From BMC Medicine, 8 March 2013 (open access journal).
A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior
Gerwyn Morris(1), George Anderson (2), Piotr Galecki (3), Michael Berk (4-8) and Michael Maes (4.9).
(1) Tir Na Nog, Bryn Road Seaside 87, Llanelli, SA152LW, UK
(2) CRC Clinical Research Centre/Communications, Laurel Street 57, Glasgow, G11 7QT, UK
(3) Department of Adult Psychiatry, Medical University of Lodz, Aleksandrowska 159, Lodz, 91229, Poland
(4) Barwon Health, School of Medicine, Deakin University, P O Box 291, Geelong, 3220, Australia
(5) Orygen Youth Health Research Centre, Poplar Road 35, Parkville, 3052, Australia
(6) Centre of Youth Mental Health, University of Melbourne, Poplar Road 35, Parkville, 3052, Australia
(7) The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Royal Parade 30, Parkville, 3 052, Australia
(8)Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, 3052, Australia
(9)Department of Psychiatry, Chulalongkorn University, Rama 4 Road 1873, Pathumwan, Bangkok, 10330, Thailand
It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acuteinfections/injury being principally mediated through proinflammatory cytokines.
Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS.
While sickness is an adaptive response induced byproinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the
pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acuteresponse to infection/injury, the trigger factors in ME/CFS are less well defined andencompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.
From Frontiers in Integrative Physiology, 15 March 2013.
Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome
Anthony J. Ocon
Medicine/Physiology, NYMC, USA
Chronic Fatigue Syndrome (CFS) is defined as greater than 6 months of persistent fatigue that is experienced physically and cognitively. The cognitive symptoms are generally thought to be a mild cognitive impairment, but individuals with CFS subjectively describe them as ‘brain fog.’
The impairment is not fully understood and often is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or a haziness in thought processes. Causes of ‘brain fog’ and mild cognitive impairment have been investigated. Possible physiological correlates may be due to the effects of chronic orthostatic intolerance in the form of the Postural Tachycardia Syndrome and decreases in cerebral blood flow.
In addition, fMRI studies suggest that individuals with CFS may require increased cortical and subcortical brain activation to complete difficult mental tasks. Furthermore, neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory. The cognitive impairments are then perceived as an exaggerated mental fatigue.
As a whole, this is experienced by those with CFS as ‘brain fog’ and may be viewed as the interaction of physiological, cognitive, and perceptual factors. Thus, the cognitive symptoms of CFS may be due to altered cerebral blood flow activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information, which is then perceived as fatiguing and experienced as ‘brain fog.’
Future research looks to further explore these interactions, how they produce cognitive impairments, and explain the perception of ‘brain fog’ from a mechanistic standpoint.
From Frontiers in Integrative Physiology, 7 March 2013.
Brain dysfunction as one cause of CFS Symptoms including difficulty with attention and concentration
Benjamin H. Natelson
Department of Pain Medicine & Palliative Care, Beth Israel Medical Center, USA
We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify CFS patients into subgroups.
To date, we have shown that stratifying based on the presence or absence of co-morbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres. We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group.
Objective evidence of orthostatic intolerance may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms.
We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.
From Kansenshogaku Zasshi, January 2013.
A case of Lyme Disease requiring over 1 year to diagnose at an infectious-disease clinic.
[Article in Japanese]
Iwata K, Shimada T, Kawabata H.
Division of Infectious Diseases, Kobe University Hospital.
A 42-year-old woman presenting with years of fever and vague symptoms could not be satisfactorily diagnosed in physical examination or conventional workups. She was presumptively diagnosed with chronic fatigue syndrome and treated symptomatically.
Fourteen months after the initial visit, she developed left facial palsy. Lyme disease serology was positive. Four weeks of oral amoxicillin ameliorated symptoms.
Only 5 to 15 cases of Lyme disease are reported annually in Japan, mostly from the northeastern-most island of Hokkaido. It may occur anywhere in Japan, however; probably is underdiagnosed. Lyme disease may cause fevers of unknown origin. Astute clinical suspicion and appropriate workups are thus needed to diagnose this infection.
From Clin Exp Immunol. April 2013.
Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls.
Bradley A S, Ford B, Bansal A S
Department of Immunology, St Helier University Hospital NHS Trust, Carshalton, Surrey, UK.
Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms.
The onset of CFS may follow a viral infection or period of stress.
Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity.
To date, defects in B cell numbers or function have not been shown in the literature.
However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients.
We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping.
We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age- and gender-matched healthy controls (HC).
CFS patients had greater numbers of naive B cellsas a percentage of lymphocytes: 6·3 versus 3·9% in HC (P=0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P=0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P=0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P=0·013).
While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.
From Autonomic Neuroscience – basic and clinical, 13 March 2013 [Epub ahead of print].
Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome.
Togo F, Natelson BH.
Educational Physiology Laboratory, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
We determined whether alterations in heart rate dynamics during sleep in patients with chronic fatigue syndrome (CFS) differed from controls and/or correlated with changes of sleepiness before and after a night in the sleep laboratory. We compared beat-to-beat RR intervals (RRI) during nocturnal sleep, sleep structure, and subjective scores on visual analog scale for sleepiness in 18 CFS patients with 19 healthy controls aged 25-55 after excluding subjects with sleep disorders.
A short-term fractal scaling exponent (α1) of RRI dynamics, analyzed by the detrended fluctuation analysis (DFA) method, was assessed after stratifying patients into those who reported more or less sleepiness after the night’s sleep (a.m. sleepier or a.m. less sleepy, respectively).
Patients in the a.m. sleepier group showed significantly (p<0.05) higher fractal scaling index α1 during non-rapid eye movement (non-REM) sleep (Stages 1, 2, and 3 sleep) than healthy controls, although standard polysomnographic measures did not differ between the groups. The fractal scaling index α1 during non-REM sleep was significantly (p<0.05) higher than that during awake periods after sleep onset for healthy controls and patients in the a.m. less sleepy group, but did not differ between sleep stages for patients in the a.m. sleepier group. For patients, changes in self-reported sleepiness before and after the night correlated positively with the fractal scaling index α1 during non-REM sleep (p<0.05). These results suggest that RRI dynamics or autonomic nervous system activity during non-REM sleep might be associated with disrupted sleep in patients with CFS.
MEA NOTE: Acetaminophen = Paracetamol
From Pain Physician, March/April 2013(full text available).
Does Acetaminophen Activate Endogenous Pain Inhibition in Chronic Fatigue Syndrome/Fibromyalgia and Rheumatoid Arthritis? A Double-Blind Randomized Controlled Cross-over Trial
Mira Meeus PhD, Kelly Ickmans PT, Filip Struyf PhD, PT, Linda Hermans PT, Kevin Van Noesel PT, Jorinde Oderkerk PT, Luc S DeClerck MD, PhD, Greta Moorkens MD, PhD, Guy Hans MD, PhD, Sofie Grosemans FN, and Jo Nijs PhD
Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown.
We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing.
Double-blind randomized controlled trial with cross-over design.
Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation.
After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant.
The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined.
This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated.