From edmesh Newsletter Issue 74 (Winter 2010)
A large audience gathered to hear Professor Julia Newton MBBS, FRCP, PhD, who is Clinical Professor of Ageing and Medicine at Newcastle University. She began by explaining that her primary interest is in the autonomic nervous system (ANS), which controls all the bodily functions that the conscious mind does not, including heart output, blood pressure and circulation.
How circulation works
In accordance with the body’s needs, the heart’s rate of pumping can quicken or slow, blood pressure may rise or fall, and blood vessels can constrict or dilate. People with fatigue are more
likely to have problems such as faintness, blackouts and lack of blood going to the muscles.
Measuring and scoring
In Professor Newton’s cardiovascular laboratory, one of the largest autonomic testing labs in Europe, various skilfully contrived assessment scales and ingenious measuring devices are used
in the study of the ANS in people with various medical conditions, including ME/CFS. The Orthostatic Grading Scale measures the number of symptoms people have on standing up, such as light-headedness, palpitations, tremulousness, fatigue, nausea etc. It has been found that 89% of those with ME/CFS have a score of over 4. The more symptoms patients have, the more fatigued they are. The Composite Autonomic Symptom Scale (COMPASS), devised in the USA, which measures symptoms of autonomic dysfunction, was used with ME/CFS patients fulfilling the Fukuda diagnostic criteria, and matched controls. Symptoms are scored on the basis of presence, severity, distribution, frequency and progression, and are grouped into 8 domains ranging from orthostatic intolerance (problems on standing up) through gastrointestinal symptoms to sleep disorders. A score of 32·5 or over on the symptom scale is abnormal: ME/CFS patients had readings of 48 on average, the highest individual reading being about 70. The degree of fatigue rose steadily with the number of symptoms. Autonomic dysfunction was present in three-quarters of ME/CFS patients, a most unexpected finding.
Those magnificent machines
The 24-hour blood pressure machine takes ameasurement every 15 minutes. This has beendone with over 100 ME/CFS patients andmatched controls. It showed that the patients’ average blood pressure was significantly lower than in the controls. Heart rate variability (the ability to adapt cardiac output to meet the body’s energy needs) is clearly less in ME/CFS. The Tilt Table is the most specialised piece ofequipment in Professor Newton’s laboratory. Itis basically a bed that can be raised at the headfrom a horizontal to a
vertical position while the“victim’s” blood pressure is measured in the fingers. Continuous beat-to-beat pressure mustbe recorded by a cardiac technician supervisedby a consultant (not Count Dracula). There areonly two centres in Britain that provide this.The equipment is primarily used to investigatesyncope (blackouts). So far 64 people withME/CFS have been tested for Postural Orthopaedic Tachycardia Syndrome (POTS), which is an increase in heart rate from the supine to the upright position of more than 30 beats per minute, or to a heart rate greater than 120 beats per minute within 12 minutes of head-up tilt. It has been found that 27% of ME/CFS patients have POTS.
The Impedance Cardiograph
Cardiac MRIs (magnetic resonance imaging) show that the structure of ME/CFS patients’ hearts is normal, so impedance cardiography, a NASA technology, is used to assess cardiac function.
Electrodes at the back of the neck and base of the spine monitor an electric current as it travels down the aorta, showing how hard the heart is pumping. The hearts of CFS/ME patients are working harder to cope with the stress of standing up compared to the control group, some to the point of being at risk of heart failure.
Can this be seen? Yes – it is known that a beating heart is rotating at top and base as it pumps (this is called torsion) but in patients with another fatigue condition, primary biliary cirrhosis (a liver disease) torsion and rotation are dramatically impaired. Studies are now being done on ME/CFS patients to see if their hearts’ torsion and rotation are affected by high fatigue.
Down memory lane
Memory problems have been described by 85-95% of ME/CFS patients. Laboratory tests using the MRI (magnetic resonance imaging) brain scanner and tilt table reveal that:
- the more the blood pressure drops on standing upright (orthostatic intolerance), the worse the memory is;
- the more fatigued a person is, the worse the memory is;
- the more fatigued, the more white matter lesions (damaged areas) there are in the brain.
(White matter is the 45% of the brain which acts as wiring, delivering instructions to the nerve cells.)
The valsalva (not quite a vuvuzela!)
Would you like to spend an hour blowing 15 times into a “valsalva” tube and having the results analysed in a scanner? Three pints of blood flow through the brain every minute, and blowing
causes a drop in blood pressure – the lower it goes, the likelier a swinging change in blood flow into the brain, when there should be a steady change.
What is “fatigue” all about?
The Newcastle Unit had 260 referrals from GPs of people with fatigue symptoms in 14 months. After thorough medical assessments, it was discovered that only 60% actually had ME/CFS. Of the rest,
47% had other chronic diseases such as fibromyalgia, non-alcoholic liver disease or primary biliary cirrhosis;
20% had a sleep disorder;
15% had primary depression or anxiety;
13% had non-ME fatigue;
5% other conditions.
Careful assessment is needed, for example to ensure that patients receive the right drug treatment.
There can be a dramatic drop-off in functional ability in ME/CFS, so the Newcastle team use the Patient-Reported Outcome Measure Health Assessment Questionnaire to look at getting in and out of the bath, reaching to a cupboard, cooking with pans and so on. This is a highly important area to work on, and it is closely associated with greater cognitive impairment (brain fog), fatigue and orthostatic symptoms.
What can be done to help patients, even at this early stage of research?
A technique called Tilt Training has been used successfully in Newcastle. It simply involves leaning against a wall at home day after day at a certain angle. This resets the baro-receptors for
people with problems on standing, but don’t try this without specialist authorisation! A study the team published in 2009 in a small trial on 59 people showed:
- significant improvements in the working of the autonomic nervous system;
- a trend towards improvement in fatigue.
This is very good news, but a bigger study is needed!
As regards the thorny question of exercise, Professor Newton explained that it causes acid to build up in the muscles. ME/CFS people accumulate more acid on exercise, and struggle to get rid of it. Studies need to be done to identify which acid or acids are involved (thought to be lactic acid); the muscles and acid-transporting system need to be looked at in detail too. Certain types of exercise are very good at clearing acid and other types make it worse, because they increase the heart rate and push people beyond their anaerobic (lactic acid) thresholds, which they mustn’t go above – up to 80% is enough. The Newcastle team offer “Individualised Activity Management” (avoiding the dreaded e-word!) believing that, as with prescribing a medical drug, the choice, dose and duration of activity needs to be carefully worked out and agreed on to suit each patient.
Additional treatments prescribed for some include drugs to reduce tachycardia (fast heart rate), drinking up to 5 cups of coffee a day to increase blood volume (luckily “5-a-day” is already a familiar phrase!) and raising salt intake to increase blood pressure.
At the question and answer session, Professor Newton explained that MRI scans are done for research purposes, and are not available for diagnosis of individuals. Pilot MRI scans have been done on 27 ME/CFS patients, to assess brain structure, blood flow, acid movement, evidence of strokes, bleeding or white matter lesions. A lot of tests have been done on the same people to provide comprehensive information, at a cost of £100, 000 altogether, funded by MERUK. People who have had a muscle MRI scan have had a muscle biopsy after exercise, looking for acid in the cells and of what type, and for what enzymes are defective. Muscle cells can even be grown and analysed in the laboratory!
The team at Newcastle have 3 cohorts of ME/CFS patients they have been following for up to 10 years, as well as groups with other conditions involving the autonomic nervous system – the
common link is inflammation. Julia Newton keeps up with the work of Dr Jo Nijs, of the Free University, Brussels, and Professor Myra Nimmo of Loughborough University in this respect.
Professor Newton recommended that ME patients who have had blackouts, or who think they have POTS, and those who have symptoms on standing up, should see their GPs to ask for a referral to the Newcastle clinic.
She explained that her team were very grateful to ME Research UK, who had funded most of this work, and to patients from ME North East, the local self-help group, who had been very cooperative.
- ME/CFS is closely associated with autonomic nervous system dysfunction.
- A COMPASS score of over 32·5 could clearly diagnose ME/CFS in the large proportion of patients with ANS dysfunction.
- Measurements of orthostatic intolerance, low heart rate variability and autonomic dysfunction in ME reinforce one another and their degrees of intensity correlate with fatigue severity.
- More work needs to be done on larger numbers of people to identify the mechanisms and causes underlying ME/CFS symptoms before appropriate treatments can be devised.
Professor Newton and her colleagues are clearly doing highly original research into the autonomic nervous system and making important discoveries about the physical symptoms of ME/CFS. They are working towards making explainable connections between the different biological systems involved in the cascade of effects produced by this condition, so that it can be diagnosed and demonstrated to be an illness of the human body.
It seems probable that when the ultimate causes are figured out, they will include a kaleidoscope of influences, including genetic sensitivity, innate or acquired defects, toxic overloads, accidents, illnesses, stressful life events or situations, and negative unconscious beliefs. Then maybe those in science, medicine and alternative therapies as well as the patients themselves will be able to pool their healing resources, and we will at last see TS Eliot’s vision of “the whole consort dancing together.”
Newton JL et al. Symptoms of autonomic dysfunction in chronic fatigue syndrome. Quarterly Journal of Medicine 2007; 100: 519-526.
Sutcliffe K et al. Home orthostatic training in chronic fatigue syndrome – a randomised placebo-controlled feasibility study. European Journal of Clinical Investigation 2010; 40.1: 18 -24. (link to abstract)
POTS – A Personal Experience. edmesh Newsletter 69: Autumn 2009
DVD of talk
Members may obtain their own free copy of the DVD of Professor Newton’s talk by emailing firstname.lastname@example.org. A copy of the DVD is also available from the edmesh library.
© edmesh 2010.
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