Clinical and Neuroradiological Manifestations of Cerebral Amyloid Angiopathy: A Closer Look into the Natural History of a Frequent Disease

Cerebral amyloid angiopathy (CAA) is one of the most prevalent small vessel diseases (SVDs). Its neuroradiological hallmarks are both hemorrhagic and non-hemorrhagic ones. Among the clinical manifestations, transient focal neurological episodes (TFNEs) are associated with an increased risk of bleeding in a short time period and with convexal subarachnoid hemorrhage (SAH). The natural history of CAA is incompletely characterized in the literature, because the focus has been mostly on hemorrhagic events, while both clinical and non-hemorrhagic presentations are possible and sometimes underestimated. Furthermore, new diagnostic criteria have incorporated non-hemorrhagic Magnetic Resonance Imaging (MRI) markers and non-hemorrhagic clinical presentations. Disease trajectories are often individual and help provide food for thought and discussion on some issues, thus allowing for a greater and deeper evaluation. We, therefore, present a case that exemplifies how the natural history of CAA can be atypical compared to its expected course, which is long and not only hemorrhagic. Several episodes of CAA-related inflammation, with prevalent, but not exclusive, leptomeningeal involvement, were evaluated and treated in the presented case, in which the intraparenchymal cerebral hemorrhagic manifestation was the last in the patient’s history. CAA may have a very long natural history. During the disease’s course, inflammatory features might be prominent in neuroimaging but not strongly symptomatic, and intraparenchymal cerebral hemorrhage (ICH) may be a late event. The awareness of this subtype of the disease allows us to better explore the pathophysiology of CAA and to increase the level of clinical suspicion for the diagnosis. Furthermore, the distinction between different disease phenotypes can provide useful information for patient management in clinical practice.