Traumatic Brain Injury Diagnostic Challenges & Emerging Tools

1. Traumatic Brain Injury Diagnostic Challenges &Emerging Tools Julie C. Chapman, PsyD

2. VA/DOD Definition of TBI • A traumatically induced structural injury AND/OR • physiologic disruption of brain function • as a result of an external force • that is indicated by new onset or worsening of • at least one of the following clinical signs • immediately following the event

3. VA/DOD Definition of TBI • At least one of the following clinical signs immediately following the event: • Any period of loss of consciousness • Any loss of memory for events immediately before or after injury • Any alteration in mental state at the time of injury • Neurologic deficits • Intracranial lesion

4. How is TBI Diagnosed? • 2nd Level TBI Evaluation: • Interview • Physical Examination • Neurobehavioral Symptom Inventory • TBI is often retrospectively diagnosed

5. Severity of Injury • Three main indices: • Duration of Loss of Consciousness (LOC) or Alteration of Consciousness (AOC) • Post-Traumatic Amnesia (PTA) • Glasgow Coma Scale (GCS)

6. Severity of Injury (VA/DOD)

7. Diagnostic Challenges • Diagnostic criteria is based largely upon patient self-report, particularly in mild TBI. • Possible threats to diagnostic accuracy: • Recall bias • Cognitive difficulties • Other factors

8. Diagnostic Challenges • Overlap of symptoms in co-morbid conditions: • Hoge et al. Study • Schneiderman et al. Study • RAND Study

9. Symptom Overlap TBI PTSD Insomnia Memory problems Poor concentration Depression Anxiety Irritability Re-experiencing Avoidance Emotional numbing • Insomnia • Memory Problems • Poor concentration • Depression • Anxiety • Irritability • Headache • Dizziness • Fatigue • Noise/light intolerance

10. Seeking Objective Markers • Biomarkers • Brain Imaging • Neurobehavioral Measures

11. Biomarkers • S-100B • Calcium binding protein found in astroglial and Schwann cells • Sensitive but not specific for brain injury • Others: • GFAP = GlialFibrillary Acidic Protein • MBP = Myelin Basic Protein • NSE= Neuron Specific Enolase

12. Diffusion Tensor Imaging • Measures the movement of water molecules in neurons. • Diffusion is an intrinsic physical process independent of the MR effect & magnetic field. • White matter tracts can be visualized and estimated in vivo.

13. Diffusion Tensor Imaging • Lipton et al. 2009 - 20 pts (2 wks post mTBI), 20 matched controls. Reduced FA in frontal WM correlated with executive function tests (IntegNeuro: CPT & EMT). • Niogi et al. 2008 - 43 patients (16.9 mths post mTBI) and 23 controls. Attentional control correlated with FA in L corona radiata. Memory performance correlated with FA in uncinate fasciculus. • Rutgers et al. 2008 - 21 patients (5.5 mths post mTBI) and 11 controls. mTBI had reduced FA in cerebral lobar WM, cingulum and corpus callosum.

14. Blast Injury Outcomes (BIO) Study • Sample of OEF/OIF Veterans and Controls with: • No prior TBI (even mild) • No current or recent or chronic substance abuse or dependence • All OEF/OIF Veterans have • Mild TBI from blast exposure and/or • Combat-related PTSD

15. Blast Injury Outcomes (BIO) Study - Chapman

16. Blast Injury Outcomes (BIO) Study-Chapman

17. Neurobehavioral Measures • Heitger et al. 2009: Antisaccades and visual tracking more impaired in patients with post-concussive syndrome at avg of 140 days post-injury than controls • Wortzel et al. 2009: Presence of frontal release signs plus paratonia predicted cognitive and functional impairment in a acute TBI. • Chapman et al. 2010: Presence of visual tracking, frontal release signs and antisaccades predicted mTBI versus No TBI group.

18. Integrative Diagnostics Patient Self-Report Objective Diagnostic Markers GESTALT

19. All Hands on Deck Epidemiology Laboratory Science Clinical Science

20. Integrative Diagnostics Clinical Algorithms

21. Markers for the Identification, Norming & Differentiation (MIND) of TBI and PTSD Principal Investigator: Julie C. Chapman, PsyD Study Chair and Co-PI: Aaron Schneiderman, PhD • Tri-WRIISC Study (DC, East Orange, Palo Alto) • Clinical Research Evaluation of OEF/OIF Veterans from the Epidemiological Study

22. Markers for the Identification, Norming & Differentiation of TBI and PTSD (MIND) • Four groups of OEF/OIF Veterans studied (total n=800): • Veterans with TBI • Veterans with PTSD • Veterans with both TBI and PTSD • Veterans with neither TBI nor PTSD

23. Phase One AimsMIND Study • Aim 1: To validate the prevalence estimate of TBI and PTSD in OEF/OIF Veterans from the Epidemiological Study. • Aim 2: To assess the effectiveness of VHA screening instruments for TBI and PTSD in OEF/OIF Veterans.

24. Phase Two AimsMIND Study • Aim 1: To identify sensitive & specific markers for both conditions from each measurement modality. • Aim 2: To develop prediction models for both conditions using multi-system, objective measures and patient self-report. • Measures include: • Cognitive • Sensorimotor • Advanced Neuroimaging • Sleep

25. Phase Three AimsMIND Study • Aim 1: To identify sensitive & specific markers for TBI from each measurement modality. • Aim 2: To develop prediction models for TBI using multi-system, objective measures and patient self-report. • Measures include: • Neuroendocrine • Sleep Medicine

26. Contact Us ADDRESS: Veterans Affairs Medical Center MS 127 Washington, DC 20422 PHONE: (202) 745-8249 EMAIL: Julie.Chapman@va.gov VISIT OUR WEBSITE: www.warrelatedillness.va.gov/dc/