VISN 6 MIRECC:Mental Illness Research, Education, & Clinical Center

Robin A. Hurley, MD, FANPAProfessor, WFUSM

Katherine 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.

Windows To The Brain: Neuropsychiatry of Brain Injury

•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

Today’s Discussion

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)

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

• 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

Post Injury Factors: missed items

Injury Types

1 2

3 4

Blast Injuries: What is known?

Taber, Warden, and Hurley; J Neuropsychiatry Clin Neurosci 18:2, Spring, 2006

Where are the injuries? Subdurals and contusions

SDH

Contusion

Diffuse Axonal Injury (DAI)

Normal axon Myelin sheath

Cytoskeleton

Injured axon

What are the injuries?Evolution

Traumatic brain injury

Release of excitatory amino acids “neurotransmitter storm”

Hemorrhage

Vasospasm

More brain injury

(Figure adapted from Yi and Hazell, 2006)

metabolic demand

Risk of ischemia

glucose metabolismcerebral blood flow

Emotion and Memory

Anatomy of Neurotransmitters:Emotion, Behavior, and Memory

www.polytrauma.va.gov• 4 Polytrauma Rehabilitation Centers

(PRC) (5th in process)

• 22 outpatient Polytrauma Network Sites (PNS)

• 83 Polytrauma Support Clinic Teams (PSCT)

Mild TBI: Clinical Practice Guidelines

www.healthquality.va.gov

• 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.

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

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.

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

Cognitive Rehabilitation Programs Mental Health Service Lines

FACT: Functional Adaptation and Cognitive re-TrainingDavid Butler; Robin A. Hurley Salisbury NC VAMC and VISN 6 MIRECCC

BRAIN BOOSTERS: A Cognitive Enhancement ProgramKathleen Goren; Mary Lu Bushnell, Phoenix VA MC

CogSMART:Cognitive Symptom Management and Rehabilitation TherapyElizabeth Twamley, Amy Jak, Kelsey Thomas, & Dean DelisCESAMH, VASDHS

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

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.

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)

Prevalence of PTSD, mTBI, and Pain

PTSD N=23268.2% 2.9%

16.5%

42.1% 6.8%

5.3%

10.3%

12.6%

TBI N=22766.8%

Chronic Pain N=27781.5%

340 OEF/OIF Veterans evaluated at VA Boston Polytrauma site, Lew et al, JRRD, 2009, 46(6): 697-702.

• Decreased concentration• Agitation/irritability• Insomnia• Social isolation / detachment• Impaired memory• Affect / Mood disturbances

Dilemma Clinicians Now FaceDilemma 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

2009 Practice Recommendations for the Treatment of Veterans with

Co-morbid PTSD, mild TBI, and Pain:

SystemsSystems

EducationEducation

Assessment/Assessment/TreatmentTreatment

Coordinate careProvider incentives Use of resources

Comprehensive treatment plansFollow clinical guidelinesMeasure/monitorConcurrent, collaborative treatments

Diagnosis Provider educationPatient/family education

Access to treatmentMenu of models of careBest practices identifiedAccessAccess

www.ptsd.va.gov

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

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 effectswww.ptsd.va.gov

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

VISN 6 MIRECC: What are we doing about TBI?

VISN 6

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

Objectives:

Investigations of tissue-level mechanisms of primary blast injury through modeling, simulation, neuroimaging & neuropathological studies

JIEDDO, $800,000 annually 2007-2010, Collaboration with MITKatherine Taber and Robin Hurley, VISN 6 MIRECC

Elucidate tissue and cell-level brain injury mechanisms due to primary blast effects

Develop validated models of brain response to blast informed with realistic tissue mechanical properties

Correlate simulations with neuroimaging and clinical studies on returnees and derive blast TBI injury criteria including pertinent metrics and thresholds.

Effects of feeling Dazed and Confused

• 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

• 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 mild TBI and PTSD on white matter integrity in post-9/11 veteransRaj Morey, VISN 6 MIRECC

Morey et al, 2011, under review

RESULTS

y=20 y=-20 y=-40 y=-60 y=-80y=0

y=40 y=20 y=0 y=-20 y=-40

y=40 y=20 y=0 y=-20 y=-60y=-40 y=-80

Effects of Loss of Consciousness

TBI vs. controls

y=20 y=-20 y=-40 y=-60 y=-80y=0

y=40 y=20 y=0 y=-20 y=-40

y=40 y=20 y=0 y=-20 y=-60y=-40 y=-80

Effects of Loss of Consciousness

TBI vs. controls

Magnetoencephalography (MEG) in PTSD and TBIJared Rowland and Jennifer Stapleton, VISN 6 MIRECC

Dwayne 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.

-2 s -1.5 s -1 s -0.5 s

0 s 0.5 s 1 s

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Example of imaging information: Absence Seizures

www.mirecc.va.gov/visn6/

www.mirecc.va.gov/visn6/

Together we can make a difference!

Thank you!