regional brain glucose hypometabolism in oif veterans with mtbi elaine r. peskind, md co-director,...
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Regional Brain Glucose Hypometabolism in OIF Veterans with mTBI
Elaine R. Peskind, MD
Co-Director, VISN 20 Mental Illness Research, Education, and Clinical Center (MIRECC)
Friends of Alzheimer’s Research Professor,Department of Psychiatry & Behavioral Sciences
University of Washington School of Medicine
The Controversy
• Controversy about etiology, course, and treatment of persistent somatic, cognitive, and behavioral symptoms in OIF/OEF veterans following mTBI.
• Do these chronic symptoms reflect persistent structural or functional brain damage?
The Controversy (continued)
• An epidemiological study in military personnel found that symptoms of chronic mTBI (except for headache) more correlated with PTSD and depression.
• However, many skilled clinicians are convinced that war combatants’ chronic symptoms of mTBI reflect real albeit subtle persistent brain damage.
Subjects
• 12 male OIF veterans with blast-induced mTBI
» Mean age 32.0 ± 8.5 years (range 24-49)
• 12 cognitively normal community volunteers
» Mean age 53.0 ± 4.6 years (range 49-56; 7M, 5F)
Neurocognitive Assessments
• Alzheimer’s Disease Research Center Uniform Dataset
• University of Pennsylvania Computerized Neurocognitive Battery
• Ruff 2 & 7 Selective Attention Test
• Controlled Word Association Test
• Sentence Repetition
• Wechsler Test of Adult Reading
• Test of Memory Malingering
Neurologic Assessments
• Neurologic exam
• Unified Parkinson’s Disease Rating Scale
• Brief Smell Identification Test
Behavioral Assessments
• Clinician Administered PTSD Scale (CAPS)
• PTSD Checklist – Military (PCL-M)
• Patient Health Questionnaire (PHQ)-9
• Alcohol Use Disorders Identification Test – Consumption (AUDIT-C)
• Pittsburgh Sleep Quality Index (PSQI)
• Neurobehavioral Symptom Inventory (NSI)
Quantification of Cumulative Blast Exposure (QCuBE)
• Numbers of exposures to blast
• Number of episodes of blast-concussion induced loss of consciousness (LOC)
• Date of first, last blast exposure
• History of non-blast head trauma (e.g., sports-related, motor vehicle accident)
Quantification of Cumulative Blast Exposure (QCuBE) - continued
• Intensive characterization of worst 5 exposures» Type of explosive device
» “Tamping” forces
» Distance from blast center
» Tactical details, e.g.:Open air vs. in building or vehicle, head/body position
relative to blastProtective equipmentSecondary, tertiary TBI
» Immediate symptoms
Recruitment/Retention Progress to Date
• 19 OIF veterans with mTBI consented
• 27 more recruited (in past month)
• 14 completed all study measures
• 2 undergoing study procedures
• 1 refused LP
• 1 failed neuropsych effort measures
mTBI Study: Subject Demographics (N = 12)
Mean ± SD Range
Age 32.0 ± 8.5 24-49
Education (yrs.) 13.8 ± 1.9 11-16
Combat Experiences Scale 12.9 ± 1.83 9-15
CAPS 56.67 ± 30.83 0-100
PCL-M 32.33 ± 18.04 5-59
PHQ-9 9.75 ± 8.53 0-25
AUDIT-C 5.58 ± 2.5 1-9
PSQI 9.09 ± 3.14 5-15
TBI Symptom Questionnaire
Ringing in ears 10 Sensitivity to light 4
Forgetfulness 9 Fatigue 4
Feeling anxious or tense 9 Poor coordination 4
Difficulty falling or staying asleep 8 Numbness on parts of body 4
Irritability 8 Loss of balance 3
Sensitivity to noise 8 Vision problems 3
Hearing difficulty 6 Getting into fights 3
Poor frustration tolerance 6 Apathy 3
Mood swings 6 Disinhibition 2
Headaches 6 Feeling dizzy 2
Feeling depressed or sad 6 Change in taste/smell 1
Slowed thinking 6 Slowness in speech 1
Poor concentration 6 Nausea 1
Difficulty making decisions 5 Loss/increased appetite 1
# endorsing moderate-severe symptoms (N = 12)
QCuBE Data (N=12)
Mean ± SD Range
Years since most recent blast 3.5 ± 1.2 2-5
# of blast-related LOCs while deployed 1.0 ± 1.35 0-4
All blasts while deployed to Iraq 13.0 ± 14.0 3-51
Received medical attention in field 2.4 ± 3.7 0-10
Total number of blasts without LOC 28.9 ± 35.4 4-100
# of blast-related LOCs while in military 1.0 ± 1.35 0-4
All military blasts 29.9 ± 35.9 5-102
All LOCs while in military (any cause) 1.5 ± 1.88 0-5
Other non-blast head trauma (# of incidents) 1.7 ± 2.0 0-5
# of times “knocked out” in entire life 1.75 ± 1.76 0-5
Range of Blast Forces
Performance on Standard Neuropsychological Assessments in
mTBI subjects (N=12)
04/19/23 Prazosin/MR 15
Penn Computerized Neurocognitive Battery Accuracy Scores (N=12)
04/19/23 Prazosin/MR 16
Penn Computerized Neurocognitive Battery Speed Scores (N=12)
04/19/23 Prazosin/MR 17
FDG PET and MRI
• Standard brain FDG PET imaging» 10 mCi [F-18]FDG» 3D Image acquisition (GE Advance scanner)
• T1-Weighted and Diffusion Tensor Imaging» 3T MR scanner (Achieva, Philips Medical Systems)» 8 channel sense head coil» 3D MPRAGE T1-weighted scans» Axial DTI of the whole brain, 32 gradient directions» Resting-state fMRI – for functional connectivity» Cross-relaxation imaging of demyelination» T2 FLAIR
Minoshima, et al. J Nucl Med 1995
Composite Z-Score Map of Brain Glucose Hypometabolism in mTBI Subjects (N=12)
Compared to Community Volunteers (N=12)
04/19/23 Prazosin/MR 21
04/19/23 Prazosin/MR 22
Conclusions
• Blast-exposed OIF veterans with chronic mTBI have persistent glucose hypometabolism in cerebellum, pons, thalamus, and medial temporal lobes years after blast exposure
• Cognitive and behavioral/emotional symptoms resemble the “cerebellar cognitive-affective syndrome”
Conclusions
• FDG-PET findings appear to be independent of the presence or absence of PTSD.
• These findings support the hypothesis that regional brain hypometabolism may provide a substrate for chronic mTBI symptoms in blast-exposed combat veterans.
Future Plans
• MRI analysis pending» Diffusion tensor imaging
» Cross-relaxation imaging
» Default state BOLD fMRI
• CSF biomarker measurements pending» Normative sample of >150 controls (age 21-50) already
collected
• Dept. of Defense grant submission
• Iraq deployed control groups: mTBI without PTSD, PTSD without mTBI, neither mTBI nor PTSD
• Longitudinal follow-up
CSF Biomarkers
• Total tau, phospho-tau181
• A42
• neurofilament low molecular mass protein (NFL)
• Brain-derived neurotrophic factor (BDNF)
• F2-isoprostanes
• Interleukin-8
• Beta2-microglobulin
• ? Acute markers: spectrin degradation products, S100, neprolysin
04/19/23 Prazosin/MR 28
Fiber Tracking
Image processing and olfactory tract localization
Winner: Society of Nuclear Medicine Correlative Imaging Council (Walter Wolf) Award