Award-winning essay of the NJME/CFSA 2017 Medical Scholar Program: "A Narrative Synthesis for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"

Ken Friedman sent me this and asked me to highlight it

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A Narrative Synthesis for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

The conceptualization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (from here on referred to as ME/CFS) has classically been frustrated by the sheer complexity and breadth of its presentation. First described operationally in the 20th century by the Center for Disease Control & Prevention ME/CFS has been reported in some manner by the medical community since at least the 19th century.1 Throughout the disease’s history it has been described as a potentially infectious process similar to mononucleosis,2 a neuroimmunologic process like multiple sclerosis,1,2 a disorder of centralized pain processing such as fibromyalgia3, and in some instances something in the realm of conversion disorder, maladaptive psychology, and even hysterical delusion1,2,4. This variety of potential models is a consequence of the historically difficult nature of this disease to be studied and represented biologically. Typical rheumatologic and autoimmune laboratory studies often fail to produce a meaningfully abnormal result even in the most symptomatic of patients.4 Until recently neural imaging was not sophisticated enough to find the differences between the brains of those with ME/CFS versus the unaffected population, and even today we still have not isolated a pathogen that can be linked definitively to the development of this cluster of symptoms.2

This lack of understanding often manifests as frustration from both patients and the physicians who treat them. Due to the complexity of this disease process treatment primarily focused on using cognitive behavioral therapy and progressive increase in exertional tolerance for symptomatic relief, coping, and rehabilitation.5 The results of these strategies were inconsistent and, in some cases, even harmful.6 This variability in outcome further contributed to doubt in some medical communities as to whether the pathology even existed at all.1,2,7 This doubt paralleled the evolution of a patient population who often felt frustrated, abandoned, lost, and consequently at risk for developing true psychopathology if they have not done so already.8

However, breakthroughs in the scientific disciplines have gotten us past the once impenetrable wall of normal results and inconclusive studies. Thanks to new research investigating both the disease process and the clinical reality we are beginning to develop a more sophisticated and clinically meaningful understanding of ME/CFS. The purpose of this writing is to discuss several of these recent studies in hopes of facilitating a better understanding of ME/CFS’s pathology, possible epidemiology, and their implications on both clinical practice and further research.

Myalgic Encephalitis/ Chronic Fatigue Syndrome is defined by the CDC as requiring three primary symptoms for diagnosis: 1. greatly lowered ability to do activities that were usual before illness lasting six months or longer; 2. Worsening of ME/CFS symptoms after physical or mental activity that would not have caused a problem before illness. This is known as post-exertional malaise (PEM); 3. Sleep problems.9 There is also a stricter criteria which has been used by many researchers since 2003 referred to as the Canadian Consensus Criteria which defines ME/CFS as a patient meeting the criteria for fatigue, post-exertional malaise, sleep dysfunction, and pain; have two or more neurologic/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations persisting for at least six months usually with a distinct onset.10 The combination of these two criteria plus the very similar Oxford criteria is what was used to define the disease for much of the research hereafter.

The first of the major breakthroughs to be discussed is the literature that collectively establishes ME/CFS as a quantifiable and distinct clinical entity. They serve as a foundation of

knowledge from which appropriate therapies and future studies can be developed. Furthermore, without these studies ME/CFS’s existence could still be considered by some to be purely in the realm of psychopathology. Having confirmation of a biological pattern that can explain a constellation of clinical symptoms is the difference between knowing one has a disease that is diagnosable and treatable versus the existential anxiety that comes with wondering if these symptoms are uniquely one’s own, unprecedented, and perhaps—untreatable.

Some of the most compelling literature has centered on describing the phenomenon of post-exertional malaise (PEM). Since PEM is the defining symptom of ME/CFS, a better understanding of it is can lead to a better understanding the overall pathology. For this we will focus on the research of Wang et al, Light et al, and Cook et al which, through different methods of analysis, come to very similar conclusions. Wang’s systematic review of polymorphisms in patients with chronic fatigue showed that patients with ME/CFS had several single nucleotide polymorphisms (SNPs) which, when searched for as a panel, were able to accurately identify ME/CFS patients from the unafflicted population 76% of the time.11 These mutations were noted to be mostly in the genes 5-HTT/TPH2, COMT, and NR3C1; these are the genes for serotonin, catecholamine, and glucocorticoid production respectively. SNPs were also found in genes involved in neurotransmission, circadian rhythm maintenance, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis.11 Thus, the evidence suggests that the genes integral to the processing of stress, arousal, and emotion are uniquely different in those with ME/CFS.11 This provides a possible explanation regarding an organic mechanism. However, genetic code and phenotypic expression are not one and the same. To go further and make this evidence pertinent these findings would need to match what was happening in actuality.

In accordance with Wang et al’s work, Light et al’s research on the epigenetics of ME/CFS showed that in response to acute exertion these patients had dramatic increases in mRNA transcribed from genes such as P2X4, P2X5, TRPV1, α-2A, β-2, COMT, and IL10.12,13,14 These genes collectively produce several of the cellular receptors and neurotransmitters responsible for energy utilization of the nervous system, the signaling of nociception, and the higher order processing of pain. His studies were able to positively correlate the level of mRNA transcription of these genes with the severity of ME/CFS patient symptoms across time.13 This is significant because it is a common report among these patients that PEM symptoms occur in the twenty-four to forty-right hours after fatiguing exertion.1,12,15 By measuring the levels of mRNA transcription during multiple time points within that forty-eight hour window he was able to represent biochemically what patients were presenting clinically. In addition Light et al. also evaluated these genes in healthy subjects and patients with other pathologies where chronic fatigue was prominent and was able to display that they had no such changes in their mRNA transcription.13,14 That is to say the evidence suggests ME/CFS had a distinct and recognizable epigenetic and, consequently, phenotypic presentation. To take this a step further it is also worth noting that the phenotypic expression correlated well with the genotypic variations described by Wang et al.

Given the altered transcription pattern some manifestation in the physiology is expected. Cook et al. was able to demonstrate using fMRI that after performing activities such as acute cardiovascular exercise or cognitively demanding visual and mathematical problems patients with ME/CFS had augmented neural firing in the regions of the brain associated with attention, higher-order information processing, pain perception, and emotional processing.15 Specifically, he was able to display heightened activity of the superior temporal lobes, the inferior-frontal lobes, the hippocampus, and the thalamus. By using this fMRI analysis in conjunction with questionnaires and evaluations of performance during the various study tasks Cook et al then correlated the augmented neural activity he was measuring with the subjective experiences of PEM. When the fMRI scans showed heightened neurologic activity in the aforementioned regions his subjects noted worsened subjective experience of fatigue, increased pain, and—almost paradoxically—worsening performance in the cognitive tasks.15 By way of fMRI Cook’s work was able to demonstrate the “brain fog” often described by ME/CFS patients in the midst of their post-exertional malaise.

This combination of increasing neurologic activity and worsening performance was contrasted against control subjects without ME/CFS. In response to the same stimuli the control subjects showed progressively diminishing levels of neural activation as the tasks were repeated.15 This phenomenon is the mark of adaptation via familiarization to novel stimuli. The current understanding of learning from the neuroscientific perspective suggests that as one becomes more familiar with a task the metabolic resources necessary to accomplish it (that is to say, the amount of cognitive effort) should decrease while the quality of the performance increases.15,16 Given this knowledge and the evidence generated by Cook et al. there is the implication that patients with ME/CFS lack the ability to adapt to stressful stimulation in the most literal sense.15

Due to the use of fMRI as the mode of evaluation Cook et al’s research also noted that these patients had preexisting differences in the inferior-frontal and temporal cortices as well as the hippocampus and thalamus when compared to control subjects. This finding was supported independently by a study in the British Medical Journal of Radiology which specifically showed that the hippocampus of ME/CFS patients had markedly decreased hippocampal volume.17 Jean-Michel Saury expanded greatly on these anatomic findings with his narrative synthesis of the functional neurologic research regarding ME/CFS. In his work he implicates the preexisting decrease in hippocampal volume as a powerful contributor to both generation and propagation ME/CFS’s symptoms of fatigue, pain, and impaired cognition.18

Saury ultimately suggests that the basic pathophysiology of ME/CFS is the dysregulated interaction between the HPA axis and the limbic system.18 The hippocampus houses the physical connection that links the HPA axis to the remaining limbic system. The hippocampus via the CA1 and CA3 areas of the subiculum projects axons directly to the parvoventricular nucleus of the hypothalamus whose role is the management of the body’s metabolic state via the adrenal glands. In response to circulating cortisol these hippocampal projections inhibit the hypothalamus and prevent it from secreting corticotropin-releasing hormone, therefore mitigating the hormonal cascade in response to acute stressors.18 This pathway forms the inhibitory arc of the HPA’s negative feedback loop. Evidence demonstrating this function is further provided by studies which show that lesions to the hippocampus lead to destruction of the negative feedback loop and, subsequently, result in chronic over-activity of the adrenal system, the effects of which are incredibly deleterious.18,19,20

Saury et al. argues that hyperactivation of the HPA axis and limbic system via an atrophied hippocampus correlates well with the neurocognitive impairment, psychological manifestations, and exertional intolerance that define ME/CFS and PEM.9,10,18 Unregulated activation of the HPA axis puts the body in a state of chronic physiologic stress whose symptoms are primarily the result of an overactive sympathetic nervous system and long-term maladaptation of the neuroendocrine structures which produce the HPA axis in the first place.16,18 Regarding the maladaptation, normally stressors activate the amygdala which in turn is modulated by the hippocampus.18 Together they form the neural computer which determines how powerfully the HPA axis becomes activated. This combined amygdala-hippocampal substructure simultaneously projects to higher order structures such as the parietal and frontal cortices generating emotional and mental states congruent with the level of activation of the sympathetic nervous system.16,18,19 In the case of chronic stress, however, the amygdala and sympathetic nervous system are abnormally augmented while the hippocampus becomes inhibited. With sufficient chronicity the amygdala itself will actually hypertrophy (i.e. strengthen its neural connections) while the hippocampus atrophies (i.e. weaken its neural connections) resulting in a preferentially activated stress response system with progressively diminishing capacity to regulate it via the higher order cognitive structures.18,19,20 Aside from its key role in modulating the HPA axis the hippocampus also plays the critical role in the creation and retrieval of episodic and procedural memory necessary for abstract thought.15,16,17 Impairment of the hippocampus, therefore, also correlates with the neurocognitive impairment that ME/CFS patients describe as a “brain fog”.

Parallel to the neuroscience, research regarding cortisol and stress physiology has produced an appropriately congruent, albeit less robust, series of conclusions. Research conducted by Rimes, Papadopoulos, Cleare, and Chalder revealed attenuated diurnal variability of cortisol in patients with ME/CFS as well as decreased cortisol levels throughout the day.22 Though the decrease in total level is modest it is the undulations of cortisol, not necessarily the total amount, which correlates with alertness and arousal.18,20,21,23 It is possible that the chronic fatigue of ME/CFS patients is being represented by this decreased variability. In another study Nijhof et al examined adolescents with ME/CFS and presented evidence suggesting that these teenagers also had mildly depressed levels of cortisol when compared against healthy peers. More importantly, however, this study demonstrated that the return of cortisol to normal levels positively correlated with self-reported recovery of symptoms.24 Lastly, a study by Hall et al regarding subject’s personal perception of ME/CFS presented two profoundly useful insights. Subject’s perceived stress management skill is positively correlated with levels of awakening cortisol, and awakening levels of cortisol is positively correlated with reduced severity of PEM exacerbations.25 The ability to link one’s mindset to one’s symptom severity lends support for continued use of well-designed cognitive behavioral therapy and stress-reducing adjustments to the environment these patients are nested in. 25

Thus, the physiologic literature emergently conceptualizes ME/CFS as the clinical manifestation of a collapsing and maladaptive stress response system.16-25, This model that focuses on autonomics, neural architecture, cortisol, and an altered ability to make use of the body’s metabolic resources complements the genetic and epigenetic literature of Light et al. and Wang et al. discussed previously. The convergence of the neurologic, endocrine, and genetic literature gives strength to this model in that if any of these findings were coincidental it is unlikely that separate methods of analysis would produce the congruent results. This congruence allows one to more confidently affirm that patients with ME/CFS indeed have measurable pathologic changes. Furthermore, one can attest that there are organic changes and searching for a biological solution is not a futile endeavor.

 

Although these studies provide validity to the diagnosis of ME/CFS, there is still no definitive explanation as to who actually develops the pathology. Clearly not every individual with chronic stress suffers from post-exertional malaise. The epidemiologic studies of ME/CFS separate it from depression, anxiety, multiple sclerosis, and other pathologies that heavily involve fatigue.1,2,5 Initially this disease was believed to be some sort of infectious disease process.2 Underhill et al’s hypothesizes that ME/CFS is an infectious disease whose causal pathogen can be transmitted by casual contact, and the causal pathogen may persists during illness.2 Host factors determine susceptibility to illness, and a healthy carrier population may be able to shed the pathogen.2 He cites that ME/CFS is globally endemic, and both sporadic and cluster outbreak disease patterns have been documented. In fact, the names Myalgic Encephalomyelitis and Chronic Fatigue Syndrome themselves were the terms used to describe what were believed to be viral outbreaks in London, UK in 1955 and Nevada, USA in 1984 respectively. During that time the UK outbreak was believed to be a variation of poliomyelitis. In the case of the U.S. outbreak it was initially thought to be a sort of chronic Ebstein Barr viral syndrome.1,2 Several more outbreaks have occurred with clinical presentations consistent with the diagnostic criteria now defined by the CDC. These various outbreaks of persistent post viral syndromes led to the initial conceptualization of ME/CFS as an overarching diagnosis.1,2

Further analysis of the epidemiology is inconsistent regarding pathogens associated with developing the symptoms. No pathogen has been definitively linked to developing ME/CFS;2,5 no pathogen has been isolated in those patients who have active ME/CFS pathology.5 This absolute inability to find a causal pathogen is contrasted with direct evidence of horizontal transmission.5 Underhill et al describes an outbreak in which five hospital personnel and one patient who were in contact with a particular nurse while she was incubating the illness developed the same illness after eight days. Evaluation of other documented outbreaks in the U.K. and U.S. suggest that the disease has an incubation period, possibly 4 to 10 days, and it appeared spread by close personal contact with the disease or carriers. Because no pathogen could be found researchers developed a hit-and-run model of the infection whereby the damage done by the infectious agent lingers even after the pathogen, itself, has been cleared.1,2,26

Dr. Megan Arroll elaborates on this hit-and-run concept by providing a reasonable hypothesis that perhaps ME/CFS is produced by a particular combination of events. She states that ME/CFS manifests in patients with predisposing risk factors who are in a state of allostatic overload who then experience an inflammatory triggering event such as a viral illness.27 In support of this hypothesis she cites the literature that correlates ME/CFS patients with confirmed viral infections such as Epstein-Barr, HHV-6, HHV-7, a number of enterobacterial infections as well as a higher than normal number of negative major life events such as divorce, death of loved ones, and changes of employment prior to illness onset.27

The idea that preceding significant life stress may predispose one to ME/CFS is plausible given the knowledge of stress’s negative impact on the development of the HPA axis and limbic system15,18,21. Several studies have demonstrated that a possible risk factor for the development of ME/CFS was extremes of stress early in development2,18,27. A physiologic explanation by Saury et al notes that such stressors experienced early in development positively correlated with attenuated growth of the hippocampus’s subiculum, potentially initiating the chain of events that culminates in ME/CFS sometime later on18. Both chronic and acute stress are noted to be capable of triggering autoimmune pathology and altering phenotypic expression of the immune system.28,29 The specifics of how this occurs, however, are poorly understood at this time. That being said, as the evidence accumulates it seems more appropriate to characterize ME/CFS as a pathology of the psychoneuroendo-immune axis.15-33 The conceptualization of ME/CFS within this framework is further supported by the evidence of autoantibodies produced by B cells targeted against the nervous system’s adrenergic, muscarinic, and serotonergic receptors.31 Aside from the presence of these B cells, literature regarding cytokines and Natural Killer (NK) cells in the context of ME/CFS has been able to show a stereotyped pattern of cytokine expression that can predict ME/CFS pathology with an accuracy of 75-88%.30,31 In combination with the characteristic mRNA profile described by Light et al these findings take us another step closer to developing a clinically available laboratory test that may help confirm the diagnosis of ME/CFS in common practice.

Taken in summation what emerges is a disease model where the combination of autoimmunity against one’s nervous system, possibly as a consequence of chronic inflammation and infection, coupled with malfunction of the nervous system’s ability to coordinate metabolites when needed, leads to the clinical presentation of a patient who is incapable of having the energy necessary to deal with life’s day-to-day occurrences.15-31 This is the current working model of ME/CFS. It is reflected in the recent efforts to update the name of this pathology to the more descriptive term Systemic Exertional Intolerance Disease (SEID). Aside from providing a better understanding of what is happening physiologically and biochemically this model also implies certain strategies for treatment. If ME/CFS is a pathology of autoantibodies directed against the neuroreceptors for energy metabolism and the conscious experience of arousal (the opposite of fatigue) then treatment strategies which remove or otherwise prevent the action of these autoantibodies ought to result in a reversal of these deficits. Thankfully—there is growing body of evidence which shows precisely that.

In a Norwegian case report Fluge et al described a patient with Non-Hodgkin’s lymphoma whose concurrent ME/CFS markedly improved after undergoing rituximab treatment.30 A subsequent study designed by Fluge et al replicated this incidental finding in two other individuals with ME/CFS.32 Afterwards, a proper double-blind and placebo-controlled RCT was performed which, also showed promising results. After several months 67% of the patients subjected to B cell depletion therapy stated meaningful reductions in fatigue and pain as well as improvements in cognition as opposed to 13% of those who received placebo.33 It was mentioned that this time delay likely reflects the time needed for prior circulating antibodies to no longer be in the blood stream. Other autoimmune diseases such rheumatoid arthritis follow a similar therapeutic delay after starting B cell depletion therapy,33 suggesting a similar mechanism between the two. This benefit persisted for upwards of one, sometimes two years.33

Given that rituximab is producing such dramatic results it is now possible that in the future management of ME/CFS will evolve to be similar to rheumatoid arthritis, lupus, or another one of the autoimmune pathologies. The presence of such a promising pharmacologic agent is unprecedented in the history of this disease. Prior to this, treatment strategies focused on patient education, cognitive behavioral therapy, and pharmacologic treatment of the symptoms of ME/CFS knowing that the underlying mechanism was most likely unaffected.5,34

That is not to say that the current manner of treatment is ineffective. There have been several studies showing the benefits of well-designed CBT both in the short and long term phases of the disease process. 5,6,35-37 In a study examining the long term effects of CBT in these patients Janse et al showed that patients who had undergone CBT for their ME/CFS showed reductions in fatigue, physical impairment, and disability. These positive effects of were stable for at least 18 months, and 5 years after completing therapy some did not even consider themselves to be suffering from ME/CFS any longer.35 These positive changes were repeated and observed organically in the research of DeLange et al. which positively correlated patients’ capacity for mental and physical exertion with increases in prefrontal cortical volume after completing six to nine months of CBT.37 The relevance of this increase in prefrontal cortical volume is further brought out by a separate study which demonstrated that patients with ME/CFS typically have decreases in their prefrontal cortical volume across time when compared to control subjects.19,37


In the context of the psychoneuroendo-immunologic model the main progenitor of the ME/CFS symptomology is the mismatch between the energy demanded and the energy mobilized. Given that premise it is reasonable to hypothesize that if one addresses the psychological comorbidities of this illness and develops positive coping strategies, then the levels of stress hormone, the demand for metabolic resources by the body, and consequently the severity of the ME/CFS symptoms ought to be minimized.12-16,18,21,25,35,37 This is especially pertinent in the case of children and adolescent cases of ME/CFS who are subjected to enough perceived stress without the additional burden of chronic disease.5 In fact, the primer on managing pediatric ME/CFS emphasizes this point in its treatment rationale. Rather than emphasizing the medical management of the various symptoms the clinician’s role tends to be ensuring that the patient, the family, and the patient’s school all have the means and the knowledge to minimize unnecessary stressors and maximize meaningful functionality.5


This model also addresses another facet of the disease management that has not been discussed much yet—graded exercise therapy. Without prior knowledge that ME/CFS is, by definition, the inability to adapt in response to an acute stressor it is perfectly reasonable to believe that physical activity and exercise training would be an appropriate strategy.1 After all, for almost all other fatigue-related pathologies exercise forms an integral part of maintaining some threshold of functionality as well as offering the usual benefits of avoiding sedentarism.6 Prior to much of the research discussed here the landmark PACE trial made the impression that patients were best served by gradually increasing exercise tolerance, CBT, and pacing of daily activities.36 These findings were in stark contrast to the experience of many patients and subsequent studies reanalyzing PACE’s claims. These stated that the combined protocol of CBT, GET, and pacing did not improve patient recovery rates and, in some cases, may have caused harm.6 These analyses also noted that CBT alone was not curative for ME/CFS which is consistent with the other literature discussed5,6,25,30. CBT could be a reasonable method of minimizing the stressors that precipitate PEM however it is doubtful that cognitive states could reliably stop B cells from producing antibodies.

Thus, ME/CFS is now conceptualized in a more rigorous manner. The disease process can most succinctly be described as a disease of multifactorial origin. A patient with an underlying allostatic state derived from genetic and environmental factors experiences an acute stressor that causes the system to produce autoantibodies which then attack the nervous system. This is by no means a complete conceptualization. The chain of events between acute viral stressor to production of autoantibodies needs further elucidation. Furthermore much of the literature shared the idea that there may be more than one phenotypic expression of ME/CFS.2,12-14,22,24,38 If valid, this can help explain some of the heterogeneity in the literature overall. For instance, in Light’s work there were two distinct phenotypes of mRNA transcription that correlated to ME/CFS patients with and without comorbid fibromyalgia.12 Another example is in a systematic review of the cortisol literature by Powell et al which commented that the attenuating in awakening levels of cortisol seemed to only occur in those who suffered severe emotional distress in their childhood.38 Another route of investigation that has yet to be explored is the pre-ME/CFS psychological characteristics of these patients. If ME/CFS is a disease that embedded in the stress response it is plausible that the manner in which one perceives stress be a pertinent risk factor.5,19,21,27,39 Given that Arroll’s model suggests allostasis it follows that such personality traits linked to high stress (whether positive or negative) should positively correlate with ME/CFS later on in life.39 Regarding treatment we now have reason to believe that immunologic therapies can offer patients relief.30,32,33 That being said, it is no small thing to start a patient on immune suppressant therapy. Perhaps insight into the functional neuroanatomy and pertinent psychology can help us develop more precise methods of psychotherapy—reducing the potential need to undergo immunosuppressive methods of treatment in the first place.


What we do know is as follows. ME/CFS is in fact an organic pathology which can be represented objectively. The caveat to this, however, is that many of the tests used to bring this pathology to light such as fMRI, ANOVA, and immunologic assays are beyond the reach of everyday clinical practice. Given this practical reality strict adherence to the criteria as defined by the CDC, CCC, or Oxford criteria and due diligence to rule out less esoteric pathologies ought to be the prudent strategy for diagnosis. Given that the criteria increasingly emphasize the neurocognitive aspects to the disease it becomes the responsibility of the physician to become familiar with performing such neurocognitive assessments or, practically speaking, to know the resources available so that this highly specialized aspect of clinical psychology can be performed well. Once the diagnosis has been made management ought to be individualized per the patient’s particular presentation and focus on reassurance, education, therapy, and structuring of the patient’s everyday life in such a way that maximizes function and minimizes suffering. Pharmacotherapy, for now, is focused on management of symptoms with particular caution to not resort to polypharmacy. This recommendation is especially pertinent as at the time of this writing there is no strong recommendation as to what medications ought to be used for this population.5,34 However, given that we do have a better understanding of the disease, more precise evidence-based guidance will surely be available in the future.

 

Reference List


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Megan Arroll is Director of Research at the Optimum Health Clinic. This part seems to be saying that better psych methods could supplant or make redundant immunotherapies. Even though the one under consideration at the time was ritux, which has since been found to be rather less interesting, this is still a crazy statement. How could psych methods be a substitute for basic biological treatments at a cellular level?

 

Another instance of people framing theories based on their preconceptions?

If this is the measure of critical thinking the education system has failed us

 

This is what the Blue Ribbon Foundation does:

http://theblueribbonfoundation.org/blue-ribbon-fellowship/

 

It's great that young intelligent minds are being channeled our way.

It sucks that this boils down in many ways to just another psych iteration. Sorry if my emotions and the stress of reading all this is too much for me....

 

It would be good if there was some way to have gotten a prize to someone like Robert Courtney, for his work.

 

I hate to discourage bright minds, and I think this kid is smart. He/she tells a plausible tale, but that plausible tales - whether true or false - are a dime a dozen is a hard fact that is cross-elastic across industries.

To me this is a good story cobbled together by theories or conjectures relayed as fact. That takes talent, and I think, in this case, good intent. But it is errant for many reasons. I will note one:

...

I challenge this, as should his/her mentor. Chia and Lerner and Peterson and Steere and others...enteroviruses and EBV and HHV and Lyme and others, have all been linked to ME/CFS. That a single pathogen has not been implicated, consistently, in all cases is no more significant that it would be in MS or Alzheimers or Parkinsons etc. That multiple pathogens may cause similar symptom clusters is just as plausible as the one set forth in this paper. Add to that the possibility of corrupted immune responses or autoantibody issues, and the need for emotional or stress factors seem no more relevant that they would in strep throat or the common cold.

Nevertheless, I think there is much to be lauded in this paper, and I applaud the effort and the interest from this budding talent.

 

ANOVA??????

Reckon I can do that on my laptop, or even online on a plug-in-the-numbers site, but only if I have some actual data first.

 

Yes, it's very muddled. The 'psycho' element seems shoehorned in so that the author can claim to be writing their Grand Unifying Theory of ME. There are several leaps of logic and bits where they openly contradict themselves.

That they simultaneously think CBT is sketchy and an alternative to immunotherapy is the most egregious of their assumptions/mistakes, but there are others too.

They seem to almost realise that psych issues may actually only be relevant for those with - surprisingly enough - psych issues (in the bit about childhood adversity), but then promptly discard following up on that thought because it doesn't fit.

(As a side point: No doubt the use of Oxford criteria studies is a confounding factor, too, for the 'psycho' part, since the criteria equally apply to many depressed patients.)

 

Thinking positively, if the student gets a placement in a *good* ME research environment, then it may disabuse them of their dafter ideas.

 

My thinking too

I wonder who judged the competition.

It'd be good if the student also received an informed critique of their essay and directions to further reading.(perhaps they did)

It is a bit of a muddle of an essay in places, even I can tell that, but it's good that new medical students are being encouraged to investigate ME, and will have time in a lab. Perhaps this person will go on to develop a career interest and contribute good things.

eta in places