Rehabilitation of Concussion and Post-concussion Syndrome

John J Leddy, Harkeet Sandhu, Vikram Sodhi, John G Baker, Barry Willer, John J Leddy, Harkeet Sandhu, Vikram Sodhi, John G Baker, Barry Willer

Abstract

Context: Prolonged symptoms after concussion are called post-concussion syndrome (PCS), which is a controversial disorder with a wide differential diagnosis.

Evidence acquisition: MEDLINE and PubMed searches were conducted for the years 1966 to 2011 using the search terms brain concussion/complications OR brain concussion/diagnosis OR brain concussion/therapy AND sports OR athletic injuries. Secondary search terms included post-concussion syndrome, trauma, symptoms, metabolic, sports medicine, cognitive behavioral therapy, treatment and rehabilitation. Additional articles were identified from the bibliographies of recent reviews.

Results: Of 564 studies that fulfilled preliminary search criteria, 119 focused on the diagnosis, pathophysiology, and treatment/rehabilitation of concussion and PCS and formed the basis of this review. Rest is the primary treatment for the acute symptoms of concussion. Ongoing symptoms are either a prolonged version of the concussion pathophysiology or a manifestation of other processes, such as cervical injury, migraine headaches, depression, chronic pain, vestibular dysfunction, visual dysfunction, or some combination of conditions. The pathophysiology of ongoing symptoms from the original concussion injury may reflect multiple causes: anatomic, neurometabolic, and physiologic.

Conclusions: Treatment approaches depend on the clinician's ability to differentiate among the various conditions associated with PCS. Early education, cognitive behavioral therapy, and aerobic exercise therapy have shown efficacy in certain patients but have limitations of study design. An algorithm is presented to aid clinicians in the evaluation and treatment of concussion and PCS and in the return-to-activity decision.

Keywords: cognitive behavioral therapy; concussion; physiology; post-concussion syndrome; rehabilitation.

Figures

Figure 1.
Figure 1.
Neurometabolic cascade following concussion. K+, potassium; CMRglucose, cerebral metabolic rate of glucose utilization; Ca2+, calcium; CBF, cerebral blood flow. With permission (adapted from Hovda et al).
Figure 2.
Figure 2.
Return-to-activity algorithm for concussion and postconcussion syndrome. *Time for symptom resolution will vary depending on clinical circumstances. Most athletes recover within 1 to 3 weeks. **Treadmill testing in patients with persistent symptoms should not be performed before 3 weeks after injury. Neuropsychological testing is not indicated, because the patient is still symptomatic. ¶If neuropsychological testing has been used, assume that there is a baseline preinjury test or valid normative data for the particular patient. †Exercise to exhaustion without exacerbation of symptoms. ‡Exercise stopped at a submaximal effort level because of symptom exacerbation. §Repeat testing interval will vary depending on clinical circumstances; it may be several days to several weeks. If athlete is not recovering, consider aerobic exercise rehabilitation. If computerized neuropsychological testing has been used and remains abnormal, continue exercise treatment and consider consultation with a neuropsychologist to evaluate for a specific cognitive deficit. RTA, return to activity; PCS: postconcussion syndrome; NP, neuropsychological.

References

    1. Agrawal D, Gowda NK, Bal CS, Pant M, Mahapatra AK. Is medial temporal injury responsible for pediatric postconcussion syndrome? A prospective controlled study with single-photon emission computerized tomography. J Neurosurg. 2005;102(2)(suppl):167-171
    1. Al Sayegh A, Sandford D, Carson AJ. Psychological approaches to treatment of postconcussion syndrome: a systematic review. J Neurol Neurosurg Psychiatry. 2010;81(10):1128-1134
    1. Alsalaheen BA, Mucha A, Morris LO, et al. Vestibular rehabilitation for dizziness and balance disorders after concussion. J Neurol Phys Ther. 2010;34(2):87-93
    1. Arciniegas DB, Topkoff JL. Applications of the P50 evoked response to the evaluation of cognitive impairments after traumatic brain injury. Phys Med Rehabil Clin N Am. 2004;15(1):177-203
    1. Baldwin SA, Fugaccia I, Brown DR, Brown LV, Scheff SW. Blood-brain barrier breach following cortical contusion in the rat. J Neurosurg. 1996;85(3):476-481
    1. Barde YA. Trophic factors and neuronal survival. Neuron. 1989;2(6):1525-1534
    1. Bazarian JJ, Atabaki S. Predicting postconcussion syndrome after minor traumatic brain injury. Acad Emerg Med. 2001;8(8):788-795
    1. Belanger HG, Vanderploeg RD. The neuropsychological impact of sports-related concussion: a meta-analysis. J Int Neuropsychol Soc. 2005;11(4):345-357
    1. Bergsneider M, Hovda DA, Lee SM, et al. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma. 2000;17(5):389-401
    1. Bergsneider M, Hovda DA, Shalmon E, et al. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86(2):241-251
    1. Berlin AA, Kop WJ, Deuster PA. Depressive mood symptoms and fatigue after exercise withdrawal: the potential role of decreased fitness. Psychosom Med. 2006;68(2):224-230
    1. Binder LM, Rohling ML, Larrabee GJ. A review of mild head trauma: part I. Meta-analytic review of neuropsychological studies. J Clin Exp Neuropsychol. 1997;19(3):421-431
    1. Boake C, McCauley SR, Levin HS, et al. Diagnostic criteria for postconcussional syndrome after mild to moderate traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2005;17(3):350-356
    1. Broglio SP, Ferrara MS, Macciocchi SN, Baumgartner TA, Elliott R. Test-retest reliability of computerized concussion assessment programs. J Athl Train. 2007;42(4):509-514
    1. Cantu RC. Second-impact syndrome. Clin Sports Med. 1998;17(1):37-44
    1. Carroll LJ, Cassidy JD, Peloso PM, et al. Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004;43(suppl):84-105
    1. Chamelian L, Feinstein A. The effect of major depression on subjective and objective cognitive deficits in mild to moderate traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2006;18(1):33-38
    1. Chen JK, Johnston KM, Petrides M, Ptito A. Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms. Arch Gen Psychiatry. 2008;65(1):81-89
    1. Cicerone KD. Remediation of “working attention” in mild traumatic brain injury. Brain Inj. 2002;16(3):185-195
    1. Del Percio C, Babiloni C, Marzano N, et al. “Neural efficiency” of athletes’ brain for upright standing: a high-resolution EEG study. Brain Res Bull. 2009;79(3-4):193-200
    1. Dimberg EL, Burns TM. Management of common neurologic conditions in sports. Clin Sports Med. 2005;24(3):637-662
    1. Dimeo F, Bauer M, Varahram I, Proest G, Halter U. Benefits from aerobic exercise in patients with major depression: a pilot study. Br J Sports Med. 2001;35(2):114-117
    1. Endo K, Ichimaru K, Komagata M, Yamamoto K. Cervical vertigo and dizziness after whiplash injury. Eur Spine J. 2006;15(6):886-890
    1. Enevoldsen EM, Jensen FT. Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury. J Neurosurg. 1978;48(5):689-703
    1. Fann JR, Uomoto JM, Katon WJ. Sertraline in the treatment of major depression following mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2000;12(2):226-232
    1. Friedman JM. Post-traumatic vertigo. Med Health R I. 2004;87(10):296-300
    1. Gaetz M, Weinberg H. Electrophysiological indices of persistent post-concussion symptoms. Brain Inj. 2000;14(9):815-832
    1. 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
    1. Gall B, Parkhouse W, Goodman D. Heart rate variability of recently concussed athletes at rest and exercise. Med Sci Sports Exerc. 2004;36(8):1269-1274
    1. Gall B, Parkhouse WS, Goodman D. Exercise following a sport induced concussion. Br J Sports Med. 2004;38(6):773-777
    1. Gebke KB. Mild traumatic brain injury. Curr Sports Med Rep. 2002;1(1):23-27
    1. Giza CC, Hovda DA. The neurometabolic cascade of concussion. J Athl Train. 2001;36(3):228-235
    1. Golding EM, Robertson CS, Bryan RM., Jr The consequences of traumatic brain injury on cerebral blood flow and autoregulation: a review. Clin Exp Hypertens. 1999;21(4):299-332
    1. Golding EM, Steenberg ML, Contant CF, Jr, Krishnappa I, Robertson CS, Bryan RM., Jr. Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury. Am J Physiol. 1999;277(4)(pt 2):H1457-H1466
    1. Goldstein B, Toweill D, Lai S, Sonnenthal K, Kimberly B. Uncoupling of the autonomic and cardiovascular systems in acute brain injury. Am J Physiol. 1998;275(4)(pt 2):R1287-R1292
    1. Gray TS. Autonomic neuropeptide connections of the amygdala. In: Tahe Y, Morley JE, Brown MR, eds. Neuropeptides and Stress. Berlin, Germany: Springer-Verlag; 1989:92-105
    1. Griesbach GS, Gomez-Pinilla F, Hovda DA. The upregulation of plasticity-related proteins following TBI is disrupted with acute voluntary exercise. Brain Res. 2004;1016(2):154-162
    1. 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
    1. Griffin SL, van Reekum R, Masanic C. A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003;15(1):17-26
    1. Guskiewicz KM. Assessment of postural stability following sport-related concussion. Curr Sports Med Rep. 2003;2(1):24-30
    1. Guskiewicz KM, Marshall SW, Bailes J, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57(4):719-726
    1. Guskiewicz KM, Marshall SW, Bailes J, et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007;39(6):903-909
    1. Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;290(19):2549-2555
    1. Hamilton MT, Hamilton DG, Zderic TW. Exercise physiology versus inactivity physiology: an essential concept for understanding lipoprotein lipase regulation. Exerc Sport Sci Rev. 2004;32(4):161-166
    1. Hanna-Pladdy B, Berry ZM, Bennett T, Phillips HL, Gouvier WD. Stress as a diagnostic challenge for postconcussive symptoms: sequelae of mild traumatic brain injury or physiological stress response. Clin Neuropsychol. 2001;15(3):289-304
    1. Heitger MH, Jones RD, Macleod AD, Snell DL, Frampton CM, Anderson TJ. Impaired eye movements in post-concussion syndrome indicate suboptimal brain function beyond the influence of depression, malingering or intellectual ability. Brain. 2009;132(pt 10):2850-2870
    1. Helmick K. Cognitive rehabilitation for military personnel with mild traumatic brain injury and chronic post-concussional disorder: results of April 2009 consensus conference. NeuroRehabilitation. 2010;26(3):239-255
    1. Hicks RR, Smith DH, Lowenstein DH, Saint Marie R, McIntosh TK. Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J Neurotrauma. 1993;10(4):405-414
    1. Ho MR, Bennett TL. Efficacy of neuropsychological rehabilitation for mild-moderate traumatic brain injury. Arch Clin Neuropsychol. 1997;12(1):1-11
    1. Hovda DA, Lee SM, Smith ML, et al. The neurochemical and metabolic cascade following brain injury: moving from animal models to man. J Neurotrauma. 1995;12(5):903-906
    1. Hovda DA, Yoshino A, Kawamata T, Katayama Y, Becker DP. Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study. Brain Res. 1991;567(1):1-10
    1. Iverson GL. Misdiagnosis of the persistent postconcussion syndrome in patients with depression. Arch Clin Neuropsychol. 2006;21(4):303-310
    1. Iverson GL, Gaetz M, Lovell MR, Collins MW. Cumulative effects of concussion in amateur athletes. Brain Inj. 2004;18(4):1.
    1. Iverson GL, Gaetz M, Lovell MR, Collins MW. Cumulative effects of concussion in amateur athletes. Brain Inj. 2004;18(5):433-443
    1. Johnston KM, McCrory P, Mohtadi NG, Meeuwisse W. Evidence-based review of sport-related concussion: clinical science. Clin J Sport Med. 2001;11(3):150-159
    1. Junger EC, Newell DW, Grant GA, et al. Cerebral autoregulation following minor head injury. J Neurosurg. 1997;86(3):425-432
    1. Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990;73(6):889-900
    1. Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab. 1992;12(1):12-24
    1. King ML, Lichtman SW, Seliger G, Ehert FA, Steinberg JS. Heart-rate variability in chronic traumatic brain injury. Brain Inj. 1997;11(6):445-453
    1. Korn A, Golan H, Melamed I, Pascual-Marqui R, Friedman A. Focal cortical dysfunction and blood-brain barrier disruption in patients with postconcussion syndrome. J Clin Neurophysiol. 2005;22(1):1-9
    1. Kristjansson E, Treleaven J. Sensorimotor function and dizziness in neck pain: implications for assessment and management. J Orthop Sports Phys Ther. 2009;39(5):364-377
    1. Kutcher JS, Eckner JT. At-risk populations in sports-related concussion. Curr Sports Med Rep. 2010;9(1):16-20
    1. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21(5):375-378
    1. Lau B, Lovell MR, Collins MW, Pardini J. Neurocognitive and symptom predictors of recovery in high school athletes. Clin J Sport Med. 2009;19(3):216-221
    1. Leddy JJ, Baker JG, Kozlowski K, Bisson L, Willer B. Reliability of a graded exercise test for assessing recovery from concussion. Clin J Sport Med. 2011;21(2):89-94
    1. 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
    1. Leddy JJ, Kozlowski K, Fung M, Pendergast DR, Willer B. Regulatory and autoregulatory physiological dysfunction as a primary characteristic of post concussion syndrome: Implications for treatment. Neurorehabilitation. 2007;22(3):199-205
    1. Levin HS, Mattis S, Ruff RM, et al. Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg. 1987;66(2):234-243
    1. Levy M, Koeppen B, Stanton B. Berne and Levy Principles of Physiology. Philadelphia, PA: Elsevier Mosby; 2006
    1. Longhi L, Saatman KE, Fujimoto S, et al. Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery. 2005;56(2):364-374
    1. Lovell MR, Collins MW, Iverson GL, et al. Recovery from mild concussion in high school athletes. J Neurosurgery. 2003;98(2):296-301
    1. Luis CA, Vanderploeg RD, Curtiss G. Predictors of postconcussion symptom complex in community dwelling male veterans. J Int Neuropsychol Soc. 2003;9(7):1001-1015
    1. Majerske CW, Mihalik JP, Ren D, et al. Concussion in sports: postconcussive activity levels, symptoms, and neurocognitive performance. J Athl Train. 2008;43(3):265-274
    1. McCauley SR, Boake C, Levin HS, Contant CF, Song JX. Postconcussional disorder following mild to moderate traumatic brain injury: anxiety, depression, and social support as risk factors and comorbidities. J Clin Exp Neuropsychol. 2001;23(6):792-808
    1. McCrea M, Guskiewicz KM, Marshall SW, et al. Acute effects and recovery time following concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;290(19):2556-2563
    1. McCrory P. Does second impact syndrome exist? Clin J Sport Med. 2001;11(3):144-149
    1. McCrory P, Johnston K, Meeuwisse W, et al. Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004 Clin J Sport Med. 2005;15(2):48-55
    1. McCrory P, Johnston KM, Mohtadi NG, Meeuwisse W. Evidence-based review of sport-related concussion: basic science. Clin J Sport Med. 2001;11(3):160-165
    1. McCrory P, Meeuwisse W, Johnston K, et al. Consensus statement on concussion in sport: 3rd International Conference on Concussion in Sport held in Zurich, November 2008. Clin J Sport Med 2009;19(3):185-200
    1. Mittenberg W, Canyock EM, Condit D, Patton C. Treatment of post-concussion syndrome following mild head injury. J Clin Exp Neuropsychol. 2001;23(6):829-836
    1. Mittenberg W, Tremont G, Zielinski RE, Fichera S, Rayls KR. Cognitive-behavioral prevention of postconcussion syndrome. Arch Clin Neuropsychol. 1996;11(2):139-145
    1. Napadow V, Dhond R, Conti G, Makris N, Brown EN, Barbieri R. Brain correlates of autonomic modulation: combining heart rate variability with fMRI. Neuroimage. 2008;42(1):169-177
    1. Nilsson P, Hillered L, Ponten U, Ungerstedt U. Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab. 1990;10(5):631-637
    1. Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness: correlation of experimental and clinical observations of blunt head injuries. Brain. 1974;97(4):633-654
    1. Oppenheimer DR. Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiatry. 1968;31(4):299-306
    1. Palmese CA, Raskin SA. The rehabilitation of attention in individuals with mild traumatic brain injury, using the APT-II programme. Brain Inj. 2000;14(6):535-548
    1. Peterson CL, Ferrara MS, Mrazik M, Piland S, Elliott R. Evaluation of neuropsychological domain scores and postural stability following cerebral concussion in sports. Clin J Sport Med. 2003;13(4):230-237
    1. Pomeranz B, Macaulay RJ, Caudill MA, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248(1)(pt 2):H151-H153
    1. Ponsford J, Willmott C, Rothwell A, et al. Cognitive and behavioral outcome following mild traumatic head injury in children. J Head Trauma Rehabil. 1999;14(4):360-372
    1. Ponsford J, Willmott C, Rothwell A, et al. Factors influencing outcome following mild traumatic brain injury in adults. J Int Neuropsychol Soc. 2000;6(5):568-579
    1. Ponsford J, Willmott C, Rothwell A, et al. Impact of early intervention on outcome after mild traumatic brain injury in children. Pediatrics. 2001;108(6):1297-1303
    1. Ponsford J, Willmott C, Rothwell A, et al. Impact of early intervention on outcome following mild head injury in adults. J Neurol Neurosurg Psychiatry. 2002;73(3):330-332
    1. Preiss-Farzanegan SJ, Chapman B, Wong TM, Wu J, Bazarian JJ. The relationship between gender and postconcussion symptoms after sport-related mild traumatic brain injury. PM R. 2009;1(3):245-253
    1. Randolph C, McCrea M, Barr WB. Is neuropsychological testing useful in the management of sport-related concussion? J Athl Train. 2005;40(3):139-152
    1. Rimel RW, Giordani B, Barth JT, Boll TJ, Jane JA. Disability caused by minor head injury. Neurosurgery. 1981;9(3):221-228
    1. Rohling ML, Faust ME, Beverly B, Demakis G. Effectiveness of cognitive rehabilitation following acquired brain injury: a meta-analytic re-examination of Cicerone et al’s (2000, 2005) systematic reviews. Neuropsychology. 2009;23(1):20-39
    1. Saija A, Hayes RL, Lyeth BG, Dixon CE, Yamamoto T, Robinson SE. The effect of concussive head injury on central cholinergic neurons. Brain Res. 1988;452(1-2):303-311
    1. Sano K, Yoshioka M, Ogashiwa M, et al. Autonomic, somatomotor and electroencephalographic responses upon stimulation of the hypothalamus and the rostral brain stem in man. Confin Neurol. 1967;29(2):257-261
    1. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298(12):1429-1438
    1. Segalowitz SJ, Mahaney P, Santesso DL, MacGregor L, Dywan J, Willer B. Retest reliability in adolescents of a computerized neuropsychological battery used to assess recovery from concussion. NeuroRehabilitation. 2007;22(3):243-251
    1. Shetter AG, Demakas JJ. The pathophysiology of concussion: a review. Adv Neurol. 1979;22:5-14
    1. Stalnacke BM, Bjornstig U, Karlsson K, Sojka P. One-year follow-up of mild traumatic brain injury: post-concussion symptoms, disabilities and life satisfaction in relation to serum levels of S-100B and neurone-specific enolase in acute phase. J Rehabil Med. 2005;37(5):300-305
    1. Strebel S, Lam AM, Matta BF, Newell DW. Impaired cerebral autoregulation after mild brain injury. Surg Neurol. 1997;47(2):128-131
    1. Taylor AR. Post-concussional sequelae. Br Med J. 1967;3(5557):67-71
    1. Taylor AR, Bell TK. Slowing of cerebral circulation after concussional head injury: a controlled trial. Lancet. 1966;2(7456):178-180
    1. Teasdale TW, Engberg A. Duration of cognitive dysfunction after concussion, and cognitive dysfunction as a risk factor: a population study of young men. BMJ. 1997;315(7108):569-572
    1. Thomas M, Haas TS, Doerer JJ, et al. Epidemiology of sudden death in young, competitive athletes due to blunt trauma. Pediatrics. 2011;128(1): e1-e8
    1. Tiersky LA, Anselmi V, Johnston MV, et al. A trial of neuropsychologic rehabilitation in mild-spectrum traumatic brain injury. Arch Phys Med Rehabil. 2005;86(8):1565-1574
    1. Treleaven J, Jull G, Sterling M. Dizziness and unsteadiness following whiplash injury: characteristic features and relationship with cervical joint position error. J Rehabil Med. 2003;35(1):36-43
    1. Tyler GS, McNeely HE, Dick ML. Treatment of post-traumatic headache with amitriptyline. Headache. 1980;20(4):213-216
    1. Vagnozzi R, Signoretti S, Cristofori L, et al. Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain. 2010;133(11):3232-3242
    1. Vagnozzi R, Signoretti S, Tavazzi B, et al. Temporal window of metabolic brain vulnerability to concussion: a pilot 1H-magnetic resonance spectroscopic study in concussed athletes. Part III. Neurosurgery. 2008;62(6):1286-1295
    1. van Ravenswaaij-Arts CM, Kollee LA, Hopman JC, Stoelinga GB, van Geijn HP. Heart rate variability. Ann Intern Med. 1993;118(6):436-447
    1. Wade DT, King NS, Wenden FJ, Crawford S, Caldwell FE. Routine follow up after head injury: a second randomised controlled trial. J Neurol Neurosurg Psychiatry. 1998;65(2):177-183
    1. Ward AA., Jr The physiology of concussion. Clin Neurosurg. 1964;12:95-111
    1. Wilde EA, McCauley SR, Hunter JV, et al. Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology. 2008;70(12):948-955
    1. Willer B, Leddy JJ. Management of concussion and post-concussion syndrome. Curr Treat Options Neurol. 2006;8(5):415-426
    1. Yamaki T, Murakami N, Iwamoto Y, et al. Cognitive dysfunction and histological findings in rats with chronic-stage contusion and diffuse axonal injury. Brain Res Brain Res Protoc. 1998;3(1):100-106

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