Multiple Sclerosis Newsletter
Northern Colorado Edition

February - March 2005

Research Updates

MULTIPLE SCLEROSIS HISTORY
Loren A. Rolak, MD, Neurologist & Medical Historian
Marshfield MS Center, Marshfield, WI (1/1/2003)

It was Dr. Jean Martin Charcot (1825 - 1893) who first scientifically described, documented, and named the disease process we still call Multiple Sclerosis. So named, from the many scars found widely dispersed throughout the central nervous system (CNS), but are usually found to be arrayed in a symmetrical pattern near the Cerebrum's Lateral Ventricles.

The first patient Dr. Freud ever treated was his former Nanny who had Multiple Sclerosis. *Creeping Paralysis*, as it was called in those days, was considered a mental condition caused by *female hysteria*. As such, little or no extensive research was conducted into the mysteries of MS, until very recent times.

Dr. V.B. Dolgopol, in 1938, described a case of Optic Neuritis, caused by severe DeMyelination and attributed it to Devic's Syndrome. This syndrome was considered to be a subclass of Multiple Sclerosis, during this time period.

Merck Manual - 16th Edition - 1992. States: "Plaques or islands of DeMyelination along with destruction of both Oligodendroglia and PeriVascular Inflammation are disseminated through the CNS. They are primarily located in the White Matter, with a predilection for the Lateral and Posterior Column (esp. in the Cervical and Dorsal Regions), the Optic Nerves and PeriVentricular Areas.

Traces of the MidBrain, Pons and Cerebellum also are affected, Cell Bodies and Axons usually are preserved, especially in early lesions. Later, Axons may be destroyed, usually in the long tracts, and Fibrous Gliosis - this is what gives the tracts their *sclerotic appearance*.

Often both early and late lesions may be found simultaneously. Chemical changes in Lipid and Protein constituents of Myelin have been demonstrated in and around the Plaques. (p. 1489). The course is highly varied and unpredictable and, in most patients, remittent. At first, months or years of remission may separate episodes, especially when the disease begins with Retro bulbar Neuritis (Optic Neuritis), but usually the intervals of freedom grow shorter, and eventually permanent, progressive disability occurs.

Some remissions have even lasted 25 years or more. However, some patients have very frequent attacks and are rapidly incapacitated; in a few, particularly when onset is in middle age, the disease course is progressively and unremittingly downhill, and occasionally it is fatal within a year."

THE EARLY HISTORY

1400 - The earliest written record of someone with MS was Lydwina of Schieden, Dutch Patron Saint of Ice Skaters.

1838 - Medical drawings clearly show what we today recognize as MS, but 19th century doctors did not understand what they saw and recorded.

1868 - Jean-Martin Charcot, professor of Neurology at the Univ. of Paris, wrote the first complete description of MS and the changes in the Brain which accompany it.

1878 - Myelin was discovered by Dr. Ranvier.

1919 - Abnormalities in the Spinal Fluid were discovered in MS, but their significance remained puzzling for decades.

1920 - Men were thought to be more susceptible to MS than women.

Why? . . .

Because women were often mistakenly diagnosed with *hysteria* - MS symptoms tend to flair each month for most female MSers, about 2 weeks before each Menstrual Cycle for many.

The elevated basal temperature during Ovulation may result in temporary symptom intensification, during the second half of the cycle.

Prostaglandins, a group of Hormones found in Menstrual Fluid and many other tissues, may play a role.

One study reported that 70 percent of women reported changes in their MS symptoms at a consistent point in their Menstrual Cycles. - Even today, most men (and too many Neurologists) remain ignorant of these facts.

SOME REMEDIES
* Taking an anti-inflammatory before you start Menstruating can help with symptoms.
* Some women say taking an Aspirin a day helps with body temperature irregularity.
* Taking a Calcium-Magnesium-Zinc compound may help some women.
*Taking Estrogen supplements, even before you enter Menopause, may prove beneficial for both your menstrual disturbances and MS symptoms.
*Taking diuretics also help many.

1925 - Lord Edgar Douglas Adrian recorded the first electrical Nerve transmissions, which helped prove DeMyelinated Nerve cannot sustain electrical impulses.

1928 - The Oligodendrocyte cell that makes Myelin was discovered.

1935 - Dr. Thomas Rives demonstrated that Nerve tissue, not Viruses, produced a MS-like illness. This animal form of MS, called EAE or Experimental Allergic Encephalomyelitis, paved the way to our present theories of Autoimmunity, for it demonstrated the body can generate an Immunologic attack against itself.

1965 - White Blood Cells that react against a protein in Nerve insulating Myelin were discovered in MS.

Medicine's History of Understanding MS:

1890's - Caused by the suppression of sweat; treated with herbs & bed rest; life expectancy after diagnosis was 5 years.

1910's - Caused by an unknown blood toxin; treated with purgatives & stimulants; life expectancy after diagnosis was 10 years.

1940's - Caused by blood clots & poor circulation; treated with drugs that improve circulation; life expectancy after diagnosis was 18 years.

1960's - Caused by allergic reaction; treated with Vitamins & Antihistamines; life expectancy after diagnosis was 25 years.

1996 - Caused by Autoimmune reaction possibly linked to Virus; treated with Steroids & Immune System regulating drugs; life expectancy after diagnosis is essentially normal for most.

NOTE: Life expectancy from time of diagnosis has increased over time as management and control of complications improved.

TAKING CONTROL OF YOUR Zzzzzs WITH EASE
Cleveland Clinic (04/04/2002)

What are sleep disorders?

Sleep disorders are conditions that prevent a person from getting restful sleep and, as a result, cause daytime sleepiness. There are about 80 different types of sleep disorders and about 70 million Americans suffer from them. The inability to fall asleep or to stay asleep, called insomnia, is the most common sleep disorder.

Are sleep disorders related to MS?

Sleep disorders are usually not caused by the changes of multiple sclerosis (MS), yet a number of people with MS complain of insomnia or broken sleep patterns. Sleep problems with MS are not a result of the disease itself but occur because of secondary factors such as stress, inactivity or depression.

How can someone with MS determine the cause of a sleep problem?

In general, certain kinds of sleep disturbances have recurrent patterns. For example, insomnia caused by depression may take two forms:
*A person will fall asleep in the evening with relatively little trouble. Several hours later he or she will wake up and find it difficult to get back to sleep for the rest of the night.
*A person will fall asleep easily then wake up like clockwork several hours later. From this point on, the rest of the night is spent tossing and turning, with occasional rest periods.

Both of these sleep patterns are typical of depression and are not related to difficulty getting to sleep and general restlessness, which are more common when the person is inactive during the day.

Two other forms of sleep disturbances are caused by spasticity and the increased need to urinate during the night.

Demyelinating disease in the spinal cord makes some people with MS more likely to have night-time spasticity, especially in the legs. Your physician may be able to treat this symptom with medications. Please discuss this with your physician.

For sleep disturbances caused by the increased need to urinate during the night, try reducing your fluid intake in the evening. Remember that it's still important to drink the recommended amount of fluids during the day. Also go to the bathroom immediately before you go to bed. Your physician may be able to treat this symptom with medications. Please discuss this with your physician.

Get into the habit of sleeping again.

One of the most important ways to ensure a good night's sleep is to create a consistent bedtime routine. You can set the stage to fall asleep and stay asleep.

First, don't go to bed until you are tired. Prepare yourself for bed by wearing comfortable nightclothes, adjust your bed pillows in a comfortable position, turn off the lights, adjust the temperature in your bedroom and position yourself comfortably in your bed. Now you are ready to listen to relaxing music, meditate or drink a cup of warm tea.

What if I cannot get to sleep?

Do you have sleepless nights and lay in bed until it seems like the sun is coming up? Once you lay down and you have not fallen asleep after 10 to 15 minutes Get Up! Do not lie in bed and watch the clock or count the cracks in the wall. Find something to do that is relaxing to you, such as putting together a puzzle, reading or writing a letter to friend. Rather than watching TV, which is a passive activity, do something active so that natural tiredness can build up. Remember your bed is only for sleeping. Any of the above activities should be done in another room. not your bedroom. Return to the bedroom only when you feel tired.

Learn how to relax. These relaxation techniques can help you fall asleep or improve your sleeping pattern:
* Repetitive Mental Exercises. Close your eyes and silently repeat a word or short phrase. Let your breathing become slow and steady. Repeat the phrase for 10 minutes until you feel more relaxed.
* Visualization. Imagine that you are in a peaceful environment, such as lying on a beautiful beach relaxing and taking in the rays.
* Progressive Muscle Relaxation. You can mentally put each part of your body to sleep by tensing and relaxing your muscles. People with spasticity should be careful because this exercise could trigger muscle spasms.

Note: Many commercial audiotapes and books are available that teach these and other relaxation techniques.

Sleep tips

Here are more ways to improve your sleep:

- Relax in the evening before going to bed. Try to not rehash the day's problems or worry about tomorrow's schedule.
- Go to be when you're tired. Try to be consistent about the time you go to bed.
- Do not nap during the day.
- Do not consume caffeine within four to six hours of bedtime.
- Do not smoke or use nicotine products close to bedtime or during the night.
- Do not drink alcoholic beverages within four to six hours of bedtime.
- Drink less fluid before going to bed.
- Do not go to bed hungry or soon after a heavy meal. If you are hungry, eat a light snack or drink a glass of warm milk.
- Exercise regularly, preferably during the day. Avoid vigorous exercise 3 hours before bedtime.
- Adopt a bedtime routine and follow it every night.
- Do not watch television, eat or read in bed. Use your bedroom only for sleeping.
- Minimize light, noise and extreme temperature changes in the bedroom.
- Get out of bed when you cannot sleep; do not lay there and stare at the clock. Find something to do that is relaxing to you until you're tired, then try to go to sleep again.
- Set your alarm to wake up at the same time every day, even on days when you're off work and on the weekends.

If these suggestions do not help or if sleep disturbances are interfering with your daily activities, please talk to your health care provider who can help you determine what's causing your sleep problems. Your health care provider can also refer you to a sleep specialist, if necessary.

NEW STUDIES ON MS, STRESS AND DEPRESSION
N.M.S.S. (Summer/Fall 2004)

The phrase, "Don't sweat it!" can be particularly aggravating to someone with a chronic disease such as MS. Aside from the stress that arises in daily life for everyone, MS creates its own emotionally taxing predicaments, not the least of which is dealing with the unpredictable course of this disease. Depression is also experienced by individuals with MS more often than the general population. And just to complicate an already complicated picture, stress has been studied as a possible theory for MS relapses. Here we describe three recent reports that explored stress and depression in MS.

MS and Stress

In a study funded partially by National MS Society postdoctoral fellowships to Laura J. Julian, PhD and Darcy S. Cox, PsyD, with participation from their mentor David Mohr, PhD, and other colleagues (University of California at San Francisco), the investigators searched medical literature for papers from 1965 to February 2003 that contain the terms "stress," "trauma," and "multiple sclerosis."

Three investigators independently reviewed the 20 papers identified analyzing methods, statistics, and outcomes. Based on specific criteria, they selected 14 and conducted a "meta-analysis" (which statistically combines findings) of the 14. They noted a significant increase in the rate of MS relapse after stressful life events in 13 of the 14 studies evaluated.

However, in their report, published online in the British Medical Journal (March 19, 2004), the authors noted a number of limitations. The quality of the studies varied significantly. Many did not consider other factors that might be triggering relapses, or relied on subjects' recall of stressful events over long periods of time, in some cases more than five years. Furthermore, an association between stress and relapse was not consistent among patients, or even in one individual over time.

While this study summarizes the existing literature concerning the possible link between stress and MS attacks, it does not resolve the issue. Rather than establishing a "causal" relationship between stress and MS, the investigators document that an association may be present and the investigators noted that these results should encourage further research to define which stressful events might affect people with MS, what other processes may be at work, and how people's individual reactions to stress may come into play.

They emphasize that these data should not be used to infer that persons with MS and their reactions to stress are responsible for the exacerbations.

"The association between stress and exacerbation in multiple sclerosis can be conclusively confirmed only with a clinical trial of a behavioral intervention that teaches patients to reduce the occurrence and impact of stress," concluded the authors.

Approaching the question in a different manner, Jiong Li, MD, MS, University of Aarhus, Denmark) and colleagues investigated the association between MS and an event bound to cause major stress: the death of a child (Neurology, March 9, 2004). They gathered information from extensive nationwide registries on 21,062 parents who lost a child younger than 18 years old from 1980 to 1996 in Denmark, comparing these data with 293,745 parents who did not lose a chi ld. The two groups were followed to track the development of MS in either parent from 1981 to 1997.

The investigators found that people who experienced the loss of a child had an increased risk of developing MS compared to individuals who, over a similar period of time, did not lose a child - an increase that was significant only eight or more years following the death of the child.

This would seem to link a significant stressful life event with development of MS. The authors noted, however, a significant limitation in their study, in that they had collected no information on lifestyle factors or physical trauma, infections, family history, or occupational exposures or factors that might also contribute to MS risk and which may have been different between the studied populations. These results, however, encourage more research on how stress may impact the biological processes that lead to disease.

MS and Depression On the flip side is the question of how having MS itself increases stress felt by those with the disease. A recent study that attempted to discern the causes of major depression in MS highlights the complexity of this issue.

Major depression is estimated to strike between 25 to 50 percent of individuals with MS at some point in their lives, compared with an estimated 17 percent of the general population. University of Toronto researchers investigated whether MS-related depression could be associated with structural changes in the brain caused by the disease (Neurology 2004;62:586-590).

Using magnetic resonance imaging, the investigators, led by Anthony Feinstein, MD, PhD, FRCPC, compared brain structures in 21 persons with MS and depression, compared to 19 persons with MS who did not have depression.

The researchers indeed found that specific areas of the brain were more likely to show signs of disease pathology, such as lesions or atrophy, in those with depression. However, these structural findings were not linked to depression in every case, and whether they actually caused depression or were caused by depression is still an open question. The investigators cited other possible factors that could be contributing to depression, such as coping ability, physical disability, uncertainty over future and perceived levels of social support, all of which have been implicated in previous studies.

MS researchers continue their attempts to sort out stress, depression and other psychosocial aspects of MS. In the meantime, since it is not impossible to avoid stress, particularly when living with MS, finding ways to better cope with stress can help. The National MS Society provides suggestions, in "Taming Stress in Multiple Sclerosis", a brochure that is available on its Web site at htt://www.nationalmssociety.org/Brochures-TamingStress1.asp.