ME Research UK Supports International ME research consensus call

ME Research UK supports calls for creation of an internationally recognised and operationalised research criteria for M.E. (also known as Enteroviral Encephalomyelitis)

In doing so, it joins leading researchers, clinicians, fellow charities, patients, advocates, and supporters from across the globe.

As pointed out by the proposal an international effort to create consensus on the criteria and methods for selecting cases in ME research would create a modern, specific research criteria to aid research efforts.

Research Case Definition Consensus Statement

Internationally, clinical definitions for Myalgic Encephalomyelitis (M.E.) (also known as Enteroviral Encephalomyelitis) or Chronic Fatigue Syndrome (ME/CFS) - un umbrella term for "heterogeneous" fatigue-defined illnesses, in which excludes "Myalgic Encephalomyelitis", have been adopted in many countries, but there is still no consensus around research criteria. 

(Well this is not true as the ICC - is literally the called the International Consenus Criteria for M.E. - even if flawed, its at least attempting to charactize the diagnosis, more specifically and overlaps closer to "Enteroviral Encephalomyelitis" compared to other criterias, and implies an acute onset neurological disease and NOT a heterogeneous fatigue-based illness)

In 2015, the Institute of Medicine in the US developed a clinical case definition for Chronic  Fatigue Syndrome (ME/CFS), but this was never meant to be used for research. 

For decades, research into M.E. (also known as Enteroviral Encephalomyelitis) has been hampered by heterogeneous diagnostic criteria and the inclusion of participants; who may not actually have M.E. (also known as Enteroviral Encephalomyelitis)

This has impacted the validity of many studies and created a risk of harm for patients. 

There is still not an international consensus on a research case definition, or case definitions.

(There is for M.E., its just been ignored)

The core problem is that many case definitions do not require key symptoms such as post-exertional malaise and do not take the severity of the symptoms into account. Further, methods for evaluating cases have been inconsistent. 

(No the larger problem is that M.E. is an acute onset brain and spinal cord infection by an enterovirus, that warrants emergency hospitalization upon onset, medical compassion, medical diagnosis, a specific clinical definition and criteria, specific medical research, and medical care and treatment, and NOT focused on what symptoms are present - thats a syndrome, not a specific neurological disease and untangled from symptom-based CFS criterias or the SEID algorithm, that are not intended for it. The reason it doesn't is because the research and charity sector has been hijacked by people with own funding and monetary (vested) interests concerns, so will bend to the will of governments' incorrect information, even if WRONG and HARMFUL - hoping to receive funding from them - in return. Institutional capture)

The time has come to improve cross-study comparability, and ensure study participants have M.E. (also known as Enteroviral Encephalomyelitis)

We the undersigned believe the time has come to sponsor an international effort to create a consensus on the criteria and methods for selecting cases in research. 

Such a consensus will need to address multiple issues, including those below. 

●        A consistent set of required inclusion criteria in which reflects an acute onset Enteroviral Encephalomyelitis. 

●        A consistent approach to exclusionary conditions. Everything that is not an acute onset M.E. (also known as Enteroviral Encephalomyelitis) requires further investigation. 

●        A consistent approach to characterizing and labeling overall disease severity of cases .^{9,10,11,12,13}

* There are many secondary symptoms that may be experienced by people with M.E. (also known as Enteroviral Encephalomyelitis) including orthostatic intolerance, pain, immune, and gastro-intestinal complaints.

** While clinically a patient can have both M.E. (also known as Enteroviral Encephalomyelitis) and other diagnoses, in research, it’s important to have a consistent approach to exclusions to improve cross-study comparability.

M.E. - International Consensus Criteria (Closest-Symptom Based criteria to "Enteroviral Encephalomyelitis"), meet many of these standards.

Definition Essentials (Byron Hyde's website)

Some of the definition essentials required to accurately diagnose either M.E. (also known as Enteroviral Encephalomyelitis) or "misdiagnosed" CFS, or any chronically ill patients group, include: 

• A working case clinical definition must be short, clear and testable. (e.g. Nightingale Research Foundation Definition, 2007 and 2016 for M.E.)

• Patients and their illness or illnesses must be part of an integrated system. Neither the patients’ patho-physiology nor their illness can be understood without a concise knowledge of their integrated pathophysiological systems.

• A statistically significant group of patients who have M.E. (also known as Enteroviral Encephalomyelitis) and "misdiagnosed" CFS type illnesses must be subjected to a complete personal and family history to map the genetic and historical causes of their illnesses. 

• Accordingly, the patient’s illness can only be understood if a complete total body mapping is performed on all systems and organs. The mammalian and animal bodies are an integrated physiological mechanism and when one major system change occurs, many physiological systems are liable to shift. 

• In the past it has been facile to pose psychiatric diagnoses on M.E. (also known as Enteroviral Encephalomyelitis) and "misdiagnosed" CFS patients since psychiatric diagnoses cannot be subjected to scientific examination. Psychiatrists rarely actually examine patients and almost never do an integrated patho-physiological patient investigation of the patient’s organs and systems. Nor have most psychiatrists been of any help in diagnosing M.E. (also known as Enteroviral Encephalomyelitis) and "misdiagnosed" CFS patients except to the insurance industry. In the more than 70 years since the first major M.E. (also known as Enteroviral Encephalomyelitis) struck the Los Angeles County General Hospital in 1934, no psychiatric treatment has proven significantly effective in treating the M.E. (also known as Enteroviral Encephalomyelitis) and "misdiagnosed" CFS patients and restoring them to health. This is understandable since neither represents a psychiatric disorder. 

• Effective treatment of the M.E. (also known as Enteroviral Encephalomyelitis) and "misdiagnosed" CFS group of patients depends upon precisely defining the organ and system pathologies and learning how to treat these patho-physiological conditions. 

• M.E. (also known as Enteroviral Encephalomyelitis) and the "misdiagnosed" CFS group of illnesses are chronic illnesses. For too long physicians have been considering chronic diseases and chronically ill patients as they would acute short-term illnesses. We believe this is an error and we direct those interested to our chapter on diagnosis. Relatively young chronically ill patients, often do not have a disease process, they often have many disease processes.

Original 1988 Holmes CFS CDC Definition, Meningoencephalitis, Limbic Encephalitis, Rhombencephalitis, Sewage Spill, Abortive Polio, Enterovirus, Myalgic Encephalomyelitis, 1984 Lake Tahoe, Incline Village CFS Outbreak and 1955 Royal Free Hospital M.E. Outbreak

• The 1984-85 Incline Village outbreak involved an acute epidemic, viral-like illness with encephalitic/neurological features, occurring after a documented sewage spill in the Incline Village/Crystal Bay area in 1983. This raises an important enterovirus hypothesis, since enteroviruses are shed in feces, can circulate through sewage and contaminated water, and include viruses capable of causing systemic illness, aseptic meningitis, encephalitis and poliomyelitis; importantly, the published CDC investigation does not report enterovirus testing, instead focusing heavily on Epstein-Barr virus (EBV) and other herpesviruses. Stephen Straus initially investigated EBV as a possible explanation for the epidemic, but EBV was subsequently not substantiated as its primary cause, while the EBV and later HHV-6 abnormalities were interpreted as reactivation rather than proof of the initiating epidemic infection, leaving the original infectious etiology unresolved. Against this background, the CDC’s Holmes working group - including Straus- introduced the 1988 “Chronic Fatigue Syndrome” (CFS) working case definition, a non-etiological research definition and essentially a diagnosis of exclusion, requiring other identifiable causes of chronic fatigue to be excluded rather than identifying the underlying infectious or neurological disease. Notably, the Holmes criteria themselves contained substantial symptom-level overlap with the clinical spectrum of enterovirus infection, including the minor or abortive form of poliomyelitis and meningitic/encephalitic (meningoencephalitis) illness: features included fever or chills, sore throat, painful lymph nodes, muscle weakness, myalgia, headache, arthralgia and neuropsychological complaints, together with physical findings such as low-grade fever, non-exudative pharyngitis and palpable or tender lymph nodes. These observations provide a historical and clinical basis for considering an enteroviral explanation for the unresolved outbreak. 

• The 1988 Holmes CFS definition may therefore overlap symptomatically with the early, minor or “abortive” form of poliomyelitis and with features occurring in meningitic or encephalitic illnesses, but such overlap should not be confused with defining Myalgic Encephalomyelitis (M.E.). The Holmes criteria were constructed as a non-etiological chronic-fatigue research case definition and did not define the neurological illness historically described following the 1955 Royal Free Hospital outbreak. In his 1959 review of the epidemic disease, epidemiologist Sir Donald Acheson considered the clinical picture consistent with an encephalomyelitis, correlating the characteristic signs and symptoms with involvement of the brain and spinal cord, and used the term “myalgic encephalomyelitis” to describe this clinical picture. The Royal Free illness was therefore historically characterised as an epidemic neurological disease with evidence considered compatible with encephalomyelitis - not simply as a syndrome of unexplained chronic fatigue. Consequently, although the Holmes CFS definition may overlap with early abortive poliomyelitis features and (meningitic/encephalitic) meningoencephalits illness, the Holmes definition does not constitute a case definition for the illness described as Royal Free Disease, or Myalgic Encephalomyelitis from a previous outbreak.

Footnotes

¹ Recently, the World ME Alliance, with 24 member organizations across 17 countries, supported the inclusion of PEM as a core symptom. Standing Strong: Global ME Community unified in support of NICE 2021 ME/CFS Guideline. 2023.

Available at: https://worldmealliance.org/2023/08/standing-strong-global-me-community-unified-in-support-of-nice-2021-me-cfs-guideline/

² Kingdon, C, Abken, E, Lacerda, E & Nacul, L.  A proposal for consensus diagnostic criteria for ME/CFS research. Poster presented at the meeting of the International Association of ME/CFS, Stonybrook University, N.Y.  2023

³ Jason, L. A. & Ravichandran, S. An effort to develop a consensus on critical ME/CFS definitional issues. Poster presented at the meeting of the International Association of ME/CFS, Stonybrook University, N.Y.  2023

⁴ Nacul L, Authier FJ, Scheibenbogen C, Lorusso L, Helland IB, Martin JA, Sirbu CA, Mengshoel AM, Polo O, Behrends U, Nielsen H, Grabowski P, Sekulic S, Sepulveda N, Estévez-López F, Zalewski P, Pheby DFH, Castro-Marrero J, Sakkas GK, Capelli E, Brundsdlund I, Cullinan J, Krumina A, Bergquist J, Murovska M, Vermuelen RCW, Lacerda EM. European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe. Medicina (Kaunas). 2021 May 19;57(5):510. doi: 10.3390/medicina57050510.

⁵ See Table 2 in Jason, L.A., Ravichandran, S., Katz, B.Z., Natelson, B.H., & Bonilla, H.F.  Establishing a consensus on ME/CFS exclusionary illnesses.  Fatigue: Biomedicine, Health & Behavior, 2023; 11(1), 1-13.    https://doi.org/10.1080/21641846.2022.2150487

⁶ Nacul L, Kingdon CC, Bowman EW, Curran H, Lacerda EM. Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior, 2017;5(1):1-4. doi: 10.1080/21641846.2017.1273863. PMID: 29250461; PMCID: PMC5730342.

⁷ Sunnquist, M., Lazarus, S., & Jason, L.A.  The development of a short form of the DePaul Symptom Questionnaire. Rehabilitation Psychology, 2019, 64(4), 453–462.  PMCID: PMC6697554   https://doi.org/10.1037/rep0000285

⁸ Cotler, J., Holtzman, C., Dudun, C., & Jason, L.A. A brief questionnaire to assess post-exertional malaise. Diagnostics, 2018, 8, 66. doi:10.3390/diagnostics8030066

⁹ Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011; 270: 327-338.

¹⁰ Bateman L, Bested AC, Bonilla HF, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: essentials of diagnosis and management. Mayo Clinic Proc. 2021;96(11):2861–2878. Available from: https://www.mayoclinicproceedings.org/action/showPdf?pii=S0025-6196%2821%2900513-9#page=10.

¹¹ Cox, D. L., & Findley, L.J. The Management of Chronic Fatigue Syndrome in an Inpatient Setting: Presentation of an Approach and Perceived Outcome. British Journal of Occupational Therapy,  1998, 61(9),  405–09. https://journals.sagepub.com/doi/10.1177/030802269806100907

¹² Conroy, K., Bhatia, S., Islam, M., & Jason, L.A. Homebound versus bedridden status among patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare, 2021, 9(2), 106.  https://doi.org/10.3390/healthcare9020106

¹³ Wiedbusch, E., & Jason, L.A. Comparing operationalized approaches for substantial reduction of functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Archives of Community Medicine, 2022, 4(1), 59-63. PMCID: PMC9168545 https://doi.org/10.36959/547/653

Research: New Study to Harmonise Research Definitions in M.E..and CFS

Understanding M.E. criteria