What are we planning to do? The goal of this project is to develop better tests for screening Gulf War veterans for a neurological illness, small-fiber polyneuropathy (abbreviated SFPN), that we think might be one cause of the puzzling symptoms now known as Gulf War Illness (GWI).

Why do we think that some cases of GWI might actually be small-fiber polyneuropathy? SFPN is the medical word for generalized problems with the thin nerve fibers that carry pain signals from the skin to the brain. These same small-fibers also help regulate the body's automatic functions, including digestion and bowel movements, maintaining normal blood pressure and heart rate, sweating, urination, and even sexual function. So, malfunctioning small-fibers might explain some of the symptoms of GWI such as unexplained chronic pain, nausea, constipation, or diarrhea, tiredness, dizziness, frequent headaches, or skin changes.

What are the benefits of being told you have small-fiber polyneuropathy rather than GWI? No one knows what causes GWI so there are no effective treatments or cures. In contrast, SFPN is often caused by known medical problems that can be cured or treated to lessen symptoms. Treatable causes of SFPN include diabetes and pre-diabetes, even in people who don't know that they have this. Others include cancer and chemotherapy and various other medical illnesses. Some Gulf War ill veterans were exposed to toxins such as organophosphates, pyrethroids, and DDT, all of which can cause SFPN. So, getting diagnosed can help patients get treated and get better.

How do doctors test for small-fiber polyneuropathy? SFPN is still not well recognized by doctors, even by neurologists who focus on nerve problems. And the symptoms can be vague and misleading, so most SFPN patients remain undiagnosed. The standard tests for nerve damage, EMG, and nerve conduction study, do not pick up SFPN and can lead to the false diagnosis that a patient's nerves are fine. Only two tests are recommended for diagnosing SFPN: One is to remove a small skin biopsy from the lower leg (under anesthesia) to count the number of nerve endings in the skin. Very few nerve endings is a sign of SFPN. The other, autonomic function testing (AFT), is a set of tests for blood pressure and heart rate and sweating under different conditions. Both are expensive and complicated and not widely available. No one has ever compared them to figure out which are best. How can this project improve testing for SFPN and help patients and veterans? The first part (years 1-2) is to test normal volunteers and SFPN patients with skin biopsies and AFT. A third test, still in development, measures blood flow under the skin, to learn which tests are best for diagnosing SFPN. We will also factor in cost and ease of use. Once we have the best tests sorted out we will use them in the second part of this project (years 2-3) to test Gulf War veteran volunteers for SFPN. We will compare test results in Gulf War-ill and non-ill veterans to find out if our idea that some GWI patients actually have SFPN is true or not. The benefits to study subjects would be immediate because we would tell them their results. When the results are published, the benefits will help other people who were not involved in the study.

How will we recruit subjects for study? All of our studies are approved by the Massachusetts General Hospital's Institutional Review Board and we offer subjects a small payment for participating. The skin biopsy and AFT tests are already widely used and have no known serious side effects, nor does the test for skin blood flow, which uses FDA-approved laser Doppler scanning equipment. Non-veteran subjects are expected to come from among suitable patients who have received care at Massachusetts General Hospital. We also need to study Gulf War veteran subjects -- those who are well and those who have GWI. We are looking for veteran subjects who are willing to come to Boston and be tested in a single half-day session in our lab at Massachusetts General Hospital in Boston.