Building Evidence for Concussion Clinical Profiles
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1 Building Evidence for Concussion Clinical Profiles Micky Collins, PhD Executive and Clinical Director- UPMC Sports Medicine Concussion Program Associate Professor- Departments of Orthopaedic and Neurological Surgery University of Pittsburgh Medical Center 1
2 Disclosure I am a co-founder and shareholder in ImPACT Applications, Inc. My research is also supported in part by grants to the University of Pittsburgh from the following:
3 Objectives Determine the frequency of the different primary clinical profiles in a large cohort of patients. Present data characterizing the clinical criteria associated with concussion clinical profiles. Apply clinical criteria for concussion profiles to a case example.
4 Growing Agreement that Concussion Involves Different Clinical Profiles/Subtypes Collins et al., Neurosurgery, 2016
5 Concussions are characterized by diverse symptoms and impairments in function resulting in different clinical profiles and recovery trajectories. Collins, Kontos, Reynolds, Murawski, Fu. KSSTA; Collins, Kontos, Okonkwo et al., Neurosurg; 2016
6 Matching targeted and active treatments to clinical profiles may improve recovery trajectories following concussion. Vestibular Rehabilitation Exercise Vision Therapy Orthoptics Manual Therapy Exercise Injection Acupuncture Biofeedback Medication Surgery Structured Rest Exercise Medication Exercise Behavioral Regulation Relaxation/Biofeedback CBT/Trigger Modification Medication
7 18 years of clinical experience and research has informed six evolving concussion clinical profiles, but... Alsalaheen, et al, 2010 Kontos et al., 2016, 2017 Mucha, et al, 2014 Sufrinko et al., 2017 Heitger, et al, 2009 Ellis, et al, 2015 Master, et al, 2015 Pearce, et al, 2015 Guskiewicz, et al, 2007 Mainwaring, et al, 2004 Hutchison, et al, 2009 Kontos et al., 2012 Kontos, et al, 2012 McCrea, et al, 2003 Collins, Kontos, Reynolds, Murawski, Fu. KSSTA; Treleaven, et al, 1994 Schneider, et al, 2014 Mihalik, et al, 2005 Kontos, et al, 2013 Sufrinko et al., 2017
8 ...How Do We Quantify the Characteristics of Clinical Profiles? To date, there are no empirically validated studies of concussion clinical profiles Inter-clinician variability likely exists regarding specific criteria for determining clinical profiles following concussion Research needs to lead the way
9 Part of the Problem: Clinical Profiles Often Overlap Ocular Anxiety/ Mood Vestibular Anxiety/ Mood Vestibular Post- Traumatic Migraine
10 Another Issue to Consider: Concussion Magnifies Pre-existing Risk Factors We have identified risk and prognostic factors that predict outcomes: Risk factors Migraine (Sufrinko et al., 2018) Motion sickness history (Sufrinko et al., 2017) Mood (Sandal et al., 2017) Vestibular dysfunction (Mucha et al., 2017) Ocular (Pearce et al., 2015) Prognostic factors Continuing to play (Elbin et et al., 2016) Dizziness (Lau, Collins et al., 2011) Post-traumatic migraine (Kontos et al., 2013) Symptom severity (Fehr et al., 2017) Sleep dysfunction (Bramley et al., 2017) Neurocognitive cut-off scores (Lau et al, 2012)
11 11 Evidence for Characterizing Criteria for Concussion Clinical Profiles
12 Purpose Determine the frequency of the different primary clinical profiles in large patient cohort To quantify the characteristics of patients with concussion clinical profiles i.e. establish empirically defined criteria for each clinical profile To evaluate the reliability of clinical agreement on patient clinical profiles
13 Study Overview De-identified review of 188 patient clinical charts from two UPMC concussion clinic sites between October 1, 2016-Nov 4, Age= 24.9 (SD= 13.8) yrs Female= 54% (n= 103) What characterizes patients with the primary profile from patients with other profiles? Chi-square analyses with odds ratios (OR) for characteristics Logistic Regression w/adjusted ORs
14 Patient Inclusion/Exclusion Criteria Inclusion Criteria Diagnosed concussion 9-40 years of age Complete test results: Symptoms/Clinical Exam Computerized neurocognitive test data Vestibular/Ocular Motor Screening (VOMS) Initial evaluation visit Exclusion Criteria No diagnosed concussion History of brain abnormalities, tumors, moderate/severe mtbis Epilepsy, seizure disorders, Hx of stroke Psychiatric disorders No clear mechanism of injury Injuries > 2 years ago Non-English speaking patients
15 Determining and Prioritizing Clinical Profiles GENDER, RISK FACTORS, MEDICAL HISTORY, SYMPTOMS CLINICAL EXAM FINDINGS VESTIBULAR/ OCULAR MOTOR SCREENING (VOMS) COMPUTERIZED NEURO- COGNITIVE DATA Profile(s)? Anxiety/ Vestibular Mood Migraine Primary= Vestibular Secondary= Migraine Tertiary= Anxiety/Mood
16 Results: How often does each profile occur?
17 Results: Primary Clinical Profiles (N = 188) Anxiety/Mood 28% Cognitive/Fatigue 12% Ocular 14% Vestibular 20% Migraine 26% Cognitive/Fatigue Migraine Vestibular Ocular Anxiety/Mood
18 Which characteristics best identify each clinical profile?
19 Cognitive/Fatigue Clinical Profile Cognitive/ Fatigue Clinical Findings: PCSS + for items: feeling slowed down, difficulty concentrating, difficulty remembering. Current symptoms: Cognitive complaints Absence of HA upon waking and increases with activity throughout day Neurocognitive: low test results (<16 th %) on 2 out of 4 cognitive composite areas Risk Factors: ADD/ADHD Other learning disability Has not modified work or activity schedule Played through injury
20 Males more likely to have Cognitive/Fatigue Profile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 70% 30% Cognitive/Fatigue 42% Other 58% Male Female χ2=6.27, p=.01, OR= 3.18 (95% CI= )
21 Patients with 2+ CNT scores <16% more likely to have Cognitive/Fatigue Profile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 80% 20% Cognitive/Fatigue 47% Other 53% 2+ CNT Scores <16% <2 CNT Scores <16% χ2=15.07, p<.001, OR= 4.44 (95% CI= )
22 Patients without Modified Work/Activity more likely to have Cognitive/Fatigue Profile 100% 90% 90% 98% 80% 70% 60% 50% 40% 30% 20% 10% 0% 10% Cognitive/Fatigue 2% Other No Modifications With Modifications χ2=7.91, p=.005, OR= 5.43 (95% CI= )
23 Male Gender and 2+ CNT Scores <16% Associated with Cognitive Fatigue Profile B SE Wald p Adj OR 95% CI Male Gender CNT Scores <16% W/out Modified Activity or Work χ 2 =19.72, p<.001, Nagelkerke R 2 =.19 Males were 3.5x more likely to have cognitive-fatigue Patients with 2+ CNT scores <16% were 5.3x more likely to have cognitive-fatigue
24 Migraine Clinical Profile Migraine Clinical Findings: PCSS + for HA and light and/or noise sensitivity; HA and nausea Current symptoms: HA Upon Waking HA and nausea HA with light/noise sensitivity Motion sickness Current medications for migraine prevention/rescue meds and/or anti-nausea Deficits with verbal and visual memory (data not in current analysis) Risk Factors: Personal history of migraine Personal history of motion sickness Family history of migraine Comorbid anxiety disorder Female gender
25 Patients with HA at Waking more likely to have Migraine Profile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 69% 31% Migraine Waking 9% NO Waking Other 91% χ2=25.36, p<.001, OR= 4.67 (95% CI= )
26 Patients with HA w/nausea and HA w/light or Noise More Likely to have Migraine Profile 100% 67% 62% 50% 33% 38% 0% Migraine Other HA w/nausea NO HA w/nausea χ2=21.67, p<.001, OR= 3.31 (95% CI= ) 100% 50% 65% 35% 51% 49% 0% Migraine Other HA w/lgt-noise NO HA w/lgt-noise χ2=5.12, p=.02, OR= 1.80 (95% CI= )
27 Patients with Personal Hx of Motion Sickness and Family Hx of Migraine more likely to have Migraine Profile 100% 66% 78% 50% 34% 22% 0% Migraine Other Personal Hx of Motion Sickness NO Hx χ2=4.67, p=.03, OR= 1.80 (95% CI= ) 100% 50% 47% 53% 33% 67% 0% Migraine Other Fam Hx Migraine NO Hx χ2=5.48, p=.02, OR= 1.80 (95% CI= )
28 Waking and w/nausea Associated with Migraine Profile B SE Wald p Adj OR 95% CI Waking < HA w/nausea HA w/lgt or Noise Per Hx Motion Sick χ 2 =19.72, p<.001, Nagelkerke R 2 =.19 Fam Hx Migraine χ 2 =42.15, p<.001, Nagelkerke R 2 =.17 Pts with Waking were 3.7x more likely to have migraine profile Pts with HA w/nausea were 2.5x more likely to have migraine profile
29 Vestibular Clinical Profile Vestibular Clinical Findings: PCSS + for dizziness and/or imbalance Current symptoms: Dizziness, dizziness with movement or change of positions, symptoms in busy environments Current motion sensitivity VOMS increase in symptoms beyond baseline with VOR/VMS Medications: meclizine, Dramamine, vestibular suppressants Deficits with visual motor speed (data not in current analysis) Risk Factors: Personal history of motion sickness Personal history of vestibular disorder Comorbid migraine Comorbid anxiety disorder
30 Patients w/dizziness and Dizziness w/movement More Likely to have Vestibular Profile 100% 74% 50% 53% 26% 47% 0% Vestibular Other Dizzy NO Dizzy χ2=9.55, p=.002, OR= 2.53 (95% CI= ) 100% 81% 50% 49% 56% 19% 0% Vestibular Other Dizzy w/movement NO Dizzy w/movement χ2=18.26, p<.001, OR= 3.34 (95% CI= )
31 Patients w/discomfort in Busy Environments and Current Motion Sensitivity More Likely to have Vestibular Profile 100% 80% 94% 50% 20% 6% 0% Vestibular Other Discomfort in Busy Environments NO Discomfort in Busy Environments χ2=13.09, p<.001, OR= 3.95 (95% CI= ) 100% 74% 88% 50% 26% 12% 0% Vestibular Other Motion Sensitivity NO Motion Sensitivity χ2=8.55, p=.003, OR= 2.62 (95% CI= )
32 Patients with Positive VOMS VOR and VMS scores more likely to have Vestibular Profile 100% 50% 0% 70% 30% Vestibular Positive VOMS VOR 46% Other 54% NO VOMS VOR χ2=12.33, p<.001, OR= 2.74 (95% CI= ) 100% 50% 80% 20% 57% 43% 0% Vestibular Other Positive VOMS VMS NO VOMS VMS χ2=10.70, p=.001, OR= 2.81 (95% CI= )
33 Dizziness with Movement and Discomfort in Busy Environments Associated with Vestibular Profile B SE Wald p Adj OR 95% CI Dizziness Dizziness w/mov t Discomfort in Busy Env Current Motion Sens Positive VOMS VOR χ 2 =19.72, p<.001, Nagelkerke R 2 =.19 Positive VOMS VMS Pts w/dizziness w/movement were 2.5x more likely to have vestibular profile Pts with Discomfort in Busy Environments were 2.9x more likely to have vestibular profile χ 2 =39.38, p<.001, Nagelkerke R 2 =.18
34 Ocular Clinical Profile Ocular Clinical Findings: PCSS + for vision problems Current symptoms: Blurry vision, diplopia, eye strain Difficulty reading or performing visual activities HA triggered specifically by visual activity VOMS NPC > 5cm or abnormal convergence noted Deficits with reaction time and visual memory (not in current analysis) Risk Factors: Personal and/or family history of eye muscle surgery, strabismus, amblyopia, or other ocular diagnosis Prescribed reading glasses before age of 30 Past participation in vision therapy and/or prescribed prism lenses.
35 Males more likely to have Ocular Profile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 68% Ocular 32% 42% Other 58% Male Female χ2=6.04, p=.01, OR= 2.97 (95% CI= )
36 Patients w/blurry, Diplopia, Eye Strain; and Difficulty Reading More Likely to have Ocular Profile 100% 50% 57% 43% 27% 73% 0% Ocular Other Blurry, Diplopia, Eye Strain NO Blurry, Diplopia, Eye Strain χ2=16.39, p<.001, OR= 3.53 (95% CI= ) 100% 88% 61% 50% 39% 12% 0% Ocular Other Difficulty Reading NO Difficulty Reading χ2=23.33, p<.001, OR= 4.93 (95% CI= )
37 Patients with NPC Distance >5cm more likely to have Ocular Profile 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 87% Ocular 13% 38% Other 62% NPC >5cm NPC< 5cm χ2=37.84, p<.001, OR= (95% CI= )
38 Male Gender, Blurry/Diplopia, Difficulty Reading and NPC Distance Associated with Ocular Profile B SE Wald p Adj OR 95% CI Male Gender Blurry, Diplopia, Eye Strain Difficulty Reading NPC >5cm < χ 2 =45.24, p<.001, Nagelkerke R 2 =.39 Males were 4.4x more likely to have ocular profile Pts w/blurry, Diplopia, Eye Strain were 3.6x more likely to have ocular profile Pts w/difficulty Reading were 4.4x more likely to have ocular profile Pts w/npc >5cm were 10.4x more likely to have ocular profile
39 Anxiety/Mood Clinical Profile Anxiety/ Mood Clinical Findings: PCSS + for irritability, nervousness, sadness, feeling more emotional; symptom report across all domains Current symptoms: Anxiety/depression, worry, difficulty turning off thoughts, rumination Sadness, limited social interaction Current psychiatric or mood medications Current psychiatry, psychotherapy Normal or inconsistent findings on neurocognitive testing (Data not in Analysis) Risk Factors: Personal and/or family history of psychiatric issues Psychiatric/mood medications taken in past Comorbid migraine Presence of significant life stressor
40 Every characteristic on the preceding slide was a significant univariate predictor of the anxiety/mood profile... reflecting the complicated presentation of this profile.
41 Anxiety/Depression, Worry, and Sadness Sx Associated with Anxiety/Mood Profile* B SE Wald p Adj OR 95% CI Anxiety/Depression Sx < Worry, Difficulty Turning off < Thoughts, Rumination Sx Sadness, Lim. Social Interact *Does not include 9 other factors that were not sig. χ 2 =138.30, p<.001, Nagelkerke R 2 =.48 Pts w/anxiety/depression were 4.7x more likely to have anxiety/mood profile Pts w/worry and related Sx were 4.2x more likely to have anxiety/mood profile Pts w/sadness/loss of Interest were 3x more likely to have anxiety/mood profile
42 Part 2- Inter-Clinician Reliability Study A total of 6 reviewers were paired into 3 teams comprising one neuropsychologist and one physical therapist 42 total patients with reliability data All blind reviews
43 Study Overview (cont.) Primary outcomes: Patient primary clinical profile Rank order of clinical profiles Primary, secondary, tertiary Patient #33 100% Agreement on Primary Profile 100% Agreement Across All Profiles Reviewer Primary Secondary Tertiary Other 1 Other 2 1- NeuroPsy Mood Vestibular Migraine PT Mood Migraine Vestibular Patient #34 Reviewer Primary Secondary Tertiary Other 1 Other 2 1- NeuroPsy Vestibular Migraine Ocular PT Migraine Vestibular Ocular Mood -- 0% Agreement on Primary Profile 100% Agreement on Combined Primary and Secondary Profiles 75% Agreement Across All Profiles
44 Percent Agreement for Clinical Profiles Primary Profile Primary/Secondary Profiles Combined ALL Profiles Range across pairs of raters 14-50% 61-68% 67-79% 80% 70% 60% 50% 40% 30% 20% 10% 0% 72% 65% 33% 20% 4% Primary Primary & Secondary All Profiles Agreement Chance
45 Summary Clinical profiles can be characterized using risk factors, symptoms, clinical findings, neurocognitive testing, and VOMS outcomes Migraine and anxiety profiles most common Ocular was most distinct; Anxiety was most complex Good agreement among reviewers for primary/secondary and all clinical profiles Challenge is in prioritizing clinical profiles Future of concussion management subtyping of injury and targeted/active treatment? Need for continued research and prospective studies Need to evolve to individualized concussion care-not just about protocol
46 46 Case Example of Clinical Criteria for Concussion Clinical Profiles
47 Demographics and Injury 16 year old male lacrosse player Date of injury: 10/21/2017 Mechanism: Checked from behind in LAX game resulting in him colliding with another player and sustained frontal H2H hit No LOC, PTA, disorientation or confusion Immediate symptoms: dizziness, foggy, vision going black, headache
48 Sub-acute Injury Despite symptoms, continued to play remainder of game (45 minutes) No report of symptoms to ATC or parents Played another 3 full games across two weekend days in LAX tournament, no known additional blows to head End of tournament, symptoms worsened: Intense headache (9/10) Nausea and vomiting (1x) Photosensitivity/phonophobia Fatigue, Foggy Motion sensitive- dynamic movement and car rides exacerbated symptoms Church on Sunday resulted in severe HA, dizziness All symptoms worsened upon going to school on Monday, and then notified his parents.
49 Biopsychosocial History High school sophomore, A/B student History of migraine HAs Onset 4 th grade, stopped in 5 th grade with no tx Occasional HAs at times (15 of 30 days prior to injury; 2/10 in terms of severity) Family history of migraines in mother & sister No history of mental health, neurological conditions, oculomotor dysfunction, carsickness, ADHD, LD
50 Initial Evaluation Evaluated 3 days post-injury Current symptoms: Headache (8/10) Nausea, photosensitivity and phonosensitivity Dizziness (slow, wavy), fogginess Fatigue, hypersomnia (taking naps) Trouble concentrating Car sickness, environmental sensitivity Denied neck pain
51 Computerized Neurocognitive Testing
52 Vestibular/Ocular-Motor Screening (VOMS) VOMS Headache Dizziness Nausea Foggy Comments Baseline Symptoms Smooth Pursuits Saccades Horizontal Saccades Vertical Convergence (Near Point) Trials 1-3= 2cm Average= 2cm VOR - Horizontal VOR Vertical Visual Motion Sensitivity Symptom Total
53 Impression? What are clinical profiles of injury?? Treatment Recommendations?? Prognosis??
54 Impression Clinical profile(s): Migraine (primary) Cognitive fatigue (secondary) Vestibular (tertiary) Treatment Recommendations? Migraine Cognitive/ Fatigue Vestibular
55 Matching targeted and active treatments to clinical profiles may improve recovery trajectories following concussion. Vestibular Rehabilitation Exercise Structured Rest Exercise Medication Exercise Behavioral Regulation Relaxation/Biofeedback CBT/Trigger Modification Medication
56 Matching targeted and active treatments to clinical profiles may improve recovery trajectories following concussion. Vestibular Rehabilitation Exercise Structured Rest Exercise Medication Medication Exercise Relaxation /Biofeedback CBT Education/Trigger Modification
57 Treatment Recommendations Treatment Recommendations: Behavioral regulation strategies for migraine Regulated sleep (no naps), hydration, diet, reduced stress (allow phone, attend team practice, keep up with homework) and prescribed exercise- stationary bike (no limitations on intensity) and walking Modified activity for cognitive fatigue: School: full days with light accommodations and 3 scheduled breaks Exercise- prescribed stationary bike and walking Vestibular therapy with Neuro-PT for vestibular
58 Course of Treatment Patient followed up for four clinic visits (weekly) Patient completed 3 session of vestibular therapy (was compliant with HEP) Dizziness with movement and environmental sensitivity abated within 14 days Progressed to targeted, sports-specific exertion therapy after 2 weeks Was consistent with behavioral management for migraine Morning headaches abated within 10 days Took breaks at school and daily exercise Afternoon headaches and fatigue improved, but persisted for 3-4 weeks after injury Grades stable, no declines-released from academic accommodations after 2 weeks Began attending LAX practice for non-contact drills 3 weeks post-injury Treatment continued until headaches improved relative to pre-injury levels Returned to play 35 days post-injury No reoccurrence of difficulties or symptoms since release
59 Last Clinic Visit (35 days post-injury) Feels 100% back to normal Has been symptom free for 2 weeks, aside from intermittent HA 2/15 days; severity 1/10 No academic accommodations Had engaged in noncontact LAX Completed EXIT test with no symptom provocation and previously discharged from vestibular/exertion therapy
60 Computerized Neurocognitive Testing
61 Vestibular/Ocular-Motor Screening (VOMS) VOMS Headache Dizziness Nausea Foggy Comments Baseline Symptoms Smooth Pursuits Saccades Horizontal Saccades Vertical Convergence (Near Point) Average= 2cm VOR - Horizontal VOR Vertical Visual Motion Sensitivity Symptom Total
62 Impression/Summary Pt Met Criteria for RTP Educated that he may be at elevated risk of concussion due to migraine history and family hx of migraine
63 Acknowledgments UPMC Sports Medicine Concussion Program Faculty Anthony Kontos, PhD, Research Director Alicia Sufrinko, PhD & Nate Kegel, PhD Clinical Neuropsychology Faculty Anne Mucha, DPT, Vestibular Therapist Tori Kochick, DPT, Exertional Therapist Concussion Research Laboratory- UPitt Cyndi Holland, MPH, Research Coordinator Valerie Reeves, PhD, Research Coordinator Hannah Bitzer, BS, Research Assistant Nick Blaney, BS, Research Assistant Clinical Neuropsychology Fellows- UPMC Daniel Charek, PhD, Senior Fellow Brandon Gillie, PhD, Senior Fellow Natalie Sandel, PsyD, Senior Fellow
64 Thank you! For more information: 64
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