Function In Traumatic Brain Injury Patients Research Articles

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Background and PurposeDysfunction of the blood–brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI. Materials and MethodsDCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (Ktrans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury. ResultsTBI patients exhibited higher mean Ktrans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated Ktrans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = −0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level. ConclusionsThis pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

The Effectiveness of Non-Invasive Brain Stimulation Alone or Combined with Cognitive Training on the Cognitive Performance of Patients With Traumatic Brain Injury: Α Systematic Review.

The present study reviewed published evidence on the effectiveness of non-invasive brain stimulation (NIBS) on the cognitive performance of patients with Traumatic brain injury (TBI). A systematic search of the PubMed and Google Scholar databases was carried out. Randomized Controlled Studies published before March 2020 were included. Methodological evaluation was performed based on the Risk of Bias Cochrane tool. A total of 10 placebo-controlled studies fulfilled the inclusion criteria and were involved in the qualitative analysis, two assessing NIBS combined with cognitive training (CT) and eight evaluating NIBS alone. All but one retrieved article were appraised as of high-risk of bias (one paper was assessed as of unclear-risk owing to considerable underreporting). With the potential exception of attention, our findings were not indicative of a superior efficacy of NIBS-CT to CT alone, regarding the improvement of any of the rest assessed cognitive deficits. Executive function, processing speed, attention, working, and visuospatial memory were only occasionally found to benefit from NIBS alone compared to sham therapy (only one study reported relevant benefits per neuropsychological outcome). Verbal memory and verbal fluency (phonemic-semantic) were consistently found not to benefit from NIBS. Depression measures were the only outcomes associated with a beneficial effect of NIBS in more than one article. Our findings did not provide sufficient high-quality evidence to support the exclusive use of NIBS or combined NIBS-CT to improve any impaired cognitive function in TBI patients. Owing to the suboptimum methodological quality of published studies, additional research is of potential value.

Omega-3 Fatty Acids and Vitamin D Decrease Plasma T-Tau, GFAP, and UCH-L1 in Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behaviors following exposure to mild TBI (mTBI). Adult, male rats were individually housed in cages fitted with running wheels and daily running distance was recorded throughout the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 days, and 30 days post-injury. Fatty acid composition of food, plasma, and brain tissues was determined. In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 days post-injury. T-tau, GFAP, and UCH-L1 plasma levels did not change at 48 h or 14 days post-injury. However, at 30 days post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). The temporal response of the four injury biomarkers examined is consistent with studies by others demonstrating acute and chronic neural tissue damage following exposure to TBI. The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP, and UCH-L1 following mTBI. Voluntary exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus, the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI.

Widespread White Matter Aberrations Are Associated with Phonemic Verbal Fluency Impairment in Chronic Traumatic Brain Injury.

Microstructural white matter (WM) disruption and resulting abnormal structural connectivity form a potential underlying pathology in traumatic brain injury (TBI). Herein, to determine the potential mechanism of cognitive deterioration in TBI, we examined the association of damage to specific WM tracts with cognitive function in TBI patients. We recruited 18 individuals with mild-to-moderate/severe TBI in the chronic phase and 17 age-matched controls. We determined the pattern of WM aberrations in TBI using tract-based spatial statistics (TBSS) and then examined the relationship between cognitive impairment and WM damage using the threshold-free cluster enhancement correction in TBSS. TBSS analysis showed that TBI patients exhibited WM aberrations in a wide range of brain regions. In the majority of these regions, lower fractional anisotropy (FA) largely overlapped with increased radial diffusivity, but not with axial diffusivity. Further, voxel-wise correction in TBSS demonstrated that higher FA values were associated with better performance in the phonemic verbal fluency task (VFT) in widespread WM regions, but not with the semantic VFT. Despite variation in the magnitude and location of brain injury between individual cases, chronic TBI patients exhibited widespread WM aberrations. We confirmed the findings of previous studies that WM integrity is lower across the spectrum of TBI severity in chronic subjects compared to controls. Further, phonemic VFT may be a more sensitive cognitive measure of executive dysfunction associated with WM aberrations in TBI compared with semantic VFT.

Understanding the neurotransmitter changes underlying cognitive dysfunction in traumatic brain injury and possible therapeutic targets: a review.

Traumatic brain injury (TBI) is the primary cause of death and disability in younger individuals [1]. To date, the mechanism behind the cognitive dysfunction following TBI remains unclear. Neurotransmitters (NT) represent a particularly important system in physiological events relevant to cognition affected by TBI [2]. Preclinical evaluations of both agonists and antagonists affecting acetylcholine (Ach) and the dopamine (DA) system have shown marked benefits for cognitive recovery. Hence, the aim of this article is to outline clinical studies that have shown potential efficacy of Ach- and DA-oriented medications in the treatment of TBI. PubMed was used to search for articles published since 1998 that reported any association between cognitive dysfunction following TBI. Before 1998, no clinical studies regarding the neurotransmitter-targeted therapies in TBI had been reported. After reviewing the abstracts, 14 articles were submitted to the final evidence review. Acetylcholinesterase (AChE) inhibitors are most beneficial for the treatment of posttraumatic cognitive impairments [3]. Principally, rivastigmine improved the cognitive function in TBI patients [4]. However, the results from randomized controlled trials have remained modest [5]. Zhang et al. [6] performed a 24-week, randomized, placebo-controlled, double-blind crossover trial to demonstrate sustained improvements in immediate auditory and visual memory, attention, working memory and information processing speed. An open-label study conducted by Tenovuo [7] also found a subjective and longer (average 24 months) improvement following donepezil (summarized in Table I). Table I Acetylcholinesterase inhibitors for cognitive rehabilitation after TBI Dopamine represents a unique role in the NT system within the central nervous system (CNS) due to its influences on a number of physiologic functions including working memory, behavioral flexibility, and decision making [8]. In 2006, the Neurotrauma Foundation (NTF) recommended three drugs with DAergic effects to be used in TBI patients to enhance cognitive recovery and rehabilitation [9]. The identified drugs were methylphenidate (MPD), amantadine hydrochloride (AMH), and bromocriptine [9]. Multiple studies have demonstrated the effectiveness of MPD used in TBI patients with cognitive dysfunction especially in information processing speed [10], attention [11, 12], alertness [13], and working memory [14] after brain trauma. However, there is no longer than six months follow-up in the clinical trials regarding MPD in patients with TBI. Amantadine hydrochloride has also been found to be effective at treating cognitive dysfunction post-TBI in both clinical trials and case reports. Kraus et al. [15] showed that AMH treatment improved prefrontal executive function in TBI patients correlated with an increase in left prefrontal cortex glucose metabolism. Patrick et al. [16] reported that AMH accelerated recovery of attention deficit in children with a lower response following brain injury. Bromocriptine is a specific D2 receptor agonist, and a past case report [17] showed improvements in motor function and executive function after administering bromocriptine in a severe TBI patient associated with Parkinson's syndrome. In contrast, McDowell et al. did not find that bromocriptine appeared to improve attentional difficulties in moderate to severe TBI patients. However, this study employed a relatively high dose of bromocriptine at 10 mg/day for a more prolonged treatment period than previously studied in TBI [18]. In addition, a 6-week placebo-controlled pilot study showed that bromocriptine in TBI patients also did not enhance attentional skills [19] (summarized in Table II). Table II Dopamine drugs for cognitive rehabilitation after TBI This brief review has sought to summarize the evidence that supports an NT-oriented hypothesis of cognitive dysfunction after TBI and provide a context for the use of Ach and DA targeted therapies during patient rehabilitation. In conclusion, it seems that applications of AChE inhibitors and DA agonists are beneficial in TBI patients with cognitive dysfunction.

Serial Mini-Mental Status Examination to Evaluate Cognitive Outcome in Patients with Traumatic Brain Injury.

ObjectiveThis study was aimed at finding out the changes in cognitive dysfunction in patients with traumatic brain injury (TBI) and investigating the factors limiting their cognitive improvement.MethodsBetween January 2010 and March 2014, 33 patients with TBI participated in serial mini-mental status examination (MMSE). Their cognitive functions were statistically analyzed to clarify their relationship with different TBI status. Patients who developed hydrocephalus were separately analyzed in regards to their cognitive function depending on the placement of ventriculoperitoneal shunt (VPS).ResultsBi-frontal lobe injury (β=-10.441, p<0.001), contre-coup injury (β=-6.592, p=0.007), severe parenchymal injury (β=-7.210, p=0.012), temporal lobe injury (β=-5.524, p=0.027), and dominant hemisphere injury (β=-5.388, p=0.037) significantly lowered the final MMSE scores. The risk of down-grade in the prognosis was higher in severe parenchymal injury [odds ratio (OR)=13.41, 95% confidence interval (CI)=1.31-136.78], temporal lobe injury (OR=12.3, 95% CI=2.07-73.08), dominant hemisphere injury (OR=8.19, 95% CI=1.43-46.78), and bi-frontal lobe injury (OR=7.52, 95% CI=1.31-43.11). In the 11 post-traumatic hydrocephalus patients who underwent VPS, the final MMSE scores (17.7±6.8) substantially increased from the initial MMSE scores (11.2±8.6).ConclusionPresence of bi-frontal lobe injury, temporal lobe injury, dominant hemisphere injury, and contre-coup injury and severe parenchymal injury adversely influenced the final MMSE scores. They can be concluded to be poor prognostic factors in terms of cognitive function in TBI patients. Development of hydrocephalus aggravates cognitive impairment with unpredictable time of onset. Thus, close observation and routine image follow-up are mandatory for early detection and surgical intervention for hydrocephalus.

Decrease in pituitary apparent diffusion coefficient in normal appearing brain correlates with hypopituitarism following traumatic brain injury

Following traumatic brain injury (TBI), there may be persistent pituitary deficits despite the presence of normal conventional magnetic resonance (MR) images. Little is known about the association of microstructural changes in the pituitary with pituitary function in TBI patients with normal appearing brain on conventional MR images. Our aim was to quantify changes in pituitary apparent diffusion coefficient (ADC) of normal appearing brain in human traumatic brain injury. Forty-two patients admitted with a diagnosis of mild head injury having normal appearing brain imaging were scanned at 7 days after injury using a quantitative echo planar imaging acquisition to obtain ADC parametric map. Mean pituitary ADC values were compared with a control group (n = 30). The TBI group showed a significant decrease in pituitary ADC compared to the controls. Furthermore, the mean ADC was much less in TBI patients with pituitary dysfunction compared to those with normal pituitary function. There was also a correlation between the development of pituitary dysfunction and decreasing ADC (r = 0.82, P<0.01). Our findings suggest that pituitary ADC is a sensitive and independent marker of pituitary damage following traumatic insult, which is useful to detect the microstructural damage in pituitary in normal appearing brain.

Why Voluntary Postural Training Improves Recovery of Mental and Motor Functions in Patients with Traumatic Brain Injury?

There are data about the positive effect of rehabilitation with postural training in traumatic brain injury (TBI) patients. Brain mechanisms of functional recovery have been investigated insufficiently. In this study, functional recovery was examined in TBI patients with primary motor (20 patients) or higher mental impairment (10 patients)—post-traumatic Korsakov syndrome compared to healthy volunteers (n = 20). Integral clinical, stabilographic, and EEG approach was used as a tool for estimation of functional deficit in TBI patients before and after rehabilitation course. Specific alterations of stabilographic and EEG parameters were observed in TBI patients with primary motor or mental deficit before rehabilitation. Rehabilitation course with postural training improved recovery of all functions in both patient groups. To understand brain mechanisms of rehabilitation, we examined EEG findings during standing and postural task performance in healthy volunteers (n = 10). EEG coherence increase was marked for different spectral bands predominantly in the right hemisphere and more in alpha-2 and beta bands during postural task performance. These EEG findings were discussed in relation to rehabilitation effect on TBI patients and proved that postural training with visual feedback may provoke primary activation of the right hemisphere and can serve as a trigger for integration of cortical and subcortical structures and for recovery of motor and higher mental function in TBI patients.

Effect of barbiturate coma on adrenal response in patients with traumatic brain injury

Barbiturate coma is the second tier measure recommended by guidelines to treat post-traumatic refractory intracranial pressure. Systemic hypotension is its most important side effect. Recent evidence suggests that low-dose corticosteroid therapy may be used in a subset of patients with traumatic brain injury (TBI) to avoid hypotension. We evaluated adrenal function in TBI patients undergoing barbiturate coma, as treatment of their refractory intracranial hypertension. We prospectively studied 40 patients with moderate to severe TBI. Group A (17 patients) were treated with barbiturate coma. Group B (23 patients) presented intracranial hypertension controlled with first tier measures, and acted as a control. Adrenal function was evaluated by using the high-dose corticotropin stimulation test within 24 h after brain injury and after barbiturate coma induction. Within 24 h after TBI, adrenal function was similar in both groups. Once barbiturate coma was induced, patients in group A treated with barbiturate coma presented a higher incidence of adrenal insufficiency compared with the control group B (53% vs 22%, p=0.03). Patients treated with barbiturates, who developed adrenal impairment, required higher doses of norepinephrine to maintain cerebral perfusion pressure than patients treated with barbiturates without adrenal impairment (1.07+/-1.04 microg/kg/min vs 0.31+/-0.32 mug/kg/min, p=0.03). Patients with TBI treated with barbiturate coma are at higher risk of developing adrenal insufficiency. This subset of patients presented higher requirements of vasoactive support to avoid hypotension. In these patients corticosteroid therapy may have potential therapeutic implications to treat hemodynamic instability.