Cerebrovascular disease
Review
Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon
Gargi Banerjee1, Kiran Samra2, Matthew E Adams3, Zane Jaunmuktane4,5, Adrian Robert Parry-Jones6,7, Joan Grieve8, Ahmed K Toma8, Simon F Farmer9, Richard Sylvester9, Henry Houlden5, Peter Rudge1, Simon Mead1, Sebastian Brandner1,2,4, Jonathan M Schott2, John Collinge1, David J Werring10
Correspondence to Dr Gargi Banerjee, MRC Prion Unit at UCL, Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London W1W 7FF, UK; g.banerjee@ucl.ac.uk
Abstract
In the last 6 years, following the first pathological description of presumed amyloid-beta (Aβ) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)—attributed to the transmission of Aβ seeds—have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA.
snip...
Questions remain about potential exposures and strategies to prevent further cases. The use of cadaveric human materials is restricted in most countries given the risk of iatrogenic CJD; it is difficult to know exactly how many people have been exposed due to variations in central record keeping. Prions can be transmitted via contaminated neurosurgical instruments and blood transfusions, and iatrogenic cases of CJD have been reported in association with both of these exposures.29 Our review identified 12 cases of iatrogenic CAA following neurosurgical procedures without exposure to cadaveric material, although proper ascertainment of this via historical records can be challenging. There is evidence from transgenic mice that Aβ can be transmitted via steel wires, and that transmission can be prevented by plasma sterilisation, but not boiling.14 There are no reported cases of iatrogenic CAA associated with blood transfusions in humans and epidemiological data to date do not support this,29 but there are experimental data suggesting that Aβ transmission can occur via this route.30 Large epidemiological studies are needed to fully evaluate the risk of Aβ transmission via contaminated instruments (MS1);29 this will inform future decision making regarding appropriate instrument sterilisation that prevents Aβ transmission, methods which also require further investigation.
Alternative explanations for the presence of early onset CAA in these and similar patients have been proposed, most notably the potential impact of traumatic brain injury (TBI).31–33 Aβ rapidly accumulates in the acute phase following TBI,34 35 perhaps due to disruption of the blood-brain barrier,36 37 and then usually clears over a period of days.38 39 Disentangling the role of TBI is challenging, as the injuries sustained in reported cases might have warranted neurosurgical intervention (either with or without cadaveric material); certainly the interval between brain injury and clinical presentation with symptomatic CAA would be in keeping with the latency expected for iatrogenic transmission of Aβ. These reports do not mention whether neurosurgical procedures were needed, and it is not clear whether this is because historical information regarding this is lacking, or whether they truly did not take place. Moreover, not all patients with evidence of early onset CAA have a preceding history of TBI, including those exposed to cadaveric dura mater via embolisation procedures (included two of the cases in this report, in addition to two others7 8) or cardiac procedures,40 and those who received cadaveric human growth hormone as children;6 these cadaveric materials are all well recognised as vehicles for prion protein transmission in the context of CJD.41–43 In view of these points, and the robust experimental evidence for Aβ transmission, it is our opinion that mechanism for early onset CAA in TBI is likely iatrogenic protein transmission, as in our cases, and that further retrospective interrogation of historical medical records may help to further clarify this.
Clinical details for the three cases reported here further expand the spectrum of presenting features for iatrogenic CAA. Cases have now been recognised worldwide, and it is likely that as more are described and published, our understanding of this unusual form of CAA will continue to expand. Confirming the means by which Aβ transmission can occur will have important public health implications for preventing future cases. We advise clinicians to remain vigilant for an iatrogenic cause when seeing patients with an early onset form of CAA, by specifically enquiring about previous medical procedures where Aβ transmission could have taken place.
snip...see full text;
Alzheimer's disease, iatrogenic transmission, what if?
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ? Posted by flounder on 05 Nov 2014 at 21:27 GMT Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
Conclusions
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
IN CONFIDENCE
5 NOVEMBER 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication.
There are also results to be made available shortly
(1) concerning a farmer with CJD who had BSE animals,
(2) on the possible transmissibility of Alzheimer’s and
(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]
re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)
Singeltary Comment at very bottom of this Nature publishing;
re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.
First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.
Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.
where have we all heard this before? it's been well documented via the BSE Inquiry. have they not learned a lesson from the last time?
we have seen this time and time again in England (and other Country's) with the BSE mad cow TSE Prion debacle.
That 'anonymous' Lancet editorial was disgraceful. The editor, Dick Horton is not a scientist.
The pituitary cadavers were very likely elderly and among them some were on their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients ?
who got pooled extracts injected from thousands of cadavers ? were 100% certain to have been injected with both seeds. No surprise that they got both diseases going after thirty year incubations.
That the UK has a "system in place to assist science journalists" to squash embargoed science reports they find 'alarming' is pathetic.
Sounds like the journalists had it right in the first place: 'Alzheimer's may be a transmissible infection' in The Independent to 'You can catch Alzheimer's' in The Daily Mirror or 'Alzheimer's bombshell' in The Daily Express
if not for the journalist, the layperson would not know about these important findings.
where would we be today with sound science, from where we were 30 years ago, if not for the cloak of secrecy and save the industry at all cost mentality?
when you have a peer review system for science, from which a government constantly circumvents, then you have a problem with science, and humans die.
to date, as far as documented body bag count, with all TSE prion named to date, that count is still relatively low (one was too many in my case, Mom hvCJD), however that changes drastically once the TSE Prion link is made with Alzheimer's, the price of poker goes up drastically.
so, who makes that final decision, and how many more decades do we have to wait?
the iatrogenic mode of transmission of TSE prion, the many routes there from, load factor, threshold from said load factor to sub-clinical disease, to clinical disease, to death, much time is there to spread a TSE Prion to anywhere, but whom, by whom, and when, do we make that final decision to do something about it globally? how many documented body bags does it take? how many more decades do we wait? how many names can we make up for one disease, TSE prion?
Professor Collinge et al, and others, have had troubles in the past with the Government meddling in scientific findings, that might in some way involve industry, never mind human and or animal health.
FOR any government to continue to circumvent science for monetary gain, fear factor, or any reason, shame, shame on you.
in my opinion, it's one of the reasons we are at where we are at to date, with regards to the TSE Prion disease science i.e. money, industry, politics, then comes science, in that order.
greed, corporate, lobbyist there from, and government, must be removed from the peer review process of sound science, it's bad enough having them in the pharmaceutical aspect of healthcare policy making, in my opinion.
my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimer's of some type (no autopsy?). just made a promise, never forget, and never let them forget, before I do.
I kindly wish to remind the public of the past, and a possible future we all hopes never happens again. ...
[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimer's and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]
Singeltary Comment at very bottom of this Nature publishing;
THURSDAY, FEBRUARY 7, 2019
In Alzheimer's Mice, Decades-Old Human Cadaveric Pituitary Growth Hormone Samples Can Transmit and Seed Amyloid-Beta Pathology
Friday, January 29, 2016
Synucleinopathies: Past, Present and Future, iatrogenic, what if?
Friday, February 4, 2022
Different α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy, iatrogenic transmission, what if?
THURSDAY, FEBRUARY 15, 2018
Iatrogenic Creutzfeldt-Jakob disease with Amyloid-β pathology: an international study
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???
Greetings Friends, Neighbors, and Colleagues,
Thursday, July 29, 2021
TSE PRION OCCUPATIONAL EXPOSURE VIA ANIMAL OR HUMAN, iatrogenic transmission, nvCJD or sCJD, what if?
TUESDAY, FEBRUARY 22, 2022
Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model
Terry S. Singeltary Sr.
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