Complexities of War Related Illnesses and Injuries Diagnosis: - PowerPoint Presentation

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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 IllnessesAfter 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 War

August 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 HealthTroops 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 Gehrig’s Disease))

Brain Cancer

Multiple Sclerosis

Lupus

10/5/2010

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Frequency of Symptoms53,835 Participants in VA Registry (1992–1997)

Symptom Percentage

Fatigue 20.5

Skin rash 18.4

Headache 18.0

Muscle and joint pain 16.8

Loss of memory 14.0Shortness of breath 7.9Sleep disturbances 5.9

(Continued)

.

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Frequency of Symptoms (cont.)Symptom PercentageSkin 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 SymptomsSomatic Medical - normal x-rays of jointsNeurological - 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 HealthInstitute 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 ContributorsChemical Weapons and other chemical exposuresSarin 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 PoisoningAt 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 - SarinSarin 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 VeteransSimilar 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 ScansSingle Photon Emission Computed Tomography – SPECTSPECT scans show blood flow through the brainSPECT 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 gradationsSPECT grade N average age0 (normal) 4 38 years1 (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 complaintsSPECT scores relative to normal elderly: p < 10-9 (very, very significant)

The pattern of changes seemed to involve primary cortical regions:

unlike Alzheimer’s 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 validPET, 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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Slide Courtesy of Katherine Taber, PhD

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

2007;44(7):xiii-xxii

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TBI DefinitionsAcute severity – mild, moderate, severeGlasgow coma scale

Mild – GCS = 13 – 15

Moderate GCS = 9-12

Severe GCS = <9

Duration of unconsciousness

Mild = less than 15 min.

Moderate = 15 min. to 6 hours, amnesia 1-24 hoursSevere = more than 6 hoursPost-traumatic amnesia – Mild = less than 24 hoursMild 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, ? Alzheimer’s disease

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Mild TBILoss 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 TBI2 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

10/5/2010

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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 rotationalNature 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 TBINeuropsychological, cognitive deficits (similarity to dementia)Memory loss – retrograde,

anterograde

(? Relation to fornix damage)

Aphasia

Apraxia

, slowed motor responsesAgnosiaExecutive 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)

ApathyDecreased bonding, libidoInappropriate behavior, disinhibition, agitationPTSD, 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 TBINeurophysiological 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 DysfunctionTBI 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 wordsAll types of thinking, including subliminal speech and abstract thinkingDecision-making planning and carrying out plansMental flexibility, adapting as rules change

Deciding which behaviors are appropriate under what circumstances

10/5/2010

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CollaboratorsVA 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, PhDLouise Mahoney, MS

Sandy Scaling, RN, MSN

Joseph Cheng, MD

Joshua

Halbauer

, MD

Jerome A.

Yesavage, MD