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CFS & impaired peripheral pulse characteristics on orthostasis a new poss biomarker

Discussion in 'Latest ME/CFS Research' started by Glynis Steele, Jan 26, 2012.

  1. Glynis Steele

    Glynis Steele Senior Member

    Newcastle upon Tyne UK
  2. Firestormm


    Cornwall England
    John Allen1, Alan Murray1, Costanzo Di Maria1 and Julia L Newton 2,3


    'Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed.

    The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue.

    In this study we explored the clinical value of noninvasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

    Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70?).

    Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beatto-beat pulse wave analysis.

    A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002).

    There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05).

    Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%.

    Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.'

    Am going to have to read the full paper methinks before commenting. Not sure I understand it!
  3. Dolphin

    Dolphin Senior Member

    A few quick comments (for what they are worth)

    I read the full paper.
    Figure 1 is very important to understanding what is being measured (for me anyway - I haven't come across the PTTf abbreviation before)

    No psychobabble or criticisms of patients.

    There is quite a bit of maths involved. Not "impossible" stuff (i.e. requiring PhD stats/similar) but does take a little work to go through exactly what they did. Some/many people may prefer just to read the introduction and discussion sections which are both relatively short (less than 2 pages combined) - these sections are certainly interesting, linking in with the ME/CFS studies previously done.

    Given how the ears were the main place to find the abnormalities (a composite measure also had a value), I thought the possible explanations (3rd last paragraph) was very interesting.

    Not sure how widely photoplethysmography is used - in the paper, most of referenced studies seem to be ones that had been done by members of the team.

    It is nice that the test can all be done non-invasively.
    And they only use a 3-minute tilt test.

    The finding of a "relationship between increasing fatigue assessed using the FIS and a reduced change in AMP" (i.e. following tilt) is very interesting if it held up to replication. It's always good to have symptoms correlating with physical changes. And perhaps with the symptom, fatigue, in particular it is is interesting, given how for many people in society, fatigue is associated with other factors e.g. mood.

    Whether the findings hold up to replication I think is the big question. There seems the possibility of over-fitting/similar in this one small study.
    The authors have other suggestions about how other measurements could be taken at the same time in a follow-up study. Given the other interesting research findings that have been coming out of this team, I hope they do it/get a chance to do it (i.e. have/get the funding).
    oceanblue and Firestormm like this.
  4. Firestormm


    Cornwall England
    Thanks Dolphin! Will take a closer look then later. Hopefully these findings will prompt another study from others and it won't become another 'interesting' bit of research that never gets followed up.
  5. Nielk


    Diagnosing Chronic Fatigue Syndrome

    Feb 10, 2012
    Diagnosing chronic fatigue syndrome

    Chronic fatigue syndrome (CFS) is a debilitating condition that currently occurs in up to 0.4% of Europe's population. Despite the sizeable volume of research into CFS, no bedside diagnostic tool currently exists, leaving patients frustrated and seeking answers. Now, however, a pilot study carried out in the UK and published in Physiological Measurement, has shown that a simple optical technique has the potential to identify individuals with CFS (Physiol. Meas. 33 231).

    "Our research study explored how we might use the properties of the peripheral pulse as a diagnostic tool for CFS," said Julia Newton, an honorary consultant physician at the Newcastle upon Tyne Hospitals NHS Foundation Trust and within Newcastle University's Institute for Ageing and Health. "Pulse wave abnormalities were observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls."

    A difficult diagnosis
    CFS can affect all ages and its cause is unclear. One of the current difficulties in recognising CFS is the lack of a suitable diagnostic biomarker. Aware that abnormalities of the autonomic nervous system are observed in over three quarters of those with CFS and that orthostatic intolerance is a common symptom, Newton and her collaborators initiated a pilot study to investigate whether peripheral pulse characteristics on orthostasis could provide the biomarker that clinicians and patients alike are searching for.

    "The normal homeostatic response to standing is to preserve the brain at all costs," explained Newton. "The body therefore aims to do what it can to get the blood back to the brain against gravity by increasing the heart rate and constricting the peripheral blood vessels. Our study focused on measuring and assessing pulses from multiple peripheral sites simultaneously in both CFS patients and controls in response to a posture change."

    Multiple peripheral pulse measurements
    The technique employed by the team is known as PPG, or photoplethysmography. PPG is a simple and safe optical way of measuring the pulse at easy-to-access peripheral sites such as the ear lobe, finger tips or toe pads.

    The researchers recruited 28 subjects: 14 patients with confirmed CFS and 14 healthy control volunteers. For each person in turn, the team simultaneously acquired data from the right and left ear lobes, the index fingers and big toes using its award-winning multi-site PPG technology. Baseline measurements were made with the patient lying supine on a tilt table and collected over 10 minutes. The patient was then tilted upright to an angle of 70 degrees to the horizontal and the changes in pulse assessed over a three minute period whilst they remained in this near-upright position. An electrocardiogram was also collected during the measurements.

    "With each heartbeat, the blood volume changes in the vascular bed of the tissue and the amount of light shone onto the skin by the probes varies in synchrony with this, giving a clear pulse with each heart beat," explained John Allen, a clinical scientist from the Regional Medical Physics Department of Newcastle's Freeman Hospital. "The pulse waveform has many features in terms of its size, shape and the time for it to get from the heart to the periphery as well as beat-by-beat variability. We used special computer analysis techniques to extract various pulse features and compared these to data from normal subjects to provide the diagnostic information."

    Following off-line analysis, the team found that there were significant differences between the CFS group and the controls for combinations of pulse amplitude and timing measurements, with a strong diagnostic bias coming from the ear lobe site.

    "We think that the ear measurements could be influenced by cerebral autoregulation (CA), the reflexes that preserve brain blood flow at all costs," said Newton. "Cognitive problems are common in those with CFS. Further research applied to a larger number of subjects should help decide the most reliable combination of pulse features to measure so that the technique can be applied to a general population for screening of CFS with full confidence."

    About the author
    Jacqueline Hewett is a freelance science and technology journalist based in Bristol, UK.
    allyann likes this.

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