Windows To The Brain: Neuropsychiatry of Brain Injury

1. Windows To The Brain: Neuropsychiatry of Brain Injury VISN 6 MIRECC:Mental Illness Research, Education, & Clinical CenterRobin A. Hurley, MD, FANPAProfessor, WFUSMKatherine H. Taber, PhD, FANPAProfessor, VCOM Disclaimer:The views expressed in this session are strictly those of the presenters (RAH & KHT). They do NOT represent those of the Veteran’s Health Administration, the Department of Defense, or the United States Government.

2. Today’s Discussion • Neuropsychiatric symptoms in TBI • Functional anatomy of emotion, memory, and behavior circuits as it relates to TBI • VA Polytrauma system of screening, care, and clinical practice guidelines • Current assessment and treatment advice for TBI-PTSD within VA • Current VISN 6 MIRECC projects and suggestions for the future

3. Reported TBI in DoD TBI Exposures entering VA Healthcare System 15%-20% entering VHA have + TBI screen (Carlson et al, 2010; Pietrzak et al, 2009) April 2007 - FY2009, 66,023 Veterans identified as possibly having a TBI through outpatient screening of individuals presenting to VA from OIF/OEF. Of those screened positive, 24,559 were confirmed to have sustained a TBI (37%). (Veteran’s Health Initiative: Traumatic Brian Injury, released April 2010. http://www.publichealth.va.gov/docs/vhi/traumatic-brain-injury-vhi.pdf)

4. Neuropsychiatry post-TBI: What do we see in clinic? • Impulsivity: common reason family brings patient to MD • Disinhibition: no “filter” on thoughts or actions (misses social cues) • Balance/dizziness/vertigo • Headaches • Visual changes (e.g. sensitivity to bright lights, decreased accommodation, convergence, and reading, oculomotor dysfunction ) • Memory/cognitive deficits • Irritability and aggression • Sleep disturbances • Ringing in ears/decreased hearing • Substance Abuse

5. Post Injury Factors: missed items • Partial Complex Seizures (especially frontal) • Verbal and social interactions & history of physical • aggression • Substance abuse, cognition, and living environment • PTSD and chronic pain • Imaging when history and clinical presentation do not • match

6. Injury Types 1 2 4 3

7. Blast Injuries: What is known? Taber, Warden, and Hurley; J Neuropsychiatry ClinNeurosci 18:2, Spring, 2006

8. Where are the injuries? Subdurals and contusions SDH Contusion

9. Diffuse Axonal Injury (DAI) Normal axon Myelin sheath Cytoskeleton Injured axon

10. metabolic demand cerebral blood flow glucose metabolism Risk of ischemia What are the injuries? Evolution Traumatic brain injury Hemorrhage Release of excitatory amino acids “neurotransmitter storm” Vasospasm More brain injury (Figure adapted from Yi and Hazell, 2006)

12. Emotion and Memory

14. Anatomy of Neurotransmitters:Emotion, Behavior, and Memory

15. www.polytrauma.va.gov • 4 Polytrauma Rehabilitation Centers • (PRC) (5th in process) • 22 outpatient Polytrauma Network • Sites (PNS) • 83 Polytrauma Support Clinic Teams • (PSCT)

16. Mild TBI: Clinical Practice Guidelines • Focus on promoting recovery • Vast majority improve without lasting • effects • Common injury with time-limited, predictable course • Diagnosis is measure of exposure and tells • you nothing about current symptoms • Education of patients and families is best • available recommended treatment • The practice guideline takes the clinician • through each symptom step-by-step for • recommended assessment and treatments. www.healthquality.va.gov

17. Clinical Practice Guidelines:Pharmacologic Treatment • No large double-blinded placebo-controlled studies or FDA-approved medications for chronic symptoms due to TBI. • Medications used are opinions of experts in field • Patients more sensitive to side effects: watch closely for toxicity and drug-drug interactions. • “Rule-out” social factors first**** abuse, neglect, caregiver conflict, environmental issues • No large quantities of lethal meds - suicide rate high! • Full therapeutic trials: under treatment common • Start low- Go slow! www.healthquality.va.gov

18. Medications* • SSRI’s: depression; +/- cognition • Anticonvulsants: mood stabilization and seizure prevention • Atypical Antipsychotics: aggression, agitation, irritability (beta blockers for severe cases) • Dopamine Agonists: cognition, concentration, focus • Cholinesterase Inhibitors: memory • Atypical Agents: Buspirone –emotional stabilization Modafinil –concentration, focus • Minimize benzodiazepines, anticholinergic, seizure-inducing or antidopaminergic agents (impairs cognition; sedation; impedes neuronal recovery) • No caffeine (agitation / insomnia) • No herbal, diet, “energy” products mania, hypertensive crisis, aggression • No lithium – delirium more likely • No MAOI inhibitors – diet noncompliance leads to HTN crisis/stroke • No tricyclics – lethal in overdose • No bupropion for smoking– seizure risk *Recommendations of practitioners in the field. There are no FDA-approved medications for the treatment of psychiatric symptoms from brain injury.

19. Therapy Programs • Multidisciplinary rehabilitation program VA Polytrauma System of care: http://www.polytrauma.va.gov • Initial Education + cognitive/behavioral therapies (includes Video feedback, role play, skills retraining (Owensworth, 1998)) • Long term support - Group psychotherapy Symptom focused: e.g., anger or substance abuse (Delmonico,1998) Process group - Family therapy (Kreutzer, 2002) - Social issues: financial, legal, vocational, education, transportation • National/local support groups and programs - Brain Injury Association: 1-800-444-6443; www.biausa.org

20. Cognitive Rehabilitation Programs Mental Health Service Lines FACT: Functional Adaptation and Cognitive re-Training David Butler; Robin A. Hurley Salisbury NC VAMC and VISN 6 MIRECCC BRAIN BOOSTERS: A Cognitive Enhancement Program Kathleen Goren; Mary Lu Bushnell, Phoenix VA MC CogSMART:Cognitive Symptom Management and Rehabilitation Therapy Elizabeth Twamley, Amy Jak, Kelsey Thomas, & Dean Delis CESAMH, VASDHS

21. Guidance on Work/School Work/school • Discuss with counselor and physician beforehand • Meet with the Disability Office before planning class schedule • Limit work hrs or class schedule at first • On-line classes not recommended at first • Follow suggested guidance on study habits/learning strategies • Ask for help when needed

22. If cognitive issues: adjust PTSD Rx for TBI • Present information at slower pace • For group: do not put “on the spot”; Allow to freely contribute or ask PTSD only to respond 1st; then ask dually dx to respond.  • Use structured intervention approach with agenda, outline, or handouts. • Use refocus/redirection to topic or short sessions with breaks. • Provide a clear transition between topics.  Use agenda, outline, or handout. • The therapist can frustrate the mTBI patient in trying to fully recall an event that was only partially encoded.

23. TBI & PTSD – Military Self Report PTSD Clinician Diagnosis at VA sites: 13%-54% (Seal et al, 2007; Hawkins et al, 2010) 37.8% VA post-deployment clinic (Jakupcak, 2008)

24. PTSD N=232 68.2% Chronic Pain N=277 81.5% 16.5% 2.9% 10.3% 42.1% 12.6% 6.8% 5.3% TBI N=227 66.8% Prevalence of PTSD, mTBI, and Pain • Decreased concentration • Agitation/irritability • Insomnia • Social isolation / detachment • Impaired memory • Affect / Mood disturbances 340 OEF/OIF Veterans evaluated at VA Boston Polytrauma site, Lew et al, JRRD, 2009, 46(6): 697-702.

25. Dilemma Clinicians Now Face • No treatment trials with FDA approved medications for co-morbidities • Current guidance: separate Clinical Practice Guidelines • Management of Post-traumatic Stress • Management of Concussion/mild Traumatic Brain Injury • Pain Management Directive 2009 • Clinicians needed information to guide clinical practice for co-morbidities • TBI-PTSD Consensus Conference held to provide clinical guidance to the field. www.ptsd.va.gov

26. 2009 Practice Recommendations for the Treatment of Veterans with Co-morbid PTSD, mild TBI, and Pain: Diagnosis Provider education Patient/family education Access to treatment Menu of models of care Best practices identified Access Education Systems Assessment/ Treatment Coordinate care Provider incentives Use of resources Comprehensive treatment plans Follow clinical guidelines Measure/monitor Concurrent, collaborative treatments www.ptsd.va.gov

27. Possible Assessment / Treatment Challenges • Key domains may require attention for treatment adjustments: • Partial responders; compliance with treatment • Memory, attention, executive functioning • Hearing loss, pain, balance, sleep • Poly-pharmacy • Substance use / abuse • Develop risk-benefit profile about medications • Med “A” may benefit mTBI symptoms but not help PTSD symptoms www.ptsd.va.gov

28. Off-label Medications for Co-morbid PTSD/TBI: A Balancing Act • Propranolol/Prazosin * PTSD - effective * TBI - may impair working memory/cognition • Methylphenidate/Stimulants * PTSD - may worsen * TBI – improves concentration & focus • Atypical Antipsychotics * PTSD - effective adjunctive agents * TBI - may impair working memory/cognition • TCAs/MAOIs * PTSD - effective for B&D cluster sx * TBI - contraindicated because of anticholinergic effects www.ptsd.va.gov

29. Current Resources Available • Current Clinical Practice Guidelines at www.healthquality.va.gov • TBI-PTSD Consensus Conference Summary: www.ptsd.va.gov/professional/pages/traumatic-brain-injury-ptsd.asp • New Evidence-Based Synthesis Report – Assessment and Treatment of Individuals with History of TBI and PTSD (August, 2009) at www.hsrd.research.va.gov/publications/esp/ • PTSD and mild TBI online course at www.ptsd.va.gov • Information about exemplary programs such as Phoenix, San Diego, and Salisbury available. • MIRECC’s and Centers of Excellence at www.mirecc.va.gov

30. VISN 6 MIRECC: What are we doing about TBI? VISN 6

31. Our MIRECC is organized as a translational medicine multi-site center focused on post deployment mental health issues. The overarching goals are improving clinical assessment and treatment and  development of novel interventions through basic and clinical research. • Research labs include: imaging, neuroscience, neuropsychology, genetics, epidemiology/health services, and clinical interventions. • Research and Clinical hubs are located at the Durham VAMC • Education hub is located at the Salisbury VAMC

32. Investigations of tissue-level mechanisms of primary blast injury through modeling, simulation, neuroimaging & neuropathological studiesJIEDDO, $800,000 annually 2007-2010, Collaboration with MITKatherine Taber and Robin Hurley, VISN 6 MIRECC Objectives: Elucidate tissue and cell-level brain injury mechanisms due to primary blast effectsDevelop validated models of brain response to blast informed with realistic tissue mechanical propertiesCorrelate simulations with neuroimaging and clinical studies on returnees and derive blast TBI injury criteria including pertinent metrics and thresholds.

33. Effects of mild TBI and PTSD on white matter integrity in post-9/11 veterans Raj Morey, VISN 6 MIRECC • Post-9/11 veterans with mild TBI (n=30) and controls (n=42) • Clinical variables : • Age • PTSD • Number of TBI events • Duration of loss of consciousness (LOC) • Feeling dazed and confused • Posttraumatic amnesia Effects of feeling Dazed and Confused RESULTS • Whole brain analysis of primary and crossing fibers measures of white matter integrity. • Widely distributed pattern of white matter differences between mild TBI and non-TBI control group. • Significant association of duration of LOC and feeling dazed and confused with white matter integrity • PTSD did not modulate white matter integrity Morey et al, 2011, under review

34. Before -2 s -1.5 s -1 s -0.5 s During 0 s 0.5 s 1 s Magnetoencephalography (MEG) in PTSD and TBIJared Rowland and Jennifer Stapleton, VISN 6 MIRECCDwayne Godwin, WFSM • Neurocognitive sequelae of mTBI and PTSD. • MEG investigation of effects of PTSD on inhibitory processes and decision making. • Individual and interactive effects of time and probability on the discounting of rewards. • Cognitive processes associated with impaired decision making with & without blast related TBI. Example of imaging information: Absence Seizures

35. www.mirecc.va.gov/visn6/

36. www.mirecc.va.gov/visn6/

37. Together we can make a difference! Thank you!