Walter Valesky, MD
Limitations in our knowledge of cerebral amyloid angiopathy (CAA) persist due to relatively small study sample sizes and a requirement for pathological specimens to confirm a diagnosis. The Edinburgh criteria is the most recent decision instrument developed to assist in the pre-mortem diagnosis of this disorder. In their logistic regression model, Rodrigues et al. utilized genetic factors (APOE ε4 genotype) and computed tomography (CT) findings (finger-like projections and subarachnoid hemorrhage) to attain a high degree of sensitivity and specificity.1 However, their cohort relied on autopsy specimens for confirmation of moderate-to-severe CAA.
To this end, van Etten et al. recruited patients with Dutch-type CAA (D-CAA) for analysis. D-CAA, a hereditary variant of CAA, causes similar radiographic features as CAA with an accelerated clinical course, and most importantly, does not require a tissue-based confirmation. Using patients with D-CAA, the investigators evaluated the aforementioned CT variables in this validation study.
The authors enrolled one-hundred and seven CT scans from fifty-five patients with an acute, non-traumatic acute lobar intracerebral hemorrhage (ICH) on CT scan with D-CAA, confirmed by genetic testing or family history of the disorder. Two authors evaluated subarachnoid hemorrhage (SAH) and finger-like projections (FLP) on CT with high Cohen κ values of 0.84 and 0.94, respectively. Sensitivities, but not specificities, were calculated as only patients with D-CAA were recruited.
The mean age of 56 years was less than the original Edinburgh criteria (median age, 83) but consistent with a previous D-CAA-based validation study of the Boston criteria.2 SAH and FLP were present in 76% and 58% of CT scans, respectively. Patients demonstrating these findings on CT scans accounted for larger intracerebral hemorrhages than those without these findings. In patients with larger hemorrhages (volume >40ml), presence of both findings give a sensitivity of 81%, but in those with smaller hemorrhages (volume ~15ml), the sensitivities are less optimal (50%).
Overall, these findings demonstrate that in large intracerebral hemorrhages, one may obtain a relatively high degree of sensitivity by identification of finger-like projections and subarachnoid hemorrhage on CT in Dutch-type CAA patients. What is less clear is if the results of this cohort of D-CAA patients may be extrapolated to a larger group of patients with cerebral amyloid angiopathy experiencing intracerebral hemorrhage at a more advanced age. In the original Edinburgh criteria, SAH and FLP were prevalent in 89% and 39%, respectively, of moderate or severe CAA in those undergoing research autopsy. These numbers compare somewhat favorably with van Etten et al.’s cohort but leave open the desire for more consistent findings in identifying patients with CAA using non-invasive methods. Only then will we be able to make more well-informed treatment decisions in order to prevent recurrent intracerebral hemorrhages.
References:
1. Rodrigues MA, Samarasekera N, Lerpiniere C, et al. The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. The Lancet Neurology. 2018;17(3):232-240. doi:10.1016/S1474-4422(18)30006-1
2. van Rooden S, van der Grond J, van den Boom R, et al. Descriptive Analysis of the Boston Criteria Applied to a Dutch-Type Cerebral Amyloid Angiopathy Population. Stroke. 2009;40(9):3022-3027. doi:10.1161/STROKEAHA.109.554378
