1. Presentation for The American Academy of Physical Medicine and Rehabilitation Annual Congress Pseudobulbar Affect Symptoms, Prevalence and Impact in Former Professional Football Players: Results of an Online Survey Co-Authors: Gregory O’Shanick, MD, Center for Neurorehabilitiation Services and Medical Director Emeritus, BIAA Andrea E. Formella, PharmD, Avanir Pharmaceuticals, Inc. Amy Kincaid, Avanir Pharmaceuticals, Inc. Charles Yonan, PharmD, Avanir Pharmaceuticals, Inc. Shereen McIntyre, MBA, Avanir Pharmaceuticals, Inc. Jay H. Rosenberg, MD, The Neurology Center

2. DISCLOSURE  I have relevant financial relationships with the products or services described, reviewed, evaluated, or compared in the presentation  Avanir Pharmaceuticals, Inc. – Consultant  This survey was conducted through The Gridiron Greats Assistance Fund in conjunction with Avanir Pharmaceuticals, Inc., who provided funding for this survey, and GfK Custom Research, LLC, who hosted the online survey and collated the survey data 2

3.  Objective :  Investigate the prevalence and impact of pseudobulbar affect (PBA) symptoms as a potential consequence of sports-related head injuries among former professional football players  Pseudobulbar Affect (PBA):  Occurs secondary to certain neurologic diseases or brain injuries  Characterized by sudden, uncontrollable, laughing and/or crying episodes that are exaggerated to situation/social context and excessive or unrelated to mood 3 OBJECTIVE & BACKGROUND

4.  Gridiron Greats was founded by Jerry Kramer in 2007  The mission is to provide support to retired football players and their families with hardships they face after their football careers such as:  Medical and dental services  Medication  Transportation costs for medical evaluations and surgeries  Housing and costs of utilities  Coordination of services for food and other daily necessities 4 http://gridirongreats.org/mission/ GRIDIRON GREATS ASSISTANCE FUND

5.  Design :  Invitation to participate in the survey was sent to all members of the Gridiron Greats Assistance Fund email list  Invitation read, “We are conducting a brief survey about certain health conditions and would like to include your opinions. This survey will take you approximately 15 minutes to complete. All survey results are anonymous and will be reported in aggregate. Occasional verbatim citations will not be attributed to a particular individual. There are no right or wrong answers, we are only interested in your opinions.” 5 STUDY METHODOLOGY

6.  Design :  Eligible participants were ≥18 years of age, and: A former professional football player; or A family member, person living with or caring for a former player  Survey questions included: Basic demographics History of head injury or concussion Center for Neurologic Study–Lability Scale (CNS-LS), a 7-item PBA self- assessment measure previously validated in ALS and MS populations 1-2 PBA symptom (excessive, uncontrollable laughing or crying) frequency and impact on activities and relationships Interactions with Medical Professionals regarding PBA symptoms 6 1. Moore SR, et al. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93; 2. Smith RA, et al. Mult Scler 2004;10:1-7. STUDY METHODOLOGY

7. 1 There are times when I feel fine 1 minute, and then I’ll become tearful the next over something small or for no reason at all 2 Others have told me that I seem to become amused very easily or that I seem to become amused about things that really aren’t funny 3 I find myself crying very easily 4 I find that even when I try to control my laughter, I am often unable to do so 5 There are times when I won’t be thinking of anything happy for funny at all, but then I’ll suddenly be overcome by funny or happy thoughts 6 I find that even when I try to control my crying, I am often unable to do so 7 I find that I am easily overcome by laughter For purposes of the survey, the presence of PBA symptoms was defined as either: a CNS-LS ≥ 13 or answering “yes” to the following question: “Have you (has the player) experienced sudden, involuntary episodes of crying and/or laughing that were exaggerated or even contrary to how you (he) felt at the time ” 1. Moore, SR, et al. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93; 2. Smith RA, et al. Mult Scler 2004;10:1-7. Center for Neurologic Study - Lability Scale (CNS-LS) 1: Never2: Rarely3: Occasionally4: Frequently5: Most of the time Describe the degree to which each item applies to you DURING THE PAST WEEK ASSESSMENT OF PBA SYMPTOMS

8. 1 There are times when I feel fine 1 minute, and then I’ll become tearful the next over something small or for no reason at all 2 Others have told me that I seem to become amused very easily or that I seem to become amused about things that really aren’t funny 3 I find myself crying very easily 4 I find that even when I try to control my laughter, I am often unable to do so 5 There are times when I won’t be thinking of anything happy for funny at all, but then I’ll suddenly be overcome by funny or happy thoughts 6 I find that even when I try to control my crying, I am often unable to do so 7 I find that I am easily overcome by laughter 1. Moore, SR, et al. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93; 2. Smith RA, et al. Mult Scler 2004;10:1-7. Center for Neurologic Study - Lability Scale (CNS-LS) 1: Never2: Rarely3: Occasionally4: Frequently5: Most of the time Describe the degree to which each item applies to you DURING THE PAST WEEK ASSESSMENT OF PBA SYMPTOMS For purposes of the survey, the presence of PBA symptoms was defined as either: a CNS-LS ≥ 13, or answering “yes” to the following question: “Have you (has the player) experienced sudden, involuntary episodes of crying and/or laughing that were exaggerated or even contrary to how you (he) felt at the time ”

9.  Sample demographics: 516 total respondents  474 former professional football players + 42 family caregivers  All former players were male  Median player age was 56 - 65 years  Most players were married (76%)  Race: 65% White, 31% Black/African American  Education: 85% had a bachelor’s degree or higher; all but 1 player had attended at least some college 9 23 (3%) did not qualify 23 (3%) did not qualify 231 (30%) terminated early 231 (30%) terminated early Approximately 7000 surveys sent 770 clicked on the survey 770 clicked on the survey 516 (67%) completed the survey 516 (67%) completed the survey DEMOGRAPHICS

10.  99% of former players had experienced some form of head injury during their football career:  73% (N=378) had “suffered from a head injury, concussion, or TBI”  Among those who did not report head injury on initial question (n=138); all but 3 reported experiencing some form of blow to the head  Most reported multiple head injuries; 60% reporting more than 5; 16% reporting more than 21 10 Former players who did not identify as having a head injury (n=138) were asked: “ During your/their football career, have you/have they ever..?” Head injury was defined as, “skull fracture, being knocked unconscious, having a head injury requiring hospitalization, feeling wobbly or disoriented after taking a hit to the head, or experiencing temporary memory loss after being hit.” Have you personally suffered/has the person you live with who played professional football suffered from a head injury, concussion or TBI? PREVALENCE OF HEAD INJURY

11. 11 Q: Due to your (the football players’) head injury(s), have you (they) ever personally experienced the following? Respondents, % 41% reported emotional lability (n=209) 13% reported laughing and/or crying (n=66) EXPERIENCE OF SYMPTOMS ATTRIBUTABLE TO HEAD INJURY (N=513)

12.  48% of former football players with a head injury (N=513) self- classified these injuries collectively as moderate or severe  Concern for future head injury-related complications increased with reported severity 12 Severe: Was hospitalized and/or diagnosed with a severe brain injury and/or experienced many long lasting effects. Moderate: Lost consciousness and/or diagnosed with a concussion/fracture and/or experienced some long lasting effects. Mild: Experienced temporary dizziness and/or other short term symptoms, but no real long lasting effects. Reported Severity of Head Injury: Thinking of all the head injuries you have/the football player has suffered collectively, how would you classify the severity? HEAD INJURY SEVERITY

13. ►Overall, 33% (168/516) of respondents had PBA symptoms; including:  31% (n=158) with a CNS-LS score ≥13; and 2% (n=10) with CNS-LS <13 who answered “yes” to the follow-on question about involuntary/excessive laughing or crying  8% (41/516) had CNS-LS ≥21, suggesting moderate to severe PBA symptoms ►The 168 with PBA symptoms were then asked about episode frequency: 13 How frequently do you (the player) experience these episodes of sudden, uncontrollable crying or laughing? 30% experienced crying or laughing episodes at least weekly Laughing/crying episode frequency correlated with increased CNS-LS score (Pearson correlation, 0.424; P<.0001) PBA SYMPTOM PREVALENCE & FREQUENCY

14. “ How often do these sudden, uncontrollable crying or laughing episodes interfere with ability to do any of the following?” PBA SYMPTOMS INTERFERED WITH ACTIVITIES AND RELATIONSHIPS (N=168) Spend time with friends and family Maintain a marriage or significant relationship Work Participate in social activities Talk on the telephone Make and keep friends Go to the movies Attending or participating in a sporting event Participate in group community activities Shop Drive a car Dine out Interact with healthcare professionals Participate in rehabilitation therapy Volunteer Attend church/synagogue/house of worship Live independently ►Increasing PBA symptoms (CNS-LS) were correlated with greater interference

15. ►Sudden uncontrollable crying/laughing episodes were associated with feelings of depression, isolation, loneliness, and embarrassment; the frequency of experiencing each of these negative emotions showed significant correlation with CNS-LS score Psychological Impact of Uncontrollable Crying or Laughing Episodes in Respondents with PBA Symptoms (N=168) Possible responses were “most of the time”, “frequently”, “occasionally” or “rarely”. Responses of “rarely” or “occasionally” are not shown. Depressed Isolated Alone Embarrassed A little bit crazy Like a burden to others Scared Out of control *Pearson correlation of CNS-LS score and frequency response for each item; P <.0001 Possible responses were “most of the time”, “frequently”, “occasionally” or “rarely”. Responses of “rarely” or “occasionally” are not shown. 0.36* 0.34* 0.40* 0.34* 0.40* 0.50* 0.42* 0.46* Pearson correlation coefficients PSYCHOLOGICAL IMPACT OF PBA SYMPTOMS

16. Don’t feel the symptoms are serious enough Thought it was just depression Too embarrassed to mention Believed it was just a symptom or part of the head injury Don’t feel the doctor can offer any answers Other Reasons for Not Discussing (N=123) Have you discussed uncontrollable laughing/crying episodes with a healthcare professional?(N=168) ► 73% (123/168) of those with PBA symptoms had not discussed laughing or crying episodes with a healthcare provider (HCP) ► Of the 16% (n=27) who discussed PBA symptoms with a HCP  14 received any diagnosis for the symptoms; most commonly depression, bipolar disorder or other mood disorder (n=6)  None were diagnosed with PBA (or related term) as a result of these discussions PBA SYMPTOMS WERE OFTEN NOT REPORTED TO HEALTHCARE PROVIDERS I DON’T KNOW

17. CONCLUSION  Most (99%) former professional football players responding to this Gridiron Greats Assistance Fund survey (N=516) reported some form of head injury during their playing career  33% (n=168) reported symptoms suggestive of PBA (either CNS-LS ≥13 or CNS-LS <13 with presence of sudden, uncontrolled, excessive or inappropriate crying or laughing)  Higher CNS-LS scores were associated with greater laughing crying episode frequency, greater psychological impact of episodes and greater interference with activities and relationships  Few players discussed laughing/crying episodes with a medical professional; when they did it did not result in a PBA diagnosis  Survey results demonstrate the need for greater awareness, screening and detection of PBA among former professional athletes; proper diagnosis may impact treatment decisions

18. THANK YOU… I would like to acknowledge and thank the Gridiron Greats Assistance Fund and the athletes and caregivers who participated in this survey.