By Richard N. Podell, M.D., MPH
For most people with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) central nervous system function is abnormal. However, we don’t understand the mechanisms involved. Many experts suspect an inflammatory component, but the results from cytokine studies of cerebrospinal fluid have been uncertain.
Now, researchers at the RIKEN Center for Life Science Technologies in Hyogo, Japan, have directly measured neural inflammation using a combination of PET scan and MRI imaging. (1)
Their key findings: Compared to healthy controls, nine patients with CFS/ME showed evidence of abnormal activation of microglia and/or astrocyte immune cells within the brain. In specific brain areas the degree of immune activation correlated closely with the severity of the patients’ symptoms.
Positron emission tomography (PET) is a nuclear medicine technique that produces a three-dimensional image of physiological processes within the body. PET works by attaching a gamma ray emitting tracer to a biological molecule that is normally processed by specific cell types. Appropriate computer soft ware can construct a three-dimension image of the tracer’s concentration. A concurrent MRI or CT scan further defines the anatomical locations.
The tracer for this study (called 11-C-(R)-PK111995) attaches to a specific translocator protein called TSPO. When microglia or astrocytes are metabolically active TSPO is expressed. PET scan imaging of TSPO is a standard technique for studying inflammation in neurological disorders.
For the nine patients in this study the intensity of PET imaging was substantially higher among the CFS/ ME patients compared to controls in the following brain areas: The cingulate cortex, hippocampus, thalamus, mid brain and pons.
Equally impressive, there was a high correlation between the TSPO image intensity and the severity of the patients’ reported symptoms. For example, the peak value signal within the left thalamic intralaminar nucleus was highly correlated with the cognitive impairment score. (r=0.86; P=0.0028) and also with the patients’ intensity of fatigue (r=0.63; P=0.0683).
If further studies confirm these findings, we should ask the following questions:
Why are the brain’s immune cells inflamed?
Is there an on-going infectious process? Did an initial but no longer active insult trigger sustained inflammation? Is the inflammation responding to other nervous system damage e.g. over-activity of neurons to compensate for the functional limitations caused by CFS/ME?
Would it be useful (or harmful) to suppress this inflammation using drugs or natural products?
As a clinician I’ll focus on the second question.
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Standard anti-inflammatories such as ibuprofen and prednisone do not help. However, other anti-inflammatories work through different pathways. Might these be worth trying?
For example, low dose naltrexone (LDN) is believed to have a “calming” effect on brain microglia cells. Two double blind studies from Stanford Medical School show improvement in fibromyalgia symptoms with LDN treatment. (2)
The tetracycline derivatives Minocycline and Doxycycline have well recognized anti-inflammatory effects. Colchicine, and pentoxifylline can act as anti-inflammatory. Quite a few herbs do as well. These include curcumin, panax ginseng, green tea, resveratrol, and Ginger. (3) None of these have been systematically tested for CFS/ME. All could be considered to be “relatively” safe.
In contrast, Rituximab, a powerful and potentially toxic B cell suppressor has one double blind study from Norway. This found a statistically significant advantage for Rituximab over placebo, dramatically reducing the symptoms of CFS/ME. (4) Fortunately, the investigators were able to fund a replication study, which is now under way.
In contrast, in the USA and most other countries CFS/ME remains an orphan disease. So it’s not likely that we will see double blind studies of treatments any time soon In the meantime, should CFS/ME clinicians selectively offer (with proper informed consent) empirical treatment with anti-inflammatory medicines or herbs? Your thoughts will be appreciated.
(1) Nakatoni, Y, Watanabe, Y, Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11 C-R-PK11195 PET Study, J Nucl Med published on March 24, 2014 as dol:10.2967/jnmed.113.131045
(2) Naltrexone and Fibromyalgia: Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15. Note; You can read the free article here.
(3) Natural Products and Microglia: Choi, D, Koppula, S, Suk, K, Inhibitors of Microglial Neurotoxicity: Focus on Natural Products, Molecules, 2011, 16, 1021-43l doi =L 19,3390/molecules 1602021
(4) Fluge Ø1, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H, Mella O. Benefit from B-lymphocyte depletion using the anti-CD20 antibody Rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358. Epub 2011 Oct 19. Note: You can read the free article here.
Richard Podell, M.D., MPH is a graduate of Harvard Medical School and the Harvard School of Public Health. He has been treating patients with ME-CFS and Fibromyalgia for more than 20 years. A clinical professor at New Jersey’s Robert Wood Johnson Medical School, Dr. Podell see patients at his Summit, NJ and Somerset, NJ offices.