Posts Tagged Traumatic Brain Injury

[Abstract] Cognitive rehabilitation post traumatic brain injury: A systematic review for emerging use of virtual reality technology

Highlights

  • Virtual reality technology improves cognitive function post-traumatic brain injury.
  • Optimal treatment protocol is; 10–12 sessions, 20–40 min in duration with 2–4 sessions per week.
  • There was weak evidence for positive effect of virtual reality on attention.

Abstract

Background

Traumatic brain injury (TBI) can causes numerous cognitive impairments usually in the aspects of problem-solving, executive function, memory, and attention. Several studies has suggested that rehabilitation treatment interventions can be effective in treating cognitive symptoms of brain injury. Virtual reality (VR) technology potential as a useful tool for the assessment and rehabilitation of cognitive processes.

Objectives

The aims of present systematic review are to examine effects of VR training intervention on cognitive function, and to identify effective VR treatment protocol in patients with TBI.

Methods

PubMed, Scopus, PEDro, REHABDATA, EMBASE, web of science, and MEDLINE were searched for studies investigated effect of VR on cognitive functions post TBI. The methodological quality were evaluated using PEDro scale. The results of selected studies were summarized.

Results

Nine studies were included in present study. Four were randomized clinical trials, case studies (n = 3), prospective study (n = 1), and pilot study (n = 1). The scores on the PEDro ranged from 0 to 7 with a mean score of 3. The results showed improvement in various cognitive function aspects such as; memory, executive function, and attention in patients with TBI after VR training.

Conclusion

Using different VR tools with following treatment protocol; 10–12 sessions, 20–40 min in duration with 2–4 sessions per week may improves cognitive function in patients with TBI. There was weak evidence for effects of VR training on attention post TBI.

via Cognitive rehabilitation post traumatic brain injury: A systematic review for emerging use of virtual reality technology – Journal of Clinical Neuroscience

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[REVIEW ARTICLE] Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy – Full Text

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management.

Introduction

Traumatic brain injury (TBI) is a common cause of disability and mortality in the US (1) and worldwide (2). Pathological responses to TBI in the CNS include structural and metabolic changes, as well as excitotoxicity, neuroinflammation, and cell death (34). Fluid biomarkers that may track these injury and inflammatory processes have been explored for their potential to provide objective measures in TBI assessment. However, at present there are limited clinical guidelines available regarding the use of biomarkers in both the diagnosis of TBI and outcome prediction following TBI. To inform future guideline formulation, it is critical to distinguish between different clinical situations for biomarker use in TBI, such as detection of concussion, prediction of positive and negative head computed tomography (CT) findings, and prediction of outcome for different TBI severities. This allows for comparisons to determine which biomarkers may be used most appropriately to characterize different aspects of TBI.

The identification of TBI severity has become a contentious issue. Currently, inclusion in TBI clinical trials is primarily based on the Glasgow Coma Scale (GCS), which stratifies patients into categories of mild, moderate, and severe TBI. The GCS assesses consciousness and provides prognostic information, but it does not inform the underlying pathologies that may be targeted for therapy (56). Furthermore, brain damage and persistent neurological symptoms can occur across the spectrum of TBI severity, limiting the use of GCS-determined injury severity to inform clinical management. Biomarkers in TBI have the potential to provide objective and quantitative information regarding the pathophysiologic mechanisms underlying observed neurological deficits. Such information may be more appropriate for guiding management than initial assessments of severity alone. Since the existing literature primarily focuses on applications of biomarkers in either suspected concussion, mild TBI (mTBI), or severe TBI (sTBI), we will discuss biomarker usage in these contexts.

Concussion is a clinical syndrome involving alteration in mental function induced by head rotational acceleration. This may be due to direct impact or unrestrained rapid head movements, such as in automotive crashes. Although there are over 30 official definitions of concussion, none include the underlying pathology. Missing from the literature have been objective measures to not only identify the underlying pathology associated with the given clinical symptoms, but also to indicate prognosis in long-term survival. Indeed, current practices in forming an opinion of concussion involve symptom reports, neurocognitive testing, and balance testing, all of which have elements of subjectivity and questionable reliability (7). While such information generally reflects functional status, it does not identify any underlying processes that may have prognostic or therapeutic consequences. Furthermore, because patients with concussion typically present with negative head CT findings, there is a potential role for blood-based biomarkers to provide objective information regarding the presence of concussion, based on an underlying pathology. This information could inform management decisions regarding resumption of activities for both athletes and non-athletes alike.

Blood-based biomarkers have utility far beyond a simple detection of concussion by elucidating specific aspects of the injury that could drive individual patient management. For example, biomarkers may aid in determining whether a mTBI patient presenting to the emergency department requires a CT scan to identify intracranial pathology. The clinical outcome for a missed epidural hematoma in which the patient is either discharged or admitted for routine observation is catastrophic; 25% are left severely impaired or dead (8). The Canadian CT Head Rule (9) and related clinical decision instruments achieve high sensitivities in predicting the need for CT scans in mild TBI cases. However, they do this at specificities of only 30–50% (10). Adding a blood biomarker to clinical evaluation may be useful to improve specificity without sacrificing sensitivity, as recently suggested (11). In addition, given concern about radiation exposure from head CT scans in concussion cases, particularly in pediatric populations, identification of patients who would be best assessed with neuroimaging is crucial. Thus, the use of both sensitive and specific biomarkers may serve as cost-effective tools to aid in acute assessment, especially in the absence of risk factors for intracranial injury (12). S-100B, an astroglial protein, has been the most extensively studied biomarker for TBI thus far and has been incorporated into some clinical guidelines for CT scans (1314). However, S-100B is not CNS-specific (1516) and has shown inconsistent predictive capacity in the outcome of mild TBI (1718). Given that several other promising biomarkers have also been investigated in this context, it is important to evaluate and compare the discriminative abilities of S-100B with other candidate blood-based biomarkers for future use.

Blood biomarkers also have the potential to help predict unfavorable outcomes across the spectrum of TBI severity. Outcome predication is difficult; in mTBI, existing prognostic models performed poorly in an external validation study (19). Identifying biomarkers that best predict delayed recovery or persistent neurological symptoms following mTBI would help with the direction of resources toward patients who may benefit most from additional rehabilitation or prolonged observation. In sTBI, poorer outcome has often been associated with a low GCS score (20). However, factors such as intoxication or endotracheal intubation may make it difficult to assess GCS reliably in the acute setting (2122). The addition of laboratory parameters to head CT and admission characteristics have improved prognostic models (23). Thus, prognostic biomarkers in sTBI could help determine whether patients are likely to benefit from intensive treatment. Several candidate biomarkers that correlate with various pathologies of mild and severe TBI have been studied (24), but their relative prognostic abilities remain unclear.

Existing reviews on biomarkers in TBI have provided valuable insight into the pathologic correlates of biomarkers, as well as how biomarkers may be used for diagnosis and prognosis (2531). However, there has been no previous quantitative comparison of the literature regarding biomarkers’ discriminative abilities in specific clinical situations. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mTBI, predicting delayed recovery after mTBI, and predicting adverse outcome after sTBI.[…]

 

Continue —-> Frontiers | Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy | Neurology

Figure 2. Anatomical locations of potential TBI biomarkers. The biomarkers included in this schematic all rated as “good” (AUC=0.800.89) or better for any of the four clinical situations studied (detecting concussion, predicting intracranial damage after concussion, predicting delayed recovery after concussion, and predicting adverse outcome after severe TBI). Biomarkers with a pooled AUC <0.8 are not shown. 1Also found in adipose tissue; 2synthesized in cells of stomach and pancreas; may regulate HPA axis; 3found mostly in pons; 4also found extracellularly; 5lectin pathway of the complement system; 6also found in endothelial cells. BBB, blood brain barrier. ECM, Extracellular matrix. Image licensed under Creative Commons Attribution-ShareAlike 4.0 International license. https://creativecommons.org/licenses/by-sa/4.0/deed.en. See Supplementary Material for image credits and licensing.

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[ARTICLE] Social cognition and emotion regulation: a multifaceted treatment (T-ScEmo) for patients with traumatic brain injury – Full Text

Many patients with moderate to severe traumatic brain injury have deficits in social cognition. Social cognition refers to the ability to perceive, interpret, and act upon social information. Few studies have investigated the effectiveness of treatment for impairments of social cognition in patients with traumatic brain injury. Moreover, these studies have targeted only a single aspect of the problem. They all reported improvements, but evidence for transfer of learned skills to daily life was scarce. We evaluated a multifaceted treatment protocol for poor social cognition and emotion regulation impairments (called T-ScEmo) in patients with traumatic brain injury and found evidence for transfer to participation and quality of life.

In the current paper, we describe the theoretical underpinning, the design, and the content of our treatment of social cognition and emotion regulation (T-ScEmo).

The multifaceted treatment that we describe is aimed at improving social cognition, regulation of social behavior and participation in everyday life. Some of the methods taught were already evidence-based and derived from existing studies. They were combined, modified, or extended with newly developed material.

T-ScEmo consists of 20 one-hour individual sessions and incorporates three modules: (1) emotion perception, (2) perspective taking and theory of mind, and (3) regulation of social behavior. It includes goal-setting, psycho-education, function training, compensatory strategy training, self-monitoring, role-play with participation of a significant other, and homework assignments.

It is strongly recommended to offer all three modules, as they build upon each other. However, therapists can vary the time spent per module, in line with the patients’ individual needs and goals. In future, development of e-learning modules and virtual reality sessions might shorten the treatment.

Traumatic brain injury refers to a brain lesion caused by an external mechanical force, leading not only to physical impairments and cognitive deficits, but also to changes in behavior and personality.1,2 Especially after damage to orbitofrontal and ventromedial prefrontal brain areas, deficits in social cognition can occur.3,4

According to Adolphs,5 social cognition consists of three stages: (1) the ability to perceive social information (i.e. emotional facial expressions, bodily language), (2) the capacity to process and interpret social information (i.e. theory of mind, perspective taking), and (3) the ability to adapt behavior in accordance with the situation. Babbage et al.6 estimated that 13%–39% of individuals with moderate to severe traumatic brain injury experienced emotion perception deficits and up to 70% reported low empathy.79

Deficits in social cognition often appear in the shape of socially inadequate behavior, such as disinhibited or indifferent emotional behavior.1012 Such behaviors have detrimental consequences for the ability of patients to establish and maintain social relationships, to hold jobs, and to participate in society.1,13,14 It has been found that poor theory of mind and behavioral problems significantly predict poor participation and community integration.15,16For all these reasons, it is important to provide a tailored rehabilitation treatment, in order to prevent an unfavorable outcome.

In their review of cognitive rehabilitation, Cicerone et al.17 stressed the need to provide detailed information about the theoretical base, the protocol design, and the ingredients of a treatment, as a prerequisite to analyze its effectiveness. In the current paper, we give a comprehensive description of the treatment of social cognition and emotion regulation protocol (T-ScEmo). The effectiveness of T-ScEmo was evaluated in 59 patients with traumatic brain injury. It was compared with a computerized control treatment in a randomized controlled trial.18 Compared to the control treatment, T-ScEmo resulted in significant improvements in emotion recognition, theory of mind, emphatic behavior, quality of life partner relationship, quality of life and societal participation, up to five months posttreatment. Patients with traumatic brain injury as well as their life partners were satisfied with the treatment.18 A detailed description of the T-ScEmo protocol is relevant for researchers and clinical therapists; they can use, replicate, or expand this newly developed treatment.[…]

 

Continue —-> Social cognition and emotion regulation: a multifaceted treatment (T-ScEmo) for patients with traumatic brain injury – Herma J Westerhof-Evers, Annemarie C Visser-Keizer, Luciano Fasotti, Jacoba M Spikman, 2019

 

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Figure 1. Thoughts–feelings–behavior scheme (module 2).

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[WEB SITE] The Comparison Trap | BrainLine

The Comparison Trap Caregiving After Brain Injury, Norma Myers

We can all relate to being guilty of spinning around in the dizzying comparison trap. Whether it’s love, family, career, financial, fashion, weight or cosmetic, somewhere along the line, we have compared ourselves to others. With the presence of social media, this trap has become even more intrusive.

From the moment we received the life-changing news of Aaron and Steven’s car accident, the comparison trap began. Aaron didn’t survive the accident that left Steven with a severe Traumatic Brain Injury (TBI). While the comparison trap from the loss of Aaron would set in later, it immediately bombarded us during Steven’s recovery.

Of all comparisons we thought we would face as parents, nothing prepared our ears to absorb the speech that began: don’t compare your child’s TBI progress to another survivor. A wonderful physician, who is now a friend, spoke those words to us. He then proceeded to inform us, “In a line-up of 10 TBI survivors, you would witness 10 different outcomes.” I did not want my son in a TBI line up or any part of the TBI community. All I wanted was to be able to turn back the calendar to August 13, 2012, and plan a totally different Sunday for our intact family of 4, a day close to home, together.

During Steven’s roller-coaster recovery, we were reminded often, felt like hourly, that with the severity of Steven’s injuries the recovery road was long, we should not get our hopes up. Really? Telling parents not to get their hopes up about their child’s survival was the same as telling us not to take our next breath! Of course, we were going to hope, pray, and never give up.

We admit, despite celebrating Steven’s recovery, we did fall into the dismal comparison trap.

Why is Steven’s rehab roommate already walking?

His accident was as severe as Steven’s; how did he escape a craniectomy and the helmet?

How did she escape the epilepsy curse?

These comparisons led me to wonder if I tapped into all available resources for Steven’s recovery?

As shock eventually lifted, we realize that some of our justifications for comparing were due to our lack of knowledge about TBI. How could we not compare? And while we have heard every lecture on not asking why, it’s human nature to ask, “Why?”

As my heart began to absorb the reality of Aaron’s death, I was faced with new comparisons. When it comes to Aaron’s life, it’s not all about comparisons; it’s more about mynatural mom instinct wondering what Aaron’s life would look like today, a mother’s shattered heart longing for what should have been.

Would Aaron be married?

Would we be grandparents?

Where would Aaron be in his career?

What would Aaron’s big trophy be this hunting season?

While I acknowledge that people mean well, and do not know what to say, the comparison that continues to leave me speechless is comparing child loss to losing a parent or a grandparent. Trust me, I have also experienced those deep losses, but it’s unequivocally not the same, it’s just not.

Lessons I learned from comparing

  • Seek connection, not comparisons. It’s most rewarding to spend time with those that nourish relationships, with those who see the real you.
  • By focusing on the good things in my life, I’m less likely to obsess about what I lack.
  • Comparisons can be never-ending and exhausting. The temptation to compare is as near as my next chat with a friend, a trip to the store, or check-in on social media. I must not get lost in others’ lives and forget to enjoy my own.
  • By shifting my focus, a comparison can turn into inspiration. Being inspired and learning from others can create happiness instead of misery.
  • When life is lived intentionally and thoughtfully, the comparison game becomes less attractive.
  • If I waste time comparing myself to others, I will rob myself of gratitude, joy, and fulfillment.
  • Even when it feels impossible, dig deep, find the courage to celebrate who you are, underneath the messiest of messes, there’s much to celebrate, we are each entirely unique.

When I find myself being drawn in as a pawn in the comparison game, I don’t beat myself up, I just say no! I refuse to stay in the game. After all, it’s not about comparisons, it’s about living for the ones I love and for those that need and love me. Instead of evaluating those in my life; past and present, I will celebrate them. I refuse to get lost in others idealizedlives, I will focus on being grateful for my life; right here, right now; a priceless lesson that Aaron taught me and one that I and the two men in my life attempt to remind each other of daily.

 

via The Comparison Trap | BrainLine

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[Abstract] Pharmacological Optimization for Successful Traumatic Brain Injury Drug Development

The purpose of this review is to highlight the pharmacological barrier to drug development for traumatic brain injury (TBI) and to discuss best practice strategies to overcome such barriers. Specifically, this article will review the pharmacological considerations of moving from the disease target “hit” to the “lead” compound with drug-like and central nervous system (CNS) penetrant properties. In vitro assessment of drug-like properties will be detailed, followed by pre-clinical studies to ensure adequate pharmacokinetic and pharmacodynamic characteristics of response. The importance of biomarker development and utilization in both pre-clinical and clinical studies will be detailed, along with the importance of identifying diagnostic, pharmacodynamic/response, and prognostic biomarkers of injury type or severity, drug target engagement, and disease progression. This review will detail the important considerations in determining in vivo pre-clinical dose selection, as well as cross-species and human equivalent dose selection. Specific use of allometric scaling, pharmacokinetic and pharmacodynamic criteria, as well as incorporation of biomarker assessments in human dose selection for clinical trial design will also be discussed. The overarching goal of this review is to detail the pharmacological considerations in the drug development process as a method to improve both pre-clinical and clinical study design as we evaluate novel therapies to improve outcomes in patients with TBI.

 

via Pharmacological Optimization for Successful Traumatic Brain Injury Drug Development | Journal of Neurotrauma

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[Abstract] Evaluation of a 12-month lifestyle intervention by individuals with traumatic brain injury.

Abstract

Weight gain and inactivity are common problems for individuals living with a traumatic brain injury (TBI). Yet, interventions to support a healthy lifestyle specific to individuals with TBI are lacking. The purpose of this study was to complete a program evaluation of a 12-month evidence-based healthy lifestyle intervention adapted for people with a TBI. Eighteen participants completed a brief interview after the yearlong intervention to determine their perceptions of the program effectiveness as well as barriers and facilitators in making lifestyle changes. Participants reported staff, tracking of dietary and activity behavior, and in-person meetings as most helpful aspects. Lack of motivation and difficulty preparing healthy meals were the primary barriers to a healthy lifestyle. Qualitative data revealed five themes that influenced healthy behaviors, including (1) self-regulation, (2) environmental resources, (3) knowledge of health behaviors, (4) TBI-related impairment and comorbidities, and (5) social support. Results suggest that future iterations of the healthy lifestyle intervention should emphasize self-regulation activities; require tracking of dietary and activity behaviors across 12 months; provide concurrent support for individual motivation issues; provide prepared meals; utilize web-based, telephonic, or hybrid approaches to delivery; further simplify the curriculum and learning tools; and include caregivers and peer accountability partners. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

 

via Evaluation of a 12-month lifestyle intervention by individuals with traumatic brain injury. – PubMed – NCBI

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[BLOG POST] 9 promising advances in the management of traumatic brain injury – The Neurology Lounge

 

Traumatic brain injury (TBI) is simply disheartening. It is particularly devastating because it usually affects young people in their prime, with the consequent personal, social, and economic consequences. This blog has previously touched a little on TBI with the post titled Will Smith and chronic traumatic encephalopathy? This was a light-hearted take on concussion in sports, but traumatic brain injury is nothing but a serious burden. So what are the big brains in white coats doing to take down this colossus? Quite a lot it seems. Here, for a taster, are 9 promising advances in the management of traumatic brain injury.

Better understanding of pathology

An amyloid PET imaging study by Gregory Scott and colleagues, published in the journal Neurology, reported a rather surprising link between the pathology seen in long-term survivors of traumatic brain injury, with the pathology seen in Alzheimers disease (AD). In both conditions, there is an increased burden of β-amyloid () in the brain, produced by damage to the nerve axons. The paper, titled Amyloid pathology and axonal injury after brain trauma, however notes that the pattern of  deposition in TBI can be distinguished from the one seen in AD. The big question this finding raises is, does TBI eventually result in AD? The answer remains unclear, and this is discussed in the accompanying editorial titled Amyloid plaques in TBI.

Blood tests to detect concussion

The ideal biomarker for any disorder is one which is easy to detect, such as a simple blood test. A headline that screams Blood test may offer new way to detect concussions is therefore bound to attract attention. The benefits of such a test would be legion, especially if the test can reduce the requirement for CT scans which carry the risks of radiation exposure. This is where glial fibrillary acidic protein (GFAP) may be promising. The research is published in the journal, Academic Research Medicine, with a rather convoluted title, Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma. The premise of the paper is the fact that GFAP is released into the blood stream from the glial cells of the brain soon after brain injury. What the authors therefore did was to take blood samples within 6 hours of TBI in children. And they demonstrated that GFAP levels are significantly higher following head injury, compared to injuries elsewhere in the body. This sounds exciting, but we have to wait and see where it takes us.

Advanced imaging

Brain Scars Detected in Concussions is the attention-grabbing headline for this one, published in MIT Technology Review. Follow the trail and it leads to the actual scientific paper in the journal Radiology, with a fairly straight-forward title, Findings from Structural MR Imaging in Military Traumatic Brain Injury The authors studied >800 subjects in what is the largest trial of traumatic brain injury in the military. Using high resolution 3T brain magnetic resonance imaging (MRI), they demonstrated that even what is reported as mild brain injury leaves its marks on the brain, usually in the form of white matter hyperintense lesions and pituitary abnormalities. It simply goes to show that nothing is mild when it comes to the brain, the most complex entity in the universe.

Implanted monitoring sensors

Current technologies which monitor patients with traumatic brain injury are, to say the least, cumbersome and very invasive. Imagine if all the tubes and wires could be replaced with microsensors, smaller than grains of rice, implanted in the brain. These would enable close monitoring of critical indices such as temperature and intracranial pressure. And imagine that these tiny sensors just dissolve away when they have done their job, leaving no damage. Now imagine that all this is reality. I came across this one from a CBS News piece titled Tiny implanted sensors monitor brain injuries, then dissolve away. Don’t scoff yet, it is grounded in a scientific paper published in the prestigious journal, Nature, under the title Bioresorbable silicon electronic sensors for the brain. But don’t get too exited yet, this is currently only being trialled in mice.

Drugs to reduce brain inflammation

What if the inflammation that is set off following traumatic brain injury could be stopped in its tracks? Then a lot of the damage from brain injury could be avoided. Is there a drug that could do this? Well, it seems there is, and it is the humble blood pressure drug Telmisartan. This one came to my attention in Medical News Today, in a piece titled Hypertension drug reduces inflammation from traumatic brain injury. Telmisartan seemingly blocks the production of a pro-inflammatory protein in the liver. By doing this, Telmisartan may effectively mitigate brain damage, but only if it is administered very early after traumatic brain injury. The original paper is published in the prestigious journal, Brain, and it is titled Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Again, don’t get too warm and fuzzy about this yet; so far, only mice have seen the benefits.

Treatment of fatigue

Fatigue is a major long-term consequence of traumatic brain injury, impairing the quality of life of affected subjects in a very frustrating way. It therefore goes without saying, (even if it actually has to be said), that any intervention that alleviates the lethargy of TBI will be energising news. And an intervention seems to be looming in the horizon! Researchers writing in the journal, Acta Neurologica Scandinavica, have reported that Methylphenidate significantly improved fatigue in the 20 subjects they studied. Published under the title Long-term treatment with methylphenidate for fatigue after traumatic brain injury, the study is rather small, not enough to make us start dancing the jig yet. The authors have rightly called for larger randomized trials to corroborate their findings, and we are all waiting with bated breaths.

Treatment of behavioural abnormalities

Many survivors of traumatic brain injury are left with behavioural disturbances which are baffling to the victim, and challenging to their families. Unfortunately, many of the drugs used to treat these behaviours are not effective. This is where some brilliant minds come in, with the idea of stimulating blood stem cell production to enhance behavioural recovery. I am not clear what inspired this idea, but the idea has inspired the paper titled Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. The authors report that the administration of G‐CSF for 3 days after mild TBI improved the performance of mice in a water maze…within 2 weeks. As the water maze is a test of learning and memory, and not of behaviour, I can only imagine the authors thought-surely only well-behaved mice will bother to take the test. It is however fascinating that G‐CSF treatment actually seems to fix brain damage in TBI, and it does so by stimulating astrocytosis and microgliosis, increasing the expression of neurotrophic factors, and generating new neurons in the hippocampus“. The promise, if translated to humans, should therefore go way beyond water mazes, but we have to wait and see.

Drugs to accelerate recovery

The idea behind using Etanercept to promote recovery from brain injury sound logical. A paper published in the journal, Clinical Drug Investigation, explains that brain injury sets off a chronic lingering inflammation which is driven by tumour necrosis factor (TNF). A TNF inhibitor will therefore be aptly placed to stop the inflammation. What better TNF inhibitor than Eternacept to try out, and what better way to deliver it than directly into the nervous system. And this is what the authors of the paper, titled Immediate neurological recovery following perispinal etanercept years after brain injury, did. And based on their findings, they made some very powerful claims: “a single dose of perispinal etanercept produced an immediate, profound, and sustained improvementin expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury”. A single patient, mind you. Not that I am sceptical by nature, but a larger study confirming this will be very reassuring.

Neuroprotection

And finally, that elusive holy grail of neurological therapeutics, neuroprotection. Well, does it exist? A review of the subject published in the journal, International Journal of Molecular Sciences, paints a rather gloomy picture of the current state of play. Titled Neuroprotective Strategies After Traumatic Brain Injury, it said “despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed“. But all is not lost. The authors promise that “recent changes in experimental approach and advances in clinical trial methodologyhave raised the potential for successful clinical translation”. Another review article, this time in the journal Critical Care, doesn’t offer any more cheery news about the current state of affairs when it says that the “use of these potential interventions in human randomized controlled studies has generally given disappointing results”. But the review, titled Neuroprotection in acute brain injury: an up-to-date review, goes through promising new strategies for neuroprotection following brain injury: these include hyperbaric oxygensex hormones, volatile anaesthetic agents, and mesenchymal stromal cells. The authors conclude on a positive note: “despite all the disappointments, there are many new therapeutic possibilities still to be explored and tested”.

What an optimistic way to end! We are not quite there yet, but these are encouraging steps.

via 9 promising advances in the management of traumatic brain injury | The Neurology Lounge

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[Graphic] BRAIN Injury Awareness

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[ARTICLE] Impact of Traumatic Brain Injury on Neurogenesis – Full Text

New neurons are generated in the hippocampal dentate gyrus from early development through adulthood. Progenitor cells and immature granule cells in the subgranular zone are responsive to changes in their environment; and indeed, a large body of research indicates that neuronal interactions and the dentate gyrus milieu regulates granule cell proliferation, maturation, and integration. Following traumatic brain injury (TBI), these interactions are dramatically altered. In addition to cell losses from injury and neurotransmitter dysfunction, patients often show electroencephalographic evidence of cortical spreading depolarizations and seizure activity after TBI. Furthermore, treatment for TBI often involves interventions that alter hippocampal function such as sedative medications, neuromodulating agents, and anti-epileptic drugs. Here, we review hippocampal changes after TBI and how they impact the coordinated process of granule cell adult neurogenesis. We also discuss clinical TBI treatments that have the potential to alter neurogenesis. A thorough understanding of the impact that TBI has on neurogenesis will ultimately be needed to begin to design novel therapeutics to promote recovery.

Introduction

Adult neurogenesis in the hippocampal dentate gyrus is widespread in mammals. Generation of dentate granule cells occurs late in embryonic development, continues after birth, and persists into old age in most mammals examined (Amrein et al., 2011Amrein, 2015Ngwenya et al., 2015). Studies in rodents indicate that adult generated granule cells play a role in hippocampal dependent learning (Nakashiba et al., 2012Danielson et al., 2016Johnston et al., 2016). Whether neurogenesis continues into old age in humans remains controversial (Danzer, 2018a), with studies finding evidence for (Eriksson et al., 1998Spalding et al., 2013Boldrini et al., 2018) and against ongoing neurogenesis (Sorrells et al., 2018). Yet there is general agreement that dentate neurogenesis occurs in childhood and continues throughout young adulthood in humans, and that newly-generated neurons are poised to contribute to hippocampal function. At a minimum, therefore, traumatic brain injuries (TBIs) occurring during adolescence have the potential to disrupt this important process.

The generation, maturation, and integration of new neurons is critical for hippocampal function. This tightly regulated process, however, is easily disrupted by pathological events, such as TBI. In this review, we discuss the coordinated process of adult neurogenesis in the hippocampal subgranular zone (SGZ) and the impact that TBI and TBI treatments have on this process. An understanding of the regulation and dysregulation of neurogenesis is important for determining whether and how therapeutic interventions targeted at adult neurogenesis are useful for TBI treatment.

Neurogenesis Is a Complex, Tightly-Regulated Process

Adult neurogenesis is characterized by multiple “control” points. The number of daughter cells produced by neural stem cells (NSC) located in the SGZ of the dentate gyrus can be modulated by the rate of cell proliferation and survival, while factors regulating fate specification control whether and how the new cells become neurons and integrate into the hippocampal circuitry (see recent review by Song et al., 2016). These control points can be regulated by signals released into the extracellular milieu by both neuronal and non-neuronal cells (Alenina and Klempin, 2015Egeland et al., 2015), neurotrophic and transcription factors (Faigle and Song, 2013Goncalves et al., 2016), neuroinflammatory mediators (Belarbi and Rosi, 2013), metabolic and hormonal changes (Cavallucci et al., 2016Larson, 2018), and direct synaptic input from both glutamatergic and GABAergic neurons (Chancey et al., 2014Alvarez et al., 2016Song et al., 2016Yeh et al., 2018). For additional information, the readers are referred to the excellent reviews cited for each mechanism, and the schematic in Figure 1. Critically, all of these factors can be disrupted by TBI, creating an environment in which immature granule cells and granule cell progenitors no longer receive the proper cues to guide their development.

Figure 1. Generation and integration of adult-born granule cells is a coordinated process that is impacted by TBI. At each stage of adult neurogenesis, the normal process (blue) has potential to be altered by TBI (orange). (1) Quiescent radial neural stem cells (NSCs) in the subgranular zone (SGZ) can be depleted by frequent activation early in life, such as by TBI-induced seizures, leading to deficiencies with age. (2) TBI and its effects, including spreading depolarizations and seizures, cause an increase in proliferation of progenitor cells. (3) Newly-generated neurons migrate from the SGZ to the granule cell layer (GCL), and after TBI abnormal hilar migration is apparent. (4) Parvalbumin interneurons and (5) mossy hilar neurons are susceptible to cell death after TBI. Reduction in their numbers results in decreased GABAergic and glutamatergic (respectively) input to the newly-generated neurons. Newly-generated neurons show additional signs of aberrant neurogenesis such as abnormal connectivity (6), hyperexcitability (7) and inappropriate integration and dendritic maturity (8) which can be caused by changes in the environmental milieu.

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Continue —>  Frontiers | Impact of Traumatic Brain Injury on Neurogenesis | Neuroscience

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[WEB SITE] Intimate partner violence and traumatic brain injury: An “invisible” public health epidemic

While studying brain injuries in the mid-1990s, I began volunteering in a domestic violence shelter. I noticed that the abuse and problems many women reported were consistent with possibly experiencing concussions. Women reported many acts of violence that could cause trauma to the brain, as well as many post-concussive symptoms. Shockingly, my search for literature on this topic yielded zero results.

When I decided to focus my graduate work on this topic, I was even more shocked by what I learned from women who had experienced intimate partner violence (IPV). Of the 99 women I interviewed, 75% reported at least one traumatic brain injury (TBI) sustained from their partners and about half reported more than one — oftentimes many more than one. Also, as I predicted, the more brain injuries a woman reported, the more poorly she tended to perform on cognitive tasks such as learning and remembering a list of words. Additionally, having more brain injuries was associated with higher levels of psychological distress such as worry, depression, and anxiety.

When I published these results, I was excited about the possibility of bringing much needed awareness and research attention to this topic. Unfortunately, over 20 years later — despite the plethora of concussion-related research in athletics and the military — concussion-related research in the context of intimate partner violence remains scant, representing a barely recognized and highly understudied public health epidemic.

What do we know about intimate partner violence-related traumatic brain injuries?

First, we need to understand that an estimated one in three women experience some type of physical or sexual partner violence in their lifetimes. IPV is not a rare event, and it traverses all socioeconomic boundaries. It is the number one cause of homicide for women and the number one cause of violence to women. For many reasons, including the stigma of being abused, many women hide their IPV — so the chances that we all know personally at least a few people who have sustained IPV are quite high.

Though we lack good epidemiological data on the number of women sustaining brain injuries from their partners, the limited data that we do have suggest that the numbers are in the millions in the US alone. Most of these TBIs are mild and are unacknowledged, untreated, and repetitive. Consequently, many women are at risk for persistent post-concussive syndrome with completely unknown longer-term health risks.

What are the signs and symptoms of IPV-related TBI?

A concussion, by definition, is a traumatic brain injury (TBI). All that is required for someone to sustain a TBI or concussion is an alteration in consciousness after some type of external trauma or force to the brain. For example, either being hit in the head with a hard object (such as a fist), or having a head hit against a hard object (such as a wall or floor), can cause a TBI. If this force results in confusion, memory loss around the event, or loss of consciousness, this is a TBI. Dizziness or seeing stars or spots following such a force can also indicate a TBI. A loss of consciousness is not required, and in fact does not occur in the majority of mild TBIs.

There are often no physical signs that a TBI has occurred. Recognizing that an IPV-related TBI has occurred will typically involve asking the woman about her experience following a blow to the head or violent force to the brain, and then listening for signs of an alteration of consciousness (such as confusion, memory loss, loss of consciousness). Within the next days or week, a range of physical, emotional, behavioral, or cognitive issues may indicate post-concussive symptoms that could include

  • headaches
  • dizziness
  • feeling depressed or tearful
  • being irritable or easily angered
  • frustration
  • restlessness
  • having poor concentration
  • sleep disturbances
  • forgetfulness
  • taking longer to think.

If a TBI is suspected, a woman should see a doctor if possible. Sustaining additional TBIs while still symptomatic will likely increase the time to recovery, and possibly increase the likelihood of more long-term difficulties.

What can we do?

An important component of addressing IPV-related TBI is to raise awareness and destigmatize intimate partner violence. IPV is unfortunately quite common, and some estimates suggest that millions of women may be sustaining unacknowledged, unaddressed, and often repetitive mild TBIs or concussions from their partners. Talking openly and honestly about this problem, especially in cases were abuse may be suspected, is critical. As we open up this conversation about the commonality of IPV with nonjudgmental acceptance of a woman’s experience, we will be in a better place to hear, understand, and support women who may be unknowing members of this invisible public health epidemic.

Resources

If you or someone you know is experiencing intimate partner violence, The Hotline is a 24/7 support service that has a wealth of resources, including access to service providers and shelters across the US.

Follow me on Twitter @EveValera2

 

via Intimate partner violence and traumatic brain injury: An “invisible” public health epidemic – Harvard Health Blog – Harvard Health Publishing

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