Neuroprotective hormone medication (10/29/20 newsletter)

Thank you for reading our Concussion Update newsletter, we appreciate your support.

We would like to acknowledge our contributors this week:

Writers: Will Altaweel, Eloïse Cowan, Malayka Gormally, Hannah Kennicott, Galen Moller, Srishti (Shelly) Seth, Ming Shen, Julian Szieff, Trinh Tieu, and Alex Whitis. 

Editors: Conor Gormally and Malayka Gormally.

Do you find the Concussion Update helpful? If so, forward this to a friend and suggest they subscribe. 

Education

Online Courses for patients and advocates

11/4/20: Mindful Gentle Yoga for Brain Injury, a free online course hosted by the Brain Injury Alliance of Washington State. 10:30 - 11:30 am PST. Registration in advance is required. 

11/5/20: Assessing Research: A Quick Guide, will provide “basic rules on how to assess research before you waste your time, money, and/or health.” This is a free online course facilitated by a Speech-Language Pathologist and a Pre-Doctoral Research Associate. 6:00 - 7:00 pm PST. Registration in advance is required.

Sports

What dancers need to know about concussions

An article in Pointe Magazine outlines concussion causes, symptoms, and risks for dancers. In the article, physical therapist and athletic trainer Carrie Gaerte acknowledges how hard it can be for dancers to admit that something is wrong. She warns dancers that if they “run into someone and jostle their head” during practice and then start to show concussion symptoms in the following days (even if they felt fine immediately after the impact), they should seek help from a sports physician. The article further describes how symptoms may manifest in dancers, which diagnostic tools they might use, what treatment could look like, and how to return to dance safely.

Cannabis

Effects of acute cannabidiol linked to increased blood flow in regions involving memory processing

A study from the Journal of Psychopharmacology investigated cerebral blood flow (CBF) in the brain's memory processing regions of healthy study participants treated with CBD. Additionally, the study investigated if CBD had any effect on their working and episodic memory task performance. Concussion Alliance would like to note that reduced CBF is typically a characteristic of acute concussion.

In a randomized, crossover, double-blind study, 15 participants were given either 600 mg of pure synthetic CBD or placebo on separate days. The authors, Michael A P Bloomfield et al., measured regional CBF before and 3 hours after receiving the treatment or placebo. Participants completed two different digit span tasks to assess working memory and three prose recall tasks to assess episodic memory. 

The study found increased CBF in the hippocampus among participants in the CBD treatment group. Although there were no differences in memory performance between the groups, researchers did find a correlation between CBD and a reduced reaction time in one of the working memory tasks. 

A limitation that the researchers acknowledge is that using a single dose of CBD in healthy adults may not have the same effects of repeated doses in patients with psychiatric disorders or cognitive impairments.

Diagnostics

Study indicates biomarkers from saliva may aid in diagnosing concussions

In a study published in Clinical and Translational Medicine, Steven Hicks et al. found that a combination of biomarkers in saliva has the potential to objectively and accurately diagnose concussions (mTBI). Because of reliance on subjective symptom reports, early diagnosis remains difficult despite its importance in improving patients’ clinical outcomes. Utilizing a 3-year study with 538 participants ages 5-66, researchers assessed the ability of salivary noncoding RNA (ncRNA) to diagnose mTBI. They compared 251 participants with a recent clinical diagnosis of mTBI to 287 individuals who did not have an mTBI in the previous 12 weeks.

“Concussions can be difficult to diagnose due to lack of objective, diagnostic testing. The diagnosis often relies on a patient’s self-reported symptoms, which are not specific to concussion,” Dr. Mohammad Haider said for UBNow. “This saliva test is a significant development because it can improve diagnostic accuracy, which could potentially improve clinical management.” 

Saliva and survey data were collected from mTBI participants at five different time points after their initial injury: 72 hours, four to seven days, eight to 14 days, 15 to 30 days, and 31 - 60 days. The researchers found that using both the saliva biomarkers and patient-reported symptoms together were 92.5% accurate in differentiating patients with and without a concussion.

“This test was compared with disorders that present with symptoms that are similar to concussion, like mood disorders, non-head-related trauma and learning disorders, and was still able to differentiate between them,” said Haider. “This means the test is specific as well as sensitive, making it superior to subjective symptom reports alone.” Haider notes that the results still require validation in a larger population.

Self-care

Free online Tai Chi classes for TBI patients

A British neuropsychologist has adapted to quarantine by creating online Tai Chi classes for stroke survivors and brain injury patients. Giles Yeates has been a clinical neuropsychologist for 17 years and is also a Tai Chi instructor. As described in NRTimes, Yeates uses Tai Chi as a physical rehabilitation tool and a mental and emotional process to help with range of motion and balance, as well as anxiety, fatigue, mood, and sleep quality. To this end, Yeates asks participants in his ongoing online weekly Tai Chi classes to fill out a surveywhen they join so that he can measure their progress.

Yeates is beginning this research in collaboration with the Centre for Rehabilitation/Department of Movement Science at Oxford Brookes University. Notably, he says that the psychological benefits for currently quarantined TBI patients can be tremendous: “tai chi can get you into a particular state of mind, where anxiety and depression go down…” Through a state of mindfulness -including attentional focus, breathing control, and stretching- patients may be able to decrease their fatigue.

There are 25 weeks of recorded sessions. Here are direct links to the first ten sessions: intro video, and sessions 2, 3, 4, 5, 6, 7, 8, 9, 10. To find additional sessions, go to the YouTube search box and use the search term Neuroflow Tai Chi session.

Therapies 

An in-depth study of one concussion clinic’s transition to telehealth

A study conducted by Todd Caze Li et al., published in JMIR Pediatrics and Parenting, evaluated current tele-concussion practices. With the Covid-19 pandemic challenging the United States’ healthcare system, many clinics have transitioned to telehealth practices to protect patients by eliminating inessential visits. However, there is no standard for online assessments or treatments in the fast-changing world of concussion treatments.

The researchers performed a descriptive study at a pediatric concussion clinic to model current “assessment, management and view treatment of acute concussion” through the lens of telehealth. By collecting patient demographics, care timelines, and return-to-learn (RLC) or return-to-play (RLP) recovery periods, they described the in-person clinic’s transition to telehealth. Of 18 patients, the clinic cleared 55.6% for RLC or RLP after a median of 15.5 days. Notably, challenges such as accessibility of technology, lack of instruction, and stability of connection all pose threats to the effectiveness of an online visit.

This paper raises critical questions about access to quality healthcare from a unique framework. However, the researchers performed the study at a clinic that had previous experience providing telehealth visits. They hoped that “providing an example of how one clinic implements tele-concussion services can spur other providers to work through concerns and implementation logistics.” Though their results are valuable to understanding online healthcare’s role during the pandemic, these results are preliminary data and therefore necessitate further discussion and research.

Therapies Being Research

Preclinical study suggests neuroprotective potential of liraglutide and twincretin in post-mTBI mice

Bader et al. investigated the treatment potential of two drugs, liraglutide and twincretin, in post-concussion mice. Previous research suggests that drug analogs of the hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) can have neuroprotective effects in animals. Liraglutide is a GLP-1 analog; twincretin is an analog to both GLP-1 and GIP. 

Published in Frontiers in Cell and Developmental Biology, the study consisted of 115 mice (6-8 weeks old) randomly assigned to one of four groups: non-mTBI, mTBI, mTBI+liraglutide, and mTBI+twincretin. Mice received daily drug (or saline) injections for a week.

Three days post-impact, mice in the mTBI group had elevated markers for neurodegeneration in several brain regions. Mice treated with liraglutide and twincretin had less-elevated microglial activity, suggesting the drugs may minimize neuroinflammation after mTBI. Further, “Both drugs ameliorated mTBI-induced cognitive impairments” and neurodegeneration.

Relative to mTBI mice, those treated with either medication had less impaired visual and spatial memory one week and one month post-impact. Mice treated with twincretin showed greater improvement in visual memory than liraglutide mice.

mTBI significantly decreased the activity of the neuroprotective protein PKA within the hippocampus and cortex (measured by phosphorylation levels) but both drug treatments mitigated this reduction. 

The study offers promising preliminary results, but further research is needed to clarify the signaling pathways that liraglutide and twincretin utilize in the brain. Also, whereas liraglutide is an FDA-approved treatment for type 2 diabetes, twincretin remains less understood.

Veterans and Service Members

Two remote clinical trials are recruiting study participants

The Portland Sleep Study is calling for study participants for a Morning Routine study for veterans. Concussion Alliance speculates that study participants may be provided with a blue light to improve sleep patterns in the morning. From the call: “Veterans Needed for a Research Study. Participate in a behavioral intervention of your morning routine at home. Participation requires use of a non-invasive device at home for 60 minutes every morning for 4 weeks. This study may improve your sleep and quality of life, and may also help other Veterans with Sleep Programs.” If interested, call (503) 468-6002.

The federal Center for Neuroscience and Regenerative Medicine is looking for study participants for research on a cognitive behavioral therapy app for insomnia and TBI. The study is open to service members and veterans, and participation is 100% virtual. Contact cnrm-ecbti@usuhs.edu or call/text (301) 456-5474.

Mental Health

Tips for budget-friend mental health support

An article in Forbes details budget-friendly mental health support options that may be helpful for concussion patients. BetterHelp and Talkspace (which includes a chat option) connect you with online therapists. PTSD Coach onlinehas a series of short videos with strategies for dealing with a range of PTSD symptoms. Code Blue is a mobile app for teens dealing with bullying or depression. 

The Open Path Psychotherapy Collective is “a non-profit nationwide network of mental health professionals” providing therapy “at a steeply reduced rate—to individuals, couples, children, and families in need.” Most therapists will be providing virtual sessions during the pandemic.

University-based therapist training clinics provide therapy on a sliding fee schedule, sometimes including a free option. The article also mentions free support groups for anxiety and depression. If you are on Medicaid, use this Psychology Today therapist database and filter for therapists who take Medicaid.

Statistics

Long-term effects of concussion seen in the aging brain

A recent study published in NeuroImage by Danielle June et al. examined the long-term effects of concussion on brain structure and activity. As summarized in an article by the National Institute on Aging, researchers selected participants with an average age of 67 who had histories of concussion (average 23 years before the study). Subjects underwent serial MRI (to see structural changes), DTI (to visualize white matter tracts), and O-water PET (to measure blood flow) over several years. Researchers then compared subjects’ results to a non-concussion control group. 

The group with prior concussions had more prevalent white matter damage in the frontal lobe, temporal lobe, and hippocampus, as well as increased ventricular tissue volume. Additionally, researchers found changes in concussion history subjects’ brain activity in the frontal and temporal lobes. The subjects also underwent neuropsychological examinations to address cognitive changes, though there were no significant differences in the two groups.

The authors conclude that “Most of the differences observed between the concussed and non-concussed groups were seen at the first imaging visit, suggesting that concussions can produce long-lasting structural and functional alterations in temporal and frontal regions of the brain in older individuals.”

Youth

Meta-analysis finds that aerobic exercise reduces symptom severity and shortens recovery time for adolescents following a concussion

A meta-analysis conducted by Xiaotian Shen et al. found that aerobic exercise reduces symptom severity and shortens recovery time in adolescents following a concussion. The study, published in World Neurosurgery, pooled the data of 230 adolescents (ages 12-19) from five different randomized controlled trials. They measured aerobic exercise’s effect by evaluating participants’ post-concussion symptom scale (PCSS) scores, time to recovery, and immediate post-concussion assessment and cognitive testing (ImPACT) scores.

Participants in the aerobic exercise group reported PCSS scores that were 6.51 points lower, on average, than the control group. The aerobic exercise group also recovered an average of 3.87 days faster than the control group. There was no difference in ImPACT scores between the two groups, suggesting that aerobic exercise may not improve neurocognitive function. Neuropsychologist Dr. William Barr, Ph.D., proposed in a recent tweet that this lack of effect might be due to the low reliability of the ImPACT scale. Therefore, future studies might examine whether aerobic exercise significantly impacts neurocognitive function when measured with a more reliable scale. See Concussion Alliance’s page on Graduated Exercise Therapy for additional information.

Women's Health

New South Wales: concussion protocol for family and domestic violence victims

The recent efforts of psychiatrist Karen Williams have prompted the New South Wales Government to develop concussion protocols for family and domestic abuse survivors, as written in an ABC News article. A study by Brain Injury Australia found that 40% of family violence patients suffered from brain injuries over a ten-year sampling period at various Victorian hospitals. Evidence from a literature review also revealed a lack of brain injury diagnoses in female domestic abuse survivors, despite 80% of the patients having facial injuries. These numbers, however, are solely representative of patients who visit hospitals.

Just as head injuries obtained from sports have specific protocols, Williams pushed to create defined protocols for abuse victims, as symptoms of head injuries can have long-term effects and be cumulative with repeated mTBIs. In response, New South Wales Health indicated in a statement that they would provide guidance and resources for screening suspected concussions and redesign their services for sexual assault, child neglect, and family and domestic violence.

Executive Editor

Concussion Alliance co-founder Malayka Gormally