Treatment trial for Florinef
Patients with CFS are more likely than healthy persons to develop neurally mediated hypotension (NMH), a disorder that involves a precipitous drop in systolic blood pressure (at least 20-25 mm Hg) in response to prolonged orthostatic stress. A recent study found that fludrocortisone (Florinef), often used to treat low blood pressure, used alone does not alleviate the symptoms of CFS patients better than a placebo.

Researchers at Johns Hopkins University and the National Institute of Allergy and Infectious Diseases studied 100 adults diagnosed with CFS and NMH. The 1994 consensus criteria were used to diagnose CFS, and NMH was identified by a two-stage tilt-table test performed by the Hopkins group.

Half of the patients received Florinef and half received a placebo for nine weeks. Based on standardized, daily self-ratings of overall wellness and other measures of illness severity, there was no significant difference in benefit. Approximately 14% of those treated with Florinef had a notable improvement in overall well-being compared with 10% in the placebo group.

The researchers cautioned that lack of symptomatic improvement with Florinef does not disprove the hypo-thesis that NMH could be contributing to some CFS symptoms, particularly because combination therapy is typically used in the treatment of NMH.

Further studies are needed to determine whether other medications, used in combination or alone, would be more effective in treating NMH in CFS patients.

Rowe et al. Fludrocortisone acetate to treat NMH in chronic fatigue syndrome. JAMA. 2001; 285: 52-9.

Sleep disorders and CFS studied
According to a study conducted by a group of Belgian researchers, CFS cannot be attributed solely to a somatic expression of a primary sleep disorder (PSD) or sleepiness.

Forty-six CFS patients were clinically examined and underwent two nights of all-night monitoring during sleep. Of the patients studied, 54% did not have PSD and 69% had no sleepiness. While 46% of the CFS patients showed signs of one type of sleep disorder—sleep apnea—none were diagnosed with narcolepsy or hypersomnia.

No association was found between the presence of a sleep disorder and the patient’s clinical status. Objective and subjective measures of sleepiness were not associated with CFS, and CFS patients without a PSD could not be distinguished clinically from those with a PSD or sleepiness.

Le Bon O et al. How significant are primary sleep disorders and sleepiness in chronic fatigue syndrome? Sleep Research Online. 2000; 3:43-8.

Possible motor cortex impairment
Researchers at the University of California compared the motor cortex excitability of 14 CFS patients to 14 age-matched healthy controls. The researchers used transcranial magnetic stimulation (TMS) to elicit motor-evoked potentials while subjects performed repetitive, bilateral opening-closing movements of the index finger onto the thumb. Evoked potentials were measured at regular intervals following periods of exercise.

The rate of movement was significantly slower in the CFS subjects than in the controls, while the threshold of TMS needed to elicit potentials was significantly higher in the individuals with CFS. 

Although the controls exhibited a delayed facilitation of evoked potentials after 15-30 minutes of rest, delayed facilitation was absent in the CFS patients.

These findings add weight to other groups’ evidence that CFS leads to measurable neurocognitive impairment.

Starr A et al. Motor cortex excitability in chronic fatigue syndrome. Clin Neuro-physiol. 2000; 111: 2025-31.

Evidence of neuro-endocrine abnormalities
Several studies have suggested hypoactivation of the hypothalamic-pituitary-adrenal axis in CFS. One possible determinant of this abnormality is reduced secretion of corticotropin-releasing hormone (CRH).

Researchers at Cornell University tested this hypothesis by measuring adrenocorticotropic hormone (ACTH) and cortisol response to a one-hour infusion of vasopressin in 19 CFS patients and 19 controls. Because CRH and vasopressin act together to stimulate ACTH secretion, the response to the vasopressin infusion acts as an indirect measure of hypothalamic CRH secretion.

The CFS patients had a reduced ACTH response and more rapid cortisol response to the infusion than the controls, providing evidence of endocrine abnormalities.

Altemus M et al. Abnormalities in response to vasopressin infusion in chronic fatigue syndrome. Psychoneuroendocrinol. 2001: 26: 175-88.