Got Muscles? Got Weakness?

Fatigue and Weakness in Scleroderma Patients
By Jane H. Park, Ph.D., Vanderbilt University School of Medicine (originally published in "Scleroderma Voice," 2003 #3)

Our studies on scleroderma started with Dr. Lloyd King, who observed that his scleroderma patients often felt fatigued and weak.

This lack of energy was reported by him in patients with diffuse, extensive skin involvement and also in patients with limited scleroderma.

Our Hypothesis
Dr. King thought this fatigue was the result of a real metabolic problem, and not just a subjective feeling of the patient.
Therefore, he suggested to Dr. Nancy Olsen and me that we examine the muscles of scleroderma patients using MRI (magnetic resonance imaging) techniques, and look for abnormalities in the energy metabolism during rest and exercise.
We were anxious to begin such a study, because fatigue and weakness can definitely impact the daily activities and lifestyle of patients.

Building on Previous Work
The investigation was quite reasonable, since a number of investigators—for example, Medsger and colleagues, and Clements and associates—had published work demonstrating weakness and non-specific fatigue in sizable groups of scleroderma patients.
Our Findings
Indeed, our studies did show that biochemical abnormalities were present in muscles of scle- roderma patients. These abnormalities could account in part for their reported lack of energy in the activities of daily living.
Our Methodology
Our results were obtained with the MRI machine and can be very simply explained.

The MRI can produce excellent pictures (images) of muscles. However, more important for our work, MRI can also measure the concentration of two essential phosphate compounds, which provide the high energy required for muscle contraction. These two essential compounds are called ATP (adenosine triphosphate) and PCr (phosphocreatine).
When the concentrations of ATP and PCr in muscles are below normal levels, then muscle contraction becomes impaired, resulting in decreased muscle strength.
ATP and PCr in Scleroderma Patients
Our studies showed that the thigh muscles of scleroderma patients at rest had an average reduction of 35% in concentrations of both ATP and PCr compared to normal muscles.
These decreases in ATP and PCR were present in patients with both diffuse or limited scleroderma. Thus our initial findings offer a partial explanation for lack of energy in both types of patients.

During exercise, the thigh muscles of scleroderma patients proved to be less efficient than normal muscles in using ATP and PCr. Decreases in ATP were accentuated in working muscles, which were contracting for as short a time as 10 minutes.

The recovery period following exercise is also important. One can see how quickly trained athletes, such as basketball players, can recover from strenuous exercise and are eager to leave the bench to begin playing again.

The recovery period is also important for each of us during all kinds of daily tasks. The faster you recovery from a given task, for example doing the laundry, the sooner you are ready to attack and complete the next job.

Recovery of muscles after exercise can be accurately measured in the MRI magnet by determining the rate at which PCr (phosphocreatine) is regenerated after exercise.
We noted that the patients required more than twice as much time to resynthesize new PCr as the normal controls. Over the course of the day, this growing deficit in PCr could be a sub- stantial factor in progressive fatigue.
The Role of Magnesium
I would like to mention one other compound, namely, magnesium, which is also essential for muscle contraction and endurance. Magnesium is important because it is required by all the muscle enzymes involved in energy production.

Magnesium and ATP always tightly bind together, and ATP is only active in the presence of proper concentrations of magnesium. The concentrations of magnesium are also low in muscles of patients with either diffuse or localized disease.

During the stress of exercise, the muscle deficit in magnesium is actually increased.Thus, reduction of magnesium provides an additional factor in the explanation of the well recognized fatigue and weakness in scleroderma.

It's Not All in the Mind
These biochemical reductions in ATP, PCr (phosphocreatine), and magnesium are helpful for patients, family, and friends in understanding the reasons for fatigue. Lack of energy is not just a simple problem of attitude, but rather a real metabolic problem.
Implications for Future Work

We hope these studies will also suggest some ways to alleviate weakness and fatigue.

For example, many studies in other laboratories have shown that giving creatine to both athletes and sedentary people can actually increase the levels of the high energy PCr (phosphocreatine) and ATP in muscles.

We are considering a controlled clinical trial to determine whether similar improvements can be observed with scleroderma patients. Magnesium also represents a possibility for future trials leading to stronger muscles and increased endurance.

Since scleroderma is such a complex disease, these biochemical findings and ideas will necessarily be complemented and enhanced by many other scientific contributions, which will lead to a more active and enjoyable lifestyle for patients.