Neurologic Abnormalities in M,E, A Review Komaroff et al

Countrygirl · Jan 20, 2018

https://www.ncbi.nlm.nih.gov/pubmed/29348374

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review].
[Article in Japanese]
Komaroff AL1, Takahashi R, Yamamura T, Sawamura M.
Author information

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by fatigue lasting for at least six months, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. ME/CFS has been a controversial illness because it is defined exclusively by subjective complaints. However, recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation - either inside or outside the brain - through release of inflammatory cytokines. In this review, we summarize potentially important recent findings on ME/CFS, focusing on objective evidence.

PMID:

29348374

DOI:

10.11477/mf.1416200948

The paper is un Japaanese.

If anyone can get access to the full paper please do provide a link or give more information. Thanks

CFS_for_19_years · Jan 20, 2018

I can't find it in http://sci-hub.la. I can see the first part of the introduction here:
http://medicalfinder.jp/doi/abs/10.11477/mf.1416200948

Click on "English" then click on the tab "Look Inside." The introduction doesn't add anything significant for a discussion.

Countrygirl · Jan 20, 2018

Someone on my newsfeed has copied this (with permission to share)

By using positron emission tomography, our study demonstrated neuroinflammation in the brain of patients with ME/CFS. Neuroinflammation was found to be widespread in the brain areas of the patients with ME/CFS and was associated with the severity of their neuropsychological symptoms. The ongoing research would lead to the establishment of objective diagnostic criteria and development of an appropriate therapy.

"WOULD LEAD to the establishment of objective diagnostic criteria and DEVELOPMENT OF AN APPROPRIATE THERAPY" Emphasis added

Diwi9 · Jan 20, 2018

Actually, there are a bunch of papers...all in Japanese! Looking forward to some good reads when we find a translation.

[Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]. by Hirohiko Kuratsune (2018) Brain and nerve = Shinkei kenkyu no shinpo

[History of Researches on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]. by Yasuyoshi Watanabe, Hirohiko Kuratsune (2018) Brain and nerve = Shinkei kenkyu no shinpo

[Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]. by Yasuhito Nakatomi, Hirohiko Kuratsune, Yasuyoshi Watanabe (2018) Brain and nerve = Shinkei kenkyu no shinpo

[New Diagnostic Biomarkers for Chronic Fatigue Syndrome]. by Emi Yamano, Yosky Kataoka (2018) Brain and nerve = Shinkei kenkyu no shinpo

[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]. by Takashi Yamamura, Hirohiko Ono, Wakiro Sato (2018) Brain and nerve = Shinkei kenkyu no shinpo

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review]. by Anthony L Komaroff, Ryosuke Takahashi, Takashi Yamamura, Masanori Sawamura (2018) Brain and nerve = Shinkei kenkyu no shinpo

Countrygirl · Jan 21, 2018

While searching for the full text, I found this interesting extract from a 2014 paper, which I will place here.

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study

+Author Affiliations

yywata@riken.jp

Abstract
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. 11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (11C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used 11C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. Methods: Nine CFS/ME patients and 10 healthy controls underwent 11C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BPND) values were determined using linear graphical analysis with the cerebellum as a reference region. Results: The BPNDvalues of 11C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%–199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of 11C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPNDvalues in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score. Conclusion: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

Keywords

Footnotes

Published online Mar. 24, 2014.

alex3619 · Jan 21, 2018

Countrygirl said:

Maybe, or its over-enthusiastic or something is lost in translation. "Could lead" is how I would put it, and that is enough to be interested.

Zara · Jan 21, 2018

Japanese study on brain inflammation in me/cfs. 120 subjects.

A follow up on 2014 with 9 subjects

Here you find initial study proposal:

https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033257

Prefect · Jan 21, 2018

The researcher is saying CFS diagnosis has so far been controversial because it is limited to subjective symptoms without objective diagnostic markers.

HPA axis suppression is a recognized phenomenon in CFS.

Why isn't HPA testing (such as ACTH stim test) used as a probable diagnostic tool? I've always wondered about this.

Learner1 · Jan 21, 2018

Prefect said:

An endocrinologist ran an ACTH stim test on me and pronounced it "normal" even though my ME/CFS doctor and people here in PR assured me it was definitely not. (I was also crashed and asleep before, during, and for 45 minutes after the test...the endocrinologist still said it was normal.

So, it goes to show that unless the test shows full blown Addisons, many docs won't recognize an HPA issue when they see one...

anni66 · Jan 22, 2018

My 16 year old daughter had ACTH test 2 weeks ago.
Crashed afterwards primarily because sleep is out and mornings are not good, compounded with energy expenditure required for round trip.
Results - normal apart from base hormone level ( ferritin hovering at low UK normal).
If you are in a low energy state, with systems compromised re energy levels, it' s perhaps not surprising that this is the case.....

Learner1 · Jan 22, 2018

anni66 said:

What were the values and ranges of "normal"? My doctors (not the endocrinologist) have me on a physiologic replacement dose of hydrocortisone, 15-25mg a day, in divided doses. It helps avoid crashing.

Prefect · Jan 22, 2018

Learner1 said:

anni66 said:

Was there a reason for the ACTH stim test to be done in your prospective cases to begin with, ie were some hormone markers shown to be abnormal in prior blood tests?

I'm asking since I'm thinking about having this done, because recent blood tests are showing me to have hypopituitarism. I'm male, 48, my Testosterone, LH, FSH, and prolactin are all at the bottom of the range and below the range at times. Free testosterone is at levels for men in their 80s.

This is odd because my testosterone was normal 3 years ago. Testosterone is supposed to only go down only 1% a year and I even conceived a child 3 years ago. Is this a phenomenon observed in men with CFS/ME?

Learner1 · Jan 22, 2018

I have other hormone problems and I'm having bone density issues, so the endocrinologist was trying to see if I really need to be on hydrocortisone. My test results didn't match the normal definition in published interpretive instructions for the test, and my other doctors and PR members interpreted my results as abnormal.

Yes, patients with ME/CFS are known to have hormone issues. Infections can throw hormones off, but there are other reasons. Getting hormones balanced can make you feel a lot better. You should also be checked for any serious glandular problems.

I found a DUTCH test to be helpful in looking at my hormones. Its a dried urine test for comprehensive hormones, and measures melatonin, cortisol, pregnenolone, DHEA, progesterone, and testosterone and estrogen metabolites. My doctors have also checked aldosterone, SHBG, and TRH to try to determine what's going on.

Prefect · Jan 22, 2018

Learner1 said:

Doesn't the hydrocortisone give you mood issues? I find even nasal steroid sprays make me depressed, which is a little shocking.

Learner1 · Jan 22, 2018

Prefect said:

Not at all.

If I experience mood issues, it tends to be for lack of methylating nutrients (folate, B12, B6, methionine) or amino acids, which is easily fixed.

Prefect · Jan 22, 2018

Learner1 said:

Yes but do you know of anyone on this forum who's been formally diagnosed by a doctor with HPA suppression through an ACTH stim test?

anni66 · Jan 22, 2018

We are in UK. Hormone health is notoriously misconstrued.
As my daughter has turned 16, she is now in adult care- i had requested either an immunologist or endocrinologist to take her on ( no ME specialists here). Immunology turned down request.
First endo appointment was on a Friday afternoon with a man who obviously had better things to do
No notes, took little history and would have dished out thyroxine like sweeties to deal with " fatigue" ( he thought i was worried about thyroid function)
I responded that there appeared to be HPA axis issues which could perhaps be checked out. Grudging ACTH test arranged.

I don' t have actual figure s, but have been advised that all values were " normal" apart from base hormone level which was low.As my daughter is mainly bedbound, i can understand the lack of cofactors - such as ATP would limit/ downregulate synthesis.

Hydrocortisone prescribed to try.
As ferritin was also on low side i think there may be other issues ( T3/4 conversion?)
Back in March for follow up

Alenka · Jul 3, 2018

Prefect said:

I was. Doc put me on HC and I've just done a MRI scan for a possible pituitary tumor. I don't think they'll find anything. Funny enough I'd prefer to have a tumor rather than stay with my ME CFS diagnosis. Or perhaps I have both! We'll see in a week's time

Neurologic Abnormalities in M,E, A Review Komaroff et al

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