Complexities of War Related Illnesses and Injuries Diagnosis: Multiple Unexplained Symptoms, Assessment of Traumatic Brain Injury (TBI)

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Complexities 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

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Problems 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.

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Gulf 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

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Summary of the Offensive Ground Campaign
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Gulf 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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Common 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

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Less-Common Illnesses

• Infertility/Miscarriage/Birth Defects
• Amyotrophic lateral sclerosis (ALS (Lou Gehrigs
  Disease))
• Brain Cancer
• Multiple Sclerosis
• Lupus

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Frequency 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)
• .

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Frequency 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

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Clinical 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

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Is 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?

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Gulf 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.

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Gulf 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

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Potential 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

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Possible 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)

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Gulf 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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Gulf 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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Significance 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)

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Future 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

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Traumatic 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
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TBI 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

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Mild 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)

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Facts 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

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Every 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

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Neuropsychiatric 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

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Neuropsychiatric 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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Neuropsychiatric 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)

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Neuropsychiatric 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

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Cognitive 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

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Collaborators

• 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