Toward a clearer diagnosis of chronic fatigue syndrome

Researchers at the RIKEN Center for Life Science Technologies, in collaboration with Osaka City University and Kansai University of Welfare Sciences, have used functional PET imaging to show that levels of neuroinflammation, or inflammation of the nervous system, are higher in patients with chronic fatigue syndrome than in healthy people.

Chronic fatigue syndrome, which is also known as myalgic encephalomyelitis, is a debilitating condition characterized by chronic, profound, and disabling fatigue. Unfortunately, the causes are not well understood.

Neuroinflammation — the inflammation of nerve cells — has been hypothesized to be a cause of the condition, but no clear evidence has been put forth to support this idea. Now, in this clinically important study, published in The Journal of Nuclear Medicine, the researchers found that indeed the levels of neuroinflammation markers are elevated in CFS/ME patients compared to the healthy controls.

The researchers performed PET scanning on nine people diagnosed with CFS/ME and ten healthy people, and asked them to complete a questionnaire describing their levels of fatigue, cognitive impairment, pain, and depression. For the PET scan they used a protein that is expressed by microglia and astrocyte cells, which are known to be active in neuroinflammation.

The researchers found that neuroinflammation is higher in CFS/ME patients than in healthy people. They also found that inflammation in certain areas of the brain — the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons — was elevated in a way that correlated with the symptoms, so that for instance, patients who reported impaired cognition tended to demonstrate neuroinflammation in the amygdala, which is known to be involved in cognition. This provides clear evidence of the association between neuroinflammation and the symptoms experienced by patients with CFS/ME.

Though the study was a small one, confirmation of the concept that PET scanning could be used as an objective test for CFS/ME could lead to better diagnosis and ultimately to the development of new therapies to provide relief to the many people around the world afflicted by this condition.

Dr. Yasuyoshi Watanabe, who led the study at RIKEN, stated, “We plan to continue research following this exciting discovery in order to develop objective tests for CFS/ME and ultimately ways to cure and prevent this debilitating disease.”

Journal Reference: Y. Nakatomi, K. Mizuno, A. Ishii, Y. Wada, M. Tanaka, S. Tazawa, K. Onoe, S. Fukuda, J. Kawabe, K. Takahashi, Y. Kataoka, S. Shiomi, K. Yamaguti, M. Inaba, H. Kuratsune, Y. Watanabe. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. Journal of Nuclear Medicine, 2014; DOI:10.2967/jnumed.113.131045

 

Source: RIKEN. “Toward a clearer diagnosis of chronic fatigue syndrome.” ScienceDaily. ScienceDaily, 4 April 2014. https://www.sciencedaily.com/releases/2014/04/140404085538.htm

 

Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity).

METHODS: We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls.

RESULTS: The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups.

CONCLUSIONS: CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS.

Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

 

Source: van der Schaaf ME, De Lange FP, Schmits IC, Geurts DE, Roelofs K, van der Meer JW, Toni I, Knoop H. Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome. Biol Psychiatry. 2017 Feb 15;81(4):358-365. doi: 10.1016/j.biopsych.2016.07.016. Epub 2016 Aug 31. https://www.ncbi.nlm.nih.gov/pubmed/27817843

 

Gray matter volumes in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue with uncertain pathologic mechanism. Neuroimage may be an important key to unveil the central nervous system (CNS) mechanism in CFS. Although most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS, there are many factors that could affect GM volumes in CFS, including chronic pain, stress, psychiatric disorder, physical activity, and insomnia, which may bias the results. In this paper, through reviewing recent literatures, we discussed these interferential factors, which overlap with the symptoms of CFS.

 

Source: Tang LW, Zheng H, Chen L, Zhou SY, Huang WJ, Li Y, Wu X. Gray matter volumes in patients with chronic fatigue syndrome. Evid Based Complement Alternat Med. 2015;2015:380615. doi: 10.1155/2015/380615. Epub 2015 Feb 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352504/ (Full article)

 

Neuroimaging and the case of chronic fatigue syndrome

Abstract:

This article analyzes the use of neuroimaging in research into chronic fatigue syndrome. It reviews some works published in the 1990 s and investigates a specific aspect of these studies, namely the search for a cerebral abnormality, in the form of an altered activation pattern, which could provide a pattern for diagnosis and treatment of the disease. The understanding of chronic fatigue syndrome as a disease reduced to some cerebral findings is analyzed, arguing in favor of a broader vision of this disease that includes psychosocial elements of the patient’s life as opposed to entirely somatic explanations.

 

Source: Ortega F, Zorzanelli R. Neuroimaging and the case of chronic fatigue syndrome. Cien Saude Colet. 2011 Apr;16(4):2123-32. [Article in Portuguese]http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-81232011000400012&lng=en&nrm=iso&tlng=en (Full article)

 

The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome

Abstract:

The article analyzes a number of conditions that allowed the brain to become established as an etiological hypothesis in the case of chronic fatigue syndrome (CFS), together with other hypotheses related to organic causes, such as viruses and immunity. It also addresses the process of cerebralization of personhood, which grew out of the use of neuroimaging for research and diagnostic purposes and according to which the brain constitutes the prime place for looking for the cause of the diseases – including CFS – within the context of a somatic culture, intensified at the end of the twentieth century.

 

Source: Ortega F, Zorzanelli R. The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome. Hist Cienc Saude Manguinhos. 2010 Jun;17(2):289-305. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-59702010000200002&lng=en&nrm=iso&tlng=en (Full article)

 

Neuroimaging in chronic fatigue syndrome

Abstract:

The diagnosis of chronic fatigue syndrome (CFS) is made difficult by the absence of specific biomedical markers, and depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of this syndrome. Reported cognitive difficulties and/or complaints of headache may instigate referral for brain imaging.

This article will discuss the value of neuroimaging in evaluating CFS, specifically reviewing studies that (1) used static magnetic resonance imaging (MRI) to assess structural abnormalities; and (2) assessed regional cerebral blood flow (rCBF) via detection of Tc-99m hexamethylpropyl-eneamine oxime distribution by single-photon emission computed tomography (SPECT). Future research design considerations are explored including (1) the utilization of positron emission tomography (PET) and other emerging neuroimaging technologies; and (2) methodological concerns, i.e., the influence of psychopathology (such as depression) and neurologic disease (such as multiple sclerosis) as possible confounding factors.

 

Source: Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):50S-53S. http://www.ncbi.nlm.nih.gov/pubmed/9790482

 

Neuroimaging in chronic fatigue syndrome

The link between viral infection, the brain, and fatiguing illnesses has a long history. This combination forced itself on the medical imagination after events in Austria in the winter of 1916-17. A virulent form of influenza was noted, characteristically, to produce lethargy and later, to leave a host of neurological deficits in its wake. By the spring of 1918 several English cases of encephalitis lethargica had been reported and in the next year the disease was notifiable. The peak of the epidemic occurred in 1924 in the United Kingdom, at which time the Board of Control reported that many cases had been admitted to hospital with psychiatric disturbances.1 Hence the notion that apparent psychiatric illnesses may be misdiagnosed manifestations of a postinfectious cerebral disease began; it refuses to disappear.23

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486356/pdf/jnnpsyc00017-0001.pdf

 

Source: Cope H, David AS. Neuroimaging in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1996 May;60(5):471-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486356/