The chronic fatigue syndrome is a recurring illness of unknown cause characterized by incapacitating fatigue and a range of symptoms and laboratory findings suggestive of hypothalamic dysfunction [1-3]. Rare patients who have died from other acute causes have had cellular infiltrates in the hypothalamus [4]. The syndrome usually follows a flu-like illness, and circumstantial evidence has implicated enteroviruses [1]. We therefore examined the central nervous system of a woman with the syndrome who died from suicide for the presence of enterovirus.

In June 1992, a 30-year-old woman who had met all criteria for the syndrome for 5 years was brought to the hospital after attempted suicide and died of complications. Immediately after death, tissue was removed from the brain, heart, skeletal muscle, lungs, and spleen and was stored at –80°C. The brain samples were from the frontal, temporal, parietal, and occipital cortices and from the mid-brain, hypothalamus, and brain stem. Control samples were obtained from four patients who died of cerebrovascular diseases and from four age- and sex-matched patients who had committed suicide during severe depression over the next 2 months.

Ribonucleic acid (RNA) from the tissues was prepared for analysis by polymerase chain reaction (PCR). The RNA samples were prepared and amplified using oligonucleotide primers.

No enteroviral sequences were detected in any of the control tissues. Positive PCR sequences were detected in the muscle, heart, and brain samples from the hypothalamus and brain stem region of our patient with the syndrome (Figure 1). Sequence analyses on the PCR products were compatible with exogenous virus and not with contamination. The results showed an enterovirus with an 83% similarity to Coxsackievirus B3. Although the findings may represent chance occurrence, they further support the possibility that hypothalamic dysfunction exists in the pathogenesis of the syndrome. Also, they suggest that the chronic fatigue syndrome may be mediated by enterovirus infection and that persistent symptoms may reflect selective persistence in affected organs.

View larger version (107K): [in this window] [in a new window]   Figure 1. Polymerase chain reaction products isolated from hypothalamic samples of a patient with the chronic fatigue-syndrome and three controls. The agarose gels were stained with ethidium bromide and were visualized in ultraviolet light. Left. The results with Zoll primers 2+3 (positive band is 155 base pairs). Right. The results with Zoll primers 1+3 (440 base pairs). Lane N shows three hypothalamic samples from controls. Lane P shows independent RNA preparations and polymerase chain reactions carried out on the hypothalamus of the patient with the chronic fatigue syndrome. Lane L = 123 base pair DNA ladder.