Iatrogenic Cerebral Amyloid Angiopathy Post Neurosurgery: Frequency, Clinical Profile, Radiological Features, and Outcome

Abstract

Background: Prion-like transmission of amyloid-ß through cadaveric dura, decades after neurosurgical procedures, has been hypothesized as an iatrogenic cause of cerebral amyloid angiopathy (CAA). We investigated new and previously described patients to assess the clinical profile, radiological features, and outcome of this presumed iatrogenic CAA-subtype (iCAA).

Methods: Patients were collected from our prospective lobar hemorrhage and CAA database (n=251) with patients presenting to our hospital between 2008 and 2022. In addition, we identified patients with iCAA from 2 other Dutch CAA-expertise hospitals and performed a systematic literature-search for previously described patients. We classified patients according to the previously proposed diagnostic criteria for iCAA, assessed clinical and radiological disease features, and calculated intracerebral hemorrhage (ICH)-recurrence rates. We evaluated the spatial colocalization of cadaveric dura placement and CAA-associated magnetic resonance imaging markers.

Results: We included 49 patients (74% men, mean age 43 years [range, 27-84]); 15 from our database (6% [95% CI, 3%-10%]; 45% of patients <55 years), 3 from the 2 other CAA-expertise hospitals, and 31 from the literature. We classified 43% (n=21; 1 newly identified patient) as probable and 57% (n=28) as possible iCAA. Patients presented with lobar ICH (57%), transient focal neurological episodes (12%), or seizures (8%). ICH-recurrence rate in the new patients (16/100 person-years [95% CI, 7-32], median follow-up 18 months) was lower than in the previously described patients (77/100 person-years [95% CI, 59-99], median follow-up 18 months). One patient had a 10 year interlude without ICH-recurrence. We identified no clear spatial relationship between dura placement and CAA-associated magnetic resonance imaging markers. During follow-up (median, 18 months), 20% of the patients developed transient focal neurological episodes and 20% cognitively declined.

Conclusions: iCAA seems common in patients presenting with nonhereditary CAA under the age of 55. Clinical and radiological features are comparable with sCAA. After diagnosis, multiple ICH-recurrences but also long symptom-free intervals can occur. Harmonized registries are necessary to identify and understand this potentially underrecognized CAA-subtype.

Keywords: amyloid; cerebral amyloid angiopathy; cerebral hemorrhage; human growth hormone; magnetic resonance imaging; neurosurgery; prions.

Figure 1.

Flowchart of patient identification, classification, and available disease course data. CAA indicates cerebral amyloid angiopathy; iCAA, iatrogenic CAA; LUMC, Leiden University Medical Center; MRI, magnetic resonance imaging; RUMC, Radboud University Medical Center; and UMCU, University Medical Center Utrecht.

Figure 2.

Magnetic resonance imaging (MRI) findings and follow-up of one patient with possible iatrogenic cerebral amyloid angiopathy (CAA). Forty-four-year-old man, with prior history of neurosurgery (1976) for an encephalocele with hydrocephalus, with confirmed use of Lyodura in the right frontal lobe, presenting 44 y later with acute aphasia due to a lobar intracerebral hemorrhage (ICH; A; fluid-attenuated inversion recovery imaging [FLAIR]; blue arrow) that was located in the proximity of the resection cavity. Baseline susceptibility weighted imaging (SWI; B) showed multiple cerebral microbleeds (CMB; red arrows) and cortical superficial siderosis (cSS; green arrow) in the vicinity of the ICH. Four mo after presentation he developed tonic-clonic seizures, no MRI was performed. Follow-up SWI after 11 mo (D) showed progression of cSS (green arrows) and new incident CMBs (red circles) in the right frontal, temporal, and both occipital lobes. Note that due to difference in angulation of slices between baseline and follow-up SWI only the frontal region can be compared on the images shown. Follow-up FLAIR-imaging showed increase of white matter hyperintensities in both parietal lobes (A denotes presentation, and C denotes follow-up; orange arrows).