Post-concussion sleep problems associated with persistent symptoms (5/18/23 Newsletter)
This week's lead article, Post-concussion sleep problems associated with persistent symptoms, is in the Statistics category.
In this newsletter: Opportunities, Cannabis, Pathophysiology, Diagnostics, Veterans and Service Members, Mental Health, Statistics, and Youth.
We appreciate the Concussion Alliance interns, staff, and Leadership Team members who created this edition:
Writers: Nancy Cullen, Minhong Kim, Susan Klein, MD, PhD, Laura Phillips, Sravya Valiveti, Aamy Woldesenbet, and Josh Wu.
Editor: Malayka Gormally
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Opportunities
Tuesday, May 30, 6 pm EST: a free webinar, Sleep Problems: Getting to Sleep and Staying Asleep, presented by Dr. Neal Parekh and hosted by the Canadian Concussion Centre. Register in advance.
Friday, June 9, 8 am PST: a free webinar, Now What? Setting your student up for success. Considerations for educators, clinicians and parents, presented by Gina Piccolini DeSalvo, Doctoral Candidate, hosted by The Center on Brain Injury Research and Training. Register in Advance.
Researchers are seeking participants for an NIH-funded (NCCIH) K23 research study at Massachusetts General Hospital and Harvard Medical School, aiming to develop and test a program to prevent persistent concussion symptoms for young adults. There is no cost for participating, no medication, and no travel. Want to learn more? See our 3/9/23 newsletter, or email MGHConcussionToolkit@partners.org.
Cannabis
More thoughts on cannabis and PTSD in veterans
Nacasch, Avni, and Toren provide a timely follow-up to our previous newsletter item on cannabis and PTSD. They avoided some of the pitfalls of studying medical cannabis for the management of PTSD and demonstrated that they recognize the complexity of studying cannabis for veterans with PTSD. In this study, published in Frontiers in Psychiatry, 14 Israeli patients with treatment-resistant combat PTSD (10-45 years after their trauma) were treated with a maximum of 20 grams of cannabis/month–at bedtime only.
Participants reported improvement in many but not all sleep characteristics. The total score of subjective quality of sleep and sleep duration improved; nightmares and difficulty falling asleep did not. The patients reported improvement in overall PTSD symptom scores, including intrusiveness, avoidance, and alertness. There was a “reduction of at least 20% in PTSD symptoms in over 65% of patients,” and almost 80% of the patients showed improvement.
Each study participant had been enrolled in a PTSD clinic from 1-17 years before this cannabis study, during which time they had been treated with conventional treatment modalities. (The mean number of years they received conventional treatment was 7.7 years.) Cannabis treatment outcome measures for sleep and PTSD symptoms were obtained through self-report questionnaires completed every six months over the 0.5-3 year follow-up period (a mean of 1.1 years follow-up period.)
Strengths of this report include:
A multidisciplinary assessment of PTSD
Identification of comorbidity (other health conditions) in the participants
The study participants had been managed with other treatments shown to be effective in PTSD for a mean of 7 years before the initiation of cannabis
Standardized outcome measurements were taken at regular intervals of time
The patients were older and had never used cannabis
All these factors point to a well-identified cohort to study.
As noted by the authors, the limitations were the small sample size and the unblinded study design without controls. We also find additional issues:
The short duration of follow-up after cannabis use, on average of only a year or so, suggesting that there were only 1-2 outcome assessments in that time frame.
The lack of knowledge about cannabis dosing in individual patients, such as the concentrations of THC, CBD, and other components
The lack of dose information, such as dose per weight or some other way to sort out how the 20 g/month was dosed over time, beyond the note that subjects used cannabis at bedtime only
Study design can overcome many of these limitations. However, it would be nice to standardize dosing characteristics of cannabis across a longitudinally-followed population.
Pathophysiology
Two or more concussions result in heightened cognitive, sleep, and neuropsychiatric symptoms
A recent study in the Journal of Neurosurgery analyzed the repercussions of multiple sport-related concussions among adolescents. The research reviewed over 25,000 Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) results collected from student-athletes (ages 12-22) between 2009 and 2019. Interestingly, patients with a history of two or more concussions reported heightened cognitive, sleep, and neuropsychiatric symptoms but not migraine symptoms. Addison Quinones et al. note that for patients, parents, and providers, migraine symptoms are more easily distinguishable, so careful monitoring for cognitive, sleep, and neuropsychiatric symptoms is critical to inform decision-making regarding patient management and return to play.
The study acknowledges the increasing societal emphasis on youth participation in sports, leading to an associated rise in concussion incidence, a major concern for parents and healthcare professionals. The CDC has reported that 20% of the annual 1.7 million pediatric concussions in the United States can be traced back to sports activities.
The research methodology involved evaluating data from the multicenter ImPACT assessments database, which prompts the participant to rate the severity of 22 neurocognitive symptoms grouped into clusters–migraine, cognitive, sleep, and neuropsychiatric. The selected participants, aged 12 to 22 years, had completed a prior ImPACT baseline test and reported any history of concussions. After a suspected head injury, participants were given an ImPACT test (PI1). If they met the ImPACT criteria for concussion, they were given a second ImPACT assessment (PI2) to track recovery.
The study revealed that patients with one previous concussion (SRC1) exhibited similar baseline characteristics to patients with multiple prior concussions (SRC2+). The initial post-injury test (PI1) showed minimal differences between the groups, with only less-severe headache symptoms emerging as a significant difference in the (SRC2+) patients. However, more significant disparities surfaced over time; the second postinjury test (PI2) showed that SRC2+ patients experienced more severe cognitive, sleep, and neuropsychiatric symptoms compared to SRC1 patients. Also, at the second postinjury test (PI2), the SRC2+ patients had the same headache severity and migraine cluster (light and sound sensitivity, etc.) as the SCR1 patients. The authors surmise that patients with multiple concussions may be more familiar with headache symptoms and so less likely to report them until they become more apparent.
This study identifies changing symptomatology over time in student-athletes with multiple concussions, which could help predict long-term outcomes and refine guidelines for return to sports and academics. This nuanced understanding of how symptoms evolve in individuals with a history of multiple concussions can inform more targeted treatment and recovery strategies. Further research could explore the implications of this symptom difference, particularly the absence of heightened migraine symptoms, and how this could affect management and recovery protocols.
Diagnostics
Exercise-induced vision dysfunction after concussion predicts risk of persistent symptoms
Vernau et al. published a study in the Clinical Journal of Sport Medicine with findings that exercise-induced vision dysfunction in adolescents within ten days of a concussion was correlated with a 3-fold risk of persistent post-concussive symptoms (PPCS). Concussions commonly affect visual function, which inspired the methods behind this study. The researchers were interested in the early identification of patients at higher risk for PPCS so these patients can be provided early, targeted treatments to improve recovery outcomes.
The study involved 99 adolescents who recently sustained a sports-related concussion up to ten days prior to testing. The researchers used a King-Devick test to discern vision dysfunction. This test captures eye movements, attention, and other sensory areas of the brain that could indicate head trauma. The King-Devick test was immediately performed two minutes after a Buffalo Concussion Treadmill Test (BCTT), a test used to determine how much aerobic activity is safe to perform after a concussion. The results identified that adolescents with higher exercise-induced vision dysfunction–a worse King-Devick test score after the BCCT – were three times more likely to develop PPCS than those without exercise-induced vision dysfunction.
This study provides a potential innovative early prognostic method for identifying patients at risk for persistent post-concussive symptoms (PPCS). They highlight the importance of evaluating visual symptoms, particularly those induced or worsened by exercise. Recognizing and addressing post-concussion, exercise-induced vision dysfunction early on may help identify individuals who are at a higher risk of developing persistent post-concussive symptoms, allowing for appropriate management and intervention strategies to be implemented.
Veterans
Early brain amyloid buildup in military instructors
A recent study published in Radiology found early brain amyloid β accumulation in military instructors (median age 33 years) exposed to subconcussive trauma. Authors Carlos Leiva-Salinas et al. examined nine military instructors routinely exposed to repeated blast events from January 2020 to December 2021, evaluating them at two points: once before blast exposure and once after routine blast exposure, approximately five months later. The military instructors were matched with nine age-matched controls not exposed to blast events.
Positron Emission Tomography (PET) scans of the brain were conducted to measure the buildup of abnormal amyloid protein. The researchers found that “in the blast-exposed participants, four brain regions showed significantly increased amyloid deposition after blast exposure: inferomedial frontal lobe, precuneus, anterior cingulum, and superior parietal lobule.” However, no amyloid buildup was found in the nine control participants. The four regions with increased amyloid deposition are known to be abnormal in Alzheimer’s Disease. The researchers posit that if individuals at risk of buildup of neurotoxic amyloid β can be identified, medication being developed for Alzheimer’s to clear amyloid might also slow or reduce the long-term development of neurodegeneration caused by traumatic injury from subconcussive blast events.
The authors conclude that “early brain amyloid accumulation was identified and quantified at PET in otherwise healthy adult men exposed to repetitive subconcussive traumatic events.” However, further studies with larger sample sizes are needed to validate these findings.
Mental Health
mTBI patients: Assessment and treatment of mental health disorders and maladaptive beliefs
In this review article, Noah Silverberg and Ana Mikolic summarize the current evidence of psychological determinants of mTBI recovery and what that means for clinicians. For mTBI patients, the factors of mental health disorders, maladaptive beliefs about their ability to cope and recover, and personality characteristics should be considered during assessment and treatment. The article, published in Current Neurology and Neuroscience Reports, discusses types of assessment tools, specific therapies (including management of psychological interventions delivered by non-psychologists), and mindfulness interventions. Silverberg and Mikolic stress that paying more attention to the psychological aspects of recovery will improve how providers manage mTBI.
People who have suffered from an mTBI consistently have higher rates of mental disorders than the general population. The disorders most commonly discussed are depression, anxiety, and post-traumatic stress disorder (PTSD). Multiple studies have found “a strong and consistent association between mental health problems and worse post-concussion symptom severity, cognition, global disability, and quality of life 3–12 months after mTBI.” What’s interesting about this, though, is that those who have a concussion also had, before their concussion, higher rates of mental health disorders than the general population; and the most consistent risk factor for a mental health disorder post-injury is having a disorder pre-injury. This means that having a mental health disorder before getting an mTBI makes a person more likely to develop a mental health disorder or symptoms after the injury, especially if other risk factors are present, such as the mTBI occurring from a traumatic event.
However, not only having a mental health disorder before the injury – or developing one post-injury – can psychologically affect recovery. Having “maladaptive illness beliefs” can also interfere with recovery time. This can be having a pessimistic outlook on one’s recovery, which can create a self-fulfilling prophecy; it’s been shown through multiple studies that having negative expectations about recovery predicts worse outcomes.
Interestingly, the authors also determined that certain personality traits can help or hinder recovery. While it’s unclear how they influence recovery or how deterministic they are, characteristics such as insecure attachment, high neuroticism, anxiety sensitivity, and perfectionism can be maladaptive. At the same time, resilience and psychological flexibility could be protective.
The authors state that mental health screening after an mTBI is critical and recommend four screening tests. Regarding when to screen for mental health disorders, the data shows that symptoms often peak around four months. Therefore, in addition to an initial screening (at 2-6 weeks post-injury), a second screening should be done in the three-to-five-month range, as early detection and prevention could improve recovery outcomes.
Mental health screening isn’t their only suggestion; they also suggest two screening tools to assess for maladaptive illness beliefs and coping behaviors. The study authors note that maladaptive beliefs are modifiable and can be a target for treatment and inform treatment tailoring.
Clinicians should also be aware of psychological influences on other aspects of mTBI assessment throughout the recovery phase. While being assessed, mTBI patients may underestimate preinjury difficulties–the “good old days” bias. However, a recent study found the reverse: mTBI patients, compared to orthopedic and healthy controls, reported more pre-existing symptoms.
They also note a bidirectional relationship between mental health disorders and cognitive impairment and that “both clinicians and patients should be cautious about attributing cognitive impairment to mTBI (brain injury and not sufficiently considering psychological contributions.”
They also have three main suggestions in terms of overall concussion management.
Conventional mental health treatment, such as cognitive behavioral therapy (CBT), including prolonged exposure and cognitive-processing therapy (CPT), can help treat diagnosed mental health diagnoses. Recent studies have found that CBT had “weak and inconsistent benefits” for overall symptom burden but stronger effects for psychological factors that can prolong recovery, such as fear avoidance behavior and catastrophizing.
Mindfulness-based interventions (meditation, yoga, etc.) have been found helpful in preventing and treating psychological post-concussion symptoms that are not diagnosed as mental health disorders.
Their final suggestion is to incorporate psychological principles such as adding CBT into treatments from non-psychologist providers, such as physiotherapists or nurses, as access to mental health professionals might be difficult.
Statistics
Post-concussion sleep problems associated with persistent symptoms
A study by Samantha N. Magliato et al. found that those who reported sleep problems in an initial clinic visit developed persistent post-concussive symptoms at twice the rate of those who did not report sleep problems after a concussion. This study, published in the Journal of Child Neurology, included 207 patients who were ≤21 days post-concussion and between 6-18 years old. Tests included the Balance Error Scoring System, single- and dual-task tandem gait tests, cognitive tests, and self-reporting questionnaires. The researchers found an association between acute post-concussion sleep issues and the development of persisting symptoms. Identifying sleep problems in the early stages of concussion recovery has the potential to allow physicians to use targeted interventions for sleep disturbances and promote an “optimal recovery environment.”
Sleep issues after a concussion are commonly reported and consist of many complaints, such as drowsiness, daytime sleepiness, sleep disruption, trouble falling asleep, and sleeping too little or too much. The authors reference other studies that have shown correlations between sleep issues and symptom burden (physical, mental, and cognitive) as well as extended recovery times. In this study, patients who reported sleep problems at their initial visit reported higher symptom severity compared to their counterparts who did not experience sleep problems, despite having similar symptom severity immediately after the concussion. The study authors suggest that between the day of injury and the initial visit (a median of ~9 to 10 days after injury), those who experienced sleep problems post-injury were not improving to the same extent as those without sleep problems. Additionally, those who experienced sleep issues had a significantly longer time before being cleared to return to sports activities than their counterparts. Those with sleep issues both pre and post-concussion had the highest incidence of pervasive concussion symptoms (67%).
There were limitations of this study that the authors noted. The population used were youths who were seen for sports-related concussions and were seen at a sports clinic. The authors point out that this might not accurately represent all children and adolescents who sustain a concussion. Secondly, it is highlighted that the use of self-reported data could be a limitation as a ‘yes’ or ‘no’ questionnaire was used to assess sleeping issues. Therefore the full extent and understanding of the issues could have been missed. Overall this study supports the early identification and treatment of sleep problems after a concussion. The authors encourage other researchers to look into this topic further and with more detail to help physicians treat sleep disturbances post-concussion.
Youth
Migraine symptoms within 48 hours of concussion associated with higher symptom burden and lower QoL three months later
According to a study by Josee van Lerssel et al., posttraumatic migraine symptoms in children within 48 hours of a concussion were associated with “higher symptom burden and lower quality of life” three months post-injury compared to children with non-migraine headaches after a concussion. Children without headaches post-concussion had the lowest symptom burden and the highest quality of life three months post-injury.
Published in JAMA Neurology, the study investigators noted, "Our findings are likely generalizable to children with varying mechanisms of injury, since recruitment was not limited to sport-related concussion. By recruiting from pediatric EDs within 48 hours of injury, we reduced the confounding effect of time to initial assessment, since late clinical care is associated with prolonged recovery."
This research was a secondary analysis of a large-scale study, Advancing Concussion Assessment in Pediatrics, which collected data from five Pediatric Emergency Research Canada (PERC) network emergency departments. The study involved 928 subjects aged 8 to 16 years with acute (defined as <48 hours of injury) concussion or orthopedic injury (OI).
Posttraumatic headaches were categorized as migraine (PTH-M) phenotype, non-migraine (PTH-NM), or no headaches (no PTH) based on self-reported post-concussion symptoms within ten days of injury. At a three-month follow-up visit, the children were assessed for symptom burden using the validated Health and Behavior Inventory (HBI) and for quality of life using the Pediatric Quality of Life Inventory–Version 4.0 (PedsQL-4.0).
Results at the three-month time point revealed that the Health and Behavior Inventory total score was significantly higher (worse health behavior) for children with migraine (PTH-M). Compared to those without headache (no PTH), those who experienced posttraumatic migraine symptoms following a concussion were two times more likely to report increases in total symptoms and nearly three times more likely to report increases in somatic symptoms. Thus, post-traumatic migraine phenotype (PTH-M) was associated with worsened symptom burden.
PedsQL-4.0 total and subscale scores, indicative of quality of life, were lower for children with migraine relative to those in the no PTH group. Of all the groups, those without posttraumatic headache symptoms reported the lowest symptom burden and highest quality of life.
According to the study authors, headaches are the most common symptom of concern associated with a pediatric concussion, which contributes to the significance and relevance of these findings. These study outcomes also necessitate further research on treatment strategies that factor in the headache phenotype, including migraine headache, while managing a patient's concussion symptoms.