Print

Posted in:

Nakatomi: neurological inflammation in ME/CFS

Correlation with the severity of cognitive symptoms

A Japanese research team has found widespread neurological inflammation in ME and CFS patients.

Nakatomi et al (2014) also found that levels of neuroinflammation correlated with the severity of cognitive symptoms.

Nine me/cfs patients and 10 healthy controls underwent PET scanning and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression.

PET imaging revealed that levels of a binding ligand were 45-199% higher in me/cfs patients than in healthy controls in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons regions of the brain.

Importantly, in CFS/ME patients, the researchers found that levels of the binding ligand in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, levels in the cingulate cortex and thalamus positively correlated with pain score, and levels in the hippocampus positively correlated with depression score.

The ligand, 11C-(R)-PK11195, is an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation.

PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction.

Neuroinflammation ignored in SEID definition

Nakatomi et al (2014) underscores several important divergences in the new CFS/SEID definition outlined in the controversial IOM report, when compared to the comprehensive 2011 ME-ICC definition developed by me/cfs researchers and clinicians and already well supported internationally.

ME advocate Jerrold Spinhirne commented on Facebook that the SEID definition overwhelmingly focused on fatigue abnormalities, and downplayed or ignored neurological impairments. Also, the IOM report failed to mention the more comprehensive ME-ICC definition which placed a higher emphasis on neurological impairment in ME.

It should be noted that the Nakatomi et al study used the 2011 ME-ICC criteria to select subjects, in addition to the broader 1994 CDC Fukuda cfs criteria, thus the results of this study may be more appropriately applied to ME patients, rather than to cfs patients.

Spinhirne said the IOM committee did discuss this study and others that also found evidence of brain abnormalities, but concluded that there was a “general lack of evidence of brain inflammation in me/cfs patients.”

As a result, cognitive impairment was omitted as a required symptom for diagnosing SEID.

“By contrast, the 2011 ME-ICC require at least THREE symptoms indicating neurological involvement for an ME diagnosis. This is consistent with the World Health Organization’s 46-year classification of ME as a neurological disease,” said Spinhirne.

Abstract

J Nucl Med. 2014 Mar 24;55(6):945-950. [Epub ahead of print]

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

Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K, Fukuda S, Kawabe J5, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K, Inaba M7, Kuratsune H, Watanabe Y.

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 BPND values 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 BPND values 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.

PHOTO: Activation of Brain Region Predicts Altruism. by –Tico–

More

  • Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. [pubmed], [full text]
  • [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen’s encephalitis. [PubMed]
  • Evidence of Neurological Abnormalities in Myalgic Encephalomyelitis Suppressed in the IOM “ME/CFS” Report [Facebook]
Shares

Written by Russell Logan

Russell Logan worked as a magazine publisher and editor until forced into early retirement through ill health with ME. He has battled with moderate to severe ME for 25 years. He now lives in Noosaville, Australia.

86 posts

2 Pings & Trackbacks

  1. Pingback:

  2. Pingback:

Leave a Reply

Your email address will not be published.