START and STOPP in GWI
Abstract
Rationale for the proposed project: GWI is a currently defined by a set of symptoms and complaints. The Institute of Medicine, Department of Veterans Affairs, Centers for Disease Control and Prevention (Chronic Multisymptom Illness), Kansas definition, and other groups have not agreed on a "final" definition of GWI in the two decades since the Gulf War. Given the lack of consensus in definition and varying presentation of GWI, treatment options are lacking. A new way of thinking about Gulf War Disease: We have established new exciting ways to define GWI from exercise stress tests, heart rate responses, magnetic resonance imaging (MRI), and innovative lab tests. The tests measure short nucleic acid strands (miRNA) in white blood cells and cerebrospinal fluid. This is the fluid from around the brain obtained by spinal taps. miRNA gives clues to what is wrong in the brain. The information will lead to new GWI drugs. These objective mechanisms and tests may lead to a better definition of GWI and specifically targeted treatments. "What types of patients will it help and how will it help them?": We need to repeat, verify, and extend our studies that discovered objective evidence of GWI disease mechanisms. For example, we found problems in the white matter "telephone lines" that connect different parts of the brain. This "communication" problem is likely present in all GWI patients. This and other discoveries will redefine Gulf War Disease. The exercise, scans and blood test identify two subtypes of GWI. This means there are at least two separate disease mechanisms causing GWI. These two subtypes are as different from each other as they are from the healthy control group. The two groups will need different diagnostic tests and treatments. Subjective complaints such of those studied in the "Case Definition Option" in this competition cannot tell these two groups apart. START subjects were defined by Stress Test Activated Reversible Tachycardia. Exercise changed their brain and heart function so they had high increases in heart rates when they stood up after lying down. The START group had smaller brainstems than other GWI and control subjects. This "reptilian brain" controls heart rate, blood pressure, migraines, and gut activity that are problems in GWI. When START subjects perform memory tests in the MRI scanner, their brain function became disorganized. New tests show changes in the cerebrospinal fluid from around the brain and white blood cells. We will search for the cause(s) of the changes in cerebrospinal fluid to determine which types of brain cells and cell mechanisms are not working properly. STOPP (Stress Test Originated Phantom Perception) subjects had MRI brain patterns similar to phantom limb and other chronic pain states. STOPP subjects activate parts of the brain that allow pain and other body messages to reach their conscious perception so that the person knows they have a problem. The brain scans and cerebrospinal fluid tests will point to the cause of this "open switch." "Benefits": Disease mechanism(s) will lead us to "retrain the brain," new therapies, and potential drugs. "Risks": The exercise is like a cardiac stress test. Subjects with possible heart disease cannot take part. Spinal taps (lumbar puncture) have been performed in 117 GWI, Chronic Fatigue Syndrome, and healthy subjects in our studies. We plan to invite participants to have spinal taps as part of this study. The benefit for understanding GWI is that the cerebrospinal fluid bathes the brain and contains mediators that give us vital information about what is going wrong in brain cells. This information cannot be obtained in any other way. It is a vital part of understanding what has gone wrong in GWI and GWI subtypes. Our tests may diagnose GWI. Safety: Spinal headaches occurred after 18 of 117 lumbar punctures. A spinal headache may be mild while lying down, but becomes very severe when sta
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510679
Entities
People
- James N Baraniuk
Organizations
- Georgetown University
- United States Army