Iatrogenic cerebral amyloid angiopathy
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.
Evidence for Aβ transmission in animal models has existed for many years.
The existence of Aβ proteopathic seeds within cadaveric material (as has been shown in historical samples of cadaveric human growth hormone and autopsy dura samples) or on neurosurgical instruments (acquired after initial use on patients with Aβ disease with inadequate decontamination afterwards) could explain transmission of Aβ pathology between people. Acquired forms of diseases caused by the prion protein (including iatrogenic CJD, variant CJD and Kuru) are characterised by lengthy incubation periods (up to several decades)
Iatrogenic Aβ transmission appears to have a similarly long latency between exposure and clinical presentation. Experimental work suggests that this is because prions propagate in a new host in two distinct phases: an initial clinically silent phase, characterised by an exponential increase in infectivity until saturation (ie, when the concentration of prions reaches a maximal level) and a second plateau phase where prion levels remain relatively constant during which time toxicity (neurodegeneration) and subsequent clinical deterioration occur. Future work on the kinetics of Aβ propagation is needed to explore whether similar mechanisms underlie the long latency observed in iatrogenic CAA
Source: Banerjee G, Samra K, Adams ME, et al Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon Journal of Neurology, Neurosurgery & Psychiatry 2022;93:693-700