Presentation delivered at University of Michigan Injury Center Sport Concussion Summit, Ann Arbor, September 24, 2015

1. Short- and long-tem outcomes from sport-
related concussion: What are the real risks?
science vs myths
Christopher Randolph, PhD, ABPP-CN
Clinical Professor of Neurology
Director, Neuropsychology Service

2. Disclosures
• Dr. Randolph has been compensated for his time in presenting
his perspective on late-life risks of sport-related head trauma
to individuals involved in litigation on the behalf of retired
players and to individuals involved on the behalf of
professional sports organizations
• There are no other relevant disclosures

3. Content
• Short term risks
– Natural history of recovery from concussion
– Role of management strategies
• Long term risks
– Epidemiology
– Survey data and clinical studies

4. Short-term risks
Myth #1: There is credible scientific evidence
that uncomplicated concussions can produce
long-lasting or permanent impairments.

5. Short-term risks: Design of prospective
studies of sport-related concussion
 Obtain baseline data on symptoms, neurocognitive
status, balance, etc. in sample at risk
 3-5% per season incidence of concussion in football
 Occurrence of concussion triggers immediate follow-
up examination sequence, with matched controls.
 Most rigorous scientific method for quantifying risk
of persistent impairments

6. JAMA 2003; 290:2556-2563
Over 25,000 Athlete Seasons, 1,500
Concussions Studied

7. 1999/2000 NCAA Study
 33 colleges, approximately 3,000 football players
 SAC scores immediately, 3 hours, 1, 2, 3, 5, 7, and 90
days post-injury.
 Concussion symptom checklist and balance testing at
same post-injury intervals.
 Follow-up more extensive neurocognitive testing 2, 7,
90 days post-injury, with case-control design.

8. Course of recovery…

9. Symptom Recovery
0
5
10
15
20
25
BL CC PG D1 D2 D3 D5 D7
Assessment Point
GSCTotalScore
Control
Injured
GSC- Graded Symptom Checklist. Self-rated checklist of 17 symptoms,
Rated 0 (none) to 6 (severe).

10. Cognitive Recovery- SAC
24
25
26
27
28
29
30
BL CC PG D1 D2 D3 D5 D7
Assessment Point
SACTotalScore
Control
Injured

11. Postural Stability Recovery
9
11
13
15
17
19
BL CC PG D1 D2 D3 D5 D7
Assessment Point
BESSTotalScore
Control
Injured

12. Additional prospective studies:
 Over one dozen additional prospective studies of
neurocognitive recovery from concussion to date.
 In general, deficits are so subtle that they don’t reach
statistical significance in group studies, even during acute
post-injury period (1-3 days).
 No prospective controlled study yet identifying neurocognitive
impairments at day 7 post-injury (Bellanger et al., 2007).

13. Multiple concussions?
• Fewer studies, but some limited data (e.g.,
Guskiewicz et al., JAMA 2003) to suggest that a
history of multiple concussions:
– Increases risk of future concussion
– Is associated with slightly slower, but no less complete
recovery
• Multiple studies of baseline performance on tests like
ImPACT do not find performance differences on the
basis of concussion history

14. Short term risks
• Myth #2: Post-concussive symptoms are
always (or even mostly) due to brain injury

15. Postconcussion symptoms
 These symptoms are highly non-specific (headache, memory
problems, concentration problems, dizziness, fatigue, irritability, nausea, sensitivity
to light, sensitivity to noise, difficulty sleeping, poor balance)
 They occur at high rates in a number of conditions
 depression, PTSD, non-tbi personal injury litigants, anxiety,
somatoform disorder, and even in the general population
 Psychological factors can play a major role in symptom
expression
 e.g., persistent PCS in clinical populations (ED admissions) not even
associated with mTBI, but are associated with attribution and
psychiatric factors (e.g. Belanger et al., 2013; Meares et al., 2011;
Ponsford et al., 2012)

16. Summary of prospective studies of sport-
related concussion:
 Measurable changes in neurocognitive status, postural
stability, and subjective symptomatology occur acutely post-
concussion, with maximal deficits/symptoms evident
immediately post-injury.
 Recovery is rapid, with no residual deficits/symptoms evident
on group studies at day 7 post-injury.
 (a small percentage of individuals may have more prolonged, but not
incomplete resolution of symptoms- e.g., McCrea 2012, Meehan 2014)
 Persistent PCS is rare in athletic samples (so far), but strongly
related to psychological factors in clinic populations

17. Management Strategies
• Myth #3: There is scientific evidence to
support some type of management strategy
with respect to sport-related concussion

18. Management Strategies
• Fact: There is not one single controlled study
suggesting that there is a “right” way to
manage concussions
• There are over a multitude of “guidelines” for
managing concussion. One commonality:
– Players should be symptom-free prior to return

19. Management Strategies
• Only one study has ever looked at the effect of
a symptom-free waiting period on outcome
from sport-related concussion
McCrea et al., 2009 Neurosurgery

20. McCrea et al., Neurosurgery 2009
• 635 concussions (HS and college football
players)
– 40% returned to play while still symptomatic
– No difference between groups with and without a
SFWP on:
• Acute injury characteristics
• Recovery on neurocognitive, balance, or symptom
measures
– 24 same-season repeat concussions
• 22/24 in the group with a SFWP (p<.005)
• 80% within 10 days

21. Management Strategies
• 1st
randomized, controlled trial of concussion
management (Thomas et al., Pediatrics, 2015)
– Adolescent ED admissions N=99
– Randomized to 5 days strict rest vs usual care (1-2 days
rest followed by stepwise return)
• Strict rest group reported more subjective
symptoms and slower recovery
– Iatrogenic PCS?

22. Management Strategies-summary
• There is no evidentiary basis to support any particular
management strategy
• Risk of repeat concussion is low and appears to be
time-based, not symptom-based
• Apart from common-sense management (i.e., not
sending an obviously impaired player back in), there
is no scientific basis for any rule-based strategy for
managing concussions

23. Long-term risks
• Myth #4: There is credible scientific evidence
that retired NFL players (or retired boxers, or
retired athletes from any sport involving
repetitive head injury) are at increased risk for
some type of late-life neurological or
neuropsychiatric disease

24. MCI& MemoryProblems byConcussion Historyin Retired Football Players
0
2
4
6
8
10
12
14
16
18
20
Self-Report MemoryProblems Spouse Report Memory
Problems
MCIDiagnosis
Clinical Criterion
%ofRespondents
0 Concussions 1-2 Concussions 3+Concussions
Risk For Late Life Cognitive Impairment?Risk For Late Life Cognitive Impairment?
Guskiewicz et al., Neurosurgery, 2005

25. Long-term risks: Epidemiology
• Only one relevant NFL study to date (Baron et
al., 2012; Lehman et al., 2012 [same dataset]):
– 3439 NFL retirees with 5+ pension-credited
playing seasons from 1959 to 1988
– Mortality rates examined through 2007
– Compared to US men demographically matched
– Key findings
• 334 total NFL deaths
• All-cause mortality only 53% of expected
• Suicide rate 41% of expected

26. Baron et al./Lehman et al 2012
• NFL death rates compared to expected:
– Cancer: 63 fewer
– TB/HIV related: 25 fewer
– Psychiatric: 8 fewer
– Cardiovascular: 60 fewer
– Injuries: 94 fewer
– Suicide: 13 fewer

27. Baron et al./Lehman et al. 2012
• Overall, 291 fewer deaths than would be
expected
• Consequentially, observed deaths would be
more likely to be related to late-life diseases
– i.e., proportion of deaths due to late-life illnesses
would be expected to increase if early and mid-life
causes of death are reduced

28. Lehman et al., 2012
• Number of NFL deaths above expected rate by
US demographically matched population
Underlying Contributing
All
neurodegenerative
6 more 13 more
Dementia/AD 1 more 5 more
ALS 4 more 5 more
PD 1 more 1 more

29. Lehman et al., 2012
• In addition, they report that neurodegenerative
death rates for “non-speed” positions were not
elevated relative to the general population
– “speed” position players have an all-cause
mortality rate significantly lower than “non-speed”
players
– Therefore, they are more likely to die of late-life
illnesses than non-speed players
– This study did not adjust for age at death

30. Savica et al., 2012
• Only other epidemiological study of death
rates in former (HS) football players (N=438,
playing between 1946-56), compared to non-
football playing male classmates
• No increase in the rate of any
neurodegenerative diseases

31. NFL Epidemiology summary
• Retired NFL players have an all-cause
mortality rate only ~ half of that expected, and
a suicide rate only ~40% of that expected.
– They are much less likely to die of illnesses and
injuries of almost any type
– Lower overall death rates invariably increases the
proportion of deaths due to late-life diseases
• NFL rates of death due to neurodegenerative diseases
may therefore be even less than might be expected if
age at death was controlled for

32. Survey/Clinical Data
• First report Guskiewicz et al., 2005.
– General healthy survey sent to retirees belonging
to NFLPA (N=3683). 69% response rate
– Follow-up survey on cognition sent to respondents
aged 50 and older (N=1754). 43% response rate
– Association identified between number of
concussions and MCI/memory problems. No
association with AD
– Limitations: response bias, self-report, no controls

33. Survey/Clinical Data
• Randolph et al., 2013
– Same survey data, analyzed 513 respondents who
completed AD8
– Informant AD8 data suggested ~35% might have
some cognitive problems
• No controls
– Sample of 41 NFL retirees selected by phone
assessments as likely having MCI recruited for
additional study…

34. Randolph et al., 2013
• 41 NFL players with probable mild cognitive
impairment were compared to 41
demographically-matched controls and 81
clinic patients with diagnosed amnestic MCI
• NFL retirees with probable MCI were highly
similar in profile to clinical patients with aMCI
– No evidence of any unique clinical syndrome

35. RBANS Profile Analysis

36. Neurocognitive profile of tauopathy?
312 PSP subjects from
davunetide study
compared to 246
subjects with probable
AD (mean MMSE=23,
SD=4), University of
Oklahoma, courtesy
Dr. Jim Scott

37. Additional NFL clinical studies
• Hart et al., 2013: Recruited 34 retired NFL
players with a mixture of depression, cognitive
complaints, and no concerns
– No evidence of a unique clinical or radiological
syndrome
• Casson et al., 2014: Recruited 45 retired NFL
players
– No evidence of a unique clinical or radiological
syndrome

38. Additional NFL clinical studies
• Stamm et al., 2015
– 42 NFL retirees, mean age 52 (1.3)
– Self-identified as having cognitive problems
– Divided into group that started playing before age
12 vs after (N=21 each)
– “focused set of neuropsychological outcome
measures selected”
• Results: Group that started earlier worse on 7
of 9 scores reported, including WRAT-4

39. Stamm et al., 2015 limitations
• No clear rationale for age 12 cutoff- if there is a
relationship, why isn’t it linear?
• Cherry-picking of tests? Why were these tests
selected from a larger battery?
• WRAT-4 is used by neuropsychologists as a measure
of premorbid function- implies developmental
difference between groups
• No unique clinical syndrome proposed

40. Survey/Clinical Data Summary
• Survey data have suggested possible higher
rates of MCI in NFL retirees, and possible
association with concussion, but:
– These studies may have suffered from response
bias and have no controls
• Direct clinical examinations of retired NFL
players have not revealed any unique clinical
syndromes (e.g., “CTE”)

41. What needs to be done
• For any suspected risk group (e.g., retired NFL players): Truly
random sampling of a sufficient N, compared to
demographically-matched controls to determine whether risk
of late-life cognitive impairment is increased
– If no, stop!
– If yes: further characterization of impairments, symptoms, natural
history, and blinded neuropath with control brains included
• Until this is done, it is all just speculation and media hype

42. Our First Job: Do No Harm

43. Questions?

44. SPORT CONCUSSION
SUMMIT
September 24, 2015#uminjuryctr