Cognitive dysfunction research: Hippocampal subfields & ME/CFS

Posted on 04/07/2022 by wames

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome, by Kiran Thapaliya, Donald Staines, Sonya Marshall- Gradisnik, Jiasheng Su, Leighton Barnden in Journal of Neuroscience Research March 31, 2022

 

 

“The hippocampus is a small, curved formation in the brain that plays an important role in the limbic system. The hippocampus is involved in the formation of new memories and is also associated with learning and emotions.” 1

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS.

We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFS Fukuda), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFS ICC), and 25 healthy controls (HC).

Group comparisons with HC detected extensive differences in subfield volumes in ME/CFS ICC but not in ME/CFS Fukuda. ME/CFS ICC patients had significantly larger volume in the left subiculum head (p<0.001), left presubiculum head (p=0.0020), and left fimbria (p=0.004).

Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFS ICC than in ME/CFS Fukuda patients. In ME/CFS Fukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume. In ME/CFS ICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume.

Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head). Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFS ICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFS ICC patients.

Research significance:

Our study found left hippocampal subiculum, presubiculum, and fimbria volumes were significantly larger in ME/CFSICC patients compared with Health Controls, but not for ME/CFSFukuda patients.

Furthermore, this study demonstrated that multiple hippocampal subfield volumes are different in ME/CFSICC patients meeting the strict ICC case definition, and they exhibited strong associations with clinical measures.

Therefore, the strict case definitions are essential in investigation of the pathophysiology of ME/CFS. Subiculum and parasubiculum volumes were larger in ME/CFS in contrast to reductions seen in other neurological disorders.

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Research: Cardiopulmonary, metabolic, & perceptual responses during exercise in ME/CFS

Posted on 04/04/2022 by wames

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study by Dane B Cook, Stephanie VanRiper, Ryan J Dougherty, Jacob B Lindheimer, Michael J Falvo, Yang Chen, Jin-Mann S Lin, Elizabeth R Unger (The MCAM Study Group) in PLoS One. 2022 Mar 15;17(3):e0265315 [doi.org/10.1371/journal.pone.0265315]

Abstract

Background

Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear.

Purpose

To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness.

Methods

As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent (, ), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated.

Exercise variables were compared using Hedges’ g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20–100% peak ). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak  (~1 ml/kg/min-1).

Results

Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20–100% peak ) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for ,  and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, , , and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., ) were generally reflective of those seen throughout exercise (i.e., 20–100%).

Conclusion

Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Excerpt from full Conclusion:

In general, the acute exercise capacity of this cohort of people with ME/CFS was in the low-to-normal range, when considering their GET and peak aerobic capacity values. However, these data do not provide a complete functional picture of the cardiopulmonary system in ME/CFS.

Ventilatory efficiency was found to be low in those with ME/CFS and significantly worse than controls. The observed responses likely reflect adequate oxygen delivery but inadequate oxygen utilization and are suggestive of disease specific adaptations that may be of pathophysiological significance but require more research. These data also highlight the importance of distinguishing fitness effects from those that are primary to the disease. By closely matching our groups on aerobic capacity/exercise time and age, many group differences were eliminated. Importantly, our data suggest that chronotropic incompetence was not present among this large sample of participants with ME/CFS.

When considering physical activity for people with ME/CFS, clinicians face the challenge of helping patients avoid the negative effects of acute exercise (e.g., symptom exacerbation) [71, 72], while moving them towards experiencing the health benefits associated with a more physically active lifestyle [73]. A logical approach is to develop exercise prescriptions which strike a balance between minimizing symptom exacerbation and maximizing function, however, there is limited information on the intensity threshold at which this ideal balance occurs or guidance on how to establish this threshold for individual patients.

It is noteworthy that in other patient care settings for which a substantial literature on exercise prescription already exists, ramped incremental CPET is considered the gold standard for physiologically comprehensive exercise intensity assessment and prescription [74]. Given that over 90% of the present sample was able to provide a valid peak effort during CPET, we conclude that there is sufficient precedent for future work testing whether CPET guided exercise prescription can help address the unique physical activity challenges experienced by people with ME/CFS. Further, we believe that these data will support current recommendations to practitioners to encourage patients with ME/CFS to maintain tolerated levels of activity, to increase activity with caution, and make adjustments to avoid post-exertional malaise.

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ME services in Wales can learn from Long COVID Adferiad programme says Health Minister

Posted on 04/04/2022 by wames

Welsh Government wants Long COVID community model to also treat and support ME, CFS and MS

 

On 31st March 2022 the Health Minister Eluned Morgan announced further funding for the Adferiad programme for Long COVID recovery:

“today I am announcing a further £5 million of Adferiad programme funding to be allocated to Health Boards in 2022/23 to support the continuation of health boards’ long COVID services.”

Again there is no funding announcement for ME services but she is “heartened” by the success of the programme and wants to “apply this knowledge to how we treat other long term conditions like MS, ME and CFS.”

“It is hoped by the end of the next six-month period in July, health boards in Wales will take the opportunity to begin to expand the community model to treat and support people with other long-term conditions which have a similar impact as long COVID, including the likes of Multiple Sclerosis (MS), Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS).  This would help create effective long term intervention services and reduce variation treating people with different conditions and diagnoses.”

WAMES intends to discuss exactly what this might mean with the soon to be appointed (we hope) Welsh Government policy officer for post viral conditions and Health Board representatives. It is not yet clear if any of the LC community services cater for people with PEM/PESE. It is also unclear if GPs and fatigue services have taken on board the NICE guideline alongside the Long COVID guideline. We’d love to hear from patients and carers whether they are seeing any sign of healthcare improving as we continue to ask NHS Wales to #ImplementNICEmecfs

The Adferiad programme covers:

Health Board services:

North Wales: Betsi Cadwaladr

Mid Wales: Powys

West Wales: Hywel Dda    Swansea Bay

South Wales: Aneurin Bevan     Cardiff & Vale     Cwm Taf

See also:

Health Education and Improvement Wales (HEIW) Long Covid Syndrome Resources 

Welsh Government statement: Further £5million investment for long COVID services

In the media:

Deeside.com: Further £5m investment in ‘innovative’ Long-COVID rehabilitation services

Nation.Cymru: Extra funding announced for innovative long-Covid treatment programme

BBC: Long Covid: People turning to opera to overcome illness

Wrexham.com: Extra £5million investment announced for long-covid services in Wales – includes some results of the review of the Adferiad programme.

The Leader: £5m announced to support long covid sufferers

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Research: Genetic association study in ME/CFS

Posted on 03/30/2022 by wames

Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci, by Riad Hajdarevic, Asgeir Lande, Jesper Mehlsen, Anne Rydland, Daisy D Sosa, Elin B  Strand, Olav Mella, Flemming Pociot, Øystein Fluge, Benedict A Lie, Marte K Viken in Brain, Behavior, and Immunity Vol 102, May 2022, Pages 362-369 [doi.org/10.1016/j.bbi.2022.03.010]

 

Research highlights

  • Largest ME/CFS genetic study to date.
  • Three different cohorts totaling more than 2500 patients.
  • First Immunochip study in ME/CFS.
  • Possible implication of TPPP genetic region.

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown etiology and pathogenesis, which manifests in a variety of symptoms like post-exertional malaise, brain fog, fatigue and pain. Hereditability is suggested by an increased disease risk in relatives, however, genome-wide association studies in ME/CFS have been limited by small sample sizes and broad diagnostic criteria, therefore no established risk loci exist to date.

In this study, we have analyzed three ME/CFS cohorts: a Norwegian discovery cohort (N=427), a Danish replication cohort (N=460) and a replication dataset from the UK biobank (N=2105). To the best of our knowledge, this is the first ME/CFS genome-wide association study of this magnitude incorporating 2532 patients for the genome-wide analyses and 460 patients for a targeted analysis. Even so, we did not find any ME/CFS risk loci displaying genome-wide significance.

In the Norwegian discovery cohort, the TPPP gene region showed the most significant association (rs115523291, P=8.5×10-7), but we could not replicate the top SNP. However, several other SNPs in the TPPP gene identified in the Norwegian discovery cohort showed modest association signals in the self-reported UK biobank CFS cohort, which was also present in the combined analysis of the Norwegian and UK biobank cohorts, TPPP (rs139264145; P= 0.00004). Interestingly, TPPP is expressed in brain tissues, hence it will be interesting to see whether this association with time will be verified in even larger cohorts.

Taken together our study, despite being the largest to date, could not establish any ME/CFS risk loci, but comprises data for future studies to accumulate the power needed to reach genome-wide significance.

Discussion – excerpt

Using genome-wide array data and large ME/CFS cohorts (>2900 patients in total), we have identified several chromosomal regions with suggestive ME/CFS associations that warrants follow-up in subsequent studies towards the future establishment of the first ME/CFS genetic risk loci at genome-wide significance…

Despite the current lack of large cohorts of phenotypically stringent and well-characterized ME/CFS patients, this study represents, to the best of our knowledge, the largest and most homogenous genetic study performed in ME/CFS so far. Ongoing projects like the DecodeME project (https://www.decodeme.org.uk) will enable future studies of larger and more powerful cohorts, which are warranted to produce the desired statistical power to definitively investigate the genetic architecture of ME/CFS.

In conclusion, we identified several potential risk loci for ME/CFS, which encourage further investigations. Future genetic studies should be performed in large cohorts of several thousand patients and strive to use strict and comprehensive phenotyping to enable analyses of homogenous sub-phenotypes.

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Research: Long-term C-19 sequelae in adolescents: the overlap with OI & ME/CFS

Posted on 03/28/2022 by wames

Long-term COVID 19 sequelae in adolescents: the overlap with orthostatic intolerance and ME/CFS, by Amanda K Morrow, Laura A Malone, Christina Kokorelis, Lindsay S Petracek, Ella F Eastin, Katie L Lobner, Luise Neuendorff & Peter C Rowe in Curr Pediatr Rep. 2022 Mar 9:1-14

 

Review abstract:

Purpose 

To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

Recent Findings

The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning.

The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

Summary

We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments. At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

Conclusion

Emerging data confirm that prolonged symptoms can develop following even mild or asymptomatic initial SARS-CoV-2 infection. The most common symptoms are fatigue, cognitive dysfunction, and headaches. As ascertainment for orthostatic intolerance in these patients improves, lightheadedness is becoming more commonly recognized. A proportion of long COVID patients meet the criteria for ME/CFS at 6 months. At present, management of post-COVID conditions focuses primarily on addressing symptoms, borrowing management strategies from conditions like OI and ME/CFS.

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WAMES AGM 11 April 2022

Posted on 03/23/2022 by wames

WAMES Annual General Meeting

 

WAMES will be holding our annual business meeting via Skye on Monday 11th April at 4pm. This is the opportunity for members to elect officers, oversee the finances and identify priorities for the coming year.

If you would like to become a member of WAMES and help us keep on course with our mission – to be the voice of people affected by ME in Wales – please contact Sharon sharon@wames.org.uk

She will also be happy to discuss any of our volunteering needs if you would like to lend a hand in other ways.

Our Vision

Our Vision is for a Wales where adults and children with ME, CFS and PVFS and their carers are taken seriously and treated with respect, where diagnosis, treatment and services are accessible without a battle.

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Welsh Government responds & asks if NICE is being implemented

Posted on 03/21/2022 by wames

Welsh Government replies to WAMES

 

WAMES wrote to the Health Minister on 8 February asking why an announcement had been made about services for recent patients with long COVID, but not about services for people who have been living with ME for decades and…

how the Welsh Government will be funding and supporting a better understanding of ME/CFS, PESE/PEM and the dangers of exercise therapy, alongside the wider range of support needed for those with post COVID symptoms. We are looking for a speedy implementation of the 2021 NICE guideline.

#ImplementNICEmecfs

The Health Minister delegated her reply (again)

A civil servant from the ‘Government and Corporate Business Team’ wrote to update us on their work on ME/CFS and to ask us about recent patient experiences within NHS Wales:

During the winter each health board was surveyed in relation to their services for ME/CFS as well as their response to the revised NICE guidance. We have received assurances that
the new NICE guidance is being adopted. If your organisation has any evidence to the contrary we would welcome hearing about this. Within the survey we also queried what support is required to help improve services for all those presenting post viral symptoms and additional funding and training was mentioned.

What is your experience?

Are health professionals implementing the new NICE guideline?

Give us your experiences in any way you wish: email any of the team including jan@wames.org.uk or phone, email, comment on social media or this post.

The Welsh Government has assured us:

We agree there is much to learn from those with other post viral illnesses, including those with ME/CFS and can reassure you that ME/CFS is discussed at the vast majority of meetings considering long covid provision. Clinicians treating those with long Covid have advised of the similarities and there is a desire to ensure all services are suitable for all those living with the conditions.

As well as surveying health boards they are:

appointing a new senior policy lead whose remit will include long Covid, post viral conditions and ME/CFS. They will be tasked with working with stakeholders to deliver equity of outcome for all those needing support and we will ensure your comments are shared with them once they take up post.

Summing up, the Welsh Gov says:

  • There is much to learn about Long COVID from other post viral illnesses
  • ME/CFS is discussed at the vast majority of meetings considering long COVID provision
  • Clinicians have advised of the similarities between long COVID & ME/CFS
  • there is a desire in the NHS to ensure all services are suitable for all related conditions
  • Welsh Government is in the final stages of appointing a new senior policy lead whose remit will include long COVID, post viral conditions and ME/CFS
  • The aim is equity of outcome for all those needing support with post viral conditions
  • NHS Wales Health Boards say they are implementing new NICE guideline but need additional funding and training
  • Welsh Gov would welcome any evidence that the NICE guideline is not being implemented
  • Welsh Gov continues to explore how to expand integrated services for all people
    with post-viral illnesses and other long-term conditions, including ME/CFS.

Read the full letter

Read WAMES’ email to the Health Minister

Blog post: Wales prioritises healthcare for post-viral condition Long COVID

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Perspective: Drawing on findings from critical illness to explain ME/CFS

Posted on 03/16/2022 by wames

Perspective: Drawing on findings from critical illness to explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Dominic Stanculescu and  Jonas Bergquist in Front. Med., 08 March 2022 [doi.org/10.3389/fmed.2022.818728]

 

Abstract:

We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research.

Specifically, we combine emerging findings regarding

(a) hypoperfusion [a reduced amount of blood flow] and endotheliopathy [damage to endothelial cells in the blood vessels] and

(b) intestinal injury in these illnesses with our previously published hypothesis about the role of

(c) pituitary suppression, [pituitary gland does not produce normal amounts of some or all of its hormones] and

(d) low thyroid hormone function associated with redox imbalance in ME/CFS.

Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS.

New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.

Discussion
Hypoperfusion and endotheliopathy, intestinal injury, pituitary suppression, and low thyroid hormone function are each central to prolonged critical illness regardless of the nature of the initial severe injury or infection (101, 173, 195, 196).  We propose that, similarly, these mechanisms and their reciprocal relationships with inflammation could underlie ME/CFS regardless of the nature of the peri-onset event (i.e., infection, stressful incident, exposure to environmental toxins or other). Moreover, the severity of ME/CFS may be a function of the strength of these mechanisms.

However, each of these pathological mechanisms has largely been studied in isolation and rarely have the linkages between them been explored. Yet, the aggregate of these mechanisms is likely necessary to fully explain the perpetuation of critical illness—and to inform the understanding of ME/CFS.

Conclusion
Decades of research in the field of critical illness medicine have demonstrated that in response to the stress of severe infection or injury, the vascular system, intestines, endocrine axes and thyroid hormone function experience profound alterations. Self-reinforcing interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation may perpetuate illness irrespective of the initial severe infection or injury.

Without excluding possible predisposing genetic or environmental factors, we propose that the pathological mechanisms—and the interlinkages between them—that prevent recovery of some critically ill patients may also underlie ME/CFS.

This initial proposal is in line with and complements several existing hypotheses of ME/CFS pathogenesis. If this hypothesis is validated, past treatment trials for critical illness may provide avenues for a cure for ME/CFS. Certainly, given the similarities described above, active collaboration between critical illness and ME/CFS researchers could lead to improved understanding of not only both conditions, but also PICS, long-COVID, PACS, and fibromyalgia.

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Research: Predictors for developing severe ME/CFS following infectious Mononucleosis

Posted on 03/14/2022 by wames

Predictors for developing severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome following infectious Mononucleosis, by Leonard A Jason, Joseph Cotler, Mohammed F Islam, Jacob Furst, Ben Z Katz in Journal of Rehabilitation Therapy, 2022;4(1):1-5, February 21, 2022

 

Research abstract:

Background:

About 10% of individuals who contract infectious mononucleosis (IM) [aka Glandular fever] have symptoms 6 months later that meet criteria for myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS).  Our study for the first time examined whether it is possible to predict who will develop ME/CFS following IM.

Methods:

We have reported on a prospectively recruited cohort of 4,501 college students, of which 238 (5.3%) developed IM.  Those who developed IM were followed-up at six months to determine whether they recovered or met criteria for ME/CFS. The present study focuses on 48 students who after six months had a diagnosis of ME/CFS, and a matched control group of 58 students who had no further symptoms after their IM.

All of these 106 students  had data at baseline (at least 6 weeks prior to the development of IM), when experiencing IM, and 6 months following IM. Of those who did not recover from IM, there were two groups: 30 were classified as ME/CFS and 18 were classified as severe ME/CFS.

We measured the results of 7 questionnaires, physical examination findings, the severity of mononucleosis and cytokine analyses at baseline (pre-illness) and at the time of IM.  We examined predictors (e.g., pre-illness variables as well as variables at onset of IM) of  those who developed ME/CFS and severe ME/CFS following IM.

Results:

From analyses using receiver operating characteristic statistics, the students who had had severe gastrointestinal symptoms of stomach pain, bloating, and an irritable bowel at baseline  and who also had abnormally low levels of the immune markers IL-13 and/or IL-5 at baseline, as well as severe gastrointestinal symptoms when then contracted IM,  were found to have a nearly 80% chance of having severe ME/CFS persisting six months following IM.

Conclusions:

Our findings are consistent with emerging literature that gastrointestinal distress and autonomic symptoms, along with several immune markers, may be implicated in the development of severe ME/CFS.

Extract from Discussion:

The current study for the first time attempted to predict onset of ME/CFS using pre-illness and illness data. If validated, these predictors of risk could significantly alter the therapeutic strategies in IM and other triggers of ME/CFS in adults and adolescents. In addition, our work may lead to a reappraisal of the ME/CFS diagnostic criteria to include objective gastrointestinal and/or autonomic criteria for diagnosis.

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ME/CFS trigger: tuberculosis

Posted on 03/10/2022 by wames

Researchers have identified the mycobacterium tuberculosis infection as a trigger for CFS, particularly amongst men and the over 65s in Taiwan. TB in Wales is in decline and numbers are small, but the NHS considers it still to be a disease of concern. England has the highest rate of TB in the UK.

 

Tuberculosis (TB) is a bacterial infection spread through inhaling tiny droplets from the coughs or sneezes of an infected person. NHS Wales

 

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study, by Tse-Yen Yang, Cheng-Li Lin, Wei-Cheng Yao, Chon-Fu Lio, Wen-Po Chiang, Kuan Lin, Chien-Feng Kuo & Shin-Yi Tsai in Journal of Translational Medicine vol 20, Article number: 99 (2022) [doi.org/10.1186/s12967-022-03301-1]

 

Research abstract: 

Background
Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms.

Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan.

Methods
7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000–2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011.

Results
The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person‐years among the non‐Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03–1.47).

In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02–1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86–3.38).

Conclusions
The data from this population‐based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

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