Introduction
Intracranial aneurysms (AA) as a source of cerebral haemorrhage affect the patient's vital, functional prognosis, and represent one of today's medical challenges. Many articles and studies on aneurysms have been published in highly technical journals (neurosurgical, neuro- radiological, neurological) but also in journals of general interest, such as the New England Journal of Medicine. Today, the possibilities of non invasive diagnosis before the acute stage of rupture, pose (amongst others) organisational, ethical, academic and public health problems: how many centres can, or should, accept patients at an acute stage? What are the respective roles of the neuro-specialists involved? Are the proposed treatments offering comparable services? Should the selection of patients be made on the basis of technical feasibility, and by whom? Is there a functioning cost beyond which a therapeutic technique should be rejected or limited? Is such limitation ethically acceptable? Up to what point should sreening tests for AA diagnosis be carried out? How often should they be repeated?
Mortality as a result of haemorrhage is still very high; it leads to emotional, vindictive, even heroic behaviour. The inability to predict the occurrence, recurrence or rupture of an arterial aneurysm leads to frustrations which generate superstition and dogmatic, or prophetic behaviour: “a few minutes before rupturing, aneurysms are all unruptured aneurysms”. That reminds me of an article in an international daily newspaper, headed “mushrooms can be toxic - better not to eat them at all”. When fear takes over knowledge, ignorance rules. Things are certainly not that simple.
The route from anecdotes, which fed experience and founded modern empirical medicine, is unable to integrate the register corresponding to statistical data and the questions that may arise from it. Some “possess knowledge” because they have the evidence, but often do not have the experience; others “know” because they have the experience but often lack the evidence. This archaic dualism which excludes doubt, prevents our community from self-evaluation and from drawing lessons from publications such as that of Wiebers. These entrenched convictions lead to all-out therapeutic treatment, with a morbidity rate today which seems not only unacceptable in many hands, but often unjustified even in the best hands.
When Disease is Hostage to Tools
The influence of mechanistic treatments (surgery and interventional neuroradiology) has reduced the debate on aneurysms to that of technical possibilities of exclusion.
Thus as for AVMs, classification is made according to the tools and material available. The attempts at understanding aneurysmal disease are concealed by the use of any means able to carry out evaluation and morphological eradication- “if I can evaluate, measure, I can understand, compare and decide. Is not true science expressed through numbers?”. Whatever this quantification is - whether epidemiological, metric, flow, pressure, speed or temperature - it can only reinforce this rigid, mechanical approach in the three dimensions of the present. .... It confines the selection of patients who might benefit from treatment to those for whom treatment is applicable; it ignores those for whom treatment might lead to a lesser risk than would naturally be incurred.
Public pressure, informed of technological progress by the non scientific press, has contributed to shift the debate from “Should we do it?” to “Who can do it?” The underlying and widely accepted thought is that there is a single and undivided medical truth. But the very same public opinion does not make a distinction between decision and actual performance. They have come to believe that the therapeutic measures recommended by their practitioner are innocuous so long as he 'speaks the truth'.
The equality of practitioners with regard to the tasks to be undertaken is tacitly established once patients believe they are speaking “the same medical truth”. The individual at risk whose illness has not been declared, the potential patient, thanks to the virtues of a postulated “natural history”, becomes a consumer of therapeutic techniques, not of health. Emphasis is placed on therapeutic choices, and doctors are forced to propose preventive treatment far too often. The well-known morbidity of preventive treatment for aneurysms today cannot be compared with that of vaccination, or any other prescribed medical treatment. When a patient requests treatment, the doctor professional response is to give honest, up-to-date information. In all cases, the patient's desire to be treated does not imply that practitioners should carry out that treatment if they are convinced that the risks outweigh the benefits.
The challenge of preventive treatment of AA, is not simply reduced to that applying treatment for the AA. This strictly technical, and public health challenge, is secondary compared to the intellectual challenge posed by the disease itself.
Little is known in AA: the appearance of aneurysms in intervals of short duration (a few hours, days or weeks) during physical or psychological stress, associated with environmental factors, dietary habits, acquired or not AA, age, the presence of a genetic or non-genetic underlying structural abnormality, represent a few of the fields that are widely opened to discussion.
This preliminary diagnosis, the development of a therapeutic decision which serves a suitable objective, before a technical choice, today constitute two of the flaws in the training of specialists called upon to intervene in this pathology.
Aneurysms do not escape globalisation. In countries where aneurysms were traditionally less frequent, changes in diet and lifestyle have affected the disease's prevalence, which is now closer to that of aneurysms in the Western world and among Caucasian populations. Although the now worldwide problem broadens the scope of discussions, it has also pulled the new markets into the same mechanistic attitude, enticing industrial appetites and raising human passions that are more or less generous.
Aneurysmal Diseases
Upon examining the various pathologies known for their association with arterial aneurysms, it should be noted that aneurysms do not occur in just any location for a given disorder. Just as remarkably, some locations are preferentially affected while others are perfectly preserved. Is this a chance finding, or are these sites closely related to the 'accompanying' disease?
These arterial localisations could reflect a focal vulnerability to systemic risk factors. Those most traditionally put forward are haemodynamic constraints beyond the limits of normal functioning; by contrast, in normal haemodynamic conditions, the revealing factor betrays a “natural” (at the level of bifurcations, for example) or structural parietal fragility, either acquired or non-acquired. Thus, isolated aneurysms (berry aneurysms) as compared to aneurysms associated with cerebral arteriovenous malformations are not found in the same area of the arterial tree. For the latter, haemodynamic factors are certainly dominant, even exclusive or aetiological. Apart from these particular cases and a few others, “haemodynamic responsibility” in pathogenetic diagnosis cannot be accepted. In most cases, a parietal structural factor (malformed or not) should be introduced, distinct from anatomy (macro or microscopic); this structural factor creates an invisible discontinuity in the arterial system over and above morphology and haemodynamics.
From Alteration to Identity
At each stage of vasculogenesis and angio- genesis, although there are several copies of the genetic programme in a cell, slight alterations occur in the programme at each stage of development, leading to permanent susceptibility (under normal conditions) or focal weakness (when conditions become abnormal) of the tissue can occur. On the whole, these anomalies are not expressed in the form of an aneurysm unless other incidents are added to preceding ones, or unless the repetition or duration of stress go beyond possible compensation for the constituted defect. The natural history of diseases associated with aneurysms favours this type of hypothesis: mirror aneurysms, multifocal aneurysms of metameric distribution, constitutional family or non-family disorders (Polycystic Kidney Disease I, Fibro Muscular Dysplasia, Ehlers Danlos and others).
Thus an aneurysm of the basilar tip could be caused by a number of pathologies which have evolved in different ways. The absence of discrimination in these pathological diagnoses establishes a mean global risk, which could be acceptable if treatment were always effective, and therapeutic risk non-existent. Such conditions not being met, an attempt to identify AA sub groups is mandatory.
Not all arteries are affected because of a focal parietal alteration, but they could be affected because of a segmental characteristic or identity: the topographic phenotype. We note, for example, that in immune deficiency pathology, aneurysms are multifocal and fusiform, and affect particular segments of the carotid and vertebrobasilar system. Other viral or infectious complaints affect specific arterial segments, such as the Ml segment (moya moya, chicken pox etc..) or M2 in mycotic lesions. These topographical phenotypes seem to reflect different “identities” and means of defence within the arterial tree, whose macroscopic, microscopic and haemodynamic morphological continuity seems, however homogenous.
Putting phylogenesis in perspective justifies these phenotypes and allows us to appreciate existing differences within the same arterial tree. The Ml segment of the middle cerebral artery is concomitant with segment Al, and it is only after birds that segments M2, then M3 appear, with the development of the hyperstria-tum and the parieto-frontal cortex, and then in primates, the frontal cortex. The tens of millions of years which separate the appearance and the development of segment M2 from segment Ml have by nature profoundly modified the molecular content of cells charged with building up and maintaining the vascularisation of this area in man. This fundamentally historic identity could be recognisable or vulnerable to intrinsic or extrinsic agents (immunological, viral and others...). The arterial tree is thus made up of segments of a very different generation and age. In the same way, the development of the internal carotid, the origin of its different cavernous or clinoid segments, branchial arteries and their programmed regression, constitute an equal number of historical anatomical events and sites which carry identity, and probably differences, with regard to diseases and means of defence.
In Practice
From these comments on aneurysms, two philosophies and two branches of research arise, which seem divergent rather than incompatible:
The first considers that aneurysm is a herniation of the lumen,
The second considers that aneurysm is a herniation of the wall.
These two fundamentally different and at times opposing philosophies have generated specific research. For the former, aetiology is almost always considered haemodynamic through the increased blood flow or arterial hypertension, a jet or drop-trigger phenomenon, the creation of turbulence or a problem of valve effects. This approach attempts to model the lumen to reproduce supposed causes and effects. Treatment is centred on the desire to correct the lumen. Pathologists, anatomists, radiologists, neuroradiologists and surgeons therefore try to repair this lumen with the help of ligatures, clips, balloons, coils, remodelling, stents, embolisation, platinum, polymers, whether enclosed in bags of silicone or latex or not. Imaging this lumen has created the 3D effect, in order to achieve a realistic and anatomical reconstitution. Thanks to virtual arterioscopy teleguiding is no longer myth, but an achievable project; it has introduced the “incredible journey” of the agents inside the lumen to reconstruct it.
Meanwhile the second hypothesis place the emphasis on the aneurysmal vasculopathy. Discussions revolve around the modalities of parietal alteration in the course of various disorders: For example, there is a distinction between:
- focal and multifocal constitutional disorders, whether familial or not;
- aneurysmal vasculopathies in abnormal conditions which are “normal” functional defects exacerbated by increased flow;
- topographical phenotypes representing targets recognised by highly specific agents, whether infectious or not;
- immature aneurysmal vasculopathies, more often focal, correspond to insufficiencies in endothelial selection during embryonic fusion (longitudinal neural arteries at encephalic level) or branchial regressions. This type of aneurysm is frequently associated with the persistence of an embryonic artery, fenestration, etc.
In this frame of mind, the desire to repair the wall and to restore or use the natural means of repair of the vascular apparatus, mobilises different specialists. Molecular biologists, immu- nologists, physiologists, pharmacologists and geneticists incline more towards biochemical characteristics, mutations and the possibilities of applying specific drugs in order to compensate or reconstitute the lost capacity for repair. This principle has already been illustrated with malignant brain tumours, with the role played by the loss of a part of chromosome 17 coded for the pro-apoptotic protein P53.
Conclusion
These two currents usually diverge, as they involve medical populations which do not meet spontaneously, and do not share the same literature. We can envisage another rupture one day over who is to deal with these illnesses, if formal cooperation is not established. This will arise from a difficulty in communicating, as the vocabulary of the two different currents is not the same.
Nonetheless, constituted and ruptured aneurysms are permanent medical challenges, and, as Bakounine said, “if progress comes one day, it will still be too late for those who need it now”. However, the aggressive therapy which some believe is necessary should be tempered by the unjustified nature of the risk involved in certain forms of aneurysm. The group of aneurysmal vasculopathies is so heterogenous that the “natural” history of each disorder requires a different therapy. Not all aneurysms respond to antibiotics and anti-inflammatory drugs, but in the same way, not all aneurysms rupture.