by Sasha Nimmo

New case definition and biomarkers suggested from Australia’s Deakin University: Neuro-Inflammatory and Oxidative Fatigue 

An Australian university is suggesting a new name to replace ME/CFS. The new name is Neuro-Inflammatory and Oxidative Fatigue or NIOF, after they studied 196 subjects with CFS (CDC criteria) and 83 with chronic fatigue and found two distinct groups.

Analysis showed two well-separated clusters with highly significant differences in symptoms and biomarkers. The biomarkers suggested for NIOF are IgM/IgA responses against LPS of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin.

“There is now evidence that ME/CFS is a neuro-psychiatric and physiosomatic disease accompanied by activated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways, lowered levels of key antioxidants, signs of immunosuppression, increased bacterial translocation or leaky gut, autoimmune responses directed against key neuronal molecules, including neurotransmitters and anchorage molecules, and CNS disorders such as a lowered brain blood flow and metabolism.”

The paper’s author states that data, not consensus amongst experts, should be used to make classification rules.

The author argues that NIOF is present when chronic fatigue is present for more than six months; and four or more of the following six symptoms are present and score higher than 4 on the Fibromyalgia and Chronic Fatigue Syndrome Rating scale, muscle tension, memory disturbances, sleep disorders, irritable bowel, headache and a flu-like malaise. Apart from the clinical diagnosis NIOF they also propose to specify the ‘stage’ of NIOF, e.g. chronic deteriorating, in remission, relapsing- remitting, and precipitated/exacerbated by infections or psychological stressors, and by biomarkers.

“This study validates a new case definition for “NIOF”, a neuroprogressive disorder, which should be further defined using 5 specifiers, i.e. with or without 1) post-exertional malaise, 2) abdominal discomfort syndrome, 3) depression, 4) hyperalgesia / fibromyalgic complaints and 5) comorbidies with medical/psychiatric diseases. Therefore, NIOF is a statistically-derived, clinically-based diagnostic label afforded to patients who suffer from a symptom cluster with a range of different clinical specifiers and neuroprogressive pathways.”

The paper briefly covers the history of ME and CFS and describes the International Consensus Criteria (ICC) as criticised and flawed. The paper says criteria published by the USA’s Institute of Medicine (IOM) are even more flawed and inadequate, as patients with psychiatric disorders may be categorised as suffering from SEID.

“The findings also show that CFS is a very simplistic, over-inclusive diagnostic label afforded to patients who in reality suffer from a cluster of symptoms with a range of different pathways. Secondly, the ICC and IOM criteria are not correct because our statistical approach showed that fatigue is a key symptom of the cluster- derived classes while these case definitions deleted chronic fatigue as a key symptom. Moreover, the ICC and IOM criteria did not take into account that post-exertional malaise (PEM) significantly divides ME/CFS into those with and without PEM showing that PEM is a specifier and that ME/CFS without PEM is also a valid diagnostic class.”

The paper includes recommendations for future research. “Further research should further refine the case definitions for NIOF criteria presented here by using 1) a broader list of illness symptoms, 2) objective measurements of symptoms such as EEG sleep patterns, neurocognitive testing, repeated cardiopulmonary tests, NMR spectroscopy to measure in vivo ATP production, etc.; and 3) staging characteristics (course, duration of illness) (Morris & Maes 2013b). Furthermore, future research should examine the 5 specifiers, (PEM, abdominal discomfort syndrome, depression, hyperalgesia/fibromyalgic symptoms and comorbidities) in order to construct precise NIOF criteria. Finally, this research should also use different omics-based biomarkers to externally validate the case definitions and specifiers.”


Prof Dr Michael Maes from Deakin University, in Victoria, Australia had the paper published in Neuroendocrinology Letters. Here is the full paper.