1. Medical Management of Concussion Matt Bayes, MD FAAP CAQSM Primary Care Sports Medicine The Sports Medicine Institute The Orthopedic Center of St. Louis

2. Outline Concussion definition Current guidelines Pathophysiology/cellular metabolism Demographics Concussion symptoms Predictors of severity/duration Clinical management Return to play Major questions for clinicians today Prevention

3. Concussion Definition “A complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces.” -3 rd International Conference on Concussion in Sport. Zurich, November, 2008 Concussion has been recognized since the 10 th century A.D., still no universal agreement on its definition.

4. Current Guidelines: Zurich, 2008 Consensus opinion Abandons concussion severity grading (simple vs. complex) Still a lack of evidence based guidelines Over 20 prior published concussion management guidelines

5. Pathophysiology of Concussion Acceleration-deceleration forces are applied to the moving brain, which in turn causes shearing forces or distortion to the vascular and neural elements of the brain Based on animal models and studies of moderate-to-severe brain injuries

6. Cellular Metabolism Animal studies: Acute neurometabolic cascade involving extracellular K+, accelerated glycolysis and increased lactate production immediately following concussion Leads to a dissociation of metabolism and cerebral blood flow, resulting in a state of metabolic depression

7. Cellular Metabolism Increased lactate is believed to leave neurons more vulnerable to secondary ischemic injury, may predispose to repeat injury Later steps in the cascade involve intracellular Ca++, mitochondrial dysfunction, impaired oxidative metabolism, decreased glycolysis, axonal disconnection, neurotransmitter disturbances, and delayed cell death

8. Cellular Metabolism Decreased cerebral blood flow lasts approx 10 days in animal models This is consistent with an apparent 7-10 day period of susceptibility to recurrent injury in a prospective cohort study by Guskiewicz et al.

9. Giza and Hovda, 2001. JAT

10. Demographics 1.6-3.8 million concussions/yr in U.S. Oft-quoted # is 300,000/yr, this was based on ER visits for head injury with LOC. Only 8-19% of sports concussions results in LOC, therefore an extrapolation of the numbers yields the more accurate number

11. Demographics Highest rates in high school sports in football and ice hockey, followed by soccer, wrestling, basketball, field hockey, baseball, softball, and volleyball Concussions account for 10% of all injuries in contact/collision sports according to U.S. high school data reporting Females have higher incidence and severity, with worse outcomes than men

12. Symptoms: Immediate Change in playing ability Vacant stare Fogginess/confusion Slowing Memory disturbance Loss of consciousness Increased emotionality Incoordination Headache Dizziness vomiting

13. Symptoms: Delayed Generally grouped into 3 domains: Somatic: HA, fatigue, low energy, sleep disturbance, nausea, vision changes, tinnitus, dizziness, balance problems, light/noise sensitivity Emotional/Behavioral: lowered frustration tolerance, irritability, increased emotionality, depression, anxiety, clinginess, personality change Cognitive: slowed thinking or response speed, mental fogginess, poor concentration, distractibility, trouble with learning and memory, disorganization, problem solving difficulties

14. Severity/Duration Predictors Many risk factors including age, gender, and comorbid conditions add variability to concussion management Comorbid conditions: mood disorder, learning disorder, migraine headache, apolipoprotein E, family history, fatigue

15. Female Gender Cause unknown May include biomechanical (stronger neck muscles in males are better able to absorb force), hormonal, and cultural (more honest symptom reporting in females) factors Classic “high achieving” female

16. Pediatric Population Developing brain has unique physiologic variables that change continuously with growth, unclear how brain development affects susceptibility to concussion Zurich consensus statement uses age 10 as a lower cut-off point, noting that children below this age need a different, age-specific symptom inventory Field et al: Although only 11% of the HS athletes had LOC w/ concussion compared with 34% of college athletes, the HS athletes had slower acute neuropsychologic recovery than the college athletes

17. Anxiety/Depression No study has looked at the risk of concussion in patients with pre-existing anxiety and depression Anxiety and depression do occur after TBI Patients with more mild brain injury are at a higher risk of developing post- concussive symptoms including fatigue, anxiety and depression

18. Learning Disorders Common effects of concussion such as decreased attention level and difficulty with learning and memory can also be an underlying problem in an athlete

19. Learning Disorders Using Neuropsychological (NP) testing to establish a baseline cognitive function is vital in these athletes Interpretation of NP scores using normative data is fraught with error Formal referral for evaluation by a neurologist or neuropsychologist is often warranted

20. Migraine headache Risk of concussion is higher in those diagnosed with having migraine headaches by a health professional Causality is unknown, the two diagnoses may share a common pathophysiologic pathway Athletes reporting migraine type symptoms (light/sound sensitivity) are more likely to have a longer time to clinical recovery

21. Apolipoprotein E ApoE is a fat-binding protein that is essential for several biological functions 3 isoforms: ε2, ε3, and ε4 ApoE-ε4 has been shown to be a risk factor for developing Alzheimer’s disease 1 prospective cohort study has shown no association between the presence of ApoE-ε4 and the incidence of concussion Further research is needed, screening athletes pre- or post-injury is not currently recommended

22. Family History No studies have examined the relationship between a family history of concussion and concussion risk, yet this is essential knowledge Example: Management of an athlete is affected if there is a 1 st degree relative w/ multiple concussions with decreasing force requirements, escalating symptoms, changing personality, retirement from contact sports, and prolonged cognitive and mood effects

23. Fatigue Physical fatigue is a risk factor for sustaining a concussion Concussion is a physiologic injury with symptoms being the result of neuronal dysfunction linked closely with an energy crisis resulting from biomechanical forces applied to the brain

24. Fatigue It follows that a concussion is more likely to occur in the setting of an energy- demand physiologic state 2008 NHL player study showed that in- game fatigue played a role in concussion risk

25. Clinical Management: On Field Concussion should be suspected if an athlete displays any concussion symptoms following a traumatic blow to the head or body ABCDE trauma evaluation, LOC assessment Unconscious athletes should be treated as having an unstable spinal cord injury

26. Clinical Management: On field Helmets and shoulder pads should not be removed on the field Immediate motor phenomena (tonic posturing) or convulsive movements may accompany a concussion These are dramatic but generally benign features that require no specific management beyond standard concussion care

27. Clinical Management: On field Prospective cohort studies have shown that brief LOC (<60 sec) does not reflect injury severity or predict time to recovery Rule of thumb: “When in doubt, sit them out!”

28. Clinical Management: Hospitalization/Imaging Immediate referral to a hospital is recommended if prolonged LOC > 5 min, focal neurologic deficit, decreasing mental status or level of consciousness, unequal pupil size, uncontrolled vomiting, suspected skull fracture or penetrating skull trauma, or worsening symptoms Other considerations: young age, lack of adequate supervision

29. Clinical Management: Sideline Complete neurologic exam, with balance testing and visual field assessment Simple person/place/time not reliable Situation relevant questions (name of opponent, score of game, time remaining) SCAT2 (Sport Concussion Assessment Tool) is an excellent standardized 5 minute sideline evaluation tool SCAT2 can be performed as a baseline test in the preseason to compare post-injury scores

30. Clinical Management: Sideline Athletes cleared and returned to the game should be re-evaluated periodically for delayed symptoms Athletes removed from the game due to concussion should be monitored for progressive decline

31. Clinical Management: Sideline Youth/HS/College athletes with diagnosed concussion should not be returned to play the same day Same day RTP addressed by Zurich guidelines: Occasionally adult athletes may be returned to play the same day if sufficient sideline resources are available (team physician, immediate neurocognitive assessment, etc…) Again: “When in doubt, sit them out”

32. Clinical Management: Office Thorough past medical hx, family hx, meds, social hx, etc… Full neuro exam including balance BESS test: standardized, easy to do Ophthalmoscope exam to r/o increased intracranial pressure

33. Clinical Management: Office CT or MRI can be considered to rule out structural abnormalities, these are normal in a concussion New imaging modalities: functional MRI, PET scan, diffusion tensor imaging, magnetic resonance spectroscopy are useful only in research setting

34. Office: Approach to the patient Stress physical and cognitive rest Important to advocate for the patient at school Removal from school early on can decrease the time to recovery Subspecialty referral is appropriate at any time, especially if diagnosis of post- concussive syndrome is made

35. Office: Educational Modification 3 ways to modify education: 1. 1. Informal: simple note written for several days off of school, extra time for tests or projects, multiple breaks during school day for rest, etc… 2. 2. Section 504 plan: official, intermediate between informal and IEP, can authorize home education, should be considered early 3. 3. IEP: Individualized Education Plan, rarely needed

36. Return To Play (RTP) It is the physicians job to provide objective assessment of the injured athlete and guidance about the advisability of safe return to competition Children/adolescents tend to have a more prolonged recovery phase than adults, with a higher risk of having a subsequent concussion

37. Return to Play Adverse effects on neurocognitive function can be cumulative and modified by proximity of successive concussions, their severity, and individual susceptibility Grading scales have been abandoned in favor of a more individualized approach to each athlete

38. RTP: Recurrent Concussions 2003 prospective cohort study of 2905 college football players from 25 US colleges found players with a hx of 3 or more previous concussions were 3 times more likely to sustain a concussion than those with no concussion hx Of in-season repeat concussions in this study 92% occurred within 10 days of the first injury 1 in 15 players with concussion may have repeat concussions in the same playing season

39. RTP: Recurrent Concussions Same 2003 study: There was no association between concussion history and the presence of either LOC or amnesia with subsequent concussions However, presence of LOC and amnesia tended to be associated with slower recovery College football players are much more likely to sustain a concussion during a game than practice

40. Graded RTP Protocol Stepwise progression, 24 hours for each step Proceed to the next level if asymptomatic at the current level Approximately 1 week to proceed through the full rehabilitation protocol If symptoms recur during the protocol, the athlete should drop back to the previous asymptomatic level and try to progress again after 24 hours of rest has passed

41. Graded RTP Protocol Rehabilitation StageFunctional Exercise at Each Stage of Rehabilitation Objective of Each Stage 1. No activityComplete physical and cognitive restRecovery 2. Light aerobic exerciseWalking, swimming, or stationary cycling keeping instensity < 70% maximum permitted heart rate No resistance training Increase heart rate 3. Sports-specific exerciseSkating drills in ice hockey, running drills in soccer, no head impact activities Add movement 4. Non-contact training drillsProgression to more complex training drills (passing drills in football and ice hockey) May start progressive resistance training Exercise, coordination, and cognitive load 5. Full contact practiceFollowing medical clearance participate in normal training activities Restore confidence and assess functional skills by coaching staff 6. Return to playNormal game play

42. Major Questions for Clinicians Neuropsychologic testing Post-Concussion syndrome Pharmacologic therapy Second Impact Syndrome Late effects of concussion Retirement decisions

43. Neuropsychologic Testing (NP) NP testing has given clinicians an additional tool to evaluate head injuries Excellent for documenting deficits Traditional paper and pencil testing is time-consuming and labor intensive Use as a diagnostic tool in sports medicine began in the mid-80’s and has grown steadily

44. Neuropsychologic Testing 4 computer based models available: ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing), CogState, Headminders, and ANAM (Automated Neuropsychological Assessment Metric) Available for adolescent through adult ages, ages 5-12 is in the final stages of development

45. Computerized Neuropsychologic Testing Take 30 minutes to perform on average Best utilization: comparison of post-injury scores to baseline scores to give objective date for cognitive deficits Alternative: In the absence of a baseline score there are extensive normative data that allow the comparison of an athlete post-injury to that of his/her peers

46. NP test: ImPACT Comprised of 7 test modules that assess multiple neurocognitive abilities Select module scores are combined to yield composite indices: reaction time, verbal memory, visual memory, processing speed, and impulse control Symptom self-report inventory is also included: 21 item scale requires the athlete to subjectively rank symptoms from 0 (not present) to 6 (severe symptoms) This can be compared to pre-injury symptoms, as well as followed during the recovery period

47. NP test: ImPACT The test results and subjective symptoms do not always correlate, and should both normalize as the athletes recover An athlete must be symptom free and cognitively intact both at rest and following exertional activity before return to play is allowed following a concussion

48. Limitations of ImPACT Use by untrained clinicians: not a yes/no Reliability has been debated Computerized tests have more test-to-test variability than traditional pen and paper test, making them more difficult to detect minor differences However, this variability protects against a practice effect

49. Limitations of ImPACT Contributing medical problems such as LD and ADD/ADHD can make test interpretation difficult, as can certain medications (some epilepsy meds can decrease reaction time as a side effect) Practice effect: Repeating a test over a short time interval may lead to artificial score inflation Interpretation of post-injury scores to normative data without a baseline can be error prone

50. Limitations of ImPACT Using normative data without baseline: -A ‘normal score’ in an individual who would score very high on baseline testing could lead to premature clearance -Individuals who would score below average at baseline may be inappropriately denied clearance

51. NP testing: How do I use it? Baseline testing is ideal: can be done in large groups in a computer lab or individually 1 st test post-concussion in the early symptomatic period (~48 hours). This is controversial: Does it change management? An early abnormal NP test gives objective data to the athlete and his/her parent, justifying their exclusion from school/play Low scores can prove a concussion to an athlete that may be minimizing symptoms Occasionally helps athletes in their interaction with overzealous coaches Repeat the NP test score after the athlete is asymptomatic, requiring ‘normal scores’ and symptom report before they are cleared to play

52. NP Testing: Summary Meant to enhance, not supersede, clinical judgment Should not be the sole basis for return to play decisions NP testing is just another tool in the toolbox of concussion management

53. Post-Concussion Syndrome (PCS) Definition: A syndrome that occurs as the result of a concussion, with its own distinct psychological pathophysiology Symptoms: Can be physical, cognitive, sleep, or mood related Symptoms are typically out of proportion to the inciting injury Considerable controversy in the literature disputing the cause, nature, treatment, and existence of PCS

54. Post-Concussion Syndrome Up to 15% of concussions can be associated with persistent symptoms Diagnosis of PCS should be considered with symptoms lasting > 3 weeks Symptoms may be prominent in one area or a blend of all four areas Unusual to develop symptoms that were not present with the original concussion

55. Post-Concussion Syndrome Post concussion syndrome is an ill- defined, ambiguous, poorly understood, syndromic cocktail of myriad symptoms and/or cognitive deficits lasting anywhere from a few weeks to a few years…maybe Jeff Kutcher, MD Director, Michigan Neurosport University of Michigan

56. Symptoms of PCS Cognitive Mood SleepPhysical

57. Role of Pharmacologic Therapy Lack of EBM for pharmacologic treatment Medications can be helpful in 2 situations: management of specific prolonged symptoms (sleep disturbance, anxiety) or to modify the underlying pathophysiology of the condition with the aim of shortening the duration of the concussion symptoms

58. Role of Pharmacologic Therapy Athletes should not be taking any meds that may mask or modify the symptoms of concussion when they return to play Anecdotal findings: -Nortryptiline 50 mg qhs is helpful in PCS to treat pain, especially in pts with hx of migraine HA or strong migraine-like concussion symptoms -Amantadine 100 mg BID is useful for cognitive symptoms

59. Second Impact Syndrome (SIS) SIS is a controversial entity Diffuse cerebral swelling is a rare but well recognized cause of delayed catastrophic deterioration resulting in death or a persistent vegetative state after an apparently minor head injury 50% mortality, 100% morbidity

60. Second Impact Syndrome Postulated that a specific form of cerebral swelling may be the consequence of a repeated minor head injury, termed the second impact syndrome SIS occurs when an athlete who has sustained an initial head injury sustains a second head injury before sx associated with the first have fully cleared

61. Second Impact Syndrome Postulated to set into motion the rapid development of cerebral vascular congestion, which in turn causes increased intracranial pressure, usually resulting in brainstem herniation and death

62. Second Impact Syndrome SIS concepts rest on 17 published case reports Review of these cases by McCrory et al in Neurology in 1998 showed that of these 17, only 5 have been shown to be probable SIS due to various factors, none of the cases were found to be definite SIS

63. Second Impact Syndrome All cases of probable SIS occur in adolescents, all were in males, 3 were in boxing, 1 in American football Although evidence is lacking for SIS, the consequence of returning an athlete at risk for a potentially life-threatening event is the basis of all return-to-play criteria that recommend removing a concussed athlete from play

64. Late effects of concussion Cognitive Impairment Depression Chronic Traumatic Encephalopathy

65. Cognitive Impairment Guskiewicz et al: questionnaire study of 2552 retired professional American football players Identified an association between recurrent concussion and clinically diagnosed mild cognitive impairment and self-reported significant memory impairments No statistical association between recurrent concussion and Alzheimer’s disease

66. Depression Same study: Retired players with 3 or more concussions were 3 times more likely to be diagnosed with depression Those with a history of 1 or 2 previous concussions were 1.5 times more likely to be diagnosed with depression This study controlled for age, # of years played, # of years since retirement, and medical co- morbidities

67. Chronic Traumatic Encephalopathy (CTE) Early clues from professional boxing, known as punch-drunk or a ‘slug-nutty’ state Described first in 1928 Is a constellation of symptoms due to lesions affecting the pyramidal, cerebellar, and extrapyramidal systems

68. Chronic Traumatic Encephalopathy Mild: slurring dysarthria, +/- subtle pyramidal disease or disequilibrium Later stage: cognitive impairment is the major neurologic feature 1/3 of cases are progressive in nature Only a handful of cases are described outside of boxing, these have had association with a strong family hx of dementia, prominent neuropsychiatric symptoms, and the use of steroids/other pharmacological agents

69. Retirement Decisions No clear empirical data Conservative approach is inarguably appropriate Contraindications to continued play: ongoing symptoms, abnormal neurologic exam, positive neuroimaging findings Evidence of impairment on NP testing may indicate ongoing cognitive problems

70. Retirement Decisions Other reasons to consider: -Evidence of increasingly prolonged recovery course after successive injuries -Less force being needed to cause concussions or lasting symptoms Many recommend disqualification for 1 season if multiple concussions are experienced, this is without clear scientific validation

71. Prevention Vital to increase public awareness of signs and symptoms of concussion, as well as the dangers of continued play while concussed Research to develop helmets that can prevent or reduce the effects of concussion is being pursued but still lacking Helmets do reduce impact forces to the brain, but this has not translated to a reduction in concussion incidence, likely related to having no effect on rotational forces “You cant put a helmet on the brain”

72. Prevention Head protectors in soccer have not shown a protective effect against concussion Appropriate mouth guard use has been shown to reduce the incidence of orofacial injuries, efficacy in prevention of concussion has not been established

73. Questions?

74. Special thanks: Jeff Kutcher, MD