Article Index

Splitting patients into subgroups and looking for more ways to differentiate

The splitter's approach

When it comes to determining a cause for Chronic Fatigue Syndrome, is it better to lump CFS patients together with other chronic conditions causing pain and fatigue, or is it better to split patients into subgroups?

Dr. Natelson takes the splitter's approach and identifies patient subgroups in order to determine the cause, or causes, of Chronic Fatigue Syndrome. Dr. Natelson's research for biomarkers, a biological characteristic that can be objectively measured as an indicator of abnormal biological processes, has pointed in the direction of a brain dysfunction in a specific subset of CFS patients.

As there are most likely several causes for CFS, the subgroups help to narrow the pool of patients in order to determine specific causes. This process is called Stratification Strategy.

While FM is another way to split out a diagnosis, FM is tenfold more common than CFS because FM is a diagnosis that is made without any exclusions.

CFS is a diagnosis of exclusion, which requires ruling out all possibilities causing fatigue such as thyroid disease, MS, Lupus, diabetes, etc. and hoping the fatigue will be resolved.

The prevalence rate for FM is 3%, being mostly a women's health issue breaking down to 75% women to 25% men. The prevalence rate for CFS is 0.3%— again favoring women.

In a research paper Natelson published 10 years ago regarding sudden onset, it looks at CFS patients and charts the dates when they became ill. Looking at the chart shows the onset was not random because if random, the charted line would have been straight across. This line went up all around the same time, in winter, suggesting an infection-related trigger.

Stratification Strategy

Co-morbidity is the existence of another diagnosis along with CFS. Dr. Natelson looked at several ways of splitting CFS patients: CFS patients with and without Fibromyalgia; sudden or gradual onset of symptoms; severe or non-severe symptoms; cognitive impairment versus normal cognition; and patients with and without a psychiatric diagnosis—usually depression. About 35% of patients in Dr. Natelson's center reported a sudden onset of symptoms, while the balance report fatigue and symptoms that increased gradually.

Are CFS and FM the same?

In his clinical sample, Dr. Natelson compared CFS and FM to determine if they are the same condition. While overlaps do exist, there are medical differences as well.

About 40% of the CFS patients fulfill the criteria for FM. About 20% of FM patients had CFS. The spinal fluid of FM patients shows an elevation of Substance P (responsible for pain), but that is not the case in CFS patients.

Another study had shown that CFS was common in patients with obstructive sleep apnea, while FM was not. Also, FM pain responds to some anti-depressant medications, but CFS fatigue does not.

Natelson concluded that CFS and FM are not the same and therefore do not have the same causes, nor should they have the same treatments.

Twenty years of research shows possible brain dysfunction

In the past twenty years, Dr. Natelson has conducted a number of studies to determine the differences, and possibly determine the causes, for CFS as compared to other syndromes, such as FM, Sjögren's and post-Lyme. 

In a recently published study looking at sleep, CFS-only patients have increased rates of REM to wakefulness (tends toward awake) while CFS-plus-FM patients tend to fall asleep, but their sleep is disrupted by transitions to wakefulness. These marked differences may prove helpful in determining treatment approaches.

In a study looking at the blood prolactin (a hormonal surrogate for brain serotonin neuron activity) response to a tryptophan infusion, CFS patients showed increased brain response to the tryptophan infusion but not those with CFS-plus-FM or healthy controls. Studies done with depressed patients show an under-response to tryptophan infusion.

His conclusion was that CFS and FM are not the same, as the lumpers believe, and patients may not respond in the same way to commonly prescribed treatments.

Natelson's hypothesis

Natelson's hypothesis is that some CFS patients, especially those that have no accompanying psychological disorders, have brain dysfunction or encephalopathy. Furthermore, Natelson believes that further study will identify biomarkers to accurately diagnose that subset of CFS patients.

In his first study, twenty years ago, Natelson compared the cognitive dysfunction in patients with CFS, MS and healthy patients. He found that CFS patients function worse than controls on timed complex attentional tasks, and that those with the most impairment could have an underlying encephalopathy, or brain dysfunction.

As an example, he offered that a CFS patient in a quiet room talking to one person would be ok, but in a room with four people talking at once, the CFS patient would have a problem.