1. DIAGNOSIS AND TREATMENT OF DELAYED COMPRESSIVE SYNDROMS ASSOCIATED WITH SILK FLOW DIVERTER Jérôme Berge, Xavier Barreau, Vincent Dousset Neuroradiology Department Isabelle Pellegrin, Patrick Blanco, Jean François Moreau Immunology Department University Hospital, Bordeaux, France.

2. Analogy with inflammation on aneurysm of abdominal aorta (Kazi M, J Vasc Surg 2003; 38:1283-92) Rupture often happens on the atheromatous covered portion : –Thrombus growth induces an increased risk of rupture –Thikness of the endoluminal thrombus is also associated with an increased risk of rupture Histology of the thrombus covered wall: –thinner aneurysmal wall on covered portion –rarefaction of elastic fibers and smooth cells –Increased number of inflammatory cells –apoptosis

4. Other exemple of IC aneurysmal wall inflammation: Frösen, Hernesniemi: (stroke. 2004; 35:2287-2293) –Histological analysis on 42 ruptured aneurysms: –« Before rupture, the wall of saccular aneurysm undergoes morphological changes associated with remodeling of the aneurysmal wall. » –Factors associated with ruptured wall: Endothelial lining absent in 62% Organized thrombus lining the wall in 60% of ruptured aneurysms Infiltrating myosin + cells in organized thrombus in 67%

5. 2005: 28 yo female: History of SAH (GCS = 14) Embolisation with12 bare coils Day 4 : fever + headache + progressive right hemiparesis => Vasospasm assumed

6. Bordeaux study about 17 patients treated by Silk Stent: patients and method 17 patients with aneurysms of average diameter = 18,1 mm All patients had non ruptured aneurysms –7 patients had history of compressive syndroms –10 were asymptomatic 17 patients treated by SILK stent –Without any association of coils in the sac. –Coils used in 2 patients for controlateral arterial feeder occlusion (ACom and controlateral vertebral artery)

7. Clinical data Delayed peri-aneurysmal inflammation. –in 7 cases out of 17 (41%) –All these patients were symptomatic before Silk. Onset of several symptoms: –Headaches in all patients (7 cases) –Increased of initial neurological symptoms (6 cases). 3 cavernous sinus, 1 optic nerve and 2 brainstem compression –No history of seizure in our serie Compression happens between day 3 and day 10 Complete recovery before day 30 in all patients. Some patients had steroids (1 mg/kg) during 3 weeks. No history of late hemorrhage in this group –With 6 months follow up

8. 57 years old female with warning hickups

9. Day 3 after Silk treatment : onset of stiff neck and intense headache re-admitted on day 5 MRI before Silk treatment MRI 10 days after Silk

10. Relationship between morphology of the sac and inflammatory symptoms Measure of aneurysmal area between thrombus and aneurysmal wall: –Following the formula of spheroïde area –two groups (day 3 to day 10 post SILK) Inflammatory group: average sac surface = 804 mm2 Asymptomatic group: average sac surface = 305 mm2

11. Endothelial activation THROMBUS: heavy load of thrombin Cytokinsactivation Vascularpermeabilityincreased Opening BBB ElastaseCollagenase Metallo proteinases Fibroblast growth factor Lysis of the aneurysmal wall Destruction of elastic fibers chimiotactism aneurysmal wall anoxia aneurysmal wall anoxia Oedema Cellular lysis => warning signal Cellular lysis => warning signal Recruitment of macrophages And astrocyts Recruitment of macrophages And astrocyts

12. Physiopathology of inflammation: 3 step chain reaction ? Inflammatory reaction : rupture premice ? 1° step: asymptomatic contrast enhancement –18 % of patients with bare coils (Fanning, TerBrugge, J.Neurosurg.2008) 2° step: peri-aneurysmal inflammation thrombosisanoxiawall lysis enzymes peri-aneurysmal macrophagic induction 3° hypothetical step: onset of aneurysmal hemorrhage –after wall lysis by macrophages activation and subacute recanalisation around the instable clot 3 / 51 patients in our multicentric French serie 8 patients in the English report on march 2010 (source: French association for sanitary security (AFSSAPS) Kulcsar (13 patients)

13. 3 ways to slow this immunological chain reaction: Preventive corticotherapy is mandatory in all patients Modify stent design to induce a more progressive flow reduction within the aneurysmal sac Flow diverters aren’t they too efficient ? Creating a core of permanent and organized thrombi would modify the delay of clot constitution Do we have to introduce some device in the sac before stenting with Flow Diverter ?