Multiple Sclerosis Society
This bulletin provides a short summary of the research relating to MS
other neurological diseases in the following major scientific journals:
A focus on neuroprotection
Title: The Prospects for Neuroprotection in MS.
Authors: R Holfield (Editorial).
Place of Report: Munich, Germany.
Journal Reference: The International MS Journal, 2003. Vol. 10, pages 103-105.
In MS a number of events occur including inflammation (the movement of cells from the immune system into the brain and spinal cord, where they wouldn’t usually be able to go), damage to myelin (the protective sheath surrounding nerve fibres) and loss of nerve fibres - which can cause permanent disability. Nerve fibre loss is linked to inflammation (unlike in other diseases e.g. Parkinson's disease), but it is not known whether this damage is caused by cells from the immune system attacking nerve fibres directly, or indirectly, as a by-product of inflammation. This suggests that effective treatments for MS need to control both inflammation and protect nerves (be neuroprotective).
However, there is growing evidence that as well as a detrimental effect, inflammation actually has a protective effect on nerve cells. Indeed, some types of immune cells produce neurotrophic factors (a supply of factors which protect nerve fibres), and a type of neurotrophic factor called Brain Derived Neurotrophic Factor (BDNF) has been found in areas of damage (lesions) in MS. Therefore, treatment to suppress inflammation needs to be selective, preserving the protective components and suppressing the harmful aspects.
Neuroprotective strategies for other diseases characterised by nerve fibre loss, such as Parkinson’s disease, cannot simply be transferred to MS, as the mechanisms behind the nerve damage may differ. One of the additional challenges in protecting nerve fibres in MS is that damage is not limited to specific areas in the brain - diffuse nerve fibre loss occurs throughout the brain and spinal cord and needs to be prevented in order to limit disability.
Some neuroprotective strategies have already been tested in MS with mixed success. An example is riluzole (refer to Research Bulletin 28), a type of neuroprotective drug used in the treatment of a form of motor neurone disease. This has been tested in people with primary progressive MS with mixed results – MRI results were positive but there was no impact on disability progression. There are a number of potential treatments which both modulate the immune system and have neuroprotective properties. Examples include:
1. Do coping strategies improve health?
Title: Self-efficacy predicts self-reported health status in
Authors: A Riazi, A Thompson & J Hobart.
Place of Report: London, UK.
Journal Reference: Multiple Sclerosis, 2004. Vol.10, pages 61-66.
MS, and the uncertainty associated with it, can have a major impact on physical activities, employment and quality of life. Positive self-efficacy (the belief that one can cope with a challenging situation) has been found to have a beneficial effect on social and psychological functioning and improve quality of life for people with MS. As self-efficacy is closely linked to health, it may be an important area to target in treatment. This study evaluated participants' daily level of self-efficacy and whether changes, following therapy, improved perception of their health.
A total of 89 people with MS took part in the study. 43 were admitted for rehabilitation (a multidisciplinary team, problem solving, goal-orientated, individually tailored approach) and 46 were admitted for steroid treatment. Self-efficacy was measured using a self-rated assessment scale before and after the therapies. Participants were also asked to rate the impact of MS (using severity measurement scales) on their daily activities and walking ability.
Improvements in self-efficacy were seen in both groups after receiving the therapies. This was not significantly different between the two groups. Higher selfefficacy scores (in both therapy groups) were strong predictors of better daily functioning and improved walking ability, both before and after therapy.
The authors acknowledge that the monitoring period was only a maximum of 6 weeks and only a small number of people took part in the study. However, they highlight that self-efficacy may be an important area to target through education or rehabilitation programmes, due to its influence over perception of health. The authors also identify the need for more research to identify how interventions might cause this effect in people with MS.
This study received support from the Multiple Sclerosis Society of Great Britain and Northern Ireland.
2. Public involvement in healthcare
Title: Public involvement in healthcare. (Education and debate).
Authors: D Florin & J Dixon.
Journal: British Medical Journal, 2003. Vol. 328, pages 159-161.
The involvement of the public and patients in the NHS is now recognised as increasingly important and is part of the new NHS policy. Public involvement is principally the inclusion of members of the public in strategic decisions about health services and policy, locally and nationally. The aim of this is to ensure that health policy decisions reflect the values of the community, as well as improving the responsiveness of services for the people who use them.
This report outlines that public involvement must be linked to precise aims within specific initiatives, otherwise there is a danger that it won’t be representative or will only have minimal impact. So far, there is little evidence that public involvement has improved care standards, satisfaction with them or had a beneficial effect on health. Practical issues such as time, resources and a lack of knowledge of how to implement changes in health services (as a result of public involvement) are also slowing this process down.
In contrast, the policy of patient involvement in the NHS, which gives individual patients a greater input into their treatment and care choices, has attracted considerable interest. This has been shown to have important health benefits for the people involved, as patients are encouraged to take part in making decisions about their own healthcare. An example of this is the successful Expert Patient Programme for the management of chronic diseases, which offers formal support in healthcare decision making.
The Commission for Patient and Public Involvement is identified as needing to clarify the different roles and aims of involving the public and patients in the NHS, as well as providing a way of evaluating this involvement to maximise the many potential benefits of the scheme.
1. Stem cell transplantation in MS – any evidence?
Title: Stem cell transplantation for multiple sclerosis: What
is the evidence?
Authors: A Fassas & V Kimiskidis.
Journal Reference: Blood Reviews, 2003. Vol. 17, pages 233-240.
MS is frequently characterised by a slow progression of disability, caused by damage to myelin (the protective sheath surrounding nerve fibres) and the loss of the nerve fibres themselves. Treatments currently available, particularly for progressive forms of MS, have not been conclusively shown to significantly slow or halt progression of the disease. Early experimental data has been collected on the use of stem cell transplants (unspecialised cells which have the potential to develop into many different cell types) for very severe cases of MS. This review covers the research evidence from early trials to assess the feasibility and effectiveness of this method.
Drugs used in chemotherapy (a type of anticancer therapy which works by destroying certain cell types) e.g. mitoxantrone, are effective at slowing, but not preventing, disability in MS. In MS, this type of treatment destroys immune cells including those which cause damage to myelin. Theoretically, completely ridding the body of all immune cells and "regrowing" the immune system could stop further damage to myelin. Replacing damaging immune cells with correctly functioning ones, which don't attack myelin and nerve fibres, could possibly halt further disease progression. However, as chemotherapy treatments do not stop the progression of MS completely, it might be that some of the damaging immune cells have not been destroyed and continue to cause damage.
Most of the studies so far have involved people with MS who were severely disabled, mainly with secondary progressive MS (SPMS). An analysis of 85 patients with aggressive MS (those experiencing frequent disabling relapses and/or rapid progression of disability) who have undergone this type of treatment, has shown that this procedure is feasible. Results have shown strong reductions in the amount of damage seen on MRI scans and some beneficial slowing in disease activity and reduced progression of disability for some recipients. However, some serious side effects and a high mortality rate of approximately 5% were also reported.
The authors highlight the importance of performing a controlled trial of this type of procedure against other therapies available for SPMS. This will clarify whether the apparent benefit of stem cell transplantation can counterbalance the associated mortality risk (although it is thought this can be lowered with correct selection of trial participants). It is highlighted that this type of therapy for a disease like MS (which in the vast majority of cases is not associated with significantly reduced life expectancy) could only be implemented if it proves to be more effective than other standard therapies. Combining this type of procedure with existing or new therapies to maximise potential benefits is also a possibility.
2. Replacing the immune system in MS?
Title: Suppressing immunity in advancing MS. Too much too late
or too late for much? (Editorial).
Authors: M Freedman & H Atkins.
Journal Reference: Neurology, 2004. Vol. 62, pages 168-169.
Title: Clinical and MRI outcomes after autologous hematopoietic stem cell transplantation in MS.
Authors: A Saiz, Y Bianco, E Carreras, J Berenguer, M Rovira, T Pujol, P Marin, T Arbizu & F Graus.
Journal Reference: Neurology, 2004. Vol. 62, pages 282-284.
In MS a number of events occur including inflammation (the movement of cells from the immune system into the brain and spinal cord, where they wouldn’t usually be able to go), damage to myelin (the protective sheath surrounding nerve fibres) and loss of nerve fibres - which can cause permanent disability. The relationship between inflammation, damage to myelin and nerve fibre loss is not fully clear although it’s well known that suppressing the immune system has a beneficial effect on MS. Initially, the body is able to replace the myelin (“remyelinate”), but this repair process gradually fails over time. The ability of the body to remyelinate also varies between types of MS and differs from person to person.
Theoretically, completely ridding the body of all immune cells and “regrowing” them could stop myelin damage and limit disability. Stem cells are unspecialised cells which have the capacity to develop into lots of cell types, including immune cells, can be collected from the patient’s own bone marrow prior to treatment to suppress the immune system. They can then be used to “regrow” new immune cells by injecting them back into the participant after the immune system suppression. This “replacement” should enable the immune system to grow back “correctly” and no longer damage myelin or nerve fibres.
There have been a number of small trials investigating the effect of wiping out the immune system in people with very aggressive MS and then attempting to use stem cells to “regrow it”. Stem cells can be obtained from a number of different adult and embryonic sources. In this study, stem cells were taken from the bone marrow (as this was an accessible source of stem cells) of 14 participants with severe relapsing remitting or secondary progressive MS. This was done before wiping out the immune system. The stem cells were then injected back into the body to grow into new immune cells. Using the participants’ own stem cells also avoids problems associated with the rejection of foreign material in the body (e.g. as in cases of rejection with kidney transplants from donors).
After a follow up period of 3 years, slight improvements in disability levels were reported in 4 participants, there was stabilisation in 8, and worsening in 2 participants. Relapse rates were significantly reduced in the majority of cases and after the first month post treatment, no new MRI lesions were found. However, although not observed in this study, there are possible substantial side effects associated with the procedure and mortality rates are a major concern. This has led to researchers recently suggesting that younger patients with less advanced disease might be more suitable recipients of this type of therapy.
This type of procedure has been reported to cause a prolonged stabilisation, or perhaps change the aggressive course of the disease. However, it is not currently a treatment option for people with MS in the UK, although some people are receiving private treatment abroad, principally in the US. This remains an experimental treatment option, which should only be considered by people with severe, aggressive MS, in the form of clinical trials or approved studies.
Drug and alcohol problems in people with MS.
Title: Alcohol and drug abuse among persons with multiple sclerosis.
Authors: C Bombardier, K Blake, D Ehde, L Gibbons, D Moore & G Kraft.
Place of Report: Seattle, USA.
Journal Reference: Multiple Sclerosis, 2004. Vol.10, pages 35-40.
Rates of alcohol and drug abuse have never been analysed in a large number of people with MS. This issue may be particularly important to address in people with MS as these types of problem may cause excessive damage to the nervous system, complications with other treatments and additional adverse effects, such as depression.
This study aimed to assess the prevalence of alcohol and drug abuse in people with MS, any links with health or mood and the proportion of people who wanted help for these problems. 739 people with MS responded to a postal questionnaire, answering questions on alcohol and drug use, health and mood.
Of the people surveyed,
The authors highlight that drug and alcohol abuse may be particularly dangerous in people with MS. Alcohol tolerance may diminish as the disease progresses.
Balance and co-ordination problems may also be exacerbated, as could any problems with cognition. There may be dangerous interactions with prescription drugs, and damage to an already compromised nervous system. In addition, any feelings of depression or suicidal thoughts may be compounded. Early identification of people with these problems should be a key priority so advice can be given to reduce this harmful use, particularly in those prone to depression.
Is pneumonia a trigger for MS onset?
Title: Chlamydophila pneumoniae infection of the central nervous
system in patients with multiple sclerosis.
Authors: S Furrows, J Hartley, J Bell, N Silver, N Losseff, S Stevenson, M Chapman, E Thompson, G Ridgeway & G Giovannoni.
Place of Report: London, UK.
Journal Reference: Journal of Neurology, Neurosurgery and Psychiatry, 2003. Vol. 75, pages 152-154.
Chlamydophila pneumoniae (CP) is a type of bacteria known to cause the respiratory disease, pneumonia. CP has been implicated as one possible factor which might be involved in triggering the onset of MS, since it is capable of causing persistent infection. However, previous studies investigating possible links have not produced conclusive results.
This study investigated whether CP was present in the fluid surrounding the brain and spinal cord (called cerebrospinal fluid: CSF) in a group of 19 people with MS and 29 “control” participants with other neurological diseases (e.g. encephalitis, epilepsy) for comparison.
A sample from only one participant with MS tested positive for CP bacteria - further testing indicated that this was due to a previous, rather than a current, case of infection. Antibodies (substances in the body able to attack CP bacteria if the body was invaded) were found in 21% of the people with MS indicating they had previously been exposed to, but were not infected with, the bacteria. However, 21% of control participants, without MS also tested positive for CP bacteria antibodies, showing CP exposure levels were not higher in people with MS.
These results do not support the theory that CP has a role in triggering or causing MS, despite the rare finding of CP bacteria in the CSF of one participant with MS. Other studies investigating a possible link have reported conflicting results and the authors highlight the need for well-designed clinical studies to fully evaluate any possible association.
This study received support from the Multiple Sclerosis Society of Great Britain and Northern Ireland.
Conductive education for MS?
Title: Conductive education: offering hope for people with multiple
Author: C Finucane.
Journal Reference: International Journal of Therapy and Rehabilitation, 2004. Vol. 11, no. 2, page 48.
Conductive education is a form of special "body re-education" for people with movement and muscle disorders. It was developed by a physician called Andras Peto and has been used by people with a number of disorders. It teaches people to re-learn skills or find alternative ways of achieving goals, which have been limited by diseases such as MS. In 1986, the Foundation for Conductive Education was set up in the UK to provide financial support for the development of the scheme.
This report describes the experiences of one person with MS who tried conductive education. After being diagnosed with relapsing remitting MS, and experiencing a series of relapses and severe symptoms, they began a course of conductive education. Standing and breathing techniques, together with a series of exercises were described as exhausting, but resulted in the participant being able to make new movements. After the end of the course, the participant (now with secondary progressive MS) reported that with continuation of the exercises, she was able to maintain some degree of increased mobility.
A lack of awareness and understanding of how to use this technique by physiotherapists are highlighted as possible reasons why it is not used as an alternative therapy in MS more often. The report also highlights the need for specifically qualified instructors to teach people, which is an additional cost for health authorities.
In summary, Chris Jones, Chief Executive of the MS Trust is quoted as saying "we are aware that some people with MS find this therapy helpful. However, it is a difficult area to research and none of the studies to date offer conclusive proof of effectiveness in MS".
A comparison of old and new criteria
Title: The epidemiology of multiple sclerosis in Devon: a comparison
of the old and new classification criteria.
Authors: C Fox, S Bensa, I Bray & J Zajicek
Place of Report: Plymouth, UK.
Journal Reference: Journal of Neurology, Neurosurgery and Psychiatry, 2003. Vol. 75, pages 56-60.
The prevalence of MS increases with distance from the equator. In the UK, Scotland and Northern Ireland have the highest prevalence, although it is not clear whether there is a gradient within the UK. Comparison of data is difficult, partly due to different diagnostic criteria. Until recently the ‘Poser criteria’ were used to diagnose MS. However, in 2001 these were replaced by the new ‘McDonald criteria’ which takes into account improved diagnostic technology, in particular MRI, and therefore should be more accurate. This study compared the number of cases of MS in Devon using both the old Poser and new McDonald criteria. An initial list of people with probable or diagnosed MS was compiled from a number of sources, including hospital admission logs, GPs, and therapy services. Cases were classified according to both the Poser and McDonald criteria.
The prevalence of possible or definite MS cases, in Devon, defined by the Poser criteria was 118 in 100,000. The prevalence according to the McDonald criteria was 117 per 100,000. Increased reliance on MRI technology meant that cases of people with symptoms suggestive of MS (and classifiable under the Poser criteria) but without MRI evidence of areas of damage in the brain and/or spinal cord, were excluded as MS by the McDonald criteria. The number of cases in Devon is one of the highest in England and Wales, indicating a difference in prevalence between the north and south of the UK.
The authors highlight the general difficulty in diagnosing MS when initial symptoms can be very different from person to person. However, they acknowledge the importance of MRI technology in diagnosis, especially as clinical symptoms, without areas of damage detected by MRI, are very rare in MS. They further suggest that if the McDonald criteria are to replace the existing criteria then the number of tests to establish diagnosis needs to be increased. They suggest that the use of lumbar punctures should become routine and MRI measures (particularly those used to detect new areas of damage) should be improved and standardised.
Does Vitamin D protect against MS?
Title: Vitamin D intake and incidence of multiple sclerosis.
Authors: K Munger, S Zhang, E O’Reilly, M Hernan, M Olek, W Willet & A Ascherio.
Journal Reference: Neurology, 2004, Vol. 62, pages 60-65.
The cause of MS is unknown, although genetic and environmental factors are thought to play a role. There is a low prevalence of MS in the tropics, with it becoming increasingly common further away from the equator. One possible theory is that sunlight (UV radiation), which increases levels of vitamin D in the body, may exert a protective effect, although evidence for this is very limited. This study investigated whether or not high vitamin D intake (obtained in the diet) reduced the risk of developing MS.
A total of 92,253 women (without MS) completed comprehensive questionnaires detailing type and frequency of the foods they ate and any vitamin supplements taken. Dietary questionnaires were updated every 4 years. The length of monitoring was between 8 and 18 years, or until diagnosis of MS. A total of 173 women went on to develop MS during the study period.
Increased vitamin D intake in the diet generally was associated with a lower risk of developing MS. Intake of vitamin D from supplements (primarily from multivitamins) and food or supplements only, was associated with a 40% lower risk of MS, in comparison with a diet with no supplements. Vitamin D intake from food alone did not appear to alter the risk of developing MS.
Although the authors suggest that vitamin D is protective against MS, a major limitation of the study is that the vitamin D was obtained from multivitamins, and was therefore associated with increased consumption of a number of other vitamins and minerals. Similarly, vitamin D obtained from UV radiation was not considered and the effect of vitamin D on the course of MS was also not monitored. These issues would need to be clarified before a possible link between MS and vitamin D can be established.
Note: In Research Bulletin 30, page 4, paragraph 1, Rebif was incorrectly classified as beta interferon 1b. Rebif is a type of beta interferon 1a.
Research Bulletins are produced by:
Alison Handford BSc - Research Officer
Marianne Miles PhD - Research Manager
Copyright © 2004, Multiple Sclerosis Society