Delayed Spontaneous Rupture of a Posterior Inferior Cerebellar Artery Aneurysm Following Treatment with Flow Diversion: A Clinicopathologic Study

Evolving Intra-Aneurysmal Thrombus May Cause a Transient Destabilization of the Aneurysm Wall, Increasing, Rather Than Decreasing its Propensity for Rupture

Intuitively, one would predict that partial thrombosis of a cerebral aneurysm would actually function in a protective manner, insulating the aneurysm wall from direct contact with blood flow and thereby reducing the forces (like wall shear stress) that could contribute to aneurysm growth or rupture. There are, however, to our knowledge, no longitudinal studies looking at the natural history of partially thrombosed large saccular intracranial aneurysms because they are relatively rare lesions and they are usually treated aggressively after identification.

AAAs, while in many ways different from cerebral aneurysms, potentially represent an analogous scenario to the progressively thrombosing or partially thrombosed very large–giant intracranial aneurysm. Thus, the existing knowledge about AAAs may potentially provide valuable insight into the index case.^{7⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓–18}

Our understanding of the evolution and effects of thrombus in AAAs is far more developed than our understanding of the same process in large-giant cerebral aneurysms for the following reasons:

• 1) AAAs are more common than very large–giant intracranial aneurysms.

• 2) AAAs frequently harbor a considerable volume of ILT at the time of diagnosis, while most cerebral aneurysms do not.

• 3) Unlike very large or giant cerebral aneurysms, unruptured AAAs are often managed conservatively and observed with serial noninvasive imaging (CT or sonography). As such, there is a very well-developed imaging literature documenting the behavior of AAAs with time.

• 4) Histopathologic specimens from autopsies or obtained during the surgical repair of AAAs are far more plentiful than are those from very large–giant cerebral aneurysms.

Any Residual Filling of Aneurysms Treated with a Flow-Diversion Strategy May Preserve the Potential for Aneurysm Rupture

Thus, we hypothesize that intracranial aneurysms may behave in a way very similar to AAAs following the induction of thrombosis after flow diversion. We propose that evolving intra-aneurysmal thrombus functions to destabilize the aneurysm wall via mechanisms of hypoxia, inflammation, and enzymatic degradation while lacking the structural integrity to adequately shield the aneurysm wall from the systemic blood flow. We theorize that flow diverters, like the PED, when used without coils, create a race between 2 simultaneous processes—progression to complete aneurysm thrombosis and thrombosis-induced destabilization of the aneurysm wall. Potentially, this may result in either of 2 outcomes:

• 1) Aneurysm cure. In most cases, the aneurysm completely thromboses, there is no residual intra-aneurysmal flow, and the neck becomes covered by a neoendothelial-intimal layer, which effectively seals off the aneurysm. Once isolated from the cerebrovasculature, the aneurysm no longer carries with it a potential for rupture. At this point, the intra-aneurysmal thrombus mass gradually undergoes regression.

• 2) Persistent intra-aneurysmal flow with maintained potential for progressive growth and/or rupture. In rare cases, intra-aneurysmal flow persists for a longer time. The hypoxic, inflammatory, and proteolytic effects of the evolving thrombus on the aneurysm wall result in a loss of structural integrity. The persistence of intra-aneurysmal flow preserves the potential for the continued accumulation of intra-aneurysmal thrombus and aneurysm growth. Similarly, any amount of intra-aneurysmal flow may penetrate into the evolving thrombus mass and gain access to the destabilized aneurysm wall, potentially leading to precipitous aneurysm rupture (as in the index case).

Thus, in some cases, a partially thrombosed aneurysm after flow diversion may be considerably more dangerous than in its previously untreated nonthrombosed state. Correspondingly, it seems that near-complete occlusion after conventional coil embolization has an entirely different implication than does near-complete thrombosis after flow diversion. While small-neck remnants after coiling have a well-described generally benign natural history, the same is not likely true for aneurysms treated with flow diversion as a stand-alone technology.

Aneurysms with Anatomic Configurations That Could Retard Progression to Complete Thrombosis are Probably Suboptimal Candidates for the Flow-Diversion Strategy

The instability of the aneurysm-thrombus mass may be prolonged by any factors that preserve intra-aneurysmal flow. There are several potential etiologies commonly encountered:

• 1) Anatomic features of the target aneurysm that perpetuate intra-aneurysmal flow after flow diversion:

  • A) Aneurysms with branches arising from the neck or fundus (such as in the index case with the incorporation of PICA into the proximal aneurysm fundus)

  • B) Aneurysms that incorporate a bifurcation (eg, basilar apex, carotid terminus).

• 2) Characteristics of the flow-diverting construct that do not promote efficient complete aneurysm occlusion:

• • A) Suboptimal device design

  • B) Technically inadequate deployment of the construct.

At this stage, it is probably prudent to avoid aneurysms with anatomic configurations that might promote continued aneurysmal filling after flow diversion. It is also important also to realize that once a flow-diverting construct is built across the neck of an aneurysm, endovascular access to the lesion is lost indefinitely and options for retreatment are essentially limited to the placement of additional flow diverters or parent artery deconstruction.