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Fatigue and MS

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Fatigue and MS

Story By Veronica Davidson

I am often reminded of the time I set out for what was to be a short shopping trip.  It was a struggle just pushing the shopping cart and then having to put the groceries into my van wasn't easy either.  Trying to lift the bags out of the cart my arms were so tired and weak they shook.  I couldn't wait to get home. Driving was even hard! Even with power steering I had a tuff time turning the wheel. Having to put my weight into the wheel just to turn it. Finally I was home!  Unfortunately for me, I couldn't find a parking space near my house and had to park around the corner.  Even with a handicapped sign in front of my home I found someone  parked there. Apparently, they were waiting under the tree while their loved one was in the doctors office down the street. 

My legs grew weary and the load heavier as I tried to make it to my house. I had to stop at every house along the way to sit on their steps for a few minutes till I could feel my legs again.  By the time I stumbled home, I was completely and deathly exhausted.  I actually thought I was going to die! 

Physical Fatigue

When asked about MS-specific fatigue, many sufferers anecdotally describe it as "bone-tired" or a "wearing a suit of armor" feeling.  It differs from normal fatigue in that there is generally no easy correlation between the amount of energy expended and the severity of the weariness.  You would expect someone who just scaled Mt. Olympus to feel extremely exhausted.  You would not expect that same level of exhaustion from someone who merely cooked a simple dinner.  Yet, the problem is not simply an amplification of normal fatigue.  There are many more nuances involved in this symptom.

MS fatigue is often variable, sometimes unrelenting, and generally appears regardless of the amount of sleep the patient gets.  Some patients find that although they regularly get a full night’s sleep, they awaken in the morning unrefreshed.  Many require a scheduled nap in the afternoon when the fatigue is at its worst levels.  For me, I have found no connection between the total rest I get, and the way I feel at any given moment.  There have been times where I have gotten plenty of sleep the night before, but spent the next day in a zombie-like stupor, where even the simplest task requires a superhuman effort.  On the other hand, there have been times where I made it through an unusually busy day, yet felt no ill effects for several days.

Mental Fatigue

Not only does MS fatigue drain a patient physically, but it can also cause mental distress.  Remember the child’s game of trying to pat your head and rub your stomach at the same time?  It was hard to concentrate on both tasks at the same time, so ultimately, you ended up not doing either chore very well.  Many people with MS can relate to that feeling of being mentally overwhelmed.  Often, the dysfunctional nervous system is working overtime, processing the enormous sensory data that we experience daily.  Because the process is disrupted and inefficient, it may be difficult to hold a conversation and listen to background music at the same time.  Or someone may find it impossible to drive at night because the array of lights and sounds are disconcerting.  Similarly, I was once struck dumb and unable to answer a store clerk who simply asked me for my telephone number.  Because my senses were already overloaded from the shopping experience, my brain simply shut down when faced with a simple question.  At that moment I was just mentally worn out.   

What Causes MS-related Fatigue?

Although scientists have no definitive answer, a couple of likely theories are presented regarding the cause of MS fatigue. 

Location, Location, Location.   One theory holds that fatigue is related to the loss of myelin--the protective coating of the nerve fiber.  The locations where the myelin loss occurs are responsible for the severity and type of fatigue.  In this scenario, it is the cerebral abnormalities themselves that contribute to fatigue.  The random placement of myelin lesions or loss could account for the variety of ways people with MS experience the symptoms of fatigue. 

Interestingly, a 1999 study found fatigue severity did not correlate with myelin scarring or deterioration as observed on MRI. (1)  Correspondingly, a 1998 study suggested that the differences in fatigue levels could not be solely explained by the degree of disease activity or disability. (2)  There is certainly a great need for more study in this area.

Poor Body Functioning.  It has also been speculated that the general deterioration of overall functioning as a result of having MS may simply exhaust the body’s storehouse of energy.  Muscle weakness and decreased nerve conduction are the obvious culprits.  But some researchers have noted that altered metabolism and inadequate respiration are other energy-depleters.  Again, further investigation is needed in this area.   


Above all, patients must consult with their physician or other health care professional to determine the value of treatments available for MS fatigue.  The prescription drug, Neurontin®, which is used to control tremors and spasms, has been reported by some users to relieve fatigue as well (although the reasons for this are not totally understood).  In addition, amantadine (Symmetrel®) and pemoline (Cylert®) have been helpful to a small number of MS patients.  Unfortunately, others have found them to be complete failures at remitting fatigue, and have caused unwanted side effects. 

Cephalon, Inc. recently reported positive findings from a new clinical study on the effectiveness of Provigil®.  Generally used for the treatment of narcolepsy, this medication was statistically successful in reducing fatigue in a study of MS patients.

Because these medications are of limited effectiveness, and can be accompanied by unwelcome side effects, many patients combat fatigue in other ways.  Patients learn how to simplify and manage their daily tasks more effectively, so as to save energy.  Physical therapy can teach some how to obtain benefits from using assistive devices to prolong energy.  In addition, avoiding heat, taking scheduled naps, limiting overexertion, managing stress, and monitoring the effects of medication are other steps taken to combat fatigue.

(1) Fatigue In Multiple Sclerosis: cross sectional correlation with brain MRI findings in 71 Patients,  Bakshi R; Miletich RS; Henschel K; Shaikh ZA; Janardhan V; Wasay M; Stengel LM; Ekes R; Kinkel PR, Neurology 1999 Sep 22; 53(5):1151-3

(2) Fatigue in Multiple Sclerosis: interrelations between fatigue complaints, cerebral MRI abnormalities and neurological disability,  Van der Werf SP; Jongen PJ; Lycklama a Nijeholt GJ; Barkhof F; Hommes OR; Bleijenberg G, J Neurol Sci 1998 Oct 8; 160(2):164-70

In the MS Pipeline: A Vaccine and a Drug That Fights Fatigue

MS is thought to occur when immune cells called T cells start attacking
nerves as if they were foreign invaders, say researchers at Baylor
University in Houston. In an attempt to target this problem, they developed
a revolutionary vaccine, comprised of normal cells that were inactivated by
subjecting them to radiation. The theory was that by injecting these
inactivated T cells back into the body, the doctors could stimulate the
healthy components of the patients' immune systems to fight the actions of
the bad cells and suppress the malfunctioning T cells.

The Texas investigators, led by Jingwu Z. Zhang, MD, vaccinated 65 MS
patients with the inactivated T cells and monitored them for 24 months. The
patients had a significant improvement in disability, and fewer relapses.
Zhang and his colleagues suggest that the vaccine may work by decreasing the
action of the abnormal T-cells and promoting the production of
anti-inflammatory proteins by the normal parts of the immune system.

In an effort to relieve the severe fatigue that afflicts many people with
MS, researchers at Ohio State University in Columbus and Kaiser-Permanente
in San Diego looked at the effects of a drug called Provigil. The drug is
now prescribed to treat narcolepsy, a condition whose chief characteristic
is uncontrollable bouts of falling asleep during the day. The doctors
suggest that Provigil may also help treat fatigue associated with other
conditions, such as chemotherapy and chronic fatigue syndrome.

More than three-quarters of MS patients suffer from fatigue, says Kottil W.
Rammohan, MD, a neurologist at Ohio State University in Columbus. "It is
something that is there with them all the time, and it can be disabling,"
Rammohan says.

The cause is unknown, but some doctors think it is related to a chemical
imbalance in the brain, possibly associated with the inflammation that is
characteristic of MS. People whose physical symptoms are most serious do not
always suffer the worst fatigue, Rammohan says. In fact, it may be the other
way around -- with the fatigue being most severe in people whose physical
problems are otherwise mild.

Currently, doctors routinely prescribe two drugs, Symmetrel and Cylert, to
treat MS-associated fatigue, but their effectiveness has not been
confirmed -- and Cylert has been shown to damage the liver. Acting on a
suggestion from a colleague, Rammohan and his co-workers decided to test
Provigil, a drug with caffeine-like effects.

The investigators studied 72 patients whose fatigue was severe but whose
physical disability was not as serious. These are "people who are up and
about and working -- or trying to work -- but they are hampered by the
fatigue," Rammohan says.

During four weeks in which the patients took Provigil at a low dose, there
was a "very highly statistically significant" change in their fatigue
levels, Rammohan says. Not only did tests at a higher dose fail to produce a
measurable improvement, but some patients complained of anxiety and
jitteriness. Headache was the most common side effect at both doses.

"I think it's an excellent study and extremely important, because fatigue is
such a disabling symptom" in people with MS, says Robin L. Brey, MD, a
neurologist at the University of Texas Health Science Center in San Antonio,
who reviewed the research for WebMD.

"This is not typical fatigue," Brey says "It is much more severe, and it can
hit a patient suddenly." For example, she says, "the patient may be fine and
then all of a sudden be too tired to walk to his or her car. We haven't had
an effective therapy to deal with that symptom. That's why [this study] is
so exciting and so promising."


Source: Ohio State University (http://www.acs.ohio-state.edu/units/research/)

Date: Posted 1/21/2002

Therapy Found To Relieve Fatigue Of Multiple Sclerosis Patients

COLUMBUS, Ohio - For the first time, researchers here have found an effective therapy that can alleviate the fatigue often accompanying multiple sclerosis. Many therapies have been developed to treat symptoms of multiple sclerosis, but few have helped, to any degree, the excessive, debilitating fatigue that accompanies other disease symptoms in some patients.
Their study appears today in the Journal of Neurology, Neurosurgery and Psychiatry.

Dr. Kottil W. Rammohan, neurologist at The Ohio State University Medical Center, and his colleagues wondered whether the drug modafinil might be effective in relieving this fatigue. Modafinil is used currently in the treatment of narcolepsy, a disease in which patients experience uncontrolled daytime sleepiness.

"We were very pleased to find that a medication that was effective against narcolepsy was able to treat the fatigue associated with multiple sclerosis."

Two doses of modafinil (200 and 400 mg) were compared against a placebo in 72 patients with multiple sclerosis ranging in age from 18 to 65. It was observed that the 200 mg dose of the drug administered once daily showed highly significant improvement in patients. Three separate instruments of rating fatigue were used, and all three showed concordant response to this drug. No previous drug has been able to show this degree of improvement in treating multiple sclerosis-related fatigue in any previous clinical trial.

"We were very pleased to find that a medication that was effective against narcolepsy was able to treat the fatigue associated with multiple sclerosis," said Rammohan, lead author of the study.

Rammohan's group also looked at the potential side effects associated with this medication and found that they were not greater than those experienced by patients in the study who received a placebo.

"It is always exciting to find an effective therapy that is void of serious side effects," said Rammohan.

Fatigue is one of the most common and disabling symptoms of multiple sclerosis. It affects 75 to 90 percent of patients with the disease. As many as 46 to 66 percent of multiple sclerosis patients experience fatigue on a daily basis.

Rammohan said that more studies are needed to better understand the dosage and length of therapy necessary for patients, but he hopes more neurologists will start using modafinil for the treatment of severe fatigue that often accompanies multiple sclerosis.

Also participating in this study were researchers at Kaiser Permanente in San Diego.

Multiple sclerosis is an unpredictable, progressive disease in which scattered patches of nerve fibers in the brain and spinal cord lose "myelin," their protective covering. Resultant loss of neurological function can manifest with a multitude of symptoms.

In addition to fatigue, patients experience a combination of a number of symptoms that include visual loss, loss of motor function, sensory impairment, imbalance, bowel and bladder dysfunction, and sometimes problems related to cognition, memory and personality. Multiple sclerosis is a common disorder and affects about 350,000 people in the United States, mostly women.


Note: This story has been adapted from a news release issued by Ohio State University for journalists and other members of the public. If you wish to quote from any part of this story, please credit Ohio State University as the original source. You may also wish to include the following link in any citation:



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