Inflammation in Chronic Fatigue
Louise - Think back to the last time you had the flu. You probably had some muscle pain and a bad headache, felt completely exhausted, and you might even have had trouble thinking straight. Most people get over the flu and other viral infections including glandular fever in a few weeks or so. But for a few people, those symptoms continue for months and years afterwards, becoming chronic fatigue syndrome. Not everyone with chronic fatigue syndrome has a viral infection before they develop the disease, but many patients do, and it is often the flu or glandular fever. And although chronic fatigue syndrome was first defined in 1988, we still don't know how, or why, these viral infections seem to be able to trigger the condition. And in fact, we have very little idea of what's happening in patients' bodies to cause their symptoms. Post mortem studies are one of the best places to start. Now, a team including Dr. Dominic O'Donovan from Addenbrooke's Hospital in Cambridge and Dr. Abhijit Chaudhuri from Queen's Hospital in Romford has looked at the nervous systems of four patients who suffered from chronic fatigue syndrome. Here's what Dr. Chaudhuri has to say.
Abhijit - It is quite clear that there is an abnormality that is directed towards specific parts of nervous system.
Louise - So, what abnormalities did they find? In the first patient Dr. O'Donovan examined, he found large numbers of deposits called corpora amylacea spread throughout the brain and spinal cord. Professor Perry is the professor of experimental neuropathology at Southampton University and although he wasn't involved in the study, he has given us his opinion of the findings.
Hugh - Corpora amylacea are little deposits that are seen in the brain of quite a lot of people who have different types of neurodegenerative disease. Precisely what their significance is, I think is really unclear, except that they are usually associated with tissue degeneration. So they could be the deposits if you like, evidence of a degeneration process.
Louise - This finding suggests that nerve cells in the patient's brain and spinal cord were being damaged or destroyed while he was still alive. But it tells us nothing about what was causing that damage. The next patient the team looked at might provide the answer. There was inflammation in the dorsal root ganglia. These are structures near where the sensory nerves enter the spinal cord and normally, they only contain nerve cells and a few supporting structures. But Dr. O'Donovan found immune cells infiltrating these ganglia and these immune cells, which are called cytotoxic T cells, normally kill other cells in the body in order to control viral infections or to remove damaged cells. Previous work has shown that patients with chronic fatigue syndrome often have more of these T cells in their blood. But what does it mean if they're infiltrating the dorsal root ganglia? Professor Perry again...
Hugh - The dorsal root ganglia are the neurons that convey sensory information into the spinal cord and that sensory information includes pain, temperature, pressure, and so forth, where possibly pain information is the most important of all in this context, as we know that there are many people with CFS who complain of pain in their extremities. So, to then find around those neurons evidence of inflammation, which is what the T cells are telling us, is there's some sort of inflammatory response, is of itself very interesting.
Louise - Both Professor Perry and Dr. O'Donovan agree that this inflammation could be causing referred pain - meaning the muscle and joint pain people with chronic fatigue syndrome often experience could actually be the result of their own immune systems attacking these nerves in the dorsal root ganglia. And when Dr. O'Donovan stained the dorsal root ganglia of two other patients to detect T cells, he found the same inflammation, although milder. So, all the chronic fatigue patients included in this study had either active inflammation in their peripheral nervous system or signs of a degenerative process in their spinal cord and brain. But it's not clear how, or if, the inflammation is related to the degeneration found in that first patient, particularly as they're affecting different parts of the nervous system. And with only four patients, this is a very small study and much more work is needed before we can be sure what these preliminary findings might mean. In particular, it is very important that we compare patients with chronic fatigue syndrome with people who do not have the disease. But this part of the nervous system is not normally examined in detail during a post mortem. Nonetheless, these results could be an interesting starting point for future research as Dr. Chaudhuri points out...
Abhijit - The fact that we are seeing an abnormality should persuade us to undertake more focused research into the neuroimmunological aspects of the disease.
Louise - And could the fact that T cells are involved in controlling viral infection such as glandular fever be the link between these infections and chronic fatigue syndrome? We'll just have to wait and see.