London criteria

The London criteria is a definition of Myalgic Encephalomyelitis for use in research, first published in 1994 and updated in 2014. It provides operational criteria for the diagnosis of myalgic encephalomyelitis corresponding to the clinical description by renowned ME-expert Melvin Ramsay. Central elements of the London criteria are post-exertional muscle fatigue, neurocognitive impairment and fluctuation of symptoms, usually precipitated by physical or mental exercise.

Definition
All patients should fulfill the following five criteria:


 * 1) A new onset of significantly abnormal levels of muscle fatigability and/or muscle weakness, precipitated by relatively minor levels of activity. Symptoms typically worsen during the next 24-48 hours.
 * 2) The presence of symptoms indicating the involvement of the brain and central nervous system (e.g. impaired short-term memory and concentration, disturbed sleep patterns, balance problems).
 * 3) Periods of impaired circulation compatible with autonomic dysfunction (e.g. facial pallor, disturbances in thermoregulation including inappropriate sweating and sensitivity to both heat and cold; postural hypotension and/or orthostatic intolerance).
 * 4) Fluctuation of symptoms, from hour to hour and day to day.
 * 5) These symptoms must have been present during the past three months (to exclude patients with the debility which often follows illnesses such as influenza).

The first version
The first version of the London criteria was formulated by Elizabeth Dowsett, Ellen Goudsmit, Anne MacIntyre and Charles Shepherd in 1993 and published a year later in the report from the National Task Force on ME. It focused on post-exertional muscle fatigue, neurocognitive impairment and fluctuation of symptoms, usually precipitated by physical or mental exercise. Autonomic and immunological symptoms were regarded as secondary. According to Charles Shepherd, the criteria were developed “in order to try and persuade researchers to carry out research into Ramsay described ME. This was obviously at a time when the medical profession had decided to rename and redene ME as CFS and (if possible) put a very thick red line through the term ME.”

The criteria were written for British patients organizations and used in several studies - most notably the study on brainstem blood perfusion by Costa et al. (1995). The criteria however failed to get wider traction in the research community, as most journals and funders preferred to use the CDC-formulated chronic fatigue syndrome-criteria.

Use in the PACE-trial
The London criteria came back into the center of attention when White et al. announced they were going to use the London criteria to diagnose ME-patients in the PACE-trial. The actual version used in the PACE-trial was however a modified version of the London criteria, not approved by any of the authors. Ellen Goudsmit for example wrote: “The version used in the PACE trial was not written by any of those who were involved with the London criteria. I’ve seen the manual and don’t recognize it.”

The PACE-authors referred to the report from the National Task Force on ME, yet not all details of the London Criteria were published in that report. The directive to exclude psychological disorders for example was not mentioned. In the 1993 version, made available online by Charles Shepherd and the ME Association, the following passage was included:"“Of particular importance is to eliminate chronic fatigue primarily associated with psychological factors. If there are signs of persistent anhedonia, apathy, low self-esteem, feelings of worthlessness and guilt, the possibility: of primary depressive illness should be actively considered and, if there is any doubt whatsoever, the subject eliminated from the research study.”"The published data of the PACE-trial do not make clear if psychological disorders had been excluded, as the original London criteria required.

According to Goudsmit, the fact that the London criteria were use in the PACE-trial, instigated a backlash against the criteria among ME-advocates: "“The LC were generally considered a good thing when the study was published in 1995. It became an issue only when the LC were included in the protocol for the PACE Trial. This introduced a political element, i.e. some argued that if one could show that the LC were no good, what was it doing in an expensive, government funded trial and the only proper action was to stop that trial. We all got that. Activists therefore began questioning everything they could about the LC.”"Malcolm Hooper had for example written: "“The 'London Criteria' have no known authors; they have never been published; there is no methods paper which specifically describes them as a “case definition”; they have never been approved nor have they even been finally defined (there are various versions); they have never been validated and they are not on PubMed thus are not available for scrutiny so they cannot be accessed for comparison. This means that Professor White was essentially able to create his own version of the “London Criteria."

The updated London criteria
With the publication of the International Consensus Criteria (ICC) in 2011, alternative criteria for the diagnosis of ME became available for researchers and clinicians. The ICC were formulated by ME-experts from 12 different countries, using a Delphi-type process. Although the ICC have been validated in research, several criticisms have arisen about its use. Leonard Jason for example noted that it is not clear if all five elements of what the ICC calls post-exertional neuroimmune exhaustion (PENE) should be present or not. A 2013 paper by Brown et al. demonstrated that the ICC identifies a patient group with more psychiatric disorders than the Fukuda (CFS) -criteria. By utilizing a wide array of symptoms in the diagnosis of ME, the ICC seems to capture a different set of patients than those originally described by Ramsay. Furthermore, muscle weakness after minimal exercise is not explicitly mentioned in the ICC-description of PENE.

The London criteria were updated in 2009 and once more in 2014, to provide research criteria that capture the clinical picture of ME as described by Ramsay and the pre-CFS literature. This updated version of the London Criteria added "impaired circulation compatible with autonomic dysfunction" as a major criterium and recommends the use of the Profile of Fatigue Related Symptoms (PFRS) in making the diagnosis of ME. Authors of the 2014 version were Ellen Goudsmit, Charles Shepherd and Sandra Howes.

Learn more

 * A Comparison of Case Definitions for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome (2017)
 * Myalgic Encephalomyelitis (ME). Criteria and clinical guidelines 2014.