Chronic Fatigue Syndrome

Lucinda Bateman MD

 The 1988 (CDC or Holmes) CFS Case Definition (or “Working Case Definition of CFS”) requires that patients meet the Major Criteria of new onset fatigue and fatigability that does not resolve with rest, that causes at least a 50% reduction in activity, for at least 6 months, and the exclusion of all other illnesses that can cause fatigue, including existing psychiatric illness, and Minor Criteria of >6 month duration, including at least 6 of 8 symptoms (fever, sore throat, painful lymph nodes, general weakness, prolonged fatigue after exercise, headaches, arthralgia, sleep disturbance, neuropsychological complaints, and sudden onset of symptoms complex) and 2 signs (low grade fever. non~exudative pharyngitis, and palpable or tender lymph nodes).

The 1994 "Revised Case Definition of CFS" (Annals of Internal Medicine December 1994, Fukuda) is reached after a process of excluding other illnesses and is defined as: clinically evaluated, unexplained persistent or relapsing chronic fatigue of > 6 month duration, not otherwise explained by another known medical or psychiatric condition (, of new or definite onset, not the result of ongoing exertion, not substantially alleviated by rest, and that results in substantial reduction in previous levels of function; plus concurrent presence of (at least 4): impairment in short term memory or concentration, muscle pain, joint pain, headaches of  a new pattern) or severity,  unrefreshing sleep, sore throat, tender cervical or axillary lymph nodes, and post exertional malaise. Specific exclusions include: an ongoing medical illness that can obviously cause such fatigue, psychiatric illness psychotic features, dementia, anorexia or bulimia, alcohol or other substance abuse and obesity defined as a Body Mass Index (BMI) >45

 Neither Case Definition was intended to exclude patients from the diagnosis, but rather to help identify and treat underlying problems, and to define a better, more homogeneous, "CFS" group for research purposes. The larger population of patients with chronic fatigue, exertion intolerance, ill defined pain, insomnia, cognitive dysfunction and other symptoms probably has a number of underlying problems that include atypical presentation of known diseases, combined processes, psychological factors, and disease processes we as yet poorly understand.

Mounting research in the last 10 years has clearly shown that in spite of their weaknesses, the 1988 and 1994 Case Definitions successfully separate a group of afflicted and often disabled patients who do not simply have depression, poor motivation or any other readily identifiable problem. These patients deserve support and medical attention both clinically and on a research basis until more data is forthcoming.  Most likely, the CFS Case Definitions encompass a group made of up more than one cause and combination of causes.

 ________________________________________________________________________

The following discussion is based on published CFS research combined with my own experience and studies of CFS, and should be considered a working hypothesis:

CFS tends to occur in a "genetically predisposed' individual, who is typically "run down" by chronic or severe physical and/or emotional stress, and usually starts with a 'flu syndrome" that leaves chronic symptoms and fatigue rather than resolving in a normal fashion.

The exact cause of CFS is unknown, No single infection has been proven a primary cause of CFS, although many pathogens are under investigation as possible primary or secondary co-factors. Research suggests that patients with CFS have mildly suppressed Natural Killer cell activity and cell mediated immunity (probably abnormal CD4 activation of CD8 viral killing), with a shift toward B-cell mediated immunity. In the later stages of illness patients have more B-cell derived illness such as "allergy" symptoms, unregulated antibody systems (and thyroid and antinuclear antibodies), and pro-inflammatory cytokine release. Flow cytometry studies of lymph node biopsy show chronically activated T-cells (compared to peripheral blood) consistent with this chronically up-regulated state. It is not clear if recurrent or latent virus(s) are currently present and driving the system, or it is chronically “immune” driven

Many patients have significant autonomic nervous system dysfunction manifest by orthostatic intolerance sweating. Sicca syndrome (dry eyes and mouth) irritable bowel and reflux, bladder spasm, etc. Neurocognitive and neuropsychological symptoms are often prominent, and flare as the symptom complex flares. Abnormal sleep patterns with alpha intrusion abnormal Stage III, IV and REM phases are often present. In addition Hypothalamic-Pituitary-Adrenal (HPA) axis dysfunction has been documented as low CRH contisol, and perhaps a contribution to the marked orthostatic intolerance or Neurally Mediated Hypotension (NMH) documented on Tilt Table testing.  Numerous forms of brain imaging have demonstrated regional flow abnormalities (SPECT), areas of hypometabolism (PET) and areas of nonspecific demyelination or infarct (MRI).

In addition these areas of research genetic studies are underway in twins and affected families in order to better understand the pattern of occurrence

Since the cause of CFS is still unknown, the best general treatments at this point for the illness complex and associated symptoms are to: 

1) Reduce “stress” of all types.  Avoid pushing into severe symptoms. Pace activity.  Prevent flares of fatigue and pain by gaining insight and taking control of activity level.

2) Treat mood symptoms whether primary or secondary by any appropriate method, drug or non-drug.

 3) Achieve restorative sleep patterns as a high priority. Remove all things that aggravate sleep.  Practice good sleep hygiene. Take medications for sleep if other interventions fail

 4) Eat a healthy diet. Avoid excessive sugar, caffeine, alcohol, etc. try not to gain weight while ill.

 5)  Become generally well conditioned in terms of stretching, strengthening, and aerobic fitness. But do it carefully and within the limits or the CFS symptoms

  Additional recommendations on an individual basis:

 ---If primary or secondary viral or bacterial infection can be identified, it might respond to empiric treatment. Some CFS patients seem to have fewer community acquired viral infections when taking gamma shots especially in the early stages of CFS, but this has not been studied as an intervention.

---If orthostatic intolerance is a prominent symptom it usually responds to standard interventions such as oral fluids (2 liters of water daily) sodium (2-4 gms per day) and electrolyte supplementation and sometimes a trial of ProAmatine 2.5-15 mg 3 -4 times a day while up and active. (I.e. not while sleeping or resting)

 ---Stimulants are occasionally helpful, but should be used cautiously because of impact on sleep, anxiety, and the tendency to over exert instead of pace appropriately.

 ---Antidepressant and anti-anxiety medications can be helpful for some parts of the syndrome besides mood.

 EVERY prominent or focal symptom should be investigated and treated in a supportive manner.

Return to Home Page