CFS treated with transcutaneous electrical acupoint stimulation (TEAS)

Research abstract:

Chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation: a randomized controlled trial, by Li J, Xie J, Pan Z, Guo X, Li Y, Fu R in Zhongguo Zhen Jiu. 2017 Dec 12;37(12):1276-9. [Article in Chinese]

OBJECTIVE:

To evaluate the clinical therapeutic effects and safety of chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation (TEAS) on the conception vessel and the governor vessel.

METHODS:

Eighty-nine patients of chronic fatigue syndrome were randomized into an observation group (46 cases) and a control group (43 cases). In the observation group, TEAS was applied at Dazhui (GV 14) and Mingmen (GV 4), Shenque (CV 8) and Guanyuan (CV 4) [the current intensity: (14±2) mA]. In the control group, the simulated TEAS was applied at the same acupoints as the observation group (the current intensity: 1 mA). The treatment was given for 30 min, once a day, 5 times a week and the treatment of 4 weeks was as 1 session in the two groups. One session of treatment was required.

Before treatment and at the end of 1 session of treatment, the fatigue severity scale (FSS) was adopted to evaluate the fatigue symptoms and the somatic and psychological health report (SPHERE) was adopted to evaluate the potential symptoms and observe the safety of TEAS therapy.

RESULTS:

At the end of treatment, FSS score and SPHERE score in the control group were not different significantly as compared with those before treatment (both P>0.05). FSS score and SPHERE score in the observation group were reduced significantly as compared with those before treatment (both P<0.01). FSS score and SPHERE score in the observation group were reduced apparently as compared with those in the control group (both P<0.001). In the entire process of treatment with TEAS, no any adverse reaction occurred.

CONCLUSION:

TEAS on the conception vessel and the governor vessel relieves fatigue symptoms and the potential symptoms in the patients of chronic fatigue syndrome. It is a safe therapy.

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Open-label pilot for treatment targeting gut dysbiosis in ME/CFS

Research abstract:

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/ chronic fatigue syndrome: neuropsychological symptoms and sex comparisons, by Amy Wallis, Michelle Ball, Henry Butt, Donald P Lewis, Sandra McKechnie, Philip Paull, Amber Jaa-Kwee, Dorothy Bruck in J Transl Med. 2018 Feb 6;16(1):24

BACKGROUND:

Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS.

METHODS:

An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes.

Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes.

RESULTS:

Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females.

CONCLUSIONS:

Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population.

Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment.

Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014

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PACE debate in House of Commons – video & transcript available

House of Commons ME/CFS PACE Trial debate 20 February 2018

Glasgow MP Carol Monaghan led a debate about the effect of the controversial flawed PACE Trial upon those living with Myalgic Encephalomyelitis (ME/CFS) in the UK and worldwide.

Official transcript

ME Association comment: Government-funded ME/CFS trial ‘one of greatest medical scandals of 21st century’

Action for ME summary: PACE trial Westminster debate – our summary 

EM Action: Le PACE trial débattu au parlement anglais

ME Action: Westminster hall debate

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Pernicious Anaemia: symptoms, diagnosis, Vitamin B12, ME/CFS & the NICE guideline review

ME Association blog post, 16 February 2018: Pernicious Anaemia: symptoms, diagnosis, Vitamin B12, ME/CFS and the NICE guideline review

Article extract:

What is pernicious anaemia?
Pernicious anaemia (PA) is the most common cause of B12 deficiency in the UK.

It is an autoimmune condition that causes the body’s immune system to attack cells in the stomach, limiting their ability to absorb B12. PA is generally treated with regular B12 injections.

For more information, see NHS Choices or the Pernicious Anemia Society.

Vitamin B12 and M.E.
Dr Shepherd, Hon. Medical Adviser, to the ME Association has talked previously with Martyn, and recognises the importance of excluding PA before a diagnosis of M.E. is made, and any treatment of M.E. with vitamin B12 is considered.

The ME Association has produced a leaflet that covers all aspects of vitamin B12 – causes of B12 deficiency, symptoms, blood tests, treatment, research into the possible link to M.E.

This leaflet can be downloaded or ordered from our online shop.

Summary of the key points:

  • Although some people with M.E. report that vitamin B12 injections have been helpful, there is no robust scientific evidence to currently demonstrate that vitamin B12 deficiency occurs in M.E.
  • There are no results from clinical trials to indicate that vitamin B12 injections are a safe and effective form of treatment in M.E.
  • If people are going to take vitamin B12 it is very important to make sure that Pernicious Anaemia (PA) has first been excluded. PA is an autoimmune condition that results in decreased absorption of B12 from the gut – hence the need for injections.
  • Excluding PA is important because it can cause very serious neurological complications (i.e. sub-acute combined degeneration of the spinal cord (https://medlineplus.gov/ency/article/000723.htm) if not properly treated.

Read the full blog post

NB   Be aware that in Wales Health Boards work by different upper and lower levels of B12.

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ME/CFS: what every family physician needs to know

Article extract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: what every family
 physician needs to know, by Mary Dimmock, Susan Levine, MD, and Terri L. Wilder, MSW in Family Doctor (journal of New York State Academy of Family Physicians) Winter 2018 6:3 pp 23-25

The onset of ME/CFS is often sudden, typically following a viral or other type of infection but may occur following other types of physical trauma. In other cases the disease may develop gradually, over a period of weeks or months. Patients describe feeling `flulike’
symptoms chronically. In addition to the characteristic postexertional malaise (PEM), patients may also experience cognitive impairment, unrefreshing sleep, autonomic manifestations, such as heart rate variability and excessive sweating, and also experience
muscle and joint pain and sound, light, and chemical sensitivity.

Elevated antibody titers to viruses may be present, in addition to low levels of autoimmune serology. ME/CFS can present with a wide range of severity. Even in the same patient, the level of severity can change over time and from day to day as symptoms wax and wane. People with ME/CFS are unable to go about their daily activities in a predictable or consistent manner.

The IOM report stated that up to 70% of patients are unable to work and one quarter remain bed- or housebound (the latter however may be an underestimate). The IOM report stated that patients with ME/ CFS are more functionally impaired than those with ”type 2 diabetes mellitus, congestive heart failure, hypertension, depression, multiple
sclerosis, and end-stage renal disease.”  Caring for severely disabled patients can put an enormous fiscal and emotional strain on family members and other caretakers.

Recovery is rare and as a result, patients can remain ill for decades. The IOM report estimated burden on the American economy is $17-24 billion annually in lost productivity and in direct medical costs.

Clinical Diagnosis
Previously, ME/CFS was considered a diagnosis of exclusion but the IOM criteria provide for the presence of certain “core” criteria in order to make the diagnosis of this disease.

The IOM clinical diagnostic criteria for ME/CFS require:

  • A substantial impairment in ability to engage in activity that lasts
    six months or more, is accompanied by fatigue, is not lifelong, is
    not the result of ongoing exertion and is not alleviated by rest
  • Post-exertional malaise
  • Unrefreshing sleep
  • At least one of cognitive impairment or orthostatic intolerance

Sleep studies may identify co-morbid sleep apnea whereas the results of a tilt table test can confirm the presence of Postural Orthostatic Tachycardia Syndrome (POTS).

Neuropsychiatric testing typically shows impaired working memory and slowed information processing. Querying the patient’s response the day after activities that were previously tolerated can help determine the presence of post-exertional malaise (PEM).

The 2-day cardiopulmonary test (CPET) is used to measure anaerobic threshold, which is reduced in this disease and confirms the seminal finding of PEM.

A number of co-morbidities can be seen in ME/CFS, the most common of which include fibromyalgia, POTS, mast cell disturbances, and certain autoimmune disorders. These will need to be managed as appropriate for each condition.

Treatment
A noted above, there are no FDA approved treatments for ME/CFS. However, there are interventions that the family physician can provide to help patients with this disease. First and foremost, the family physician can explain post-exertional malaise and the associated aerobic metabolism impairment. For some people, exertion as minor as tooth brushing or eating can trigger PEM and a crash. People with ME/CFS should not exceed their “energy
envelope” and they should use an activity management approach called “pacing” to not exceed their limits.

Family physicians can also prescribe therapies that relieve symptoms, including those for sleep, pain, and orthostatic intolerance, including IV saline and Florinef. For patients with elevated viral titers, antiviral medications can help reduce symptoms. Patients often use earphones, earplugs, sunglasses, and eye masks to relieve the sensitivities to light and sound. Family physicians can also support patients by explaining the disease to the family and supporting applications for disability.

Social security accepts the 2-day CPET as objective evidence to support a disability claim. If this test is not easily available, a thorough explanation from the clinician caring for a patient with ME/CFS that describes the patients’ daily activities may suffice.

Conclusions
Family physicians have an important role to play in the diagnosis and care of people with ME/CFS. In May 2017, New York State Commissioner of Health Dr. Howard Zucker sent a letter to NYS physicians encouraging them to include ME/CFS as part of the differential diagnosis when evaluating patients with these symptoms.

The clinical diagnostic criteria published by the Institute of Medicine (IOM) are an important tool in this differential diagnosis that can result in faster and more accurate diagnosis. They can also provide the basis for treatment recommendations that can relieve symptoms and minimize postexertional crashes.

Most importantly, the family physician can validate the patient’s experience and ensure that the patient is not harmed by inappropriate treatment recommendations for exercise or talk therapy intended to convince the patient they are not ill.

Read the full article

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Post-Exertional Malaise & GET in ME/CFS – a guide to the research

ME Action blog post, 9 Feb 2018: Post-Exertional Malaise & GET in ME/CFS – a guide to the research

“Post-Exertional Malaise & Graded Exercise Therapy in ME/CFS” Primer,
December 2017

A member of #MEAction Network Australia has written a primer, outlining the flaws in the graded exercise therapy (GET) research and explaining why GET is likely to be harmful for people with ME/CFS.

The primer has been endorsed by Emerge Australia Inc and infectious disease specialist, Dr John Whiting. It was submitted to the Australian Senate during the most recent Senate Estimates, in October 2017, has been sent to the President of the Royal Australian College
of General Practitioners, as well as several Australian politicians, and has been used by patient advocates in meetings with politicians in Australia and Ireland.

Now it is being made available for patients to download and give to their health professionals, or attach to their applications for disability support.

Key points in the primer:

  1. PEM, not fatigue, is the cardinal feature of ME/CFS.
  2. GET research uses broad diagnostic criteria that doesn’t require PEM for diagnosis and, instead, focuses on fatigue. In order to be studying ME/CFS, study participants must experience PEM, but there is no way of knowing how many (if any) participants in GET studies do.
  3. GET research primarily uses subjective outcome measures, which are subject to bias. When objective outcome measures are used, evidence does not support the use of GET for ME/CFS.
  4. GET research has been criticised for inadequate reporting of harm. Patient surveys indicate that many patients experience harm from GET treatment.
  5. Despite the flawed nature of GET research, patients are routinely rejected from support services because ME/CFS is seen to be both temporary and treatable with GET, despite ME/CFS having a low recovery rate.

The document also includes a two page summary at the beginning, for those who are unable to read the entire document.

This primer is available on Emerge Australia’s website

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A unifying theory for cognitive abnormalities in functional neurological disorders, FM & CFS

A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: Systematic review; by Tiago Teodoro, Mark J Edwards, Jeremy D Isaacs in Journal of Neurology, Neurosurgery, and Psychiatry 2018 [Preprint: May 7, 2018]

Review abstract:

Background:
Functional cognitive disorder (FCD) describes cognitive dysfunction in the absence of an organic cause. It is increasingly prevalent in healthcare settings yet its key neuropsychological features have not been reported in large patient cohorts. We hypothesised that cognitive profiles in fibromyalgia (FM), chronic fatigue syndrome (CFS) and functional neurological disorders (FNDs) would provide a template for characterising FCD.

Methods:
We conducted a systematic review of studies with cognition-related outcomes in FM, CFS and FND.

Results:
We selected 52 studies on FM, 95 on CFS and 39 on FND. We found a general discordance between high rates of subjective cognitive symptoms, including forgetfulness,  distractibility and word-finding difficulties, and inconsistent objective neuropsychological deficits.  Objective deficits were reported, including poor selective and divided attention, slow information processing and vulnerability to distraction. In some studies, cognitive performance was inversely correlated with pain, exertion and fatigue. Performance validity testing demonstrated poor effort in only a minority of subjects, and patients with CFS showed a heightened perception of effort.

Discussion:
The cognitive profiles of FM, CFS and non-cognitive FND are similar to the proposed features of FCD, suggesting common mechanistic underpinnings. Similar findings have been reported in patients with mild traumatic brain injury and whiplash. We hypothesise that pain, fatigue and excessive interoceptive monitoring produce a decrease in externally
directed attention. This increases susceptibility to distraction and slows information processing, interfering with cognitive function, in particular multitasking. Routine cognitive processes are experienced as unduly effortful.

This may reflect a switch from an automatic to a less efficient controlled or explicit cognitive mode, a mechanism that has also been proposed for impaired motor control in FND. These experiences might then be overinterpreted due to memory perfectionism and heightened self-monitoring of cognitive performance.

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Neuroinflammation in the brain of patients with ME/CFS

Research abstract:

[Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome] by Y Nakatomi, H Kuratsune, Y Watanabe in Brain Nerve. 2018 Jan;70(1):19-25 [Article in Japanese]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and chronic widespread pain. By using positron emission tomography, our study demonstrated neuroinflammation in the brain of patients with ME/CFS.

Neuroinflammation was found to be widespread in the brain areas of the patients with ME/CFS and was associated with the severity of their neuropsychological symptoms. The ongoing research would lead to the establishment of objective diagnostic criteria and development of an appropriate therapy.

NB The researchers’ older paper is available in English.

Dr Montoya at Stanford announced at the end of 2017 that they plan to replicate the Japanese findings with even more sensitive tests.

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Value of circulating cytokine profiling during submaximal exercise testing in ME/CFS

Research abstract:

Value of circulating cytokine profiling during submaximal exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, by Kegan J. Moneghetti, Mehdi Skhiri, Kévin Contrepois, Yukari Kobayashi, Holden Maecker, Mark Davis, Michael Snyder, Francois Haddad & Jose G. Montoya in Nature, Scientific Reports 8: 2779 (2018) [Published online 9 February 2018]

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous syndrome in which patients often experience severe fatigue and malaise following exertion.

Immune and cardiovascular dysfunction have been postulated to play a role in the pathophysiology. We therefore, examined whether cytokine profiling or cardiovascular testing following exercise would differentiate patients with ME/CFS.

Twenty-four ME/CFS patients were matched to 24 sedentary controls and underwent cardiovascular and circulating immune profiling.

Cardiovascular analysis included echocardiography, cardiopulmonary exercise and endothelial function testing. Cytokine and growth factor profiles were analyzed using a 51-plex Luminex bead kit at baseline and 18 hours following exercise.

Cardiac structure and exercise capacity were similar between groups. Sparse partial least square discriminant analyses of cytokine profiles 18 hours post exercise offered the most reliable discrimination between ME/CFS and controls (κ = 0.62(0.34,0.84)).

The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1.

In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.

Scope blog post from Stanford Medicine, by Bruce Goldman, February 15, 2018: Exercise elevates blood signature difference between people with, without chronic fatigue syndrome

Health rising blog post, by Cort Johnson, 5 March 2018: Stanford Exercise Study Shows Different Immune Response in Chronic Fatigue Syndrome (ME/CFS)

Solve ME/CFS Initiative blog post: Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in ME/CFS, March 2018

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Cerebral blood flow and heart rate variability in CFS

Cerebral blood flow and heart rate variability in Chronic Fatigue Syndrome: a randomized
cross-over study, by Anneleen Malfliet, Roselien Pas, Raf Brouns, Joris De Win, Samar M Hatem, Mira Meeus, Kelly Ickmans, Robbert-Jan van Hooff, and Jo Nijs in heart 2018; 21:E13-E24

BACKGROUND:

Pain, fatigue, and concentration difficulties are typical features of chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms are still unknown, but available evidence suggests an important role for impaired pain modulation. As evidence also suggests that pain modulation is related to cardiovascular mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart rate variability (HRV) are altered in these patients.

OBJECTIVES:

We aimed to investigate the role of the cardiovascular system in pain modulation and symptoms of CFS; the response of CBF and HRV to physical stress and their relation to the change in temporal summation (TS) of pressure pain and self-reported symptoms was evaluated.

STUDY DESIGN: A controlled, randomized cross-over trial.

SETTING: University Hospital Brussels.

METHODS: Twenty CFS patients and 20 sedentary healthy controls were included in this study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial Doppler), and HRV (using finger plethysmography) was examined during physical and emotional stress (to control for potential bias), as well as their association mutually and with self-reported symptoms of pain, fatigue, and concentrations difficulties.

RESULTS:

There was no significant interaction or group (F-values ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV and CBF did change during physical exercise, but the changes did not differ between patients and controls. While pain scores during TS at the trapezius site reduced in the control group after the physical exercise protocol (P = .037), they did not change in the CFS group (P = .108), suggesting impaired pain modulation. There were no significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values of correlation analyses > .01).

LIMITATIONS:

Although effect sizes were medium to large, the study sample was relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild exercise was able to provoke endogenous pain modulation in the control group, which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are more applicable to daily physical activities in CFS patients than vigorous exercises.

CONCLUSION:

These results seem to refute the previously suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters appear not to explain pain before, during, and following exercise.

Disclaimer: The study was funded by ME Research United Kingdom, a national charity funding biomedical research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. The funder did not have any influence in the study design, the collection or analysis of the data, or the conception of this manuscript.

ME Research UK comment

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