The chronic fatigue syndrome is a disorder characterized by severe disabling fatigue that often begins after an acute viral illness. Patients often have a combination of symptoms in addition to severe fatigue. These include impaired concentration and short term memory, sleep disturbances, recurrent lightheadedness, and pain in the muscles and bone. To meet criteria for the diagnosis of chronic fatigue syndrome, these symptoms must have persisted for at least 6 months, and alternative medical and psychiatric explanations must have been excluded. Many patients with chronic fatigue remain functionally impaired for several years. The cause of this syndrome remains unclear. There are no definitive tests to diagnose chronic fatigue syndrome and no therapy has been consistently proven to be effective.

Symptoms suggestive of low blood pressure

Many patients with chronic fatigue complain of lightheadedness after they have been standing up for a short time. Patients sometimes become nauseated and sweaty, they develop a pit in their stomach, and they feel that they might faint if they don't sit down or lie down. These symptoms suggest that some reaction produces a sudden drop in blood pressure, called neurally-mediated hypotension. In some patients, blood pressure may drop low enough to cause a brief loss of consciousness or a fainting spell (the medical term for fainting is syncope). This reaction, when it produces fainting, is often called vaso-vagal syncope or neurally-mediated syncope. In fact, neurally-mediated syncope is the most common cause of fainting spells.

Neurally-mediated hypotension

Neurally-mediated hypotension results from a reaction that involves the reflexes of the autonomic nervous system. These reflexes regulate and control the heart and blood pressure. The autonomic nervous system works automatically and subconsciously, regulating the body's most basic processes including the action of the heart, the blood pressure, respiration, and digestion. The reaction that causes neurally-mediated hypotension is triggered by sensors embedded in the muscle of the heart when they detect an excessive squeezing action of the heart. This reaction causes a drop in blood pressure (and sometimes a decrease in heart rate) which can produce lightheadedness, nausea, or a cold sweat. If the blood pressure drops low enough it can cause loss of consciousness or fainting.

A number of factors can cause the squeezing action of the heart to increase to the point of triggering these sensors. Anxiety, dehydration, and exercise normally cause the squeezing action of the heart to increase. In addition, any time the amount of blood filling the heart decreases, another set of autonomic reflexes cause the squeezing action of the heart to increase slightly. This happens every day: whenever someone stands up, gravity forces blood to pool from the chest and abdomen into the lower extremities. These factors do not normally trigger the reaction that causes neurally-mediated hypotension. However, the squeezing action of the heart will further increase when more than one of these factors is present. We believe that the squeezing action must increase above a certain threshold to trigger the reaction. Neurally-mediated hypotension occurs most commonly when a person is standing up and is a little dehydrated.

It appears that some people are more susceptible to the triggering of this reaction than other people. A large number of patients who suffer from recurrent fainting spells appear to be more susceptible. We have also begun to recognize that patients with chronic fatigue syndrome are extremely susceptible. At this point, we are not sure what it is about a person that makes then more susceptible to this reaction.

Tilt Table testing

We have learned a great deal about this reaction through the use of tilt table testing. Tilt table testing determines a person's susceptibility to the triggering of the reaction that causes neurally-mediated hypotension. It involves having a patient lie on a table which tilts the patient head-up; the patient is observed in the vertical position for a prolonged period of time. In many patients, this simple test triggers neurally-mediated hypotension. Sometimes, a drug called isuprel (like adrenaline) is used during the tilt table test to mildly increase the squeezing action of the heart.

In one published study and a number of unpublished studies, we have learned that 75 - 90% of patients with chronic fatigue syndrome are susceptible to neurally-mediated hypotension during tilt table testing. The first research published about chronic fatigue syndrome and tilt table testing was done at the Johns Hopkins University Hospital by Dr. Hugh Calkins. In an article published in September of 1995 in the Journal of the American Medical Association, Dr. Calkins evaluated 23 patients with chronic fatigue syndrome and found that 22 of the 23 patients had positive tilt table tests, in other words developed neurally-mediated hypotension when tilted upright. At Columbia, we have studied more than 100 patients with chronic fatigue syndrome and the vast majority have had positive tests.

This discovery has a number of important implications. First, the susceptibility to neurally-mediated hypotension may explain some of the symptoms common in patients with chronic fatigue syndrome. Second, this test may become a reliable way of diagnosing chronic fatigue syndrome. Third, and most importantly, this new knowledge of the link between chronic fatigue syndrome and neurally-mediated hypotension may suggest new therapeutic approaches for treating chronic fatigue syndrome. Treatment of neurally-mediated hypotension in patients with chronic fatigue syndrome

As it became known that patients with chronic fatigue syndrome were more susceptible to neurally-mediated hypotension, physicians began to treat patients with chronic fatigue syndrome with medications that are known to prevent neurally-mediated hypotension. There are two ways in which these treatments prevent neurally-mediated hypotension. One type of treatment blocks the squeezing action of the heart to prevent the sensors in the heart from triggering the reaction. Another type of treatment increases the amount of blood in the body and therefore increases the filling of the heart. This indirectly prevents the autonomic reflex which increases the squeezing of the heart when a person stands up.

In the research study mentioned above at Johns Hopkins University Hospital, these treatments were used in nineteen patients with chronic fatigue syndrome who had positive tilt table tests. The results were promising. Nine of the nineteen patients treated were cured of their symptoms of chronic fatigue and another seven patients significantly improved. In all, sixteen of nineteen, or 84% of patients improved or were cured.

This study is small, and did not include a randomized comparison group treated with a placebo; but it is the first study to provide new and encouraging evidence that treating neurally-mediated hypotension in patients with chronic fatigue syndrome may help large numbers of patients. Further research needs to be done to help us better understand the relationship between neurally-mediated hypotension and chronic fatigue syndrome.