Considerations in establishing a post-mortem brain and tissue bank for the study of ME/CFS: a proposed protocol, 2014, Nacul et al

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https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-7-370
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Luis Nacul,
Dominic G O’Donovan,
Eliana M Lacerda,
Djordje Gveric,
Kirstin Goldring,
Alison Hall,
Erinna Bowman &
Derek Pheby

Abstract
Background
Our aim, having previously investigated through a qualitative study involving extensive discussions with experts and patients the issues involved in establishing and maintaining a disease specific brain and tissue bank for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol for a UK ME/CFS repository of high quality human tissue from well characterised subjects with ME/CFS and controls suitable for a broad range of research applications. This would involve a specific donor program coupled with rapid tissue collection and processing, supplemented by comprehensive prospectively collected clinical, laboratory and self-assessment data from cases and controls.

Findings
We reviewed the operations of existing tissue banks from published literature and from their internal protocols and standard operating procedures (SOPs). On this basis, we developed the protocol presented here, which was designed to meet high technical and ethical standards and legal requirements and was based on recommendations of the MRC UK Brain Banks Network. The facility would be most efficient and cost-effective if incorporated into an existing tissue bank. Tissue collection would be rapid and follow robust protocols to ensure preservation sufficient for a wide range of research uses. A central tissue bank would have resources both for wide-scale donor recruitment and rapid response to donor death for prompt harvesting and processing of tissue.

Conclusion
An ME/CFS brain and tissue bank could be established using this protocol. Success would depend on careful consideration of logistic, technical, legal and ethical issues, continuous consultation with patients and the donor population, and a sustainable model of funding ideally involving research councils, health services, and patient charities. This initiative could revolutionise the understanding of this still poorly-understood disease and enhance development of diagnostic biomarkers and treatments.

Other threads on tissue donation
UK brain banks that accept ME/CFS donors
Exploring the feasibility of establishing a disease-specific post-mortem tissue bank in the UK: a case study in ME/CFS, 2010, Lacerda et al
Open ME Association: The UK ME/CFS Post Mortem Tissue Bank and Tissue Donation
Post mortem tissue donation and autopsies (Members only)
 
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The poor understanding and lack of consensus on the causes and pathophysiological mechanisms involved in ME/CFS and the lack of specific animal models suggest its suitability for study through pathology. However, and rather surprisingly, only a very small number of (ad hoc) pathological studies have been conducted in people who have died with ME/CFS. A few but not all autopsies conducted have shown nervous system abnormalities, including inflammation in the dorsal root ganglia [2] and evidence of viral encephalitis [20, 21]. These do not, however, constitute sufficient evidence to confirm the role of the central or peripheral nervous system in its aetiology or pathogenesis.
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The CFS Peer Reviews for the Centers for Disease Control (CDC) in the US recommended the establishment of a CFS patient brain bank for “neuropathological analysis for tissues not available by other mechanisms” [24]. Nevertheless no action from the CDC or others has yet resulted from that recommendation, and no initiatives have been reported towards systematically addressing the use of pathology for the study of ME/CFS. The only related initiative has come from the Sun Health Research Institute in Sun City, Arizona, US [25], which reported the creation in 1997 of the first and still incipient tissue bank for the study of fibromyalgia, a condition closely related to ME/CFS.
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Our conclusions were that this would best be met by situating the ME/CFS Tissue Bank within an operational tissue bank, thus benefiting from existing infrastructure and experience whilst optimizing the use of resources....The Addenbrooke’s Hospital Brain and Tissue Bank in Cambridge is very well placed for this purpose due to its long-term experience in tissue banking and previous involvement in ME/CFS research, and is intended as the initial site for the ME/CFS Tissue Bank.
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The ME Biobank - live blood only: https://meassociation.org.uk/research/research-projects/uk-mecfs-biobank/

Dealing with cadavers is legal and cost intensive, and needs prior engagement with the deceased's relatives and/or persons with power of attorney, these are not small hurdles to overcome. There is though a bigger problem: Who are the PwME that are dying ?

(broken record - epidemiology !!!) but if one doesn't know the character of a patient population and not have a clear picture of the pattern of disease progress over a lifetime it is not possible to make informed sampling of donated cadavers or cadaver tissue. If a patient population is, despite its disease status, relatively long lived then even where there is a high rate of donation there are inevitable confounders of multiple comorbidities and senescence which may not be easily addressed even where there is adequate control matching.

For cadaver sampling the ideal patient population is one with a high percentage of young males who ride motorcycles and engage in extreme sports - the combination of exposure to danger and risky behaviour provides a ready supply of cadavers which have few health confounds; compare that to the average 80 year old who (in the UK) will have a decades long history of being overweight and sedentary behaviour, having high blood pressure, a 50/50 chance of at least one cancer episode, and an 18% of having dementia.

The issue of confound isn't simply to identify a difference between ME/CFS cadavers and non ME/CFS cadavers, but the whole question of what the difference means at different ages at death - finding the presence of an endemic pathogen in the body of an 80 year old with ME/CFS may mean something wholly different from finding it in an 18 year old.
 
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BrightCandle said:
Its made even worse when the NHS actually ends up killing a young ME/CFS patient with negligence that it then goes into cover up mode, does a dreadful autopsy where it can't explain cause of death and just moves on as if nothing happens. Its killing people with negligence a lot, multiple times a year, which is more than enough bodies to investigate but because the NHS doesn't accept the condition its unable to even do that. The issue isn't even the age of those dying, its that they don't accept the deaths they do have were from the disease the patient says they had or that an expert outside the NHS had diagnosed them with. The system is designed to fail to find the cause of ME/CFS.
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Coroner and/or Medical autopsy/postmortem are different from research, they are mostly organ specific and are looking for known pathologies which are likely to have caused a specific death. People with ME/CFS may die from anything that would cause death in any other person and without far greater understanding of the pathology of ME/CFS it would be very difficult to work backwards from a death to understand the role that ME/CFS may play.

There has been at least one coroner verdict in the UK that attributed death to ME/CFS but there was no specified pathology that explained what underlying disease process of ME/CFS led to the death, so the verdict was bit circular from a pathology perspective. And it's important to acknowledge that not every death is easily explicable, death is rarely a simple process and multiple organs may be involved and autopsies are mostly about finding a headline cause.

I can't see the NHS putting resources into investigating the deaths of PwME without far greater evidence of direct and singular lethality. The limited data that there is on ME/CFS points to heterogenaity between patients and multiple mis/dys-functions in individuals without any single suspect showing up.
 
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