Multiple Unexplained Symptoms Assessment of Traumatic Brain Injury TBI J Wesson Ashford MD PhD Director War Related Illness and Injury Study Center VA Palo Alto Health Care System ID: 915225
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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
Slide2Problems 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.
Slide3Gulf 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
Slide4Summary of the Offensive Ground Campaign
Slide5Gulf 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
5
Slide6Common 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
Slide7Less-Common Illnesses
Infertility/Miscarriage/Birth Defects
Amyotrophic lateral sclerosis (ALS (Lou Gehrig’s Disease))
Brain Cancer
Multiple Sclerosis
Lupus
10/5/2010
Slide8Frequency 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)
.
Slide9Frequency 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
Slide10Clinical 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
Slide11Is 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?
Slide12Gulf 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.
Slide13Gulf 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
Slide14Potential 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
Slide15Possible 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)
Slide16Gulf 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
Slide17Slide18Slide19Slide20Slide21Slide22Slide23Slide24Slide25Slide26Gulf 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
Slide27Slide28Significance 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)
Slide29Future 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
Slide30Slide 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
Slide31TBI 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
Slide32Mild 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)
Slide33Facts 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
Slide34Every 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
Slide35Neuropsychiatric 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
Slide36Neuropsychiatric 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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Slide37Neuropsychiatric 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)
Slide38Neuropsychiatric 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
Slide39Cognitive 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
Slide40CollaboratorsVA 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