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Archive Articles
Professor David Scott, Dr Yuen-Li Chung, and Dr
Nicolo Pipitone
- Professor Scott writing in Newsletter
60, April 2006
- Dr Pipitone writing in Newsletter
55, December 2003
- Professor Scott writing in Newsletter
51, March 2002
- Professor Scott writing in Newsletter
49, March 2001
- Meeting Report (Professor Scott)
in Newsletter 48, September 2000
- Meeting Report (Dr Chung) in Newsletter
48, September 2000
- Professor Scott and Dr Chung writing
in Newsletter 44, March 1999
- Dr Chung writing in Newsletter 41,
March 1998
- Dr Chung writing in Newsletter
37, Autumn 1997
- Dr Chung writing in Newsletter 35, Spring 1996
- Professor Scott writing in Newsletter
31, Winter 1994
» Medical
Papers
» Research
Professor Scott writing in Newsletter 60, April
2006
Professor David Scott Inaugral Lecture "Patients
Perspectives"
"In November 2005 I gave my Inaugural Lecture
on "Patients' Perspectives". An inaugural lecture is traditionally
given soon after becoming a Professor, but so many idealized views
are influenced by the uncertain effects of time and chance. So when
I was invited to give my own lecture after being a professor for
almost a decade, it seemed best to show a mixture of grace and enthusiasm
and get on with preparing the best possible talk.
I thought my inaugural should be both relevant to the average person
and comprehensible to the non-expert. After so many years working
with patient groups, including the Myositis Support Group, I wanted
to highlight the importance of patients' views. Hence the title
and subject matter. But filling an hour is no easy matter. I aimed
to talk for three-quarters of an hour and let introductions and
thanks take care of the rest.
I spoke of two disorders that have dominated my last decade - rheumatoid
arthritis and myositis. My themes were "stories, strategies and
standards". Stories are explanations we have about the nature of
diseases and their treatment. Sometimes these stories are correct
and occasionally they are misleading. However, they are important
ways of explaining the effects and complexities of treatment. Strategies
are ways of optimizing treatment, and represent ways in which treatments
can be used in the best way to maximize benefits to patients. Finally
standards are definitions of what is high quality care. Along the
way I gave examples of the impact of these disorders on individuals,
and how they coped and often overcame problems.
I was able to contrast rheumatoid Arthritis and myositis, which
are both long-term inflammatory disorders seen by rheumatologists.
Both are characterised by disturbed immunity. Rheumatoid arthritis
affects about one in one hundred adults and its end result is joint
damage. Myositis but comparison affects about one in 50,000 adults
and its end result is weak muscles. Some aspects of treatment, such
as the use of immunosuppressive drugs to switch off the immunological
disturbance and physiotherapy to overcome the muscle weakness are
common to both diseases. Many other aspects differ between them.
Given the complexity of modern clinical research it is helpful to
reflect on its benefits. The first of these is a sense of enquiry,
which makes medical practice more interesting. Secondly, there is
a need to gain evidence about effectiveness, as better care accompanies
research. Finally there is the issue of equity, as patients with
rheumatic diseases including myositis need the limelight that follows
from research. "On Adversity", one of the classic essays written
in Elizabethan times by Sir Francis Bacon, highlights the problems
of difficult times and shows the importance of overcoming difficulties.
Bacon wrote "the good things, which belong to prosperity, are to
be wished, but the good things that belong to adversity, are to
be admired". I was able to complete my lecture by showing how patients
and their carers are able not only to cope with illness but often
to add to their own lives and those of others by some of their remarkable
responses to the problems of illness.
Many of my patients cope with the unique problems brought on by
their illness through the remarkable way in which they cope with
it. Clinical science and moral philosophy interact in many different
ways. Patients' reactions to their disease - their perspectives
on life and illness - are a fascinating and important area. They
link together both research and our individual philosophical views
of the world. My inaugural lecture gave me some time to reflect
on my own views on medical care in this area.
It seems to me that good treatment is essential. But by itself it
may not be enough to cope with long-term disorders. People need
something else. Whilst not suitable for all, patients support groups
represent an ideal way of helping others and therefore making the
road easier for all. A simple idea simply expressed can be very
powerful. Inevitably my inaugural lecture turned out to be a simple
idea expressed with some difficulty. But along the way in its preparation
I learned new lessons about the interaction between patients and
their illnesses. Each patient's story is unique and important to
themselves and their family. Perhaps the natural urge of researchers
to simplify is unrealistic when placing patients' perspectives into
a broader framework. Rather than reaching to a crisp conclusion
my views became more complex as I worked on the lecture. That may
seem an unlikely paradox, but it is an interesting and unexpected
result. Whilst I could argue it's just the effect of too little
knowledge, I am unconvinced that thirty years is too short a time.
My final thought is that patients' perspectives are fascinating
and highly variable but of immense importance in defining the outcome
of long-term disorders. From a personal viewpoint I would be fascinated
to learn from people with myositis how the disorder has affected
them and how they have coped with the difficulties it has thrown
up."
Dr Pipitone writing in Newsletter 55, December
2003
Creatine Supplementation Trial: Preliminary
Results
"Hypothesis. Myositis causes
significant muscle weakness. In this study, we tested the hypothesis
that creatine supplementation with physical exercise is superior
to physical exercise alone in improving muscle strength of myositis
patients with stable disease and significant muscle weakness.
Design. 30 patients in the UK and 8 patients in
Sweden were randomly allocated to receive creatine (20g a day for
8 days followed by 3 g a day) or placebo. A home exercise program
was prescribed to all patients. Patients were evaluated at baseline
and at month 1, 3, and 6 with various questionnaires, muscle strength
assessments, and different laboratory tests.
Preliminary results. So far, we have analysed the results
of the 30 UK patients without breaking the randomisation codes,
i.e., we are still blinded as to which group received creatine and
which group had placebo. There was a significant improvement in
both groups compared with baseline for the functional aggregate
score, a composite measure of various physical activities (50ft
walk time and walking up and down stairs). The improvement was larger
in group A compared with group B. Muscle strength measured using
the MRC extended scale (0-5, 0: no strength, 5:normal strength)
improved significantly compared with baseline in some muscle groups
in group A but not group B.
Conclusions. Physical exercise has a moderate beneficial
effect. Our results show a greater improvement in group A. If it
is confirmed that group A received the creatine, this may suggest
that creatine can improve muscle strength in myositis patients.
We are waiting for Sweden to complete their part of the trial before
we can reveal which group was which."
Professor Scott writing in Newsletter 51, March 2002
1) King's College Research Team
“Throughout much of the last decade the
Department of Rheumatomolgy have established a close working relationship
with the Myositis Support Group. During this time the Support Group
have helped establish a growing programme of research in Inflammatory
Muscle Diease in the UK, both through directly supporting research
and by helping foster the development of national clinical trials.
At present there are two principal areas of research,
both involving clinical trials. The first of these is the Creatine
Supplementation Trial in which the Support Group are the main sponsors.
The second in the Arthritis Research Campaign funded national trial
of combination therapy in Myositis known as SELAM; Second Line Agents
in Myositis, in which the Support Group are acting as patient advocates.
Dr Pipitone is an accredited specialist in rheumatology
who has been working in our unit for nearly 2 years after completing
his specialist training in the UK and Italy. He has spent the last
year in developing his expertise in Myositis and has taken over
responsibility for the current Creatine Supplementation Trial and
is also involved in recruiting patients and liaison for the SELAM
Trial. Additionally, Dr Pipitone undertakes a regular muscle biopsy
session and a muscle clinic in conjunction with rheumatology and
neurology. The Support Group is at present part funding Dr Pipitone
to continue the Creatine Trial.
Dr Pipitone is keen to pursue further Myositis
research and develop more comprehensive programme of research following
completion of the Creatine Trial. This comprehensive programme of
research will involve both a greater understanding of the genetics
of Myositis and an assessment of disease outcomes. He has submitted
one grant proposal written in cooperation with Dr Michael Rose (Consultant
Neurologist at King’s College and Guy’s Hospitals),
to the Special Trustees of Guy’s Hospital for funding. The
aim of the grant is to determine whether looking for a special class
of molecules, called HLA-I molecules, in the muscle biopsies of
patients with connective tissue disease is a reliable additional
tool in diagnosing Myositis (see following Lay Summary). The second
grant, which is currently being worked on, aims to establish the
role of microchimerism (the presence of small amounts of cells from
a different subject) in the pathogenesis of Myositis.”
2) Lay Summary of the Role of HLA-Class I Molecules
in the Diagnosis of Myositis
“Myositis are a rare group of diseases characterised by inflammation
of the muscles. This condition causes muscle weakness and sometimes
muscle pain; rarely, internal organs may also be affected. To diagnose
Myositis, usually one has to rely on a number of investigations and,
in particular, one has to examine a sample of affected muscle. He
typical changes found in Myositis patients include inflammatory cells,
that is, cells that migrate from the blood vessels into the muscle,
where they cause damage. However, since we can only examine a small
piece of muscle, the particular muscle sample obtained may not show
the presence of the inflammatory cells. Nether the less, in this case
Myositis, can be diagnosed if muscle expresses some molecules, called
HLA-I molecules, which are known to be found in inflamed but not in
normal muscles. Myositis can sometimes occur in patients who suffer
from connective tissue diseases (CTD). CTD are diseases that affect
multiple organs and often cause joint pain. Diagnosing correctly Myositis
in patients with CTD is important, because patients who have Myositis
may require more aggressive treatment, it is difficult to diagnose
Myositis in CTD patients because in these patients the pain and the
muscle weakness may be due not to only to true muscle disease, but
may also be a consequence of arthritis. For this reason the diagnosis
of Myositis in patients with CTD more strongly relies on finding evidence
for inflammation in their muscle biopsy such as the presence of HLA-I
molecules. However since CTD are characterised by generalised inflammation,
HLA-I molecules may be over-expressed in the muscles of CTD patients
either because of the widespread inflammation, or because there is
an ongoing Myositis. To answer the question as to whether, “looking
for HLA-I molecules in the muscle biopsies of patients with CTD is
a reliable means of assessing whether they have Myositis”, we
need to establish whether in CTD patients muscle HLA-I molecules are
over-expressed and whether any such over-expression represents Myositis.
We intend to evaluate muscle HLA-I molecule expression in three groups
of CTD patients; patterns with clinical evidence of Myositis (Group
1), patients with some aches and pains and some degree of muscle weakness
(Group 2), and patients without evidence of Myositis (Group 3). If
muscle HLA-I molecule expression is indeed specific for Myositis,
HLA-I molecules should be up-regulated in Group 1 but not Groups 2
or 3. Clarification of the role of muscle HLA-I molecules in CTD may
result in more accurate diagnosis of Myositis and prompter treatment.”
Professor Scott writing in Newsletter 49, March 2001
News From Kings College London
“Research progresses rather like
the great passenger liners of the last century, which appeared to
sail serenely and almost without motion through the waters, and could
only turn very slowly traversing massive circles when they needed
to change route. Once a research direction is set, those involved
have a feeling of inevitability as the work gradually advances towards
its end. At any moment the process seems almost static. Yet there
is an inevitable and imperceptible momentum forwards.
Our unit has been working on four related strands of research in myositis.
The first of these is assessing the severity and impact of the disease.
Many months, if not several years, after we started to collect data
on health status, in the form of Nottingham Health Profiles, we have
finally had our definitive paper accepted for publication. It will
appear in Clinical And Experimental Rheumatology in a few months time.
I anticipate our research on urine assessments will be accepted for
publication later this year. So often we think of clinical research
as being rapidly moving. But my own experience suggests it is a rather
slower and often uphill battle towards eventual publication. On the
other hand it is immensely rewarding when the paper is eventually
published.
The second area is redefining the disease. This needs international
co-operation and consultation rather than original research. We have
been delighted to work with a large international group led by Dr
Frederick Miller from the FDA in North America and promoted by Professor
David Isenberg from University College in London. So far we have had
meetings in Oxford and Philadelphia and this March we meet in London.
Inevitably the discussions are rather circular. Nevertheless, I anticipate
that by the end of the year we will have completed a report on the
optimal assessment of myositis in terms of activity, damage and disability.
The next step will be redefining the diagnostic criteria for myositis.
The third and final area is clinical trials. Every patient wants to
have treatment that has been tried and tested. Yet this is only possible
through the process of clinical trials, which involve patients comparing
one or more therapies. Advances are particularly slow, as each step
forward must be built on firm foundations. From time to time patients
feel concerned that they may be "guinea pigs" for a new
experimental treatment. But this is usually a mistaken view. To ensure
the results of treatment improve we have to innovate and the only
way to do this is to undertake a national programme of clinical trials.
Everyone has to play a small part, including both clinicians and patients.
My own view is that it is wrong for some patients to take part in
trials, for the benefit of all, while others do not. Of course for
this to be sensible it is essential that we only undertake clinical
trials that are needed and are well designed.
At the moment we are pursuing trials in two areas. The first involves
patients with long-standing myositis and aims to see whether creatine
supplements are beneficial. The second is for patients with more active
disease and aims to see if combination therapy adding cyclosporin
and methotrexate to steroid therapy is better than merely using steroids
by themselves. With creatine supplements we are on the home straight
and I hope that we will be able to complete this study in the near
future. With combination therapy we are just beginning and it will
be some years before the results are known.
A moment’s reflection about treating myositis suggests this
can be divided into stages. Initially we need bring the disease under
control. This usually requires steroid therapy. After this we need
to damp down the inflammatory response. This requires therapy with
immunosuppressant drugs like cyclosporin and methotrexate. Finally
we need to improve the function of damaged muscles. Physiotherapy
is important in this phase and it is at this point that creatine therapy
may be a helpful adjunct. It is very difficult to devise trials to
improve the initial phase of steroid therapy and seems most sensible
to focus on the latter stages of immunosuppression and improving the
function of damaged muscles. Even in this more limited setting there
are several management uncertainties. For example, one question is
should we always use intravenous gammaglobulin or is this best reserved
fornon-responding cases? Another question is how much physiotherapy
is needed? Fine tuning treatment will require a prolonged programme
of clinical trials. At the same time we can only tackle one or two
questions at a time.
What we need is to work in collaboration with patients so that a prolonged
programme of research can gradually improve the outcome of myositis.
Like an old-fashioned liner, once the direction of research has been
set it is best not to change it too often. Indeed it can be both difficult
and disruptive to change course. The most difficult part of the whole
exercise is making a start. No matter how long the research journey,
it must always begin with a single step. Although clinical research
programme has now taken several steps, there remains an infinitely
long way to travel along the research road.”
Report written for Newsletter 48 September 2000 based
on the talk given by Professor Scott at the Myositis Support Group
Meeting 2000
Diagnosis and New Approaches for
Myositis
Professor Scott
gave a two-part presentation. The first part focused on how myositis
should be diagnosed, the problems specialists have distinguishing
myositis from other conditions and why there is a move towards reclassifying
the diseases. The second part was dedicated to explaining the forthcoming
SELAM clinical trial and possible novel therapeutics for the future.
Part 1
Dermatomyositis, Polymyositis and Inclusion Body Myositis are rare
diseases and fall into Neurology, Rheumatology and Dermatology.
It is very difficult to define an individual specialist category
for myositis. Therefore, when redefining the diseases the medical
profession must work closely with sufferers. The Dermatomyositis
and Polymyositis Support Group is able to achieve this by providing
patient’s perspectives and patient focused responses.
A prominent characteristic of Dermatomyositis
is the heliotrope rash. This name used to describe the rash actually
derives from a pink/red flower so named because it ‘follows
the sun’. Professor Scott is a rheumatologist and openly admits
that he would find it difficult to distinguish one rash from another
and would require the expertise of a dermatologist. This highlights
how the diseases can overlap into many medical categories and that
diagnosing the illnesses by observations alone would not be advisable.
Certain diagnostic tests should be performed, and include a muscle
biopsy, an electromyogram, a CPK level and sometimes a MRI scan.
These tests though good for diagnosing the conditions (providing
they are performed by an expert) are not very good at monitoring
the disease or predicting outcomes.
As well as establishing effective and standardised
diagnosis and treatment it is important to study the consequences
of myositis. Professor Scott described how establishing a Disease
Index Score to measure disease activity will be an important step
forward in judging the improvement a myositis sufferer is making.
It is important to quantify improvement as this may determine the
type of treatment a sufferer undertakes. These ideas have already
entered stage one of discussion in the medical field. The recent
international workshop in Oxford enabled doctors to discuss the
development of a Scoring Index for myositis. This Index should take
into account activity tests e.g., CPK level and stamina/strength
tests. These proposals will be further examined and developed in
October in Philadelphia, USA.
To make a correct diagnosis expertise is required.
The diagnostic criteria for myositis is being reviewed and when
the new criteria are introduced it is likely to take into account
the possibility of various forms of Polymyositis. To be included
in the myositis research at Kings College hospital, patients have
to have their diagnosis reconfirmed. In doing so many cases of misdiagnosis
have been discovered. This is because muscle weakness is a common
symptom of many illnesses but it is only in myositis that it is
the cause of the symptoms.
Part 2
The SELAM Trial due to start next year is a result of the ARC new
initiative programme to provide funding for alternative research
projects. Dr Choy submitted an application for a treatment trial
in myositis and the ARC accepted his proposal and awarded £308,520
funding to the trial. The trial will involve the use of steroids,
methotrexate and cyclosporin to establish what combination of immunotherapy
provides the best effects with respect to controlling the diseases,
stabilising activity, etc.
Some of the new drugs that are being introduced
to alleviate the symptoms of arthritis may have a novel role in
myositis. In his opinion the TNF-alpha drugs are a possibility for
the treatment of myositis though they do not yet have a licence
for its use in myositis.
Report written for Newsletter 48 September 2000
based on the talk given by Dr Chung at the Myositis Support Group
Meeting 2000
Christine Saunders Memorial Lectureship Post
Holder
Dr Yuen-Li Chung has held this post supported by the Support Group
for the past 5 years. She has performed novel research into myositis
and gave a summary of the projects that she had been involved with.
Dr Chung explained the benefits of the non-invasive techniques,
magnetic resonance imaging (MRI) and magnetic resonance spectroscopy
(MRS) and how they were being applied to the study of myositis.
MRI can provide a picture of the muscle and it is typically the
thigh muscle that is scanned. MSR can provide a biochemical picture
of the muscle. These techniques are useful for the measurement of
myositis disease activity.
In a MRI scan of normal thigh muscle, the muscle is surround by
fat. The muscle and fat are clearly distinguishable from each other.
However, in Polymyositis the fat has infiltrated into the muscle
fibres and it is difficult to define the areas. The more severe
the Polymyositis the more infiltration of fat into the muscle.
A chart of MRS was shown and it was explained how biochemical changes
of lipids and other metabolites can be seen. MRS analysis of urine
demonstrates that there are changes in the energy metabolites found
in muscle and are fairly specific for myositis. Myositis patients
have a higher concentration of the metabolite creatine in their
urine. These muscle energy metabolites found in urine of myositis
patients have probably passed out from the damaged muscle.
Once a myositis patient is undergoing drug treatment inflammation
goes down but weakness and fatigue persist. MRI is able to show
reduction in inflammation but is not able to measure weakness and
fatigue. Thus, the MRI may show that the muscle damage is improving
yet the patient may not be feeling well due to weakness and fatigue.
MRS is a better way for measuring myositis activity than MRI. MRS
is able to detect small changes in energy metabolites being passed
into the urine and may be a more sensitive test than the CPK level
currently used. The changes in urine of creatine levels measured
by MRS have been demonstrated to be the same in adults and children
with myositis.
Professor Scott and Dr Chung writing in Newsletter
44, March 1999
Ongoing Research in Myositis Supported by the
D & P Support Group
“Background:- Myositis means inflammation of muscles. It occurs
in several related forms. Some patients have Polymyositis when most
of the inflammation is within the muscles. Others have Dermatomyositis
and they have involvement of the skin as well as the muscles. There
are various subgroups including Juvenile Dermatomyositis and Inclusion
Body Myositis.
When muscles are inflamed patients feel weak, they often have muscle
pain and they feel unwell, in the long term patients may lose muscle
strength, they are restricted in everyday activities and they often
become very tired.
The disease is uncommon with about 5-10 new cases per million people
each year, this means there will be slightly less than 500 cases
in the United Kingdom each year. It may last for many years and
this means that there are likley to be over 10,000 people with the
disease in the UK.
The clinical features of Myositis mean various specialists including
rheumatologists, neurologists and dermatologists can see patients.
The chronicity of Myositis, its relative infrequency and the involvement
of different medical specialists have all made research difficult.
The involvement and commitment of patients and their carers and
relatives through the Dermatomyositis and Polymyositis Support Group
is providing a unique opportunity to develop and promote research
and understanding of Myositis.
Research Themes:- The key research issues include identifying the
causes of the disease, measuring its effects, treating the muscle
and skin inflammation and treating the resulting muscle weakness.
Not all of these themes can be dealt with by a single group or at
one centre. Therefore collaboration is needed between a variety
of groups. Understanding why people develop Myositis is especially
difficult and requires considerable basic science and molecular
biology expertise. By contrast clinical research on controlling
inflammation, reversing muscle weakness and measuring the response
to treatment is less problematic and is more likely to produce immediate
returns. Our own group is featuring on these latter issues.
The inflammation of Myositis responds well to steroids and immunosuppressive
therapy with the exception of Inclusion Body Myositis, Although
most patients improve, such therapies are not always curative, and
muscle weakness often persists even when treatment has been effective.
We need to move towards establishing long-term national clinical
trials to define the optimal immunosuppressive therapy. This is
a slow process and the D and P Support Group has helped one programme
start, we anticipate that over the next 2-3 years such national
studies will be in place.”
Dr Chung writing in Newsletter 41, March 1998
Christine Saunders Memorial Lectureship - News
from the Lab
“Since the report in the last Newsletter we have been busy
collating and analysing data and preparing manuscripts for publication.
We have also been setting up new collaborations with research groups
in America and Sweden. We have obtained two years funding from King’s
to support our initial urine studies and to help with the work,
I now have an assistant to work with me in July ’97.
Our first paper has been published in the European Journal of Medical
Research. This paper showed changes in the muscle anatomy and biochemistry
in a group of chronic Polymyositis and Dermatomyositis patients
when compared with healthy controls, using magnetic resonance imaging
(MRI) and proton spectroscopy (MRS). From MRI, we found that atrophy
and fat infiltration were observed in the muscle of myositis patients
using MRS.
We have now processed all the Nottingham Health Profile questionnaires
that you kindly completed for us a while ago. 155 questionnaires
were returned and out of these we had 65 Polymyositis sufferers,
70 Dermatomyositis sufferers, 6 Inclusion Body Myositis sufferers
and 14 Juvenile Dermatomyositis. We have compared our results with
data collected from Rheumatoid Arthritis patients and community
controls (from published surveys of healthy subjects and patients
with common diseases). We found that the levels of morbidity were
comparable to those seen with Rheumatoid Arthritis. The Myositis
patients had especially high scores for energy, physical mobility
and social isolation. Patients with Polymyositis had higher physical
mobility scores than those with Dermatomyositis, patients with Inclusion
Body Myositis had the worst physical mobility. High energy section
scores were seen in all cases except those that were in remission
and were off all therapy. The higher the score the more severe the
problems. Juvenile Dermatomyositis cases showed marginal differences
from other cases with lower energy scores and more pain. A manuscript
reporting the results of this study has been prepared and submitted
for publication.
Thank you to those who sent me a urine sample. Thee samples are
being analysed at the moment and will later be used to validate
our urine method as a possible technique of assessing disease activity.
The preliminary work of this urine study (comparing MRS urinary
profile of a group of chronic Myositis patients with other groups
of controls) has been completed. A manuscript has been prepared
and submitted for publication. The data of this work was presented
at international meetings. As a result we have set up a collaboration
with a research group in the NIH (National Institute of Health,
USA) to study Juvenile Dermatomyositis, which may further validate
our technique as a possible approach for assessing disease activity.
For the next step, we are planning to further validate our urine
method as a possible approiach for assessing disease activity (which
can then be used to monitor efficiency of treatment) and to determine
the affect of dietary supplementation on Myositis.”
Dr Chung writing in Newsletter 37, Autumn 1996.
Dr Christine Saunders Memorial Lectureship
“Since I started at King’s last August, the protocol
of examination for new referral polymyositis and dermatomyositis
(PM/DM) patients to King’s has been established. A series
of tests and examinations are undertaken in one day and the patients
(if practical) are asked to attend the muscle clinic at King’s
about six weeks after their initial visit. The results of their
tests are available for the consultants to decide on a regime of
management. Patients will continue to be followed up.
In Vivo Muscle Proton-MR; I have used in vivo proton MR imaging
and spectroscopy to examine the anatomical and biochemical exchanges
of muscle in PM/DM. our study has shown differences in both MR images
and the profile of proton spectra in PM/DM patients compared to
normal healthy controls. In acute, untreated PM, there was oedema
in the muscles which became apparent in the T2-weighted MR images
(TE/TR=80/2000 ms). In chronic PM/DM fat infiltration within muscles
was apparent. The biochemical profile of the localised MR spectra
of the thigh muscle showed reduction in both choline to lipid and
creatine to lipid ratios in acute and chronic PM/DM patient when
compared to controls. This data is being correlated with clinical
examinations, myometry measurements, muscle enzyme activities and
muscle histology.
In Vitro Urinary Proton-MRS; I have analysed urine obtained from
PM/DM patients and a few control group using in vitro proton MR
spectroscopy to look for urinary profiles that are specific to the
disease, five patient groups are examined: i) PM/DM patients, ii)
healthy controls, iii) stroke patients (to eliminate changes from
natural muscle breakdown, due to lack of usage), iv) rheumatoid
arthritis patients who are on long-term steroid (to eliminate changes
from drug effects) and v) alcoholic myopathy patients (to ensure
the changes that we have observed are specific to PM/DM). the urinary
profile may provide us with quantitative markers for measuring disease
activity and treatment response, measures which are lacking at present.
Preliminary study has shown promising results, where consistent
and highly significant changes in the urinary metabolite patterns
were found in PM/DM. Creatine, taurine and choline-containing compounds
are significantly elevated when compared to controls. The level
of these metabolites were found to be decreased when patients are
improved clinically. The elevation of taurine level are also observed
in stroke and alcoholic myopathy patient groups. This appears to
arise from general muscle breakdown. However, the increase in creatine
and choine-containg compounds occurs only in the PM/DM patient group.”
Dr Chung writing in Newsletter 35, Spring 1996.
Magnetic Resonance Imaging and Assessing Polymyositis
“I started working at King’s in August 1995 and the
initial few months have been taken up in organising my programme
of work and getting used to a new field of research.
My first task has been to complete the project of MR imaging of
muscles and developing a protocol for the clinical assessment of
patients. We now have a programme for each patient referred with
Polymyositis and Dermatomyositis, this involves: a detailed clinical
review by Dr David Scott and Dr Elaine Smith (senior registrar in
Rheumatology), collection of serum for phosphocreatine kinase measurement,
myometry for muscle power by Dr Mike Hurley (an academic physiotherapist),
MR imaging and spectroscopy of the thigh by Dr Steve Williams and
myself, and needle muscle biopsy for histological examination by
Dr Wassif and Dr Jon Salisbury.
So far we have shown differences in both MR images and the profile
of the proton spectra in PM and DM patients when compared to healthy
controls, from the MR images of the thigh, we found oedema in the
muscles of the untreated PM patients and fat infiltration in the
muscle of chronic PM patients. Abnormal biochemical profile of the
proton MR spectra of the thigh in both patients groups were observed
when compared with controls. Our MR results are currently being
correlated with clinical assessment, myometry and, muscle biopsy
so that biochemical changes that are associated with the disease
can be examined, we have reported our results at the American College
of Rheumatology meeting in San Francisco and plan on publishing
a first paper next spring.
We are now moving on to undertake a definitive study. Apart from
examining untreated PM/DM patients (before and after treatment),
partially treated PM/DM and healthy controls, we are also planning
to study another two groups of controls, one being a group with
long term steroid therapy (e.g., asthma sufferer) and the other
group with muscle wasting disease due to lack of usage. The affect
of steroid therapy and muscle wasting can then be evaluated.
I have been very pleased by all the help and support I have received
since starting this new post. I formed collaborations with Dr Vic
Preedy in Biochemistry who is setting up experimental models of
muscle disease, I have also been linking with Dr Jimmy Bell at the
Hammersmith Hospital who is an expert in MR spectroscopy and will
set up phosphorous scans in January for patients with Myositis.
Finally several neurologists are helping to organise a multidisciplinary
muscle clinic from next spring which will enable me to gain access
to more clinical expertise.”
Professor Scott writing in Newsletter 31, Winter
1994.
Magnetic Resonance Imaging and Assessing Polymyositis
“Assessing disease activity in polymyositis and dermatomyositis
is difficult. This is especially true in partially treated cases
where serum muscle enzyme changes are minimal. New imaging methods
may help both diagnosis and disease assessment. We have been looking
at the value of magnetic resonance imaging combined with proton
nuclear magnetic resonance spectroscopy in the clinical assessment
of muscle disease. This is part of our programme to develop an inflammatory
muscle disease unit at King’s College hospital. These tests
are done simultaneously. The magnetic resonance imaging gives pictures
of the muscles in the leg. The spectroscopy allows us to identify
specific biochemical constituents of the muscles. The spectroscopy
can give direct evidence of muscle damage. This means it provides
information of immediate pathophysiological relevance.
Our preliminary studies have looked at 5 treated cases of Polymyositis
and dermatomyositis with persisting symptoms, we compared these
to 5 controls without muscle disease. The imaging is in the Neuroscience
Centre at the Maudsley hospital which is next to King’s College
hospital. For those with technical inclinations we used a GE Sigma
system at 1.5T *which us one of the most powerful machines in the
UK). The method is to collect water-suppressed proton spectra from
a standardised volume defines n magnetic resonance imaging.
There are two types of change shown by this approach. First of all
the magnetic resonance imaging showed excess lipids (body fats)
outside mucels fibres in polymyositis cases. This allowed an appreciation
of the severity of the disease, these imaging results were complemented
by biochemical changes defined using proton spectroscopy. There
were striking reductions in the polymyositis cases in the ratios
of choline compared to lipids (body fats) and also creatine compared
to lipids.
We believe these results highlight the potential of combined magnetic
resonance imaging with proton nuclear magnetic resonance imaging
with proton nuclear magnetic resonance spectroscopy to evaluate
disease activity in polymyositis. They are sensitive methods which
may provide an objective outcome measure against which to titrate
therapy, reduced creatine levels may mirror active Myositis more
accurately than serum creatine phosphokinase activity, the reduced
choline peak potentially results from changes in cell membranes
in active disease.
Of course it is early days in the development of this method to
determine its true value. We are now collecting a larger group of
patients and controls, we are looking at the relationship to serum
enzymes and muscle histology, we are also trying to improve the
method. We need to get a special coil to allow imaging of the thigh
rather than the lower leg. But it is an attractive concept that
by lying down in a machine for about half an hour we should be able
to both diagnose and assess the severity of the disease. Ultimately
this could remove the need for lots of blood tests and muscle biopsies,
there are no X-rays involved and the method is simple and painless.”
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