Genetic risk for aneurysm and frequency of screening

[colorcat3]

My mother had a ruptured cerebral aneurysm at age 83 with massive bleed and severe permanent brain damage. Her first cousin died of a rupt. cerebral aneurysm in her 30s. I have had a baseline screening by MRI of my brain in 2007 (age 59) which showed no aneurysms. My husband's father died of a rupt. abdominal aneurysm. He was told that he should have ultrasounds on a two year frequency to rule out developing aneurysms. How often should I have repeat MRI to rule out developing cerebral aneurysm for myself?

[MG (Admin)]

Just wanted to check..did you have an MRI with angiography (sometimes called an MRA)? or just a regular MRI?

[MG (Admin)]

Here is the text of an article that deals with it..bottom line is that screening recommended every couple of years.
I will send you full article via email

Repeated screening for intracranial aneurysms in
familial subarachnoid hemorrhage
M.J.H. Wermer, G.J.E. Rinkel and J. van Gijn
88
Chapter
Abstract
Background and purpose
In families with two or more fi rst-degree relatives with subarachnoid hemorrhage (SAH)
screening for aneurysms is often recommended. The benefi t of repeated screening and the
interval at which screening should be performed are unknown. We studied patients’ compliance
and the yield of repeated screening for familial intracranial aneurysms.
Methods
Relatives with familial SAH screened between 1990 and 1997 were advised to return every
fi ve years for follow-up screening with magnetic resonance angiography (MRA). In case
neurosurgical clipping had been performed in the past screening was done with computed
tomographic angiography (CTA). We analyzed the results for the group as a whole, and for
the subgroups of relatives with and without previous aneurysms.
Results
Of 129 relatives who were advised to undergo further screening 27 did not return, 74 had one
repeat screening and 28 a second repeat screening. We detected 10 new aneurysms in nine
of the 102 screened relatives (9%), three of the 19 (16%) relatives with previous aneurysms
and six of the 83 (7%) relatives without previous aneurysms. One of the nine subjects with
a new aneurysm and one other relative had an SAH three years after a negative screening
procedure.
Conclusions
In persons with familial occurrence of aneurysms the motivation for repeated screening every
fi ve years is high and the yield is considerable, particularly in relatives who have been treated
for aneurysms in the past. The occurrence of SAH less than fi ve years after a negative screen
suggests that screening may have to be repeated at shorter intervals.
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Introduction
Familial clustering occurs in around 10% of patients with subarachnoid hemorrhage (SAH).1,
2 The risk of SAH in family members with two or more fi rst-degree relatives with SAH or unruptured
aneurysms is not exactly known. Presumably, this risk is higher than in fi rst-degree
relatives of patients with sporadic SAH, who have already a three to sevenfold higher risk of
SAH than the general population.3
The yield of screening in persons with two or more affected relatives is high; in about 8% an
aneurysm is found.4, 5 According to the guidelines of the American Heart Association, screening
should be considered in such relatives.6 Because aneurysms are not congenital but develop
over time, the issue of repeated screening should be considered.6, 7 Repeated screening often
is already often performed in clinical practice, but the yield of repeated screening and the
interval at which screening should be performed have never been properly assessed.
We assessed the yield of repeated screening in members of families with familial SAH by
investigating the proportion of relatives who returned for repeated screening, the number
of newly detected aneurysms, the time of detection, and the characteristics of the relatives
with new aneurysms.
Methods
All patients with SAH and their relatives who attend our hospital for screening are recorded
in a database. We retrieved from this database all relatives who were screened for familial
intracranial aneurysms between 1990 and 1997; they were all advised to undergo follow-up
screening. Familial SAH was defi ned as two or more fi rst-degree relatives (parents, siblings,
children) known to have SAH or unruptured aneurysms. The advice for follow-up screening at
an interval of fi ve years was given to the relatives after the initial screening and was included
in a letter to the family physician about the result of this initial screening. Relatives were
told that they would not be invited for follow-up screening but that they had to make an appointment
at the outpatient clinic at their own initiative. We did not recommend follow-up
screening in relatives from around the age of 65 years because the benefi t of screening at
the age of 70 would probably not exceed the risk of preventive treatment.
From 1993, relatives who had not previously been treated for aneurysms were screened with
magnetic resonance angiography (MRA). If neurosurgical clipping had been performed in the
past, screening was done with computed tomographic angiography (CTA). If an aneurysm was
detected on CTA or MRA catheter angiography was performed for confi rmation of the CTA or
MRA fi ndings and for planning the optimal treatment, i.e. surgical clipping or endovascular
coiling. Aneurysms smaller than four millimeters in patients without previous SAH were followed
up with MRA or CTA over time.
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Chapter
We recorded how many relatives visited our outpatient clinic for repeated screening. If relatives
had not returned six years after the initial screening, we classifi ed them as nonattendants.
Relatives who had not returned after fi ve years but had not passed the 6-year interval were
classifi ed as pending because some relatives contacted us between fi ve to six years after the
initial screening. For all relatives who had not returned for follow-up screening, we contacted
the family physician to fi nd out if the person was still alive, had had an SAH after the initial
screening procedure, or had been screened elsewhere. We classifi ed the newly developed
aneurysms as de novo (aneurysm located at a site that previously showed no abnormalities),
regrowth (aneurysm located at the site of an originally treated aneurysm), or additional (in
relatives with previous aneurysms in whom the second aneurysm was seen in retrospect
but had not been identifi ed on initial screening with MRA or CTA). We constructed pedigree
trees for all families. The characteristics of relatives with new aneurysms in terms of degree
of kinship, age, sex, and previous SAH or unruptured aneurysms were compared with those
of relatives without aneurysms detected on repeated screening. We calculated proportions
and relative risks with corresponding confi dence intervals for the group as a whole, and for
the subgroups with and without previous aneurysms (ruptured or unruptured).
Results
In total, 129 relatives in 26 families with familial SAH had been advised to undergo follow-up
screening every fi ve years. Of these 129 relatives, 102 (79%) from 19 families actually returned
for repeated screening; 42 were men and 60 women. The mean age of the screenees at the
time of the initial contact was 37 years (range 18-62 years). The mean number of relatives per
family was fi ve (range 1-17). Of the 102 relatives, 57 were siblings of affected relatives, 33 were
children, 10 had an affected parent and an affected sibling, one was a parent and one had
an affected parent and an affected child. One relative was known to have autosomal dominant
polycystic kidney disease (ADPK). Nineteen relatives had been treated for aneurysms
in the past; 11 after SAH and eight for an asymptomatic aneurysm. Seventy-four relatives
had a single follow-up investigation, 28 had two follow-up screens. The total follow-up time
between the initial screen and the fi rst follow-up screen was 552.3 years (5.4 years/relative).
The total follow-up time between the fi rst and second repeated screens was 104.3 years (3.7
years/relative). Of the 27 relatives who had not returned, eight relatives were pending. All 27
relatives were found to be alive; one of them had been screened in a hospital closer to her
residence, reportedly with normal results. Twenty-six had no SAH after the initial screening;
for one relative, this information was lacking. The characteristics of the relatives who did not
return for screening were similar to those of the patients who did return except that only one
of the 27 nonattendants had been treated for an aneurysm in the past.
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New aneurysms detected with screening
At follow-up screening, we detected 10 aneurysms in nine (9%) of the 102 repeatedly screened
family members. Of the 10 detected aneurysms, three were treated with coiling and three
with clipping. No complications occurred during treatment, and all treated patients had a
good recovery. The remaining four aneurysms were smaller than four millimeters and are
followed up over time. In all patients, the angiogram performed after the positive screening
confi rmed the fi ndings on MRA or CTA. In the patient with two new aneurysms, the second
one was initially not detected on the CTA but was found on the angiogram performed for
the other new aneurysm (Table 1, patient 7). The number of relatives needed to screen per
fi ve years to fi nd one aneurysm was 13. The characteristics of the nine subjects and the newly
developed aneurysms are shown in Table 1.
Relatives without previous history of SAH or unruptured aneurysms
Six of the 10 new aneurysms were found in six (7%) of the 83 relatives without previous aneurysms.
In three patients, a new aneurysm was detected at the fi rst follow-up investigation
and in three patients at the second. One of the aneurysms detected at the second visit was
in retrospect visible on the MRA fi ve years before but not on the initial MRA; in the interval
it had grown from 4 to 9 millimeters. In another patient, an aneurysm found on the fi rst follow-
up screen could in retrospect be identifi ed on the initial MRA; this aneurysm had grown
from 5 to 7 millimeters over a period of six years.
Relatives with previous history of SAH or unruptured aneurysms
Four of the 10 new aneurysms were found in three (16%) of the 19 relatives with previous
aneurysms (ruptured or unruptured). All aneurysms were detected at the fi rst follow-up
screening. One new aneurysm was seen in retrospect on the angiogram that had been
performed at the time of the SAH and was therefore classifi ed as additional. This aneurysm
had not increased in size in the 5-year interval. One aneurysm developed adjacent to the clip
placed at an earlier operation and was classifi ed as a regrowth. The remaining two aneurysms
were classifi ed as de novo.
Subarachnoid hemorrhage in the interval between two screening procedures
In one relatives without previous aneurysms, an SAH occurred in the interval between the
two screening procedures. A new aneurysm of the anterior communicating artery was found
and treated with neurosurgical clipping (Figure 1). Four years after the SAH, a new aneurysm
was detected on follow-up screening. This small aneurysm of the middle cerebral artery was
clipped, and the patient again made a good recovery (Table 1, patient 4).
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Chapter
No Birth yr Sex History
SAH or UA
Degree of
kinship
Initial screen Result First
follow-up
Result Second
follow-up
Result Aneurysm
classifi cation
Size
mm
Treatment
1 1945 F No Sib+Child 1993 Negative 1997 Negative 2002 P com A De Novo 9 x 5 Coiling
2 1945 F No Sib 1995 Negative 2001 MCA A - - De Novo * 7 Coiling
3 1972 F No Child 1990 Negative 1995 Negative 2001 Basilar A De Novo 3 Follow-up
4 ** 1957 F No Sib 1995 Negative 2000 Negative 2002 MCA A De Novo 2 Clipping
5 1950 F No Sib 1995 Negative 2003 MCA A - - De Novo 3 Follow-up
6 1948 M No Sib 1995 Negative 2000 P com A - - De Novo 4 Clipping
7 1956 F UA Sib 1996 4 MCA A 2001 A com A
MCA A - -
Additional
De Novo 3 x 4
2 Follow-up
8 1949 F SAH Sib 1993 SAH A com A 2001 ICA A - - De Novo 5 Coiling
9 1929 M SAH Sib 1980 SAH MCA A 1993 MCA A 1997 Negative Regrowth 15 Clipping
Table 1 Location of aneurysms and characteristics of patients with newly detected aneurysms
SAH / UA = subarachnoid hemorrhage / unruptured aneurysm
Initial screen/ fi rst follow-up/ second follow-up= year of initial/ fi rst follow-up/ second follow-up screening
Size mm = size of the aneurysm in millimeters
F / M= female / male
4 = number of aneurysms
ICA A = aneurysm of the internal carotid artery
MCA A = aneurysm of the middle cerebral artery
A com A = aneurysm of the communicating anterior cerebral artery
P com A = aneurysm of the communication posterior cerebral artery
Basilar A = aneurysm of the basilar artery
* this aneurysm was in retrospect visible on the initial screen of 1995
** patient 4 had an SAH in 1998 from an aneurysm of the anterior communicating artery despite negative screening in 1995 (Figure 1)
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One relative with SAH fi ve years before had a single follow-up screening that showed no
abnormalities. Three years later, she was admitted to another hospital with a CT proven SAH.
She died, and at autopsy an aneurysm of the vertebral artery was found. In contrast with the
other patient who had an SAH in the interval between the two screening procedures this
aneurysm was in retrospect visible on the initial angiogram.
Risk factors for development of new familial intracranial aneurysms
A history of ruptured or unruptured aneurysms was associated with a relatively high risk
of the development of new aneurysms. A new aneurysm developed in three (16%) of the 19
relatives with previous aneurysms and six (7%) of the 83 relatives without previous aneurysms.
Women had a higher risk than men for developing aneurysms, and siblings had a higher risk
than children and parents (Table 2).
A woman born in 1957 had an initial negative screening with MRA in 1995 (left). Three years later she
was admitted to another hospital with an SAH from an aneurysm of the anterior communicating artery
(right). The aneurysm was in retrospect not visible on the fi rst MRA. She was treated with clipping and
made a good recovery.
Figure 1
94
Chapter
Subgroup of relatives Number of relatives Number of relatives
with new aneurysms Relative Risk (95% CI)
No previous aneurysm
Previous aneurysm
83
19
6 (7%, CI 3-16%)
3 (16%, CI 4-40%)
Reference
2.2 (0.6 to 8.0)
Children*
Siblings*
Parents*
44
67
2
2 (5%)
7 (10%)
0
Reference
2.3 (0.5 to 10.6)
-
Men
Women
42
60
2 (5%)
7 (12%)
Reference
2.6 (0.6 to 11.
< 40 years**
40-60 years
> 60 years
60
40
2
4 (7%)
5 (13%)
0
Reference
1.9 (0.5 to 6.6)
-
Table 2 Relative risk for the development of new aneurysms or aneurysms detected after growth in
subgroups of relatives
CI = Confi dence Interval
* = Cumulative number since relatives can be classifi ed in more than one category
** = Age at initial screening
A woman born in 1949 was admitted in 1993 with an SAH from an aneurysm of the anterior communicating
artery. An angiogram in 1993 did not show any additional aneurysms (left). Screening in 2001 with CTA
showed an internal carotid aneurysm (middle). She was treated with coiling and made a full recovery
(right).
Figure 2
Discussion
We found that the yield of repeated screening for familial intracranial aneurysms is high;
in 16% of the relatives with previous aneurysms and in 7% of the relatives without previous
aneurysms new aneurysms were detected, mostly within fi ve years. In addition, two relatives
had an SAH in the 5-year interval between two screening procedures; one from a newly
developed aneurysm and one from an additional aneurysm that was missed on the initial
angiogram and the fi rst follow-up screen. These results indicate that persons with two or more
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fi rst-degree relatives with SAH are at high risk for the development of new aneurysms.
There was a trend for an increased risk of new aneurysm formation in relatives with a
previous aneurysm, women, siblings, and relatives between 40 and 60 years of age but these
results were not statistically signifi cant. Because we had no data on smoking habits and
hypertension in most of the relatives, we were not able to assess the impact of these risk
factors in our study.
Seventy-nine percent of the relatives who were advised to return for follow-up screening
actually returned. This proportion is high. We could not fi nd attendance rates of comparable
screening programs in other medical fi elds. One explanation for the high compliance might
be pressure on the relatives from other family members. The motive for the nonattendance
remains unknown because we considered it unethical to contact them and ask why they did
not return for screening.
In our study, we tried to avoid any bias. All relatives were informed and treated in the same way
and only one nonattendant was partly lost to follow-up (we knew she was alive but we had
no information on whether she had a SAH after the initial screening). In addition, relatives of a
large number of families were screened, which increases the generalizability of the results.
This is the fi rst study to assess the yield of repeated screening in a large series of subjects
with two or more fi rst-degree relatives with SAH or unruptured aneurysms. Three decision
analyses have been performed on the issue of screening for familial aneurysms, but none has
specifi cally or properly addressed repeated screening in persons with two or more affected
fi rst-degree relatives.8-10
Screening for aneurysms carries benefi ts but also risks. Screening can prevent new episodes
of SAH but can lead to disability and death from preventive treatment. With the ongoing
improvement in MRA and CTA techniques, more small aneurysms will be detected that
will often not be treated but followed up over time. The knowledge of having an untreated
aneurysm will negatively infl uence the quality of life.11 On the other hand, with the advent
of endovascular treatment, many unruptured aneurysms can now be treated with relatively
low risk of complications.12 The outcome after sporadic SAH is still very poor and probably is
even worse in familial cases.13 Until now no population-based clinical study has assessed the
risks and benefi ts or the cost-effectiveness of repeated screening in familial SAH. The high
yield of repeated screening in this study is a factor in favor of screening and indicates that
repeated screening should be considered for every relative in familial SAH.
The appropriate interval at which repeated screening should be performed has not yet been
established. It is often assumed that aneurysms need some years to develop. In our study,
two relatives were admitted for SAH within three years after a negative screening. Others
have reported a member of a family with intracranial aneurysms in whom SAH occurred
only two years after a negative angiography.14 These three examples show that screening
at an interval of fi ve years is not suffi cient to detect all new familiar aneurysms. In some
families, screening may have to be performed at intervals shorter than an arbitrary period
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Chapter
of fi ve years. The follow-up interval may have to be tailored to individual relatives according
not only to the family but also to individual risk factors. Smoking, hypertension and female
sex are important risk factors for the growth and development of intracranial aneurysms.15
Although we are not yet able to identify all characteristic features indicating high risk of rapid
aneurysm formation, individual risk factors should be taken into account in determining the
interval of repeated screening.
We conclude that repeated screening for familial intracranial aneurysms has a high yield,
especially in relatives with previous SAH. The attendance for repeated screening is high. The
interval at which screening should be performed remains uncertain and may have to be
tailored according to phenotype, genotype and additional risk factors.
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References
1. van Gijn J, Rinkel GJE. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;
124:249-78.
2. Schievink WI. Genetics of intracranial aneurysms. Neurosurgery 1997; 40:651-62.
3. Bromberg JE, Rinkel GJE, Algra A, Greebe P, van Duyn CM, Hasan D, Limburg M, ter Berg HW,
Wijdicks EF, van Gijn J. Subarachnoid haemorrhage in fi rst and second degree relatives of patients
with subarachnoid haemorrhage. BMJ 1995; 311:288-9.
4. Raaymakers TW, Rinkel GJE, Ramos LM. Initial and follow-up screening for aneurysms in families
with familial subarachnoid hemorrhage. Neurology 1998; 51:1125-30.
5. Ronkainen A, Hernesniemi J, Puranen M, Niemitukia L, Vanninen R, Ryynanen M, Kuivaniemi H, Tromp
G. Familial intracranial aneurysms. Lancet 1997; 349:380-4.
6. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC, Jr., Brott T, Hademenos G, Chyatte D,
Rosenwasser R, Caroselli C. Recommendations for the management of patients with unruptured
intracranial aneurysms: A Statement for healthcare professionals from the Stroke Council of the
American Heart Association. Stroke 2000; 31:2742-50.
7. Rinkel GJE, Djibuti M, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic
review. Stroke 1998; 29:251-6.
8. Dippel DW, ter Berg JW, Habbema JD. Screening for unruptured familial intracranial aneurysms. A
decision analysis. Acta Neurol Scand 1992; 86:381-9.
9. Crawley F, Clifton A, Brown MM. Should we screen for familial intracranial aneurysm? Stroke 1999;
30:312-6.
10. Leblanc R, Worsley KJ, Melanson D, Tampieri D. Angiographic screening and elective surgery of
familial cerebral aneurysms: a decision analysis. Neurosurgery 1994; 35:9-18.
11. van der Schaaf IC, Brilstra EH, Rinkel GJE, Bossuyt PM, van Gijn J. Quality of life, anxiety, and
depression in patients with an untreated intracranial aneurysm or arteriovenous malformation.
Stroke 2002; 33:440-3.
12. Brilstra EH, Rinkel GJE, van der Graaf Y, van Rooij WJ, Algra A. Treatment of intracranial aneurysms by
embolization with coils: a systematic review. Stroke 1999; 30:470-6.
13. Bromberg JE, Rinkel GJE, Algra A, Limburg M, van Gijn J. Outcome in familial subarachnoid
hemorrhage. Stroke 1995; 26:961-3.
14. Schievink WI, Limburg M, Dreissen JJ, Peeters FL, ter Berg HW. Screening for unruptured familial
intracranial aneurysms: subarachnoid hemorrhage 2 years after angiography negative for
aneurysms. Neurosurgery 1991; 29:434-7.
15. Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a
long-term follow-up study. Stroke 2001; 32:485-91.