1. "De Novo" Aneurysms: Radiologic and Clinical Analysis of Our Eleven Years Experience G. Di Lella, S. Gaudino, P. Colelli, M. Rollo, B. Tirpakova*, C. Colosimo Dept. of Bioimaging and Radiological Sciences - * Institute of Neurosurgery Catholic University of Sacred Heart - Rome, ITALY.

2. INTRODUCTION Clinical evidence and multiple reports in the literature suggest that patients successfully treated for aneurysmal rupture should be considered at risk to develop new lesions: –adjacent to the former aneurysm (regrowth*), –or in a new site (de novo, additional*), where no pathology was found in previous neuroradiologic studies. The real incidence of new aneurysms is unknown due to inhomogeneity of data in the literature, being comprised between 0.8-2.2% for “de novo”, while the “regrowth” occurs in 0.5%. De novo lesions represents the most common cause of recurrent post-clipping SAH. –Familiarity, female sex, smoke, age at first bleeding and hypertension are considered to be risk factors. –There is a correlation, due to genetic factors, between de novo lesions and the finding of multiple aneurysm when the first SAH occurs. *Wermer MJ, Greebe P et al. Late recurrence of subarachnoid haemorrhage after treatment for ruptured aneurysms: patient characteristics and outcomes. Neurosurgery 2005; 56: 197-204

3. PURPOSE The aim of this study was to evaluate frequency, risk factors and epidemiology of “de novo” aneurysms in our series of patients, previously treated for intracranial anerysms, in the last 11 years.

4. MATERIALS AND METHODS 298 patients with 318 aneurysms (F/M=3:2, mean age 54.8 years) treated with surgery (225 patients, 239 lesions) and/or by endovascular approach (73 patients, 77 aneurysms) in our institution, between 1998 and 2009, were retrospectively reviewed. 105 surgical Pts with 114 aneurysms were 0 on Hunt-Hess scale, while 120, with 125 aneurysms, had SAH. Among Pts treated with embolization 33 were free of haemorrhage while 40 had SAH.

5. RESULTS - 1 Ten patients ( 7 F, 3 M, mean age 44.1 years) developed 13 de novo lesions with an average interval of 13 years. All but one of the patients were under 40 years of age at the diagnosis of the first aneurysm. Four patients were smokers, while three had hypertension. Only one patient, a young female, had a familiar history of brain aneurysm, while another female and a young male developed multiple lesions. Two patients, both with SAH at the time of first diagnosis, had new haemorrhage. In one case a de novo aneurysm occurred less than one year after the first treatment. Regarding the site all but one of the lesions were in the anterior circulation, ICA and MCA being the most frequent locations.

6. RISK FACTORS Major risk factors were, also in our series, female sex, age and smoke

7. Our results are in accordance with the literature regarding the higher female prevalence, younger age of discovery of the first aneurysm and smoke as risk factors in de novo lesions, while hypertension was found only in three cases, and familiarity in one. The percentage of de novo lesions in our series (3%), higher than other reported series, may be due to the retrospective analysis of the older cases, of which sometimes were available for comparison only the more important DSA frames. RESULTS - 2

8. RESULTS - 3 In one case infact the last CT-angio showed a third lesion, not present at the time of first bleeding but visible, also if not detected, in a review of the previous CTAs performed between 2005 and 2008: this small (3mm) aneurysm may thus be considered both “de novo” and “additional”. The first lesion was treated by surgical clipping in 8/10 Pts (2/10 received endovascular coiling), while 5/10 underwent second surgery to treat the “de novo” lesion. 4/10 were untreated and 1/10 had endovascular approach. All Pts had good outcome, certainly favoured by the low Hunt-Hess grade (4/6 grade 0, 2/6 grade 1-2), with the exception of a transitory language impairment in a Pt treated for a de novo lesion in the L MCA.

10. Pt 10 male 25y.o. Pre-treatment DSA 07-1998 Post-treatment angiograms 03-1999: note the regular profile of the cavernous and ophthalmic R ICA and absence of lesions in the L MCA trifurcation

11. First follow up CTA (05-2005) demonstrated a de novo lesion located on the ophthalmic R ICA (white arrows).

12. Last CTA (02-2009) shows slight progressive increase of the aneurysm located on R ICA, also depicting another, smaller lesion on the trifurcation of L MCA (green arrows).

13. The retrospective review of first CTA (05-2005) demonstrated the presence of the second de novo aneurysm, on the L MCA.

14. Pt 3 A.P. female, 28yrs: post-surgical rotational DSA shows a clip located on the Acom and demonstrate normal profile of left ICA

15. Follow up CTA after 13 yrs demonstrate a de novo lesion located on the L ophtalmic ICA, under the anterior clinoid (arrows). A successive DSA confirmed the shape, size and location of the new aneurysm

17. CONCLUSIONS Our data, in accordance with the literature, suggest that SAH from brain aneurysms may not be a "one time" event. Patients treated have a higher risk (30/1)* to develop a new lesion and, if younger of 45 yrs at the time of first treatment, should be evaluated by CT or MR angiography, depending on the previous surgical or endovascular procedure, one year after the surgery and subsequently every two years. The type and incidence of risk factors suggest a genetic influence, despite the fact that in our series only one Pt had a familiar history of brain aneurysm. *Wermer MJ, Greebe P et al. Late recurrence of subarachnoid haemorrhage after treatment for ruptured aneurysms: patient characteristics and outcomes. Neurosurgery 2005; 56: 197-204

18. CONCLUSIONS Dedicated genetic studies on the aneurysm wall are trying, in the Neurosurgical department of our Institution, to find patients with higher risk of aneurysm development and those, between them, with higher rupture risk. Higher expression of apoptotic phenomena was found in a preliminary study on the aneurysm wall, compared with samples of extracranial arteries of the same Pt, published in 2004*. Another more recent study^ found higher expression of genes favouring proapoptosys in Pts harbouring intracranial aneurysms. *Pentimalli L, Modesti A, Vignati A et al. Role of apoptosis in intracranial aneurysm rupture. Journal of Neurosurgery 2004; 101: 1018-25. ^Marchese E, Vignati A, Albanese A, et al. Comparative evaluation of genome-wide gene expression profiles in ruptured and unruptured human intracranial aneurysms. Journal of biologic regulators and homeostatic agents. Vol 24, no2, 185-195 (2010)

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