Norman Swan: Welcome to the program. Today, what makes us go to sleep, what wakes us up; a call to revolution in immunology which shakes the way the experts believe the body defends itself. If the theory's true, then they'll have to rethink transplant rejection and some cancer therapy.
Plus a chance finding which may indicate what's going wrong in people who suffer from Chronic Fatigue Syndrome, also called Myalgic Encephalomyelitis, M.E.
The person who happened upon the results is Dr Frank Duffy, a Professor of Neurology at Harvard Medical School who specialises in a way of measuring brain waves known as Quantitative EEG.
The first task of course, when talking about Chronic Fatigue Syndrome, is to define it.
Frank Duffy?
Frank Duffy: To begin with, it has to persist beyond six months, and there's no key laboratory test. It has a number of sub-types that cause some confusion in nomenclature. For example, there's a peripheral form called fibromyalgia, where the primary complaints are muscle pain, joint pain, muscle fatigue. Then there's the real chronic fatigue syndrome more patients complain of - being tired, but not in the muscular sense; they also complain of memory loss, but primarily the fundamental underlying problem is that their constellation of syndromes prevent them from functioning as they did before in a job.
Norman Swan: What work have you done in this area?
Frank Duffy: I'm a neurophysiologist, and we apply modern techniques to recording brain electrical activity. Quite surprisingly, a little over two years ago, a patient was referred to us with chronic fatigue syndrome and the EEG showed some dramatic changes. I had really been among the individuals who thought that chronic fatigue syndrome was probably a psychiatric disorder allied to either malingering or to conversion disorder. That is to say, it was largely an emotional problem rather than an organic problem, simply because we couldn't find anything. So when I found these rather profound changes, and they consisted of very high amplitude alpha rhythm --
Norman Swan: That's a sleep rhythm, isn't it?
Frank Duffy: It's a 10 Hz rhythm that occurs in the back of the head when you close your eyes. It's called alpha because it was the first EEG rhythm discovered by Burger in the '20s. The finding was that it was extremely high amplitude and very sharp. The second finding was that discharges of the sort that one often associates with epilepsy, were seen in the temporal lobes - not something one would expect to see in a psychiatric disorder. So I turned to my colleague who was visiting us from Switzerland, and I said, 'Let's go and look over the past five years and pull out all the chronic fatigue patients who we have studied, and see if this is a chance finding.'
So we went through our database and discovered 25 patients with chronic fatigue syndrome that had been referred by other Harvard professors in neurology and psychiatry, so we were quite sure of the diagnosis. And lo and behold, virtually all of them demonstrated these same findings.
Norman Swan: How come you hadn't noticed them before, if they were so gross?
Frank Duffy: Well I almost hadn't noticed the case that toggled this whole process, and frankly, high amplitude alpha all by itself has very little clinical meaning. Now however, we've come to re-think this, that it seems to travel specifically with chronic fatigue syndrome. Now one of the issues here is chronic fatigue syndrome needs to be differentiated between patients who are depressed and manifesting difficulty with their sleep and with their ability to have energy to perform on the job. So we compared these patients with chronic fatigue syndrome to 25 age-matched patients who were depressed, on medications, 25 off medications, and some 25 normal subjects from our normal database, and discovered that it was the chronic fatigue patients who stood out on all of these parameters from the other groups. In other words, chronic fatigue patients don't look like depressed patients, on or off medication, or normals.
Norman Swan: Have you since studied this prospectively - looking forward, so that now that you know that you've got the diagnosis right since you can never be sure going back, that you've got an accurate diagnosis?
Because the other thing that people who work in the chronic fatigue syndrome area say, that every so often somebody will come up with a new laboratory test, and all they've actually discovered is a slight variation on normal. People have found slight abnormalities in red blood cells, slight abnormalities in the immune system, but when you study enough people, you find you've really just ended up with a variation of normal.
Frank Duffy: I'm working with Tony Komaroff at the Brigham & Women's Hospital in Boston. Basically we went back and we looked retrospectively at the diagnostic characteristics of the 25 we originally reported, which was a fairly pure study, because this study was read by me at a time when I had the bias that there were no findings. So I had no preconceived notions when we went in.
Prospectively we have studied now up to 80 additional patients and we were writing this up and analysing it at the time and double-blind readings of the EEGs and the findings are holding up very nicely.
The other interesting thing was that although these patients complain of fatigue, virtually no patient with true chronic fatigue syndrome falls asleep during our study, whereas many normal and depressed patients do.
Norman Swan: I think you're finding a disorder of sleep.
Frank Duffy: I think it raises interesting questions of what these individuals mean by fatigue. You see, you put to them the dichotomy, 'Well are you fatigued the way you would be if you had run the marathon and all you needed to do was to sit down and rest? Or are you fatigued as if you'd stayed up all night and all you need to do is sleep a little bit?' And they have a great deal of difficulty choosing one or the other and they say it's a little bit of both. Well when you really talk to them, what they have is a problem with attention. They cannot sustain attention, and they cannot absorb material. A specialist at Mass.General in Boston thinks that there's a primary memory difficulty; others think that it is an attentional problem. A child with attentional deficit disorder, when they sit down and try to work, they will become angry after a short period of time if you constrain them to their task, because it's too hard, too difficult. I think adults express this inability to sustain attention in the workplace as fatigue, when in fact they're not really tired in the traditional sense, either muscularly or from the sleep deprivation standpoint.
Norman Swan: So does this study tell you anything practical in terms of chronic fatigue, in terms of what might be causing it, or how you might treat it differently?
Frank Duffy: Well we've extended the alpha finding to realise that they actually have very high amplitudes in their occipital and temporal regions.
Norman Swan: Occipital being the back of the head, temporal being the side of the head just above and behind the ear.
Frank Duffy: Right. That's a finding that one sees after head injury, drug abuse, extreme sleep deprivation, encephalopathy, and we believe that it's concrete evidence that the chronic fatigue syndrome in the population, we have defined it clinically, represents a form of organic brain damage, or encephalopathy. The pattern of the discharges, the spikes or sharp waves is temporal, and it's well known that the temporal lobes have a predilection for infection by the herpes virus in acute herpes encephalopathy and encephalitis. And Tony Komaroff and I are suspicious that there may be a post-viral mild encephalopathy affecting primarily the temporal lobes because of the distribution of the discharges and because of the memory and attentional problems that these patients report.
Norman Swan: Of course the problem is whenever they look for an infection they can't find one, or signs of a previous infection.
Frank Duffy: Right. So that based on the clinical data of consistency of finding of either in the spinal fluid of the blood, you can't find it. One would not anticipate therefore, finding anything in the central nervous system by other measures, yet here we have our findings which are we think very reliable and repeatable.
Norman Swan: And just a final question about quantitative EEG, because I know a few neurologists who are still quite sceptical of this technique saying, 'Look, it hasn't been verified over large numbers of people in terms of a diagnostic test and that it's still a research tool.' And one wonders just how confident you are in this if you were to use it as a diagnostic technique?
Frank Duffy: Well of course, like any research technique, it's only as good as the individual who does it, and the data that they use. Quantitative EEG is nothing more than the applications of physical analytic tools to brain signals, and that doesn't necessarily fill one with confidence. I can only speak for what we do, and that our results so far appear to have replicated, and I think it's imperative in assessing studies with quantitative EEG that replication be built in to any understanding of it. For example, in clinical work that we do, we require that every finding be present in three replicates.
Norman Swan: Provocative and interesting research there. Dr Frank Duffy is Director of Clinical Neurophysiology at Boston Children's Hospital and he's also Professor of Neurology at Harvard Medical School.
What may be going wrong in people who suffer from CFS, also called Myalgic Encephalomyelitis (M.E.).