Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature

Abstract

Background: The transmission of amyloid β (Aβ) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. Aims: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. Methods: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. Results: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4–18, range = 0–26 years) years. The median symptom latency was 39 years (IQR = 34–41, range = 28–49). The median age at symptom onset was 49 years (IQR = 43–55, range = 32–70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. Conclusions: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

Acquired cerebral amyloid angiopathy: more questions than answers

“…Transmission of exogenous amyloid in humans was initially observed in association with iatrogenic Creutzfeldt-Jakob disease [3], and only later also in the absence of it [2]. To date, many individual cases and some case series of iatrogenic CAA have been reported, mostly consisting of patients with childhood neurosurgery and occurrence of symptomatic CAA after a latency period of several decades [4,5].…”

“…Transmission of exogenous amyloid in humans was initially observed in association with iatrogenic Creutzfeldt–Jakob disease [3], and only later also in the absence of it [2]. To date, many individual cases and some case series of iatrogenic CAA have been reported, mostly consisting of patients with childhood neurosurgery and occurrence of symptomatic CAA after a latency period of several decades [4, 5]. The main described sources for transmission of pathological Aβ were human cadaveric‐derived lyophilized dura derivates used as patch and embolization material in neurosurgical procedures, the uses of which had stopped in the late 1980s due to the recognized association of those products with iatrogenic Creutzfeldt–Jakob disease.…”

Recurrent Intracerebral Haematomas Due to Amyloid Angyopathy after Lyodura Transplantation in Childhood

“…CAA is mostly a sporadic disease of the elderly. However, occasionally, it does occur in younger patients due to specific genetic mutations of Aβ such as APP mutations or duplications and PSEN1 or PSEN2 mutations [ 4 ]; it can also be associated with inflammation, significant traumatic brain injury (TBI) [ 5 ] and neurosurgery in childhood [ 3 , 4 ]. A review of the literature suggests that a history of significant traumatic brain injury (TBI), predominantly in young male patients, may be associated with CAA [ 4 , 5 ].…”

“…Edinburgh criteria with computed tomography (CT) head scans [ 6 ] and Boston criteria with magnetic resonance imaging (MRI) head scans [ 7 ] are used. Reduced levels of Aβ, particularly Aβ-42 and ratio Aβ-42/Aβ-40, high values of p-Tau and Tau protein in the cerebrospinal (CSF) fluid, and amyloid positron emission tomography (PET) imaging have also been of a relevant diagnostic value [ 3 , 4 ].…”

“…As already mentioned in the last few years, iatrogenic CAA (iCAA), which has similarities to prion diseases, has been recognized [ 4 , 8 ]. The transmission of Aβ during neurosurgery with the use of a cadaveric material (like cadaveric dura mater or dura of uncertain type, human cadaveric pituitary-derived growth hormone and possibly even surgical instrument) in the central nervous system (CNS) can occur in childhood.…”