ME Research UK – American ME and CFS Society

Visual aspects of reading performance in myalgic encephalomyelitis (ME)

Reprinted with the kind permission of ME Research UK.

Abstract:

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) report vision-related reading difficulty, although this has not been demonstrated objectively. Accordingly, we assessed reading speed and acuity, including crowded acuity and acuity for isolated words using standardized tests of reading and vision, in 27 ME/CFS patients and matched controls. We found that the ME/CFS group exhibited slower maximum reading speed, and had poorer crowded acuity than controls. Moreover, crowded acuity was significantly associated with maximum reading speed, indicating that patients who were more susceptible to visual crowding read more slowly. These findings suggest vision-related reading difficulty belongs to a class of measureable symptoms for ME/CFS patients.

Publication

Wilson et al, Frontiers in Psychology, 2018 August 17; 9:1468

Authors

Rachel L. Wilson, Kevin B. Paterson, Victoria McGowan and Claire V. Hutchinson

Institution

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, UK

Funding

This work was funded by an ME Research UK (Grant No. SC036942) to CH and KP. VM was supported by an Economic and Social Research Council (Grant No. ES/L010836/1).

Comment by ME Research UK

Many people with ME/CFS suffer from problems with their eyes and vision, such as oversensitivity to light, troubles with focusing, and dry eyes. Reading can therefore be challenging, particularly for long periods, and pattern glare, headaches and difficulty tracking lines of text are commonly reported. However, before now, the reading performance of ME/CFS patients had not been assessed objectively.

Over the last few years, Dr Claire Hutchinson and her colleagues at the University of Leicester have been looking in depth at some of the vision-related problems associated with ME/CFS, supported in part by grants from ME Research UK.

The group has found that most ME/CFS patients experience a degree of eye pain and sensitivity to bright lights. Using sophisticated eye-tracking techniques, they have also shown that patients struggle to focus on one object and ignore irrelevant information, are slow in shifting attention between objects, are slower than normal and less accurate in their eye movements, and are vulnerable to pattern-related visual stress.

In their latest ME Research UK-funded study, published in the journal Frontiers in Psychology, the Leicester team set out to evaluate what impact ME/CFS has on reading performance. A total of 27 ME/CFS patients and 27 healthy control subjects took part in the research; all had normal vision or corrected-to-normal vision (i.e. they wore spectacles or contact lenses) and none had any history of eye disease.

Reading performance was assessed using two standardised tests, the Minnesota Reading Acuity Chart and the Radner Rate of Reading Chart, which between them produced the following measures:

Reading acuity (the smallest print size that can be read without significant mistakes),
Maximum reading speed (not limited by print size),
Average reading speed, and
Critical print size (the smallest print size that can be read at maximum speed).

As expected, the maximum reading speed was significantly slower in ME/CFS patients than in control subjects, and patients also tended to have a slower average reading speed. However, reading acuity and critical print size were not different between the two groups, indicating that the reading difficulties were not due to an inability to make out smaller print.

Furthermore, ME/CFS patients and control subjects performed similarly on a vocabulary test, showing that the differences in reading performance between the two groups were unlikely to be due to cognitive problems.

The researchers also looked at uncrowded visual acuity for individual words and letters (identifying a word or letter on its own) and crowded visual acuity (identifying a target letter surrounded by other letters), using the logMar Crowded Test.

While uncrowded visual acuity appeared to be similar in patients and controls, ME/CFS patients did have greater problems with visual crowding and performed less well on that test. Furthermore, those individuals who were more susceptible to visual crowding were also shown to read more slowly.

These findings build on a considerable body of work from Dr Hutchinson and her team in which they have detailed and explored the vision-related symptoms associated with ME/CFS. While many people with he illness know full well how difficult it can be to read comfortably, particularly for long periods, this is the first time these problems have been assessed objectively in a laboratory setting.

As the researchers conclude, ‘identifying and treating vision-related symptoms of ME/CFS could provide a means of improving the everyday lives of patients’.

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ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS.

Comment by ME Research UK: Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study

Reprinted with the kind permission of ME Research UK.

Authors

Newton JL, Finkelmeyer A, Petrides G, Frith J, Hodgson T, Maclachlan L, MacGowan G and Blamire AM

Institution

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne Hospitals NHS; Newcastle Magnetic Resonance Centre, Newcastle upon Tyne, UK

Published abstract

Objectives

To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.

Methods

Cardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin.

Results

The CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r2=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r2=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities.

Conclusions

This study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.

Publication

Newton et al, Open Heart, 2016 Jun 24; 3(1):e000381

Funding

Medical Research Council, ME Research UK

Comment by ME Research UK

Over the years, a number of reports in the scientific literature have pointed to the presence of abnormalities of heart (cardiac) function in ME/CFS. For example, a study in 2006 found that ME/CFS patients had relatively short QT intervals (measures of the heart’s electrical cycle) compared with healthy people (read more). Also, in 2009, Japanese researchers reported cardiac dysfunction with low cardiac output in some oriental patients (read more), and another investigation found that cardiac function was diminished (read more).

Alongside these reports, ME Research UK-funded investigations by Prof Julia Newton, Dr Kieren Hollingsworth and colleagues at Newcastle University have also throw up some intriguing findings concerning the function of the heart in ME/CFS. For example, they have shown that ‘bioenergetic abnormalities’ could be found both in heart muscle and in the muscles of the skeleton, with a correlation between the two suggesting the existence of linked underlying mechanisms (read more). In the same investigation, they found that the hearts of the ME/CFS patients had to work harder during prolonged standing than in healthy people. The research group has also looked at the function of the heart using cardiac MRI tagging to identify defects that are not yet clinically apparent. One of their main findings has been a dramatic increase in ‘residual torsion’ in patients compared with controls. This is a measure of the efficiency of the release of torsion and strain during the relaxation phase of the heartbeat, and ME/CFS patients had 200% more residual torsion than healthy people, indicating that their heart muscle was taking longer to relax. Also, the left ventricular mass (the thickness of the heart wall at the ventricle) was reduced compared with controls; and cardiac output (the output of blood by the heart per minute) was lower (read more).

The Newcastle researchers have been continuing their investigations, and their latest report has just been published in the journal Open Heart (read more). It describes work to confirm these previous findings in a larger group of new patients and controls, and extend them to include cardiac output and blood volume. In the experiments, cardiac magnetic resonance examinations were performed in 47 patients with ME/CFS who had been ill for 14 years on average and 47 case-matched controls, and blood volume measurements in 41 CFS and 10 controls. Patients with a diagnosis of depression were specifically excluded from the study so that depression could be ruled out as a potential, if unlikely, cause of the abnormalities.

The results were fascinating. Compared with healthy controls, stroke volume(the amount of blood pumped by the left ventricle in one contraction) was 23% lower in the ME/CFS patients; end-diastolic volumes were 25% lower; end-systolic volumes were 29% lower; and end-diastolic wall masses were 26% lower (all p<0.0001). In essence, these findings confirm, in a larger and different group of patients, the reductions in cardiac volume observed previously in ME/CFS patients in Newcastle.

The total volume of blood (plasma and red cells) was 4% lower in the ME/CFS group compared with controls, though this difference was not statistically significant. In 63% of the patients, however, the volume of red blood cells was below 95% of the expected levels for healthy people. Also, there were strong positive correlations between blood volume measurements and cardiac end-diastolic wall mass, and a weak relationship between plasma volume and fatigue severity. Importantly, the length of illness was not related to any cardiac magnetic resonance or volume measurements, suggesting that deconditioning (which would be greater the longer a person was ill) was unlikely to be the cause of these abnormalities.

The finding that red cell volume was low is intriguing, and it may be that blood volume plays at least a part in the symptoms experienced by ME/CFS patients. One intriguing possibility alluded to by the researchers is that the abnormalities detected in this study, particularly the reduction in end-diastolic blood volume, may be due to problems with venous compliance (see diagram above), as nearly two-thirds of the blood in the systemic circulation is stored in the venous system and compliance is controlled by the autonomic nervous system which is also affected in ME/CFS. In fact, low total blood volume has been proposed as part of the disease process in subgroups of ME/CFS patients before. One investigation in 2002 found a 9% lower blood volume in ME/CFS patients than in controls (read more). A further study in 2009 showed that the reductions in cardiac output and end-diastolic volume in ME/CFS could be entirely accounted for by a reduction in the total blood volume (read more), and an accompanying editorial pointed out that the results did not imply heart disease, but rather pointed to “circulatory impairment” (read more).

Overall, these findings using state-of-the art MRI confirm the presence of cardiac abnormalities in people with ME/CFS. It remains unknown, however, whether these are caused by ME/CFS and its consequences per se or whether, for instance, a (pre-existing) reduced cardiac volume may make people more vulnerable to the development of the illness. As regards low blood volume, there is anecdotal evidence that the symptoms of ME/CFS improve in some patients after treatment with intravenous fluid (although the procedure is not without drawbacks and risks), and the team in Newcastle intend to explore interventions to restore fluid volume in ME/CFS patients in further studies.

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ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS.

Comment by ME Research UK: Elevated brain natriuretic peptide levels in chronic fatigue syndrome associate with cardiac dysfunction: a case control study

Reprinted with the kind permission of ME Research UK.

Publication

Tomas et al, Open Heart, 2017 Dec 27; 4(2):e000697

Comment by ME Research UK

An increasing amount of research has revealed heart abnormalities in patients with ME/CFS. For example, people with the illness have been found to have a short QT interval (a measure of the electrical activity of the heart) and a reduced cardiac output (the amount of blood pumped by the heart per minute). These changes may occur before any symptoms are apparent.

Much of the recent work on cardiac dysfunction in ME/CFS has been carried out by Prof. Julia Newton and her team at Newcastle University, including studies funded by ME Research UK.

In 2012, they used magnetic resonance imaging and cardiac tagging technology to asses a group of ME/CFS patients, and found that several measures of the heart were lower in patients than in healthy control subjects:

left ventricular mass (the thickness of the wall of the left ventricle, the main pumping chamber of the heart),
stroke volume (the amount of blood pumped by the left ventricle in one contraction),
cardiac output, and
end-diastolic volume (the volume of blood in each ventricle after they have refilled).

Then, in 2016, they repeated some of these assessments along with measures of blood volume. The total volume of blood (plasma plus red cells) was slightly less in ME/CFS patients than in controls, but there was a strong association between blood volume and cardiac end-diastolic wall mass.

Continuing their work in this area, the team has recently published a paper in the journal Open Heart looking at levels of brain natriuretic peptide in ME/CFS, and correlating these with measures of cardiac dysfunction.

Despite its name, brain natriuretic peptide (or BNP) is a hormone that is actually secreted by the muscle cells of the heart, and is produced when the ventricles are overstretched to accommodate an increase in blood volume.

Circulating BNP causes a decrease in blood pressure and in cardiac output, and has found use clinically as a diagnostic and prognostic marker of heart failure.

In their current study, the investigators recruited 42 patients with ME/CFS and no other illness, as well as 10 sedentary control subjects matched for age and sex.

The participants’ hearts were examined using magnetic resonance techniques to provide a number of measures of cardiac function, including cardiac volumes at the end of systole (after the ventricles have contracted and pumped out their blood) and at the end of diastole (when the ventricles are relaxed and have refilled with blood).

In addition, blood samples were taken, and plasma BNP levels were measured using an enzyme immunoassay.

The first important finding was that BNP levels were significantly higher in ME/CFS patients than in sedentary control subjects, with mean levels of approximately 500 versus 300 pg/mL, respectively.

Furthermore, both end-systolic and end-diastolic cardiac volumes were significantly lower among patients with high BNP levels (defined as being greater than 400 pg/mL) than in those with low BNP levels.

BNP tends to be a sign of cardiac volume overload, so this association is not what one would normally expect to see. One explanation suggested by the researchers is that the high BNP is causing an excessive production of urine, which reduces the total volume of circulating blood (as seen in their earlier study), leading to a smaller cardiac volume.

It is important to note that none of these measures were related to the patients’ duration of ME/CFS, indicating that the results are unlikely to be due to deconditioning (i.e. they were not the result of the heart adapting to less physical activity).

What might these results mean to patients? One possibility put forward by the investigators is that measurement of BNP levels may be a convenient way by which to identify those ME/CFS patients with cardiac abnormalities who might benefit from specific treatments, although additional studies would be needed to confirm this.

This approach may also be valuable in identifying a specific cardiac subgroup of ME/CFS patients, and better understand the diverse nature of this illness.

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ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS.