VISN 6 MIRECC: Mental Illness Research, Education,

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

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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). (Veterans Health Initiative Traumatic
Brian Injury, released April 2010.
http//www.publichealth.va.gov/docs/vhi/traumatic-
brain-injury-vhi.pdf)
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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

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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

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Injury Types
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2
4
3
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Blast Injuries What is known?
Taber, Warden, and Hurley J Neuropsychiatry Clin
Neurosci 182, Spring, 2006
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Where are the injuries? Subdurals and contusions
SDH
Contusion
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Diffuse Axonal Injury (DAI)
Normal axon
Myelin sheath
Cytoskeleton
Injured axon
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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)
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Emotion and Memory
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Anatomy of NeurotransmittersEmotion, Behavior,
and Memory
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www.polytrauma.va.gov

• 4 Polytrauma Rehabilitation Centers
• (PRC) (5th in process)
• 22 outpatient Polytrauma Network
• Sites (PNS)
• 83 Polytrauma Support Clinic Teams
• (PSCT)

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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
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Clinical Practice GuidelinesPharmacologic
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
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Medications

• 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

• SSRIs 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

Recommendations of practitioners in the field.
There are no FDA-approved medications for the
treatment of psychiatric symptoms from brain
injury.
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Therapy Programs

• Multidisciplinary rehabilitation program
• VA Polytrauma System of care http//www.polytrau
  ma.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

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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 CogSMARTCognitive Symptom
Management and Rehabilitation Therapy Elizabeth
Twamley, Amy Jak, Kelsey Thomas, Dean
Delis CESAMH, VASDHS
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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

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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.

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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)
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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.
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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
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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
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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
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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 BD cluster sx
• TBI - contraindicated because of
  anticholinergic effects

www.ptsd.va.gov
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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.go
  v/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.
• MIRECCs and Centers of Excellence at
  www.mirecc.va.gov

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VISN 6 MIRECC What are we doing about TBI?
VISN 6
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• 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

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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
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.
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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 (n30) and
  controls (n42)
• 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
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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
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www.mirecc.va.gov/visn6/
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