Tuesday, June 30, 2015

Ricky Gervais, ridiculing patients and Pinocchio Psychiatry

Dear Mr Gervais,

  You said: "I believe the greatest privilege in this world is to use your freedom of speech for those who have no voice."

  I believe that the greatest privilege in this world is to respect everything that lives, unless they have broken that respect themselves.

  Please remember that if you ridicule people with a disease based on what psychiatrists or other doctors say that psychiatrists never ever have any evidence that a disease is psychosomatic or doesn't exist. WHY, because that sort of evidence doesn't exist.

  So all you do if you ridicule ME patients is you show total lack off respect for people who are ill.

  Or to quote exercise physiologist Professor Keller, who wrote in January 2015: "Given what we have learned in the past eight years about this illness, it is intellectually embarrassing to suggest that ME is a psychological illness." 

  So instead of ridiculing us, you should try and help us get proper medication / treatment so that we get our health and independence back so that we can come off benefits and go back to work.

  Regards,

  Dr Maik Speedy, a Doctor who has been bedridden with severe ME for more than a decade thanks to harmful graded exercise therapy which breaches the Do No Harm principle of the GMC / Medical Profession.

 

Monday, June 29, 2015

Unworthy of good Medical Practice in the 21st century

Just posted the following comment on Amazon UK in response to the review by Norfok reader "Straithern".

  Sad to see that you as a colleague GP, or family doctor as you call it, ignore all the evidence, just like doctor O'Sullivan, that ME is a debilitating neuro immune disease. Unworthy of good Medical Practice in the 21st century.

  Or to quote exercise physiologist Professor Keller, who wrote in January 2015: "Given what we have learned in the past eight years about this illness, it is intellectually embarrassing to suggest that ME is a psychological illness."

Sunday, June 28, 2015

Research shows that mostly raw vegetarian diet helps many patients with Fibromyalgia

@ PubMed:

  BMC Complement Altern Med. 2001;1:7. Epub 2001 Sep 26. Fibromyalgia syndrome improved using a mostly raw vegetarian diet: an observational study. Donaldson MS1, Speight N, Loomis S .Author information

  Abstract

  BACKGROUND: Fibromyalgia engulfs patients in a downward, reinforcing cycle of unrestorative sleep, chronic pain, fatigue, inactivity, and depression. In this study we tested whether a mostly raw vegetarian diet would significantly improve fibromyalgia symptoms.

  METHODS: Thirty people participated in a dietary intervention using a mostly raw, pure vegetarian diet. The diet consisted of raw fruits, salads, carrot juice, tubers, grain products, nuts, seeds, and a dehydrated barley grass juice product. Outcomes measured were dietary intake, the fibromyalgia impact questionnaire (FIQ), SF-36 health survey, a quality of life survey (QOLS), and physical performance measurements.

  RESULTS: Twenty-six subjects returned dietary surveys at 2 months; 20 subjects returned surveys at the beginning, end, and at either 2 or 4 months of intervention; 3 subjects were lost to follow-up. The mean FIQ score (n = 20) was reduced 46% from 51 to 28. Seven of the 8 SF-36 subscales, bodily pain being the exception, showed significant improvement (n = 20, all P for trend < 0.01). The QOLS, scaled from 0 to 7, rose from 3.9 initially to 4.9 at 7 months (n = 20, P for trend 0.000001). Significant improvements (n = 18, P < 0.03, paired t-test) were seen in shoulder pain at rest and after motion, abduction range of motion of shoulder, flexibility, chair test, and 6-minute walk. 19 of 30 subjects were classified as responders, with significant improvement on all measured outcomes, compared to no improvement among non-responders. At 7 months responders' SF-36 scores for all scales except bodily pain were no longer statistically different from norms for women ages 45-54.

  CONCLUSION: This dietary intervention shows that many fibromyalgia subjects can be helped by a mostly raw vegetarian diet.      

  PMID:   * 11602026   * [PubMed - indexed for MEDLINE]   *       PMCID:   * PMC57816  *

  Free PMC Article @ PubMed:

 

Friday, June 26, 2015

Editorial in Jacobs Journal of Physiotherapy and Exercise: it is essential to protect ME patients against harm by exercise regimes

Prolonged Abnormal Effects of Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

  Editorial in Jacobs Journal of Physiotherapy and Exercise by Frank N.M. Twisk, May 2015 :

  Exercise, especially exercise programs, has various beneficial health effects. However, in the case of Myalgic Encephalomyelitis and chronic fatigue syndrome physical exertion can induce prolonged negative effects on the patient’s condition (post-exertional “malaise”).

  The exacerbation of symptoms after exercise can plausibly be explained by exertion-induced abnormalities in ME/ CFS. In order to unravel the pathophysiology and to protect the patients’ from iatrogenic harm of exercise regimes, it is essential to asses and diagnoses patients objectively.

 

Sunday, June 21, 2015

My response to Brian R Martin, who deleted himself but then came back, and to Mr Richard Gipps "rgtgipps" on Amazon UK:

It's interesting to read that Brian R Martin deleted his "review in praise of the book", because he "got tired of" "abusive" comments from people who would not "consider anything other than their fixed views."

By writing this he shows no insight into the real problem.

Let me just quote what Mr Martin wrote himself in his deleted review: "and referring to the authority of the Countess of Mar, herself a sufferer of chronic fatigue syndrome, who without any apparent scientific/medical training quotes papers she undoubtedly has not read and who would not understand even if she had,"

So no wonder that people responded to this. I responded by saying: "That's an interesting observation, so if you don't like the evidence which is quoted, and you don't have any arguments to counter the evidence, you just say someone has no "apparent scientific/medical training", doesn't read articles and wouldn't be able to understand them anyway. So you just become very personal. That's not the right way to have a scientific debate or for science to move forward and you as a scientist should know that." I've since learnt that Mr Martin is an emeritus professor in physics in his mid seventies which makes his remarks about the Countess even sadder and more unprofessional.

As far as Mr Martins remark that people should "consider anything other than their fixed views" it's Mr Martin, Dr O'Sullivan and many 5 star commenters of her book, who refuse to consider anything other than their fixed views that ME is psychosomatic for which there is no evidence, why, because evidence that something is psychosomatic or psychological doesn't exist, and he refuses to accepts that a few days ago the Institute of Medicine and the National Institute of Health published the final version of their reports on ME/CFS, analysing more than 9000 research papers, concluding that ME is a devastating multisystem disease, and not a psychiatric or psychological one.

I always thought that physics was a science of evidence but Mr Martin's refusal to accept the overwhelming amount of evidence that ME is a devastating physical disease, is another reason why Mr Martin removed his review. It is clear that he as a professor cannot accept that there are mere mortals/others who know more about something than he does. And if people point out the evidence to him which he can't counter with any arguments because they don't exist, he becomes very personal as he did with the Countess for example, as if he is saying, how dare you say something to a professor.

As far as the review by Richard Gipps "rgtgipps" is concerned, who writes that ME "is best understood psychologically" and that patients with this disease have "frequent difficulty shown in accepting the possibility of psychological origin and maintenance" and that sufferers "from other debilitating conditions who are often far more ready to accept the possible impact of stress".

Those two last remarks however are 2 different things. Anybody healthy or ill knows that stress can have an impact but that has nothing to do with the underlying problems in ME, or to use Mr Gibbs his words, with the "origin and maintenance" of ME.

It's like saying to people with Parkinson's that they should go to a psychologist instead of treating them with anti Parkinson medication. And if they start to complain you just say that they have difficulty in accepting the possibility of psychological origin and maintenance, ignoring all the evidence that Parkinson is a physical disease.

Or to quote exercise physiologist Professor Keller, who wrote in January 2015:
"Given what we have learned in the past eight years about this illness, it is intellectually embarrassing to suggest that ME is a psychological illness." 

There is one more interesting observation and that is that doctor O'Sullivan is from UCL London and surprise surprise, Mr Martin, emeritus professor, is from UCL London as well.

For your information, I am a medical doctor, to be more precise a GP. And it's really sad to see that an emeritus professor in physics, ie Mr Martin, but also another doctor, ie neurologist Dr O'Sullivan, ignore all the evidence that what they say is wrong, and as you know doctors and professors should not do that, and that Dr O'Sullivan hasn't done her homework. Which is even sadder because in this day and age you can do most of it at home, behind your computer, articles are accessible via PubMed and many are open access these days.
Meaning everybody can read them, free of charge.

So therefore the conclusion is that Dr O'Sullivan's chapter about ME is intellectually embarrassing and should be removed from the book. 


Friday, June 19, 2015

My response to Brian R Martin on Amazon UK



Dear Mr Martin,

  you wrote a number of interesting things, for example:

  "The cases discussed are ones where Dr O'Sullivan considered that the evidence was in favour of a psychosomatic origin,"

  Doctors or others who say that a disease is psychosomatic do not have any evidence for that; why not because it does not exist. The mere fact that routine testing is normal is not evidence that something is psychosomatic. But many doctors do not understand or realise this. In Parkinson or ALS for example, routine testing is also normal. 

  You continue by saying: "but nowhere do I find that she dismiss the possibility that in future a physical origin for the symptoms may be found, another false charge made against her."

  A few days ago the Institute of Medicine and the National Institute of Health published the final version of their reports on ME/CFS, analysing more than 9000 research papers, concluding that ME is a devastating multisystem disease, and not a psychiatric or psychological one.

  Or to quote exercise physiologist Professor Keller, who wrote in January 2015: "Given what we have learned in the past eight years about this illness, it is intellectually embarrassing to suggest that ME is a psychological illness." 

  You also write that: "I do know that in SOME cases treatment based on the assumption that the cause is psychosomatic does work. So in the absence of definite treatments based on anything else, why not try it. It does not rule out better treatments in the future."

  As there are no proper treatments at present, most patients with ME have tried CBT, because they are desperate to get better, but CBT for ME at best is totally useless. And graded exercise therapy causes severe relapses if people really have ME and breaches the do No Harm principle of the GMC/Medical Profession.

  You also say: "and referring to the authority of the Countess of Mar, herself a sufferer of chronic fatigue syndrome, who without any apparent scientific/medical training quotes papers she undoubtedly has not read and who would not understand even if she had,"

  That's an interesting observation, so if you don't like the evidence which is quoted, and you don't have any arguments to counter the evidence, you just say someone has no "apparent scientific/medical training", doesn't read articles and wouldn't be able to understand them anyway. So you just become very personal. That's not the right way to have a scientific debate or for science to move forward and you as a scientist should know that.

  For your information, I am a medical doctor, to be more precise a GP. And it's really sad to see that another doctor, ie neurologist Dr O'Sullivan, ignores all the evidence that what she says is wrong, and as you know doctors should not do that, and that she hasn't done her homework. Which is even sadder because in this day in age you can do most of it at home, behind your computer, using PubMed, and many articles are open access these days. Meaning everybody can read them, free of charge.

  So I'm afraid to say that therefore the conclusion is that Dr O'Sullivan's chapter about ME is intellectually embarrassing and should be removed from the book.


  PS Saturday, June 20, 2015: interesting find by Linda.

 Brian R. Martin is emeritus professor of physics at University College London. And where is Dr Suzanne O'Sullivan from ?? Neurology Hospital from the University College London.

 PS 2: Brian Martin has now deleted his book review / thread on Amazon because he as a professor can't handle it when other people know more about something then he does. And he got very annoyed because he didn't have any arguments to counter things.

Thursday, June 18, 2015

Massachusetts Medical Society's NEJM Journal Watch: "There is still no cure, or even any reliably effective treatment, for CFS"

Diane E. Judge, APN/CNP, contributing editor, NEJM Journal Watch, June 15, 2015:

  Dispelling the myth that CFS is “all in your head”

  Chronic fatigue syndrome (CFS) is a devastating illness that can interfere with all facets of life.

  You might also see CFS called by an older name, myalgic encephalomyelitis (ME), or a combination of the two names (ME/CFS).

  Yes, It's “Real”

  When we first began hearing about CFS decades ago, many clinicians (doctors, nurse practitioners, physician assistants), and even friends and relatives of people with CFS questioned whether it was a “real disease” or “just a mental health condition” or a “figment of the imagination.” They had a hard time believing that a condition that couldn't be diagnosed with a blood test, x-ray, or physical examination could be real. Diagnosis depended (and still depends) solely on what the patient reports.

  Recently the Institute of Medicine (IOM) and the National Institutes of Health took a strong stand on CFS. Based on more than 9000 research studies, these organizations concluded that CFS has a biological basis (occurs because of one or more body malfunctions), declaring it “a serious, chronic, complex systemic disease that can profoundly affect the lives of patients.” They also stated that CFS is not “a psychological problem.”

  The studies identified many differences between people with CFS and healthy people or those with other conditions that cause severe fatigue (such as depression or multiple sclerosis). Differences were identified in the brain and nervous system, the immune system (which defends the body against infection), and the endocrine system (which regulates body function through glands and hormones).

  "In Conclusion

  There is still no cure, or even any reliably effective treatment, for CFS. But the IOM report should dispel the myth that CFS is “all in your head.” With more research, more clinician education, and more support for those who have CFS, this illness should receive the validation and attention it deserves."

  NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society.  

Wednesday, June 17, 2015

P2P final report: the Oxford definition impairs progress, may cause harm and should be retired, just like the PACE trial that used them

@ Ann Intern Med., 16 June 2015:

  "Furthermore, the multiple case definitions for ME/CFS have hindered progress. In particular, continuing to use the Oxford definition may impair progress and cause harm. Therefore, for progress to occur, we recommend that this definition be retired; the ME/CFS community concur on a single case definition (even if it is not perfect); and patients, clinicians, and researchers agree on a definition for meaningful recovery."

Tuesday, June 16, 2015

Countess of Mar to Dr O'Sullivan: it is intellectually embarrassing to ignore all the evidence that ME/CFS is a serious neuro-immune disease

Countess of Mar response to Dr O'Sullivan.pdf

Countess of Mar to Suzanne O'Sullivan in response to the chapter about ME in 'It's All in Your Head: ....'.


Permission to Repost

(Header unable to copy)

Dr SuzanneO’Sullivan
NationalHospital for Neurology and Neurosurgery
33 QueenSquare
LONDON
WC1N 3BG

9 June 2015



Dear DrO’Sullivan

I write toyou as an Independent crossbench member of the House of Lords where I have been since 1975. I am a Deputy Speaker in the House. For more than 20 years I have represented the interests of people with ME/CFS and other MUPS. I am patron of several ME charities and Chairman of Forward-ME.

I have read David Aaronovitch’s review of your book: “It’s all in Your Head – True Stories of Imaginary Illness” and I have listened to what you had to say on Radio 4’s Start the Week programme yesterday, though I have not read your book.Aaronovitch quotes you in the introduction to the chapter on ME as admitting that “to include ME/CFS in a book primarily concerned with the description of those suffering from psychosomatic illness is foolhardy to say the least.” He goes on to say that “This is because the reaction of many ME sufferers, their relatives and friends and the organisations that represent them, to the idea that the condition is psychosomatic – caused by the mind and not by a disease –is intensely hostile. I have experienced this hostility.” I assume the last sentence refers to him personally.

Sadly, both you and he are right about the hostility to the views you both promote, but you give the wrong reasons for that hostility. In recent years there have been a host of papers that demonstrate that ME/CFS is a disease as well as an illness.Firstly the Canadian Consensus document on ME/CFS, published in 2003, gave good guidelines for diagnosis and treatment of people with ME. This was followed by the more comprehensive Myalgic Encephalomyelitis - International Consensus Document published in 2011. More recently, the highly respected US Institute of Medicine in its report “Beyond Myalgic Encephalomyelitis/ Chronic fatigue Syndrome: Redefining the Illness” released on 10 February 2015, made clear that the primary message of the Committee’s report is that “ME/CFS is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients.”  Patients with the disease have always known this and are, understandably, deeply hurt and offended by the denigration they receive from some medical practitioners.

I admire the fact that you believe that people who suffer psychosomatic illnesses should be treated with compassion and understanding but I am equally disappointed that you appear to have failed dismally to keep abreast of current research into ME/CFS.  Had people like you in senior positions really tried to discover what is at the root of the symptoms suffered by the patients that you see more progress might have been made in the diagnosis and treatment of this dreadfully neglected disease.

For example,on 30 May this year in Metabolomics Armstrong et al wrote: “Metabolic profiling reveals anomalous energy metabolism andoxidative stress pathways in chronic fatigue patients.” Have you ever thought of metabolic profiling for your profoundly fatigued patients, I wonder? I do realise that there are vast numbers of papers of variable quality published each year, but I really do think that if one is professing an expertise in a particular disease or illness one should try to keep abreast of current research, don’t you?

You appear to be unaware that research shows that ME is an organic multi-system neuro-immune disorder with protean symptomology; some consider it likely to bean autoimmune disease with the target organ being the vascular endothelium.

For the avoidance of doubt, here are some facts that may have escaped you:

·        Since 2005 ME has been included in the UK National Framework for long-term neurological conditions.
·        On 30 January 2006 the then health Minister,Lord Warner, said on record: “There is only one World Health Organisation International Classification of Disease code for chronic fatigue syndrome/Myalgic encephalomyelitis, which is G93.3.” (HL3612)
·        On 2 June 2008 the Parliamentary Under-Secretary of State, Department of Health (Lord Darzi of Denham) stated: “My Lords, the Government accept the World Health Organisation’s classification of CFS/ME as a neurological condition ….MyLords, I have acknowledged that CFS/ME is a neurological condition.” (HLPQ:Health: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis)
·        On 21 November 2011 Lord Freud, Minister fo rWelfare Reform, confirmed in a letter to me that the Department for Work and Pensions does not consider ME/CFS to be a mental disorder. The letter was unequivocal: “the Department of Health has indicated that they have ‘always relied on the definition set out by the World Health Organisation in its International Classification of Diseases (ICD)under the ICD code G93.3, subheading other disorders of the brain’. The DWP isin agreement with this view. Therefore, for the avoidance of doubt, I can be clear that the Department does not classify CFS/ME as a mental health disorder.”
·        The US National Institutes of Health, one of the world’s foremost medical research centres, convened a Pathways of Prevention working group which, in December 2014, published its draft Statement entitled“Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”.It is an important document as it signifies a major change in attitude towardsME/CFS. For example:
Strong evidence indicates immunologic and inflammatory pathologies, neurotransmitter signalling disruption, microbiome perturbation, and metabolic or mitochondrial abnormalities in ME/CFS.
“This is not a psychological disease in aetiology.
“fMRI and imaging technologies should be further studied as diagnostic tools and as methods to better understand the neurologic dysfunction of ME/CFS.”

As a neurologist, I am sure you will find theseviews of interest.

Further research from the US posits that true ME(as distinct from the ubiquitous chronic “fatigue”) is indeed an autoimmune disorder: “Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases consistent with immune activation in the central nervous system, and a shift towards an allergic or T-helper type-2 pattern associated with autoimmunity….Profiles of ME/CFS subjects also differed from those of MS subjects, withME/CFS cases showing a markedly greater degree of central nervous system immuneactivation as compared with those with MS” (M Hornig et al: Molecular Psychiatry 31 March 2015: doi:10.1038/mp.2015.29)

The evidence is now so strong that ME/CFS is a serious multisystem neuro-immune disease that it becomes intellectually embarrassing for anyone to continue to consider it to be a psychosomatic disorder.  


I do hope that you will take my submission seriously and reconsider your belief thatME/CFS is a psychosomatic disorder.

I look forward to receiving your considered response.

Yours sincerely


Countess ofMar

Copy: DavidAaronovitch.

          Chatto and Windus – Lisa Gooding,Publicity.


Countess of Mar response to Dr O'Sullivan.pdf

Saturday, June 13, 2015

Evidence that a disease is psychosomatic doesn't exist

Doctors or others who say that a disease is psychosomatic do not have any evidence for that; why not because it doesn't exist.

  The mere fact that routine testing is normal is not evidence that something is psychosomatic. But many doctors do not understand or realise this.

  In Parkinson or ALS for example, routine testing is also normal.

  And in MS even with the advent of the MRI scan, on average it still takes 1 to 3 years to be diagnosed, meaning that these patients according to doctors like Dr O'Sullivan, have a psychosomatic disease, before after 1-3 years they are finally diagnosed with MS by a proper doctor.

  By simply checking the cytokine levels you can find that Abnormal cytokine levels distinguish ME/CFS from Gulf War Syndrome and healthy subjects, ( http://www.sciencedirect.com/science/article/pii/S1043466614006024) which clearly shows that ME is a physical disease and not a psychosomatic one.

  But many doctors do not know what cytokines are, which are hormonal messengers of the immune system, and you need specialised Laboratories who can do difficult immunological testing for this.

  Venus Williams, the successful American professional tennis player, who has won 7 grand slam singles titles, including Wimbledon 5 times, had a psychosomatic disease for 5 years before she saw a proper Dr and was diagnosed with an autoimmune disease (Sjögren's).

  A very sporty friend of mine had vague cardiac problems when he was 26, I sent him to a cardiologist, all tests were normal, so the cardiologist said it was psychosomatic, 2 weeks later during a 10 kilometre run he collapsed shortly before the finishline, a doctor who happened to be there tried resuscitation which didn't work and my friend died of a psychosomatic disease.

  Did the cardiologist apologize to his family, obviously not.

  Every doctor can tell you those sort of stories, including Dr O'Sullivan, but self reflection, just like doing research and not ignoring it, is not one of her good points.

  All this and more illustrates that if you don't do the right test, you don't get the right answer.

Friday, June 5, 2015

Coroner concludes awareness and care services for ME/CFS are insufficient

Emsworth police officer’s suicide prompts concern over care

  May 2015:

  "By then Emily was being treated by a Southbourne GP called Pippa Lally who Emily preferred, but Emily could not sleep, was bed-bound and spent much of her time in the dark, with ear protectors on."

  ############

    "“There was a total lack of facilities. It seemed bizarre we had our own specialist service in Haywards Heath but because she had severe symptoms, they weren’t able to help her, which seems ludicrous.”"

  ############

    "West Sussex Coroner Penelope Schofield questioned Emily’s care team and concluded awareness and care services for chronic fatigue syndrome were insufficient."

Thursday, June 4, 2015

When does ignoring evidence by doctors become serious professional misconduct ?

Professor Hooper, 19 February 2010:

   "For the psychiatrists to amalgamate 25 different disorders (Holgate, RSM July 2009) and to focus on “medically unexplained fatigue” whilst ignoring cardinal symptoms of ME is a travesty of medical science.

  Of special concern and relevance are the legal and ethical requirements facing doctors today, in particular, the legal requirement for doctors to keep up to date with developments in medicine and medical science (as clearly set out in" “Good Medical Practice: Duties of a doctor."

  "The duties of a doctor registered with the General Medical Council: "'Keep your professional knowledge and skills up to date' and 'Never abuse your patients' trust in you or the public's trust in the profession'(http://www.gmc-uk.org/guidance/good_medical_practice/duties_of_a_doctor.asp).

  Ignoring vast swathes of evidence is not keeping up to date.  For any registered medical practitioner – consultant or GP -- to dismiss or ignore this widely available evidence which invalidates the behavioural model of “CFS/ME”, together with the prescription of inappropriate interventions, is in clear breach of the GMC regulations and consequently raises issues of medical indemnity.

  As noted in the report: “"since the general body of knowledge known about by other clinicians and researchers working in the field of ME/CFS is now so great, the question repeatedly asked is: at what point will that body of scientific knowledge be so great that it will be considered serious professional misconduct to ignore it and to continue to deceive patients by pretending that it does not exist?”".

 

Wednesday, June 3, 2015

Discovered: the central nervous system lymphatic system

@ Nature, Published online 01 June 2015:

  Structural and functional features of central nervous system lymphatic vessels

 * Antoine Louveau ,  * Igor Smirnov ,  * Timothy J. Keyes ,  * Jacob D. Eccles ,  * Sherin J. Rouhani ,  * J. David Peske ,  * Noel C. Derecki ,  * David Castle ,  * James W. Mandell ,  * Kevin S. Lee ,  * Tajie H. Harris  * & Jonathan Kipnis

Nature  (2015)  doi:10.1038/nature14432       Received: 30 October 2014        Accepted: 20 March 2015      Published online: 01 June 2015

One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment1, 2, 3, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood4, 5, 6.

In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses.

These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system.


  1. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. _________________________________________

Missing link found between brain and immune system

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). "It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."
"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role," Kipnis said. "Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation - and they've done many studies since then to bolster the finding - that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."
Even Kipnis was skeptical initially. "I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," he said. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."

'Very Well Hidden'

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges - the membranes covering the brain - on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'"

As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer's, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

The findings have been published online by the prestigious journal Nature and will appear in a forthcoming print edition.
 Explore further: Surprising contributor to Rett syndrome identified

More information: Structural and functional features of central nervous system lymphatic vessels, DOI: 10.1038/nature14432

Journal reference: Nature

Provided by University of Virginia

Tuesday, June 2, 2015

Different immune cell abnormalities in patients with severe ME compared to those with moderate ME

Hardcastle et al, BMC Immunology, 2nd of June 2015:

Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Sharni Lee Hardcastle*Ekua Weba BrenuSamantha JohnstonThao NguyenTeilah Huth,Naomi WongSandra RamosDonald Staines and Sonya Marshall-Gradisnik


National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Centre, School of Medical Science, Griffith University, Gold Coast, QLD, Australia
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BMC Immunology 2015, 16:35  doi:10.1186/s12865-015-0101-4
The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2172/16/35

Received:28 November 2014
Accepted:21 May 2015
Published:2 June 2015
© 2015 Hardcastle et al.; licensee BioMed Central. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


Abstract

Background

Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients. CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls. Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors.

Results

CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4+T and CD8+T cells. Moderate CFS/ME patients had increased CD8+ CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5+ on CD4+T cells and BTLA4+ on CD4+T central memory cells. Moderate CFS/ME patients also had reduced CD8+T central memory LFA-1, total CD8+T KLRG1, naïve CD4+T KLRG1 and CD56dimCD16 NK cell CD2+ and CD18+CD2+. Severe CFS/ME patients had increased CD18+CD11c in the CD56dimCD16 NK cell phenotype and reduced NKp46 in CD56brightCD16dim NK cells.

Conclusions

This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.
Keywords: 
Chronic fatigue syndrome; Natural killer cell; Receptors; CD8+T Cell

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