Research provides insight into treating persistent post-concussion symptoms (PPSC), Long-Covid, and chronic fatigue syndrome (6/13/24 Newsletter)
This week’s lead article, Research provides insight into treating persistent post-concussion symptoms (PPSC), Long Covid, and chronic fatigue syndrome, is in the Pathophysiology category.
In addition to the usual synopses, this newsletter features a spotlight on Concussion Alliance resource pages, a popular newsletter synopsis from our Archives, and a powerful 4-minute video from concussion patient Michelle Limmer about her experience dealing with persisting concussion symptoms and finding Concussion Alliance
In this newsletter: Opportunities, Sports, Pathophysiology, Therapies & Diagnostic Tools Under Research, Archives Highlight, Patient Interview Video, and Pertinent Concussion Alliance Resources.
We appreciate the Concussion Alliance volunteers and staff members who created this edition:
Writers: Keya Mookencherry, Padmini Konidena, Fadhil Hussain, Minhong Kim, and Malayka Gormally.
Editors: Conor Gormally and Malayka Gormally
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Opportunities
Participate in concussion research: Are you between 18 and 65 and have experienced at least one concussion in the last five years? Researchers at the University of Colorado invite you and a significant other (friend, partner, family member, etc.) to participate in an online study assessing neuropsychological symptoms that may be linked to your concussion history. The study takes 45-60 minutes per person, and each participant will receive a $12.50 virtual gift card. See our blog post for information on how to enroll.
Participate in CTE research: researchers are recruiting for the BANK CTE study to “see if blood can be used to detect CTE. Once CTE can be diagnosed in life, then researchers can explore treatments, and hopefully a cure.” Eligible participants are at least 40 years old, have played an organized or collisions sport for at least 5 years, have served in the military, or are individuals who have not sustained a head injury (for the control group). The Boston University CTE Center is sponsoring the research; see their website for more details and a recorded webinar about participating in the study produced by the Concussion Legacy Foundation.
Sports
A SCAT assessment modified for para-athletes could work for concussion assessment in some types of disabilities
A major concern with concussion policies in sports is that most current methods to diagnose concussions are inadequate for para-athletes with a wide variety of disabilities. A study published in the British Journal of Sports Medicine examined whether the sports concussion assessment tool, version 5 (SCAT5), could be utilized for para-athletes with a visual impairment, a spinal cord injury, or a limb deficiency. Authors Bryce Dyer et al. conclude that the SCAT5 could be conducted on athletes with spinal cord injuries or limb deficiencies with minor modifications. For those athletes with visual impairments, however, the study authors do not recommend using the SCAT5 “in its current form.” It should be noted that this study was conducted before the release of SCAT6, although most updates in SCAT6 do not affect the recommendations provided in this study.
The research team studied three types of impairments with high prevalence in para-sport: visual impairments (low vision or absent vision), limb deficiency (upper, unilateral, or bilateral lower limbs), and spinal cord injuries (quadriplegia and paraplegia). To evaluate the use of SCAT5 among these types of disabilities, the researchers established a 16-member panel and used the Delphi technique to develop a consensus opinion.
For para-athletes with a suspected concussion who had limb deficiencies or spinal cord injuries, the expert panel agreed that a modified SCAT5 evaluation would be effective once created. However, athletes would still need to complete a baseline assessment with modified SCAT5 to have a comparison point. For para-athletes with visual impairment, the authors found that “some tests were difficult, infeasible, or should be omitted entirely depending on the visual impairment type.” The researchers found that 31-41% of tests in the SCAT5 shouldn’t be used* in clinical assessment of suspected concussion in para-athletes, depending on the impairment. Further, 24-31% of SCAT5 tests need modifications before they can be used for para-athletes. (* See page 16.)
In a Bournemouth University press release, Dr. Bryce Dyer, the first author of this study, notes that “The issue is that most of the policy regarding concussion in sport is directed towards non-disabled athletes. While para-athletes are also assessed for suspected concussions, our current methods require tailoring to their unique needs, and this isn’t fully understood how yet, with no simple process to quickly do it.” Further research on identifying and validating alternative assessment methods is needed to examine how potential concussions can be more effectively evaluated in para-athletes with a wide variety of disabilities.
Pathophysiology
Research provides insight into treating persisting post-concussion symptoms (PPSC), Long-Covid, and chronic fatigue syndrome
A BBC article explains how patients with persisting post-concussion symptoms (PPCS) and Long Covid exhibit similar symptoms, including fatigue, exercise intolerance, sleep disturbances, memory and concentration problems, light and sound sensitivity, and visual dysfunction, such as impairments in eye tracking. BBC journalist David Cox describes researchers in the U.K. and U.S. who have developed different theories of the potential overlaps in pathophysiology behind PPCS and Long Covid and how assessment and treatment options for the two conditions could be similar. Another researcher in Germany sees an overlap between PPCS, Long Covid, and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and has treatment ideas–including the use of the psychedelic drugs ibogaine, psilocybin, and ketamine.
Since the onset of the COVID-19 pandemic, U.K. researcher, concussion specialist, and neurologist Ioannis Mavroudis found that he was increasingly treating patients with Long Covid and found that patients with both Long Covid and PPCS have similar symptom expression. Mavroudis theorizes that PPCS is “related to the energy demand on the brain’s neurons as a result of the head trauma.” The concussed brain cannot meet this demand, causing fatigue and locking the brain into a “vicious cycle,” similar to what may occur in the brains of those with Long Covid. (See Moavroudis’s related paper on the relationship between PPCs and functional neurological disorders.)
Similarly, researchers from the University of Denver conducted balance and spatial reasoning studies on patients with Long Covid, concluding that “the patients had effectively experienced a traumatic injury to the brain.” The University of Denver researchers suggest that concussion diagnostics could be used to assess the progress of Long Covid patients. In addition, they hypothesize that targeting the vestibular system (which includes the brainstem) may help treat patients with Long Covid––a treatment method already employed with patients with PPCS. For further information, see the team’s preprint article on medRxiv, our Concussion Update Newsletter synopsis about the team’s research, and our interview with Allison Grossberg, one of the team’s researchers. Additionally, see our resource on Vestibular Therapy.
Herbert Renz-Polster, an ME/CFS researcher in Germany, believes that the ME/CFS, Long Covid, and PPCS symptoms may be due to impairment in the brainstem causing mitochondrial dysfunction, found in all three conditions. Constriction in the brainstem could occur from a concussive impact or because “A very significant portion of ME/CFS patients have abnormalities in how the head is supported.” “The brainstem coordinates connectivity in the brain,” states Renz-Polster. “So, when it gets squished, that leads to a complete disruption of the connectivity and flow of information between the various centers that underlie our brain functions.”
Renz-Polster’s brainstem constriction theory is supported by new research showing that the brainstem is particularly susceptible to viral infection. So, TBI or a virus could damage the lining around the brain and brainstem, resulting in an influx of inflammatory molecules that harm the blood vessels feeding the mitochondria. Without ample blood flow, the mitochondria cannot produce enough energy for the brain and body to function properly, which may be the cause of the cognitive and neurological symptoms seen in patients with ME/CFS, PPCS, and Long Covid. Fortunately, Renz-Polster says that his theory could be tested using an advanced MRI technique to study the brainstem; the results of such research would be something to look forward to. If his brainstem constriction theory is correct, it has the potential to revolutionize treatment options and provide new insights into the mechanisms resulting in symptoms for patients with ME/CFS, PPCS, and Long Covid.
Renz-Polster also notes that the brainstem is part of the default mode network and that psychedelics have the potential to modulate this network with therapeutic benefits. He references a recent study where treatment with the psychedelic ibogaine improved the functioning of veterans with a history of TBI; see our blog post about this groundbreaking ibogaine study. Additionally, the BBC article references a case study of Long Covid symptoms improving after MDMA and psilocybin therapy.
Therapies & Diagnostic Tools Under Research
Study finds low-level light therapy results in increased brain connectivity within the first 2-3 weeks of moderate traumatic brain injury
A study published in Radiology discovered that low-level light therapy (LLLT) administered within 72 hours of a moderate traumatic brain injury (TBI) showed increased resting-state functional connectivity in the brains of participants during the early recovery stages. While still in the preliminary research phase, light therapy could be a highly accessible rehabilitation method due to its safety, non-invasiveness, ease of administration, and suitability for use outside hospital settings. This study contributes to a growing body of evidence that light therapy could be used in disorders that impact brain connectivity. According to a news release from the Radiological Society of North America, the study’s co-lead author, Dr. Rajiv Gupta, MD, PhD, said, “There are lots of disorders of connectivity…where this intervention may have a role. PTSD, depression, autism: these are all promising areas for light therapy.” While this study focuses on moderate TBI, photobiomodulation (LLLT) is also being researched as a treatment for mild TBI.
In the prospective study, researchers at Massachusetts General Hospital investigated whether LLLT altered resting state functional connectivity in patients with moderate TBI. Moderate traumatic brain injury, as defined by the US Veterans Affairs/Department of Defense, is a traumatic brain injury that results in a loss of consciousness for 30 minutes to 24 hours, accompanied by between 1 and 7 days of post-traumatic amnesia. The study included 38 participants who had suffered a moderate traumatic brain injury, with 17 participants in the LLLT group and 21 participants in the sham group. Additionally, there were 23 participants in a healthy control group. The LLLT group received low-level near-infrared light therapy, delivered by a Photomedex helmet, in three 20-minute sessions within 72 hours of their injuries. The sham group received the same procedure; however, the light-emitting diodes in the helmet were turned off. The control group did not receive LLLT or sham procedures. The participants’ functional MRI (fMRI) results were then compared at three time points: acute (within one week of injury), subacute (2-3 weeks), and late subacute (3 months).
Between the acute and subacute time points, the LLLT group showed increased resting state connectivity in 14 of 82 brain region pairs analyzed, with 7 of these region pairs showing significantly greater (positive) changes when compared to the sham group. Interestingly, connectivity continued to change between the subacute and late-subacute time points, although the researchers found no significant differences between connectivity changes experienced by the LLLT and sham treatment groups during this time. The researchers postulate that the continued changes “may suggest a natural healing process.”
These results add to a growing body of evidence that LLLT can modulate brain activities at rest. However, the cause and mechanism of the therapy are unclear. In the news release, Dr. Gupta stated that light therapy may alter an enzyme in cells’ mitochondria, which “leads to more production of adenosine triphosphate, a molecule that stores and transfers energy in the cells. Light therapy has also been linked with blood vessel dilation and anti-inflammatory effects.”
Despite the changes in brain connectivity, there were no observed differences in clinical outcomes between control participants and those in the LLLT- or sham-treated groups. The researchers stated that “as major improvement in life functioning can occur between 2 weeks and 12 months of natural recovery…it is too early to define the therapeutic role, if any, of LLLT.” Future research could explore how the connectivity changes observed in the present study compare with larger sample sizes, other imaging results, and clinical outcomes to help surmise the therapeutic role of LLLT in moderate TBI.
We have covered studies for photobiomodulation for mild TBI (here, here, here, and here) and a set of case studies of photobiomodulation for suspected CTE (preliminary results here and a synopsis of published results here.)
From the Archives
New York Times review of controversial Q-Collar identifies concerns about efficacy, safety
Is the Q-Collar effective at concussion prevention, and is it safe? Matthew Futterman wrote a well-rounded critique of the device for The New York Times. Concussion Alliance wrote about the Q-Collar when the FDA first cleared it. Futterman directs the reader to the FDA summary, which states that the Q-Collar was not approved to prevent concussions and there are some risks to the device.
The Q-Collar was inspired by the observation that woodpeckers don’t get brain injuries from repetitive hits (in fact, woodpecker brains do show damage). Researchers developed a collar that “restricts the flow of blood from the head” on the theory that slightly more blood in the head would give the brain “an extra layer of cushioning,” protecting it “from effects associated with repetitive sub-concussive head impacts.” This last statement is from the October FDA summary of its decision, which Futterman points out is “far more measured than the February 2021 approval announcement.” This summary lists the limitations of the Q-Collar, which include the following:
“The Q-Collar has not been demonstrated to prevent long-term cognitive function deficits and the ultimate impact on clinical outcomes has not been evaluated.”
“Data do not demonstrate that the device can prevent concussion or serious brain injury.”
In the FDA summary, the Q-Collar’s “probable benefits” outweigh the “probable risks.” The risks include a risk of syncope (passing out) and giving the user a “false sense of protection,” which Futterman also discusses. “The danger with a device like this is that people will feel more protected and play differently and behave differently,” according to physiology professor James Smoliga, “who has led a crusade in academic journals against the device.”
In terms of the probable benefits, the studies (funded by the Q30, which makes the device) showed “it might limit damage to brain tissue.” However, the FDA cited “uncertainty surrounding the imaging technology that the studies relied on” and that “a link between the changes the studies revealed and actual brain injuries has not been ‘validated.’”
Fetterman states, “And yet the longing for equipment that can prevent traumatic brain injury and make dangerous sports feel safe is intense. The FDA experts cited the urgent need for devices that ‘may’ protect the brain from mild impacts in sports and the low risk of the Q-Collar.” And the market for the Q-Collar is anticipated to be worth $30 million.
4-min patient interview: Michelle Limmer Video
We love this four-minute video, in which concussion patient Michelle Limmer talks about the challenges she faced getting appropriate care and how Concussion Alliance helped her recovery journey.
Concussion Alliance resources related to the research studies in this newsletter
Individuals with a Pre-Existing Disability
Our Individuals with a Pre-Existing Disability resource addresses identifying and treating concussions in individuals with a disability, concussion education for athletes with a pre-existing disability, return-to-sport guidelines for this population, an interview with Paralympic skier Millie Knight, plus mental health and persisting symptoms in athletes with disabilities. Osman Ahmed, PhD, PGDip (Sports Physiotherapy), worked with us to create this resource, and he is a co-author of the SCAT5 study discussed earlier in this newsletter. Our website is supported by Recite Me accessibility software; see our Accessibility Statement and Accessibility Tool User Guide.
Long-Covid
Our Long-Covid resource covers common symptoms of and risk factors for Long-Covid, how Long-Covid affects the brain, possible treatments, and similarities to persisting post-concussion symptoms.
Prolonged Symptoms
This resource on Prolonged Symptoms discusses the four categories of prolonged symptoms, factors that make someone more vulnerable to persisting symptoms, assessment and treatment, prognosis, and how prolonged symptoms can affect your life.
Vestibular Therapy
Our Vestibular Therapy resource describes symptoms that may indicate a disruption of the vestibular system, describes an assessment for vestibular dysfunction and what to expect from vestibular therapy, provides instructions for finding a vestibular specialist, and explains the vestibular system.
Light Therapy (Photobiomodulation)
Our Light Therapy resource and related light therapy blog posts cover ongoing research into light therapy for persisting symptoms after concussion, as well as for individuals who have a history of long-term exposure to repetitive subconcussive impacts and for those with suspected CTE. Topics include a description of transcranial light therapy, its safety, the science behind light therapy, and how to access light therapy devices.