Multiple Sclerosis Newsletter

Multiple Sclerosis Newsletter
Northern Colorado Edition

February - March 2006

Research Updates

STRESS - a possible link to MS?
"The role of stress-response systems for the pathogenesis and progression of MS"
SM Gold, DC Mohr, I Huitinga, P Flachenecker, EM Sternberg and C Heesen
Trends in Immunology. 12/05 V26 #12 644-52

Research Summary: Psychological stress has been suggested as a trigger for relapses in MS. Recent studies have suggested a link between the occurrence of stressful life events and a higher risk of relapses. One of these studies, using MRI to visualize the amount of MS-related damage, showed that eight weeks after a stressful life event, people with MS had a significantly higher risk of developing new lesions (areas of damage) in the brain.

The area of the brain called the hypothalamo-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS) are involved in responding to stress. The HPA releases various hormones in response to stress, whereas the ANS is the part of the nervous system which controls "automatic" body functions like breathing and heartbeat. The two systems are closely linked and respond to stress as well as having an effect on the immune system.

Research has indicated that people with MS have a higher level of HPA activity than people without the condition. An increase in general HPA activity has been shown in people with progressive MS, which was associated with higher levels of disability and cognitive problems. Research suggests that increased HPA activity may also be associated with neurodegeneration (nerve fibre loss) during the later stages of MS. Studies have shown a relationship between inflammation and increased HPA activity. The production of stress hormones increases during relapses, but not during remission or in progressive forms of MS.

Damage to the autonomic nervous system in MS can cause bladder, bowel and sexual problems. Adrenaline is a hormone released by the autonomic nervous system and is responsible for "fight or flight" actions during stressful situations. Levels of adrenaline are higher in people during a relapse than when in remission. Nuradrenaline is another hormone released by the autonomic nervous system and involved with maintaining normal body function. Noradrenaline has been shown to protect against the progression of autoimmune disease by altering the immune system. Levels of this hormone are significantly lower in people with relapsing remitting MS.

In conclusion, there is some research that suggests that changes occur in the two major stress systems (the HPA axis and autonomic nervous system) during MS. This review also indicates that immune cells are insensitive to the stress hormones and adrenaline and this may play a role during relapses. Further work on the interaction of hormones and the immune system in MS is required.

AN EXPERT VIEW ON SLEEP AND MS
M. Boggild and M. Thorpy
Advances in Clinical Neuroscience and Rehabilitation Nov/Dec 05 V5 #5 pp38-41

Research Summary: Fatigue is a common and often disabling symptom of MS, which can arise as a direct result of MS or secondary to other symptoms. While a large number of people with MS may use the term "fatigue", for many people this can actually be classified as excessive daytime sleepiness, due to a poor night's sleep. Research has shown that up to 50% of people with MS report that the quality of their sleep is inadequate.

People with MS experience sleeping disorders to the same extent as the general population and, as over 30% of the general population suffer from insomnia which is not related to any psychiatric, medical or identifiable reason, it is probable that people with MS have the same issues. However, people with MS may have additional sleep disruption problems compared to the general population, such as leg-jerking movement which affect the quality of sleep (reported in over a third of people with MS).

It is important to differentiate between sleep disorders resulting in daytime sleepiness and MS fatigue, as treatment strategies may be more effective at treating one or other form. Completion of a sleep diary and analysis of a symptom history can be helpful in deciding whether there is a sleep disorder unrelated to MS. It is also possible that medications that a person is taking may affect sleep patterns and quality of sleep.

Electrophysiological tests, which look at the electrical activity of the brain are sometimes used to determine the quality of night time sleep and sleepiness throughout the day. Similarities between the sleep disorder narcolepsy and MS have been reported, with people affected by both types of these disorders having a predisposition to excessive sleepiness. Napping throughout the day can also affect the quality of night time sleep and should be evaluated as part of a management program.

Some MS related fatigue can be reduced by avoiding excessive heat, modifying time management of daily activities, and identifying whether depression is an underlying factor. In some cases, drug treatment such as Amantadine or Modafinil may be useful. However, this report highlights the importance of obtaining a correct diagnosis and whether the problem is related to MS fatigue or an underlying sleep problem.

STAYING WARM: THE IMPACT OF WINTER TEMPERATURES ON MULTIPLE SCLEROSIS
Gabrielle Strasun @ 2005 multiplesclerosis.com

Weather and the seasons can adversely affect daily living in many people with multiple sclerosis (MS). The greatest number of relapses or flare-ups occurs in the coldest months (January and February) as well as in the warmest months (July and August). This is because both the extreme cold of winter and the extreme heat and humidity of summer can worsen existing symptoms as well as produce new symptoms of MS.

Response to Temperature is Variable: Many aspects of MS (symptoms, age of onset, and course of illness) are highly variable. So is response to temperature and to temperature change, also known as thermosensitivity. In highly thermosensitive people, it only takes a temperature change of a few degrees to affect MS symptoms.

Extremely cold weather can temporarily worsen MS symptoms, while moderate cooling can be beneficial, causing some symptoms to improve for a time. For example, moderately cool baths, moderate air conditioning, or liquid cooling vests and passive cooling garments can temporarily lessen fatigue and increase strength in some people with MS. Also, moderate cooling before excercise, a process called pre-cooling, can allow some people with MS to exercise with greater physical comfort.

Response to Temperature may be Contradictory: Sometimes a temperature change may produce a temporary improvement in one symptom and, at the same time, a temporary worsening in another symptom. For example, in one person with MS, a hot bath resulted in the improvement of numbness and walking, but caused a temporary blurring of vision in the left eye. This is called a "dual response" to temperature. In another kind of "dual response", heat and cold may produce worsening of existing symptoms as well as the development of new symptoms.

Response to Winter Temperatures: Exposure to cold weather resulting in lower body temperatures can produce increased difficulty in walking, decreased strength, spasticity (rigidity or stiffness), numbness, and bladder symptoms. In addition, the icy cold of winter can cause te development or worsening of abnormal touch sensations such as burning or prickling and can also lead to loss of bowel muscle control.

How to Keep Yourself Comfortable in Winter:
* Dress warmly but don't overdress. The slightest rise in body temperature (as little as one degree Fahrenheit) can temporarily worsen some existing symptoms and cause new symptoms to appear in some people with MS. It's not that heat makes MS worse; it's that heat, some medical researchers believe, makes for a less efficient conduction of electrical impulses in nerves in which the myelin covering is destroyed by MS (demyelination).
* Don't overheat your house or apartment during the winter months.
* Don't let yourself get overheated when you exercise or go about your daily activities.
* Do your best to avoid exposure to extreme cold or to sudden sharp cooling.
* If cold weather makes your symptoms worse, and you're thinking of moving to a warmer climate, visit the new location first to make sure it is truly beneficial.

DIAGNOSIS - Markers to Identify Relapse Risk
"CD26+, CD4+ T cell counts and attack risk in interferon-treated MS"
F Sellebjerg et al.
Multiple Sclerosis, 12/05 V11 pp. 641-45

Research Summary: Beta interferon is one of the main disease modifying therapies used in the treatment of relapsing remitting MS and on average reduces the relapse rate by around a third. However, many people taking beta interferon treatment still continue to experience relapses. This report investigates whether biological indicators that can product when a person might be about to have a relapse can be identified. People may benefit from treatment with other drugs or combination therapy if the threat of an impending relapse could be identified.

T cells are a type of white blood cell generated by the immune system. This report investigated whether certain proteins (called CD25, CD26 and CCR5) that are found on T cells can be used to identify if a person has an increased risk of a relapse. T cells are further categorized into two main groups called CD4+ or CD8+ depending on whether they have these proteins on them.

This study investigated 113 people with relapsing remitting MS who had been treated with beta interferon therapy (13 with Avonex, 58 Rebif and 42 Betaseron) for at least six months and 51 people without MS to act as a control measure. All relapses were documented and people were studied for six months.

Blood samples were taken from all the participants at the beginning and throughout the trial. An important part of the study was to see whether people produced "neutralizing antibodies" to the beta interferon. Neutralizing antibodies are made by the body, in some cases, in response to beta interferon and can make the therapy less effective.

The results showed that the risk of a relapse was associated with having CD4+ T cells that also contain CD26 proteins on their outer surface (called CD26+CD4+ T cells). CD8+ cells that have CD26 also show an increased risk of a relapse occurring, although the risk was not as great.

The risk of having a relapse when having these types of cells (CD26+CD4+ T cells) was not altered by the type of interferon treatment that people were receiving. The chance of a new relapse occurring was not related to age, sex, time since diagnosis, the time from the most recent relapse or the number of relapses in the two years before commencing beta interferon treatment.

Participants were more at risk of having a relapse if they had developed neutralizing antibodies to beta interferon. Conversely, participants who had no neutralizing antibodies and low levels of CD26+CD4+ T cells had a lower risk of a relapse than the other people in the trial.

This research indicates that the measurement of CD26+CD4+ T cells can be used as an indicator to show an increased risk of a relapse in people with relapsing remitting MS who are taking beta interferon.

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