It is increasingly recognised that the individual's own "software"- the genetic information carried by a persons cells- plays an important role in the susceptibility to brain aneurysm. This is partly by rendering some of us more likely to develop aneurysms in the first place and partly by increasing the likelihood they might rupture. This may in part be an increased vulnerability to the effects of known environmental aneurysm "promoters" such as cigarette smoke or hypertension. Other genetic changes have been linked to alteration in the tissues that make up the blood vessel itself.
Aneurysms That Run in The Family.
It is estimated that between 7% and 20% of aneurysms occur in individuals with a family history of same.
A multi centre study screened first degree relatives of those affected by brain aneurysms and who were over the age of 30 years, smoked or had a history of hypertension. 19% were found to harbour an asymptomatic cerebral aneurysm. It is not known whether that prevalence would have been less if those screened had not smoked or had their hypertension treated.
A meta-analysis of published data on familial aneurysms suggested that the risk of rupture was substantially (1.2 to 5 times greater) greater for those a first degree relative affected by aneurysm. It is important to remember that would still translate into an absolute risk in small anterior circulation aneurysms (i.e. most) which was lower than projected risk of treatment in the short to medium term. Despite this the risk of dying from a familial aneurysm does not appear greater in those with sporadic non-familial aneurysms.
A meta-analysis is a study that amalgamates data from other studies that meet certain quality criteria and applies rigorous statistical analysis to draw conclusions form the pooled results. Conclusions can vary both as a result of the way the analysis is carried out but also as a result of how it is decided which published evidence may be included. A good meta-analysis will set a high bar for the quality of the studies included.
The environmental influences of smoking and hypertension affect the risk of future bleeding similarly to those without a family history. So quitting cigarettes or sustained normalisation of blood pressure is likely to bring benefits in terms of reduced risk of bleeding.
A study of a UK population found that those with two or more first degree relatives affected by brain aneurysms were at a higher risk of harbouring a brain aneurysm- about 8% compared to 2% of the general population. Those with only one first-degree relative had a similar risk to the rest f the population and on that basis screening for aneurysm was not recommended unless there are two or more cases in a family.
Other Genetic Associations.
There are multi-system diseases which are caused by gene lesions (mutations) where an increased susceptibility to brain aneurysm is observed.
Adult Polycystic Kidney Disease
Amongst the best studied is Adult Polycystic Kidney Disease (APCKD). Cysts develop in the kidneys which ultimately may cause them to fail. Blood may issue in the urine, high blood pressure develops and the large cysts may produce abdominal pain. The child of an affected parent has a 50% chance of developingthe condition although 1 in 4 cases develop without any known family history.
The responsible genes are known and named PKD1 (85% of cases) and PKD2 (15%).The chance of developing brain aneurysm in APCKD is increased approximately seven-fold over the usual. 5-40% of those with APCKD have been observed to harbour aneurysms in various studies and 10-30% develop multiple aneurysms. However It is not demonstrated that the risk of bleeding from aneurysms is higher than in those without APCKD.
Neurocutaneous Disorders and Vasculopathies
This is a broad collection of disorders that share the finding of developmental vascular anomalies in the skin, peripheral and central nervous systems. The increased prevalence of aneurysm encountered in these conditions may be explained by the frequency of developmental arteriovenous shunts that are seen in these conditions.
Blood is diverted from the high-pressure arterial circulation to the lower pressure venous circulation causing excessive wear-and-tear on these blood vessels. The aneurysms are mostly a secondary manifestation of the increased stresses on these blood vessels.
Neurofibromatosis type 1 is a relatively common condition affecting 1 in 4000 people approximately. A faulty gene results in cell producing an abnormal version of a protein called neurofibromanin which is normally necessary for the normal formation of many different types of tissues. The condition can be characterised by skin lesions, disordered bone growth and tumours of the peripheral and central nervous system.
Less commonly it is associated with misshapen and narrowed blood vessels resulting in aneurysms or MoyaMoya Syndrome.Other conditions in this group include Hereditary Haemorrhage Telangectasia (HHT), PHACE Syndrome, CM-AVM, Craniofacial Arteriovenous Metameric Syndromes (CAMS 1-3), HANAC, Loeys-Dietz Syndrome and Klippel-Trenaunay Syndrome. Most of these are very rare and many have been only recently recognised.
Is it Beneficial To Screen Healthy People for Brain Aneurysms?
This is a contentious question. It is superficially attractive to have an opportunity to treat an unruptured brain aneurysm before something as serious as subarachnoid haemorrhage occurs.However unruptured aneurysms may be present in about 1 in 50 of us and it is understood that only a tiny proportion of these will ever rupture or do the person any harm. Treatment carries risks, however small they may be. Is it worth accepting such risks to treat an aneurysm?
Screening is typically carried out using CT or MR scans. One of the unanticipated results may be the discovery of a potential health condition that might never translate into actual harm. This is not limited to just brain aneurysms. One has to carry out only 37 MRI scans of the brain to discover 1 unanticipated finding. These include brain aneurysms, vascular malformations of the brain, cavernous malformations or brain tumours. The risk of treatment may not be advisable for some of these but once discovered their presence must inevitably present something of a psychological burden.
For this reason we recommend that if considering undergoing a scan for a brain aneurysm, speak to a specialist who actually treats them before undergoing any imaging and talk through the reasons for doing so as well as what steps to take if something is discovered.
Limitations of Screening.
There is no rule that means an aneurysm may not rupture just before or just after a scheduled scan
A negative CT or MR is not a guarantee against the development of aneurysms in the future particulalry in smokers or those with uncontrolled hypertension.
There is presently no strong scientific basis for recommending any particular schedule of re-imaging to those at high-risk. Our current practice is to recommend re-evaluation at an interval of 2-5 years in such cases.
Aneurysms can develop or grow over a short period of time before rupturing and no matter how intense a program of screening they may not be detected before rupture.
