury (mTBI, n = 29) within a month after injury, and age- and sex-matched healthy controls (n = 29) were included. Graph-theory measures on functional connectivity assessed using resting state functional magnetic resonance imaging data were acquired from each participant. These included betweenness centrality, strength, clustering coefficient, local efficiency, and global efficiency. Multi-domain cognitive functions were correlated with the graph-theory measures. RESULTS: In comparison to the controls, the mTBI group showed preserved network characteristics at a global level. However, in the local network, we observed decreased betweenness centrality, clustering coefficient, and local efficiency in several brain areas, including the fronto-parietal attention network. Network strength at the local level showed mixed-results in different areas. The betweenness centrality of the right parahippocampus showed a significant positive correlation with the cognitive scores of the verbal learning test only in the mTBI group. CONCLUSION: The intrinsic functional connectivity after mTBI is preserved globally, but is suboptimally organized locally in several areas. This possibly reflects the neurophysiological sequelae of a concussion. The present results may imply that the network property could be used as a potential indicator for clinical outcomes after mTBI.

Fracture risk and impact of osteoporosis in patients with Parkinson's disease: a nationwide database study.

INTRODUCTION: Patients with Parkinson's disease (PD) showed an increased risk of fractures in previous studies and a high prevalence of osteoporosis is reportedly a potential contributor. We conducted a nationwide database study on the risk of fractures and the impact of osteoporosis on patients with PD compared to controls. MATERIALS AND METHODS: Using a nationwide database in South Korea, we identified incident patients with PD in 2004-2006 and selected four age- and sex-matched controls. We checked the occurrence rates of overall and hip fractures and plotted Kaplan-Meier curves and a Cox proportional hazards model to determine risk. We also conducted stratified analyses according to the presence or absence of osteoporosis. RESULTS: We identified 9126 patients with PD and 35,601 controls. Patients with PD had a greater probability of fractures throughout the study period in Kaplan-Meier curves, and an increased risk of overall (aHR 1.35, 95% CI 1.297-1.405) and hip (aHR 1.814, 95% CI 1.66-1.983) fractures in a Cox proportional hazards model. In the stratified analysis, the increased risk of overall fracture (aHR 1.333, 95% CI 1.273-1.396 and aHR 1.412, 95% CI 1.301-1.532, respectively) and hip fracture (aHR 1.773, 95% CI 1.604-1.96 and aHR 2.008, 95% CI 1.657-2.434, respectively) due to PD was similar between patients with and without osteoporosis. DISCUSSION: Patients with PD, with or without osteoporosis, are more likely to experience fractures, especially hip fractures. There seems to be no interaction between PD and osteoporosis in regard to the occurrence of fractures, and therefore no effect modification by osteoporosis.

A systematic review and data synthesis of longitudinal changes in white matter integrity after mild traumatic brain injury assessed by diffusion tensor imaging in adults.

PURPOSE: This study aimed to review diffusion tensor imaging studies of mild traumatic brain injury (mTBI) in adults with longitudinal acquisition of data and investigate the variability of findings in association with related factors, such as the time post-injury. METHODS: Eligible studies from PubMed and EMBASE were searched to identify relevant studies for review. Of the 540 studies, 23 observational studies without intervention and with the following characteristics were included: original research in which adults with mTBI were examined, diffusion tensor imaging was acquired at least twice, white matter integrity was investigated by estimating diffusion metrics, and mode of injury was not restricted to sport- or blast-related mTBI. RESULTS: Baseline scans were acquired within 3 weeks post-injury, followed by longitudinal scans within 3 months and at 12 months post-injury. During the acute/subacute period, mixed results (increase, decrease, or no significant change) of fractional anisotropy (FA) were observed compared to those in controls. Some studies reported increased FA during the acute/subacute period compared to controls, followed by normalization of FA. Decreased FA was also reported during the acute/subacute period, which lasted long into the chronic phase. In the acute phase, the mean diffusivity (MD) was greater than that in the controls. Compared to the early phase of injury, MD was reduced in the follow-up phase in most studies in the mTBI group. Insignificant differences in FA and MD have been reported in several studies. Such variability limits the clinical usefulness of diffusion tensor metrics. CONCLUSIONS: There was a high variability in reported changes in white matter integrity. Decreased FA not only in acute/subacute but also in long-term period after injury may indicate long-term neurodegenerative processes after mTBI. Nevertheless, longitudinal changes in MD towards normalization suggest possible recovery. Long-term cohort studies with research initiatives should be considered to elucidate brain changes after mTBI.

Development of a Novel Prognostic Model to Predict 6-Month Swallowing Recovery After Ischemic Stroke.

Background and Purpose- The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm. Methods- Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function. Results- Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status (P<0.001), bilateral lesions at CR/BG/IC (P=0.001), and clinical dysphagia scale (P=0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study. Conclusions- Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.

Differential kinematic features of the hyoid bone during swallowing in patients with Parkinson's disease.

This study aimed to investigate spatiotemporal characteristics of the hyoid bone during swallowing in patients with Parkinson's disease (PD) and dysphagia. Spatiotemporal data of the hyoid bone was obtained from videofluoroscopic images of 69 subjects (23 patients with PD, 23 age- and sex-matched healthy elderly controls, and 23 healthy young controls). Normalized profiles of displacement/velocity were analyzed during different periods (percentile) of swallowing using functional regression analysis, and the maximal values were compared between the groups. Maximal horizontal displacement and velocity were significantly decreased during the initial backward (P = 0.006 and P < 0.001, respectively) and forward (P = 0.008 and P < 0.001, respectively) motions in PD patients compared to elderly controls. Maximal vertical velocity was significantly lower in PD patients than in elderly controls (P = 0.001). No significant difference was observed in maximal displacement and velocity in both horizontal and vertical planes between the healthy elderly and young controls, although horizontal displacement was significantly decreased during the forward motion (51st-57th percentiles) in the elderly controls. In conclusion, reduced horizontal displacement and velocity of the hyoid bone during the forward motion would be due to combined effects of disease and aging, whereas those over the initial backward motion may be considered specific to patients with PD.

Spinal Cord Injury During Ultrasound-Guided C7 Cervical Medial Branch Block.

Ultrasound-guided cervical medial branch block (CMBB) is commonly performed to diagnose and treat head, neck, and shoulder pain. However, its use at the C7 level has been shown to be less accurate than at other levels, which may increase the chance of injury owing to the imprecision of needle site provided by the ultrasound guide. We report the first case of iatrogenic spinal cord injury from an ultrasound-guided C7 CMBB. The patient, upon receiving this procedure, had fainted shortly after experiencing an electrical sensation that ran from the neck to the toe. The patient complained of weakness and tingling sensation in the left upper extremity. Cervical magnetic resonance imaging revealed a hematoma in the cervical spinal cord, and an electrophysiological study, which was performed at 3 weeks after the incident, revealed an injury at the left C3-T2 anterior horn. After 2 months of rehabilitation, the patient showed moderate improvement in the strength of the left proximal upper extremity; however, there was no improvement in the strength of the left distal upper extremity. Therefore, we recommend caution when performing ultrasound-guided CMBB at the C7 level, as the guide particularly at this level is relatively inaccurate, posing a risk of spinal cord injury.