Elaine R. Peskind, MD 

Co-Di t rec

t

or 

VISN 20 Mental Illness Research, Education, and 

Center 

( ) MIRECC

)

Friends of Alzheimer’s Research Professor 

D t t f P hi t & B h i l S i Depar

tmen

t of 

Psychi

a

try & 

B

e

havioral S

cienc

University of Washington School of Medicin

Staff Psychiatrist, Joint Base Lewis McChord, Taco
3.5 million Soldiers and Marines have been deployed to I

Afghanistan; approximately 9 Afghanistan; approximately 

9

-18% return with symptomat

18% return with symptomat
NFL Pro-Bowl 1988

Photo provided to Bostonian (Winter/2009) by Virginia Grimsley Mc

McKee et al., J Neuropathol Exp Neurol 68:709-735, 2009
Goldstein et al., Sci Transl Med. 2012 May ; ( ) y 16;4(134):134ra60.
Tau pathology in the brain of a

27 year old Iraq Veteran

Photomicrographs of tau-immunostained section of the frontal cortex showing frequent neuroand neuritic threads (Omalu et al, Neurosurg Focus 31:E3, 2011). 
•Repetitive sports concussion is ass

Repetitive sports concussion is ass

with increased risk of the mid-lif

dementing disorder chronic traumatdementing disorder, chronic traumat

encephalopathy (CTE) 

•T i raumatic b rai n i nj (TBI) jury (TBI) i 

s curre

best characterized environmental ris

f d l i h for developing the late-life 

dementing disorder, Alzheimer’s dis
• Controversy about etiology, course, 

Controversy about etiology, course, 

treatment of persistent somatic, cog

and behavioral symptoms in Iraq anand behavioral symptoms in Iraq an

Afghanistan Veterans following mTB

• An epidemiological study in military An epidemiological study in military 

personnel found that symptoms of c

mTBI (except for headache) more mTBI (except for headache) more 

correlated with and 
• However many skilled clinicians are However, many skilled clinicians are 

convinced that war combatants’ chro

symptoms of mTBI reflect real albeit symptoms of mTBI reflect real albeit 

persistent brain damage. 

• Do these chronic symptoms reflect 

persistent changes in brain 

and/or cerebrospinal fluid 

biomarkers of neurodegeneration? 
-

• 34 male Iraq/Afghanistan Veterans with 

induced mild traumatic brain injury 

– Mean age 31.6 ± 9.2 years 

• 16 non blast 16 non blast -exposed Iraq/Afghanistan V

exposed Iraq/Afghanistan V

– Mean age 32.8 ± 7.3 years (15M, 1F) 

• 12 civilian community controls – FDG-P

– Mean ag e 53 ± 2.0 y ( , ) ears (7M, 5F)

• 55 male civilian community controls – C

– Mean age 31.8 ± 6.8 years 
t t

• 17 f th TBI V t l t DSM 17 of the mTBI Veterans also met DSM-

(via CAPS interview) for combat operatio

posttraumatic stress disorder (PTSD) posttraumatic stress disorder (PTSD). 

• The mTBI group had higher scores for d

and alcohol use and had poorer sleep and alcohol use and had poorer sleep. 

• Nearly all the mTBI Veterans had persist

postconcussive symptoms. 
Forgetfulness 

Feeling anxious or tense Difficulty falling or staying asleep Difficulty falling or staying asleep Ringing in ears Irritability Headaches Sensitivity to noise Poor concentration/attention Hearing difficulty Slowed thinking Slowed thinking 

TBI (N=33)

67 %

67 %

64 % 

64 % 

61 % 

61 % 

58 % 

52 % 

52 % 

52 % 

Control (N=15)

20 %

13 %

13 %

0

13 %

7 %

0

13 %

0

13 %
t t t

t

• A i i Average time since l ast bl 4 ast exposure was 4 yea

• The average number of blast exposures resulting 

consciousness was 1. consciousness was 1. 

• Majority had repetitive mTBI. Average number of b

exposures in Iraq or Afghanistan in the mTBI grou

– single blast-mTBI 9% – 2-5 blast mTBIs 29.4% – 6-10 blast mTBI s 20 6%. – 11-15 blast mTBIs 6% – 16-20 blast mTBIs 20 blast mTBIs 14 7%.– 21-50 blast mTBIs 9% – 51 -100 blast mTBIs 100 blast mTBIs 11.8% 
t t

• Structural Neuroimaging Structural Neuroimaging 

– Diffusion Tensor Imaging – M l acromolecul ar P F roton Fracti on (MPF

Mapping 

• Functional Neuroimaging: 

– [18F]-Fluorodeoxyglucose Positron Em

Tomography ([18F]-FDG-PET) 
• Magnetic Resonance (MR) Diffusion Tens

Imaging Imaging 

– Levin et al., NeuroImage, 2010 – MacDonald et al MacDonald et al., New England Journa

New England Journa

Medicine, 2011 

– Davenport et al Davenport et al., Neuroimage Neuroimage, 2012 – Morey et al., Human Brain Mapping, 20– Bazarian et al., J Head Trauma Rehab
Diffusion Tensor Imaging: 

Composite Z-score subtraction maps of FA values 

mTBI Veterans (N=15) compared to mTBI Veterans (N=15) compared to 

Nonblast Veterans (N=12) 

RESULTS: RESULTS:• Decreased fractional anisotropy in genu of corpus callosum in mTcompared to Nonblast Veterans (p <0.05) •Within mTBI group, no differences between Veterans with and wit

Within mTBI group, no differences between Veterans with and wit

•DTI studies in Iraq/Afghanistan Veterans vary among labs – both iand Results 
Macromolecular Proton Fraction (MPF) Ma

Macromolecular Proton Fraction (MPF) Ma

• Are there other structural MRI technique

Are there other structural MRI technique

may be more sensitive to chronic chang

following blast concussion mTBI? following blast concussion mTBI? 

• MPF is a magnetization transfer structur

imaging technique which provides an indimaging technique which provides an ind

macromolecular composition. 

• MPF correlates with indices of central m

MPF correlates with indices of central m

integrity in humans and in animal modelmultiple sclerosis and spinal cord injury. 
Magnetization Transfer Molecular Proton Bound Frac

Z-score subtraction maps of MPF values in Blast-mT

(N 27) d t (N

=27) compared 

to N bl t Nonblast V t (N 

V

e

terans (N

=

RESULTS: Reduced MPF in numerous subgyral, cortical-subcortical, and longitumatter (WM) tracts (Zs>4.0, all p’s <0.05) •Within mTBI group, no differences between Veterans with and witho•Findings consistent with the mechanism of and 

in white matter tracts known to be vuln

d i amage in diff l diffuse axonal i njury. 

as prospective quantitative biomarker of blast-induced mTB
Fluorodeoxyglucose-Positron Emission Tomography (

Composite Z-score subtraction maps of regional bra

metabolism in Blast metabolism in Blast

-mTBI Veterans (N=33) mTBI Veterans (N=33) 

vs. Nonblast Veterans (N=16) 

RESULTS: 

• Regional glucose hypometabolism in parietal lobes bilaterally, left cortex and right visual cortex in mTBI Veterans (all p’s < 0.05) •Within mTBI group, no differences between Veterans with and with
FDG-PET: Composite Z-score subtraction maps of region

glucose metabolism in Blast-mTBI Veterans vs. civilian cont

and Nonblast Veterans vs civilian controls Veterans vs. civilian controls 

RESULTS: • Compared to civilian community controls, both Blast-mTBI and N

Veterans have glucose hypometabolism in the cerebellum, pons, thmedial temporal lobes bilaterally (all p’s < 0.05). 
*p<0.0005, one-way ANOVA 
• Hypotheses/Speculation about etiology: 

– Pre 

-military (and post military (and post 

-military) vulnerabilities a

military) vulnerabilities a

“lifestyle

” (including other head trauma, alcoho

bodybuilding supplements) 

– Eff t f ilit t i i ( b ti ) Effec

ts o

f military 

training 

(e.g., com

b

atives) 

– Hyperthermia in Iraq combat operations enviro– Other environmental/behavioral combat zone 

including stress 

– High % of Non High % of Non

-blast Veterans with APOE blast Veterans with APOE

-

4 a

4 a
• Both structural and functional imaging modalities 

a coherent picture of in I /Af h i t V t ith bl t ( d i tIraq/Af

g

hanis

tan 

V

e

terans with blas

t

(an

d impact

concussion mTBI specific to TBI and not attributaPTSD.

• Unexpected brain abnormalities in Iraq and Afgh

Veterans inde

p p endent of head trauma ex

posure

– Glucose hypometabolism in cerebellum, pons, thalamu

temporal lobes 

– Elevation in CSF 

p-tau181p :tau ratio suggests 

possible 181 gg p

neurodegenerative changes

• Lon

g-term conse

quences of these brain abnorm

make long-term follow-up of these Veterans esse
– Murray Raskind, MD

– Eric Petrie, MD – Donna Cross, Ph– Kathleen Pagulayan, PhD

– Jim Leverenz, MD

– Cynthia Mayer, DO

– Satoshi Minoshim– Vasily Yarnykh, P

Cynthia Mayer, DO – Natalia Kleinhan

– Kim Hart, PA-C– David Hoff, PA-C

J Sh f MS

Natalia Kleinhan

– Todd Richards, P– Raimondo D’Am

– Jane Shofer, MS– Bertrand Russell Huber, MD, 

PhD

– Tom Montine, MD

– Jing Zhang, MD

– Nathalie Martin, 

David Cook PhD

• Bennett Risk, 

– Ray Bennett, P

– David Cook, PhD– Charles Wilkinson, PhD– Chang-En Yu, PhD
–Command Sg j( ) t Maj (ret) Thomas Adam

–Command Sgt Maj Robert Prosser–First Sgt (ret) Creed McCaslin First Sgt (ret) Creed McCaslin

Biomarker)discovery)through)neurobehavioral,)

neuropathological)and)molecular)

characteriza9on)of)mouse)models)of)TBI))

Fiona&Crawford,&Ph.D.&

Associate&Director,&Roskamp&Ins;tute&

Sarasota, Florida 
Roskamp Institute 

Traumatic Brain Injury research program

Neurobehavior 

Neuropathology 

Rodent models 

of TBI:– 

CCI; mild TBI 

Molecular 

profiling of 

brain tissue 

and blood 

Identify and 

validate 

molecular targets 

and biomarkers 

Deliverables: 

•TBI-targeted 

therapeutics 

• Diagnostic 

and prognostic 

markers 

Active military 

TBI patients 

Blood 

biomarker 

profiling 
 Controlled Cortical Impact – CCI 

 APOE genotype 

 Mild Closed Head Injury TBI model - mTBI

 Single injury 

 Repetitive injury (5 hits over 9 days with 

 an inter-injury interval of 48hrs) 

Mouse Models 
CCI&and&APOE&

• ApoE&has&3&main&isoforms&@&ApoE2,&ApoE3,&ApoE4&

• Human&APOE4&carriers&show&poorer&acquisi;on&and&recall&

following&TBI&compared&to&those&without&an&APOE4&allele&

(Crawford&2002,&Friedman&1999,&Sabo&2000,&Smith&2006)&

• Used&LC@MS&approaches&to&compare&brain&and&plasma&

proteomic&profiles&of&mice&transgenic&for&human&APOE3&and&

APOE4&over&a&null&background&at&mul;ple&;me&points&post@TBI

• Extensive&and&complex&datasets&–&focus&on&APOE&influence&on&

TBI&profiles&–&the&INTERACTIVE&term&–&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

to&determine&favorable&versus&unfavorable&responses&to&TBI&
Proteomic&Analysis&

• Samples&were&collected&from&APOE&transgenic&mice&at&

mul;ple&;mepoints&a\er&CCI&

– Severe&and&mild&injuries&(1.8mm&depth&or&1.3&mm&depth&at&5m/s)&

– 24&hours,&1&month,&and&3&months&(severe&only)&a\er&surgery&

– Plasma&and&ipsilateral&Hippocampus&and&Cortex&were&analyzed&

• We&used&iTRAQ&labeling&to&enable&quan;ta;ve&as&well&as&

qualita;ve&proteomic&profiling&

• Sta;s;cal&analyses&were&used&to&determine&the&differen;al&

response&of&APOE3&and&APOE4&to&TBI&

• Ingenuity&Pathway&Analysis&was&used&to&aeribute&func;onal&

significance&to&the&observed&proteomic&responses&
Plasma&Datasets&&

(Crawford,&J&Neurotrauma&2011)&

Func;onal&Clustering&(1)&
Func;onal&Clustering&(2)&
Mouse&–&Human&transla;on&

Detailed characterization of behavior, brain pathology and plasma profiles 

in mouse models at a range of timepoints after injury 

Time since TBI 

Correlation of plasma profiling in mouse 

models with human plasma profiling 

will identify diagnostic and potentially 

prognostic biomarkers for TBI. 

By relating human plasma to mouse 

plasma to mouse brain we may be 

informed regarding ongoing pathogenic 

processes in the human brain. 

Plasma 

profiling in 

human 

samples 
mTBI&model&

(Mouzon&J&Neurotrauma&2012)&

• Greater&relevance&to&human&condi;ons&

• Mild&but&progressive&pathology&

• Axonal&injury,&inflamma;on,&developing&tau&pathology&

• Acute&cogni;ve&deficits&in&both&single@mTBI&and&

repe;;ve@mTBI&models&compared&to&anesthesia&

controls&

• Persistent&cogni;ve&deficits&in&repe;;ve@mTBI,&

analyses&to&date&show&impaired&Barnes&Maze&

performance&at&18&months&post&injury.&
6 months 

after last 

injury 

0&

5&

10&

15&

20&

25&

30&

35&

s=sham) r=sham) s=mTBI) r=mTBI)

Mean)9me)to)zone)(s))

s=sham) r=sham) s=mTBI) r=mTBI)

s=sham) r=sham) s=mTBI) r=mTBI)

0&

5&

10&

15&

20&

25&

30&

35&

s=sham)r=sham)s=mTBI)r=mTBI)

Mean)9me)to)zone)(s))

* 

* 

* 

* 

* 

24 hours 

after 

last 

injury 

12 

months 

after last 

injury 

18 months 

after last 

injury 

Novel mTBI model shows persistent 

cognitive problems after repetitive injury 
Tau&pathology&(CP13)&in&the&CA1&&

in&the&repe;;ve&mTBI&model&
s-sham s-mTBI r-mTBI 

CA1 CA3 CORTEX

Increased CP13 in r-mTBI hTau mice 24hrs post TBI 
Plasma&lipidomic&analyses&in&the&&

wild&type&mTBI&model&at&24hrs&post@TBI&
Plasma&lipidomic&analyses&in&the&&

wild&type&mTBI&model&12&months&post@TBI&
Ac;ve&Duty&Troop&study&

(Captain/Dr.&Michael&Dretsch&at&USAARL)&

• 470&troops&recruited&through&Ft.&Riley&and&

Camp&Shelby&–&full&neuropsychological&

assessment&and&blood&samples&for&gene;c&and&

omic&analyses&

• Pre@&and&Post@deployment&evalua;ons&

• Pilot&data&in&a&cohort&of&50&troops&to&detect&

deployment&related&changes&in&plasma&

profiling&correla;ng&with&clinical&grouping&
Pilot&blood&profiling&from&troops&&

pre@&and&post@&deployment&reveals&changes&in&

&lipid&species&specific&to&clinical&subgroups&

0&

20&

40&

60&

80&

100&

120&

140&

160&

180&

200&

Post@deployment&as&%&of&pre&deployment&

PC(32:1))

Control&n=22&

PTSD&n=10&

TBI&n=13&

TBI+PTSD&n=5&

*&

&&&Control&&&&PTSD&&&&&TBI&&&&&&TBI+PTSD&

0&

20&

40&

60&

80&

100&

120&

140&

160&

Post@deployment&as&%&of&pre&deployment&

PC(32:2))

*&

&&&Control&&&&PTSD&&&&&TBI&&&&&&TBI+PTSD&

0&

20&

40&

60&

80&

100&

120&

140&

Post@deployment&as&%&of&pre&deployment&

PC(34:4))

*&

&&&Control&&&&PTSD&&&&&TBI&&&&&&TBI+PTSD&

0&

50&

100&

150&

200&

250&

Post@deployment&as&%&of&pre&deployment&

PC(36:5))

*&

&&&Control&&&&PTSD&&&&&TBI&&&&&&TBI+PTSD&
Conclusions&

• Mul;@disciplinary&approaches&are&essen;al&to&tackle&the&

complexity&of&TBI&and&aeempt&transla;on&from&

laboratory&models&to&humans;&

• Detailed&characteriza;on&of&laboratory&models&of&TBI&will&

provide&a&more&complete&understanding&of&pathogenesis&

and&a&planorm&for&transla;on&of&biomarkers&and&

poten;al&therapeu;cs&to&human&popula;ons;&

• Omics&technology&is&a&powerful&tool&with&which&to&

iden;fy&molecular&signatures&of&TBI;&

• &Immune,&inflammatory&and&lipid&pathways&are&

significantly&disrupted&in&response&to&TBI;&

• Plasma&and&brain&molecular&responses&to&TBI&progress&

and&persist&a\er&the&injury,&affording&larger&detec;on&

and&therapeu;c&windows&than&originally&an;cipated.&
Acknowledgments&

Funding: 

VA Merit award (Crawford) 

Department of Defense awards 

W81XWH-07-1-0700 and 

W81XWH-10-1-0759 (Crawford) 

MOMRP (Dretsch) 

Roskamp Foundation 

Dr. Michael Dretsch and his team at 

USAARL, Ft. Rucker, 

Alabama 

Dr. Gogce Crynen Jon Reed 

Benoit Mouzon Dr. Scott Ferguson 

Jim Evans Dr. Laila Abdullah 

Dr. Corbin Bachmeier Alex Bishop 

Hannah Montague Robert Pelot

Benjamin Katz Helena Chaytow 

 Dr. Michael Mullan 

Dr. Risa Richardson Dr. Rodney Vanderploeg 

Jill Massengale Dr. Marissa McCarthy 

 Dr. Steven Scott 
Diag g nosin Residu

Brain Injury followi

mTBI among O /O IF 

Veterans

Robert L. Ruff, MD, PhDRonald G Riechers, MDSuzanne S Ruff, PhD Suzanne S Ruff, PhDLouis Stokes Cleveland VAM
Financial Disclosure 

Drs. RL Ruff, RG Riechers and SS Ruff hafi i l di l financial disclosures

Drug/Product Off-Label Use Disclo

None

Grant Support

This presentation is supported in part b

y 

obt i d f Pil t St d t d b 

bt

aine

d

from a Pil

o

t St

u

dy suppor

t

e

d

by 

Center of Excellence Grant from VHA OffRehabilitative Research and Developmen

Any opinions or conclusions presented aAny opinions or conclusions presented a

those of the author and do not necessarireflect those of the Department of VeteraAffairs.
• Combat mild TBI in OIF/OEF is often asso

Background

Combat mild TBI in OIF/OEF is often asso

with PTSD , neurological deficits, impaireand pain (headache) 

• There can be confusion between having 

(historical diagnosis) and having residua

from a TBI (important to VBA)

• Epidemiological connection between mT

PTSD

• Questions – 1) What is the most sensitive 

exam t t f id l d fi it f test for residual deficits from a mTB

• 2) How Can CNS damage predispose to P
2091 OIF/OEF

veterans

Initial screen18 4%. +

385

A t2 d l l Study Group Agree to 2nd level

screen - 90.9%

350

126 Veterans6% of initial group

2nd level

Screen + 60%

Clinician-confirmed Combat mTBI and ≥ 

70.1%

210

Agree to 

178

Further Eval -84.8%
A - OIF/OEF mTBI + LOC Group (n=

B

- OIF/OEF OIF/OEF mTBI w/o LOC Group (

w/o LOC Group (

C - OIF/OEF injury w/o TBI (n=52)D - Ci ili ith Ci

vilians with mTBI + LOC ( 21

+ LOC

(n=21

E - Civilians without TBI (n=21)• N l i l i ti i l d d tit 

Neurological examination inclu

d

e

d a quantit

olfaction test (BSIT-12, Sensonics, Haddon 

• PTSD severity assessed by PCL PTSD severity assessed by PCL

-

M

• Montreal Cognitive Assessment test (MOCA

sleepiness scale (ESS) headache pain levesleepiness scale (ESS), headache pain leve

from 0 to 10 and number of headaches/mon

• mTBI + LOC

- Neurological Deficits: olfactio

Neurological Deficits: olfactio

balance – 14, eye movements – 13, motor – sensor

y

– 2.
Frequencies of abnormalities on neurological testing, PTSD and 

Probabilities for comparisons to veterans who had mTBI + LO

Patient Group Deficit on 

Neurological 

Neurological Deficits other than 

PTSD 

Examination olfaction 

Combat mTBI & LOC 65 (52%) 65 (52%) 29 (23%) 29 (23%) 83 (6

83 (6

Combat mTBI w/o LOC 0 (0%) 0 (0%) 2 (9.5Combat w/o TBI 0 (0%) 0 (0%) 5 (9.6Civilian mTBI & LOC 2 (9.5%) 1 (4.8%) 1 (4.8Civilian w/o mTBI 0 (0%) 0 (0%) 0 (0%
Olfaction severity r

of episodes of mTB

PTSD severity relate

f episodes of mTB

PTSD severity relateepisodes of mTBI wCognitive performanrelated to # episoderelated to

# episode

with LOC 

The likelihood of PTS

related to # episodes 

with LOC
Olfactory Dysfunction

• Regional Vulnerability•

Alcohol swab not acce

ptable

• http://sensonics.com/ Neuro Deficit 

O act o lfactio

n 

Balance Eye movements M t o

tor 

Sensory 
Amygdala and VMpfc

Associated with PTSD

• Model

–

– PTSD associated with dysregulated am

activity

– VMpfc and to a lesser extent hippocam

regulate amygdala activity

– VMpfc regulation of amygdala is comp

not 

py y urel

y inhibitor

y

– Damaging the amygdala/VMpfc interac

can facilitate PTSD 

genesis

– Obliterating amygdala or both pfc can 

against PTSD (block the emotional exc
Anatomic Relationships Anatomic Relationships
Ψ Stress Alters VMpfc an

A dl myg a a neuron st t ruc u

The Journal of Neuroscience 2002 Neuroscience, 2002, 

22(15):6810–6818Chronic Stress Induces Contrasting Patterns of Dendritic Remodeling in 

Hippocampal and Amygdaloid Neurons A Vyas, R Mitra, S Rao, S Chattarji

PNAS June 28, 2005 vol. 102 no. 26 

J. J. Radley et al. / Neuroscience 125 (2004) 1–6 (pfc pyramidal cell)
PTSD: Amygdala & pfc

Arch Gen Psychiatry. 2012 69(4) 360 371

Psychiatry Res. 2009 June 30; 172(3): 2Pediatric PTSD – MRI study – note parti

2012;69(4):360-371Women with PTSD due to Partner violence - fMRI
Damage to Amygdale Damage to Amygdale

↓PT

Koenigs M, Huey ED, Raymont V, Cheon B, Solomon J, Wassermann EM. Focal protects against post-traumatic stress disorder in combat veterans. Nat Neurosci 
Damage to superior Damage to superior pfc

↓P
Role of TBI in PTSD Gene
•Warden DL. Military TBI during the Iraq and Afghanistan wars. J. Head Trauma R

2006;21:398-402.•Lew HL Lin P

H Fuh

J L Wang S J Clark DC Walker WC Characteristics and 

Selected References

•Lew HL, Lin

P-H, Fuh

J-L, Wang

S-J, Clark DC, Walker WC. Characteristics and 

Headache After Traumatic Brain Injury: A Focused Review. Am. J. Phys. Med. Re2006;85:619-627.•Theeler BJ, Erickson JC. Mild head trauma and chronic headaches in returning 

Headache 2009;49(4):529 Headache 2009;49(4):529-534.

•Ruff RL, Ruff SS, Wang X-F. Headaches Among Veterans of Operations Iraqi FrEnduring Freedom with Mild Traumatic Brain Injury Associated with Exposures to 2008;45:941-953.

•Doty RL Olfaction Ann Rev Psychol 2001;52:423 Doty RL. Olfaction. Ann. Rev. Psychol. 2001;52:423-452.

•Ruff RL, Riechers RG, Ruff SS. Relationships between mild traumatic brain injurcombat and post-traumatic stress disorder. F1000 Medicine Reports 2010;2:64. http://www.ncbi.nlm.nih.gov/pubmed/21173852

•Raskind MA Peskind ER Hoff DJ Hart KL Holmes HA Warren D et al A para

Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren

D, et al. A para

controlled study of prazosin for trauma nightmares and sleep disturbance in compost-traumatic stress disorder. Biol. Psychiatry 2007;61:928-34.•Gironda RJ, Clark ME, Ruff RL, Chait S, Craine M, Walker R, et al. Traumatic Br

Polytrauma, and Pain: Challenges and Treatment Strategies for the and Pain: Challenges and Treatment Strategies for the Polytrauma Polytrauma R

R

Network. Rehabil. Psychol. 2009;54(3):247-258.

•Peskind ER, Petrie EC, Cross DJ, Pagulayan K, McCraw K, Hoff D, et al. Cerebhypometabolism associated with repetitive blast exposure mild traumatic brain inj

Veterans with persistent post Veterans with persistent post-concussive symptoms concussive symptoms. NeuroImage NeuroImage 2011;54 ( 2011;54 (Supp

•Ruff RL, Riechers RG, Wang X-F, Piero T, Ruff SS: A Case-Control Study ExamNeurological Deficits and PTSD in Combat Veterans Are Related to Episodes of MOpen Mar 18;2(2):e000312, 2012, PMID: 22431700 doi:10.1136/bmjopen-2011-
Thank You and Questions

Robert L. Ruff, MD, PhDR ld G Ri h MD Ronald

G Riec

hers, MD

Suzanne S. Ruff, PhDCleveland Dept of Veterans Affairs MediCleveland OH 44106 Cleveland OH 44106rob t ff1@ ber

t.ruff1@va.gov

ronald.riechers@va.gov

suzanne.ruff2@va.gov