Evidence of iatrogenic beta-amyloid transmission was identified in two patients who developed early-onset cerebral amyloid angiopathy decades after undergoing pediatric cardiac surgery.
The findings suggest that the use of cadaveric dura mater patches in cardiac surgery seeded amyloid pathology, leading to neurovascular complications 40 years later, report Jean-Baptiste Brunet de Courceau, MD, MSc, of the University of Versailles Saint-Quentin-en-Yvelines in France, and colleagues.
“We hypothesize that amyloid-beta seeds present in the cadaveric dura mater move directly into the bloodstream or induce the spread of plasmatic amyloid-beta, ultimately crossing the blood-brain barrier and causing iatrogenic cerebral amyloid angiopathy,” wrote Brunet de Courso and co-authors. neurology.
In cerebral amyloid angiopathy, amyloid protein deposits in the walls of the brain’s arteries, increasing the risk of hemorrhagic stroke and cognitive decline. Cerebral amyloid angiopathy usually occurs in older adults and is related to dementia.
The two patients in the case report – a 43-year-old man and a 42-year-old woman – both had symptomatic lobar hematomas and imaging features consistent with probable cerebral amyloid angiopathy, Brunet de Courso and colleagues reported. Amyloid PET imaging showed diffuse brain amyloidosis with abnormal cerebrospinal fluid amyloid levels at analysis.
Clinical presentations occurred approximately 40 years after surgery for transposition of the great vessels, a rare congenital heart defect in which the aorta and pulmonary artery are replaced. The use of cadaveric dura mater during surgery was confirmed in one case and considered probable in another. Genetic testing for hereditary causes of cerebral amyloid angiopathy was negative, and both patients were APOE3 homozygous
Iatrogenic transmission of amyloid pathology has been reported previously, particularly after neurosurgical procedures involving cadaveric dura mater grafts.
“Our cases extend this concept by suggesting that this type of transmission may also occur in other surgical settings,” said study co-author Sandrine Deltour, MD, PhD, of Versailles Saint-Quentin-en-Yvelines University.
“This is the first well-documented report of iatrogenic cerebral amyloid angiopathy associated with cardiac surgery,” he said. Medpage Today.
“These cases provide evidence that cerebral amyloid angiopathy may be acquired rather than entirely sporadic or genetic,” Deltour said. “They support the hypothesis of long-term iatrogenic transmission of amyloid pathology after exposure to cadaveric dura mater grafts.”
Human-to-human transmission of amyloid-beta pathology was first reported in 2015 in patients who died of iatrogenic Creutzfeldt–Jakob disease after cadaveric human growth hormone treatment.
Gargi Banerjee, MD, and David Waring, PhD, of University College London, said the first human report of early-onset cerebral amyloid angiopathy in patients who had childhood medical procedures using cadaveric dura mater suggests that amyloid-beta transmission may result in disease later in life.
“There have been several subsequent case studies, with emerging evidence that the clinical phenotype has features atypical for sporadic cerebral amyloid angiopathy (for example, hemorrhagic lesions in non-lobar locations and imaging changes suggestive of vessel leakage or inflammation),” Banerjee and Waring write in an article. with editorial.
Editorial Experts said that although acquired prion diseases are rare, the concept of protein misfolding and propagation may extend beyond classic prion disorders.
“The broader biological implications are enormous; the existence of iatrogenic cerebral amyloid angiopathy suggests that prions are not necessarily specific or exclusive to disorders associated with prion proteins and instead prion biology has direct clinical relevance to other disorders involving misfolded protein aggregation,” they observed.
“In the case of amyloid-beta, we are in the dark: what exactly is arising from these contaminated grafts, where does it go and spread, and how does it ultimately reach the brain and leptomeninges? Given the reports of iatrogenic Alzheimer’s disease after treatment with cadaveric human growth hormone and the possibility of amyloid-beta transmission through blood transfusion, these questions have clinical and public health consequences and should be considered among the research priorities. Should be recognized as such,” Banerjee said and Wareing wrote.
Although cadaveric dura and cadaveric human growth hormone are no longer used, the potential risks of amyloid-beta transmission through blood transfusion or organ transplantation require further study, they suggested.
Deltour said that iatrogenic cerebral amyloid angiopathy is challenging to diagnose. “What is particularly striking is the very long latency between the surgical procedure and clinical presentation, often lasting several decades,” he said.
“This highlights that patients can present with intracerebral hemorrhage or cognitive symptoms much later in life, and this aetiology can be easily overlooked,” Deltour explained. “Our observations emphasize the need for physicians to carefully examine remote cardiac surgical history, especially in relatively young patients with imaging features suggestive of cerebral amyloid angiopathy.”
