Self-management of CFS in adolescents

Self-Management of Chronic Fatigue Syndrome in adolescents, by Katherine Rowe, Amanda Apple and Fiona McDonald in Paediatric Neurology [Working Title] Published online: February 28th 2020 [DOI: 10.5772/intechopen.91413]

 

Book chapter abstract:

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a condition of unknown aetiology that commonly follows an infection. There are no known predictors for recovery or established treatments.

At the Royal Children’s Hospital (RCH) in Melbourne, Australia, the majority of young people with CFS are provided with symptom management and lifestyle guidance in an outpatient setting. However, for some, educational or social issues preclude progress and for those who request this assistance, since 2012, the Victorian Paediatric Rehabilitation Service has offered an Intensive Self-Management Program.

For this program, participants engage in both group and individual sessions, attending 3 days per week for 4 weeks in small groups of 3–4. Interdisciplinary input is from Occupational Therapy, Physiotherapy, Education and Psychology to assist with goal setting and strategies. Outcome measures are obtained at initial assessment, 6 weeks and 6 months post-program. Support is offered for 12 months post-program.

For both the outpatient program and the intensive program the outcomes and feedback from patient and family has influenced the approach and focus. This chapter outlines the current approach and how it has evolved over time.

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Peripheral endothelial dysfunction in ME/CFS

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome, by Nadja Scherbakov, Marvin Szklarski, Jelka Hartwig, Franziska Sotzny, Sebastian Lorenz, Antje Meyer, Patricia Grabowski, Wolfram Doehner, Carmen Scheibenbogen in ESC Heart Failure, 10 March 2020  [https://doi.org/10.1002/ehf2.12633]

 

Research abstract:

Aims:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance. The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS.

Methods and results:

Thirty‐five patients [median age 40 (range 18–70) years, mean body mass index 23.8 ± 4.2 kg/m2, 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria. Nine of these patients with elevated antibodies against β2‐adrenergic receptor underwent immunoadsorption and endothelial function was measured at baseline and 3, 6, and 12 months follow‐up.

ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of similar age and body mass index were used as a control group. Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05). Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue‐related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0–10.0) vs. 7.5 (interquartile range 6.0–9.25), P = 0.04]. Peripheral ED showed correlations with more severe immune‐associated symptoms (r = −0.41, P = 0.026), such as sore throat (r = −0.38, P = 0.038) and painful lymph nodes (r = −0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = −0.59, P = 0.005).

There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels. At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06).

Conclusions:
Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.

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Can the light of immunometabolism cut through “brain fog”?

Can the light of immunometabolism cut through “brain fog”?  by Mady Hornig in J Clin Invest. 2020;130(3):1102-1105 [doi.org/10.1172/JCI134985] First published February 10, 2020

 

Commentary abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a highly debilitating disease with heterogeneous constitutional and neurological complaints. Infection-like symptoms often herald disease onset, but no pathogen or immune defect has been conclusively linked.

In this issue of the JCI, Mandarano et al. illuminate bioenergetic derangements of ME/CFS T cell subsets. CD4+ and CD8+ T cells had impaired resting glycolysis. CD8+ cells additionally showed activation-related metabolic remodeling deficits and decreased mitochondrial membrane potential; a subset had increased resting mitochondrial mass.

Immune senescence and exhaustion paradigms offer only partial explanations. Hence, unique mechanisms of disrupted immunometabolism may underlie the complex neuroimmune dysfunction of ME/CFS.

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The Role of the GP in caring for patients with ME/CFS

Cardiff University medical student Emilia Allwright tells us about her research project: 

 

In October 2019, I presented a poster for my project at the National RCGP conference. This was a wonderful opportunity to highlight ME/CFS and hopefully lead to changes in care.

As part of my medical degree, in Spring 2019, I spent 6 weeks looking at ‘The Role of the GP in caring for patients with ME/CFS’.

I was touched by the response of the ME/CFS community and so grateful to WAMES for helping me to find participants.

I was able to complete 10 telephone interviews- each participant shared their personal story which provided an amazing volume of data to use.

I went through each interview and identified key ideas and themes that formed my results:

  • Patients would appreciate having a single healthcare practitioner who would offer consistent care
  • All but one participant had experienced feeling dismissed by a GP
  • There were examples of positive relationships with GPs where both the patient and GP benefited through working together, but also where relationships had broken down

“They just need to be honest and kind and respectful and together we’ll figure out what the best way forward is.” 

“You hope to have a supportive GP because he will help you, even if he can’t treat you, he will help you.”

“And I just found it too upsetting to keep going because nothing was happening.”

“He’s just been sympathetic to what I’m going through which is a big thing.”

Conclusion:

Overall, my results emphasised the idea that a supportive GP who is honest and open with patients can make a significant impact, regardless of their ability to cure the patient.

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ME, Covid-19 & self-isolating

What do people with ME need to know about Covid-19 and self-isolating?              updated 10 April 2020

 

The Health Minister for Wales has confirmed that people over 70 and people with a range of health conditions, including  neurological conditions, should self-isolate. People with a cough and/or high temperature are asked to self isolate for 7 days. Those who have had contact with someone with confirmed Covid-19 should self-isolate for 14 days. Everybody should stay at home except for essential shopping, short daily exercise a day, essential medical needs, travelling to and from essential work, but only where this cannot be done from home. Social distancing is required by all people when outside the home.

Many people with ME have been self-isolating to some extent for years, because they have been too ill to mix with others. They will be practised in ensuring they have enough food, cleaning products, personal care items, ‘distractions’ and medications, but the coronavirus Covid-19 poses some extra problems and questions.

Much is still not known about this new virus, but some clues are emerging from US research and from the badly affected countries of China and Italy.

People don’t have to have symptoms to be infectious

  • symptoms appear 2-14 days after infection
  • infection can last weeks, up to 37 days (China)
  • people can be infectious before & after symptoms are apparent, or without symptoms
  • it is uncertain how many have no obvious symptoms and are spreading the virus
  • no symptoms doesn’t necessarily mean less able to spread the virus

Infected people without symptoms might be driving the spread of coronavirus more than we realized

 

What are the symptoms?

Regular flu has similar symptoms to COVID-19. However, COVID-19 is more likely to cause shortness of breath and other respiratory symptoms. Some people have only mild symptoms while others are very ill and struggle to breathe.

Coronavirus symptoms            Check your symptoms

 

How does the virus spread?

  • it might be airborne to a small extent
  • it definitely remains on surfaces
  • it probably doesn’t survive in water
  • it survives to some extent in faeces
  • they are unsure if it survives in sewerage systems
  • it enters the body via the eyes, nose, mouth, not through the skin
  • cats can catch it but it is uncertain if they can infect humans

Coronavirus can stay infectious for days on surfaces. But it’s still okay to check your mail

 

Who is most at risk?

Early indications in China and Italy was that the majority of people who died were over 60 with certain underlying health conditions, (but anyone can catch and pass on the virus):

  • heart disease
  • diabetes
  • hypertension – high blood pressure
  • chronic lung disease
  • some cancers

It has now become clear that younger people with no known health conditions can also be at risk.

It is unknown to what extent people with ME are at greater risk but Dr Nancy Klimas believes we could be, as ‘one of the underlying problems is that the cells protecting you against viruses are less functional because overworked.’  Dr Charles Shepherd says: ‘an infection such as this will almost certainly cause a relapse, or significant exacerbation of symptoms’.

Public health England’s updated list of those at risk & requiring social distancing,  which includes Neurological Conditions, the obese and pregnant women.

 

What distance is safe when social distancing?

It may not be possible to avoid close contact with people giving you care, or for whom you care, but all sources say where possible stay 2 metres or 6 feet away from other people. If people are moving (cyclists or runners) it may be wise to stay up to 10m away. Face masks won’t stop you catching the virus, but they may reduce the likelihood of passing it on to others.

Prof Hugh Pennington adds: “This virus needs 15 minutes of close contact with someone carrying it for you to have a reasonable chance of contracting it…But if someone who is infected coughs or sneezes on you directly then the droplets can infect you — that will be a much higher risk.”

 

How long does it last on surfaces?

When self isolating we will need to receive post, groceries etc. Are they safe? US researchers measured how long the virus stays active on various surfaces:

  • up to 24 hours on cardboard
  • up to 2 or 3 days on plastic and stainless steel.
  • it remained viable in aerosols—attached to particles that stay aloft in the air—for up to 3 hours.

Accept goods from outside, then put away perishables without contaminating other items. Either thoroughly wash the outside of the items or leave them until they are safe to touch.  Wash your hands and don’t touch your face!!

 

Can you become re-infected?

  • it is uncertain if or how long immunity lasts
  • it appears to be possible to relapse, though numbers are small
  • there are 2 variations of the virus and potentially it could mutate, though probably unlikely
  • in some countries testing for the presence of the virus may not be reliable so people only think they have recovered
  • most people recover but some experience reduced lung function following recovery, which will require some rehab
  • some concerns have been expressed that the virus may trigger an ME-like reaction as happened with SARS.

Coronavirus: can you get covid-19 twice or does it cause immunity

 

What kills the virus?

  • soap & water – dried by single use paper or warm air
  • alcohol based sprays on surfaces – leave 5 mins before wiping
  • hand sanitisers
  • chlorine
  • cooking removes any danger from food
  • bleach – disinfects, but pollutes- 5 tbsp (1/3 cup) of bleach per gallon of water

BBC: How long does the coronavirus last on surfaces?

 

When to get tested?

The UK is stepping up testing of frontline workers but still only wants to test those whose symptoms become serious due to shortage of tests – if experiencing severe symptoms ring 111 anywhere in Wales.  (Don’t press any numbers, just hold to be connected to NHS Wales, rather than NHS England)

 

How should it be treated?

Treatment for Coronavirus Disease (COVID-19)

 

How can I self-isolate?

Information on what it means to self-isolate in your home, or in a room within your home can be found on the UK Government website.  Increasingly local support schemes are being set up by concerned citizens to make it possible for people to self-isolate, even when they don’t have friends or family nearby, or access to online deliveries.

For info about how to get or give support, find your COVID-19 Facebook support group here Some Council & AVO websites list local sources of help and delivery services. Age Cymru and RVS provide support.

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Interventions to treat pain in paediatric CFS/ME: a systematic review

Interventions to treat pain in paediatric CFS/ME: a systematic review, by Caitlin Ascough, Hayley Kin, Teona Serafimova, Lucy Beasant, Sophie Jackson, Luke Baldock, Anthony Edward Pickering, Jonathan Brooks, Esther Crawley in BMJ Paediatrics Open Vol 4, #1, March 2020

 

 

What is known about the subject?

  • Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is prevalent (1%–2%) in adolescents and nearly two-thirds of patients report moderate or severe pain
  • Pain is associated with worse fatigue and poorer physical function in adolescents with CFS/ME.

What this study adds?

  • Despite the prevalence and impact of pain in children with CFS/ME few treatment studies have measured pain as an outcome and no interventions targeted pain.
  • There is insufficient evidence to suggest that the treatment of fatigue also improves pain in paediatric CFS/ME.
  • Patients who recover from CFS/ME appear to have less pain at follow-up than those who do not recover.

Research abstract:

Background
Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is common (prevalence 1%-2%). Two-thirds of children experience moderate or severe pain, which is associated with increased fatigue and poorer physical function. However, we do not know if treatment for CFS/ME improves pain.

Objective
Identify whether specialist treatment of paediatric CFS/ME improves pain.

Methods
We conducted a detailed search in MEDLINE, EMBASE, PsycINFO and the Cochrane Library. Two researchers independently screened texts published between 1994 and 24 January 2019 with no language restrictions. Inclusion criteria were (1) randomised controlled trials and observational studies; (2) participants aged <19 years with CFS/ME; and (3) measure of pain before and after an intervention.

Results
Of 1898 papers screened, 26 studies investigated treatment for paediatric CFS/ME, 19 of which did not measure pain at any time point. Only five treatment studies measured pain at baseline and follow-up and were included in this review. None of the interventions were
specifically targeted at treating pain. Of the included studies, two showed no improvement in pain scores, one suggested an improvement in one subgroup and two studies identified improvements in pain measures in ‘recovered’ patients compared with ‘non-recovered’ patients.

Conclusions
Despite the prevalence and impact of pain in children with CFS/ME surprisingly few treatment studies measured pain. In those that did measure pain, the treatments used focused on overall management of CFS/ME and we identified no treatments that were targeted specifically at managing pain. There is limited evidence that treatment helps improve pain scores. However, patients who recover appear to have less pain than those who do not recover. More studies are needed to determine if pain in paediatric CFS/ME requires a specific treatment approach, with a particular focus on patients who do not recover following initial treatment.

Read full paper (pdf)

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Cytomegalovirus, Epstein‐Barr virus, & human herpesvirus‐6 infections in patients with ME/CFS (Bulgaria)

Cytomegalovirus, Epstein‐Barr Virus and Human Herpesvirus 6 infections in patients with Myalgic Еncephalomyelitis/Chronic Fatigue Syndrome, by Evelina Shikova, Valentina Reshkova, Аntoniya Kumanova, Sevdalina Raleva,Dora Alexandrova, Natasa Capo, Modra Murovska ( on behalf of the European Network on ME/CFS (EUROMENE) in J Med Virol.  Mar 4 2020 [doi.org/10.1002/jmv.25744]

 

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and human herpesvirus‐6 (HHV‐6) are suspected as etiological agents for ME/CFS.

This study aims to estimate prevalence and type (active/latent) of EBV, CMV and HHV‐6 infections in Bulgarian ME/CFS patients. In the study were included 58 ME/CFS patients and 50 healthy controls.

Virus‐specific antibodies were detected by ELISA and viral genomic sequences in PBMCs and plasma samples ‐ by nPCR. We did not observe any significant differences in virus specific IgG and IgM positivity rates between ME/CFS patients and control group. In ME/CFS plasma samples EBV DNA was found in 24.1%, CMV DNA – in 3.4% and HHV‐6 DNA in 1.7% of samples. EBV DNA was detected in 4%, CMV and HHV‐6 DNA were not found in plasma samples of controls.

The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV‐6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (p=0.0027). No ME/CFS and control individuals with active CMV and HHV‐6 infection were observed.

In conclusion, our study using both serological and PCR‐based techniques for distinguishing between active and latent infection, showed high rate of active EBV infection among ME/CFS patients indicating that at least in a subset of cases EBV is important factor for development of disease.

 

Simmaron research: Active Epstein-Barr Infections Found in Large ME/CFS Study, 18 Jul 2020

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From IBS to ME – the dysbiotic march hypothesis

From IBS to ME – The dysbiotic march hypothesis, by Arnold Berstad, Olav Hauso, Ketil Berstad, Johanna ER Berstad in Medical Hypotheses Vol 140, July 2020, 109648 [https://doi.org/10.1016/j.mehy.2020.109648]

 

Research abstract:

Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown.

Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”.

In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

Conclusion:

The main findings among 1100 consecutive patients with IBS are an extensive past medical history (on average 26 years), during which 80%–90% of the patients, in addition to IBS, developed joint/muscle pain and chronic fatigue, and 65% developed ME. The vast majority of the 200 patients (86%) who were asked, reported extensive treatment with antibiotics during childhood. The observations suggest that IBS and subsequent comorbidities represent “a dysbiotic march” in response to antibiotic-induced “missing microbes”

Hence, our hypothesis is that «the dysbiotic march” begins with antibiotic-induced “missing microbes”, via abdominal discomfort, food intolerance and IBS, then years later, joint/muscle pain and chronic fatigue may develop and ultimately progress to ME. The progress of the disease, i.e. the march from IBS to ME, may well be due to new microbes or other infectious agents invading and conquering the biofilm to exploit its growth conditions.

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Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue

Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue, by Yves Jammes, Chloé Stavris, Caroline Charpin, Stanislas Rebaudet, Gerard Lagrange, Frederique Retornaz in Clinical Biomechanics Vol 73, pp 162–165, March 2020 [ doi.org/10.1016/j.clinbiomech.2020.01.003]

 

Highlights

  • Patients with chronic fatigue have often difficulties to perform a maximal exercise test.
  • Maximal handgrip strength was used to predict maximal exercise performance.
  • We explored 98 severely fatigued patients, 66 of them with chronic fatigue syndrome.
  • Handgrip strength was correlated with peak values of oxygen uptake and work rate.
  • Thus, handgrip strength is helpful when an ergometric cycle test cannot be performed.

Research abstract:

Background:
Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.

Methods:
hand grip dynamometerSixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.

Findings:
No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.

Interpretation:
We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.

Conclusion: when an ergometric cycle test cannot be easily performed, the simple, low cost MHGS measurement may be useful to evaluate the maximal physical performance of patients with chronic fatigue, including those with ME/CFS. However, in ME/CFS patients the sole MHGS measurement cannot replace the information given by a maximal exercise test that are the altered muscle membrane excitability and the associated increase in exercise induced oxidative stress. MHGS can be used as a screening tool for patients who need to undergo a maximal exercise test. The usefulness of MHGS in chronic fatigue possibly opens future ways of research.

Read full paper

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Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography, by C (Linda) MC van Campen, Freek WA Verheugt, Peter C Rowe, Frans C Visser in Clinical Neurophysiology Practice Vol 5, 2020, pp 50-58 [https://doi.org/10.1016/j.cnp.2020.01.003]

 

Highlights:

  • Extracranial Doppler technique to measure cerebral blood flow is feasible during head-up tilt testing.
  • Cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients is reduced during head-up tilt testing compared to healthy volunteers.
  • Using a lower limit of normal of the cerebral blood flow reduction during head-up tilt testing of 13%, 90 percent of ME/CFS patients showed an abnormal cerebral blood flow reduction.
  • Reduction in cerebral blood flow is correlated with symptoms of orthostatic intolerance.

Research abstract:

Objective:

The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using
Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.

Methods:
429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we
administered a verbal questionnaire to ascertain for 15 OI symptoms.

Results:
End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P<.0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI
symptoms with the degree of CBF reduction at mid-tilt (P<.0005).

Conclusions:
During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.

Significance:
This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.

Comment: Could Improved Testing for Orthostatic Intolerance Lead to Better Clinical Care for People with ME/CFS?

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