Sport-related concussion is a common injury that has garnered the attention of the media and general public because of the potential for prolonged acute symptoms and increased risk for long-term impairment. Currently, a growing body of evidence supports the use of various therapies to improve recovery after a concussion. A contemporary approach to managing concussion symptoms is to use aerobic exercise as treatment. To date, several studies on both pediatric and adult patients have established that controlled aerobic exercise is a safe and effective way to rehabilitate patients experiencing delayed recovery after concussion. However, less is known about the utility of an early exercise protocol for optimizing recovery after acute concussion and reducing the risk for persistent postconcussive symptoms, particularly in pediatric populations. Thus, the purpose of our paper was to review and evaluate the available literature on the implementation of aerobic exercise for the treatment of acute pediatric concussion.

Since 2000, the number of pediatric patients diagnosed with concussions in both outpatient and inpatient clinical settings has increased significantly.1,2  Recent estimates suggest that between 1.1 to 1.9 million sport- and recreation-related concussions occur annually in the United States to children or youths who are 18 years of age or younger.3  Pediatric patients who experience concussions may present with a variety of physical, cognitive, affective, and behavioral signs and symptoms, including headaches, nausea or vomiting, loss of consciousness, fatigue, confusion, and difficulty focusing or remembering.2,4  Fortunately, most pediatric patients experience relief of symptoms in the first few weeks after injury, with only a small percentage of patients experiencing delays before making a complete recovery.5  The earlier treatment paradigm for concussion management consisted of placing patients of all ages on strict physical and cognitive rest until the patient's symptoms resolved and before any return to physical activity would be considered.6  Recent consensus-based recommendations7,8  have instead advocated for a more active approach to concussion care. In fact, a growing body of evidence916  suggests that the addition of symptom-limited aerobic exercise to the rehabilitation regimen is well tolerated by pediatric and adult patients and appears to improve self-reported symptoms without negative consequences. However, much of the research919  performed to date on this topic has focused on symptom-limited aerobic exercise for improving recovery in pediatric and adult patients who specifically experienced chronic or prolonged concussion symptoms (>28 days).

Aerobic exercise can improve brain health by promoting brain vascularization and increasing levels of brain-derived neurotrophic factor.20,21  Brain-derived neurotrophic factor is known to promote the growth of new neurons (neurogenesis) as well as help repair and protect neurons from degeneration or other adverse conditions.20,21  Yet the chief physiological basis for recommending subsymptom aerobic exercise for the treatment of patients with prolonged or delayed recovery is to address the postinjury autonomic nervous system dysfunction and cerebral blood flow changes.17  Patients with concussions are unable to properly regulate cerebral blood flow, which can exacerbate clinical symptoms during exercise.10,15,17  Subsymptom aerobic exercise may, over time, help to correct impaired local blood flow in the brain and thereby reestablish normal control of cerebral blood flow.10,15 

In light of the promising findings indicating that pediatric and adult patients who were slow to recover from concussion injury benefitted considerably from engaging in subsymptom aerobic exercise,916  attention has turned to whether aerobic exercise can also be implemented as a rehabilitation strategy in the more acute stages of recovery as a way to optimize the recovery period or perhaps lessen the risk of developing persistent postconcussion symptoms. Emerging data10,15,2224  have shown that autonomic nervous system dysfunction and abnormal cerebral blood flow may develop soon after a concussion injury. Thus, it is believed the early introduction of aerobic exercise to the management plan may bestow positive benefits similar to those observed in patients with protracted recovery. Therefore, the goal of our review was to provide a summary of recently published research regarding early aerobic exercise (ie, exercise initiated in the acute stages of injury) and its efficacy for reducing acute concussion symptoms and facilitating recovery in the pediatric population.2529  In addition, we describe the exercise guidelines that have been used by investigators so as to allow clinicians to decide if and how to potentially incorporate these exercise protocols into their clinical practice.

METHODS

We used a deliberate and effective bibliographic research strategy to conduct this review in order to reduce bias in the selection of articles (Table 1). To find the best available evidence to influence practice, we formulated a well-constructed clinical question using the patient, intervention, comparison, outcome(s), time method. Using predetermined inclusion and exclusion criteria, we then performed several searches across multiple databases to obtain the best available evidence.

Table 1

Research Strategy Used to Select Articles for Review

Research Strategy Used to Select Articles for Review
Research Strategy Used to Select Articles for Review

Search Results

The literature search yielded 1623 potential articles for analysis (Figure). The criteria for article selection were designed to target the most contemporary literature related to early aerobic exercise for the treatment of acute pediatric concussion. After the inclusion and exclusion criteria were applied, only 5 relevant studies2529  were identified based on their patient populations, interventions, and outcomes. The 5 studies have been categorized based on the Strength of Recommendation (SOR) Taxonomy (Table 2).30  This framework allows for the grading of each article's methods to deliver an overall recommendation for incorporating this information into clinical practice. Of the 5 studies identified, 3 were classified as level 2 evidence and 2 as level 1 evidence. Level 1 studies demonstrate good quality in their design and methods.30  The subsequent levels represent decreases in quality and applicability to a clinical recommendation.30  The characteristics and critical appraisal of each of the applicable studies examined in this review are provided in Tables 2 and 3.

Figure

The literature review process.

Figure

The literature review process.

Table 2

Study Details and Classification of Level of Evidence Continued on Next Page

Study Details and Classification of Level of Evidence Continued on Next Page
Study Details and Classification of Level of Evidence Continued on Next Page
Table 3

Appraisal of Research Studies

Appraisal of Research Studies
Appraisal of Research Studies

Feasibility and Safety of an Early Exercise Intervention Program After Concussion

Authors of preclinical studies20,31  on rodents demonstrated that an exercise program that was implemented too soon after a concussion may have negative repercussions for recovery, yet a great deal of interest remains in assessing whether aerobic exercise can be recommended to humans in the early acute stages of injury. To ascertain the clinical utility of aerobic exercise as a treatment option for humans, the requisite first step is to establish whether this type of exercise can be safely tolerated without consequence so soon after a concussion. Fortunately, among the current evidence, investigators25, 2729  in 4 preliminary studies have directly (although not uniformly) addressed the feasibility or safety or both of prescribing aerobic exercise during the acute stages of recovery.

In 3 of the aforementioned studies,25,27,28  the feasibility or tolerability of an exercise program was determined by assessing the number of patients who, by virtue of participating in an exercise program, experienced a delay in their recovery. In 1 study of male patients,27  not a single person in the exercise group had a prolonged recovery, whereas 4 participants (13%) in the control group (ie, those who were asked to rest only) reported delays in their recovery that averaged 113 ± 73.6 days. Similarly, other researchers28  reported that 2 patients (4%) in an aerobic exercise group had a delayed recovery (ie, recovery time >30 days) as compared with 7 patients (14%) in the control group who were engaged in a stretching regimen postinjury. In a third study, patients who initiated a self-selected exercise program were less likely to experience a delayed recovery—as determined by the incidence of persistent postconcussion symptoms—versus patients who stated they had not participated in any physical activity postinjury.25 

Instead of using delayed recovery as the criterion for determining the feasibility of administering an aerobic exercise intervention postinjury, authors of a fourth study29  defined their inclusion criteria as (1) symptoms not being exacerbated during or immediately after exercise compared with pre-exercise levels and (2) participants in the exercise group being able to complete the prescribed exercise program.29  Symptom status did not worsen either during or immediately after any exercise session for any participant. Also, all participants were able to complete all requisite exercise sessions over the 11-day study period.

It is worth noting that a fifth set of investigators26  did not explicitly address or disclose whether any of their participants who engaged in early aerobic exercise experienced any negative consequences (eg, worsening symptoms) during the study period. Interestingly, these patients began an exercise program sooner than any others: 3% (n = 8) within 2 days and 21% (n = 52) within 4 days. It is not clear, however, if any of the participants who began an exercise program had a setback as a result of such early intervention. Perhaps future authors should document and report data related to adverse outcomes. Nonetheless, the researchers26  concluded, without any details or supporting evidence, that early initiation of exercise was safe.

Recommendation: The inclusion of an active intervention early in the treatment plan after pediatric concussion appears to be safe and well tolerated.

The relative safety of initiating an aerobic exercise program in the early stages of recovery after injury has been determined by noting if exercise participation resulted in the exacerbation of symptoms, the inability to complete the prescribed aerobic exercise program, or delayed recovery. Although most of the available evidence regarding the initiation of early aerobic interventions after concussion has been favorable,24,2628  feasibility and safety were not uniformly addressed among the studies that were evaluated and, in 1 study,25  not directly addressed at all. Additional high-quality research studies in which this issue is addressed further using specific outcome measures would be helpful, but the initial body of evidence is good.

SOR: B

Symptom Resolution and Recovery Time

Despite considerable advances supporting the use of active rehabilitation strategies as a way to reduce the severity and prevalence of symptoms1214,16  and promote recovery in patients experiencing persistent postconcussive symptoms,9,1315  only recently have investigators begun to explore if similar benefits are conferred to patients with acute concussions. To date, all studies2529  of the efficacy of aerobic exercise initiated within the first week of injury have generally demonstrated positive benefits.

The first authors to examine the role of acute exercise in concussion recovery were Grool et al,25  who reported in an observational cohort study that, of the 1677 children and adolescent patients who engaged in early physical activity, 48% (n = 803) had at least 3 persistent or worsening postconcussive symptoms at 7 days after enrollment, compared with 79.5% of patients who were not physically active. At 28 days postenrollment, 28.7% of those who were physically active reported persistent or worsening symptoms, compared with 40.1% of those who rested. Unfortunately, of all the relevant studies, this was the only one we evaluated that did not provide the average time to achieve a full recovery.

The remaining 4 studies2629  reviewed addressed the effects of early exercise on both symptom resolution and recovery time. In the first of 2 reports published by Leddy et al,27  patient recovery was confirmed by physician examination and defined as a return to baseline symptoms. The total recovery time after the onset of injury was more than twice as long for those who had been prescribed rest only postinjury. More specifically, those who were prescribed aerobic exercise achieved recovery in an average of 13 days versus 28 days for the rest group (P = .052). At the end of the study, 8% of patients in the exercise group still reported symptoms as compared with 33% of patients in the rest group (P = .028).

In a second publication by Leddy et al28  (a randomized clinical trial), recovery was defined as resolution of symptoms to normal levels, which was again confirmed by physician assessment and the ability to exercise to exhaustion. The median recovery period for participants who performed aerobic exercise was less: 13 days versus 17 days for those participants in a stretching group (P = .009). In addition, total symptom scores decreased at a much faster pace in the exercise group than in the stretching group, although this difference was not statistically significant.

In the only other randomized control study we reviewed, Micay et al29  observed that an aerobic exercise group experienced greater resolution of symptom severity over the first 4 weeks postinjury than a control group that received the current standard of care for concussions at that time (ie, the usual recovery care the treating physician would normally prescribe). However, this finding was not different, as the investigation was statistically underpowered due to a small sample size. Interestingly, recovery, which was based on time to full medical clearance to return to play, was slower in the exercise group versus the control group (36.1 ± 18.5 days and 29.6 ± 15.8 days, respectively), but again, this result was not statistically significant. The researchers suggested that the acute symptom burden may have played a role in this conflicting outcome, as participants in the exercise group had higher (but not statistically significant) mean symptom severity scores than the control group at the beginning of the study. Supporting this claim was the significant correlation between acute symptom severity and the overall time to medical clearance.

Finally, in a retrospective report by Lawrence et al,26  all participants were required to complete the same prescribed exercise program (ie, no control group was present), with the main difference between participants being the time (in days) from injury until the initiation of the exercise program. Recovery was defined as the time to full return to sport, school, or work, but the results were presented as the reduction in the probability of a faster full return to sport, school, or work as compared with starting the exercise program on day 1 postinjury. In general, the shorter the time to the initiation of aerobic exercise, the faster the return to sport, school, or work. Unfortunately, without a control group, it is difficult to assess the actual benefits of an early exercise program versus not exercising.

Recommendation: Introducing aerobic exercise during the acute stage of injury (ie, within 1 week) may be useful for symptom improvement.

Four of the 5 studies showed that implementing an aerobic exercise program within the first week or so of concussion offered some degree of benefit related to symptom improvement, which included a reduction in symptom severity (symptom burden) and a faster resolution of symptoms. Additional work is needed to further strengthen this recommendation.

Also, although positive outcomes related to overall recovery time (ie, decreased time) occurred in 3 of the 4 studies,2628  time to recovery was increased among those who pursued an exercise program in a randomized controlled study.29  Therefore, the ability of early aerobic exercise to optimize recovery and reduce recovery time after a concussion remains uncertain, and no recommendation is provided at this time. Further higher-quality research is needed to fully ascertain whether participation in an aerobic exercise program soon after concussion can consistently reduce the time needed to achieve full recovery.

SOR: B

Exercise Prescription

The exercise program used in 4 of the 5 studies reviewed2629  was typically well defined and prescribed by either a physician or the researchers. However, given the novelty of prescribing aerobic exercise as treatment for concussion in the early stages of recovery, it is not surprising that these exercise programs lacked uniformity because the topic had not been examined previously (Table 4). In particular, the exercise programs in these early investigations varied in the frequency, intensity, duration, and type of activities, as well as the time between the injury and when the exercise program was initiated. These components, many of which are elements of a framework for the frequency, intensity, time, and type of exercise prescribed, are important in determining the exercise dosage. As with any evaluation of exercise efficacy, the exercise dosage needs to be well defined so that the minimum level at which exercise begins to confer health benefits can be ascertained. The concept of exercise dosing is also important because it can affect the benefits achieved at various levels of prescribed exercise.

Table 4

Exercise Protocols Used in Preliminary Studiesa

Exercise Protocols Used in Preliminary Studiesa
Exercise Protocols Used in Preliminary Studiesa

Authors of most of the investigations2629  to date have relied on either a stationary bike or treadmill as the preferred choice of aerobic exercise. These modes of exercise were likely chosen for convenience and perhaps as a way for participants to more easily control exercise intensity. Besides exercise mode, several other exercise factors have varied. For example, session durations lasted 10 to 20 minutes29  or 15 to 30 minutes26  or were maintained at 20 minutes.27,28 

Exercise frequency varied to a lesser degree: sessions for 2 consecutive days followed by a day of rest for a total of 8 sessions over 11 days29  or daily exercise sessions.2628 

Perhaps the most variable exercise factor was intensity. Typically, researchers based their exercise intensity on the age-predicted maximal heart rate (HR) or a subsymptom threshold aerobic exercise prescription target HR. In 1 experiment,29  the exercise program began with the participants exercising on a stationary bike at 50% of their age-predicted maximal HR and steadily increased to 70% over the course of the study. In another,26  exercise intensity was also initially set at approximately 50% of maximum HR but increased to 70% of maximum HR over time and ultimately progressed to maximal sprints (1 minute in length repeated every 5 minutes for 30 minutes). In contrast, authors of 2 other studies27,28  set the initial intensity at 80% of the HR at which symptom exacerbation occurred. This target HR was initially determined using the Buffalo Concussion Treadmill Test and adjusted thereafter, if needed, depending on the weekly reevaluations. It should be noted that the subsymptom threshold target HR may not parallel the age-predicted maximal HR and, therefore, these 2 strategies represent distinctly different approaches to establishing exercise intensity. (Tables 5 and 6 demonstrate how these 2 strategies differ and how they would be applied for a sample patient.)

Table 5

Sample Progression of Low- to Moderate-Intensity Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Micay et al29)

Sample Progression of Low- to Moderate-Intensity Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Micay et al29)
Sample Progression of Low- to Moderate-Intensity Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Micay et al29)
Table 6

Sample Progression of Subsymptom Threshold Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Leddy et al27,28)

Sample Progression of Subsymptom Threshold Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Leddy et al27,28)
Sample Progression of Subsymptom Threshold Exercise for a 15-Year-Old Patient Recovering From Concussion (Adapted From Leddy et al27,28)

Finally, in regard to the time from injury occurrence until the start of an exercise program (ie, start time postinjury), participants in 1 study29  began exercise on day 6 postinjury, compared with days 2 to 6 in another (retrospective) study.26  Results of the latter study indicated that the shorter the time to initiation of an exercise program postinjury, the faster the return to sport, school, and work. Although patients in the 3 remaining studies25,27,28  began their exercise programs within the first 7 days after injury, the effect of the exercise start time on recovery from concussion was not examined.

Recommendation: Both subthreshold exercise and low- to moderate-intensity exercise programs (based on age-predicted maximum HR) performed either daily or intermittently may impart beneficial effects to pediatric patients recovering from concussion.

Individually, the various exercise programs that were examined all appear promising (ie, effective); however, a consensus on which exercise protocol or dosage provides the greatest benefit in terms of symptom resolution or time until recovery is lacking. Therefore, more high-quality (level 1), patient-oriented evidence obtained from larger prospective studies that further examine the role of relevant exercise factors on recovery from concussion are needed. Also, the clinician wishing to implement an exercise program with patients as part of a broader rehabilitation plan would, in all likelihood, prefer that a standardized exercise protocol be adopted or that greater conformity and agreement be reached on the specific exercise factors (as detailed by the frequency, intensity, time, and type of exercise training) that best facilitate recovery.

SOR: B

CONCLUSIONS

Research that examined the effect of early aerobic exercise for the treatment of acute pediatric concussions has shown promising results, although more high-quality evidence to firmly support its implementation is needed. Data from early studies have provided limited but good-quality evidence that aerobic exercise, when appropriately prescribed during the acute stages of recovery (ie, within 7–10 days of injury), is safe and well tolerated by pediatric patients. Additionally, introducing aerobic exercise early as part of a comprehensive treatment program does not appear to increase the risk of protracted recovery in this specific population. The emerging evidence also moderately supports the use of early subsymptom aerobic exercise as a way to either lessen the symptom burden or expedite symptom resolution. More consistent investigations are needed to assess the role of an early active intervention to accelerate the time needed by patients to fully recover from concussion. Furthermore, none of the authors who assessed the effectiveness of early active exercise on concussion recovery evaluated the influence of exercise on specific physiological measures of autonomic nervous system function or cerebral blood flow. Therefore, at present, the mechanism of action that appears to facilitate recovery in patients who engage in early active interventions has not yet been fully elucidated and requires additional attention. Finally, to attain the full benefits associated with administering early aerobic exercise in pediatric patients with concussion, clinicians should use a validated protocol that offers the greatest possible benefit. Currently, however, more research is needed to better establish the exercise factors, such as frequency, intensity, and duration of exercise, as well as the optimal timeframe for initiating an exercise program, that are most important for enhancing the recovery process after a concussion injury.

REFERENCES

REFERENCES
1. 
Almeida
AA,
Lorincz
MT,
Hashikawa
AN.
Recent advances in pediatric concussion and mild traumatic brain injury
.
Pediatr Clin North Am
.
2018
;
65
(6)
:
1151
1166
.
doi: 10.1016/j.pcl. 2018.07.006.
2. 
Mannix
R,
O'Brien
MJ,
Meehan
WP
3rd.
The epidemiology of outpatient visits for minor head injury: 2005 to 2009
.
Neurosurgery
.
2013
;
73
(1)
:
129
134
.
3. 
Bryan
MA,
Rowhani-Rahbar
A,
Comstock
RD,
Rivara
F;
Seattle Sports Concussion Research Collaborative. Sports- and recreation-related concussions in US youth
.
Pediatrics
.
2016
;
138(1):e20154635.
doi: 10.1542/peds. 2015-4635.
4. 
McCrea
MA,
Nelson
LD,
Guskiewicz
K.
Diagnosis and management of acute concussion
.
Phys Med Rehabil Clin N Am
.
2017
;
28
(2)
:
271
286
.
5. 
O'Connor
KL,
Baker
MM,
Dalton
SL,
Dompier
TP,
Broglio
SP,
Kerr
ZY.
Epidemiology of sport-related concussions in high school athletes: National Athletic Treatment, Injury and Outcomes Network (NATION), 2011–2012 through 2013–2014
.
J Athl Train
.
2017
;
52
(3)
:
175
185
.
6. 
McCrory
P,
Meeuwisse
W,
Johnston
K,
et al.
Consensus statement on concussion in sport: the 3rd International Conference on Concussion in Sport held in Zurich, November 2008
.
J Athl Train
.
2009
;
44
(4)
:
434
448
.
7. 
McCrory
P,
Meeuwisse
W,
Dvořák
J,
et al.
Consensus statement on concussion in sport: the 5th International Conference on Concussion in Sport held in Berlin, October 2016
.
Br J Sports Med
.
2017
;
51
(11)
:
838
847
.
8. 
Harmon
KG,
Clugston
JR,
Dec
K,
et al.
American Medical Society for Sports Medicine position statement on concussion in sport
.
Br J Sports Med
.
2019
;
53
(4)
:
213
225
.
9. 
Chrisman
SPD,
Whitlock
KB,
Somers
E,
et al.
Pilot study of the sub-symptom threshold exercise (SSTEP) for persistent concussion symptoms in youth
.
NeuroRehabilitation
.
2017
;
40
(4)
:
493
499
.
10. 
Clausen
M,
Pendergast
DR,
Willer
B,
Leddy
J.
Cerebral blood flow during treadmill exercise is a marker of physiological postconcussion syndrome in female athletes
.
J Head Trauma Rehabil
.
2016
;
31
(3)
:
215
224
.
11. 
Cordingley
D,
Girardin
R,
Reimer
K,
et al.
Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes
.
J Neurosurg Pediatr
.
2016
;
25
(6)
:
693
702
.
12. 
Dobney
DM,
Grilli
L,
Kocilowicz
H,
et al.
Evaluation of an active rehabilitation program for concussion management in children and adolescents
.
Brain Inj
.
2017
;
31
(13–14)
:
1753
1759
.
13. 
Gagnon
I,
Galli
C,
Friedman
D,
Grilli
L,
Iverson
GL.
Active rehabilitation for children who are slow to recover following sport-related concussion
.
Brain Inj
.
2009
;
23
(12)
:
956
964
.
14. 
Kurowski
BG,
Hugentobler
J,
Quatman-Yates
C,
et al.
Aerobic exercise for adolescents with prolonged symptoms after mild traumatic brain injury: an exploratory randomized clinical trial
.
J Head Trauma Rehabil
.
2017
;
32
(2)
:
79
89
.
15. 
Leddy
JJ,
Cox
JL,
Baker
JG
et al.
Exercise treatment for postconcussion syndrome: a pilot study of changes in functional magnetic resonance imaging activation, physiology and symptoms
.
J Head Trauma Rehabil
.
2013
;
28
(4)
:
241
249
.
16. 
Leddy
JJ,
Kozlowski
K,
Donnelly
JP,
Pendergast
DR,
Epstein
LH,
Willer
B.
A preliminary study of subsymptom threshold exercise training for refractory post-concussion syndrome
.
Clin J Sport Med
.
2010
;
20
(1)
:
21
27
.
17. 
Leddy
JJ,
Haider
MN,
Ellis
M,
Willer
BS.
Exercise is medicine for concussion
.
Curr Sports Med Rep
.
2018
;
17
(8)
:
262
270
.
18. 
Leddy
JJ,
Sandhu
H,
Sodhi
V,
Baker
JG,
Willer
B.
Rehabilitation of concussion and post-concussion syndrome
.
Sports Health
.
2012
;
4
(2)
:
147
154
.
19. 
Leddy
JJ,
Willer
B.
Use of graded exercise testing in concussion and return-to-activity management
.
Curr Sports Med Rep
.
2013
;
12
(6)
:
370
376
.
20. 
Griesbach
GS,
Tio
DL,
Vincelli
J,
McArthur
DL,
Taylor
AN.
Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury
.
J Neurotrauma
.
2012
;
29
(7)
:
1426
1433
.
21. 
Cotman
CW,
Berchtold
NC.
Exercise: a behavioral intervention to enhance brain health and plasticity
.
Trends Neurosci
.
2002
;
25
(6)
:
295
301
.
22. 
Bishop
S,
Dech
R,
Baker
T,
et al.
Parasympathetic baroreflexes and heart rate variability during acute stage of sport concussion recovery
.
Brain Inj
.
2017
;
31
(2)
:
247
259
.
23. 
Dobson
JL,
Yarbrough
MB,
Perez
J,
Evans
K,
Buckley
T.
Sport-related concussion induces transient cardiovascular autonomic dysfunction
.
Am J Physiol Regul Integr Comp Physiol
.
2017
;
312
(4)
:
R575
R584
.
24. 
Johnson
BD,
O'Leary
MC,
McBryde
MM,
Sackett
JR,
Schlader
ZJ,
Leddy
JJ.
Face cooling exposes cardiac parasympathetic and sympathetic dysfunction in recently concussed college athletes
.
Physiol Rep
.
2018
;
6
(9)
:
e13694
.
25. 
Grool
AM,
Aglipay
M,
Momoli
F,
et al.
Association between early participation in physical activity following acute concussion and persistent postconcussive symptoms in children and adolescents
.
JAMA
.
2016
;
316
(23)
:
2504
2514
.
26. 
Lawrence
DW,
Richards
D,
Comper
P,
Hutchison
MG.
Earlier time to aerobic exercise is associated with faster recovery following acute sport concussion
.
PloS One
.
2018
;
13
(4)
:
e0196062
.
27. 
Leddy
JJ,
Haider
MN,
Hinds
AL,
Darling
S,
Willer
BS.
A preliminary study of the effect of early aerobic exercise treatment for sport-related concussion in males
.
Clin J Sport Med
.
2019
;
29
(5)
:
353
360
.
28. 
Leddy
JJ,
Haider
MN,
Ellis
MJ,
et al.
Early subthreshold aerobic exercise for sport-related concussion: a randomized clinical trial
.
JAMA Pediatr
.
2019
;
173
(4)
:
319
325
.
29. 
Micay
R,
Richards
D,
Hutchison
MG.
Feasibility of a postacute structured aerobic exercise intervention following sport concussion in symptomatic adolescents: a randomized controlled study
.
BMJ Open Sport Exerc Med
.
2018
;
4
(1)
:
e000404
.
30. 
Ebell
MH,
Siwek
J,
Weiss
BD,
et al.
Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature
.
Amer Fam Phyicians
.
2004
;
69
(3)
:
548
556
.
31. 
Griesbach
GS,
Hovda
DA,
Molteni
R,
Wu
A,
Gomez-Pinilla
F.
Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function
.
Neuroscience
.
2004
;
125
(1)
:
129
139
.