Category: Symptoms

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

Abstract:

BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms.

METHODS: This was a cross-sectional study of 395 UK ME/CFS Biobank participants, recruited from primary care and the community, using similar standardised protocols, and matched by age, sex and geographical area. Data were collected from participants using a standardized written questionnaire at clinical visits. Cognitive symptoms included problems with short-term memory, attention, and executive function. Sleep symptoms included unrefreshing sleep and poor quality or inadequate duration of sleep. All participants reported symptoms based on an ordinal severity scale. Multivariable logistic regression was carried out in the ME/CFS group to investigate socio-demographic factors associated with severe symptoms.

RESULTS: All cognitive and sleep symptoms were more prevalent in the ME/CFS group, with 'trouble concentrating' (98.3%) the most commonly reported symptom. Severe symptoms were also more commonly reported in the ME/CFS group, with 55% reporting 'severe, unrefreshing sleep'. Similarly, in the MS group, the most commonly reported severe symptoms were sleep-related. Logistic regression analysis revealed that ME/CFS patients aged over 50 years were more than three times as likely to experience severe symptoms than those younger than 30 (OR 3.23, p = 0.031). Current smoking was associated with severe symptoms, increasing the risk by approximately three times (OR 2.93, p = 0.003) and those with household incomes of more than £15,000 per year were less likely to experience severe symptoms compared to those earning less than this (OR 0.31, p = 0.017).

CONCLUSIONS:Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Our findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms. Future research should aim to develop strategies to prevent the progression of severe cognitive and sleep symptoms through early interventions that prioritise patients identified as being at highest risk.

Source: Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. doi: 10.1186/s12883-017-0896-0. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0896-0 (Full article)

Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) share some similar symptoms with fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, post-exertional malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor.

PURPOSE:The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors.

METHOD: An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness.

RESULTS: Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM.

DISCUSSION: The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Source: McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. https://www.ncbi.nlm.nih.gov/pubmed/28603794

Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study

Abstract:

BACKGROUND: Commonalities in the core symptoms of fatigue and cognitive dysfunction experienced by chronic fatigue syndrome (CFS, also known as ME) and multiple sclerosis (MS) patients have been described. Many CFS and MS patients also experience chronic pain, which has been attributed to central sensitization in both groups of patients. However, the characteristics of pain in CFS and MS patients have not been compared.

OBJECTIVES: To compare experimental pain measurements in patients with CFS or MS and healthy controls.

STUDY DESIGN: Observational study.

SETTING: This study took place in Belgium at Vrije Universiteit Brussel and the University of Antwerp.

METHODS: Pressure pain thresholds, temporal summation, conditioned pain modulation, and occlusion cuff pressure thresholds rated as painful (1st cuff pressure threshold) and as 3/10 on a verbal numerical scale (2nd cuff pressure threshold) were measured in patients with CFS (n = 48), MS (n = 19) and healthy pain-free controls (n = 30). Adjusted between-group differences were estimated using linear regression models.

RESULTS: Finger pain pressure thresholds of patients with CFS, compared with patients with MS, were 25% lower (difference ratio 0.75 [95% CI 0.59, 0.95], P = 0.02) and shoulder pain pressure thresholds were 26% lower (difference ratio 0.74 [0.52, 1.04], P = 0.08). Compared with patients with MS, patients with CFS had 29% lower first cuff pressure threshold (difference ratio 0.71 [0.53, 0.94], P = 0.02) and 41% lower 2nd cuff pressure threshold (0.59 [0.41, 0.86], P = 0.006). Finger temporal summation was higher in patients with CFS than in patients with MS (mean difference 1.15 [0.33, 1.97], P = 0.006), but there were no differences in shoulder temporal summation or conditioned pain modulation at either site. Differences between patients with CFS and MS tended to be greater than between either patient group and healthy controls. Pain pressure thresholds and cuff pressure thresholds tended to be positively correlated, and temporal summation negatively correlated, with higher physical function and lower fatigue in both groups of patients. Subjective pain in patients with CFS but not in patients with MS was strongly negatively correlated with pain pressure thresholds and cuff pressure thresholds, and positively correlated with temporal summation.

LIMITATIONS: The main limitations of our study are the relatively small sample sizes, its cross-sectional design, and its exploratory nature.

CONCLUSIONS: We found differences in the characteristics of pain symptoms reported by patients with CFS and patients with MS, which suggest different underlying mechanisms. Specifically, overactive endogenous pain facilitation was characteristic of pain in patients with CFS but not in patients with MS, suggesting a greater role for central sensitization in CFS.

Source: Collin SM, Nijs J, Meeus M, Polli A, Willekens B, Ickmans K. Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study. Pain Physician. 2017 May;20(4):E489-E497. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=20&page=E489 (Full article available as PDF.)

Differences in ME and CFS Symptomology in Patients with Normal and Abnormal Exercise Test Results

Abstract:

Post-exertional malaise (PEM) is a cardinal symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS), which often distinguishes patients with this illness from healthy controls or individuals with exclusionary illnesses such as depression. However, occurrence rates for PEM fluctuate from subject to how the symptom is operationalized. One commonly utilized method is exercise testing, maximal or submaximal. Many patients with ME and CFS experience PEM after participating in these tests, and often show abnormal results. However, some patients still exhibit normal results after participating in the exercise testing.

This study examined the differences between two patient groups with ME and CFS, those with normal results and those with abnormal results, on several PEM-related symptoms and illness characteristics. The results suggest those that displayed abnormal results following testing have more frequent and severe PEM, worse overall functioning, and are more likely to be bedbound than those that displayed normal results.

 

Source: Stephanie L McManimen and Leonard A Jason. Differences in ME and CFS Symptomology in Patients with Normal and Abnormal Exercise Test Results. Int J Neurol Neurother, IJNN-4-066, (Volume 4, Issue 1), Research Article; ISSN: 2378-3001 DOI: 10.23937/2378-3001/1410066 (Full article)

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People

Abstract:

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS.

OBJECTIVES: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity.

STUDY DESIGN: A controlled experimental study.

SETTING: The study was conducted at the Human Physiology lab of a University.

METHODS: Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis.

RESULTS: Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability.

LIMITATIONS: Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.

CONCLUSIONS: Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.

 

Source: Oosterwijck JV, Marusic U, De Wandele I, Paul L, Meeus M, Moorkens G, Lambrecht L, Danneels L, Nijs J. The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People. Pain Physician. 2017 Mar;20(3):E389-E399. https://www.ncbi.nlm.nih.gov/pubmed/28339438

 

Link between early menopause, chronic fatigue syndrome discovered

A newfound link between chronic fatigue syndrome (CFS) and early menopause was reported online today in Menopause, the journal of The North American Menopause Society (NAMS). This link, as well as links with other gynecologic problems and with pelvic pain, may help explain why CFS is two to four times more common in women than in men and is most prevalent in women in their 40s. Staying alert to these problems may also help healthcare providers take better care of women who may be at risk for CFS, say the authors of this population-based, case-control study.

Based on a long-term study of CFS and fatiguing illnesses in Georgia, this analysis from Centers for Disease Control scientists included 84 women with CFS and 73 healthy control women who completed detailed gynecologic history questionnaires. Striking differences emerged from the comparison between those groups.

The women with CFS were some 12 times more likely to have pelvic pain that wasn’t related to menstruation (such as pelvic floor dysfunction, interstitial cystitis/painful bladder syndrome or IC/PBS, and irritable bowel syndrome) than the control women. The women with CFS also reported excessive bleeding (74% vs 42%) much more often as well as significantly more bleeding between periods (49% vs 23%) and missing periods (38% vs 22%). In addition, they used hormones for purposes other than contraception (such as to treat irregular periods, menopausal symptoms or bone loss) much more often (57% vs 26%).

Also striking, most women with CFS–66%–had undergone at least one gynecologic surgery, compared with only 32% of controls, most commonly hysterectomy (55% versus 19%). Women with CFS underwent menopause early (at or before age 45) because of hysterectomy much more often (62% vs 33%). (Surgical menopause occurs immediately when both ovaries are removed at hysterectomy and often prematurely even when ovaries are preserved.) Bleeding as the reason for hysterectomy was significantly more common in the women with CFS. They also underwent natural menopause earlier, but the numbers were too small to show a significant difference.

Although CFS has previously been linked with pelvic pain and gynecologic conditions such as endometriosis, IC/PBS, polycystic ovaries, and menstrual abnormalities, this is the first study to show a link with early menopause. Sex hormone abnormalities or their early decrease or disappearance may underlie these links, and the authors called for more research to find out whether they do play a role in causing or perpetuating CFS in some women. But meanwhile, they emphasized, women’s healthcare providers need to stay alert for symptoms of CFS, such as sleep or memory problems, muscle and joint pain, and worse symptoms after exertion, developing in women who have these gynecologic or pelvic pain problems.

“CFS can take a tremendous toll on women’s lives at midlife and on our society and healthcare system. Being aware of the association of CFS and earlier menopause can help providers assist women in sorting out symptoms of CFS from symptoms of menopause,” says NAMS Executive Director Margery Gass, MD, NCMP. This paper also raises the chicken and egg question: Is early menopause the cause of later health problems or simply the result of earlier health problems not recognized as the cause of early menopause?

Journal Reference: Roumiana S. Boneva, Jin-Mann S. Lin, Elizabeth R. Unger. Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women. Menopause, 2015; 1 DOI: 10.1097/GME.0000000000000411

 

Source: The North American Menopause Society (NAMS). “Link between early menopause, chronic fatigue syndrome discovered.” ScienceDaily. ScienceDaily, 4 February 2015.  https://www.sciencedaily.com/releases/2015/02/150204075324.htm

 

Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests

University of Leicester research team discovers vision-related abnormalities that could help in diagnosis of illness

People suffering from Chronic Fatigue Syndrome (CFS) could experience higher levels of visual stress than those without the condition, according to new research from the University of Leicester.

CFS, also known as Myalgic Encephalomyelitis (ME), is a condition that causes persistent exhaustion that affects everyday life and doesn’t go away with sleep or rest. Diagnosis of the condition is difficult as its symptoms are similar to other illnesses.

A research team from the University of Leicester led by Dr Claire Hutchinson from the Department of Neuroscience, Psychology and Behaviour has examined patients with and without CFS and has found that those suffering from the condition are more vulnerable to pattern-related visual stress, which causes discomfort and exhaustion when viewing repetitive striped patterns, such as when reading text.

The results of the study, which is published in the journal Perception, could help in the diagnosis of CFS, as the findings suggest that there are visual system abnormalities in people with ME/CFS that may represent an identifiable and easily measurable behavioural marker of the condition.

Dr Hutchinson explained: “Diagnosis of ME/CFS is controversial. With the exception of disabling fatigue, there are few definitive clinical features of the condition and its core symptoms, overlap with those often prevalent in other conditions. As a result, ME/CFS is often a diagnosis of exclusion, being made as a last resort and possibly after a patient has experienced a series of inappropriate treatments of misdiagnosed disorders.

“It is imperative therefore that research focuses on identifying significant clinical features of CFS/ME with a view to elucidating its underlying pathology and delineating it from other illnesses. Doing so will help researchers and healthcare professionals gain important insights into the condition, aid diagnosis and, in the longer term, inform evidence-based therapeutic interventions.”

The study assessed vulnerability of ME/CFS patients to pattern-related visual stress using a standardised test called the pattern glare test, in which people report the number of visual distortions they experience when looking at three repetitive striped patterns of different levels of detail.

During the study twenty patients with CFS and twenty patients without the condition were recruited.

Participants viewed 3 patterns, the spatial frequencies (SF) of which were either 0.3 (low-SF), 2.3 (mid-SF) and 9.4 (high-SF) cycles per degree (c/deg). They then reported the number of distortions they experienced when viewing each pattern.

Patients with ME/CFS reported more distortions on the intermediate striped pattern (Pattern 2) than people without the condition.

Dr Hutchinson added: “The existence of pattern-related visual stress in ME/CFS may represent an identifiable and easily measurable behavioural marker of ME. This could, in conjunction with other diagnostic tests, help delineate it from other conditions.”

The work was funded by ME Research UK who provided funding for a 1-year MPhil studentship, awarded to Rachel Wilson, who was supervised by Drs Claire Hutchinson and Kevin Paterson from the University of Leicester’s Department of Neuroscience, Psychology and Behaviour.

Dr Neil Abbot, Research & Operations Director at ME Research UK, added: “Around three-quarters of people with ME/CFS report a range of eye and vision-related symptoms that interfere with their everyday lives, yet there has been very little scientific investigation of the problem.

“Dr Claire Hutchinson and her team have previously confirmed the existence of eye movement difficulties in ME/CFS patients, and that symptoms, including eye pain, can be severe. Her new report in Perception extends these findings and raises the possibility that vision anomalies, including pattern-related visual stress, may have a diagnostic role in the disease.”

The study ‘Increased vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis’ was published in the journal Perception.

Journal Reference: Rachel L. Wilson, Kevin B. Paterson and Claire V. Hutchinson. Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. Perception, November 2015 DOI: 10.1177/0301006615614467

 

Source: University of Leicester. (2015, November 24). Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2015/11/151124082235.htm

 

Gross and fine motor function in fibromyalgia and chronic fatigue syndrome

Abstract:

PURPOSE: This paper aimed to investigate motor proficiency in fine and gross motor function, with a focus on reaction time (RT) and movement skill, in patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS) compared to healthy controls (HC).

METHODS: A total of 60 individuals (20 CFS, 20 FM, and 20 HC), age 19-49 years, participated in this study. Gross motor function in the lower extremity was assessed using a RT task during gait initiation in response to an auditory trigger. Fine motor function in the upper extremity was measured during a precision task (the Purdue Pegboard test) where the number of pins inserted within 30 s was counted.

RESULTS: No significant differences were found between FM and CFS in any parameters. FM and CFS groups had significantly longer RT than HC in the gait initiation (p=0.001, and p=0.004 respectively). In the Purdue Pegboard test, 20% in the FM group, 15% in the CFS groups, and 0% of HC group, scored below the threshold of the accepted performance. However, there were no significant differences between FM, CFS, and HC in this task (p=0.12).

CONCLUSION: Compared to controls, both CFS and FM groups displayed significantly longer RT in the gait initiation task. Generally, FM patients showed the worst results in both tests, although no group differences were found in fine motor control, according to the Purdue Pegboard test.

 

Source: Rasouli O, Fors EA, Borchgrevink PC, Öhberg F, Stensdotter AK. Gross and fine motor function in fibromyalgia and chronic fatigue syndrome. J Pain Res. 2017 Feb 7;10:303-309. doi: 10.2147/JPR.S127038. ECollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304994/ (Full article)

 

Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise.

Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.

 

Source: Cook DB, Light AR, Light KC, Broderick G, Shields MR, Dougherty RJ, Meyer JD, VanRiper S, Stegner AJ, Ellingson LD, Vernon SD. Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Behav Immun. 2017 Feb 16. pii: S0889-1591(17)30051-X. doi: 10.1016/j.bbi.2017.02.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28216087

 

A systematic review of the association between fatigue and genetic polymorphisms

Abstract:

Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes.

To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue.

SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue.

We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.

Copyright © 2017 Elsevier Inc. All rights reserved.

 

Source: Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017 Jan 12. pii: S0889-1591(17)30007-7. doi: 10.1016/j.bbi.2017.01.007. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28089639