This paper appeared some time ago but it was difficult, given its highly technical nature, to understand its significance. It appears that it may be highly significant indeed. Visible and near infrared spectroscopy has been used in a wide variety of applications involving such diverse fields as agriculture, chemistry, pharmaceuticals and the petrochemical industries. Somehow these innovative researchers thought to try it out on CFS patients and it worked – in spades.

Thankfully, this study, with 92 CFS patients and 71 controls, was quite large and therefore probably quite robust. Two different statistical analyses identified 95% of the CFS serum samples (220/231) and 98% of the healthy serum samples (209/213) correctly. This is far more accurate than any other putative biomarker that has been proposed with respect to CFS. Rich Van Konynenburg queried Dr. Kuratsune about just what proteins the spectroscope was picking up but patent issues precluded him from divulging them.

This process is unbelievably easy to use. Dr. Sakudo noted that in contrast to the lengthy and subjective process now required to diagnose CFS patients that the NIH spectroscopy is objective, very rapid (takes less I second) and requires no experience and no skill (!). It looks like one simply attaches a probe to ones thumb and the machine quickly analyses the data and spits out the answer! In his overview Dr. Lapp said it was like Star Trek!

This study will only apply to a subset of CFS patients but its findings were so compelling that it was one of the highlights of the conference. The authors identified their patients as having ‘virus induced fatigue with central nervous dysfunction’ – not CFS per se but if they didn’t have ‘CFS’ they must have been darn close. These patients had high antibody titers to two common, opportunistic viruses, the HHV-6 and Epstein-Barr viruses that have long been of interest in CFS. This small study contained just 9 patients.

These patients were treated with the antiviral drug Valganciclovir for six months. Interestingly not all had declines in their antibody levels; some in fact had increased antibody titers (!), and all felt worse between weeks two and four, but all reported greatly increased energy levels. In fact the energy scores were high enough to suggest that almost all were well or nearly well, and most remarkably, they appeared to stay that way even after the medication was discontinued. Dr. Montoya pointed out one patient who must have been bedridden (5% energy level) before the trial but who had essentially recovered her health by the end of it. She had been ill for over 7 years. The consistency of the improvement was dramatic. No side effects were seen.

The above finding was probably not surprising to Martin Lerner, who has been finding that well targeted antiviral treatments have been effective in CFS for years. Dr. Lerner explained that he had been stricken with tremendous fatigue, light-headedness, muscle aches and exercise intolerance in 1988. An examination indicating his heart was dilated sparked his interested in cardiac issues in CFS. He was cured in an antiviral trial in the mid 1990’s. Dr. Lerner is quite old now – he walks with a stoop – but he gave an impressive presentation.

All his patients (37) meet the criteria for CFS and Dr. Lerner required that is study patients have initially high antibody titers to EBV and human cytomegalovirus (HMCV). Patients were given an oral form of the antiviral valganciclovir. Various measures of cardiac functioning and energy levels were assessed.

One exercise study showed that CFS patients have increased levels of a powerful pro-inflammatory anaphylatoxic component (C4a) of the complement response after exercise. Despite its positive result this study seemed to be doomed to the dustbin of CFS research history as it has never been replicated and is now only rarely mentioned. Dr. Shoemaker certainly took notice of it, however, as he reports here that he has found that levels of the C4a protein have been commonly elevated in the 1000 CFS patients he has seen. Consider that earlier study replicated!

Erythropoietin (EPO), interestingly, given its function as a blood volume enhancer, is apparently also very effective at reducing C4a levels in inflammatory diseases. This lead to Dr. Shoemaker giving 60 CFS patients 8000 units of EPO five times over 15 days and then measuring their C4a and symptom levels.

The results had an interesting dichotomy; while the C4a levels in all the patients dropped, about 80% of the patients symptomatically improved while 20% did not. It turns out that the 20% who did not improve had exceptionally high C4a levels. Normal C4a levels are below 2830 ng/ml. The responders dropped their C4a levels from 8300 to near normal, about 3200 ng/ml. The non-responders initial levels were so high, about 19,500 ng/ml that even substantial improvement still left them with higher levels than the responders had at baseline (12,500 ng/ml). In short, it appeared that their C4a levels were too high for the EPO to give them relief at the dosage given.

What happens after CFS patients get off a drug is almost as important as what happens when they are on it. Dr. Shoemaker found that 2/3^rds of the responders relapsed while 1/3^rd of them did not. This short test of EPO appeared to fix the C4a problems in the non-relapsed group - their C4a levels remained low – but did not in those who relapsed – their C4a levels zoomed up again.

EPO has neuroprotective as well as anti-inflammatory (and blood volume) properties. There are two ways it protects nerve cells, both of which are of high interest in CFS; it improves blood flows in the capillaries and it prevents nerve cell apoptosis or suicide.

Dr. Shoemaker gave the same amount of EPO (5 doses of 8,000 units over two weeks) to 35 CFS patients and measured the metabolite levels in their hippocampus before and after treatment. Interestingly his initial testing found the same thing Paul Nestadt did in his MRS study (see Brain section); high lactate levels (77% of CFS patients) plus abnormal glutamate/glutamine ratios (97% of CFS patients).

He found that lactate levels normalized on EPO in all cases and glutamate/glutamine ratios normalized in just over half. He believes, in common with Dr. Park, that CFS is characterized by a systemic (central nervous system) inflammation and that bringing down the inflammation was the key to the cognitive improvements seen. He did note that the cognitive problems in his patients were not resolved. Both Dr. Natelson’s and Dr. Baraniuk’s cerebrospinal fluid studies may also suggest CNS inflammation is present.

Dr. Cheney, Dr. Park and Dr. Shoemaker all believe that elevated pulmonary artery pressure (PAP) plays a role in the cardiac problems seen in CFS. Dr. Cheney and Dr. Park have flagged cognition; here Dr. Shoemaker focuses on exercise intolerance. Dr. Shoemaker noted that drops in PAP during exercise allow for increased venous blood flows to the heart. Echocardiography tests provide indirect evidence that PAP does not drop in CFS patients during exercise. This suggests that reduced blood flows to the heart could play a role in the exercise intolerance seen in CFS.

Tadalafil also improves erectile dysfunction. Tadalafil is, in fact, the last of the big three drugs (Viagra, Levitra, Cialis) that have recently been introduced in the American market to improve male sexual performance. A study by the Los Angeles researcher, Dr. Friedman, is attempting to increase brain blood flows in CFS patient with Viagra.

Dr. Shoemaker gave 20 mg. tadalafil every 3 days to 30 CFS male patients for a total of 5 doses. Changes in erectile ‘behavior’ were noticed in 93% of males, symptom reduction occurred in 90% and PAP improved in 84%. Both shortness of breath and fatigue after exercise improved. Once again CFS patients appeared to respond quickly and positively to Dr. Shoemaker’s regime.