Embarking on New Era of a Treatment and a Diagnosis of an Intracranial Aneurysm

Abstract

  The poor outcomes of subarachnoid hemorrhage following the rupture of pre-existing intracranial aneurysms necessitates that novel diagnostic or therapeutic strategies be developed. Recent experimental findings, including those obtained from human specimens, have highlighted the key role of macrophage-mediated chronic inflammation to the machinery that regulates the formation and progression of intracranial aneurysms. In this way, such aneurysms can be recognized as a macrophage-mediated chronic inflammatory disease affecting intracranial arteries. Such a conceptualization and understanding is important for two reasons : 1) it can help develop novel therapeutic drugs to prevent rupture ; 2) it can help develop a diagnostic modality to estimate the qualitative nature of a lesion for proper stratification of rupture-prone intracranial aneurysms.

   In animal models, several drugs with anti-inflammatory effects can successfully prevent the disease formation and progression. Furthermore, in cross-sectional studies of human cases, the usage of potent anti-inflammatory HMG-CoA reductase inhibitors and the usage of non-steroidal anti-inflammatory drugs are significantly lower in cases of unruptured intracranial aneurysm. These results clearly suggest that a medical therapy capable of targeting the factors that mediate chronic inflammatory responses in the microenvironment of lesions could prevent intracranial aneurysms from progressing. In addition, macrophage imaging has been reported as a potential aid in diagnosing the inflammatory status of each intracranial aneurysm, acting as a surrogate marker of disease activity. In this imaging technique, a macrophage is labeled by engulfed iron-containing nanoparticles and visualized by T2*images on magnetic resonance imaging. Because the positive rate in macrophage imaging is positively related to the aneurysm’s size, this technique can stratify intracranial aneurysms into rupture-prone and stable lesions. A new era of diagnosis and treatment is therefore expected.

  In this, unruptured intracranial aneurysms will be identified through brain imaging, rupture-prone lesions will be selected by macrophage imaging, and pre-emptive medical therapy or surgery will be used to prevent subarachnoid hemorrhage in appropriately selected cases.