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Pikija et al.
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which can result in intracerebral or sulcal subarachnoid
hemorrhage, cognitive impairment, transient focal neurological
episodes, or seizures.4 The management and prognosis
of iCAA are not well understood.
The Queen Square diagnostic criteria (QSC) for iCAA
allow a more consistent diagnosis of probable and possible
iCAA.4 Using standardized criteria is crucial for future
case sampling, research, and planning appropriate health
interventions to recognize and mitigate the impact of
iCAA. Since the QSC publication, 48 cases of iCAA had
been reported overall, with patients having been exposed
to neurosurgery or cadaveric dura at a mean age of 6 years.
Symptoms typically manifest after a mean latency period
of 35 years after exposure.4-7 Previous studies on iCAA
have been limited by a small number of published cases,
mostly from single-center experiences, and a lack of
larger quantitative studies. In addition, there has been no
previous international collaboration in investigating
iCAA. To better understand the spectrum of iCAA, we
aimed to build a large multinational cohort of patients
with iCAA.
In particular, we planned to investigate potential factors
associated with the wide range of observed latency. We also
explored whether older age at exposure and presentation
aligned with current diagnostic criteria. Furthermore, a particular
focus was given to cerebrospinal fluid (CSF) biomarkers.
Reduced CSF Aβ-42 and Aβ-40 form a component
of the broader iCAA criteria as one of the pieces of evidence
of Aβ accumulation in the central nervous system
(CNS). Based on what has been established in sporadic and
hereditary CAA disease,8 CSF analysis may provide an
opportunity to assess the severity or even recognize iCAA
at an earlier stage. Therefore, we examined the relationship
between CSF biomarker levels, latency, and age at the onset
of symptoms.
Methods
Study design and participants
This study is a multicentre retrospective observational
investigation of patients with iatrogenic iCAA, including
subsequent individual patient data analysis of previously
reported cases. Data were collected from nine centers in five
participating countries (Austria, Croatia, Italy, Slovenia, and
Spain) between August 2020 and June 2023. Neurovascular
specialists in tertiary care centers were asked to report cases
coming to their attention of suspected iCAA which fulfilled
the criteria for CAA (Boston criteria 1.5/2.0 or Edinburgh
CT criteria for probable CAA, regardless of age limits).9,10
Patient data were obtained from extensive retrospective
chart review (including electronic and written information)
that had been collected in each center, with searches extending
to the most remote records available as of June 2023.
Classification
Patients were eligible for inclusion if they met the QSC for
iCAA. According to the QSC, a diagnosis of probable
iCAA required a history of potential exposure, clinical and
radiological features consistent with CAA, evidence of Aβ
deposition in the CNS, and exclusion of genetic causes.
For possible iCAA, patients had to have symptom onset
before the age of 55, a history of potential exposure, and
clinical and radiological features consistent with CAA
(Supplemental Table 1).
Data collection
In each center, clinical data were collected from patients
who were screened for this study. This included a detailed
history of exposure to potentially transmissible agents
1Department of Neurology, Christian Doppler University Hospital, Salzburg, Austria
2Neuroscience Institute, Christian Doppler University Hospital, Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
3Department of Vascular Neurology, Faculty of Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
4Department of Neurology, Zagreb School of Medicine, University Hospital Center, Zagreb, Croatia
5Department of Neurology, Medical University of Graz, Graz, Austria
6Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria
7Department of Neurology, Krankenhaus der Barmherzigen Brüder, Eisenstadt, Austria
8Department of Neurology, Alessandro Manzoni Hospital, Lecco, Italy
9Division of Neurology, University Medical Centre Maribor, Maribor, Slovenia
10Department of Vascular Neurology, University Medical Centre Innsbruck, Innsbruck, Austria
11Karl Landsteiner Institute for Neurorehabilitation and Space Neurology, Salzburg, Austria
12Department of Public Health, Health Services Research, and Health Technology Assessment, Hall in Tirol, Austria
13Department of Pathology, Paracelsus Medical University, Salzburg, Austria
14Department of Neurology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
15Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
16Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
17Stroke Unit, Donostia University Hospital, Neurovascular Diseases, Biodonostia Institute, San Sebastián, Spain
*Shared authorship.
Corresponding author:
Slaven Pikija, Department of Neurology, Christian Doppler University Hospital, Ignaz-Harrer Straße 79, Salzburg 5020, Austria.
Email: s.pikija@salk.at
International Journal of Stroke, 19(3)
WSO - March 2024

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