By Anton Valavanis
The term“intracranial aneurysm” is a purely descriptive term meaning a widening of the lumen of a segment of an intracranial artery. It is also a collective term for a rather large group of different diseases affecting the extra- and/or intradural portions of intracranial arteries in a segmental, focal or multifocal pattern. Since the currently available non-invasive and invasive neuroimaging modalities, i.e. cross-sectional native and contrast-enhanced CT and MRI, CT- and MR-angiography, or DSA, almost exclusively depict the lumen of intracranial aneurysms but not, or insufficiently, their other components (i.e. the wall and the perianeurysmal space), neurointerventionists tend to base their research and collaboration on developing treatment tools, their clinical decisions, therapeutic actions and follow-up evaluations on the easily visualised lumen. Accordingly, the majority of the currently used classification systems and treatment guidelines for such aneurysms are lumen-oriented and therefore incomplete. This misleads one to view intracranial aneurysms as simple, more or less focal expansions or ectasias of the parent artery lumen induced by haemodynamic forces, such as flow, shear stress and turbulence, instead of considering them to be pathomorphological expressions of distinct pathobiological processes leading to degradation, activation, overproduction or proliferation of a distinct, genetically or otherwise vulnerable segment of the wall of an intracranial artery within a specific local perianeurysmal environment.
As a logical consequence of this misconception, the radiologically visible lumen becomes the primary target of treatment, while the other components of the disease are mostly ignored.
All currently available endovascular techniques for treating intracranial aneurysms such as coiling, balloon-remodelling technique, stent-assisted coiling and flow-diverting treatment are primarily lumen-based. Although this “lumen-targeting” treatment proved to be beneficial for many patients and in the case of acutely ruptured intracranial aneurysms even life-saving for certain patients, it remains in the strict sense of the term non-curative. This explains why, despite a so-called “angiographic cure”, we observe a relatively high mid- or long-term recanalisation rate, or further growth of many partially-thrombosed aneurysms, or late haemorrhagic events in certain dysplastic aneurysms treated with flow-diverting devices, or perianeurysmal inflammatory reactions with oedema formation in the brain parenchyma after flow-diversion treatment and other unwanted phenomena arising from the wall itself and not from the excluded lumen.
Important abluminal factors
One has to distinguish between the typical and more common so-called saccular or berry aneurysms and a heterogenous group of aneurysms and aneurysm-like lesions of very different aetiologies and clinical manifestations. Characteristic to all of them are distinct pathobiological and histopathological alterations of the involved vessel wall and interactions, with both the haemodynamics of the lumen and the various components of the perianeurysmal space. As far as the typical saccular aneurysms are concerned, abluminal factors involved in their initiation, enlargement, shaping and possible rupture include a genetically determined susceptibility to aneurysm formation, various degrees of alterations of smooth muscle and endothelial cells, focal disruption of the internal elastic lamina and mural inflammation prior to rupture. Depending on the cistern within which an intracranial aneurysm is located, different interactions of its wall with the cisternal arachnoid walls, intracisternal arachnoid membranes and fibres, but also intracisternal segments of arteries and nerves will take place, which influence its orientation, its shape, expansion pattern, behaviour and risk of rupture.
Classification of intracranial aneurysms based on the vessel wall and environment
The classification concept of intracranial aneurysms has to change from a purely descriptive one, based on locations, sizes and shapes to an aetiopathological one, which takes into consideration the pathobiology of the aneurysm wall and its interaction with the perianeurysmal space as well as with the luminal haemodynamics. As techniques for “vessel wall imaging” are steadily improving, it can be expected that in the near future direct visualisation of the specific alterations of the vessel wall, such as degradation of certain wall components, inflammatory changes, vasa vasorum-proliferation and angiogenesis will become possible. Currently, the technique of double inversion-recovery black-blood imaging with pulse-gating at high-field strengths is being investigated in this regard.
Intracranial aneurysms encompass a broad spectrum of different diseases originating or secondarily affecting the vessel wall, i.e:
- Typical saccular or berry aneurysms (single or multiple with random or mirror distributions)
- Segmental ectasias representing spontaneous repair of dissections (inappropriately called fusiform aneurysms)
- Ischaemic dissections with aneurysm formation
- Haemorrhagic dissections with and without pseudoaneurysm formation
- Giant, partially-thrombosed aneurysms with recurring intramural haemorrhages
- Infectious aneurysms (transendothelial invasion of microorganisms from the lumen, transadventitial invasion from the perivascular space)
- Inflammatory aneurysms linked to immunodeficiency conditions
- Oncotic (neoplastic) aneurysms
- Traumatic pseudoaneurysms (wrongly called “traumatic aneurysms”)
- High-flow aneurysms as an expression (marker) of established high-flow arterial angiopathy induced by an arteriovenous malformation.
Impact of abluminal factors on therapeutic strategy
There are two main issues arising from the inclusion of the abluminal factors in the therapeutic strategy for intracranial aneurysms. The first issue concerns the indication of treatment, its timing, the selection of the appropriate technique and the estimation of its risk.
The second issue concerns the possible or predictable short-, mid- and long-term responses of either the wall or the perianeurysmal environment following treatment.
For example, in the following conditions invasive treatment should not be the primary therapeutic consideration:
- Fusiform aneurysms representing segmental ectasias as the end-stage of the repair process of a previous dissection
- Infectious or inflammatory aneurysms, as their majority responds favourably to antibiotic or steroid medication, respectively
- Saccular aneurysms without imaging findings which may indicate the presence of weakened mural areas and without change of size or shape on sequential imaging follow-ups
- Flow-related aneurysms in conjunction with arteriovenous malformations, as the majority of them will regress or disappear following appropriate elimination of the arteriovenous malformation nidus
Examples of possible or predictable responses of the wall following the application of inappropriate treatment techniques or timing include:
- Post-treatment haemorrhage of large or giant partially-thrombosed aneurysms following endovascular treatment with flow-diverters induced by the altered haemodynamics on the aneurysm wall, which may initiate a progressive autolytic process of the preexisting mural thrombus, in those cases which exhibit abnormal subadventitial enhancement on preoperative MRI as a result of vasa vasorum induced angiogenesis.
- Further or new growth of large partially-thrombosed aneurysms, treated by simple, or balloon-assisted or stent-assisted luminal coiling.
- Increased recanalisation risk of ruptured aneurysms treated in the early acute phase of subarachnoid haemorrhage, as a certain proportion of acutely ruptured intracranial aneurysms, especially in patients with higher Hunt and Hess grade, may undergo temporary reduction in size and deformation of their shape due to the subarachnoid haemorrhage-induced alterations of the cisternal fibre system transmitted upon the wall of the aneurysm.
Message to neurointerventionists
The fact that we do not see abluminal factors with our currently available imaging modalities does not justify ignoring them in our diagnostic and therapeutic considerations. We need to learn more about them and develop imaging modalities which will allow us to visualise them directly. This will allow us to accomplish the conceptual and technical paradigm shift in targeting of aneurysm treatment, from the lumen to the wall and its environment and therefore the transformation of the endovascular aneurysm treatment from a currently mostly symptomatic, to a hopefully, truly curative one.
Anton Valavanis is a professor, founder and chairman of the Institute of Neuroradiology at the University of Zurich, Switzerland.
