Title: Complexities of War Related Illnesses and Injuries Diagnosis: Multiple Unexplained Symptoms, Assessment of Traumatic Brain Injury (TBI)
1Complexities of War Related Illnesses and
Injuries Diagnosis Multiple Unexplained
Symptoms, Assessment of Traumatic Brain Injury
(TBI)
- J. Wesson Ashford, M.D., Ph.D.
- Director, War Related Illness and Injury Study
Center, - VA Palo Alto Health Care System
- Clinical Professor (affiliated), Department of
Psychiatry and Behavioral Sciences, Stanford
University
2Problems of War-Related Illnesses
- After every war, a particular group of illnesses
or symptoms appears to stand out as the
signature illness of that conflict. - It is frequently uncertain what the cause of the
symptoms are. - No matter what, it is the obligation of the
treating doctors to address the concerns of the
Veterans.
3Gulf WarAugust 1990-June 1991
- 697,000 U.S. troops deployed to the Persian Gulf
- Few battle casualties
- After deployment, Veterans reported many health
problems that they attributed to their
participation in the Gulf War. - Estimates suggest 100,000 have had diffuse
symptoms since returning, now referred to as Gulf
War Illness
4Summary of the Offensive Ground Campaign
5Gulf War I and Health
- Troops were potentially exposed to
- Sand
- Smoke from oil-well fires
- Paints
- Solvents
- Insecticides insect bites
- Petroleum fuels and their combustion products,
- Organophosphate nerve agents,
- Pyridostigmine bromide (PB)
- Depleted uranium (DU)
- Anthrax botulinum toxoid vaccinations
- Infectious diseases
- Psychological and physiological stress
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6Common Illnesses/Complaints
- Fatigue
- Persistent Headaches
- Muscle Aches/Pains
- Neurological Symptoms e.g. tingling and numbness
in limbs - Cognitive Dysfunction - short term memory loss,
poor concentration, inability to take in
information - Mood and Sleep Disturbances - Depression,
Anxiety, Insomnia. - Dermatological Symptoms - Skin Rashes, Unusual
Hair loss. - Respiratory Symptoms - Persistent Coughing,
Bronchitis, Asthma - Chemical Sensitivities
- Gastrointestinal Symptoms - Diarrhea,
Constipation, Nausea, Bloating. - Cardiovascular Symptoms
- Menstrual Symptoms
7Less-Common Illnesses
- Infertility/Miscarriage/Birth Defects
- Amyotrophic lateral sclerosis (ALS (Lou Gehrigs
Disease)) - Brain Cancer
- Multiple Sclerosis
- Lupus
4/3/2015
8Frequency of Symptoms
- 53,835 Participants in VA Registry (19921997)
- Symptom Percentage
- Fatigue 20.5
- Skin rash 18.4
- Headache 18.0
- Muscle and joint pain 16.8
- Loss of memory 14.0
- Shortness of breath 7.9
- Sleep disturbances 5.9
- (Continued)
- .
9Frequency of Symptoms (cont.)
- Symptom Percentage
- Skin and subcutaneous tissue 13.4
- Digestive system 11.1
- Chest pain 3.5
- Musculoskeletal and connective tissue 25.4
- Mental disorders 14.7
- Respiratory system 14.0
- SOURCE Murphy et al., 1999
10Clinical Findings in Gulf War Veterans with
Multiple Unexplained Symptoms
- Somatic Medical - normal x-rays of joints
- Neurological -
- peripheral electrophysiological abnormalities
- normal MRI scans
- abnormal SPECT, MR spectroscopy
- Psychiatric -
- depression
- neuropsycological dysfunction - borderline
11Is Gulf War Illness real?
- Could it be due to compensation neurosis?
- Could it be a conspiracy among Gulf vets?
- Could it be mass hysteria? (like other wars)
- Could functional brain changes be induced by
psychological phenomena? - Is there a relation to chronic fatigue syndrome,
fibromyalgia, multiple chemical sensitivity?
12Gulf War I and Health
- Institute of Medicine (IOM) conducted a review of
the scientific literature - Published 9 volumes and reported on the strength
of the scientific evidence concerning the
association between health effects and the
chemical and biological compounds that were
likely present during the Gulf War.
13Gulf War I and Health Volumes 1 - 8
- Reports on status of research on
- Depleted Uranium, Sarin, Pyridostigmine Bromide,
and Vaccines - Volume 1 - Insecticides Solvents - Volume 2
- Fuels, Combustion Products, Propellants -
Volume 3 - Health Effects of Serving in the Gulf War -
Volumes 4 8 - Infectious Disease - Volume 5
- Physiologic, Psychologic, and Psychosocial
Effects of Deployment-Related Stress - Volume 6 - Long-term consequences of Traumatic Brain Injury
- Volume 7
14Potential Contributors
- Chemical Weapons and other chemical exposures
- Sarin and Cyclosarin, Pyridostigmine Bromide,
Organophosphate Pesticides, other chemical
pesticides, CARC - Chemical Agent Resistant
Coating, fuel, decontamination solution, oil fire
smoke (note, no sarin deaths observed) - Infectious Diseases (occult)
- Leishmaniasis, travelers diarrhea, sandfly fever,
Q fever, malaria, and viscerotrophic
leishmaniasis found in 12 U.S. Veterans, exotic
normal flora - Multiple vaccinations
- Anthrax vaccine containing squalene as an
adjuvant - Depleted Uranium (possible heavy-metal toxicity
no cases ever seen) - Aspartame/Methanol Poisoning
- At 85 F, aspartame breaks down into methanol
which then breaks down into formaldehyde - Biological Weapons
- mycoplasma fermentans may be combined with part
of the AIDS virus
15Possible Chemical Weapon Exposure - Sarin
- Sarin was known to be in the possession of the
Iraqis - Sarin depots were bombed by the US and sarin
plumes were produced (like a terrorist booby
trap) - Sarin can produce many of the symptoms and
neuro-electrophysiologic changes seen in Gulf
Veterans - Similar findings occurred in the Tokyo subway
victims in 1995 (though many had sx of hypoxia) - Pyridostigmine could block peripheral receptors,
shunting sarin into the unprotected brain! - There were no obvious sarin-related deaths (?
rules out)
16Gulf War Veteran SPECT Scans
- Single Photon Emission Computed Tomography
SPECT - SPECT scans show blood flow through the brain
- SPECT scans were done at the VA Medical Center in
Lexington, Kentucky on over 100 Persian Gulf
Veterans with memory complaints
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26Gulf Vet SPECT gradations
- SPECT grade N average age
- 0 (normal) 4 38 years
- 1 (near norm) 4 36
- 2 (mild) 14 40
- 3 (mild-mod) 17 36
- 4 (moderate) 4 40
- 5 (mod-severe) 3 29
- 6 (severe) 3 31
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28Significance of SPECT changes in Gulf Vets with
memory complaints
- SPECT scores relative to normal elderly
- p lt 10-9 (very, very significant)
- The pattern of changes seemed to involve primary
cortical regions - unlike Alzheimers disease.
- Decreased blood flow also seen in other brain
regions (thalamus, basal ganglia)
29Future Directions
- Proving that Gulf War Illness is valid
- PET, SPECT scanning with computer analysis
- Hi-field strength MRI with DTI
- population sampling, multiple control groups
- Searching for the etiology
- comparison of populations - detective work
- Institute of Medicine examining possibilities
- Consideration of interim treatments???
- Apparent benefit of galantamine (Reminyl)
- A cholinesterase inhibitor which could block AChE
toxicity - Symptomatic treatment
- Complimentary and alternative medicine
30Traumatic Brain Injury (TBI) in the Military
- Vietnam War
- 40 of fatalities were due to head and/or neck
wounds (mine, mortar blasts, etc.) - 14 surviving wounds had head injury
- Operation Desert Storm
- 20 surviving wounds had head injury
- OEF OIF
- 28 evacuated to WRAMC had a TBI
- Schwab et al. Journal of Rehabilitation Research
and Development 200744(7)xiii-xxii
Slide Courtesy of Katherine Taber, PhD
31TBI Definitions
- Acute severity mild, moderate, severe
- Glasgow coma scale
- Mild GCS 13 15
- Moderate GCS 9-12
- Severe GCS lt9
- Duration of unconsciousness
- Mild less than 15 min.
- Moderate 15 min. to 6 hours, amnesia 1-24 hours
- Severe more than 6 hours
- Post-traumatic amnesia Mild less than 24
hours - Mild TBI No penetrating brain injury, no focal
neurological findings. - Chronic severity
- Functional level established at one year (Rancho
Los Amigos Scale) - Results of focal cortical contusion
- Consequences of diffuse axonal injury
- Chronic development of dementia, ? Alzheimers
disease
32Mild TBI
- Loss of consciousness (LOC) duration is
relatively short less than 1 minute versus less
than 10 minutes vs less than 30 minutes - Post-traumatic amnesia (PTA) less than 24 hours
- Glasgow Coma Scale (GCS) 13-15 (acutely)
- No penetrating brain injury
- No focal neurological findings
- (different groups use different definitions)
33Facts about TBI
- 2 million in US sustain TBI each year
- 1.1 million are treated in emergency rooms and
released - 500,000 are hospitalized
- 50,000 die from their injury
- 5.3 million Americans have long-term problems
resulting from TBI - Cost - 60 billion to treat the 2 million patients
4/3/2015
34Every Traumatic Brain Injury is Unique(just as
no 2 brain tumors, strokes, seizures are the same)
- Individual head habitus (e.g., age, skull
thickness, protective gear) - Brain reserve (cognitive, neuronal), prior injury
history - Individual repair mechanisms (e.g., genetics -
APOE genotype) - Type of injury, non-penetrating, penetrating (may
not be noted) - Direction of physical force impacting head
- Orientation / location of force translational vs
rotational - Nature of physical energy
- Amplitude, rise-time, wave-length, duration,
reflection - Effects on brain brain stem, cortex,
white-matter - Complexity, multiplicity of injury, contusion,
bleeding, infection - Psychological stress, social imperatives
- Immediate care after injury
- Chronic care after injury, rehabilitation,
support - CANNOT GROUP PATIENTS FOR PARAMETRIC STATISTICS
OR COMPARE ARTIFICIAL GROUPINGS WITH NORMATIVE
SCORES
35Neuropsychiatric Sequelae
- Halbauer J, Ashford JW, Zeitzer JM, Adamson, MM,
Lew HL, Yesavage JA. Neuropsychiatric diagnosis
and management of chronic sequelae of war-related
mild to moderate traumatic brain injury. Journal
of Rehabilitation Research Development.
46(6)757-796, 2009
36Neuropsychiatric sequelae of mild TBI
- Neuropsychological, cognitive deficits
(similarity to dementia) - Memory loss retrograde, anterograde
- (? Relation to fornix damage)
- Aphasia
- Apraxia, slowed motor responses
- Agnosia
- Executive function / decision making impairment,
decreased attention span
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37Neuropsychiatric sequelae of mild TBI
- Neurobehavioral problems
- Depression, mood instability, mania
- (? Relation to norepinephrine, 5HT)
- Apathy
- Decreased bonding, libido
- Inappropriate behavior, disinhibition, agitation
- PTSD, anxiety disorders
- (? Relation to shearing of NE, 5HT neurons)
- Psychosis
- Aggression (possible relation to premorbid and
predisposing factors)
38Neuropsychiatric sequelae of mild TBI
- Neurophysiological symptoms
- Disruption of sensory systems, smell,
hypersensitivity to light, dizziness, tinnitus - Headache
- Sleep difficulties, fatigue (disruption/shearing
of brainstem axons?) - Autonomic instability
39Cognitive Dysfunction
- TBI can affect specific mental functions
depending on where the injury occurred in the
brain. - Temporal lobe
- Difficulties with perception, language, and
detail memory - Parietal lobe
- Problems with spatial orientation
- Frontal lobe
- Difficulties with executive functions
- Speaking, organizing words
- All types of thinking, including subliminal
speech and abstract thinking - Decision-making planning and carrying out plans
- Mental flexibility, adapting as rules change
- Deciding which behaviors are appropriate under
what circumstances
4/3/2015
40Collaborators
- VA Lexington (Kentucky) Gulf War I patients,
SPECT scans) - Jonathan Sickman (changed name of clinic)
- Rose Denman (her idea)
- Linda Godfrey (knows all the patients)
- Joel Stephenson (motive force)
- Wei-Jen Shih (made the observation)
- Cathie Cool (did most of the evaluations)
- VA Palo Alto Health Care System (TBI, PTSD
issues) - Maheen Adamson, PhD
- Louise Mahoney, MS
- Sandy Scaling, RN, MSN
- Joseph Cheng, MD
- Joshua Halbauer, MD
- Jerome A. Yesavage, MD