New BMJ guidelines

Although not perfect, these new guidelines represent a shifting tide away from NICE CBT & GET ridiculousness. Read the full document here. (Note this was issued in July and updated in nov 2017 to remove peter smiths name)

Some highlights:

‘The chronic disability leads to a sedentary lifestyle that may foster deconditioning of muscular, cardiovascular, and autonomic nervous systems. This provides the rationale for supervised, very low impact exercise if a suitable, well-tolerated programme can be individualised for each patient. However, exercise may be counterproductive in severe and/or bedridden CFS because the treatment may induce post-exertional malaise (PEM) and prolonged exercise-induced exacerbations. Mandated exercise programmes with predetermined goals cannot be endorsed because of their potential to harm patients whose primary problem is exercise-induced loss of function.’

‘Exercise may be beneficial for recovery of athletes, healthy individuals, cardiac patients, and others who may experience temporary immobility, but it is not clear whether patients with CFS respond in the same way’…
‘This highly generalised view and exercise prescription may not apply to the theories of metabolomics dysfunction and post-exertional malaise in CFS’… ‘What appears to be deconditioning may in fact represent the inability to generate adequate ATP for muscular work,and intolerance of exercise-induced acidosis as the diagnostic PEM epitomises’.

GET is recommended for mild fatigue only: ‘with mild fatigue: consider individualised exercise program’.

‘CBT may help in dealing with a new diagnosis of CFS, improve coping strategies, and assist with rehabilitation…
‘to take advantage of periods during the day where fatigue is felt the least…
‘However, the prospect that CBT can change the illness beliefs of a patient, and that graded activity can reverse or cure CFS, is not supported by post-intervention outcome data. Furthermore, in routine medical practice CBT has not yielded clinically significant long-term benefits in CFS.’

‘Non-adherence with prescribed exercise protocols may indicate that the protocol is too aggressive for the patient. Patients should be provided time to recover between each exercise session. Imposing strict adherence to a uniform exercise regimen will generally not be tolerated by patients with CFS. Other factors contributing to non-adherence include severe fatigue, pain, difficulties in travelling to the physician, and severity of PEM following visits to the physician’…
‘Family, financial, and other conflicts may interfere with the physician-patient relationship. Sleep disruption with reversal of day-night cycles may confound patient travel plans and appointments. Furthermore, concomitant problems such as IBS with uncontrolled explosive diarrhoea can be an embarrassment that keeps the patient housebound. Social withdrawal with depression should be addressed, and all such patients asked about suicidal ideation’…
‘Patients with severe CFS may be bed-ridden and require home visits and in-home therapy sessions because severe pain and discomfort will prevent them from travelling. Severe CFS represents about 5% to 10% of cases. It is not known if this group represents a separate disease or aetiology, or is the extreme end of a continuous distribution of CFS severity.’

‘The presence of inflammation in CFS pathology may contribute to inflammatory dysaffective disorders (IDD) that will require a reassessment of potential treatment options.’
– This is not discussed further and google pulls up little information. Theoretically, given our recent understanding that inflammation can be associated with depression, this could be saying that depression isn’t causative or comorbid but is in fact secondary to the disease process itself.

‘The focus of treatment should be orientated toward symptom management and functional improvement, and away from repeated, extensive diagnostic procedures, or ongoing referrals to additional specialists.’
– This is counterproductive for evidence gathering for disability.

The review recommends use of the Canadian consensus criteria (CCC) and dropping the oxford criteria and studies which were based on it.
‘It is inappropriate to use the 1991 Oxford criteria of fatigue as an alternative for CFS because the Oxford criteria are based on ‘mild fatigue’, do not require PEM, and allow inclusion of chronic idiopathic fatigue, depression, and other fatiguing conditions. Up to 30.5% of the population have chronic fatigue and would meet Oxford criteria for study inclusion. Studies that used the Oxford criteria are not representative of the more severe and restricted definitions of CFS that the CDC, Canadian Consensus, or SEID criteria define. Exercise and cognitive behavioural therapy studies that used the Oxford criteria for study inclusion are biased and misleading because people with true CFS are underrepresented, with excessive recruitment of people with chronic idiopathic fatigue and depression who are known to respond well to these modalities.’

‘Myalgic encephalomyelitis (ME) is more strictly defined than CFS. ME is defined by: disabling fatigue; post-exertional malaise; sleep, pain, cognitive and autonomic dysfunction; and chemical irritant sensitivity.’

Regarding ‘false illness beliefs’ (on which PACE trial based):
‘The biopsychosocial model of CFS and its treatment with CBT has been adopted by many governmental organisations with the aims of eliminating many presumed psychogenic and socially induced factors that maintain illness behaviours. The literature does not justify the biopsychosocial model of CFS when studies are limited to CFS patients with moderate to severe fatigue, and PEM in accordance with the Centers for Disease Control and Prevention (CDC) and Canadian Consensus Criteria.’

‘Chronic pelvic pain, vulvodynia, interstitial cystitis, IBS, and other functional somatic syndromes should be treated as significant components of the CFS panoply, with appropriate diagnosis and treatment.’
– Ridiculous that IBS would still be listed as ‘somatic’.

‘There is currently no evidence showing one drug regimen to be more effective than another. Choice of drug should be based on the side-effect profile of the drug and the patient’s initial response to treatment. Some patients have hypersensitivity to medication side effects.’

‘Metabolomics dysfunction and beneficial effects of rituximab provide new insights into the pathophysiological mechanisms of CFS. These studies of biological dysfunction suggest that CFS does not overlap with chronic idiopathic fatigue or depression.’

The review also includes some information about differential diagnoses which may present as ME/CFS, for example, Major depression: ‘Diagnosis is clinical but the affective dysfunction does not follow an infection, and is not typically associated with new onset of pain, migraine, irritable bowel, or autonomic dysfunction. It is generally improved by exercise instead of exhibiting post-exertional malaise and exhaustion.’

Note: The review at times seems to be presenting two contradictory views at once, presumably main peer-reviewer Peter White (involved with PACE) contributed the pro CBT & GET sentences which are not in alignment with the conclusions. ‘Disclosures: PDW does paid and voluntary work for the UK government and a reinsurance company’.

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LP, attachment & the placebo effect 

Recent research by prominent  biopsychosocial researchers Crawley et al is prompting furious backlash amongst patients arguing for better care and the validity of ME/CFS. Some patients have posted about the ‘lightening process’ saying ”Don’t beckon lightning and invite it in for tea; it will burn your house to the ground with you inside until you’re nothing but ashes.’ It certainly seems true that the expectation to exercise and ‘push through’ is responsible for vast reported harm by patients.

What may be equally as important to patient outcomes is the presence or absence of true support, a feeling of safety and security, emotionally and biologically, at the individual, familial and societal levels. This is rarely the ME/CFS patient experience. 

Researcher and author Lissa Rankin talks about support as a crucial element to initiate self-healing, with physical health the most fragile element which is dependant on more than good diet and exercise. 

Relationships matter to health. Strong social network reduces heart disease. Married’s are twice as likely to be long-lived. I’ve written at length on the aetiology of relationship dysfunction stemming from the inability to form secure attachments, and theoretically this could be extended to a larger sense of societal and cultural safety, such as (for example) not being expected to work when it causes suffering and worsening, or to not be dismissed, blamed, ridiculed or otherwise abused by the medical establishment. 

‘Stephen Porges, Ph.D., a pioneer in the field of neuroscience and one of the world’s leading experts on the autonomic nervous system, confirms that we have an imperative for safety deeply wired into our minds and bodies.
Porges’ Polyvagal Theory describes how our autonomic nervous system mediates safety, trust, and intimacy through a subsystem he calls the social engagement system. Our brain is constantly detecting through our senses whether we are in a situation that is safe, dangerous, or life threatening’

~The Gottman Institute

Lissa rankin talks about loneliness, overwork, lack of spirituality or negative attitudes as affecting physical health. All of this is perceived as the brain and communicated via hormones and neurotransmitters as a threat, as something wrong. The amygdala turns on hypothalamus, to both the pituitary and the adrenals for cortisol, norepinephrine & epinephrine for a sympathetic (mal)adaptive stress response. Relaxation from a sense of safety, on the other hand, triggers oxytocin, dopamine, nitric oxide, endorphins—which are natural, healing, self repair mechanisms. Meditation, creativity, massage, yoga, laughter, sex and time with animals can trigger this response. 

If LP is working for some ME/CFS patients, this is likely (apart from issues with overdiagnosis) to be due to a placebo affect triggering the parasympathetic system response described above. What is most problematic however, is when this is used in a manipulative fashion, for example, to reduce costs for insurance companies, or is abusive as it is accompanied by denial of the existence of ME/CFS as a biological illness, dismissal of patients realities (gaslighting) or used as a justification for the denial of medical and social support (neglect). In this context, it is not safe.

As with any serious and incurable illness, spontaneous remission is possible, and is proof that nature is better than all of men’s medical knowledge and technology—but this cannot just be expected of patients, especially in a hostile environment where they are unsupported by doctors, policy makers and society at large. It’s one thing to empower and support patients to heal themselves, it’s another entirely to demand and expect it while denying rest, medical care and social security.

‘I believe that just as there are no incurable illnesses, there are no incurable systems. But it’s gonna take all of us, needing to open our hearts and our minds, and bring care back to healthcare.’ 

~Lissa Rankin.

The black loom

When we as a community say ‘this illness is biological’ or ‘CFS is not psychological’ or when we argue against theories of ‘MUPS’ or ‘somatisation’,

We are fighting for the right to be treated with kindness and compassion, to be given appropriate medical and other support, and to not be blamed. More than that though, what we are really saying is that we don’t agree we have the control being attributed to us. That if this debilitating disease state was ‘psychological’, we would do whatever we could to sort it out just to end the relentless suffering. 
The real issue is this Cartesian dualism, the concept of mind and matter as separate, which relies upon a fantastical conception of the mind as some kind of floating omnipotent entity entirely separate from the body. (It also relies on a denial of the impact of environment, past experiences, and cultural pressures on physical health and emotional wellbeing). Such a mind is endowed with the complete capacity for free will, something which is not possible within the realms of science. 

Logically this is contradictory: if we have total or even partial free will, which allows us to control our physiology with our minds, where does that leave the medical establishment? What is the point of the whole thing? And how is it even possible for a mind to function within a brain, but discrete from its biological realities anyway? At best it is a cause and effect program of infinite intricacy, much of which is created by genetics, in the womb and first 18 months of life.

When we say of any illness that it’s ‘just psychological’, we are banishing it from the realms of scientific measurement (and therefore medical assistance) and making the individual’s suffering entirely their responsibility, their problem to fix, their inadequacy and their mistake.

This is very convenient, not just to underfunded social services or medical facilities (liberalisation does not support those who cannot pay to play), but also to highly paid specialists for whom the problem outstrips their understanding and capacity. Rather than say ‘medicine doesn’t know, we can’t help, we’re sorry, here’s your $350 back’, they say ‘you’re somatising, you’re food adverse, you’re exaggerating, if you just exercise more you’d be fine’. 

Rather than the physicians sitting with this inadequacy, the patients (the ones already suffering) do. The end result is a deep sense of failure, shame, confusion and frustration.

~~~~

Yesterday, after overheating outside, turning blue inside, and using my arms more than I can safely do, I found myself very car sick. As we drove from the house we were leaving to where we would be staying, wave after wave of nausea washed over me. I found myself thinking ‘is this nausea caused by stress? What can I think about that will calm my body?’ I tried distracting myself, closing my eyes and meditating, focussing on counting, taking deep breaths, looking out the window at a distant point… and then I filled the hood of my fleecey jumper with projectile vomit.

I don’t get car sick and I definitely don’t puke—except when I ‘overdo it’ and trigger ME symptoms, the mechanism of which is mostly unknown. In this case, stressful thoughts may or may not have been the straw that broke the camels back, due to an intolerably high allostatic load which left no room for human error (or human emotions), but ultimately I just desperately wanted a sense of control over what can be tortuous (and seemingly unending) discomfort. 

I fall into the trap of a dualistic approach when all physical means fail me. It’s easier to believe I can somehow fix this illness with my mind, then it is to sit with the sense of hopelessness that comes from just NOT KNOWING what is wrong, how to possibly make it better, or how to stop it happening again.
There is much unseen beyond the comprehension of the intellect. If anything, it’s not just ‘body and mind’, but mind body and SPIRIT. If the mind is real (lol), then the spirit is more real. As a third year psych student, I found myself in complete crisis after I realised that psychology could only be a science if the mind is a cause and effect machine—which leaves no room for free will, spontaneous change, spirit, or revelation which stems from the interconnectedness beyond the reach of our logical ‘mind’. Ultimately, I suspect there is a reality which will always remain beyond the capacity of measurement, due to the infinite variables. And this may be directly impacted by prayer, or reiki, or other woo woo, ra ra. 

It’s possible that we create disease with our thought patterns, habits, and toxic programming stemming from adapting to a dysfunctional world, or from childhood trauma or neglect. We have different vulnerabilities which show up as gout, migraines, or leukaemia. The effect of toxic environments and toxic cultures is not discrete and saved only for those of us with ‘medically unexplained illness’. The ability to manage symptoms by exercising extraordinary restraint, diligence and spiritual fucking awakening is also not unique to us, and neither is the failure to do so. 

If we didn’t have a known aetiology for cancer, biopsy to examine it, and chemo to treat it, we’d be telling cancer patients they need to stress less, eat better, micromanage their physical environments and time and exertion and nutrient intake. We’d be telling them that CBT was the only treatment and they better do it (even if it achieved little but wasting their time and money), and if they didn’t get better we’d leave them to their own devices. Our illness is only our problem to bear the weight of alone until science (and therefore medicine) can achieve dominance enough to confidently assume responsibility—and sell us a medication to match. Even if that medication comes with side effects and causes iatrogenic disease. Even if the knowledge doesn’t lead to vibrant health. Even if meds only bandaid and superficially alleviate the symptoms of underlying issues, which actually stem from generations of living in discord to what is healthy for human beings—caused by adulterated food, decimation of and war with the microbiome, disconnection from our communities, and a lack of entitlement to food, water, and a chunk of land to sleep on. Problems which take a lifetime or more to remedy…. or perhaps are just part of suffering as an inevitable component of the human condition. Not be a pleasant tone to end on, but possibly true; I wish this meandering train of thought had lead somewhere more uplifting.

‘And when the black thread breaks, the weaver shall look into the whole cloth, and he shall examine the loom also’. 

~Kahlil Gibran

We are banished from the (cold) embrace of modern medicine for the very reasons it is flawed, inadequate, and ultimately failing humanity as whole. It’s possible ME/CFS may be a keystone illness, one which when we understand will unravel the whole cloth, and lead to deep and systemic change. 

We can only hope.

‘The phrase “it’s all in the mind” suggests that all we need do is change it. Change our mind and the problem dissolves. But such a view of mental phenomena is puerile. Our minds are not sovereign over themselves in these things. And the quicker we ditch that stale and exhausted canard the better.’

BMJ Review

Potential medication: Florinef

Regarding pharmacotherapy for POTS, UpToDate states ‘There have
not been long term, high quality trials testing the efficacy of any pharmacologic approach in POTS. All suggested medications are off label’, and ‘The optimal therapy of POTS is not established’.

The use of fludrocortisone as the first line of therapy for POTS has Grade 2C evidence (UpToDate).

Beyond this, studies specific to orthostatic intolerance in CFS found fludrocortisone to be no more efficacious than placebo for amelioration of symptoms (Rowe. et al, 2001).

A 2011 RACGP review found this medication not effective and potentially harmful/damaging in ME/CFS, with serious side-effects
from long-term corticosteroid therapy (RACGP, 2011).

The NICE 2007 guidelines (on which much of  the Australian guidelines are based) also explicitly state ‘1.4.6.1 The following drugs should not be  used for the treatment of CFS/ME: mineralocorticoids (such as fludrocortisone)’.

Regarding neuroendocrine function, as stated in the 2002 RACP quoted by the HPAU, impaired hypothalamic– pituitary–adrenal (HPA) axis activation has been shown in CFS (Level III-2).

****

Fludrocortisone works to raise blood pressure primarily by increasing blood volume, assumed to be a cause of POTS in CFS patients, as deconditioning or time in bed reduces blood volume.

2017 Me/Cfs Symposium highlights

Video link: OMF symposium on YouTube

Time stamps (care of Melbourne bioanalytics)

Full overview: http://scopeblog.stanford.edu/2017/08/25/at-symposium-researchers-and-patients-examine-molecular-basis-of-chronic-fatigue-syndrome/

Highlights:

(Note the colour coding appears to be reversed in this graphic)

<break>

More slides can be found as images here Myalgic encephalomyelitis post

Sex differencess

Women are affected by ME/CFS at much higher rates. Presumably the factors which lead to this may play a role in treatment response and recovery rates.

Recent metabolomics studies show a different pattern of disruption, with differences in the protein deficiencies and pathways affected between males and females. Similar to other autoimmune diseases like lupus, 80-90% of ME/CFS patients are women.

Anecdotally, CFS recovery, especially through exercise, seems more common amongst men (and many of the researchers and clinicians advocating GET are also male). Perhaps men are originally affected at similar rates to women (without being diagnosed) but are able to recover. Testosterone may play a role, given the role of muscle wasting, as testosterone makes it easier to build muscle. It may also be anti-inflammatory (ref). Menstruation may also play a maintaining role.

2015 study on gender differences in CFS: Only 9.1% of patients were men.

‘Widespread pain, muscle spasms, dizziness, sexual dysfunction, Raynaud’s phenomenon, morning stiffness, migratory arthralgias, drug and metals allergy, and facial oedema were less frequent in men. Fibromyalgia was present in 29% of men vs. 58% in women. The scores on physical function, physical role, and overall physical health of the SF-36 were higher in men. The sensory and affective dimensions of pain were lower in men.’
‘Men had less pain and less muscle and immune symptoms, fewer comorbid phenomena, and a better quality of life.’

‘More men reported an initial infectious process (26.9 versus 13.0%), while pregnancy-partum issues were precipitating factors in 11.3% of women.’

Ratios of male to female differ and differing case definitions confuse the issue even more so. A 2014 Norwegian study found the female to male incidence rate ratio of CFS/ME was 3.2 (75.4% women).

Metabolic features of me/cfs Naviaux 2016 study showed distinct patterns for males versus females. This could theoretically explain higher incidence of me/cfs in females, the above lower quality of life for females, and potential differences in treatment response.

Fluge and Mella found sex differences also:

Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients.

‘Sex appeared to be an important factor in interpretation of the results, with significant reductions of mean serum levels of category II and III amino acids evident in female ME/CFS patients’


Infections reveal inequality between the sexes

Hormones also play a part. Oestrogen can activate the cells involved in antiviral responses, while testosterone suppresses inflammation. Cyclical estrogen fluctuations may reinforce MCAS, with raised circulating histamine.

Historically, vaccines have been more effective in girls (TB), others have killed girls (measles in 1992).

‘Genetic factors may also guide how the sexes deal with infection. Meyaard studies a protein called TLR7, which detects viruses and activates immune cells. Encoded by a gene on the X chromosome, the protein causes a stronger immune response in women than in men. Meyaard suspects that this is because it somehow circumvents the process whereby one of the two X chromosomes in women is shut down to avoid overexpression of proteins.’

This is particularly interesting in light of the protein deficiencies found in women but not men by naviaux (above).

As a result of these differences, many ME/CFS researchers (such as the Armstrong lab in Melbourne Australia and Nauvieux with his suramin research) are now using a female only cohort to reduce variability.

________

There may also be a social dimension whereby men are more likely to be believed by doctors, family members and peers. See for example Women are dying because doctors treat us like men or the ABC podcast on the same topic. This article regarding the psychologisation of illness may also be of interest.

Here is a related segment on sex hormones in fibromyalgia.

——–

On autoimmunity, sex & ACE scores

https://twitter.com/donnajacknak/status/980570944900161536

Women are, generally, physically smaller than men and our hearts and lungs are much smaller in size. Yet our anatomy makes added room to carry a fetus in order to create new human life.

Our smaller heart, lungs, and organs still have to be able to do everything a human male does – pump oxygen, circulate blood, run fast, think fast, be awake 16 hours a day – and have the necessary fuel to carry a child to term. We have to do double duty, on half the machinery. Women can do so much more on less because we also have higher baseline levels of the hormone estrogen. Oestrogen acts as a kind of messenger, carrying information between groups of our cells. Say we are stressed, or catch a flu, or get a vaccine – estrogen helps women have a more robust immune response. This more robust immune response is also thanks to steroid hormones known as glucocorticoids (or GCs).l, which are produced by the adrenal gland and are anti-inflammatory. They help regulate inflammation. This heightened female immune response also means that when our immune system sets out to fight off any foreign invader, such as a virus or bacteria, as women we also produce more of what are called antibodies, or fighter immune cells. That’s good BUT it can also be a problem. As women, when we produce more antibody fighter cells, we also produce more autoantibodies. Autoantibodies are rogue fighter immune cells that can mistakenly attack the body’s own tissue or organs, in what we refer to as friendly fire/ #autoimmunedisease.

When girls repeatedly face #toxicstress during the developmental years, over time, their stress response begins to be dysregulated. Glucocorticoids, or GCs, become less able to properly regulate a healthy, appropriate immune response, which leads to more inflammation. Boys immune systems become dysregulated in response to #toxicstress too — e.g. boys who face #ACEs are more likely to show decreases in brain matter volume in the caudate region of the brain — related to impulse control and behavior), whereas for women risk of autoimmunity is increased 20% for every ace score. Women develop Hashimoto’s thyroiditis at a rate of 10:1 compared with men. In lupus, that rate is 9:1. In Sjögren’s syndrome, 9:1. #AutoimmuneDisease is one of the top ten leading causes of death in women under the age of sixty-five. Women are also twice as likely as men to have chronic pain syndromes. Women with an ACE score of 3 are significantly more likely to have chronic pain syndromes including headaches, back and neck problems. Both boys and girls who grow up with #toxicstress demonstrate, on brain scans, fewer neural connections between the pre-frontal cortex (the decision-making center of the brain) and the hippocampus (area of the brain that helps us to make sense of our emotions and experiences). But, in girls who grow up with #toxicstress and #ACEs, another area of neural connectivity is affected. It goes offline. Synaptic connections between an area of the brain known as the amygdala (fear-and-alert center of the brain) and the pre-frontal cortex are also weakened. the risk that growing up with #toxicstress and #adversechildhoodexperiences will lead to neuroinflammatory diseases such as depression and anxiety disorders is, as with autoimmune disease, 2x as high for women as it is for men. Having experienced 6 categories of childhood adversity can take 20 years off your lifespan. #toxicstress each ace is 20% increased fish for women but only 10% for men. And girls face more #ACEs growing up in general. In fact, girls are 50% more likely to have experienced 5 or more categories of childhood adversity

Swallowing & tachycardia

The ‘cardiac chronotropic response’ on swallowing is where there is an abrupt initial rise in heart rate on swallowing, slowed rise in heart rate, and then recovery. he acceleration is due to inhibition of vagal activity. ‘Deglutination tachycardia’ is the average resting heart rate beforehand compared with peak during swallowing.
In normies, ‘the contribution of each swallow is lower than that of the previous one’ and  the parasympathetic compensation actually causes HR to drop after. The mechanism of swallowing is designed to be completed quickly to allow the resumption of breathing. 
The ranges for heart rate rise found in the attached study were:
supine position (13.1 +/- 5.6 bpm)
standing position (8.5 +/- 3.8 bpm).
Thus in the normal population 95% of people’s HR raised:
laying flat 2-24bpm
Standing 1- 16bpm
In the study, tests were performed in the morning (as mine was), after 10 mins rest in supine position (from resting), each patient completed a single swallow, three swallows, and five swallows one at a time, and then 7-10 water swallows through a tube (like i did using a straw). This is shown in the attached image, 1 is deglutination tachycardia, 2 is the addition of each bpm for 2 heart beats, across 1,3,5 swallows.
17884568_10158581185730711_5021883625651955366_n.jpg

This video documents a rise of 68-92 bpm, laying reclined. The following day sitting knees up in a crouch position, resting 59 went up to 94bpm, a raise of 36bpm). Once PEM improved, EG able to move more under 100bpm, the repeat test of 7 swallows of water elevated heart rate 20bpm only (Resting 63- peak 83- dropped back to 61). This return to bradycardia is noted as part of normal parasympethic compensation. 

In PEM for patients the sympathetic dominance can cause high heart rates and breathlessness when eating or drinking. Difficulties swallowing can also be an issue due to swollen glands, sinus congestion, muscle weakness, stress etc.

The parasympathetic nervous system slows heart rate through the action of the vagus nerve. The response relies on the vagus nerve, which may be lacking tone, or inflamed? in ME/CFS/fibro. Thus in PEM there is sympathetic dominance, the HR isn’t slowed by the parasympathetic response, the parsympathetic response may not occur and the heart rate may continue to elevate beyond the third swallow. This may likely be inflammation, as if it was just a lack of tone it would presumably be constant across time, not just in crashes. This seems to be readily documentable evidence of vagus nerve problems, specific to PEM.

IOM 2015 report

The 300 page IOM report ‘“Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness” funded by the American National Academies of Medicine, written by a committee, is not without criticism. For the most part, its suggestion of the name ‘SEID, systemic exertion intolerance disorder’ has not been accepted by the ME/CFS community (primarily as its suggested criteria is too wide, conflates CFS, ME and would not exclude those with primary depression). However, the content was written by a respected committee, is evidence based and provides a thorough overview. Here is a snapshot of some good points (Taken from phoenix rising, Discussion in ‘Institute of Medicine (IOM) Government Contract‘ on phoenix rising, started by DanMEFeb 11, 2015).

About ME/CFS/SEID in general:

“The primary message of this report is that ME/CFS is a serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients. In its most severe form, this disease can consume the lives of those whom it afflicts. It is “real.” It is not appropriate to dismiss these patients by saying, “I am chronically fatigued, too.”

“The cause of ME/CFS remains unknown, although in many cases, symptoms may be triggered by an infection or other prodromal events such as “immunization, anesthetics, physical trauma, exposure to environmental pollutants, chemicals and heavy metals, and rarely blood transfusions.”

“Seeking and receiving a diagnosis can be a frustrating process for patients with ME/CFS for several reasons, including a lack of understanding of diagnosis and treatment of the condition among health care providers and skepticism about whether it is in fact a true medical condition. Less than one-third of medical schools include ME/CFS-specific information in their curriculum (Peterson et al., 2013), and only 40 percent of medical textbooks include information on the condition (Jason et al., 2010). Some studies on awareness of ME/CFS have found high awareness among health care providers, but many providers believe it is a psychiatric/psychological illness or at least has a psychiatric/psychological component (Brimmer et al., 2010; Jason and Richman, 2008; Unger, 2011).”

“ME/CFS can cause significant impairment and disability that have negative economic consequences at the individual and societal levels. At least one-quarter of ME/CFS patients are house- or bedbound at some point in their lives (Marshall et al., 2011; NIH, 2011; Shepherd and Chaudhuri, 2001). The direct and indirect economic costs of ME/CFS to society are estimated to be between $17 and $24 billion annually (Jason et al., 2008), $9.1 billion of which can be attributed to lost household and labor force productivity (Reynolds et al., 2004)”

“Although a variety of names have been proposed for this illness, the most commonly used today are “chronic fatigue syndrome,” “myalgic encephalomyelitis,” and the umbrella term “ME/CFS.” Reaching consensus on a name for this illness is particularly challenging in part because its etiology and pathology remain unknown (CFS/ME Working Group, 2002).”

“In addition to difficult interactions with health care providers, patients have reported several other ways in which the stigmatization of ME/CFS affects them, including financial instability (such as job loss or demotion), social disengagement, and feeling the need to hide their symptoms in front of others (Assefi et al., 2003; Dickson et al., 2007; Green et al., 1999).”

“Symptoms can persist for years, and most patients never regain their premorbid level of health or functioning (Nisenbaum et al., 2000; Reyes et al., 2003; Reynolds et al., 2004). The duration of ME/CFS and the potentially debilitating consequences of symptoms can be an enormous burden for patients, their caregivers, the health care system, and society.”

“Patients with ME/CFS have been found to be more functionally impaired than those with other disabling illnesses, including type 2 diabetes mellitus, congestive heart failure, hypertension, depression, multiple sclerosis, and end-stage renal disease.”

About fatigue:

“Regardless of what criteria are used, however, ME/CFS patients often have a level of fatigue that is more profound, more devastating, and longer lasting than that observed in patients with other fatiguing disorders. In addition, fatigue in ME/CFS is not the result of ongoing exertion, not lifelong, and not particularly responsive to rest (Jason and Taylor, 2002).”

“However, ME/CFS should not be considered merely a point on the fatigue spectrum or as being simply about fatigue. Experienced clinicians and researchers, as well as patients and their supporters, have emphasized for years that this complex illness presentation entails much more than the chronic presence of fatigue. Other factors, such as orthostatic intolerance, widespread pain, unrefreshing sleep, cognitive dysfunction, and immune dysregulation, along with secondary anxiety and depression, contribute to the burden imposed by fatigue in this illness.”

About PEM:

“As described by patients and supported by research, PEM is more than fatigue following a stressor. Patients may describe it as a post-exertional “crash,” “exhaustion,” “flare-up,” “collapse,” “debility,” or “setback.” PEM exacerbates a patient’s baseline symptoms and, in addition to fatigue and functional impairment (Peterson et al., 1994), may result in flu-like symptoms (e.g., sore throat, tender lymph nodes, feverishness) […]”

“PEM is worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset. Subjective reports of PEM and prolonged recovery are supported by objective evidence, including failure to normally reproduce exercise test results (2-day CPET) and impaired cognitive function. These objective indices track strongly with the presence, severity, and duration of PEM.”

“Many studies have demonstrated that pain is increased and prolonged after a physical stressor in ME/CFS subjects compared with healthy or sedentary controls. Similar to the evidence base for fatigue, reports of increased pain among ME/CFS subjects are consistent across maximal exercise tests (Davenport et al., 2011a,b; VanNess et al., 2010) and other physical stressors (Black et al., 2005; Nijs et al., 2010).”

About Sleep:

“It is clear, however, that people with ME/CFS universally report experiencing unrefreshing sleep, and further research will be important to determine whether there is a specific sleep abnormality common to ME/CFS patients or a heterogeneity of abnormalities that may define subsets of ME/CFS patients.”

“Despite the absence of an objective alteration in sleep architecture, the data are strong that the complaint of unrefreshing sleep is universal among patients with ME/CFS when questions about sleep specifically address this issue.”

“ME/CFS patients are more likely than healthy controls to experience sleep-related symptoms occurring at least half of the time and of at least moderate severity (see Figure 4-2) (Jason et al., 2013b). Although sleep- related symptoms also are reported by healthy persons and by chronically fatigued persons who do not fulfill ME/CFS criteria, a greater percentage of people fulfilling ME/CFS criteria report unrefreshing sleep, sleep distur- bances, and difficulties falling asleep or waking up early in the morning (Komaroff et al., 1996a; Krupp et al., 1993; Nisenbaum et al., 2004) relative to these other groups.”

About neurocognitive function:

“Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS. Patients describe these symptoms as debilitating and as affecting function as much as the physical symptoms that accompany this disease. During a survey of ME/CFS patients, descriptions of neurocognitive manifestations included, among others, “brain fog,” “confusion,” disorientation,” “hard to concentrate, can’t focus,” “inability to process information”.

“Collectively, the studies reviewed here support the notion that ME/CFS patients present with neurocognitive impairment. Slowed information pro- cessing, demonstrated by objective neuropsychological testing and potentially related to problems with white matter integrity, is one of the strongest neurocognitive indicators in support of a diagnosis of ME/CFS, particularly if there is evidence of normal functioning on untimed tests and impaired functioning on time-dependent tasks.”

About OI:

“There is consistent evidence that upright posture is associated with a worsening of ME/CFS symptoms, as well as the onset of other symptoms such as light-headedness, nausea, and palpitations. While there is variability in the reported prevalence of orthostatic intolerance in ME/CFS, heart rate and blood pressure abnormalities during standing or head-up tilt testing are more common in those with than in those without ME/CFS. Heart rate variability analyses demonstrate a sympathetic predominance of autonomic tone in those with ME/CFS, including during sleep.”

“Orthostatic intolerance can occur as an isolated syndrome or in association with a variety of other comorbid disorders, including ME/CFS (Benarroch, 2012). The most prevalent forms of orthostatic intolerance in the general population, as well as among those with ME/CFS, are POTS and neurally mediated hypotension (NMH), with delayed variants of orthostatic hypotension and orthostatic tachycardia also being seen.”

About Pain:

“Sufficient evidence shows that pain is common in ME/CFS, and its presentation supports the diagnosis. However, while pain worsens ME/CFS when present, there is no conclusive evidence that the pain experienced by ME/CFS patients can be distinguished from that experienced by healthy people or those with other illnesses. Further, pain may be experienced in many areas, and while comprehensively assessing a patient’s pain symptoms is a challenging task, it is not specific to ME/CFS.”

About Immune Impairment:

“Symptoms related to inflammation are reported frequently by ME/CFS patients. When attempting to convey their illness experience to healthy persons, many patients describe it as similar to a perpetual flu-like state (Maupin, 2014). Patients also report persistent or recurrent sore throats, tender/swollen cervical and/or axillary lymph nodes, muscle pain, achy joints without swelling or redness, headaches, chills, “feverishness” (but not necessarily meeting objective criteria for fever), and new or worsened sensitivities to certain substances (e.g., foods, odors, medications) (FDA, 2013).”

“One of the most consistent findings in ME/CFS subjects is poor NK cell function. Using K562 cells as target cells, 16 of 17 studies reviewed found poor function in subjects compared with healthy controls. However, this finding should be interpreted with caution as even the strongest of these studies are subject to methodological limitations discussed at the beginning of Chapter 4.”

“Low NK cytotoxicity is not specific to ME/CFS. It is also reported to be present in patients with rheumatoid arthritis, cancer, and endometriosis (Meeus et al., 2009; Oosterlynck et al., 1991; Richter et al., 2010). It is present as well in healthy individuals who are older, smokers, psychologically stressed, depressed, physically deconditioned, or sleep deprived (Fondell et al., 2011; Whiteside and Friberg, 1998; Zeidel et al., 2002).”

About Autoimmunity:

“In other studies, ME/CFS or postviral fatigue syndrome patients showed antibodies to smooth muscle (36 percent) (Behan et al., 1985), heat shock protein 60 (24 percent) (Elfaitouri et al., 2013), and endothelial antigens (30 percent) (Ortega-Hernandez et al., 2009). The only clinical trial targeting antibodies found moderate to marked clinical improvements in 10 of 15 subjects treated with rituximab, a B cell depleting antibody, and 2 of 15 placebo arm subjects at a single time point (Fluge et al., 2011). This, however, was a post hoc analysis as the trial failed to meet its primary endpoint. Currently, researchers in the United Kingdom and Norway are conducting further studies addressing this question (Edwards, 2013; Mella and Fluge, 2014).”

About Neueoendocrinic Function:

“Patients with ME/CFS may have relatively reduced overnight cortisol, 24-hour urinary cortisol, CRH and/or AVP, and ACTH levels compared with healthy controls. The current preponderance of evidence points to normal adrenal function in such patients and suggests a secondary (central) rather than a primary (adrenal) cause of reduced but not absent cortisol production at the level of the pituitary, the hypothalamus, or higher. Patients with ME/CFS may have defective serotonergic signaling in the brain, localized to the level of the hypothalamus or higher, resulting in downstream dysregulation that may play a role in ME/CFS. The exact mechanism is not clear.”

About Infection:

“The literature indicates a possible relationship between EBV and ME/CFS. The evidence suggests that ME/CFS can be triggered by EBV infection, but there is insufficient evidence to conclude that all ME/CFS is caused by EBV or that ME/CFS is sustained by ongoing EBV infection. Improved diagnostic techniques may reveal as yet undetected associations. Further research in this area is warranted to determine whether patients in whom disease was triggered by EBV or patients with evidence of an ongoing abnormal response to EBV represent clinically significant subsets of ME/CFS.
There is insufficient evidence for an association between ME/CFS and bacterial, fungal, parasitic, and other viral infections. These infectious agents may, however, be comorbidities, and their presence may reflect the presence of problems with immune function in these patients. Future research may clarify the role of these infections in this illness.”

 

gut studies

April 2017

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

(Study first of many by lipkin with multicentre colab with klimas, bateman and others, crowdfunded as part of the microbe discovery project, summary on sciencedaily))

2016

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome Ludovic Giloteaux,

The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome (increase in Clostridium spp. and a decrease in Bacteroides spp)

****

Here’s my (messy) cheat sheet of the bacterial changes found in me/cfs the above three studies and whether they’re increased or decreased. The right column is my personal results in relation to what’s expected (left column)

Testing available through Ubiome covers most of the mentioned bacteria with the exception of enterococcus, coprococcus, coprobacillus, and strain specific information. The ‘explorer kit’, available internationally, also includes metabolism details such as those below.

 

 

Brain Imaging: Lyme, ME, depression

This summary includes information on Single Photon Emission Computerized Tomography (SPECT) scans & MRI’s. Here are examples of normal spects,

normal SPECT

And a guide (from a primary CFS SPECT study) to brain regions in the SPECTS

17887005_10158557634035711_379738459_o
note: it is standard for the SPECT to reverse left and right; this is labelled on the sheet

CFS
Swartz et al found hypofusion in areas 5, 2 & 6.
Mena & Villaneueva-Meyer found hypofusion in temporal lobes 1 & 2
Ichise et al found decreased radionuclide uptake mainly in 1,2/4,5, but also in 8, 3 & 6.

These are reversible and correlate with changes in clinical severity.

LYME

SPECT: In Lyme Disease, the most common finding is of heterogeneous hypoperfusion diffusely throughout the brain, similar to in Lupus, chronic cocaine abuse or other vasculitic inflammatory disorders. This pattern is different to primary depression or Alzheimer’s disease. Approximately 70% of patients with chronic Lyme disease will have multiple areas of hypoperfusion, but it cannot be used for diagnosis, as blood flow is rated relative to the cerebellum or deep grey matter which is presumed to be normal.

The above images are from hypobaric treatment where SPECT can be used as a marker of improvement.

From ‘looking at lyme‘:

SPECT scan of the brain before (A) and after (B) antibiotic brain specttreatment.

These transaxial images are from a 51-year-old man diagnosed with Lyme disease with a recent change in memory. Representative pretreatment images show hypoperfusion within the mid posterior and mid temporoparietal cortex bilaterally. Representative posttreatment images (14 months later) reveal improved perfusion to the posterior temporoparietal cortex bilaterally, correlating with improved symptoms. Perfusion within the remaining cerebral cortex, basal ganglia, thalamus, and cerebellum was normal.

MRI:  Looks similar to MS: Up to 40% of adults with Lyme disease may have small white matter hyperintensities suggestive of inflammation or areas of demyelination., but it should be noted that the number of hyperintensities increase with age – even among patients who do not have Lyme disease.

Youtube has many video tutorials on interpreting brain mri.

ME

SPECT: Hyde considered an abnormal SPECT as well as an abnormal EEG or PET scan and/or neuropsychological abnormalities required for ME diagnosis, in particular decreased perfusion of blood in the left middle cerebral artery and the branches of the parietal lobes, present very early in the illness. He strongly emphasised vascular issues (moreso than PEM), and ‘difficulty concentrating and finding words, etc, problems sleeping, poor muscle functioning, trouble standing without exaggerated heart rates and dizziness, little ability to exert themselves, cold fingers, loose joints and gut problems’.

Screenshot (47)

EG “Intrinsic Functional Hypoconnectivity in Core Neurolocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis”, PMID: 26869373 or “Functional Neural Network Connectivity in Myalgic Encephalomyelitis

The ICC for ME notes SPECT abnormalities, however it specifies *with contrast*. Contrast can be reactive and cause side effects. Repeated SPECT scans done at the same medical center to allow for a fair comparison across images can track progress of treatment or disease progression.

ICC case study : Extensive areas of hypoperfusion are characteristic of ME… marked hypoperfusion in the lateral aspects of the temporal lobe, extending to the frontal and parietal lobes… extensive hypoperfusion in the limbic system involving anterior, medial and posterior cingulates. There is left temporal medial hypoperfusion that denotes hypofunction in the projection of the hippocampus. Both posterior cingulate and hippocampal hypofunction denote cognitive impairment. Finally, there is hypoperfusion in the occipital lobe.

Taken from Ireland ME which has good overview brain abnormality summary and study quotes.

brain areas

Medial temporal lobes (area 1) hypofusion seen in concussion, head injuries, hippocampus, memory impairment

Fibromyalgia

 

2008_10_31_14_13_54_357_2008_10_31_fibromyalgia_resized
Both hypo and hyperfusion is found in fibromyalgia.

Red: HYPOfusion, green: HYPERfusion

The images show the anatomical localization of peak significant differences between brain SPECT of patients with fibromyalgia and healthy subjects. Patients with fibromyalgia exhibited posterior hyperperfusion (red), including of the somatosensory cortex, and hypoperfusion (green) of frontal, cingulate, temporal, and cerebellar cortices. Images courtesy of the Journal of Nuclear Medicine

 

Severity was “positively correlated with bilateral parietal perfusion, including postcentral cortex. These clusters of correlation were included in the areas of significant hyperperfusion. [Severity] was also negatively correlated with perfusion of a left anterior temporal cluster, included in the areas of significant hypoperfusions. No other clinical correlation was observed with regional cerebral blood flow.”

Compared with healthy controls, patients with fibromyalgia exhibited posterior hyperperfusion, including of the somatosensory cortex, and hypoperfusion of the frontal, cingulate, temporal, and cerebellar cortices in particular, the temporal hypoperfusion including the polar and mediobasal cortices.

Positive correlations (both on left) represent hyperfusion, negative (right) represents hypofusion- ie low blood flow.

fibro

Brain perfusion abnormalities in patients with fibromyalgia “are independent of the patient’s anxiety and depression status and correlate with the clinical severity of the disease, expressed by the disability and evaluated by the FIQ total score.”

PTSD
shows increased activity in the thalamus and basal ganglia (study)

below- here is an example of normal basal ganglia flow, the basal ganglia is in the centre
(note the rest may be abnormal as this woman had tremors.
note- basal ganglia abnormalities may also occur with lupus).

Normal-uptake-of-the-basal-ganglia-in-ECD-SPECT

This same region is relevant for ADD: people with Anxious ADD show the hallmark ADD signature of low prefrontal cortex activity (image on the right) combined with overactivity in the basal ganglia (image on the left)—a region of the brain that allows for smooth integration of emotions, thoughts, and physical movement.

Anxious-ADD-SPECT

Depression

One review found differences between cfs & depression spects, with significantly more defects in the occipital lobe in depression; fischler found major depression showed significantly lower left superofrontal regional perfusion, in line with previous reports

while note: its normal to see more activity in the right than the left temporal lobe, with slightly larger left than right volume; this assymetry may be more pronounced in depression

depression            depression brain scan

depression         e7e6d170266384b583dfb80ba97875d9

3DActiveSPECTAnxietyDepression.540xdepression-depressed-hypomanic-brain-scan.previewinnerviews

ADD

types-of-add

Anxiety

severe anxiety neurosis revealed hyperactive prefrontal cortices and basal ganglia in technetium-99m-hexamethylpropyleneamineoxime brain perfusion single photon emission computed tomography images. (a) Transverse view, (b) sagittal view, (c) right lateral view of three-dimensional Talairach cortical perfusion report, (d) extracted basal ganglia and thalamus by “Neurogam” processing, (e) color scale for (c and d):

anxiety

See: Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics to clinical practice

IndianJNuclMed_2014_29_4_210_142622_t12

On CFS vs Depression, and CFS neurology scans in general:

spect textbook neurology.png

NOTES: my results ‘ischemia

‘A mild-moderate symetrical reduction uptake in the posterior tempero-parietal cerebral cortex is seen. There is a sparing of the posterior cingulate and the visual association cortex. Normal perfusion within the basal ganglia and the cerabellum… Bilateral mild to moderate posterior tempero-parietal cortical hypoperfusion’.

The ICC for ME says: ↓ reduced blood flow in temporal lobes may contribute to memory and cognitive impairment & fatigue

Hyde mentions abnormalities in the parietal lobe and the left middle cerebral artery: The middle cerebral artery is the largest branch of the artery that supplies a portion of the frontal lobe and the lateral surface of the temporal and parietal lobes, including the primary motor and sensory areas of the face, throat, hand and arm, and in the dominant hemisphere, the areas for speech. Low blood flow in the temporal and parietal lobes likely results from not enough blood coming through the cerebral artery.
There was no hyperperfusion, as seen in PTSD or fibromyalgia, or hypofusion in the superofrontal lobes, as seen in depression. Brain stem was not reported on; this is used to differentiate depression & ME. FND/conversion disorder expects abnormal functional but normal structural imaging, as I have, but is a debatable clinical entity.
This does not rule out lyme which shows a similar pattern, abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes- those these may be asymmetrical?
I have orthostatic intolerance, which can be linked to low blood volume. I was well hydrated, and as I was laying down, this may be of negliable significance, especially as only some regions of the brain were affected

The ICC also states: Greater source activity and more parts of the brain are utilized in cognitive processing, which supports patients’ perception of greater effort… These observed pathological changes are consistent with neurological disorders but not psychiatric conditions…

 

The parietal lobes involves sensation and perception and integrates sensory input, primarily with the visual system. Neurons in the parietal lobes receive touch, visual and other sensory information from a part of the brain called the thalamus. The thalamus relays nerve signals and sensory information between the peripheral nervous system and the cerebral cortex. The temporal lobes are involved in high-level auditory processing such as selective listening, language recognition of words, and Mathematical Computation! Problems include the inability to recall the correct names of everyday items, difficulty in making exact movements, inability to perform complex tasks in the proper order

The temporal lobes play an important role in organizing sensory input, auditory perception, language and speech production, language comprehension, as well as memory association and formation. Structures of the limbic system, including the olfactory cortex, amygdala, and the hippocampus are located within the temporal lobes. Damage to this area of the brain can result in problems with memory, understanding language, and maintaining emotional control. This is also important for facial recognition and regulating fight or flight!

The frontal lobes are involved in reasoning and personality expression is fine! The posterior cingulate is between the frontal and parietal lobes and is considered part of the default mode network, a group of brain structures that are more active when an individual is not involved in a task that requires externally-focused attention, also implicated in moral judgments

 

fig-29-05brain diagram amygdala 416

 

Hypoperfusion Neuro-SPECT ↓ regional blood flow (rCBF), ↓ absolute cortical blood flow ↓ hypoperfusion in brainstem distinguishes ME from depression ↓ further reduction in cerebral blood flow after exercise; Greater involvement of the brain correlates with greater severity