THE "MYALGIC ENCEPHALOMYELITIS" (also known as "Enteroviral Encephalomyelitis") and "non-cytolytic persistent enterovirus" DILEMMA

THE "MYALGIC ENCEPHALOMYELITIS" (also known as "Enteroviral Encephalomyelitis") DILEMMA

By Dr Irving Spurr — John Richardson Research Group

"Epidemic" Myalgic Encephalomyelitis (M.E.), also known as Enteroviral Encephalomyelitis, is recognised by the World Health Organization (WHO) as a neurological disease. Unfortunately, this recognition continues to be thwarted by influential psychiatric "roadblocks" that obstruct pure, unbiased M.E. research.

This detrimental situation has been compounded by [a] the lack of viral surveillance ["Oh! It's just another virus." - "Yes, but which one?"] and [b] the establishment of psychiatric-led CFS clinics.

No one benefits from this situation, least of all the patients.

HISTORICAL FACTS

The term Benign Myalgic Encephalomyelitis (M.E.), associated with "enteroviral" infection, is documented in the post-World War II medical literature. Far from benign, the illness is also far removed from current perceptions.

Enteroviruses: Most infections are subclinical or cause only minor illness, with relatively few progressing to serious disease.

Nevertheless, "enteroviruses" are a major cause of "aseptic meningitis", "limbic encephalitis", "rhombencephalitis" (brainstem encephalitis), "myelitis" and "poliomyelitis-like syndrome", "acute flaccid myelitis", "myositis", "pericarditis", "myocarditis", "pancreatitis" and "thyroiditis".

To the astute clinical mind, these are recognised manifestations of enteroviral infection. It is also unsurprising that persistent infections during pregnancy may contribute to foetal abnormalities affecting the brain and heart.

Furthermore, what genetic and environmental factors influence host susceptibility to such serious illnesses?

WHAT HAPPENS?

Why does the host's immune system fail to clear enteroviruses from infected cells? Why are infected cells neither lysed nor instructed to undergo apoptosis [programmed cell death]?

In serious multi-organ illnesses, such as those associated with Original CFS or M.E. (also known as Enteroviral Encephalomyelitis), one possible explanation immediately comes to mind.

We, as viral hosts, strive to survive, albeit at a cost.

What, then, are the mechanisms of self-preservation? Which inhibitory factors influence the activity of Natural Killer (NK) Cells and Cytotoxic T-Cells? Could the explanation be as simple as T-cell exhaustion?

How do enteroviruses, at least in part, evade our immune defences and coexist with our cellular proteins?

They appear capable of doing so, but potentially at the expense of cellular and organ function:

A sick cell → A sick organ → A sick host.

Alas, there are more questions than answers.

That is why this disease should be "clearly defined" and "distinguished" from the "comedy sink" of symptom-based, non-diagnostic CFS criteria and the SEID ("ME/CFS") algorithm, both of which classify illnesses whose underlying causes remain "unknown".

THE FUTURE

Viral–host coexistence is beneficial only when the host can maintain a near-normal quality of life, as may occur with certain latent herpesvirus infections (e.g., Epstein–Barr virus and varicella-zoster virus).

However, these latent infections differ fundamentally from persistently replicating enteroviral infections, which may be associated with a substantially reduced quality of life.

This provides further justification for clearly defining, treating and ultimately preventing the illness.

RESEARCH SHOULD INVOLVE:

[a] Correctly selected patients.

The late Dr John Richardson developed the John Richardson Research Group (JRRG) M.E. Score Chart, which he used for patient selection and clinical assessment.

Supporting investigations described by the JRRG include:

• Enterovirus VP1 antigen testing in blood.
• Buspirone challenge testing to investigate hypothalamic dysfunction [Demitrack, 1991; Bakheit, 1992; J. Richardson, Journal of Chronic Fatigue Syndrome].
• SPECT brain perfusion scans [Duval, De Costa and J. Richardson].

[b] Thorough clinical examination.

Patients should undergo a comprehensive clinical examination by a competent physician, incorporating the investigations described above.

[c] Investigation of persistent infection and immune responses.

Once viral–host coexistence has become established and IgM antibodies have disappeared, identifying the responsible virus, its genome or its molecular footprint within M.E.-affected tissues may become extremely difficult.

However, advances in immunobiology may provide new opportunities to establish causality and develop effective treatments.

Recent developments in understanding T-memory cell morphology and function are particularly promising.

Expansion of central memory T-cells (TCM) within the inguinal lymph nodes, together with measurements of cytokine and chemokine concentrations following a cognate viral challenge, could potentially contribute to the development of a viable diagnostic test.

TREATMENT

The John Richardson Research Group's clinic has continued to combine carefully paced activity with immune modulation, including intramuscular immunoglobulin (IgG), with the aim of reducing patients' JRRG scores over time.

Antiviral agents available at the time had not demonstrated sufficient effectiveness.

However, identifying the viral "switch" that enables enteroviruses to hijack cellular protein production could provide a potential therapeutic target and, ultimately, an opportunity to develop more effective treatments.

PREVENTION

Vaccination

Considering the mortality and morbidity associated with enteroviral infections throughout life, the development of effective enterovirus vaccines is strongly justified.

Such vaccines could potentially reduce deaths associated with myocarditis, dilated cardiomyopathy and Myalgic Encephalomyelitis / Aseptic Meningitis (also known as Meningo-encephalomyelitis).

They might also reduce the incidence of certain enterovirus-associated complications, including Primary Thyroid Failure and Type 1 Diabetes, where a causal relationship can be established.

Ultimately, effective prevention of the enteroviral infections implicated in M.E. could substantially reduce the burden of this illness.

THE BENEFITS OF IMMUNOGLOBULIN

Immunoglobulin G (IgG) may exert its therapeutic effects through a multistep immunomodulatory mechanism.

Following administration, IgG may form immune complexes within the patient. These immune complexes can subsequently interact with activating Fc receptors on dendritic cells, potentially mediating anti-inflammatory effects.

Such mechanisms may help reduce the severity of inflammatory responses and influence the development or progression of autoimmune conditions, including Primary Thyroid Failure and Type 1 Diabetes.

IgG may also interact with Fc receptors on immune cells, including macrophages, thereby modifying their activation and regulating phagocytosis.

Furthermore, IgG may influence immune responses through interactions with membrane receptors on T-cells, B-cells and monocytes involved in autoreactivity and the induction of immunological tolerance to self-antigens.

Research has also suggested that IgG treatment of activated T-cells may reduce their capacity to interact with microglia.

In T-cell–microglia co-culture experiments, IgG treatment has been associated with reduced concentrations of tumour necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10).

These findings contribute to our understanding of how immunoglobulin therapy may influence inflammation within the central nervous system, particularly in autoimmune and inflammatory neurological disorders.

IN CONCLUSION

Sadly, rather than achieving greater clarity, we continue to muddy the waters surrounding disease causation.

Without appropriate research, accurate disease classification, effective prevention and targeted treatment, future generations may remain condemned to the continuing misery of M.E.