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Multiple Sclerosis Society: Research Bulletin 27: October 2003

http://www.mssociety.org.uk/docs/Research_Bulletin_27.pdf

October, 2003
Multiple Sclerosis Society

This bulletin provides a short summary of the research relating to MS and other neurological diseases in the following major scientific journals:

The articles are organised according to topic as follows: MRI

The role of MRI in the diagnosis of MS.

Title: The utility of MRI in suspected MS. Report of the Therapeutics and
Technology Assessment Subcommittee of the American Academy of Neurology.
Authors: E Frohman, D Goodin, P Calabresi, et al.
Place of Report: Dallas, USA.
Journal Reference: Neurology, 2003. Vol. 61, pages 602-611.

Title: Is multiple sclerosis still a clinical diagnosis? (Editorial).
Authors: J Simon & A Thompson.
Place of Report: London, UK.
Journal Reference: Neurology, 2003. Vol. 61, pages 596-597.

Research Summary

MS is usually diagnosed by physical assessment by a doctor combined with the results of MRI (imaging) of the brain and spinal cord. However, MRI is becoming increasingly important in the diagnostic process and in predicting who will go on to develop MS after a “clinically isolated syndrome” (CIS - one specific symptom e.g. optic neuritis). In 50-80% of people with a CIS there are MRI characteristics consistent with MS.

Until recently MS could not be diagnosed unless the person had two distinct “attacks” separated by generally more than a month, and areas of damage in two different parts of the central nervous system (CNS – brain and spinal cord). However, these existing criteria mean there could be a significant delay in diagnosis, as a second event might not occur for some years. This is especially important as MS is often diagnosed when the person has apparently few symptoms but when extensive damage has already occurred, as shown by MRI.

This report outlines the American Academy of Neurology recommendations for the
MRI component of the diagnostic procedure of MS. The new recommendations
proposed in this report are:

The authors highlight that despite advances in MRI technology and these new recommendations, the diagnosis of MS is still dependant on a high level of expertise by the examining doctor. The authors also make recommendations for future research, highlighting the need for assessment of the lesion characteristics in a person with a CIS, to determine whether these affect susceptibility to development of MS. Studies to assess the use of MRI in “surveillance monitoring” should also be undertaken in order to assess the response to different therapies. In addition, studies are also needed to investigate the usefulness of MRI in the diagnosis of primary progressive MS. Similarly, additional long-term follow up studies and better standardisation of MRI data acquisition and interpretation are needed to further support MRI diagnostic criteria.

Key messages

DIAGNOSIS

Assessment of the diagnostic process in MS.

Title: Diagnosis of MS: a comparison of three different clinical settings.
Authors: B Porter, E Keenan, E Record & A Thompson.
Journal Reference: Multiple Sclerosis, 2003. Vol. 9, pages 431-439.

Research Summary

The time of diagnosis is a crucial time for people with MS and has been described as a time of “anxious waiting”, with delayed test results a repeated complaint. There is currently wide variation in the availability and amount of support, information and education for people, at the time of diagnosis. The MS Society has issued guidance on the type of clinical setting for carrying out the diagnostic procedures for people suspected of having MS, but there is currently no evidence to support one type of setting over another. This report compared three different types of clinical setting used to establish the diagnosis:

The study used an audit questionnaire to review past patient notes over a twelve month period. Performance of the three settings against key MS Society guidelines was assessed. These included short referral time, diagnostic investigations to be completed within a month, the results to be communicated to the patient four weeks after completion and the provision of information and a nurse/support worker in the period following diagnosis.

Referral time within four weeks was achieved in one third of all groups, although the average waiting time was shorter for the DDC. Only DDC patients had all the diagnostic investigations carried out at their first appointment and the results of these tests were communicated to 40% of primary, and 70% of secondary referrals, within four weeks. None of the GNC (or IIU, where tests were delayed until admission) patients had testing at their first appointment. 20% of GNC patients, but none of the IIU received results four weeks after testing. 100% of the DDC group, 40% of the GNC group and 65% of the IIU group were offered medical follow up between visits, with all DDC patients receiving specialist nurse support post diagnosis. 20 and 25% of GNC and IIU patients respectively, were referred to MS nurses for post diagnosis support and were subsequently involved in education sessions.

This study shows wide variation between the three clinical settings but indicates that the standards are achievable in all areas, with the possible exception of the four week waiting time from referral to clinic appointment. The DDC offers advantages to the other two settings but was specifically designed to meet these standards. The need for more consistent follow-up support, including referral to an MS nurse is identified at both the GNC and IIU. The authors also recommend an expansion of the DDC and adoption of its procedures in other diagnostic settings.

Key messages

STATINS

Statins as a treatment for MS?

Title: Statins in multiple sclerosis: a new therapeutic option.
Authors: O Neuhaus & H Hartung (Editorial).
Journal Reference: Multiple Sclerosis, 2003. Vol. 9, pages 429-430.

Research Summary

MS is the most common disabling neurological condition affecting young adults and although there are disease modifying therapies available, new therapies are also needed. Statins are effective cholesterol-lowering drugs currently used by people with high cholesterol and heart problems. However, they have been recently shown to relieve, or in some cases, prevent MS in animal models of the disease. They appear to dampen down the immune system, and may thus act to inhibit brain inflammation. They have also been shown to reduce the amount of inflammatory substances in human blood samples to a similar level as beta interferon. However, some immune signalling molecules such as gamma interferon, which have been linked to the immune attack in MS, have been shown to be increased by statins. Results from initial laboratory studies using statins and beta interferon in combination have also shown that they had additive antiinflammatory properties when used together.

The first trial of statins (using a particular type called simvastatin) given to people with relapsing remitting MS showed that although the drug did not affect disability or relapse rate it significantly reduced the number of new lesions (areas of damage) seen on MRI scans. This beneficial effect began 3 months after starting treatment and lasting for a further 3 months, until the end of the trial. It was also “well tolerated” with no serious side effects. Despite these promising results it is however, still not yet clear how statins work and what sort of an effect they have on the human immune system.

The authors highlight the need for further studies on statins to see whether they could be used as a therapy for MS, either alone or in combination with current treatments, such as beta interferon (since statins are thought to work via a different mechanism). If statins are shown to be effective they offer several advantages over current therapies, including the fact that they are taken in tablet form and they could simultaneously lower blood cholesterol and heart problems. They have already been evaluated for safety and side effects and so theoretically would be available much sooner than a drug in the early stages of testing.

Key messages

RELAPSE MANAGEMENT

Rehabilitation Vs standard treatment after a relapse.

Title: A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment.
Authors: J Craig, CA Young, M Ennis, G Baker & M Boggild.
Place of Report: Liverpool, UK.
Journal Reference: Journal of Neurology, Neurosurgery and Psychiatry, 2003. Vol. 74, pages 1225-1230.

Research Summary

The main therapy used in the treatment of relapses in relapsing remitting MS is steroid treatment using intravenous methylprednisolone (IVMP), which quickens time to recovery. However, it is also believed that physical therapy during steroid treatment and immediately afterwards may improve longer term functioning. Similarly, studies on the benefits of physiotherapy and occupational therapy have generally shown this type of therapy to be beneficial to people with MS. The aim of this study was to evaluate the benefits of combining IVMP treatment with a focused multidisciplinary team (MDT) approach in the treatment of relapses. This was compared to IVMP treatment combined with the usual standard of care given.

40 people, all with relapses requiring hospital admission, were recruited. Half received IVMP and standard (“control”) care and the other half received IVMP and the planned MDT approach. The MDT treatment offered an array of interventions and was based on goals set during the initial assessments. Self rated assessments measuring disability, activity levels, independence and (health related) quality of life were completed on admission, one month and three months after the first day of IVMP treatment. In addition, an assessment of leg movement was also completed by a physiotherapist at these same points.

General disability and leg function was significantly better in the MDT group than the control group at three months after treatment, indicating a sustained improvement. There were also significant improvements in activity and dependence levels, with participants receiving MDT therapy reporting better physical and social functioning. Physiotherapy, occupational therapy and specialist nurse provision were the main therapy interventions, and more people in the MDT group received these therapies and for a longer time than people receiving standard care.

The results show that IVMP treatment in combination with planned MDT rehabilitation (on an inpatient or day care basis) is better than IVMP treatment and standard care alone, producing a reduction in impairment and disability. This study has shown that this type of intervention can provide lasting benefit for the recipient, in term of movement, disability and several factors which increase quality of life. Consequently the authors highlight the importance of using a problem focused, integrated team approach at the point of relapse.

Key messages

SYMPTOM MANAGEMENT

Does deep brain stimulation improve tremor?

Title: Chronic deep brain stimulation for the treatment of tremor in multiple sclerosis: review and case reports.
Authors: H Wishart, D Roberts, R Roth, B McDonald, D Coffey, A Mamourian, C Hartley, L Flashman, C Fadul & AJ Saykin.
Place of Report: New Hampshire, USA.
Journal Reference: Journal of Neurology, Neurosurgery and Psychiatry, 2003. Vol. 74, pages 1392-1397.

Research Summary

Tremor, particularly when reaching for, or wanting to do something (called “action” tremor), is a widespread symptom of MS, and most commonly affects the upper body. However, available therapies are limited, and in severe cases surgery is sometimes used to try and alleviate the tremor. A procedure called deep brain stimulation (DBS) involves implanting tiny electrodes in a part of the brain called the thalamus. These produce very small electric currents and calm the tremor. This paper reviews previous reports of DBS carried out in people with MS, to evaluate the success and side effects of this treatment.

DBS was typically used for people with MS who had severe or disabling tremor, that did not respond to other medical treatment, had no other sensory or movement problems (which might negate the potential beneficial effect of relieving the tremor), and no relapses or sudden change in symptoms or disability levels.

In total, 75 published cases of DBS implantation (in people with MS who had severe disabling tremor) were found. Complete alleviation of tremor was not necessarily achieved although tremor reduction and some improvement in daily functioning were achieved in the majority of cases. The studies also report that in some cases the tremor gradually returned and the implant needed to be “reprogrammed”. One person of the 75 developed a reoccurring infection at the implantation site and two had seizures after the surgery. Other adverse events tended to be mild.

However, few of the studies reviewed stated whether effectively suppressing tremor translated into a long-term improvement e.g. enabled a person to feed themselves or write. The authors highlight that giving the person the ability to do these things can significantly improve quality of life and reduce the level of care needed. Consequently they suggest that longer-term studies are needed on the effectiveness of this type of technique.

Key messages

2. Is Botox effective in relieving pain?

Title: A randomised, double-blind, placebo controlled study on analgesic effects of botulinum toxin A.
Authors: B Voller, T Sycha, B Gustorff, L Schmetterer, S Lehr, HG Eichler, E Auff & P Schnider.
Place of Report: Austria.
Journal Reference: Neurology, 2003. Vol. 61, pages 940-944.

Research Summary

Pain and spasticity are common symptoms in people with MS. Botox is a potent nerve toxin and injections of Botox (into the muscles) have recently been successfully developed to relax muscle spasticity and ease the stiffness and rigidity. Botox acts by blocking the nerve signalling which causes muscle spasms. During some previous studies of people affected by spasticity, participants receiving Botox also reported that the pain associated with the spasticity was significantly reduced or even disappeared. However, pain was also reduced in people who’s posture didn’t improve, raising the possibility that Botox might directly reduce pain. Therefore, this study aimed to investigate whether Botox was, itself, effective in relieving pain or whether this was a secondary effect, caused by an effective reduction in spasticity.

The study used 16 healthy volunteers (without any spasticity) who weren’t taking any medication. The investigators injected Botox into one arm and a “control” substance known to have no effect into the other arm. Neither the nurses who injected the substances nor the participants knew which substance had been injected in which arm. The injected areas on each arm were then tested for sensitivity to heat and electrical current (to simulate pain). The level at which participants could detect the heat or pain and their maximum tolerance of it were recorded.

Investigators found that Botox made no difference to heat or pain perception indicating that Botox does not have any direct pain-relieving properties. They suggest that the anecdotal reports of a beneficial effect of Botox on pain may be caused by the muscle relaxation (caused by the Botox) and not the Botox itself. Reducing the muscle tone can also relieve some of the pressure on the nerves, which activate the muscles, possibly relieving some of the pain. Restoring normal or greater blood flow to the affected area, through relaxing the muscles, could also help to relieve pain through increasing the amount of oxygen available to the muscle and removing factors which can cause increased sensitivity to pain. The authors suggest that these factors should be studied in their own right and compared to the effect of Botox,

Key messages

For further information, please contact:
Alison Handford BSc or Marianne Miles PhD
Research Officer Research Manager
 

Copyright © 2003, Multiple Sclerosis Society