Aneurismi dissecanti e patologia della parete

Georges Rodesch MD PhD

Dept of Diagnostic and Therapeutic Neuroradiology

Hôpital Foch, Suresnes, France

Pathological mechanism and 3D structure of cerebral dissecting aneurysmsMizutani T et al , JNS 2001

The substantial pathological mechanism creating a dissecting aneurysm is createdby a sudden widespread disruption of the IEL

IEL : *mainly elastic fibers *most important layer of cerebral arterial wall for protection against

hemodynamic stress* supports blood pressure of 600 mm Hg (Glynn LE, J Pathol Bacteriol, 1940)

Endoth cellsconjonctive t

Smooth m cExtracell components (elastin, collagen, proteoglycanes…)

CollagenThick elastic fFibroblasts

Media is always disrupted adjacent to disrupted IEL

Plane of dissection extends through loose portion of media and is determinedby the extent of disruption of the media

If disruption of media is minimal, dissecting plane is between IEL and media

If the media is totally disrupted, dissecting plane is between media and adventicia

Dissecting aneurysms accompanied by infarction have less medial damage than those with SAH

Usually occurs in pts in 5 th or 6 th decades

Primary cause of dissection is unknown : Infection? Ischemia? Mechanical constraints? HTA?

Since Turnbull 1915 : syphilitic arteritis, rupture of vasa vasorum, medial degeneration, congenital defect in media and/or IEL…

Dissections : mechanical or biological phenomenon?

The tear…

« Entry only » vs. « Entry- Exit »

Immune: inflammatory, infectious, deficiency (HIV, candidosis…)Hemodynamic (BAVM+ AA…)Genetical: NF1, PKD, ED, FMD, Marfan…

Intracranial dissection

Surgical removal D35 post SAH

Disruption of IEL

Wall adjacent to rupture: thin fibrin and collagen

Most frequent type (?)Age at time of SAH: hrs-1w(no healing process)

Pseudolumen is « dead end »Blood flow unstable. Rebleed++If thrombosis: stenosis at A°Mizutani JNS 2001

Autopsy D35 post SAH

Disrupture of IEL + media« Entry only »

« Entry only »

Mizutani JNS 2001

Dense collagen proliferation atsurface of pseudo lumen

A°: smooth margins if patentpseudolumen

Age of « Entry-Exit » aneurysm?

Several weeks till time of bleeding because of dense proliferation of collagen at surface of pseudolumen

Constant stable flow throughpseudolumen for long periodswithout clinical symptoms

« Entry- Exit »

42y M

HIV+SAH

Dissecting Aneurysms

Stehbens (1963) MCA 41%VB 23%ICA 21%ACA 13%other 2%

Segmental vulnerability

Angiographic diagnosis (may be challenging)

arterial pouch/focal enlargement/fusiformstenosis proximal/distal

82% were subintimal (without SAH)

If distally located AA (PICA, PCA, MCA, ACA…): raise the possibility of dissection

Difficult to distinguish effects produced by triggersvessel wall diseaserepair processes

Stagnation in (false) AA, stenosis arterial segment, fusiform aspect artery…

Interest of MRI

Horie N et al, JNS 2011

Day 7

Mizutani 1999 4 types

1. Classic dissecting AA SAHfusiform; irregular wallrebleeding ++; death ++

disruption of elastic laminano intimal thickeningfalse lumenfragile adventiciano thrombus in AA

Acute process

EL regeneration in healed dissecting AA

61 Y maleSudden loss of consciousness

2. Segmental ectasia fusiform AA, smooth walllarge lumenno thrombus

stretched/fragmented ELmoderately thick intima

« placid » evolutionEL compensation by intimaChronic response?

3. Dolichoectatic dissecting AA

tortuous fusiform appearanceintraluminal organized thrombiintimal flapprogression giant size

fragmented ELdissections thickened intimathrombus at site intimal dissection

Recurrent hemorrhages inside walland thrombus

CourtesyT Siniluoto

4. Saccular AA unrelated to branchingSAH +++

EL disrupted, fragmenteddistended fragile adventicia

Blister AA

High frequency of rebleed in dissecting AA with SAH (57.1% within 1 week after initial SAH) (10% after 1 month)

Mizutani et al Recurrent SAH from untreated ruptured VB dissecting aneurysms

Neurosurgery 1995

Rebleed rate decreases after 1 WLongest interval between first SAH and rebleeding : 41 days=> Some healing mechanisms (scar…) are at work after SAH

Mizutani et alHealing process for cerebral dissecting aneurysms presenting with SAH

Neurosurgery 2004

13 pts: 9 VA, 2 ICA, 1 ICA, 1 SCA

43 y female dissection L VA autopsy D14Ruptured media + IEL no neo intima ruptured portion covered by thrombus

Healing process for cerebral dissecting aneurysms presenting with SAHMizutani T et al, Neurosurgery 2004

67 Y male Dissect VA Prox clipping D1Autopsy D14

Silent repair of IEL disruptionLocal thickening of neointima

Disrupted ends of IELDisruptend ends of adventicia

AA at the ruptured portion

34 y female Dissection L SCA. Resection D 23

Disruption of IEL Circumferential prolif of neointima

The time of genesis of dissecting AA can be determined on the basis ofclinical presentation (headaches, SAH, stroke…)

According to the time after presentation: chronological changes in arterial wall(healing process)

Injured arterial wall is repaired with other matrix components in a biological reaction (and many repairs can occur silently)

1st day: leucocytes + macrophages3-5 days: endothelial coverage4 days: smooth muscle cells1 week: neo intima (ceases at 3 months)

Pool et al Am J Pathol 1971Mizutani et al , JNS, 2004

*Newly synthetized smooth muscle cells (in neo intima)(from the disruptured ends of media towards ruptured part)*Extracellular matrix (collagen, elastic fibers, proteoglycans etc)

( determines the strength of the repaired vessel)

consists

4th dimension….Time

Healing mechanism may be delayed in certain conditions

*A longer time is needed for repair tissue over the whole vessel circumference : large dissecting aneurysms carry rebleed risk for a long time

*if thrombus in AA (neointima may appear in accordance to retraction of thrombus)

•AA where IEL and media are completely separated from adventitia

Theoretically: wall repair completed after full coverage of arterial wall by neointima

Rate of rebleed after one week ~ standard time for appearance of neointima

Mizutani 2004: neointima did not reach ruptured portion of dissection in most cases=> Pathological confirmation of safety from the risk of rebleed is not obtained…

Mizutani 2004

Initial FU

Decision to treat (sacrifice) when

progressive enlargement

Angio when trtt was decided. E° withdrawn at that stage

Further control

Because first « deflatening » of the sac was obtained during A°under GA and hypoAT, pt was proposed GA and hypoAT for 24hrs in ICU to promote

thrombosis. Angio confirmed the previous finding

Control shows

appearance of stenosis

on AICA proximal to AA

Healing process was

Suspected.

P1-P2 dissecting AA presenting with CVA treated with anticoagulation

Courtesy KTB

Intracranial Aneurysms in the pediatric population

• Traumatic

• Associated with BAVM

• Dissecting

• Inflammatory and infectious

• Hereditary (Familial)

• Collagen disorders

• “Congenital” or berry type (ruptured, unruptured)

• Atherosclerotic (fusiform, giant size etc)

1 y boy

3w earlier V+, « not well »gastroenteritis ? 1st HB ?

Dissection from mural hematoma

ExtrinsicFactors

Inflammation(Auto) immune

IschemiaAtherosclerosisHemodynamics

TraumaHTA

IntrinsicFactors

Systemic diseaseSegment. vulner.Dysplastic wallVasa Vasorum (?)Altered repair

mechanisms

Sub adventicial(transmural)

Subintimal

Reopeningof vessel lumen

Completerepair

SAH Distal emboli Normal aspect orfusiform dolicho a

Acute Subacute

Modified from P Lasjaunias 2006

Dissection from mural hematoma

ExtrinsicFactors

Inflammation(Auto) immune

IschemiaAtherosclerosisHemodynamics

TraumaHTA

IntrinsicFactors

Systemic diseaseSegment. vulner.Dysplastic wallVasa Vasorum (?)Altered repair

mechanisms

Sub adventicial(transmural)

Subintimal

Reopeningof vessel lumen

Completerepair

Recurrentdissections

SAH Distal emboli Normal aspect orfusiform dolicho a

Partiallythromb.AA

Acute Subacute Chronic

Modified from P Lasjaunias 2006

A form of « chronic » dissection: partially thrombosed AA

Schubiger et al, Neuroradiology 1987

« slow growth by recurrent hemorrhagesinto the lesion »

« recurrent hemorrhages from capillaries sprouting within the membrane of the lesion »

« the highly vascularized membranous wallof a giant intracranial aneurysm seems tobehave like the membrane of a chronic subdural hematoma »

«the giant intracranial aneurysm grows byrecurrent hemorrhage into its wall and behaves like growing encapsulated hematomas »

Zhao et al, Nat Med 2004 Krings et al, Neuroradiology, 2005

5-LO expressed in mast ¢,leucytesand macrophages

Once these ¢ are activated, 5-LO creates mediators of inflammation(leukotrienes) =>activation +recruitment

mast¢,leucytes,macrophages

Inflammatory process of vessel wall

Leucotriene binding to vasa vasorum leucocyte extravasation

proliferation of vasa vasorumweakening of vessel wall

arterial aneurysm formation »

Growth and rupture of these lesions depend on biological

factorsthat are induced from the outside with help of vasa

vasorum(« abluminal aneurysmal

vasculopathy »)P. Lasjaunias

Partially thrombosed AA

Other names?

AA with intramural haemorrhageChronic dissecting AA

Key words : vasa vasorum dissectioninflammation

Consequences: mass effectthrombus different agescontinuous growing (sometimes even after vessel occlusion)spontaneous thrombosis

PRE EMBO

Cause of dissection is unclear triggers: infection, ischemia ?...underlying disease ?biological disorders ?

Evolution variable : repeated ischemia /Hbspontaneous healing

no recurrence after healing/trtt

Sacrifice. Stent. FD? . Anatomy

SUMMARY

Frequent rebleed if presentation with hemorrhageRare bleeds if initial non hemorrhagic presentation