Symptom presentation and pre-existing anxiety following concussion among youth athletes

Abstract

Our purpose was to evaluate the effect of self-reported pre-injury anxiety diagnosis on persistent symptom development, vestibular symptom severity, and balance control among youth who sustained a concussion. We performed a retrospective study of patients seen at a specialty pediatric concussion clinic. Patients were 18 years of age or younger, examined within 10 days of concussion, and received care until full recovery. A questionnaire was used to assess pre-existing medical and psychiatric conditions, including anxiety. Our main outcomes were prolonged symptom recovery defined as persistent symptoms for >28 days after concussion) and severity of vestibular symptoms. Patients who reported pre-injury anxiety (n=43; median age=14.9 years; 37% female) were more likely to experience symptoms > 28 days post-injury (76% vs. 54%; p=0.04) than those without pre-existing anxiety (n=241; median age=14.9 years; 53% female). After adjusting for sex, history of migraine, depression and ADHD, however, there was no independent association between pre-existing anxiety and prolonged symptom duration (adjusted odds ratio=2.34; 95% CI=0.083–6.63; p=0.11). Pre-existing anxiety was independently associated with self-reported nausea/vomiting severity (β coefficient=0.59, 95% CI=0.07–1.11). A pre-existing anxiety diagnosis does not appear to be associated with persistent symptoms after concussion, although it may be associated with post-injury nausea.

Introduction

Concussion is increasingly recognized as a substantial public health problem with more than 1 million sports-related traumatic brain injuries occurring annually, the vast majority of which are concussions.[1] Although most sport-related concussion symptoms resolve in fewer than 2–4 weeks among adolescents,[2,3] approximately 33% of concussions result in prolonged recovery—defined as symptoms lasting greater than 28 days.[4] Identification of risk factors for prolonged recovery may help clinical decision-making. Currently, risk factors for a prolonged recovery identified from a pediatric cohort of individuals seen in an Emergency Department include, female sex,[5,6] history of physician diagnosed migraine, prior concussion with symptoms lasting more than 1 week,[5] and answering questions more slowly.[7] In the same study, those with ≥ 4 errors on the Balance Error Scoring System (BESS) and symptoms including headache, noise sensitivity, and fatigue on the Post-Concussion Symptom Scale (PCSS) experienced prolonged recoveries.[7] Higher initial symptoms on the PCSS [5,8]—specifically higher vestibular-ocular symptom scores—have been associated with prolonged recovery for adolescent athletes, while higher somatic symptom scores were associated with prolonged recovery in children under 13 years old.[9] Furthermore, others have reported that acute post-injury dizziness is associated with prolonged recovery among high school football players.[10] Therefore, several potential risk factors for prolonged recovery following concussion have been identified across different populations and settings.

Additionally, psychiatric history, including a diagnosis of a pre-existing anxiety disorder, has been examined as a potential risk factor for prolonged recovery.[11–14] Two studies have investigated the role of pre-existing anxiety within recovery, finding that pre-injury anxiety is associated with longer time to full clearance, and a non-significant association with prolonged symptom duration (>28 days).[7,15] This growing empirical evidence suggests that understanding anxiety both before and after a concussion can assist clinicians with assessment and treatment and warrants further investigation.[16]

Anxiety disorders are marked by chronic episodes of excessive fear and worry occurring most days of the week and persisting for > 6 months, and can exist with other psychiatric comorbidities including depression, ADD/ADHD, and bipolar disorder.[17,18] Physical comorbidities include gastrointestinal issues, neurologic disorders, cardiac problems,[19] migraine,[20] motion sickness susceptibility (MSS)[21] and balance dysfunction.[22,23] The association between motion sickness susceptibility, balance dysfunction and anxiety has been explored through the relationship between anxiety networks and the vestibular system.[20,24] Evidence suggests that anxiety disorders cause the vestibular system to rely more heavily on visual inputs for balance than those without anxiety—leading to Vestibular-Ocular Dysfunction (VOD).[22] VOD following concussion has been independently associated with a 4x greater risk of prolonged recovery.[25] Therefore, pre-existing VOD may be associated with pre-injury anxiety disorders. This may be due in part to the higher prevalence of MSS in individuals with anxiety disorders, as previous work has established a relationship between pre-existing MSS and prolonged VOD following concussion.[26] Together these conditions may lead to prolonged recovery and greater vestibular symptoms such as nausea, balance problems, dizziness, or blurry vision following concussion.

The primary purpose of this study was to evaluate the independent effect of self-reported pre-injury anxiety diagnosis on prolonged recovery and vestibular-ocular symptoms among adolescents who sustained a concussion within 10 days of initial evaluation. A secondary purpose was to determine the effect of pre-existing anxiety disorders on balance test performance using the Balance Error Scoring System (BESS). We hypothesized that pre-existing anxiety disorders would predict more severe vestibular-ocular symptoms as well as prolonged recovery following concussion. We also hypothesized that pre-existing anxiety disorders would result in a greater number of errors on the BESS.

Materials and Methods

Study design and participants

We conducted a retrospective medical records review of patients with a concussion cared for at the Boston Children’s Hospital Concussion Clinic between May 1, 2013 and October 1, 2017. Patients self-presented or were referred for care, and were included in the analysis if they were evaluated and diagnosed with a concussion within 10 days of their injury, were experiencing concussion symptoms at the time of evaluation, and were between the ages of 8–19 years old. We excluded patients who had no clear symptom resolution date, were seen for a structural brain injury, or sustained their injury with a higher force mechanisms than typically occurs during sports (e.g. motor vehicle collision). Thus, patients who were injured during sports or through a mechanism involving forces similar to sports (e.g. falling from ground level or being injured during recreational activities), were included, while those with more severe injury mechanisms (e.g. falling from a height or motor vehicle collision), were excluded. Concussion was diagnosed by a sports medicine physician and defined according to the most recent consensus definition on concussion in sport.[27] The local institutional review board approved this study, and ethical standards were met when conducting the study.[28]

Grouping variable

All patients completed standardized intake forms addressing their demographics, medical history, concussion history, and current symptom status. To determine prior history of mental health conditions, patients were asked to identify if they have been diagnosed during their lifetime with any of the following conditions: depression, anxiety, migraines, bipolar disorder, or post-traumatic stress disorder. In order to address our primary research question, we grouped patients based on whether they reported being diagnosed with an anxiety disorder previous to their injury.

Outcome variables

Our outcome variables included whether the patient experienced persistent symptoms (>28 days), as well as vestibular symptom severity at the time of initial clinical evaluation, and performance on the modified Balance Error Scoring System (mBESS) at the time of initial clinical evaluation. In order to determine symptom status, participants completed the Post-Concussion Symptom Scale (PCSS).[29] On this scale, patients were asked to identify the number and severity (from 0–6) of 22 different concussion symptoms. As concussion symptoms are non-specific and participants may endorse symptoms for reasons unrelated to the injury, the PCSS instructions asked them to rate those symptoms that started at the time of injury and that they were experiencing 24 hours prior to completing the questionnaire. They completed the PCSS at each clinical visit, and if they no longer reported the presence of concussion symptoms, they recorded the last date they did experience symptoms and we calculated their symptom duration. The presence of persistent symptoms were thus defined as concussion symptoms that started at the time of injury and did not resolve within the first 28 days of injury. Patients without a reliable date of symptom resolution were not included in the persistent symptom analysis. We selected 28 days as our cutoff for prolonged concussion recovery consistent with past research, as this is the time when most children report symptom recovery after a concussion, and because if symptoms persist beyond 28 days post-injury, management strategies may change and specialist referral may occur.[3,7,30,31]

In order to assess vestibular symptom severity at the time of clinical evaluation, we analyzed responses to the PCSS for nausea/vomiting, balance problems, dizziness, and blurry vision from 0 (no symptoms) to 6 (maximum severity). Each rating was treated as a discrete variable in the analysis.

We then assessed balance control using the mBESS.[32,33] During this test, patients stand in three conditions (double leg, single leg, and tandem) for 20 seconds with their eyes closed and their hands on their hips. During double-leg stance, participants were instructed to stand with their feet positioned side by side. During single-leg stance, participants stood on the foot that they identified as their non-dominant kicking leg. The tandem stance consisted of participants standing with their feet positioned where the non-dominant foot was placed directly behind the dominant foot. The clinician administering the test recorded an error any time an athlete took their hands off of their iliac crests, opened their eyes, stumbled, flexed or abducted the hip greater than 30 degrees, lifted their forefoot off of the floor, or remained out of the proper position for greater than 5 seconds. Per mBESS protocol, the maximum amount of errors per stance is 10.

Statistical Analysis

Continuous variables are presented as medians [interquartile ranges]; categorical variables are presented as number included and corresponding percentages. We first compared demographic and medical history factors between those with and without pre-injury anxiety using Mann-Whitney U or Fisher’s exact tests. We then conducted univariable comparisons of vestibular symptom severity and mBESS errors between groups using Mann-Whitney U tests, and whether the patient experienced persistent concussion symptoms using Fisher’s exact test.

In order to identify the independent association between pre-injury anxiety disorders and persistent concussion symptoms, we constructed a multivariable logistic regression model where persistent symptoms (yes/no) was the outcome variable, self-reported pre-injury anxiety diagnosis was the predictor variable, and covariates were included as patient characteristics that demonstrated potential differences between groups, defined as p < 0.20 (sex, history of migraine, history of ADHD, and history of depression) on univariable comparisons. In order to identify the independent association between pre-injury anxiety disorders and vestibular symptom severity, we used a series of multivariable linear regression models. Our predictor variable was a pre-injury anxiety diagnosis, our outcome variables were symptom severity for each vestibular symptom, and our covariates were used as described above. We assessed collinearity using condition indices and corresponding variance inflation factors. A condition index >30 was determined to require individual collinearity assessments, which were performed using variance inflation factors. Collinearity between two variables was detected with a variance inflation factor (VIF) >2.5.[30] All statistical tests were two-sided, significance was determined as p < 0.05, and statistical analyses were performed using Stata version 15 (StataCorp, College Station, TX).

Results

There were a total of 999 patient charts reviewed during the study period. After applying inclusion/exclusion criteria, there were a total of 284 patients included in the current analysis: 43 (15%) of which reported a pre-injury anxiety disorder diagnosis. A higher proportion of those who reported a pre-injury anxiety diagnosis also reported pre-injury a migraine diagnosis, an ADHD diagnosis, and a depression diagnosis than patients who did not have a pre-injury anxiety diagnosis (Table 1). A higher proportion of those with a diagnosis of anxiety prior to injury were male (Table 1). The pre-injury anxiety diagnosis group was seen for initial evaluation at a similar average time as the no pre-injury anxiety diagnosis group (average= 5.8, SD= 2.6 days post-injury vs. average=5.6, SD= 2.7 days post-injury; Table 1).

Table 1.

Univariable patient characteristic comparisons between patients who did and did not report pre-injury anxiety.

Variable	Pre-injury anxiety (n=43)	No pre-injury anxiety (n=241)	P value
Age (years)	14.9 [13.5–16.8]	14.9 [13.0–16.9]	0.80
Sex (female)*	16 (37%)	128 (53%)	0.07
Evaluation time (post-injury days)	6 [3–8]	5 [3–8]	0.52
Prior history of concussion?	27 (63%)	138 (58%)	0.62
History of migraine?*	8 (22%)	26 (13%)	0.20
History of ADHD?*	13 (31%)	22 (9%)	< 0.001
History of depression?*	11 (26%)	3 (1%)	< 0.001
LOC at time of injury?	4 (10%)	27 (11%)	> 0.99
Sport-related injury?	28 (82%)	194 (88%)	0.40

^*Variables that demonstrated potential between-group differences (p < 0.20) were included as covariates in multivariable models.

On univariable examination, a higher proportion of those with a pre-injury anxiety disorder (n=22/29; 76%) went on to develop persistent concussion symptoms compared to those without a pre-injury anxiety disorder (n=105/193; 54%; OR= 2.63, 95% CI = 1.07, 6.46; Table 2). Furthermore, pre-injury anxiety disorders were associated with a higher self-reported symptom severity rating for nausea/vomiting (OR= 1.42, 95% CI = 1.14, 1.79; Table 2) and balance problems (OR= 1.29, 95% CI = 1.05, 1.58; Table 2). There were no significant differences between those with and without a pre-injury anxiety disorder on the number of errors made during the mBESS (Table 3).

Table 2.

Univariable comparisons between patients with and without pre-existing anxiety for persistent concussion symptoms and vestibular symptom severities.

Variable	Pre-injury anxiety		No pre-injury anxiety		P value
Symptoms persisting > 28 days post-concussion?*†	22/29 (76%)		105/193 (54%)		0.043
	Median [IQR]	Number included	Median [IQR]	Number included	P value
Nausea/vomiting symptom severity*	1 [0–3]	40	0 [0–1]	215	0.003
Balance problems symptom severity*	1.5 [0–3]	40	0 [0–2]	217	0.013
Dizziness symptom severity	1 [0–3]	35	1 [0–2]	192	0.24
Blurry vision symptom severity	0 [0–1]	32	0 [0–1]	198	0.44

^*Pre-injury anxiety was associated with a greater odds of developing persistent concussion symptoms, as well as higher nausea/vomiting and balance problems self-reported symptom severities.

^†Data are reported for patients who had a reliable date of symptom resolution: n=29 patients in the pre-injury anxiety group and n=193 in the no pre-injury anxiety group.

Table 3.

Performance on the mBESS among those with and without pre-injury anxiety.

mBESS Condition	Pre-injury anxiety	No pre-injury anxiety	P value
Double-leg stance	0 [0–0]	0 [0–0]	0.98
Single-leg stance	2 [1–4]	2 [1–4]	0.93
Tandem stance	1 [0–3]	1 [0–3]	0.20

After adjusting for history of migraine, depression, ADHD and sex, pre-injury anxiety disorders did not independently predict persistent concussion symptoms (adjusted OR= 2.34; 95% CI=0.83–6.63; p=0.11). Pre-injury anxiety disorders were, however, independently associated with a higher nausea/vomiting symptom severity score, but not the other vestibular symptoms assessed (Table 4).

Table 4.

The independent association between pre-injury anxiety and vestibular symptoms, while adjusting for the effect of covariates.

Symptom	β coefficient	Standard Error	95% Confidence Interval	P value
Nausea/vomiting symptom severity*	0.59	0.26	0.07–1.11	0.026
Balance problems symptom severity	0.41	0.32	−0.22–1.03	0.20
Dizziness symptom severity	−0.22	0.35	−0.72–0.68	0.95
Blurry vision symptom severity	0.14	0.26	−0.37–0.65	0.60

^*95% confidence interval did not cross zero.

Discussion

Results from our investigation indicate a pre-injury anxiety diagnosis is not independently associated with a prolonged recovery from concussion, although it may be associated with nausea symptom severity following concussion.

Although the relationship between pre-existing anxiety disorders and post-injury nausea is not well established, the connection may be attributed to an overlap between anxiety networks and the vestibular system.[20,24] Previous work has established a connection between vestibular dysfunction and anxiety—specifically balance dysfunction[22] and motion sickness suceptibility.[21] Motion sickness arises when there is a neural mismatch between an internal model of how a dynamic environment should respond and the actual behavior of the environment.[34] The neural mismatch leading to motion sickness and subsequent nausea may be amplified post injury due to vestibular dysfunction associated with concussion.[25] This mismatch may be further exacerbated in a cohort with pre-existing vestibular deficits, which may explain the higher incidence of post concussive nausea we observed in the pre-injury anxiety group. The higher nausea symptom burden observed may not significantly alter the morbidity of patients in this cohort; however, this result is not without clinical relevance. This information allows clinicians to identify the underlying deficits common to concussion in this population. As evidenced in previous work, concussions can be characterized into six distinct, but overlapping subtypes each with unique underlying mechanisms, symptoms and treatments [35,36]. Timely identification of the primary subtypes may both speed up recovery times and reduce morbidity through the prompt initiation of individualized treatments.[35,36]

When we examined a pre-existing anxiety diagnosis through univariable analysis it was associated with balance problems, nausea and prolonged recovery. However, once we adjusted for sex, migraine, ADHD, and depression, these relationships were no longer significant. This suggests that there is likely a large overlap between pre-injury anxiety and other common mental health conditions. However, we cannot conclude if each condition contributes to the overall effect in a unique manner, or if the effect is largely mediated by an individual mental health condition. Our findings align with prior work that have established ADD/ADHD,[17] depression[10, 12] and migraine[20] as conditions often comorbid with anxiety disorders. This suggests that pre-injury anxiety may be one of many potential factors that contribute to prolonged recovery. However, this relationship is likely far more complex and multifactorial.[38] The results of our study are consistent with a previous study that did not find an independent association between pre-existing anxiety and prolonged recovery (>28 days).[7] However, pre-existing anxiety has been reported as an independent factor associated with a longer time to full medical clearance.[15] These mixed findings reflect the need for additional research on the relationship between pre-existing anxiety and concussion recovery.

The independent effect of pre-injury anxiety disorders on concussion recovery cannot be determined solely by our study, due to limitations in the sensitivity of our anxiety measures. Prior work further supports this notion by establishing a connection between pre-existing psychiatric conditions—including depression and ADD/ADHD—and prolonged recovery.[11,12,14] This suggests that although pre-existing anxiety disorders are not independently predictive of prolonged recovery or balance problems, patients with a pre-existing anxiety disorder are more likely to have comorbid conditions which together may lead to prolonged recovery and balance dysfunction.

We did not observe a significant association between pre-existing anxiety disorders and performance on the BESS. The vestibular system is composed of the vestibulospinal system and the vestibular-ocular system, however, the BESS primarily identifies dysfunction in the vestibulospinal system.[39] Visual input has been shown to be more important for vestibular function in patients with anxiety,[22] suggesting that the vestibular-ocular aspect of the vestibular system may be relied on more in patients with anxiety. This is supported by our findings that pre-existing anxiety does not predict a greater number of errors on the BESS. It is possible, however, that if anxiety had been quantified using more sensitive measurements, such as the State-Trait Anxiety Inventory, we may have seen an association between BESS performance and the degree of pre-existing anxiety. Additionally, the BESS has been shown to return to baseline 3–5 days following concussion.[40] As our study included participants who completed the mBESS test within 10 days post-injury, examination of patients presenting within a more acute post-injury timeframe (i.e. 72 hours post-injury) may have led to better analyses of association between pre-existing and mBESS performance.

Our study was not without limitations, and our findings should be interpreted in context of them. All patients reported to a specialty clinic, reducing the generalizability of our findings to other settings. We attempted to mitigate this limitation by only including patients who were evaluated within 10 days of injury. All patients were children or adolescents, therefore caution should be taken when attempting to extrapolate to other age groups. In addition, the retrospective nature of a medical record review reduces the ability to control for factors pertaining to medication use prior to and after injury, treatment, management, and medical decision-making. Additionally, pre-existing anxiety was assessed using self-reported methods. Thus, patients may have reported subclinical levels of anxiety as a diagnosed anxiety disorder. On the contrary, individuals with high levels of anxiety may not have received a formal anxiety disorder diagnosis. The degree of anxiety in individuals with diagnosed anxiety disorders may also be highly variable. Our intake form did not differentiate types of anxiety disorders, which may each lead to different outcomes following concussion. Quantifying levels of anxiety would allow for evaluation of a dose-response effect between levels of pre-existing anxiety and post-concussion symptoms and recovery times. Knowledge on the independent effect of anxiety disorders on concussion symptoms allows more insight on the potential mechanisms underlying the prolonged recovery associated with pre-existing mood disorders that has been previously established.[11–15]

In conclusion, pre-existing anxiety disorders were independently associated with post-concussion nausea/vomiting symptom severity among youth athletes who sustained a concussion and were evaluated within 10 days of the injury, but were not associated with prolonged symptom recovery. Nausea associated with exacerbated pre-injury vestibular deficits including motion sickness susceptibility might be amenable to treatment,[41] including strategies such as vestibular therapy or avoidance of visually complex environments.[35]