Disclosure Statement. Objectives. Micky Collins May Rehabilitation and Treatment of Sports Concussion: What are we Learning?

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Collins, PhD is Vice President, Chief Clinical Officer, and Co-Founder of ImPACT Applications, a computerized neurocognitive test battery designed to assess sports concussion and Mild Traumatic Brain

1 Rehabilitation and Treatment of Sports Concussion: What are we Learning? Micky Collins, Ph.D. University of Pittsburgh Medical Center Associate Professor Department of Orthopaedic Surgery Department of Neurological Surgery Director UPMC Sports Concussion Program Disclosure Statement Micky Collins, PhD is Vice President, Chief Clinical Officer, and Co-Founder of ImPACT Applications, a computerized neurocognitive test battery designed to assess sports concussion and Mild Traumatic Brain Injury. Objectives Present data pertaining to acute and subacute predictors of outcome following sports concussion. Discuss models of care in assessment/treatment of sports concussion. Discuss role of vestibular screening and vestibular rehabiliation in evaluation and treatment of sports concussion Present outcome study on use of Amantadine for treating post-concussion syndrome. 1

2 WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 40% RECOVERED 60% RECOVERED 80% RECOVERED N=134 High School Male Football Athletes All Athletes No Previous Concussions 1 or More Previous Concussions Predicting Protracted Recovery Following Sports Concussion: Syndrome: What are we Learning? Established (?) Constitutional Risk Factors For More Complicated Recovery Age - Field, Lovell, Collins et al. J of Pediatrics, Pellman, Lovell et al. Neurosurgery, 2006 Migraine History & Symptoms - Mihalik, Pardini, Collins, Lovell et al, J Neurosurgery, 2006 Learning Disability - Collins, Lovell et al, JAMA, 1999 Repetitive Concussion? - Collins, Lovell et al, Neurosurgery, Guskiewicz et al, CJSM, 2003 Gender? - Colvin, Lovell, Pardini, Mullin, Collins, AJSM,

176 Male HS Football Players (Mean Age = 16.2 years) Athletes had baseline computerized testing and were revaluated within 3 days of injury. All followed until clinical recovery (Mean = 4.

3 Which Acute and Sub-Acute Symptom Profiles Predict Protracted Recovery? Which 0n-Field Symptoms Predict Protracted Recovery? Lau B, Kontos A, Lovell MR, Collins MW, Data Under Review Which On-Field Symptoms Increase Risk of Post Concussion Syndrome in High School Football Players? 176 Male HS Football Players (Mean Age = 16.2 years) Athletes had baseline computerized testing and were revaluated within 3 days of injury. All followed until clinical recovery (Mean = 4.1 evaluations) Within RCI of baseline for neurocognitive/symptom scores 32% of sample required < 7 days until recovery (N =56) Rapid Recovery (Mean = 4.9 days) 39% of sample required 7-14 days until recovery (N = 68) 17% of sample required > 21 days until recovery (N = 31) Protracted Recovery (Mean = 33.2 days) 12% lost to follow up (e.g. did not RTP or no follow-up in clinic) (N = 21) MANOVA used to determine differences between rapid/> 3 week recovery ATC s documented on-field markers (e.g. LOC, Amnesia) and on-field Symptoms (e.g. headache, dizziness, etc) Lau B, Kontos A, Lovell MR, Collins MW, Data Under Review 3

Which On-Field Markers/Symptoms Predict 3 or More Week Recovery from Sports Concussion **p<.01 On-Field Marker N Chi 2 P Odds Ratio 95% Confidence Interval Posttraumatic Amnesia 92 1.29 0.257 1.721 0.

4 Which On-Field Markers/Symptoms Predict 3 or More Week Recovery from Sports Concussion **p<.01 On-Field Marker N Chi 2 P Odds Ratio 95% Confidence Interval Posttraumatic Amnesia Retrograde Amnesia Confusion LOC On-Field Symptom N Chi 2 P Odds Ratio 95% Confidence Interval Dizziness** Headache Sensitivity LT/Noise Visual Problems Fatigue Balance Problems Personality Change Vomiting The total sample was 107. Due to the normal difficulties with collecting on-field markers, there were varying degrees of missing data. The number of subjects who had each coded ranged from The N column represents the number of subjects for whom data were available for each category. Markers of injury are not mutually exclusive. Lau, Kontos, Collins, Lovell, Data Under Review On-Field Symptom Summary Brief LOC (<30 sec) not predictive of subacute or protracted outcomes following sports-concussion (Collins et al 2003) Amnesia important for sub-acute presentation, but may not be as predictive of protracted recovery (Collins et al 2003) On-Field dizziness best predictor of protracted recovery and post concussion syndrome Etiology of dizziness? Migraine variant? Central Vestibular Dysfunction? Peripheral Vestibular Dysfunction? Cervico-genic? Psychiatric? Need clinical tools/physical examinations to better assess dizziness construct UPMC Sports Concussion Program 2010 Physical Vestibular/Balance Exam (Furman, Mucha, Collins Lovell et al) Screen for Vestibular Abnormalities Concussion Program P hysical Exam: A. Ocular Motor/Vestibulo-Ocular a. Abnorm al Pursuits? b. Abnorm al Saccades? c. Abnorm al Convergence (<6 cm )? d. Any observable nystagm us? e. Blurring/dizziness with VOR (focus on stationary object while moving head side to side)? B. Balance Screen: a. Rom berg Eyes Open < 30 sec or unsteady b. Rom berg Eyes Closed < 30 sec or unsteady---- c. Tandem Romberg Eyes Open < 30 sec or unsteady d. Tandem Rom berg Eyes Closed < 20 sec (unless age >50) e. Compliant Foam Eyes Open < 30 sec or unsteady f. Compliant Foam Eyes Closed < 30 sec or unsteady g. Tandem gait unsteady Possibly central vestibular disorder, particularly if a, b, or c abnormal Abnormality on any item suggests a balance disorder Modified 10/04/10 4

5 Which Subacute Symptoms Predict Protracted Recovery? Lau B, Lovell MR, Collins MW; Pardini J; AJSM 2009 (3): concussed high school football players Athletes had baseline computerized neurocognitive testing and were revaluated within 3 days of injury (Mean = 2.2 days) All followed until clinical recovery Within Reliable Change Score of baseline for neurocognitive/symptom scores 43.5% of sample recovered < 10 days = Quick Mean = 5.9 Days 56.5% of sample required >10 days until recovery = Protracted Mean = 29.2 Days MANOVA conducted on which individual symptoms and neurocognitive domains predicted quick versus protracted recovery Lau B, Lovell MR, Collins MW; Pardini J; CJSM 2009 (3): Current Symptoms Headache Nausea Vomiting Balance Problems Dizziness Fatigue Trouble falling asleep Sleeping more than usual Sleeping less than usual Drowsiness Sensitivity to light Sensitivity to noise Irritability Sadness Nervousness Feeling more emotional Numbness or tingling Feeling slowed down Feeling mentally foggy Difficulty concentrating Difficulty remembering Visual problems (blurry or double vision) 5

6 2 FOGGY DIFF CONC VOMIT DIZZY NAUSEA HEADACHE SLOWNESS BALANCE LIGHT SENS NOISE SENS NUMBNESS Expressed as Effect Sizes (Cohen s D). Only includes symptoms with large (greater than.80) effect sizes. Sample is composed of 108 male HS football athletes. It is like going from a high definition TV world to standard TV world Feeling one step removed from my surroundings It is like my vision is impaired, but it isn t Feeling like I am underwater Factor Analysis, Post-Concussion Symptom Scale (Pardini, Lovell, Collins et al. 2004) More emotional Sadness Nervousness Irritability Headaches Visual Problems Dizziness Noise/Light Sensitivity Nausea Attention Problems Memory dysfunction Fogginess Fatigue Cognitive slowing N=327, High School and University Athletes Within 7 Days of Concussion Difficulty falling asleep Sleeping less than usual 6

Variables Classification Z-Score (Simple vs. Complex) Fogginess Cognitive 4.3* Difficulty Concentrating Cognitive 2.46 Vomit Migraine 2.391* Dizziness Migraine 2.09 Nausea Migraine 1.

231* Visual Problems Migraine 0.97 Difficulty Remembering Cognitive 0.93 Sleeping Less Sleep.52 Drowsiness Cognitive 0.5 Fatigue Cognitive 0.48 Emotional Neuropsychiatric 0.

7 Variables Classification Z-Score (Simple vs. Complex) Fogginess Cognitive 4.3* Difficulty Concentrating Cognitive 2.46 Vomit Migraine 2.391* Dizziness Migraine 2.09 Nausea Migraine 1.96 Headache Migraine 1.71 Slowness Cognitive 1.53 Balance Migraine 1.53 Light Sensitivity Migraine 1.52 Noise Sensitivity Migraine 1.52 Numbness Migrainei 1.46 Trouble Sleeping Sleep 1.231* Visual Problems Migraine 0.97 Difficulty Remembering Cognitive 0.93 Sleeping Less Sleep.52 Drowsiness Cognitive 0.5 Fatigue Cognitive 0.48 Emotional Neuropsychiatric 0.37* Irritability Neuropsychiatric 0.3 Sadness Neuropsychiatric 0.09 Nervousness Neuropsychiatric Sleeping More Cognitive *Symptoms with the largest contributions to differences between quick and protracted recovery in each symptom factor. ImPACT yields summary composite scores for: -Verbal Memory - Visual Memory - Reaction Time - Visual Motor Speed Neurocognitive Summary Scores SCORES PREDICTIVE OF PROTRACTED RECOVERY (Greater than 10 days to Recovery) Deficit in Reaction Time Best Predicts Protracted Recovery REACTION TIME PROCESSING SPEED D=.838 (Large) p <.001 D=.663 (Medium) p<.001 VISUAL MEMORY VERBAL MEMORY D=.466 (Medium) p<.01 D=.221 (Small) p<.05 N = 108 Effect Sizes compare quick recovery to protracted recovery groups. (Cohen s D) 7

Surgery Neuro Surgery Sports Concussion /

8 The UPMC Sports Concussion Program Department of Orthopaedic Surgery The UPMC Sports Concussion Program Pediatric Practices ATC from Contracted Schools Emergency Departments UPMC Concussion Program (Neuropsych) Primary Care Physicians Parents /Schools Parents / School PM & R Vestibular / Physical Therapy Neuro Radiology Orthopaedic Surgery Neuro Surgery Sports Concussion / mtbi Clinic Pediatric Practices ATC from Contracted Schools Emergency Departments PMR, Sports Med, Neurology, Pediatrics, Ortho, etc. Primary Care Physicians Parents /Schools Parents / School Neuropsych Neuro Radiology Vestibular / Physical Therapy Orthopaedic Surgery Neuro Surgery 8

Key Personnel-UPMC Concussion Program Neuropsychology Point guard of program PMR Medication/medical management Athletic Training Vestibular Therapy Physical

Year UPMC Typical Evaluation Detailed Clinical Interview Vestibular Screening Computerized Neurocognitive Testing Same day patient feedback Severity of Injury?

Communication to ATC, Team Physician, Referring Physician, etc.

9 Key Personnel-UPMC Concussion Program Neuropsychology Point guard of program PMR Medication/medical management Athletic Training Vestibular Therapy Physical Therapy Exertional training/therapy Secondary referral sources Sports Medicine/Primary Care Neuroradiology Neurosurgery Neurology Over 10,000 Patient Visits per Year UPMC Typical Evaluation Detailed Clinical Interview Vestibular Screening Computerized Neurocognitive Testing Same day patient feedback Severity of Injury? Prognosis for Recovery? Neuroimaging indicated? Level of Physical Exertion Allowed? Level of Cognitive Exertion Allowed? Academic Accommodations? Return to Play? Communication to ATC, Team Physician, Referring Physician, etc WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 40% RECOVERED 60% RECOVERED 80% RECOVERED N=134 High School Male Football Athletes All Athletes No Previous Concussions 1 or More Previous Concussions 9

10 Factor Analysis, Post-Concussion Symptom Scale (Pardini, Lovell, Collins et al. 2004) More emotional Sadness Nervousness Irritability Headaches Visual Problems Dizziness Noise/Light Sensitivity Nausea Attention Problems Memory dysfunction Fogginess Fatigue Cognitive slowing N=327, High School and University Athletes Within 7 Days of Concussion Difficulty falling asleep Sleeping less than usual Vestibular Screening and Vestibular Rehabilitation ti of Post- Concussion Syndrome Vestibular Screening: Physical Examination Ocular-Motor: Smooth Pursuits ( H-Test ) Saccades (Vertical/Horizontal) Any dizziness, blurriness, over/under shoots? Vestibular-Ocular: Gaze Stability (focus on stationary ti object while moving head side to side/up and down) Vertical/Horizontal Any observable nystagmus, provocative dizziness/bluriness, slowed movements? Convergence In high school/college aged athletes, near point < 6-8 cm Balance Examination Romberg, Compliant Foam-eyes open/eyes closed 10

UPMC Vestibular Screening Evaluation FURMAN, MUCHA, COLLINS, LOVELL ET AL 2010 Screen for Balance/Vestibular Abnormalities Concussion Program Physical

---------------------------- No - No c. Abnormal Convergence (<6 cm)? ------------- No d. Any observable nystagmus? ------------------- No e.

Romberg Eyes Open < 30 sec or unsteady- No b. Romberg Eyes Closed < 30 sec or No unsteady---- c.

Tandem Romberg Eyes Closed < 20 sec --- (unless age >50) e.

11 UPMC Vestibular Screening Evaluation FURMAN, MUCHA, COLLINS, LOVELL ET AL 2010 Screen for Balance/Vestibular Abnormalities Concussion Program Physical Exam: A. Ocular Motor/Vestibulo-Ocular a. Abnormal Pursuits? No b. Abnormal Saccades? No - No c. Abnormal Convergence (<6 cm)? No d. Any observable nystagmus? No e. Blurring/dizziness with VOR (focus on stationary object while moving head side to side)? B. Balance Screen: a. Romberg Eyes Open < 30 sec or unsteady- No b. Romberg Eyes Closed < 30 sec or No unsteady---- c. Tandem Romberg Eyes Open < 30 sec or No unsteady No d. Tandem Romberg Eyes Closed < 20 sec --- (unless age >50) e. Compliant Foam Eyes Open < 30 sec or No unsteady f. Compliant Foam Eyes Closed < 30 sec or No unsteady No g. Tandem gait unsteady Modified 10/04/10 Possibly central vestibular disorder, particularly if a, b, or c abnormal Abnormality on any item suggests a balance disorder Pursuits- H-Test Saccades-Horizontal and Vertical 11

12 Gaze Stability-Horizontal/Vertical Convergence A. Romberg (Feet Together) 1. Eyes Open 2. Eyes Closed 3. Arms Folded/Shoes on ok 4. Abnormal if cannot do for 30 seconds or excessive sway 12

13 B. Foam Cushion/Feet Together 1. Eyes Open 2. Eyes Closed 3. Arms folded/shoes on - ok 4. Abnormal if cannot do for 30 sec. or excessive sway C. Tandem Stance 1. Eyes Open/Arms Crossed Abnormal if < 30 sec or unsteady 2. Eyes Closed/Arms Crossed Abnormal if <20 sec (unless age >50) D. Tandem Walk Abnormal if unsteady or unable 13

Pharmacologic Treatment of Post- Concussion

Symptom Scale (Pardini, Lovell, Collins et al.

High School and University Athletes Within 7

14 Pharmacologic Treatment of Post- Concussion Syndrome Factor Analysis, Post-Concussion Symptom Scale (Pardini, Lovell, Collins et al. 2004) More emotional Sadness Nervousness Irritability Headaches Visual Problems Dizziness Noise/Light Sensitivity Nausea Attention Problems Memory dysfunction Fogginess Fatigue Cognitive slowing N=327, High School and University Athletes Within 7 Days of Concussion Difficulty falling asleep Sleeping less than usual 14

Escitalopram (Lexapro) Sertraline (Zoloft)

Sleep Disturbance Melatonin Trazodone Cognitive

Methylphenidate* Atomoxetine (Strattera)* NOTE:

as a Pharmacological Treatment following

Dopamine and inhibits reuptake Anti-viral,

15 Somatic Symptoms Headaches Prophylaxis Propranolol* Verapamil* Amitriptyline* Escitalopram (Lexapro) Sertraline (Zoloft) Vestibular Therapy Emotionality SSRIs Escitalopram (Lexapro) Sertraline (Zoloft) Therapy Sleep Disturbance Melatonin Trazodone Cognitive Symptoms Neurostimulants Amantadine* Methylphenidate* Atomoxetine (Strattera)* NOTE: *Off-label use Evidence for the Use of Amantadine as a Pharmacological Treatment following Concussion Camiolo-Reddy, Collins, Lovell, Sabini, Twichell, Kontos, In review. Amantadine for Cognitive Symptoms and Neurocognitive Function How it works: Presynaptically facilitates the release of Dopamine and inhibits reuptake Anti-viral, Parkinson s s Disease Theoretically Improves: Arousal, Vigilance, Processing Speed, General Cognitive Functioning 15

Study Overview Subjects 1. 25 male (n=11) and female (n= 14) concussed adolescents, and 2.

16 Study Overview Subjects male (n=11) and female (n= 14) concussed adolescents, and male (n=11) and female (n=14) age-, sex-, and concussion Hx-matched controls Groups Treatment =100mg of amantadine 2x/day (200mg total per day) Concussed Controls= evaluated and treated conservatively without medication Computerized neurocognitive scores and symptoms Demographics Total Amantadine Controls T-test M SD M SD M SD t P Age (yrs) Concussion History (#) Injury to first-test (days) Injury to Post-tx test (days) Groups were Similar ImPACT and Symptom Scores for Amantadine and Control Groups (N= 50) Amantadine Control Pre Post Pre Post M (SD) M (SD) M (SD) M (SD) Wilk s λ F η 2 p Symptoms (#) (20.81) (11.79) (18.59) (16.24) Verbal Memory (% correct) (20.76) (9.13) (7.57) (10.18) Visual Memory (% correct) (16.37) (14.16) (9.14) (14.62) Visual Processing Speed (#) (9.95) (9.13) (7.06) (7.69) Reaction Time (sec) (0.16) (0.13) (0.11) (0.10) 16

Comparison of symptoms from pre- to posttest for the amantadine (n= 25) treatment and matched control (n= 25)

Comparison of Verbal Memory scores from pre- to posttest for the amantadine (n= 25) treatment and matched

17 Comparison of symptoms from pre- to posttest for the amantadine (n= 25) treatment and matched control (n= 25) subjects (p<.05). Comparison of Verbal Memory scores from pre- to posttest for the amantadine (n= 25) treatment and matched control (n= 25) subjects (p<.05). Conclusion Tentative support for the efficacy of amantadine as pharmacological treatment for intractable patients (i.e., >3 weeks) following concussion Corroborates anecdotal support Study Limitations: Sample size No placebo group Future: Double-blind randomized control trial of the efficacy of amantadine following concussion in a sufficiently large sample to corroborate the current study s findings 17

18 Thank You 18

Prognosticating Protracted Recoveries from Sports Concussion: What are we Learning?

Prognosticating Protracted Recoveries from Sports Concussion: What are we Learning? Associate Professor UPMC Department of Orthopaedic Surgery UPMC Department of Neurological Surgery Director UPMC Sports