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Non-Cognitive Diagnostic Assessment of TBI/Sports Concussion Barry D. Jordan M.D., M.P.H. Director, Brain Injury Program Burke Rehabilitation Hospital.

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Presentation on theme: "Non-Cognitive Diagnostic Assessment of TBI/Sports Concussion Barry D. Jordan M.D., M.P.H. Director, Brain Injury Program Burke Rehabilitation Hospital."— Presentation transcript:

1 Non-Cognitive Diagnostic Assessment of TBI/Sports Concussion Barry D. Jordan M.D., M.P.H. Director, Brain Injury Program Burke Rehabilitation Hospital Associate Professor Clinical Neurology Weill Medical College of Cornell University Former Chief Medical Officer New York State Athletic Commission

2 Concussion Evaluation Neurodiagnostic Testing Neurodiagnostic Testing  Neuropsychological Testing  Neuroimaging  Biomarkers of brain injury  Objective Balance Assessment  Electrophysiological testing  Genetic testing  Eye tracking techniques

3 Non-computerized cognitive assessment Standardized Assessment of Concussion (SAC) Standardized Assessment of Concussion (SAC) Sport Concussion Assessment Tool 2 (SCAT 2) Sport Concussion Assessment Tool 2 (SCAT 2) McGill On-Field Concussion Evaluation McGill On-Field Concussion Evaluation Maddocks Score Maddocks Score Military Acute Concussion Evaluation (MACE) Military Acute Concussion Evaluation (MACE) Standard pencil paper neuropsychological testing Standard pencil paper neuropsychological testing

4 Neuroimaging Traditional structural neuroimaging Traditional structural neuroimaging  CT  MRI Newer structural neuroimaging Newer structural neuroimaging  DTI Functional and metabolic scanning Functional and metabolic scanning  PET  SPECT  fMRI  MRS  NIRS

5 strong directional dependence of water diffusion decreased directional dependence of water diffusion Diffusion anisotropy: fiber tract integrity CST damaged fiber tract healthy fiber tract

6 Fiber Tractography in TBI Anterior corona radiata and genu of CC Anterior corona radiata and genu of CC Uncinate fasiculus Uncinate fasiculus Cingulum bundle and body of CC Cingulum bundle and body of CC Inferior longitudinal fasciculus Inferior longitudinal fasciculus

7 a c b d Figure 2. Diffusion anisotropy maps (a) of a representative boxer (27 yo) and (b) a control (29 yo). Intensity is proportional to anisotropy and color shows the direction. Boxer has decreased FA in genu CC, anterior and posterior limb of IC than those of the normal control. Fiber tracking showed overall less trackable white matter fibers in this boxer’s brain (c) when compared to control (d). The difference in fibers through the corpus callosum is particularly striking.

8 old study new study

9 DTI in Boxing Zhang et al. (2006)   49 professional boxers and 19 controls   42 boxers had normal conventional MRI   7 boxers had NSWM changes   None of the boxers exhibited neurological signs or symptoms   Boxers had decreased FA in the CC and IC

10 FA splenium FA genu FA post. FA ant. BD av of CC of CC limb of IC limb of IC (10 -5 cm 2 /s)

11 DTI and ATBI Cubon et al 2011 Cubon et al 2011  Assessed WM fiber tract integrity 10 varsity college athletes and controls  Also included moderate and severe TBI patients and controls  Symptomatic 1 month after sports-related concussion

12 DTI and ATBI Cubon et al (cont’d) Cubon et al (cont’d)  Increased mean diffusivity (MD) among athletes c/w controls in several WM tracts in the left hemisphere  Inferior/superior longitudinal fasciculus  Fronto-occipital fasciculi  Retrolenticular part of internal capsule  Posterior thalamic and acoustic radiations

13 DTI and ATBI Cubon et al Cubon et al  No difference in fractional anistropy (FA) between athletes and controls  FA decreased with the level of severity  MD may be more sensitive in detecting mild injury and FA more sensitive in detecting more severe injury

14 DTI and ATBI

15 fMRI and TBI Jantzen et al. (2004) Jantzen et al. (2004)  Prospective investigation of 8 collegiate football players had preseason fMRI scans obtained during a finger sequencing task  4 players experienced a concussion during the season and had a f/u fMRI within 1 week of the injury and the 4 controls had a /f/u at the end of the season  Concussed players had marked increased activation in the areas of the parietal, lateral frontal and cerebellar regions

16 fMRI and TBI

17 Brain Metabolism is Related to Recovery Over 200 High School Athletes Studied using fMRI Tested w/in 7 days of concussion and at point of clinical recovery Hyperactivation predicts CLINICAL recovery time Resolution of hyperactivation correlates with recovery on ImPACT Lovell et al., Neurosurgery, 2007

18 SPECT Referred population of 17 professional boxers Referred population of 17 professional boxers 14 (82%) had abnormal SPECT scans 14 (82%) had abnormal SPECT scans  7 cases with frontal lobe hypoperfusion  3 cases with temporal lobe hypoperfusion  1 case temporoparietal hypoperfusion  1 case with frontoparietal hypoperfusion  1 case with diffuse diminished perfusion in an irregular and patchy distribution  1 case bilateral cortical thinning

19 SPECT Scanning

20 SPECT scanning

21 PET Scanning

22 PET 19 boxers c/w 8 normal controls SPM analysis 19 boxers c/w 8 normal controls SPM analysis 8 hypometabolic areas 8 hypometabolic areas  Bilateral posterior parietal lobes that extended to the lateral occipital lobes  Bilateral frontal lobes  Bilateral cerebellar hemispheres  Posterior cingulate cortex

23 Decreased Glucose Uptake Among Boxers (SPM and ROI) Posterior cingulate Bilateral parietal- occipital cortices Bilateral frontal cortices (Broca’s area) Cerebellum

24 PET/SPECT IN MTBI Umilie et al Umilie et al  20 patients with MTBI and persistent PCS underwent neuropsychological testing and PET or SPECT  19 (95%) had neurobehavioral deficits  18 (90%) had abnormal dynamic imaging on PET or SPECT

25 PET/SPECT IN MTBI Umile et al (2002) (cont’d) Umile et al (2002) (cont’d)  75% - temporal lobe abnormalities  30% - frontal lobe abnormalities  40% - nonfrontotemporal abnormalities  Correlations between neuropsychological testing could be established but not consistently  Postulated that there was a temporal lobe vulnerability to TBI

26 Magnetic Resonance Spectroscopy Provides in vivo neurochemical information Provides in vivo neurochemical information Metabolites Metabolites  N-aceytlaspartate (NAA): neuron specific metabolite and is a marker on neuronal health  Choline (Cho): marker of inflammation  Creatine (Cr): stable brain metabolite and a marker of cellular energy status  Myo-inositol: glial marker  Lactate: indirect indicator of ischemia/hypoxia Can detect areas of neuronal dysfunction in the absence of detectable structural injury Can detect areas of neuronal dysfunction in the absence of detectable structural injury

27 Magnetic Resonance Spectroscopy Vagnozzi et al Vagnozzi et al  Compared 14 concussed athletes (4 boxers) with 5 controls  3 days after concussion observed a decrease in the NAA/Cr ratio that resolved after 30 days  Concluded that concussion opens a temporal window of metabolic imbalance

28 MRS

29 Magnetic Resonance Spectroscopy Henry et al Henry et al  Compared 12 concussed athletes with 12 non-concussed athletes hrs post concussion  Concussed athletes had more symptoms  Concussed athletes had decreased NAA in the prefrontal and motor cortices

30 Near Infrared Spectroscopy (NIRS) Non-invasive technique for evaluating cerebral blood volume and oxygenation Non-invasive technique for evaluating cerebral blood volume and oxygenation Technology is based on the transmission and absorption of near-infrared light as it passes through tissue Technology is based on the transmission and absorption of near-infrared light as it passes through tissue Role in the diagnosis of concussion has been limited Role in the diagnosis of concussion has been limited May be more useful in the identification of intracranial hematomas May be more useful in the identification of intracranial hematomas

31 NIRS Leon-Carrion et al 2010 Leon-Carrion et al 2010  Used an infrascanner NIRS device to calculate optical density in brain regions  35 TBI patients admitted into Neuro ICU  Detected  90% of extra-axial hematomas  88.9% of intra-axial hematomas  93% of nonsurgical hematoma (< 25 ml)

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33 Infrascanner NIRS device

34 NIRS Cote et al Cote et al  Monitored cerebral hemodynamics during acute exercise following concussion in 14 male university hockey players  Cerebral oxygenation was reduced up to 35% on day 1 following concussion  Blood volume increased immediately following a concussion at rest and during exercise at day 1 and returned to baseline by day 7  Concluded that there is an increased demand for oxygenated blood following concussion

35 BIOMARKERS S100β S100β Neuron specific enolase (NSE) Neuron specific enolase (NSE) Glial fibrillary acidic protein (GFAP) Glial fibrillary acidic protein (GFAP) Tau (cleaved tau, phospho tau, total tau) Tau (cleaved tau, phospho tau, total tau) Neurofilament light protein (NFL) Neurofilament light protein (NFL) Microtubular associated protein 2 (MAP2) Microtubular associated protein 2 (MAP2) CK-BB Spectrin breakdown products β amyloid protein (Aβ) Apolipoprotein (Apoe) Myelin basic protein (MBP) Ubiquitin C-terminal hydrolase L1 (UCH-L1)

36 S100 β Most extensively studied serum biomarker Most extensively studied serum biomarker Variable relationship between S100β and outcome following MTBI Variable relationship between S100β and outcome following MTBI Needs to collected within 4 hours of injury Needs to collected within 4 hours of injury There are extracranial sources of S100β There are extracranial sources of S100β

37 S100 β Hasselbatt et al 2004 Hasselbatt et al 2004  18 marathon runners without brain injury  Found an increase in postrace serum S100β from extracranial sources  No significant change in GFAP

38 Biomarkers of ATBI in Boxing Zetterberg et al. (2006) Zetterberg et al. (2006)  14 amateur boxers and 10 healthy controls  CSF analysis 7-10 days and 3 months post bout  Neurofilament light protein (NFL)  Total tau (T-tau)  Phosphorylated tau (P-tau)  Glial fibrillary acidic protein (GFAP)  β amyloid protien (Aβ)  Assessed the number and severity of the hits by interview

39 Biomarkers of ATBI in Boxing Zetterberg et al. (2006) (cont’d) Zetterberg et al. (2006) (cont’d)  Increases in NFL, T-tau, and GFAP post bout compared to levels post 3 months of rest  NFL and GFAP were higher in boxers post bout compared to controls  No difference in biomarkers between boxers at 3 months and controls except for NFL (remained elevated)  P-tau and Aβ were not elevated  Concluded that amateur boxing was associated with neuronal and astroglial injury

40

41 Balance and Agility Testing Balance Error Scoring system (BESS) Balance Error Scoring system (BESS) Sensory Organization Test (SOT) Sensory Organization Test (SOT) Gait Testing Gait Testing Virtual Reality Virtual Reality Instrumented Agility Task Instrumented Agility Task

42 Balance Error Scoring System Hands lifted off iliac crest Hands lifted off iliac crest Opening eyes Opening eyes Step, stumble or fall Step, stumble or fall Moving hip more than 30 degrees of flexion or abduction Moving hip more than 30 degrees of flexion or abduction Lifting forefoot or heel Lifting forefoot or heel Remaining out of testing position for more than 5 seconds Remaining out of testing position for more than 5 seconds

43 Balance Error Scoring System Several studies have identified BESS deficits ranging from 3-5 days post concussion when compared to baseline and controls Several studies have identified BESS deficits ranging from 3-5 days post concussion when compared to baseline and controls The best sensitivity is at the time of injury The best sensitivity is at the time of injury

44 Sensory Organization Test (SOT) Technical force plate system to assess balance Technical force plate system to assess balance Disrupts sensory selection process by altering information from the somatosensory and/or visual inputs while measuring ability to maintain stance Disrupts sensory selection process by altering information from the somatosensory and/or visual inputs while measuring ability to maintain stance Uses 6 different conditions Uses 6 different conditions

45

46 Sensory Organization Test (SOT) SOT appears to be a sensitive in detecting balance deficits following concussion SOT appears to be a sensitive in detecting balance deficits following concussion Limited use on the field secondary to size and technology needs Limited use on the field secondary to size and technology needs May provide a more technical or refined measure of balance performance May provide a more technical or refined measure of balance performance BESS is rapid, easy to administer and inexpensive BESS is rapid, easy to administer and inexpensive

47 Postural Stability Guskiewicz et al. (2001) Guskiewicz et al. (2001)  36 concussed athletes compared with 36 matched controls  Assessed postural stability using the SOT and BESS along with neuropsychological testing  Injured subjects demonstrated postural stability deficits on both SOT and BESS

48 Postural Stability Guskiewicz et al. (2001) Guskiewicz et al. (2001)  These deficits were significantly worse than preseason scores and scores of the matched controls on postinjury day 1

49 Gait Analysis Parker et al 2007 Assessed 29 concussed athletes and 29 uninjured matched controls Gait was assessed while completing a simple mental task At 28 days noted a statistically significant difference in gait stability between concussed athletes compared to controls

50 Virtual Reality Slobounov et al 2006 Slobounov et al 2006  Assessed balance deficits induced by visual field motion using a virtual reality environment  8 concussed athletes exhibited balance deficits up to 30 days despite having symptoms and neuropsych testing return to baseline

51 Instrumental Agility Test Johnson et al. (2002) Johnson et al. (2002)  Assessed 9 concussed athletes and 9 matched controls  Time to complete an agility task on the Cybex reactor  Although concussed athletes had more symptoms than controls there was no difference agility performance

52 Electrophysiological testing Quantitiative Electroencephalogram (QEEG) Quantitiative Electroencephalogram (QEEG) Event-related Potentials (ERP) Event-related Potentials (ERP)

53 Quantitative EEG (QEEG) McCrea et al 2010 McCrea et al 2010 Prospective, non randomized study of 396 high school and college football players Prospective, non randomized study of 396 high school and college football players Included cohorts of 28 concussed athletes and 28 matched controls Included cohorts of 28 concussed athletes and 28 matched controls All underwent preseason baseline testing All underwent preseason baseline testing Postconcussive symptoms Postconcussive symptoms Postural stability Postural stability Cognitive functioning Cognitive functioning QEEG QEEG

54 Brain scope NT-1000 Brain scope NT-1000  Self contained EEG monitor  Acquires data from 5 active regions of the forehead  Provides immediate, actionable information to drive timely medical intervention in many cases of brain dysfunction, such as stroke and concussion

55 Quantitative EEG (QEEG) McCrea et al 2010 (cont’d) McCrea et al 2010 (cont’d)  Clinical testing was repeated on the day of injury and days 8 and 45 post injury for the concussion and control group  Injured athletes performed poorer on neuro-cognitive testing than controls on the day of injury but not days 8 or 45  Concussed athletes had abnormal electrical activity noted on the day of injury and day 8 but not day 45  Suggested that the duration of physiological recovery may last longer than observed clinical recovery

56 Event-Related Potentials (ERP) Dupuis et al 2000 Dupuis et al 2000  ERP visual oddball paradigm to assess cerebral activity in 20 college athletes with MTBI  Concussed athletes had a decrease in the P300 amplitude  Presumed to reflect alterations in attentional-cognitive processes

57 ERP

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59 Genes influencing non-sports related TBI outcome  Apolipoprotein E (APOE)  APOE promotor gene  Catechol-o-methyltransferase (COMT)  Dopamine D2 receptor (DRD2) (ANNK1 gene)  Interleukin  p53  Angiotensin converting enzyme (ACE)  CACNA1A

60 APOEε4 and TBI Outcome Overall unfavorable outcome (GOS) Overall unfavorable outcome (GOS) Increased duration of posttraumatic unawareness Increased duration of posttraumatic unawareness Larger CT documented hematomas Larger CT documented hematomas Increased risk of posttraumatic seizures Increased risk of posttraumatic seizures Increased association with cerebral amyloid angiopathy Increased association with cerebral amyloid angiopathy Greater incidence of autopsy confirmed moderate and severe contusions Greater incidence of autopsy confirmed moderate and severe contusions Poorer rehabilitation outcome Poorer rehabilitation outcome Lower cognitive function follow TBI Lower cognitive function follow TBI Higher association with dementia and subclinical dementia among TBI patients assessed long term post injury Higher association with dementia and subclinical dementia among TBI patients assessed long term post injury

61 APOE and TBI Zhou et al (2008) Zhou et al (2008)  Meta-analysis  14 cohort studies  ε4 allele was not associated with initial injury severity  ε4 allele was associated with poorer outcome at 6 months after injury

62 APOE Promoter and TBI Terrell et al. (2008) Terrell et al. (2008)  195 college athletes (football / soccer)  Cross-sectional study investigating the association between APOE, APOE promoter, and tau polymorphisms and self reported history of concussion over the previous 8 years  3 fold increase in risk of history of concussion in those TT genotype of G-219T polymorphism relative to the GG genotype  4 four-fold increased risk with self reported history of concussion associated with LOC  No association with APOE or tau genotype

63 APOE and ATBI in Sports Kristman et al. (2008) Kristman et al. (2008)  Prospective cohort study of 318 collegiate athletes in various sports  Compared concussion rates in athletes with and without APOE ε4 allele  No association between ε4 allele and sustaining a concussion

64 APOE and ATBI in Sports Tierney et al Tierney et al  196 college athletes (163 male football and 33 female soccer players)  Multi-center cross sectional study evaluating the association carrying 1 or more APOE rare (or minor) alleles (APOE ε2, APOE ε4 and T allele of G-219T APOE promoter polymorphism) and self reported history of concussion via a questionnaire and self reported history of concussion via a questionnaire  Athletes carrying all 3 rare alleles were 9.8 times more likely to report a previous concussion and concluded that carriers may be at greater risk of concussion  Athletes carrying the T allele of the APOE promoter gene were 8.4 more likely to report multiple concussions and concluded that carriers may be greater risk of multiple concussions

65 Eye tracking technology ID Coach ID Coach King-Devick Test King-Devick Test

66 ID Coach Sideline Concussion Tracker Uses eye-gazing technology to assist in the assessment of concussions Uses eye-gazing technology to assist in the assessment of concussions

67 ID Coach Sideline Concussion Tracker Player is positioned in front of a monitor and focuses on a fixed point while pupil size is analyzed Player is positioned in front of a monitor and focuses on a fixed point while pupil size is analyzed The player is then asked to follow a moving object across the screen without head movement (baseline eye tracking is established) The player is then asked to follow a moving object across the screen without head movement (baseline eye tracking is established) Blurred/double vision or inability to focus may be indicative of concussion Blurred/double vision or inability to focus may be indicative of concussion

68 King-Devick (K-D) Test Measurement of speed of rapid number naming Measurement of speed of rapid number naming Reading aloud a series of single digit numbers on 3 test cards from left to right Reading aloud a series of single digit numbers on 3 test cards from left to right Sum of the 3 test card time scores and the number of errors are scored. Sum of the 3 test card time scores and the number of errors are scored. Captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function Captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function

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70 King-Devick (K-D) Test Galetta et al 2011 Galetta et al 2011  K-D test was administered to a cohort of boxers (n=27) and MMA (n=12) pre and post fight  Also administered the MACE  Postfight K-D time scores were significantly higher (worse) for participants who had head trauma (59 vs 41 seconds)

71 King-Devick (K-D) Test Galetta et al 2011 (cont’d) Galetta et al 2011 (cont’d)  Among those with head trauma, participants with LOC had higher postfight K-D scores than those without LOC (65.5 vs 52.7 seconds)  Worse postfight scores also correlated with postfight MACE scores  Suggested that this could serve as a rapid sideline screening test

72 King-Devick (K-D) Test

73 Conclusions There is no single test available to diagnose sports concussion There is no single test available to diagnose sports concussion Various devices/tests that may assist in the diagnosis Various devices/tests that may assist in the diagnosis Remains a clinical diagnosis Remains a clinical diagnosis

74 THANK YOU QUESTIONS?


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