Short- and long-tem outcomes from sport-related concussion:

What are the real risks?

science vs myths

Christopher Randolph, PhD, ABPP-CNClinical Professor of NeurologyDirector, Neuropsychology Service

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

Content

• Short term risks– Natural history of recovery from concussion

– Role of management strategies• Long term risks

– Epidemiology– Survey data and clinical studies

Short-term risks

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

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

JAMA 2003; 290:2556-2563

Over 25,000 Athlete Seasons, 1,500 Concussions Studied

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.

Course of recovery…

Symptom Recovery

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BL CC PG D1 D2 D3 D5 D7Assessment Point

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GSC- Graded Symptom Checklist. Self-rated checklist of 17 symptoms,Rated 0 (none) to 6 (severe).

Cognitive Recovery- SAC

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Postural Stability Recovery

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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).

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

Short term risks

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

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)

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

Management Strategies

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

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

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

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

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?

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

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

MCI & Memory Problems by Concussion History in Retired Football Players

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MCI Diagnosis

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Risk For Late Life Cognitive Impairment?Risk For Late Life Cognitive Impairment?

Guskiewicz et al., Neurosurgery, 2005

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

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

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

Lehman et al., 2012

• Number of NFL deaths above expected rate by US demographically matched populationUnderlying Contributing

All neurodegenerative

6 more 13 more

Dementia/AD 1 more 5 more

ALS 4 more 5 more

PD 1 more 1 more

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

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

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

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

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…

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

RBANS Profile Analysis

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

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

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

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

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”)

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

Our First Job: Do No Harm

Questions?

SPORT CONCUSSION SUMMIT

September 24, 2015 #uminjuryctr