Unruptured Aneurysms Pipeline Onyx Coils Jawad F. Kirmani, MD

CREDITS Adnan Qureshi, MD For content and some of the power point slides

Pathophysiology of aneurysm rupture

GDC delivery into the aneurysm sac

Thrombogenesis during GDC embolization - Electrothrombosis - - - Platinum - + + + + Electrolysis Stainless steel Electric charge

Different size and shapes of GDC

Unstable GDC in broad neck aneurysms Cath ICA

Balloon Stent/Coil Occlusion GDC Aneurysm Aneurysm ACA Balloon Cath GDC Cath MCA ICA

Stent-assisted GDC placement

Histological appearance GDC intermingled with thrombus with subsequent organization

Gross morphology Damiani

Histological Appearance

Histological Appearance

Basilar apex aneurysm Pre-procedure Post-procedure

Middle cerebral artery aneurysm Pre-procedure [lateral] Post-procedure [AP]

A. Before Coil Treatment Internal carotid artery aneurysm  A. Before Coil Treatment  B. After Coil Treatment

Internal Carotid Artery Aneurysm Cruz

Balloon assisted GDC embolization Cruz

Balloon assisted GDC embolization Cruz

Dissecting vertebral artery aneurysm Ward

Stent assisted GDC embolization Ward

Who to treat? All ruptured intracranial aneurysms should be considered. All unruptured intracranial aneurysms >10mm should be considered. Unruptured intracranial aneurysms >2mm that are symptomatic may be considered. Unruptured intracranial aneurysms>5 mm in patients with family history of subarachnoid hemorrhage or intracranial aneurysms or previous rupture of another aneurysm.

Tools for estimating the Life-time risk of rupture & Effect of intervention on life-expectancy

Unruptured aneurysms Increasing numbers being diagnosed 45% - 80% of patients with ruptured aneurysm may die Not all rupture Treatment morbidity 0-16%; mortality 0-25% Treat those at high risk of rupture

ISUIA 2003 Prospective Multi-centre 1692 patients did not have treatment Selection bias Not randomised Aneurysms < 2mm not included Mean duration of follow-up was 4.5 years Patients who subsequently underwent treatment excluded from analysis Included only North America and Europe

ISUIA, 2003 The best we have Findings of ISUIA (2003), could be incorporated into the global view of UIA Considered along with other data pertaining to the patient

Objective Tools for calculating rapidly at: Neurovascular MDT meetings Clinics

Method Cumulative risk (%) = 100 x {1- [(1-annual risk)/100]^years}

Maths of Probability Annual risk of no-rupture = 98% 2 1.96 100 98 Annual risk of rupture = 2% Annual risk of no-rupture = 98% 2 1.96 100 100 × 0.98 98 100 × 0.98 × 0.98 96.4 100 × 0.98 × 0.98 × 0.98 Chance of non-rupture = 100 × (risk of no-rupture) years Chance of rupture = 100 – chance of no-rupture

Calculation: Simple Vs Actual 1% annual risk over 10 years 10 9.6 3 % annual risk over 20 years 60 46

Updated ISUIA (2003) 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms.

Updated ISUIA (2003) < 7 7-12 13-24 ≥25 Group 1 Group 2 Cavernous carotid 3% 6.4% AC/MC/IC 1.5% 2.6% 14.5% 40% Post-P comm 2.5% 3.4% 18.4 % 50% 5 year cumulative rupture rate. Wiebers DO et al. Lancet 2003; 362: 103-10

Annual risk of rupture of unruptured aneurysm < 7 7-12 13-24 >=25 Group 1 Group 2 Cavernous carotid 0.6 1.3 AC/MC/IC 0.3 0.5 3.1 9.7 Post-P comm 0.7 4 13

UCAS The UCAS study assessed 5720 patients with 6697 aneurysms. 2722 patients with 3050 aneurysms underwent surgical or endovascular repair, while the remainder received conservative treatment. The follow-up period was 3 months to 9 years with a total of 11660 aneurysm-years.

UCAS Aneurysm location was categorized into seven groups: 1. Middle cerebral artery 2. Anterior communicating artery 3. Internal carotid artery 4. Internal caotid – posterior communicating artery 5. Basilar tip and basilar – superior cerebellar artery 6. Verterbal arteries, the posterior inferior cerebellar arteries and vertebro-basilar junction 7. Others

UCAS The size of the aneurysms was categorized into five groups: 1. 3-4 mm 2. 5-6 mm 3. 7-9 mm 4. 10-24 mm 5. ≥ 25 mm

UCAS (annual chance of not bleeding) x expected years of life  = risk of hemorrhage http://www.kockro.com/en/calculators

UCAS As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48).

Risk of Intervention Vs natural history Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient. The Risk of intervention is immediate Risk of natural history is distributed over the life-time

Need to take into out those who will have a good outcome following rupture

Life table Life-expectancy tables for 2001-2003 Constructed abridged life-tables

Look-up tables ‘Actuarial-type’ table Gender specific Calculations performed using Microsoft® Excel® Table laid out using Adobe® Illustrator CS2® and Adobe® InDesign CS2®

‘Hope’ calculator Life-time risk of rupture of unruptured aneurysms Effect of intervention on the life-expectancy Software developed with Macromedia® Flash 8® Both Windows and Mac compatible

55 year old male with sah with an incidental 5 mm Acomm Aneurysm

A 50 year old female with 8 mm rt. PICA aneurysm

AVM’s-Background Arteriovenous Malformations (AVMs) are direct arterial-to-venous shunt without an intervening capillary bed. Prevalence of Cerebrovascular arteriovenous malformations is between 0.8% to 1.4% in the population Current Treatments: Surgery Radiosurgery Embolization Combined Treatment Arterial Phase Venous Phase

Direct Supply Fistula and Plexiform AVM Morphology Direct Supply Plexiform “En Passage” Plexiform with Venous aneurysm Feeding Artery Draining vein Direct Supply Fistula and Plexiform

Embolic materials Solid agents: Polyvinyl alcohol particles, Fibers, Microcoils, Microballoons. Liquid agents: I-butyl cyanoacrylate (IBCA) N-butyl cyanoacrylate (NBCA) Absolute ethanol. Henkes H. Nahser HC. Berg-Dammer E. Weber W. Lange S. Kuhne D. Endovascular therapy of brain AVMs prior to radiosurgery. Neurol Res 20(6):479-92, 1998 Sep

Embolization with NBCA Mixtures Embolic Agent NBCA Visualization Lipiodol Ethiodol Pantopaque Tantalum Tungsten Polymerization Lipiodol Ethiodol Pantopaque Glacial Acetic Acid

Preoperative embolization of AVMs Decrease the nidus size Occlude deep, surgically inaccessible or deep arterial feeding vessels to facilitate Can favorable effect the operative times, intra-operative blood loss, and even neurological outcomes Complete surgical removal can be achieved in up to 96% of the patients

Preoperative embolization of AVMs

Pre-radiosurgical intervention for AVMs Reduce the lesion to less than 3 cm Obliterate intranidal or venous aneurysms Radiosurgery produces total occlusion in 65% of the partially embolized AVMs

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