GWIRP 2012 Investigator Vignette

Title: Undiagnosed Small Fiber Polyneuropathy: Is It a Component of Gulf War Illness?

Investigators: Max Klein, PhD and Anne Louise Oaklander, MD, PhD; Massachusetts General Hospital

Oaklander: Our grant is to test the hypothesis that what we call Gulf War Illness may in some patients be a signal of underlying peripheral neuropathy.

Klein: And so we're recruiting 150 Veterans who are ill with Gulf War Illness and also 150 Veterans who are free of Gulf War Illness. And we're comparing their results with these test results that we've obtained in the past to see which ones give us the best indication of Gulf War Illness and hence, small fiber polyneuropathy.

Oaklander: Gulf War Illness is a mysterious constellation of symptoms, so-called multi-organ symptoms, meaning they affect a lot of different parts of the body. Other labs have established that Gulf War Illness is a true medical problem, but no one has been able to figure out what the underlying cause is. And that's really important because when you don't know the cause of something it's very hard to treat it effectively.

Klein: What we're studying right now is the hypothesis that there's a component of Gulf War Illness that may be due to a specific type of small fiber polyneuropathy; that would be a disorder of some small nerve fibers. And it turns out that the symptoms from this small fiber polyneuropathy bear a strong resemblance to a lot of the symptoms of Gulf War Illness. And so what we're trying to do is to establish a relationship between the two with a series of tests.

Oaklander: This research grant has two parts to it. The first is to study normal non-Veteran as well as Veterans to find out what are the best tests to diagnose this kind of small fiber polyneuropathy.

The second part of the study is to apply these best tests specifically to Gulf War Ill Veterans and controls to see if we can detect small fiber polyneuropathy disproportionately among the Gulf War-Ill population. Specific tests include the use of skin biopsies that are specially stained to reveal the nerve endings within. These are counted and compared to what we would expect from a normal person to look for evidence of neuropathy. We also use a battery of tests of autonomic function, things such as heart rate, blood pressure, and sweating activity. These are all under neural control, and so if they're abnormal, it can be a sign of neuropathy.

Klein: So the first one is a sweat test and we introduce a little chemical into the skin that will actually make you sweat in a certain area, and we actually collect the sweat and measure it and see how much sweat has been produced in that area.

And another test is a tilt table test. And all we do there is we're simulating the action of say when you stand up suddenly from a crouched position. You sometimes get lightheaded because your body hasn't quite reacted to restored blood flow to your brain fast enough. So we do exactly that; and all the while we're monitoring their heart rate and blood pressure.

What we're really looking for mostly is a reaction to the-the stress that we're putting on the body. So the difference between being recumbent and being tilted upward should result in a characteristic change in your blood pressure and heart rate, which if your body is functioning correctly will then recover from.

So we have of course the biopsy where we're looking for abnormal densities of nerve fibers in the skin. So that tells us one thing. These autonomic function tests tell us if there's a malfunction in the nerve fibers.And it turns out that results of the skin biopsy and results with the autonomic function test don't always correlate at the same time; so in other words, it may be that one-one effect is seen before the other. So we're trying to establish that as well.

Oaklander: It's too soon for us to have answers concerning Gulf War Illness and neuropathy. But we've made already a very interesting observation which is that in addition to those Gulf War Veterans who were certified as Gulf War Ill there are a substantial number of noncertified Gulf War Veterans who consider themselves to have Gulf War Illness and are still seeking certification. They've turned out in large numbers for our study, meaning that our so-called normal control population may not be quite so normal. We've thus had to modify our study to gather more data about symptoms even among the normal control population.

Klein: If we're able to establish this relationship between small fiber polyneuropathy and Gulf War Illness then it turns out that for many forms of small fiber polyneuropathy there is a treatment available or sequence of treatments that can be tried. And so what we envision in the future is there may be an opportunity to help treat Veterans suffering from Gulf War Illness.