Research, ongoing studies, and use of new technology

Research finding

He is now looking at the brain by studying spinal fluid—the fluid that bathes the brain—and using brain imaging techniques.

Brain MRIs showed more abnormalities in CFS subjects with no psychiatric disorder as compared to CFS with a psychiatric disorder or to healthy controls. This finding again points to encephalopathy, especially in CFS patients without a coexisting psychiatric disorder.

The study also found significantly more abnormalities in the frontal lobe of the brain, as well as a reduction of the brain blood flow than the other groups.

Spinal taps on forty-four CFS patients showed that 30% of those patients had spinal fluid outside the norm, including elevated protein and increased white blood cells. Again, there were more spinal fluid abnormalities in patients without psychiatric comorbidities and 27% of the normal spinal fluid patients had depression.

While one-third of CFS patients experience a sudden flu-like onset of symptoms, Dr. Natelson looked for viral infections while studying the spinal fluid and found no convincing data for persistent viral infections. Only a small fraction of patients had shown evidence of reactivated Epstein Barr Virus (EBV).

He also found that Xenotropic Murine Leukemia Retrovirus (XMRV) was negative in the spinal fluid. Once an exciting possible cause for CFS, Natelson did not find the presence of the retrovirus in the spinal fluid. "That story is behind us," said Natelson.

He was also unsuccessful in replicating studies that showed immune activation, in which the immune system is turned on by a virus and then keeps running in CFS patients.

The search for biomarkers

Over time, reduced natural killer cells seem to be the only evidence of a reduced immune system that holds true across many studies. However, Natelson has found evidence for the opposite.

While the pro-inflammatory cytokines make you feel sick, he has found evidence that one of the anti-inflammatory cytokines, IL-10, was elevated and may contribute to disturbing sleep.

With today's technology, Dr. Natelson has come closer to finding biological abnormalities that could be used to unequivocally identify and diagnose Chronic Fatigue Syndrome in a specific subset of patients.

Using MRIs to look at chemicals in the brain, Natelson compared Ventricular Lactate in CFS and controls as a possible biomarker. He found that CFS patients without a coexisting psychiatric disorder had higher lactate, and he has now replicated this study.

Natelson also believes that 15% of CFS patients have an autoimmune disorder that is being missed.

He discussed Sjögren's Syndrome, another autoimmune illness, the main early symptoms of which are dry eyes and dry mouth but also include prolonged fatigue. A lip biopsy is the definitive way to diagnose Sjögren's, in which the body attacks its own tear and salivary glands.

In his small study, all the patients had a negative result to Sjögren's antibody blood test, but about half of the 25 patients reported dry eyes and mouth. Then the tear production was measured and it was found 10 of those 13 patients had abnormal tear production.

When lip biopsies were done on those patients, 1/3 were found to have an abnormal biopsy. Dr. Natelson thinks even though this was a small study, it may prove to be reliable in predicting autoimmune disease.

New technology

New technology now allows researchers to identify all the proteins in the spinal fluid. Through the use of mass spectrometry, an analyzer that separates proteins and breaks them down further and further than ever before, Natelson compared the proteins in spinal fluid between healthy controls, CFS patients and those with Post Lyme Fatigue Syndrome.

There are 305 proteins common to both CFS and Post-Lyme disease.

Natelson found 738 proteins unique to those with CFS. He is now working to identify three or four of those proteins that are specific to CFS to be used as a biomarker to diagnose at least a subset of CFS patients.

Findings so far

Some CFS patients have poorer neuropsychological test results, abnormal brain MRI imaging, poorer function in health related quality of life, wider reduction in brain blood flow, more abnormal spinal fluid results, and higher levels of ventricular lactate, all which point to a brain disease.

Ongoing studies

Natelson is looking to better define the subgroup with a neurological cause and develop specific treatments and medications for them. In order to complete this new study, the National Institutes of Health (NIH) has awarded him a grant to repeat all of his past studies, including neuroimaging, neuropsychology and spinal taps, but all on the same group of patients.

There is also a new grant from the CDC to find out if the diagnosis of CFS is the same across centers.

This has never been done. This study will compare how Dr. Natelson, a neurologist from NY, Dr. Nancy Klimas, an immunologist from Florida, and a leading CFS researcher/clinician, and another large group of practitioners expert in CFS make the CFS diagnosis.

There is a pharmaceutical industry study on using Milnacipran (brand name Savella) to see if it proves useful in reducing fibro-fog in FM patients. Milnacipran is a class of medications called selective serotonin and norepinephrine reuptake inhibitors.

Colleagues of Dr. Natelson's from Cornell have just recently received notice that a study to try to improve brain chemistry with an available food supplement will be funded.