Some years ago we began to be particularly interested in myasthenia gravis (MG) in elderly people. We had been struck by the large numbers of more elderly patients who were being diagnosed as having myasthenia on the basis of the acetylcholine receptor antibody (AChR Ab) test that is performed in Oxford and elsewhere. The top Figure shows a frequency distribution plot demonstrating, for one year in the Oxford lab, the number of patients at different ages (divided into decades) with positive AChR Abs . These samples were all sent for diagnosis, so we can assume that the patients have MG. On this basis, it is appears that although quite a few are under the age of 40 years, the majority of patients being diagnosed with MG are 60 or older and a surprisingly high proportion are in the 70s and 80s!
One possibility is that the samples being sent to Oxford are not representative of all patients, but are biased for some reason. Although we did not think that this was the case, we decided to do a National survey. I managed to convince all the eight other laboratories in the UK that perform the test to send me their results (anonymised, of course) for three years (1997-1999) so that I could pool the data. The results were very reassuring. The same trend towards more elderly individuals is seen in every laboratory, and the frequency distribution plot for all the UK is even more convincing than the Oxford one (middle figure). Moreover, this shows that whereas females are more likely to get MG when they are younger, in the older age group males predominate. When you take into consideration that there are less individuals alive in the later decades, the age-related yearly incidence of positive AChR Ab tests is even more impressive (bottom figure). But importantly, it looks as if it is falling off in later years. Is this because patients are not being diagnosed (see below)?
One of the advantages of doing this for the whole country (and Northern Ireland) is that one can make use of national statistics to get further information. Dr Peter Rothwell, who is a neurologist at the Radcliffe Infirmary with particularly experience and expertise in epidemiology, has been helping. We have worked out, for men and women separately, the cumulative incidence, and the expected prevalence in the population as a whole. In each case we have to make assumptions, and we are still checking our figures. But it looks as if anyone who lives to be 90 has a roughly 1:400 chance of developing MG/AChR Abs and that as many as 40 people in every 100,000 may have the disease overall! These figures are much higher than those that are based on identifying the patients individually, as was the case in previous studies.
Only one woman had ever had a diagnosis of MG. What sort of diseases might be confused with MG? In the elderly, one of the most common causes of muscle weakness is a stroke. Moreover, in the scientific literature there are several case reports of patients with MG who were first misdiagnosed as having had a stroke. It was interesting, therefore, that of the eight individuals who had AChR Abs and no diagnosis of MG, three of them had been thought to have stroke-like episodes - perhaps they really do have MG.
All of this has whetted our appetite for learning more about the incidence of MG in the elderly, why they get MG and whether there is anything different about their AChR Abs. We know from Dr Camilla Buckley (MGA-funded Clinical Research Fellow, just submitting her DPhil and starting a Registrar job in Oxford) that elderly patients with MG often have antibodies to a muscle protein called titin as well as to AChR. We dont know whether these antibodies contribute to their weakness. Nor do we know whether elderly MG patients can be seronegative for AChR Abs. As reported in a previous issue of MGA News, we have identified antibodies to a protein called MuSK in some patients who have MG without AChR Abs. But most of the patients that we have studied for MuSK antibodies, so far, are in the younger age group, and we need to do a survey to find out how many elderly patients have this new antibody. Finally, we want to test lots of patients who have been diagnosed as having a stroke, to see whether some of them actually have MG. Peter Rothwell is keen to help with this.
All of this sounds like a new project, and we are very much hoping that the MGA with our help can put together a good proposal to submit to the National Lottery. Learning more about MG in the elderly is clearly going to be important for the health of the community, and may well provide us with some new puzzles to get our teeth into (while Prof Nick Willcox and I still have some).
These results are shown as the number of patients in each age group (divided up into decades) who have positive AChR Abs. Top, all positive results in Oxford in 1997. Middle, all positive results for the UK for the three years 1997-1999, with males and females shown separately. Bottom, the number of positive results for males and females for each million people in each age group.
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