New Lipkin study discovers evidence of classical and atypical me/cfs

[Anomie]

http://microbediscovery.org/2017/04/04/new-research-discovers-evidence-of-atypical-classical-mecfs/

 

[Remy]

This latest research is the first to report evidence differentiating Atypical and Classical ME/CFS
The researchers measured 51 different cytokines (immune messenger molecules) in cerebrospinal fluid. Their immune network analysis of these cytokines provided evidence that Atypical and Classical cases of ME/CFS have differing immune signatures within the central nervous system. This work suggests distinct presentations and course of disease for these different subgroups or phenotypes.
The new research paper; ‘Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations’ has been published in the Nature Publishing Group journal, Translational Psychiatry.
This work is a further continuation of collaborative work on cerebrospinal fluid and cognitive dysfunction by scientists at Columbia University Center for Infection and Immunity (CII) and Simmaron Research.
Abstract

“Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and debilitating disorder marked by cognitive and sensory dysfunction and unexplained physical fatigue. Classically, cases present after a prodrome consistent with infection; however, some cases are atypical and have a different presentation and comorbidities that pose challenges for differential diagnosis. We analyzed cerebrospinal fluid (CSF) from 32 cases with classical ME/CFS and 27 cases with atypical ME/CFS using a 51plex cytokine assay. Atypical subjects differed in cytokine profiles from classical subjects. In logistic regression models incorporating immune molecules that were identified as potential predictor variables through feature selection, we found strong associations between the atypical ME/CFS phenotype and lower CSF levels of the inflammatory mediators, interleukin 17A and CXCL9. Network analysis revealed an absence of inverse inter-cytokine relationships in CSF from atypical patients, and more sparse positive intercorrelations, than classical subjects. Interleukin 1 receptor antagonist appeared to be a negative regulator in classical ME/CFS, with patterns suggestive of disturbances in interleukin 1 signaling and autoimmunity-type patterns of immune activation. Immune signatures in the central nervous system of ME/CFS patients with atypical features may be distinct from those with more typical clinical presentations.”​

Press Release

Scientists Discover Biological Evidence of “Atypical” Chronic Fatigue Syndrome

Defining subgroups may help clinicians identify and treat the complex, debilitating disease also known as myalgic encephalomyelitis or ME/CFS
NEW YORK (April 4, 2017)—Scientists at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health are the first to report immune signatures differentiating two subgroups of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): “classical” and “atypical.” This complex, debilitating disease is characterized by symptoms ranging from extreme fatigue after exertion to difficulty concentrating, headaches, and muscle pain.
Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses.
To uncover evidence of these disease types, first author Mady Hornig, MD, director of translational research at CII and associate professor of Epidemiology at Mailman, and colleagues used immunoassays to measure levels of 51 immune biomarkers in cerebrospinal fluid samples taken from 32 cases of classical and 27 cases of atypical ME/CFS. All study participants were diagnosed using the same standard criteria, but atypical cases either had prior histories of viral encephalitis, illness after foreign travel or blood transfusion, or later developed a concurrent malady—seizure disorders, multiple sclerosis-like demyelinating disorders, Gulf War Illness, or a range of cancers—at rates much higher than seen in the general population.
Their analysis revealed lower levels of immune molecules in individuals with atypical ME/CFS than those with a classical presentation and course of illness, including dramatically lower levels of interleukin 7 (IL7), a protein linked to viral infections, and interleukin 17A (IL 17A) and chemokine (C-X-C motif) ligand 9 (CXCL9), inflammatory molecules implicated in a variety of neurological disorders.

“We now have biological evidence that the triggers for ME/CFS may involve distinct pathways to disease, or, in some cases, predispose individuals to the later development of serious comorbidities,” says Hornig. “Importantly, our results suggest that these early biomarker profiles may be detectable soon after diagnosis of ME/CFS, laying a foundation for better understanding of and treatments for this complex and poorly understood illness.”
“Early identification of patients who meet the usual clinical criteria when first diagnosed but then go on to develop atypical features would help clinicians like myself identify and treat these complex cases and even prevent fatal outcomes,” says co-author Daniel L. Peterson, MD, principal clinician at Sierra Internal Medicine in Incline Village, NV.​

Subgroups

The new study builds on earlier research by Hornig and collaborators that found robust evidence of distinct stages in ME/CFS. A pair of 2015 publications based on analyses of blood and cerebrospinal fluid showed differences in the immune signatures of ME/CFS patients who had the disease for three years or less as compared with those who had been ill for more than three years. The researchers reported that patients were flush with cytokines and chemokines until around the three-year mark—suggesting an over-activated immune response in that phase of the illness; thereafter the immune system showed evidence of “exhaustion,” and levels of immune molecules dropped.
In the new study, both subsets of ME/CFS patients showed signs of an unbalanced or dysregulated immune system within the central nervous system, with immune markers different than those seen in healthy individuals. However, the dampened immune profiles previously observed after the three-year mark were only observed in individuals with the classical form of the disease, not in those with atypical ME/CFS. Among subjects in the atypical group, levels of cytokines and chemokines were more likely to remain steady or increase.
According to Hornig, instead of the immune exhaustion seen in later phases of classical ME/CFS, atypical patients may be experiencing a “smoldering inflammatory process” in which the immune system is still working to recover, although she acknowledges that much work remains to be done to confirm this hypothesis. Alternatively, these findings could suggest a pathway to disease in atypical individuals that involves biomarkers not captured in the 51-molecule assay, potentially even involving non-immune-related processes. Atypical individuals may also have genetic susceptibilities that lead their immune systems to respond differently than in classical cases.
Ongoing studies at CII are exploring other subgroups, including patients with allergic disorders, high levels of cognitive dysfunction, and gastrointestinal disturbances.

“Multiple biological pathways are likely involved in the pathogenesis of ME/CFS, with a range of clinical subtypes relating to variability in the types of environmental triggers, genetic and epigenetic vulnerability, as well as comorbidity patterns,” says senior author Ian Lipkin, MD, director of CII. “Shedding light on these pathways may help us to identify the various agents that precipitate disease as well as to design more precise, targeted treatments.”​

The study was supported by the Chronic Fatigue Initiative/Hutchins Family Foundation and the Edward P. Evans Foundation. Additional authors include Meredith L. Eddy, Xiaoyu Che, and Joy Ukaigwe at the Columbia University Mailman School of Public Health; and C. Gunnar Gottschalk at Sierra Internal Medicine. The authors declare no conflicts of interest.”

Dr. Ian Lipkin, Dr. Mady Hornig and the scientists at the Center for Infection and Immunity at Columbia University Mailman School of Public Health need help to fund an exceptionally comprehensive and robust study for ME/CFS. Please read about this monster of a study and consider making a donation.

 

[Remy]

I really wish they would have expanded and replicated their original hypothesis about a shift in cytokine parameters at about the 3 year mark.

I still don't feel confident that this group includes whatever illness I have. I'd have liked to see that part firmly accepted into prior to making even more speculations as to the typical or not-typical presentation.

How do you know atypical when garden variety is still an elusive construct?

 

[weyland]

I really wish they would have expanded and replicated their original hypothesis about a shift in cytokine parameters at about the 3 year mark.

That finding was on plasma and not CSF cytokines, and this is a followup to the CSF study (same patients from the original CSF study as best I can tell). With that said, looking at the first figure, it seems they did break down the results into duration and there were several statistically significant results between long and short within the "classic" cohort. Correct me if I'm misunderstanding.

Otherwise, yeah, it would be nice to see this replicated outside of Peterson's cohort. I think the only reason they could do this study is because Peterson does routine CSF collection on his patients and has had it banked for many years. Also he has devised this classification of an atypical ME patient, which is different than what the consensus criteria authors consider atypical ME, which is ME without PEM, so I don't think many or any other ME clinicians make this sort of distinction between their ME patients as Peterson has done.

 

[ankaa]

Plus, why published in a psychiatric journal! I'm so tired of the Med community gaslighting patients into believing this is not a biological illness & publishing in psych journals doesn't help at all

 

[weyland]

Plus, why published in a psychiatric journal! I'm so tired of the Med community gaslighting patients into believing this is not a biological illness & publishing in psych journals doesn't help at all

Well, Hornig is a psychiatrist so it's not that unusual. This journal at least appears to be heavily tilted towards biomedical research.

 

[ankaa]

Well, Hornig is a psychiatrist so it's not that unusual. This journal at least appears to be heavily tilted towards biomedical research.

Lol... that makes sense, and I'm not surprised there's a good reason, it's just annoying because it perpetuates the bs psychological narrative...

 

[JennyJenny]

Those that are beholden to the BPS model will only use it to further their agenda, I am sure. They are already claiming brain inflammation as proof of depression, therefore any brain images that show inflammation will only bolster their BPS claims.

It isn't that I mind it being published in a Psych journal as much as it is ridiculous no other journal is publishing it. I am sure she submitted her findings to other medical/science journals.

 

[ankaa]

Those that are beholden to the BPS model will only use it to further their agenda, I am sure. They are already claiming brain inflammation as proof of depression, therefore any brain images that show inflammation will only bolster their BPS claims.

It isn't that I don't mind it being published in a Psych journal as much as it is ridiculous no other journal is publishing it. I am sure she submitted her findings to other medical/science journals.

Good points.. the medical silos are frustrating

What is BPS?

 

[JennyJenny]

Good points.. the medical silos are frustrating

What is BPS?

Biopsychosocial model. Psychiatrists (mostly in the UK) are saying patients suffering from ME/CFS minds' are responsible for our symptoms.

 

[Merida]

Progress may be slow and difficult until researchers begin to understand the function of the central nervous system - how spinal fluid circulates from the brain to the sacral bulb and back. There is a sophisticated craniosacral pump involving micro movements of the cranial bones, jaw, and sacrum. The occiput and sacrum have a reciprocal motion, which is part of the system that allows spinal fluid to move against gravity .

When the sacrum becomes destabilized due to ligament incompetence ( fall on tail bone, pregnancy, certain sports, hitting the car brakes etc.) the entire system can be affected, allowing for microorganism mayhem.

The system is also affected by scoliosis, which can cause the sacrum to rotate. The sacrum changes will influence the occiput, other cranial bones, and position of the jaw. How many of us have TMJ dysfunction?

This theory explains why women are so much more likely to get diagnosed with CFS/ FM. We have wider inherently more unstable pelvises, which ultimately could cause inflammation in the CNS.

The great osteopaths ( Sutherland, Upledger) researched and began to understand cranial/ sacral function decades ago.

 

[ankaa]

Ive had mild scoliosis & intermittent TMJ

Cranial sacral therapy is really helpful, too! This thing is even helpful

https://jet.com/product/detail/2615...2&code=PLA15&gclid=CLzjh6yikdMCFURcfgodVeEHrA

 

[Natalie S]

Plus, why published in a psychiatric journal! I'm so tired of the Med community gaslighting patients into believing this is not a biological illness & publishing in psych journals doesn't help at all

Seemed like a strange choice of journal for a disease that people have been fighting for it to be recongised as biological... One of their last papers was in Molecular Psychiatry, equally strange