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1 Supplementary Online Content Zafonte R. Diagnosis and management of sports-related concussion: a 15-year-old athlete with a concussion. JAMA. 011;306(1): eappendix 1. Symptoms of Concussion eappendix. Review Search Criteria etable. Long-term Sequelae of Concussion in Athletes This supplementary material has been provided by the authors to give readers additional information about their work. 011 American Medical Association. All rights reserved. Downloaded From: on 03/13/017

2 eappendix 1. Symptoms of Concussion Headaches Fatigue Mood swings Neck pain Nausea or vomiting Dizziness Blurred vision Balance difficulty Photosensitivity Phonosensitivity Cloudiness Difficulty concentrating Memory problems Slowed reaction times Cognitive impairment Confusion Drowsiness Insomnia Emotional lability Irritability Anxiety or nervousness Sadness/depression Amnesia 011 American Medical Association. All rights reserved. Downloaded From: on 03/13/017

3 eappendix. Review Search Criteria The author surveyed articles from the PubMed online database ( ) using the following search terms: concussion, pathophysiology, adolescent, mild Traumatic Brain Injury, sports-related concussion, evaluation, risk factors, long-term outcome, neurocognitive outcome, and prognosis. Articles were selected for inclusion based on direct applicability to each question posed. Randomized trials, systematic reviews, or prospective cohort studies with level 1 or evidence were selected whenever possible. 011 American Medical Association. All rights reserved. Downloaded From: on 03/13/017

4 etable. Long-term Sequelae of Concussion in Athletes Source Study Type Study Population Population Size Study Method Results Level of Evidence 1 Guskiewicz et al, 007 Questionnaire/retr ospective survey Retired professional football players Weir et al, Rao et al, McKee et al, Cross-sectional questionnairebased survey Prospective cohort study, although analyzed using a nested casecontrol design Case series and case review Retired professional football players Mild TBI patients from the trauma unit of hospitals; followed longitudinally for 1 year Football players, autopsy N = 3683 players contacted, 55 respondents N = 165 players contacted, 1063 participated N = 43 N = 5 (case series), case review of N = 48 previously published cases Metric: General health questionnaire, SF-36. A second questionnaire about mild cognitive impairment (MCI)-related issues were also used for a subset of athletes. Metric: Questionnaire based on major national health surveys Metric: Structured Clinical Interview for the DSM-IV Axis 1 disorders; clinical information, including psychosocial functioning and family history, from interviews and medical record review; General Medical Health Rating scale; CT scans; a battery of cognitive tests. Neuropathology and immunocytochemical analysis; clinical history review 69 (11.1%) respondents had a prior history of or current diagnosis of clinical depression. 3 or more prior concussions were associated with an OR of 3 for likelihood of depression compared with athletes with no history of concussion. 1- prior concussions were associated with an Or of 1.5 for likelihood of depression. Pertinent to TBI: Retired NFL players had a higher rate of dementia. In men aged 30-49, 1.9% of NFL retirees vs. 0.1% in the general male adult population. In men aged 50+, 6.1% of NFL retirees vs. 1.% in the general male adult population. 18% prevalence of new-onset depression; higher incidence of depression in patients of older age or with frontal subdural hemorrhages Neuropathology demonstrated cerebral and medial temporal lobe atrophy, ventriculomegaly, enlarged cavum septum pellucidum, and extensive tau-immunoreactive pathology throughout the neocortex, medial temporal lobe, diencephalon, brainstem, and spinal cord American Medical Association. All rights reserved. Downloaded From: on 03/13/017

5 etable. Long-term Sequelae of Concussion in Athletes (continued) Source Study Type Study Population Population Size Study Method Results Level of Evidence 1 Moser et al, Prospective cohort study High school athletes from multiple sports N = 38 Iverson et al, Case-control study Amateur (high school and college) athletes Collie et al, Cohort study Elite male Australian-rules footballers Mihalik et al, Cohort study High-school and collegiate athletes that had sustained concussions N = 19 athletes with a history of 3 or more concussions, matched with a group of athletes without a concussion history N = 51 N = 61 divided into 3 groups: posttraumatic migraine (PTM), n = 74; headache (HA), n = 14; and nonheadache, n = 63 Metric: Structured clinical interview, demographic form, symptom checklist, a battery of neuropsychological tests Metric: Computerized neuropsychological battery (ImPACT) preseason and within 5 days (mean = 1.7 days) after sustaining a concussion Metric: Clinical history questionnaire, preseason computerized examination (CogSport) and a battery of cognitive tasks assessing reaction time, decision making, attention, learning, and memory Metric: Computerized neurocognitive testing using ImPACT Compared with athletes without a history of concussion, athletes with recent concussions and those with a history of multiple concussions, despite being symptom-free, performed significantly worse on tests of attention and concentration and had lower grade point averages. Compared with athletes without a prior history of concussion, athletes with a history of multiple concussions had more symptoms at baseline and had an OR of 7.7 for having a decline on memory testing. They also scored lower on memory tests at about days after concussion compared with athletes who had 1 prior concussion No significant difference in the number of prior concussions and current cognitive performance. Compared with the HA and non-ha groups, the PTM group had significantly greater neurocognitive deficits and impairments American Medical Association. All rights reserved. Downloaded From: on 03/13/017

6 etable. Long-term Sequelae of Concussion in Athletes (continued) Source Study Type Study Population Population Size Study Method Results Level of Evidence 1 Iverson et al, Cohort study Macciocchi et al, Cohort study Male high school and university amateur athletes College football players who sustained 1 and grade 1 concussive injuries N = 867; 3 groups: n = 664 athletes without history of concussion, n = 149 with 1 prior concussion, and n = 54 with prior concussions N = 4, selected from a larger sample (N = 300) from Division I-A collegiate football players Metric: Computerized neuropsychological testing with ImPACT version.0 Metric: Neuropsychological tests, symptoms checklists, standardized physical assessments No significant difference in neuropsychological test performance or symptom reporting among the groups. No statistically significant difference in performance between players with 1 or concussions. Symptoms increased in athletes that sustained a concussion, but these improved and were back to baseline by 10 days after concussion. Abbreviations: CT, computed tomography; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition); ImPACT, Immediate Post-Concussion Assessment and Cognitive Testing; NFL, National Football League; TBI, traumatic brain injury. References 1. Obremskey WT, Pappas N, Attallah-Wasif E, et al. Level of evidence in orthopaedic journals. J Bone Joint Surg Am. 005;87(1): Guskiewicz KM, Marshall SW, Bailes J, et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 007;39(6): Weir DR, Jackson JS, Sonnega A. National Football League Player Care Foundation Study of Retired NFL Players. Ann Arbor: University of Michigan Institute for Social Research; Rao V, Munro CA, Rosenberg P, et al. Neuroanatomical correlates of depression in posttraumatic brain injury: preliminary results of a pilot study. J Neuropsychiatry Clin Neurosci. 010;(): McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 009;68(7): Moser RS, Schatz P, Jordan BD. Prolonged effects of concussion in high school athletes. Neurosurgery. 005;57(): Iverson GL, Gaetz M, Lovell MR, Collins MW. Cumulative effects of concussion in amateur athletes. Brain Inj. 004;18(5): Collie A, McCrory P, Makdissi M. Does history of concussion affect current cognitive status? Br J Sports Med. 006;40(6): Mihalik JP, Stump JE, Collins MW, et al. Posttraumatic migraine characteristics in athletes following sports-related concussion. J Neurosurg. 005;10(5): Iverson GL, Brooks BL, Lovell MR, Collins MW. No cumulative effects for one or two previous concussions. Br J Sports Med. 006;40(1): Macciocchi SN, Barth JT, Littlefield L, Cantu RC. Multiple concussions and neuropsychological functioning in collegiate football players. J Athl Train. 001;36(3): American Medical Association. All rights reserved. Downloaded From: on 03/13/017