On the origin of

cerebral
aneurysms
a scientific model
Haim Ezer, MD
 “Aneurysms are
nature’s way of
preventing cerebral
arterial dissection”
Unpublished data
 Introduction
• The problem – social and economic, initial
injury
• Aneurysms – current knowledge
• Study aim – develop a scientific model,
explain observations and provide a tool for
screening and prevention
• The future - Differential equations for definite
proof of pathogenesis
 Aneurysms Primer
• Saccular (berry) aneurysms only
• Location: circle of Willis
• Ruptures in 10/100000 (30000)
• Huge social and economical burden
• Half die within one month, third of rest
moderate to severe disability
• The answer doesn’t lie in clipping or coiling
but rather in screening and prevention
 Primer
• 1-5% of the population have cerebral aneurysms
• Most do not! Rupture (2/1000)
• Median rupture age is 57
• Up until 100 years ago, life expectancy was less than 40.
• Aneurysms, practically didn’t rupture
• Histopathologic data suggest that hemodynamic stress
leads to arterial wall degeneration and eventually to
aneurysm formation1
1. Youmans neurological surgery, 4-volume set: expert consult - online and print, 6e chapter 361 pathobiology of intracranial aneurysms page
3752
 Study questions
• What is the pathogenesis of cerebral aneurysms
• Why are they distributed in an anatomical
fashion?
• Why does one individual develop an aneurysm,
and another does not?
• Could we screen for cerebral aneurysm
• Why does a certain individual develops an
aneurysm, in a certain location and not in
another?
 Medial defects
• Many believed that aneurysms are the result of congenital defects
in the media at the bifurcations of intracranial arteries
• The distribution of aneurysms does not correspond to that of the
defects
• Extra cranial saccular aneurysms are unusual, while defects are
common
• In 1983, Stehbens demonstrated that the so-called medial defects
are actually physiologic intersections of two muscle layers1
• Accordingly, experimentally induced intracranial aneurysms in
rats were shown not to originate at the site of these
medial gaps1
1. Youmans neurological surgery, 4-volume set: expert consult - online and print, 6e chapter 361 pathobiology of intracranial aneurysms page 3748
 Primer – Rhotons rules
1. Aneurysms arise at a branching site on the parent
artery.
2. Aneurysms arise on the convex, not concave, side of
the curve.
3. Aneurysms point in direction the blood would have
gone if the curve (what we call jet impact zone or JIZ).
4. Aneurysm dome or fundus
points in the direction of
maximal hemodynamic
thrust in the pre-aneurysmal
segment of the parent artery.
 Social and economic burden
• Mean hospital charges, for ruptured aneurysm 170000$1
• 27000 cases of SAH per year.2
• Other charges: Life insurance, lifetime care, loss of incomes…
• Total cost is billion 5.6$ / year

1: 2010;41;337-342; Stroke
2: N Engl J Med 2006;355:928-39.
 Rt. And Lt dissimilarity
R

Mrs. Tamburo
Past work
The “perfect” normal group
 Aneurisk group
• Similar age distribution
• 55 unruptured 44 ruptured
• Median age 54
• 62 females 37 males
20-30 3
30-40 12
40-50 26
50-60 23
60-70 23
>70 13

MCA 24
ACA 23
ICA 45
BAS 7
The JIZ – Jet Impact Zone
 The curvature:
Intuitively, curvature is the amount by which a geometric
object deviates from being flat, or straight 
The “kink” point
 Methods
1. Original MRA 2. Segmentation & 3D reconstruction
 Methods
3. Centerline extraction 4. Curvature calculation High curvature

Low curvature
 Methods
High curvature

But on aneurysms:

Low curvature
 Study conclusions:

• 1. Cerebral arterial 3D curvature is kept

below a threshold of 0.7mm-1
• 2. The parent artery to an aneurysm, is at least
2mm in diameter.
• 3. Aneurysms develop only in the jet impact
zone.
 The wall stresses
Blood Jet hits
the arterial
wall

Aneurysm
initiation
 Fatigue (material)
•  weakening of a material caused by repeatedly applied
loads
• progressive and localized structural damage
•  If the loads are above a certain threshold, microscopic
cracks will begin to form at the stress concentrators
• The shape of the structure will significantly affect the
fatigue life; square holes or sharp corners will lead to
elevated local stresses where fatigue cracks can
initiate
SN curve
Very high cycle fatigue  (Nf > 107)
 Answered questions
• Why do certain individuals develop aneurysms
and others don’t.
• Why do they develop them in certain locations
• A screening tool possible
• High correlation to circle of Willis 3D
geometry
Transcranial Doppler (TCD)
TCD

MRA reconstruction
 Unanswered questions
• Why do certain individuals have theses sharp
bends and others don’t. (diff equations)
• Does beta blockers prevent aneurysm
formation
• Could TCD give a better resolution image