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Spring 2003

AACFS Conference Highlights

New research and treatment options for chronic fatigue syndrome (CFS) were the focus at The American Association for Chronic Fatigue Syndrome’s biannual scientific conference held February inChantilly, Va.

The event featured presentations on breaking CFS research results and, for the first time, a day-long session on treatment strategies for clinicians with CFS patients. More than 190 researchers, doctors and other healthcare professionals from around the world attended the meeting.

Below is a summary of some of the key presentations given during the conference.

Epidemiology
Recent sleep research indicates that CFS patients experience true fatigue and not simply feelings of sleepiness. Elizabeth R. Unger, PhD, MD, of the U.S. Centers for Disease Control and Prevention (CDC), reported that 62.5 percent of study subjects with CFS showed non-restorative sleep, with 66.7 percent exhibiting restlessness during sleep and 33.3 percent showing insomnia. These figures compared to 2.4 percent, 9.8 percent and 0 percent of non-CFS controls who showed no signs of fatigue.

A study from the University of Medicine and Dentistry of New Jersey found that pain was a greater limiting factor than fatigue in CFS patients who report chronic impairment in their ability to perform routine domestic and work-related tasks.

Biochemistry
Suzanne Vernon, PhD, a CDC research microbiologist, and Wilhemina Behan, MD , of Glasgow University in Scotland , presented an overview of gene expression profiling. They reported that it is now possible to take blood or other tissue and apply it to a small glass slide containing more than 20,000 gene identifiers. When the samples are processed and scanned, scientists can determine which genes are turned on, off or somewhere in between. The vast array of information is specific for various states of health and disease in each individual. For example, gene profiling can now distinguish between several types of lymphoma in a patient, thereby allowing more specific treatment for the patient.

Using 25 cases of CFS supplied by the CDC, Vernon could accurately distinguish CFS from healthy controls, and seven specific genes were identified as “turned on” in the disorder. Behan, meanwhile, studied muscle biopsies of three patients with CFS and found three genes upregulated and 33 genes downregulated. Twenty-four genes were positive in controls but absent in CFS.

Patrick Gaffney, MD, of the University of Minnesota also studied gene profiling and found 166 genes “different” in CFS when compared to normal controls. The implication is that gene profiling might some day provide a diagnostic test, as well as a means to distinguish infectious, immunological or other causes of CFS.

Infection and Immunology
Kevin Maher, PhD, of the University of Miami Medical School, described the molecular basis of immunological defects found in CFS, including activated T cells, elevated cytokines and immunoglobulins, reduced NK cell activity, and poor delayed skin hypersensitivity. His studies concluded that perforin and granzymes (used by T-cells for killing other sick or infected cells), were depressed in the T cells of people with CFS. Also, activation of T cells is correlated with increased Interleukin 4 and decreased Interleukin 6, as typically seen in CFS patients.

Immunity in some CFS patients may be disturbed by repeated or persistent bacterial infection, according to Olof Zachrisson, MD, PhD, of Göteberg University in Sweden . He treated 51 CFS patients with a staphyloccal (bacterial) vaccine for 12 weeks, and obtained a positive response in 16 patients. There were modest decreases in pain and fatigue that correlated with antibody production in the individuals. However, the response was not maintained unless the vaccine was continued monthly. The vaccine is produced privately in Switzerland , but is neither publicly nor commercially available.

Central Nervous System
Richard H. Gracely, PhD, of the University of Michigan , presented two papers on functional MRI (fMRI), which rapidly measures cranial blood flow in response to physical challenges such as pain. His group applied thumb pain either intermittently or constantly, and obtained fMRI scans of the fibromyalgia (FM) subjects every five seconds. This demonstrated that with intermittent pain the FM patients had decreased blood flow in the cingulated, secondary somatosensory cortex, cerebellum, and insula; only patients with FM showed activation (increased flow) in the thalamus and putamen.

With constant thumb pain, FM subjects showed increased cranial blood flow in the mid-frontal gyrus and inferior frontal gyrus (Broca’s speech area); only FM subjects showed activation in the caudate and lentiform areas. Only control subjects, on the other hand, had activation when the pain stimulus was released. These studies confirm that people with FM respond differently to painful stimuli than do normal controls.

New Technology
Yoshi Yamamoto, PhD, from the Educational Physiology Lab at the University of Tokyo , demonstrated that autonomic symptoms can be improved modestly by distraction with extraneous noise or electrical stimulation. That is, abnormal autonomic responses were blunted when the subject was distracted. This fits clinically because many patients report that their symptoms are not as noticeable when they are distracted by noise, bright lights, activity, commotion or discomfort; however, it was not previously clear if such stimuli simply distracted the subject or actually improved the dysautonomia.

Physiology
Daniel J. Clauw, MD, of the University of Michigan reported that patients with CFS and FM both show higher catecholamine levels — particularly norepinephrine — than controls while performing a series of activities. These activities included pain testing, cognitive challenges and sub-maximal exercise. Clauw noted that the catecholamine responses were consistently different between the CFS and FM groups during the testing, possibly a sign that the patients have slightly different responses of the hypothalmic pituitary adrenal (HPA) axis. 

This report was compiled by Charles M. Lapp, MD, an AACFS board member and founder of the Hunter-Hopkins Center, P.A., in Charlotte, N.C.; and Mark Giuliucci, editor of The CFS Research Review.

Controlling CFS Pain: One Doctor’s Advice

During a presentation on pain management in patients with CFS, Benjamin Natelson, MD, professor of neurosciences at the University of Medicine and Dentistry of New Jersey , offered pharmacological advice based on his clinical experience. Natelson said he progresses through four stages of medication, choosing drugs appropriate to each patient's presentation.

Stage One

Nonsteroidal anti-inflammatory drugs (NSAIDs): Includes ibuprofen at maximum doses or Celebrex (200 mg twice daily). “It’s a reasonable thing to try,” Natelson said. “The problem with NSAIDs is that they usually don’t work.”

Tricyclic antidepressants (TCAs): Amitriptyline can be effective, particularly in patients who have trouble sleeping. Use lower doses than prescribed for depression.

Effexor (venlafaxine): Try this antidepressant when mood disorder is also present. The long-lasting version is best; dosage may vary from 75 mg to 225 mg once daily.

Stage Two — Anti-epileptics

Neurontin: “ Start low and go slow” with 100 mg at bedtime for 4-5 days, increasing to 100 mg four times per day and working to 300 mg four times per day. A dose of 1,200 mg per day is the first threshold where pain relief may be noticed. Can be increased to anywhere from 2,400 mg to three grams daily.

If this is not effective, Neurontin can be combined with Lamotrigine starting at 25 mg per day at bedtime, then increasing to 25 mg three times per day, and then increasing again to 100 mg three times per day.

Trileptal: Start with 150 mg twice daily, and increase to 600 mg twice daily.

Topamax: This can be useful in patients with weight problems.

Dr. Natelson said he usually tries at least three anti-seizure medications before moving to the next stage.

Stage Three

Plaquenil: Used as an anti-malarial agent during World War II, this drug can raise pain thresholds. But it carries a number of difficult side effects, and can take six months for patients to decide its effectiveness.

Tizanidine: Start with 2 mg per day, and progress to 2 mg twice per day and then 4 mg twice per day.

Mexelitine: Start with 150 mg per day, progressing to 200 mg and 300 mg per day. Can go as high as 10 mg per kilogram of body weight.

Tramadol: In doses up to 50 mg four times daily.

Lidocaine: Patches may help with localized pain.

Stage Four — Opiates

Dr. Natelson advised staying away from short-acting opiates, but said he does sometimes start with Darvon. He also will use Methadone, which is inexpensive, and MS Contin (not OxyContin, which has “street concerns” due to illegal use).

Dr. Natelson said that doctors should be careful with opiates, but should not avoid prescribing them to patients with persistent, extreme pain. “You can’t be frightened,” he said. “You will definitely improve that person’s quality of life.”

He also stressed that more research is needed into pain relief for patients with CFS. “We desperately need trials,” he said. “The drug companies don’t understand our patients and their need for pain relief.”

—Mark Giuliucci