Hi Rusty (and thanks to Hip for clarifying the full interpretation of 'myel').
Correct me if I'm wrong but wasn't the term myalgic encephalomyelitis first coined following the Royal Free outbreak? From the few original papers I've read I don't recall any physiological/histological evidence to support 'myelitis' in these folks.
That's a good point: how did they know in the 1950s that there was brain and spinal cord inflammation in ME/CFS, so as to be able to call it "myalgic encephalomyelitis"?
In two published studies about the Royal Free Hospital outbreak in London 1955, the authors already described the condition as "encephalomyelitis" (but without using the "myalgic"), so even in this 1955 outbreak, they must have known it involved brain and spinal cord inflammation. The two Royal Free Hospital outbreak papers are these:
Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital, London, in the summer of 1955
An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955
From the second paper cited above, I quoted a text extract below which seems to provide possible physical evidence of brain inflammation: it details a
postmortem brain examination of one of the Royal Free ME/CFS patients who committed suicide using the barbiturate drug Carbrital.
In the brain of this patient they actually found demyelination; however they diagnosed this as the patient having an early stage of multiple sclerosis, in addition to simultaneously having what we now call ME/CFS.
In this brain autopsy, the main abnormality they found, in addition to the typical multiple sclerosis brain lesions, was to quote: "
one section taken from the hypothalamus which showed intense perivascular cuffing."
Perivascular cuffing means the accumulation of lymphocytes or plasma cells in a dense mass around the blood vessel, and this
perivascular cuffing is indicative of inflammation or of an immune reaction.
So this is possible evidence of brain inflammation in ME/CFS, back in the 1950s. Although the authors stated that it is more probable than the intense perivascular cuffing in the hypothalamus represents an unusual reaction associated with multiple sclerosis.
Presumably though there must have been other good indicators of brain and spinal cord inflammation in these Royal Free outbreak patients for this outbreak to be described as encephalomyelitis.
It is interesting that another ME/CFS brain autopsy published in 1994 found what appeared to be coxsackievirus B infection in the
hypothalamus and
brainstem of the patient. So here we see a hypothalamus infection again implicated in ME/CFS. Reference:
here. Full paper
here.
@Marco, from the perspective of sensory gating dysfunction, the brainstem infection is very relevant, since "studies on rats show the brain stem, thalamus, and primary auditory cortex play a role in sensory gating for auditory stimuli." Reference:
here.
Here is the text from the Royal Free Hospital ME/CFS 1955 outbreak study (terms in bold are defined in the glossary below):
"
The second fatality, due to acute “carbrital” poisoning [ie, suicide], occurred in a woman, aged 32, who had the epidemic disease seven months before death, and who had had definite clinical evidence of organic disease of the central nervous system for the last seven months of her life.
In her case it was considered on clinical grounds that she had disseminated sclerosis as well as the epidemic disease. Post-mortem examination revealed small circumscribed grey or yellowish plaques in the white matter of the cerebral hemispheres, mainly paraventricular in distribution. In the brain stem and in the spinal cord, particularly in the cervical segment.
Microscopical examination showed multiple small well or fairly well demarcated areas of demyelination with associated microglial and astrocytic proliferation and a variable degree of gliosis. There was no evidence of primary neuronal damage, and no viral cell-inclusions were seen. Occasional cellular foci composed of lymphocytes and cerebral histiocytes, mainly perivascular in distribution, were present in the leptomeninges overlying the brain, but this was not a marked feature except in one section taken from the hypothalamus which showed intense perivascular cuffing.
The distribution and character of the lesions in the central nervous system, with the exception of the changes in the hypothalamus, were typical of disseminated sclerosis, and a histological diagnosis of disseminated sclerosis in a fairly early phase was made. The lesion in the hypothalamus in this case may represent the of a superadded [ie, additional] viral encephalitis, but such an explanation is conjectural, and it is more probable than the intense perivascular cuffing represents an unusual but not unknown reaction associated with disseminated sclerosis."
Source: page 901,
An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955
Glossary or Medical Terms Used
Epidemic disease = the term the authors use to refer to the ME/CFS outbreak at the Royal Free Hospital.
Gliosis = nonspecific reactive change of glial cells in reactiveesponse to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, microglia, and oligodendrocytes. In its most extreme form, the proliferation associated with gliosis leads to the formation of a glial scar.
Viral cell-inclusions (aka: viral inclusion bodies) = abnormal structures which appear within the cell nucleus, the cytoplasm, or both, during the course of virus multiplication.
Disseminated sclerosis = another name for multiple sclerosis.
Histiocyte = a tissue macrophage or a dendritic cell.
Perivascular cuffing = the accumulation of lymphocytes or plasma cells in a dense mass around the vessel. An indication of inflammation or of an immune reaction.
Plasma cells (aka: plasma B cells, plasmocytes, and effector B cells) = white blood cells that secrete large volumes of antibodies.
