The Nightingale Research Foundation is a Canadian non-profit organisation founded in 1988 by Dr Byron Hyde. It is named after Florence Nightingale, the renowned British nurse, who some speculate may have had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on retrospective accounts – though the illness had not yet been defined during her lifetime. The Foundation published he Nightingale definition for ME in 2007, later revised in 2016. This case definition is one of the lesser known and rarely cited definitions/criteria for ME.
The 2016 criteria document asserts – “This definition of M.E. is distinct and exclusive of the various Chronic Fatigue Syndrome definitions. It is based upon over 30 years of patient investigation and M.E. literature. This definition proposes M.E. and CFS should be considered as separate entities.”
The 2007 document also mentions that the Nightingale definition was prepared “as a result of an invitation to attend two meetings at the British House of Commons with the Honourable Dr. Ian Gibson, Member of Parliament for Norwich North.” Importantly, the authors allude to the evolving nature of case definitions: “As with all definitions, the Nightingale Research Foundation’s Definition of M.E. will have to be looked at by many clinicians and researchers and increasingly knowledgeable patients and over the years, disagreed about, changed and improved upon.”
Summary of the Nightingale definition (2016)
Clinical history
ME is described as a biphasic illness with an acute onset followed by a chronic phase.
First phase – Acute illness
Symptoms may be “minor or missed”, resembling a flu-like illness or an upper respiratory tract infection. In some cases, more severe second-phase symptoms may appear early. The criteria emphasise that ME is “rarely taken seriously at onset” and is often mistaken as influenza, EBV, or a short-term viral illness. Testing for enteroviruses is essential for diagnosis (as enteroviruses are primarily considered to be the trigger of ME according to the Nightingale definition).
Second phase – Chronic illness
Begins “day 1 to day 10 following the initial onset phase” and is divided into two parts:
- Part one:
Can include symptoms from the acute phase and additional signs such as:- Severe, ” apparently inexplicable” exhaustion
- Pain (including severe headaches, retro-orbital eye pain, muscle spasms, and chest/abdominal pain)
- Paresthesia (pins and needles)
- Fear (a profound sensation of impending death)
- Largely negative physical examination findings
- Part two:
Encompasses the chronic, disabling features of ME, which become apparent as “early acute complaints become subdued or the new norm”. Noted symptom categories include:- Neurological associated symptoms: Central nervous system-related symptoms such as memory impairments, anomia (word-finding difficulties), visual and auditory abnormalities, temperature dysregulation, major sleep dysfunctions, bladder issues, tachycardia, and dysautonomia. A key diagnostic feature included within this category is “inability to return to a normal physical state after minor physical activity.”
- Muscular dysfunction: Persistent weakness and pain after minimal exertion, difficulty climbing stairs or walking normal distances without prolonged aftereffects. Muscle spasms and intercostal pain may also occur.
- Psychological symptoms: Including reactive depression.
- Gastrointestinal and related dysfunction
Enteroviral infection
Central to the Nightingale definition is the assertion that ME is caused by chronic enteroviral infection. According to Dr Hyde, “the cause of primary M.E. is related only to chronic enteroviral infections, close cousins of paralytic poliomyelitis.”
Brain imaging
The criteria recommend the use of SPECT imaging and specialised analytical software to detect hypoperfusion (reduced blood flow) in specific brain regions (at least the left temporal lobe and cingulate gyri). Further findings may include:
- “Increased M.E. disability is associated with an increased and irregular brain hypoperfusion of both cerebral hemispheres, midbrain and basal ganglia injuries.”
- Motor cortex involvement in cases with motor difficulties
- Insular lobe hypoperfusion associated with to dysautonomia
Additionally, it is stated that “multiple tests can confirm M.E. disability,” including cardiopulmonary exercise testing.
Considerations
This criteria may appeal to those who regard ME as distinct from CFS and prioritise measurable neurological dysfunctions as key to diagnosis. It also makes an interesting point about the lack of mention of fatigue – “…Fatigue was never a major diagnostic criterion of M.E. Fatigue, loss of stamina, failure to recover rapidly following exposure to normal physical or intellectual stressors occur in most if not all progressive terminal diseases and in a very large number of chronic non-progressive or slowly progressive diseases. Fatigue and loss of stamina are simply indications that there is something wrong. They cannot be seriously measured, are generally subjective and do not assist us with the diagnosis of M.E. or CFS or for that matter any disease process.”
Interestingly, the Nightingale criteria focus on enteroviruses – gut-based viruses spread via the faecal-oral route. The enteroviral family does not include, herpesviruses (such as Epstein Barr virus) which are commonly thought to be a trigger for ME/CFS.
Despite its detail, the criteria may be difficult to operationalise. It lists a broad array of symptoms, references an external source for additional signs and symptoms, and lacks clarity on which symptoms are compulsory for diagnosis. Moreover, the need for advanced neuroimaging and enteroviral testing may limit accessibility. While the illness is described in distinct “phases,” the way way these phases are outlined seems to lack precision. Additionally, some repetition of symptom descriptions throughout the document reduces clarity and impacts overall structure.
References:
Hyde, B. (2007). The Nightingale, Myalgic Encephalomyelitis (M.E.) Definition. [online] Ottawa, Canada: The Nightingale Research Foundation. [Accessed 25 Jul. 2025].
Hyde, Byron (2016). “The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.)” (PDF). The Nightingale Research Foundation. [Accessed 25 Jul. 2025].
