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FI
ISCHEMIC STROKE
• 3rd most common cause of death and permanent disability with 30-
50% do not regaining functional independence. The majority of these
events are ischemic (87%), as opposed to intracerebral (10%) and
subarachnoid hemorrhages (3%) (AHA. Heart and Stroke Update. 2010)
• ~780,000 new or recurrent stroke cases annually
CEREBRAL CIRCULATION
The brain receives its blood
supply from four main
arteries: the two
internal carotid arteries and
the two vertebral arteries.
CEREBRAL CIRCULATION
Management of acute ischemic stroke
• Management of acute ischemic stroke was previously geared toward
prevention, supportive care, and rehabilitation.
• The medical management of stroke has progressed exponentially,
with FDA approval of r-TPA, alteplase in 1996.
• Intravenous administration of r-TPA within a limited 3-hour window
from symptom onset has shown a significant improvement in patient
outcome at 3 months. Fagan SC, Morgenstern LB, Petitta A, et al. Cost-effectiveness of tissue plasminogen activator for acute ischemic
stroke. NINDS rt-PA Stroke Study Group. In: Neurology; 1998:883-90
• Current stroke guidelines have extended the therapeutic r-TPA
administration window to 4.5 hours..
IV TPA Trials
6 major randomized placebo-controlled trials
1)Alteplase Thrombolysis for Acute Non interventional
Therapy in Ischemic Stroke [ATLANTIS] I and II
2) European Cooperative Acute Stroke Study [ECASS] I and II
3) NINDS I and II
•2775 pts treated with IV rtPA or a placebo within 6 hrs of onset
•Confirmed the benefit up to 3 hrs
ECASS III subsequently confirmed benefit of IV tPA in a 3 to 4.5-hr window
IV TPA - LIMITATIONS
•ICA and M1 occlusions have lower rate of recanalization than
M2–M4 occlusions.
•52% with NIHSS <10 will reach NIHSS of 1 after IV tPA, but
only 8% with NIHSS >20
•30% of MCA occlusions recanalize with IV tPA only within 2
hours
•ICA occlusions recanalize only at 1/3 of the rate of MCA
occlusions.
1Del Zoppo Ann Neurol 1992; 32:78-
86
2)NINDS Stroke 1997;28:2119–2125
3)Linfante Stroke 2002;33:2066-2071
M1: from the origin to bifurcation/trifurcation (the limen insulae); also known as
horizontal or sphenoidal segment
M2: also known as insular segment, from bi(tri)furcation to circular sulcus of insula
where it makes hairpin bend to continue as M3
M3: opercular branches (those within the Sylvian fissure); also known as opercular
segment
M4: branches emerging from the Sylvian fissure onto the convex surface of the
hemisphere; also known as cortical segment
Logistic regression curve representing an estimate of the probability for
successful recanalization of occluded vessels by IVT depending on
thrombus length
• Christian H. Riedel et al. Stroke.
2011;42:1775-1777
Length of the HMCAS (MM)
Probabilityofrecanalization
Endovascular management.
• Sussman and Fitch described the IA treatment of acute carotid
occlusion with fibrinolysin injection in 1958.
• Late1990’s experienced exponential progress and
development.
• Recent advances in endovascular techniques have increased
the therapeutic window of r-TPA administration.
• The newer IA devices for clot retrieval and vessel
recanalization has revolutionized the neuroendovascular
management of acute ischemic stroke.
Sussman BJ, Fitch TS. Thrombolysis with fibrinolysin in cerebral arterial occlusion. In:Journal of the American Medical Association; 1958:1705-9.
Patient selection and imaging
• An initial evaluation with a non-
contrast computerized tomography
(CT) head scan is necessary.
• Penumbra Pivotal Stroke Trial
1. Retrospective analysis of 85
patients
2. Results:
• Baseline CT scan by ASPECTS
score>7 had a 50% chance of a
favorable clinical outcome with
early recanalization (p=0.0001).
• In addition, ASPECTS scores of
less than 4 did not show clinical
improvement regardless of
endovascular recanalization
Goyal M, Menon BK, Coutts SB, Hill MD, Demchuk AM, Penumbra Pivotal Stroke Trial Investigators CSP, and the Seaman MR Research Center.
Effect of baseline CT scan appearance and time to recanalization on clinical outcomes in endovascular
thrombectomy of acute ischemic strokes. In: Stroke; 2011:93-7.
• Large territorial infarcts  High risk hemorrhagic conversion
 poor candidates for endovascular therapy.( Vora NA, Gupta R, Thomas AJ, et al.
Factors predicting hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke. In: AJNR American
journal of neuroradiology; 2007:1391-4)
• Intra-parenchymal hematoma is a contraindication to
endovascular recanalization.
• Presence of a hyperdense MCA sign on the initial head CT
does not have a significant prognostic value in patient outcome
and vessel recanalization rates.[ Gönner F, Remonda L, Mattle H, et al. Local intra-arterial thrombolysis in
acute ischemic stroke. In: Stroke; 1998:1894-900.)
CT PERFUSION SCANS
• CT perfusion scans
“salvageable” tissue.
• Perfusion scan demonstrates
the pneumbra lesion volume
or mean transit time which is
essential for determing
outcomes.. Konstas AA, Goldmakher GV, Lee TY, Lev MH.
Theoretic basis and technical implementations of CT perfusion in acute
ischemic stroke, part 1: Theoretic basis. In: AJNR American journal of
neuroradiology; 2009:662-8.
• NIHSS and AGE No statistical significance with ICH(vora et
al)
• Hyperglycemia >200 mg/dl  Increase risk of ICH(vora et al)
• Previous administration of intravenous tPA is not a
contraindication to IA intervention (Vora NA, Gupta R, Thomas AJ, et al. Factors predicting
hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke. In: AJNR American journal of neuroradiology; 2007:1391-4.)
• Zacharatos and colleagues study
Retrospective study of 156 pts.
Results: Thrombolytic therapy (chemical or mechanical)
showed a favorable clinical outcome versus supportive
management in the 80 years and older age group. (Zacharatos H, Hassan
AE, Vazquez G, et al. Comparison of acute nonthrombolytic and thrombolytic treatments in ischemic stroke patients 80 years or older. In: The
American journal of emergency medicine; 2011.)
Angiographic evaluation
• To see for ischemic etiology and initiation of treatment.
• Examination of the cerebrovascular anatomy begins with the
aortic arch.
• Based on the patient symptomatology and pre-procedure
imaging, selective catheterization of the carotid or
vertebrobasilar circulation supplying the affected territory is
performed
• Attention is paid to the extracranial collateral circulation, the
leptomeningeal anatomy, the circle of Willis, and overall
global cerebral perfusion.
• Grade of angiographic collaterals is a decisive factor for the
degree of reperfusion and clinical improvement. Bang OY,Saver JL, Kim SJ, et al.
Collateral flow predicts response to endovascular therapy for acute ischemic stroke. In: Stroke; 2011:693-9
Conscious sedation Vs GA
• The use of general anesthesia is preferred due to motion
elimination contributing to procedural safety and efficacy.
• Newer studies suggest that conscious sedation or local
anesthesia may lead to more favorable radiographic and
clinical outcomes by decreasing time delay and cerebral
ischemia from hypoperfusion
• (McDonagh DL, Olson DM, Kalia JS, Gupta R, Abou-Chebl A, Zaidat OO. Anesthesia and Sedation Practices Among Neurointerventionalists
during Acute Ischemic Stroke Endovascular Therapy. In: Frontiers in neurology; 2010:118.
• Gupta R. Local is better than general anesthesia during endovascular acute stroke interventions. In: Stroke; 2010:2718-9.)
REPERFUSION STRATEGIES1
• Recanalization or antegrade reperfusion
• Global reperfusion (flow augmentation or transarterial retrograde
reperfusion)
• Transvenous retrograde reperfusion (flow reversal)
Intra-arterial chemical thrombolysis
• Agents converts plasminogen into plasmin degrades fibrin and
products.
• Recombinant tissue plasminogen activator (r-tPA) and recombinant
pro-urokinase (rpro-UK) have been widely studied and used most
frequently. (Berenstein Alejandro, Lasjaunias Pierre, G. ter Brugge Karel. Surgicalneuroangiography. Vol. 2, Clinical and endovascular
treatment ... . In.)
• Alteplase (r-tPA), is a serine protease, has a half-life of 3.5 minutes
and a dosage range of 20-60 mg.
• Pro-UK has a halflife of 7 minutes and may be favorable to r-tPA
due to decreased side effects
• Third-generation agents, such as reteplase and tenecteplase, have
longer half-lives (15-18 minutes) and theoretically favorable vessel
recanalization and local recurrence rates.( Nogueira RG, Schwamm LH, Hirsch JA. Endovascular
approaches to acute stroke, part 1: Drugs, devices, and data. In: AJNR American journal of neuroradiology; 2009:649-61.)
• The aforementioned agents have prothrombotic effects by the
production of thrombin during thrombolysis, and subsequent
activation of platelets and fibrinogen.( Nogueira RG, Schwamm LH, Hirsch JA. Endovascular
approaches to acute stroke, part 1: Drugs, devices, and data. In: AJNR American journal of neuroradiology;2009:649-61.)
• Concomitant use of systemic anticoagulation during IA
thrombolysis is recommended with caution to risk of ICH.
• Widely used adjuvant systemic agent is heparin.
Memon and colleagues Study
1. Reviewed 35 cases of adjunctive use of eptifibatide in
salvage reocclusion and thrombolysis of distal thrombi with a
single bolus of 180μg/kg.
• They reported a partial to complete recanalization of 77% with
incidence of post-operative hemorrhage was 37% . Memon MZ, Natarajan SK,
Sharma J, et al. Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischemic stroke. In: J Neurosurg; 2010.
Anterior circulation
Middle cerebral artery
• Three major clinical trials evaluated the efficacy of IA
thrombolysis in the Middle Cerebral Artery (MCA) circulation
1. PROACT I and II (Prolyse in Acute Cerebral
Thromboembolism)
2. MELT trials (Middle Cerebral Artery Local Fibrinolytic
Intervention Trial)
• The average intervention time varies from 45 to 180 minutes,
high-risk patients should be treated within 4-5 hours from
ischemia onset. (Brott T. Thrombolytic therapy. In: Neurologic clinics; 1992:219-32.)
PROACT 1
• 40 patients were randomized for treatment of acute ischemic
stroke within 6 hours of symptom onset
• Cerebral angiography was performed, and M1 or M2 occlusions
were treated with 6 mg of rpro-UK (n=26) or placebo (n=14).
• Results:
Rpro-UK treated patients had higher vessel recanalization rates
compared to placebo (57.7% versus 14.3%). The incidence of
ICH was higher in the rpro-UK group (15.4% versus 7.1%) (del
Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: aphase II randomized trial of recombinant pro-urokinase by direct
arterial delivery)
PROACT 2
• This randomized, controlled clinical trial treated patients
with MCA occlusion within 6 hours of symptom onset
with either 9 mg of IA rpro-UK and heparin infusion
(n=121) or heparin infusion alone (n-59).
• Results:
• Patients who received IA rpro-UK had significantly
lower Rankin scores at the 90-day endpoint compared to
heparin only treated patients. The MCA racanalization
and mortality rates favored the rpro-UK group as opposed
to the control group (66% versus 18%) (Furlan A, Higashida R, Wechsler L, et al.
Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral
Thromboembolism. In: JAMA; 1999:2003-11.)
Theron et al Study
• Investigated the efficacy of IA thrombolysis in patients who
had acute internal carotid artery (ICA) with MCA occlusion.
(Theron J, Courtheoux P, Casasco A, et al. Local intraarterial fibrinolysis in the carotid territory. In: AJNR American journal of neuroradiology;
1989:753-65).
Results:
1. IA fibrinolysis of the MCA should be performed within 6
hours from ischemia onset, when the occlusion involves
the horizontal segment of the MCA extending into the
lenticulostriate arteries.
2. If the occlusion does not involve the horizontal MCA
segment and the lenticulostriate arteries, then the treatment
window can be extended to 12 hours following symptoms.
Acute right MCA occlusion
Mid-arterial digital subtraction angiogram of right ICA shows complete MCA occlusion at
the level of the bifurcation, frontal and lateral views
Mechanical thrombolysis with Penumbra device
showing recanalization of the superior
M2 division in a frontal high magnification view
Frontal and lateral views of right ICA
angiograms following MCA mechanical
recanalization.
Internal carotid artery
• Occlusions of the proximal ICA (extra-cranial)
generally have a better prognosis than intracranial
occlusions
• Patients with insufficient extracranial-intracranial
anastomoses or an incomplete circle of Willis may
be predisposed to developing significant
neurological symptoms. These patients are
potential candidates for IA intervention.
• Mechanical thrombolysis, in addition to
pharmacological thrombolysis, is of paramount
importance for recanalization.
• Negative prognostic factors include distal ICA
distribution involving the M1 and A1 segments
(“T” occlusion) and poor neurological presentation
. In a 25-patient series, Jovi and colleagues demonstrated successful
revascularization in 92 % of patients followingthrombolysis and ICA stenting.
• Bhatia et al, recanalization following IV r-tPA in patients with
T occlusion is the lowest at 4.4%.( Bhatia R, Hill MD, Shobha N, et al. Low rates of acute
recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for
action. In: Stroke; 2010:2254-8).
• Arnold and colleagues presented a series of 24 patients with
distal ICA occlusions treated with IA urokinase. Favorable 3-
month functional outcome was present in only 16% of
patients, and the mortality rate was approximately 42%. (Arnold M,
Nedeltchev K, Mattle HP, et al. Intra-arterial thrombolysis in 24 consecutive patients with internal carotid artery T occlusions. In: J Neurol
Neurosurg Psychiatr; 2003:739-42.)
• Flint et al published a series of 80 patients with ICA occlusion
who were treated with combinations of the Merci retriever
with or without andjunctive endovascular therapy.
Recanalization rates were higher in the combination group
(63%) as opposed to the Merci group (53%). Flint AC, Duckwiler GR, Budzik
RF, Liebeskind DS, Smith WS, Committee MaMMW. Mechanical thrombectomy of intracranial internal carotid occlusion:
pooled results of the MERCI and Multi MERCI Part I trials. In: Stroke; 2007:1274-80.
Adjuvant mechanical assistance with devices for balloon angioplasty, clot retrieval, and vessel
stenting enhance the probability of vessel recanalization
Case
• Acute left ICA occlusion. The patient
presented 6 hours following onset of global
aphasia and R hemiplegia
A-B. Mid-arterial digital subtraction angiogram of left ICA artery
showing complete occlusion of the distal ICA (T occlusion), frontal and lateral
views.
C. Frontal view of balloon angioplasty and recanalization of the distal left
ICA.
D-E. Frontal and lateral views of left ICA angiograms following mechanical
and chemical recanalization with balloon angioplasty, Merci device, and
administration of of Urokinase.
Central retinal artery
• Occlusion of the Central Retinal Artery (CRA) is an
ophthalmologic emergency with natural history that leads to
loss of vision.
• Conventional medical therapy have limited efficacy.
• In most studies, IA alteplase is most commonly used within 4-
6 hours from symptom onset.
• Padolecchia and colleagues showed that intervention within
4.5 hours of ischemic onset leads to visual improvement in all
patients. (Padolecchia R, Puglioli M, Ragone MC, Romani A, Collavoli PL. Superselective intraarterial fibrinolysis in central retinal
artery occlusion. In: AJNR American journal of neuroradiology; 1999:565-7.)
Posterior circulation
• Acute basilar artery (BA) occlusion is a life-threatening event
with untreated BA occlusion having mortality rates ranging
from 86% to 100%.
• In a series of nearly 300 patients, Furlan and Higashida
reported an IA recanalization rate of 60%, and mortality rates
of 31% in at least partially recanalized patients as opposed to
90% in nonrecanalized patients. (Furlan A, Higashida, R. Intra-arterial thrombolysis in acute ischemic
stroke. In: Stroke: Pathophysiology, Diagnosis, and Management. 4th ed. Philadelphia: Churchill Livingstone; 2004:943-51.)
IA Vs IV
• Lindsberg and Mattle compared BA occlusion treatment with
IV or IA thrombolysis.
• Results:
They found that although recanalization rates were higher
with IA treatement (65% versus 53%), dependency or death
rates were equal between the two groups (76-78%).
• Conclusion:
Emergent thrombolysis via either technique is of paramount
importance to the survival of this patient population.
BASICS STUDY
• Basilar Artery International Cooporation Study (BASICS),
624 patients with radiographically confirmed occlusion of the
BA were enrolled in nearly 50 centers over a 5-year period.
• Results:
All patients (n=41) treated with IA or IV thrombolytics
beyond 9 hours from symptom onset had a poor reported
outcome.
• Conclusion:
The therapeutic window can be successfully extended upto 6-9
hours but not more than 9 hours.
Schonewille WJ, Wijman CA, Michel P, Algra A, Kappelle LJ, Group BS. The basilar artery
international cooperation study (BASICS). In: International journal of stroke : official journal of the International Stroke Society; 2007:220-3.
LEVY et al study
• In a metaanalysis of 164 patients with BA occlusion over a 10-
year period
• Factors with a negative prognostic value were
1. Coma at initial presentation
2. Failure of vessel recanalization
3. Proximal vessel occlusion.
• Distal BA occlusions are more commonly embolic in nature
and therefore have a better response to thrombolytic agents. (Levy
EI, Firlik AD, Wisniewski S, et al. Factors affecting survival rates for acute vertebrobasilar artery occlusions treated with intra-arterial
thrombolytic therapy: a meta-analytical approach. In: Neurosurgery; 1999:539-45; discussion 45-8.)
Normal angiographic picture of
posterior circulation
A-B. Mid-arterial digital subtraction
angiogram of the right vertebral artery (dominant) showing complete
occlusion with no distal
filling of the basilar artery, frontal and lateral views
C. Frontal view of balloon angioplasty of
the right vertebro-basilar junction
Road map during deployment of Wingspan stent at
the
vertebro-basilar level
E-F. Frontal and lateral views of right vertebral artery mid-arterial
angiograms depicting vessel recanalization following mechanical
thrombolysis.
Intra-arterial mechanical thrombolysis
Broadly categorized into the following
categories:
• thrombectomy,
• thromboaspiration,
• thrombus disruption,
• augmented fibrinolysis,
• thrombus entrapment.
1) Endovascular thrombectomy
• Devices under this category apply a constant force to the clot material
at its proximal or distal end and facilitate clot removal. Proximal end
forces are applied through grasp-like attachments, whereas distal end
forces are applied via basket-like devices.
• The advantage of these devices is their decreased association with
embolic material since there is no attempt for mechanical clot
disruption.
• Some of the most widely used examples are the Merci retriever
(Concentric Medical, Mountain View, California), the Neuronet
device (Guidant, Santa Clara, California), the Phenox clot retriever
(Phenox, Bochum, Germany), the Catch thrombectomy device (Balt
Extrusion, Montmorency, France), and the Alligator retrieval device
(Chestnut Medical Technologies, Menlo Park, California).
• FDA approved in
August 2004
• Flexible nitinol
wire with coil
loops that is used
in conjunction
with a
microcatheter and
an 8-Fr or 9-Fr
balloon guide
catheter
Recent analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI)
and Multi Merci trials showed that patients with M2 occlusions had higher
recanalization rates, decreased procedure duration and similar complication rates
with M1 occlusion patients
Shi Z-S, Loh Y, Walker G, Duckwiler GR, Investigators MaM-M. Clinical outcomes in middle cerebral artery trunk occlusions versus
secondary division occlusions afte mechanical thrombectomy: pooled analysis of the Mechanical Embolus Removal I Cerebral Ischemia
(MERCI) and Multi MERCI trials In: Stroke; 2010:953-60.
2) Endovascular thromboaspiration
• The functioning mechanism in this category utilizes an aspiration
technique, which is suited for fresh non-adhesive clots. These devices
also have the advantage of fewer embolic material and decreased
vasospasm.
• Some examples in this category are the Penumbra system (Penumbra,
Alameda, California) and the AngioJet system (Possis Medical,
Minneapolis, Minnesota).
• The Penumbra stroke system (Penumbra, Inc, Alameda, CA) is
increasingly popular and uses 2 types of devices to remove occlusive
thromboembolus in acute ischemic stroke.
•FDA approved in
January 2008
•The Penumbra devices act
on the proximal face of the
occlusion without
traversing the occluded
artery.
• An aspiration device is
used to debulk and extract
the clot.
•A second retriever device
resembling a stent attached
to a guidewire is used to
remove resistant clot.
ENDOVASCULAR
THROMBOASPIRATION CAUSE FEWER
EMBOLIC EVENTS AND VASOSPASM
R.G. Nogueira, L.H. Schwamm, and J.A. Hirsch Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices,
and Data AJNR Am J Neuroradiol April 2009 30: 649-661
3) MECHANICAL THROMBUS DISRUPTION - PTA -
Microwire/microcatheter fragmentation
R.G. Nogueira, L.H. Schwamm, and J.A. Hirsch Endovascular Approaches to Acute Stroke, Part 1: Drugs,
Devices, and Data AJNR Am J Neuroradiol April 2009 30: 649-661
In this category, mechanical disruption of the clot is accomplished via a
microguidewire or a snare.
Some devices utilizing this mechanism are the EPAR (Endovasix, Belmont,
California) and the LaTIS laser device (LaTIS, Minneapolis, Minnesota).
Risks of vessel rupture and distal embolization (generally reserved as salvage
therapy)
4) Augmented fibrinolysis
• These devices, such as the MicroLysUS infusion catheter
(EKOS, Bothell, Washington), utilize a sonographic micro-tip
to facilitate thrombolysis through ultrasonic vibration.
• The clot removal is augmented without any additional
fragment embolization to the distal circulation.
5) Thrombus entrapment
• The underlying mechanism of these
devices utilizes a stent to recanalize
the occluded vessel and therefore trap
the clot between the stent and vessel
wall.
• Stents can be deployed via a balloon
mechanism or could be self-
expandable. The latter are becoming
increasingly popular due to their
flexibility and ease of navigation
Solitaire & Trevo
“Stentriever“:
•Self-expandable
•Retrievable
•Dual functionality:
•1) Acts as a temporary
intracranial bypass
providing immediate
flow restoration through
the thrombus
•2) Acts as a clot
retriever, trapping
thrombus into its cells
allowing for clot removal
•The first 4 stents are
utilized in stent-assisted
coiling of wide-neck
aneuryms, whereas the
Wingspan is the only stent
approved for intracranial
treatment of
atherosclerotic disease
Machi et al. Solitaire FR thrombectomy system: immediate results in 56 consecutive acute ischemic stroke patients. J
NeuroIntervent Surg 2012;4:62-66
NEUROFORM STENT (BOSTON SCIENTIFIC) ENTERPRISE
STENT (CORDIS, MIAMI LAKES, FLA) LEO STENT (BALT
EXTRUSION, MONTMORENCY, FRANCE) SOLITAIRE/SOLO
STENT (EV3) WINGSPAN STENT (BOSTON SCIENTIFIC)
Illustration depicting the major steps in evolution of thrombectomy devices,
beginning from the first-generation concept to state-of-the-art approaches.
Advantages of intra-arterial
mechanical thrombolysis
• In their multi-center review, Gupta and colleagues have demonstrated
that multimodality approach with chemical and mechanical
thrombolysis leads to higher recanalization rates. (Gupta R, Tayal AH, Levy EI, et al.
Intra-arterial thrombolysis or Stent Placement during Endovascular Treatment for Acute Ischemic Stroke Leads to the
Highest Recanalization Rate: Results of a Multi-center Retrospective Study. In: Neurosurgery; 2011.)
• The mechanical disruption of the arterial clot has several
advantages to IA management of acute stroke.
1. First, it increases the working surface area for thrombolytic
agents thereby enhancing their efficacy.
2. Even partial removal of clot via retrieval or thromboaspiration
techniques lessens the concentration of IA agent required to
dissolve the remainder pieces and risk of ICH is reduced.
3. Provides patients with contraindications to anticoagulation
with a reasonable alternative to endovascular therapy.
Risk
• The use of mechanical thrombolysis is associated with several
associated risks.
1. The endovascular trauma to the blood vessel could cause
endothelial damage, permanent vascular injury, and
ultimately vessel rupture, especially in old friable vessels.
2. The technical skills needed for the endovascular navigation
of such devices, especially through severely occluded
segments, are substantial, and require rigorous training.
3. Finally, the dislodged clot material could become an embolic
source, exposing the already compromised distal circulation
to additional ischemic risks.
REPERFUSION STRATEGIES1
• Recanalization or antegrade reperfusion
• Global reperfusion (flow augmentation or transarterial
retrograde reperfusion)
• Transvenous retrograde reperfusion (flow reversal)
GLOBAL REPERFUSION / FLOW
AUGMENTATION
• Cerebral reperfusion during acute ischemic stroke can be
augmented via alternative strategies that utilize an anterograde
or retrograde route.
• Anterograde reperfusion can be facilitated systemically with
vasopressors leading to global reperfusion by increasing the
mean arterial blood pressure.
• Retrograde reperfusion can be facilitated with a trans-arterial
or trans-venous approach.
• The transarterial approach involves the endovascular
deployment of the NeuroFlo device (CoAxia, Maple Grove,
Minnesota). This dual balloon catheter allows for partial
occlusion of the aorta above and below the level of the renal
arteries, therefore diverting flow away from the systemic and
toward the cerebral circulation (Lylyk P, Vila JF, Miranda C, Ferrario A, Romero R, Cohen JE. Partial aortic
obstruction improves cerebral perfusion and clinical symptoms in patients with symptomatic vasospasm)
REPERFUSION STRATEGIES1
• Recanalization or antegrade reperfusion
• Global reperfusion (flow augmentation or transarterial retrograde
reperfusion)
• Transvenous retrograde reperfusion (flow reversal)
COMPLETE ARTERIO-VENOUS FLOW
REVERSAL
Frazee JG, Luo X, Luan G, et al. Retrograde transvenous neuroperfusion: a back doortreatment for stroke. In: Stroke; 1998:1912-6.
•Transvenous retrograde reperfusion is an experimental
technique with potential benefit in acute ischemic stroke.
•Animal studies suggest that diversion of blood from the
femoral artery into the transverse venous sinuses via
transvenous catheters could lower infarction size and improve
neurological outcome in the setting of acute cerebrovascular
ischemia.
Complications of Endovascular
Treatment
• Morbidity and Mortality of
endovascular treatment- 5-
10%.
• Cerebral Infarction
• Cerebral Hemorrhage
• Cerebral Edema
Cerebral Infarction
• Thrombus formation
– Intra procedure
– Post procedure
• Parent artery dissection
• Parent artery occlusion
– Coil migration
– Stent migration
• Cerebral vasospasm
• Vessel Re-stenosis
Cerebral Hemorrhage
• Aneurysm rupture
• AVM rupture
• Ischemic reperfusion injury
– Hemorrhage
– Contrast extravasations
• Parent artery perforation
Cerebral Edema
• Peaks 3 to 5 days following
injury
• Increased risk with large
hemorrhage or hemispheric
infarcts
• Increased risk of brain
herniation.
RECANALIZATION SCORING
TICI (Thrombolysis In Cerebral Infarction)
0
No perfusion
1
Penetration, but no distal branch filling
2a
Perfusion with incomplete (<50%) distal branch filling
2b
Perfusion with incomplete (>50%) distal branch filling
3
Full perfusion with filling of all distal branches
CLINICAL OUTCOME MEASURE / FUNCTIONAL INDEPENDENCE
Modified Rankin Score (MRS)
0
No symptoms at all
1
No significant disability despite symptoms; able to carry out all usual duties
and activities
2
Slight disability; unable to carry out all previous activities, but able to look
after own affairs without assistance
3
Moderate disability; requiring some help, but able to walk without assistance
4
Moderately severe disability; unable to walk without assistance and unable to
attend to own bodily needs without assistance
5
Severe disability; bedridden, incontinent and requiring constant nursing care
and attention
6 Dead
SUMMARY OF PROSPECTIVE AIS TRIAL DATA
Conclusion
• Current recommendation of 120 mins
from door-to-treatment is too long
• Relatively rapid rate of infarct growth
and the dramatic effect of infarct
volume on clinical outcome
• In order to achieve optimal outcomes
in ischemic stroke, door-to-puncture
times will ultimately need to be
shorter than the 60-min benchmark for
tx of AMI
• Should be dispatched to the highest
level of care available in the shortest
time possible (Mehta et al. J Am Heart Assoc.2014; 3:
e000963originally published November 11, 2014doi: 10.1161/JAHA.114.000963 )
~12% decline in outcomes for q 30 min delay to puncture
VIDEO
References
• Endovascular Management of Acute Ischemic Stroke
(Stavropoula I. Tjoumakaris,Pascal M. Jabbour, Aaron S. Dumont, L. Fernando Gonzalez and Robert H. Rosenwasser Thomas
Jefferson University, Philadelphia, USA)
• Mechanical Thrombectomy in Acute Stroke: Prospective
Pilot Trial of the Solitaire FR Device while Under
Conscious Sedation (S. Soize, K. Kadziolka, L. Estrade, I. Serre, S. Bakchine, and L. Pierot)
• ENDOVASCULAR TREATMENT IN ACUTE ISCHEMIC
STROKE (Silva Andonova1, Zvetomila Dimitrova1, Еvgenia Кalevska1, Мarina Petkova1, Vania Аrgirova1, Penka
Кirilova1, Zvetan Zvetkov1, Мarianna Novakova2, Radoslav Georgiev)
• ENDOVASCULAR TREATMENT OF ACUTE
ISCHEMIC STROKE (Biraj M. Patel, MD)
• The MCA is divided into four segments:
• M1: from the origin to bifurcation/trifurcation
(the limen insulae); also known as horizontal or
sphenoidal segment
• M2: also known as insular segment, from
bi(tri)furcation to circular sulcus of insula where it
makes hairpin bend to continue as M3
• M3: opercular branches (those within the Sylvian
fissure); also known as opercular segment
• M4: branches emerging from the Sylvian fissure onto
the convex surface of the hemisphere; also known as
cortical segment
• Branches
• M1
• medial lenticulostriate penetrating arteries
• lateral lenticulostriate penetrating arteries
• anterior temporal artery
• polar temporal artery
• uncal artery (which may branch from the anterior choroidal artery)
• M2
• Division of the MCA is variable after the horizontal segment, although
most commonly, it divides into two trunks-superior and inferior:
• 78% bifurcate into superior and inferior divisions
• 12% trifucate into superior, middle and inferior divisions
• 10% branch into many smaller branches
• Superior terminal branch
• lateral frontobasal artery
• prefrontal sulcal artery
• pre-Rolandic (precentral) and Rolandic (central) sulcal arteries
• Inferior terminal branch
• three temporal branches (anterior, middle, posterior)
• branch to the angular gyrus
• two parietal branches (anterior, posterior)
• Supply
• The middle cerebral arteries supply the majority of the lateral surface of the
hemisphere, except the superior portion of the parietal lobe (via ACA) and the
inferior portion of the temporal lobe and occipital lobe (via PCA). In addition, they
supply part of the internal capsule and basal ganglia.
• In its territory lie the motor and sensory areas excluding leg and perineum and
auditory and speech areas.
Endovascular treatment in acute cerebral ischemia

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Endovascular treatment in acute cerebral ischemia

  • 1. FI
  • 2. ISCHEMIC STROKE • 3rd most common cause of death and permanent disability with 30- 50% do not regaining functional independence. The majority of these events are ischemic (87%), as opposed to intracerebral (10%) and subarachnoid hemorrhages (3%) (AHA. Heart and Stroke Update. 2010) • ~780,000 new or recurrent stroke cases annually
  • 3. CEREBRAL CIRCULATION The brain receives its blood supply from four main arteries: the two internal carotid arteries and the two vertebral arteries.
  • 5. Management of acute ischemic stroke • Management of acute ischemic stroke was previously geared toward prevention, supportive care, and rehabilitation. • The medical management of stroke has progressed exponentially, with FDA approval of r-TPA, alteplase in 1996. • Intravenous administration of r-TPA within a limited 3-hour window from symptom onset has shown a significant improvement in patient outcome at 3 months. Fagan SC, Morgenstern LB, Petitta A, et al. Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group. In: Neurology; 1998:883-90 • Current stroke guidelines have extended the therapeutic r-TPA administration window to 4.5 hours..
  • 6. IV TPA Trials 6 major randomized placebo-controlled trials 1)Alteplase Thrombolysis for Acute Non interventional Therapy in Ischemic Stroke [ATLANTIS] I and II 2) European Cooperative Acute Stroke Study [ECASS] I and II 3) NINDS I and II •2775 pts treated with IV rtPA or a placebo within 6 hrs of onset •Confirmed the benefit up to 3 hrs ECASS III subsequently confirmed benefit of IV tPA in a 3 to 4.5-hr window
  • 7. IV TPA - LIMITATIONS •ICA and M1 occlusions have lower rate of recanalization than M2–M4 occlusions. •52% with NIHSS <10 will reach NIHSS of 1 after IV tPA, but only 8% with NIHSS >20 •30% of MCA occlusions recanalize with IV tPA only within 2 hours •ICA occlusions recanalize only at 1/3 of the rate of MCA occlusions. 1Del Zoppo Ann Neurol 1992; 32:78- 86 2)NINDS Stroke 1997;28:2119–2125 3)Linfante Stroke 2002;33:2066-2071 M1: from the origin to bifurcation/trifurcation (the limen insulae); also known as horizontal or sphenoidal segment M2: also known as insular segment, from bi(tri)furcation to circular sulcus of insula where it makes hairpin bend to continue as M3 M3: opercular branches (those within the Sylvian fissure); also known as opercular segment M4: branches emerging from the Sylvian fissure onto the convex surface of the hemisphere; also known as cortical segment
  • 8. Logistic regression curve representing an estimate of the probability for successful recanalization of occluded vessels by IVT depending on thrombus length • Christian H. Riedel et al. Stroke. 2011;42:1775-1777 Length of the HMCAS (MM) Probabilityofrecanalization
  • 9. Endovascular management. • Sussman and Fitch described the IA treatment of acute carotid occlusion with fibrinolysin injection in 1958. • Late1990’s experienced exponential progress and development. • Recent advances in endovascular techniques have increased the therapeutic window of r-TPA administration. • The newer IA devices for clot retrieval and vessel recanalization has revolutionized the neuroendovascular management of acute ischemic stroke. Sussman BJ, Fitch TS. Thrombolysis with fibrinolysin in cerebral arterial occlusion. In:Journal of the American Medical Association; 1958:1705-9.
  • 10. Patient selection and imaging • An initial evaluation with a non- contrast computerized tomography (CT) head scan is necessary. • Penumbra Pivotal Stroke Trial 1. Retrospective analysis of 85 patients 2. Results: • Baseline CT scan by ASPECTS score>7 had a 50% chance of a favorable clinical outcome with early recanalization (p=0.0001). • In addition, ASPECTS scores of less than 4 did not show clinical improvement regardless of endovascular recanalization Goyal M, Menon BK, Coutts SB, Hill MD, Demchuk AM, Penumbra Pivotal Stroke Trial Investigators CSP, and the Seaman MR Research Center. Effect of baseline CT scan appearance and time to recanalization on clinical outcomes in endovascular thrombectomy of acute ischemic strokes. In: Stroke; 2011:93-7.
  • 11. • Large territorial infarcts  High risk hemorrhagic conversion  poor candidates for endovascular therapy.( Vora NA, Gupta R, Thomas AJ, et al. Factors predicting hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke. In: AJNR American journal of neuroradiology; 2007:1391-4) • Intra-parenchymal hematoma is a contraindication to endovascular recanalization. • Presence of a hyperdense MCA sign on the initial head CT does not have a significant prognostic value in patient outcome and vessel recanalization rates.[ Gönner F, Remonda L, Mattle H, et al. Local intra-arterial thrombolysis in acute ischemic stroke. In: Stroke; 1998:1894-900.)
  • 12. CT PERFUSION SCANS • CT perfusion scans “salvageable” tissue. • Perfusion scan demonstrates the pneumbra lesion volume or mean transit time which is essential for determing outcomes.. Konstas AA, Goldmakher GV, Lee TY, Lev MH. Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 1: Theoretic basis. In: AJNR American journal of neuroradiology; 2009:662-8.
  • 13.
  • 14. • NIHSS and AGE No statistical significance with ICH(vora et al) • Hyperglycemia >200 mg/dl  Increase risk of ICH(vora et al) • Previous administration of intravenous tPA is not a contraindication to IA intervention (Vora NA, Gupta R, Thomas AJ, et al. Factors predicting hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke. In: AJNR American journal of neuroradiology; 2007:1391-4.) • Zacharatos and colleagues study Retrospective study of 156 pts. Results: Thrombolytic therapy (chemical or mechanical) showed a favorable clinical outcome versus supportive management in the 80 years and older age group. (Zacharatos H, Hassan AE, Vazquez G, et al. Comparison of acute nonthrombolytic and thrombolytic treatments in ischemic stroke patients 80 years or older. In: The American journal of emergency medicine; 2011.)
  • 15. Angiographic evaluation • To see for ischemic etiology and initiation of treatment. • Examination of the cerebrovascular anatomy begins with the aortic arch. • Based on the patient symptomatology and pre-procedure imaging, selective catheterization of the carotid or vertebrobasilar circulation supplying the affected territory is performed • Attention is paid to the extracranial collateral circulation, the leptomeningeal anatomy, the circle of Willis, and overall global cerebral perfusion. • Grade of angiographic collaterals is a decisive factor for the degree of reperfusion and clinical improvement. Bang OY,Saver JL, Kim SJ, et al. Collateral flow predicts response to endovascular therapy for acute ischemic stroke. In: Stroke; 2011:693-9
  • 16. Conscious sedation Vs GA • The use of general anesthesia is preferred due to motion elimination contributing to procedural safety and efficacy. • Newer studies suggest that conscious sedation or local anesthesia may lead to more favorable radiographic and clinical outcomes by decreasing time delay and cerebral ischemia from hypoperfusion • (McDonagh DL, Olson DM, Kalia JS, Gupta R, Abou-Chebl A, Zaidat OO. Anesthesia and Sedation Practices Among Neurointerventionalists during Acute Ischemic Stroke Endovascular Therapy. In: Frontiers in neurology; 2010:118. • Gupta R. Local is better than general anesthesia during endovascular acute stroke interventions. In: Stroke; 2010:2718-9.)
  • 17. REPERFUSION STRATEGIES1 • Recanalization or antegrade reperfusion • Global reperfusion (flow augmentation or transarterial retrograde reperfusion) • Transvenous retrograde reperfusion (flow reversal)
  • 18. Intra-arterial chemical thrombolysis • Agents converts plasminogen into plasmin degrades fibrin and products. • Recombinant tissue plasminogen activator (r-tPA) and recombinant pro-urokinase (rpro-UK) have been widely studied and used most frequently. (Berenstein Alejandro, Lasjaunias Pierre, G. ter Brugge Karel. Surgicalneuroangiography. Vol. 2, Clinical and endovascular treatment ... . In.) • Alteplase (r-tPA), is a serine protease, has a half-life of 3.5 minutes and a dosage range of 20-60 mg. • Pro-UK has a halflife of 7 minutes and may be favorable to r-tPA due to decreased side effects • Third-generation agents, such as reteplase and tenecteplase, have longer half-lives (15-18 minutes) and theoretically favorable vessel recanalization and local recurrence rates.( Nogueira RG, Schwamm LH, Hirsch JA. Endovascular approaches to acute stroke, part 1: Drugs, devices, and data. In: AJNR American journal of neuroradiology; 2009:649-61.)
  • 19. • The aforementioned agents have prothrombotic effects by the production of thrombin during thrombolysis, and subsequent activation of platelets and fibrinogen.( Nogueira RG, Schwamm LH, Hirsch JA. Endovascular approaches to acute stroke, part 1: Drugs, devices, and data. In: AJNR American journal of neuroradiology;2009:649-61.) • Concomitant use of systemic anticoagulation during IA thrombolysis is recommended with caution to risk of ICH. • Widely used adjuvant systemic agent is heparin. Memon and colleagues Study 1. Reviewed 35 cases of adjunctive use of eptifibatide in salvage reocclusion and thrombolysis of distal thrombi with a single bolus of 180μg/kg. • They reported a partial to complete recanalization of 77% with incidence of post-operative hemorrhage was 37% . Memon MZ, Natarajan SK, Sharma J, et al. Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischemic stroke. In: J Neurosurg; 2010.
  • 20. Anterior circulation Middle cerebral artery • Three major clinical trials evaluated the efficacy of IA thrombolysis in the Middle Cerebral Artery (MCA) circulation 1. PROACT I and II (Prolyse in Acute Cerebral Thromboembolism) 2. MELT trials (Middle Cerebral Artery Local Fibrinolytic Intervention Trial) • The average intervention time varies from 45 to 180 minutes, high-risk patients should be treated within 4-5 hours from ischemia onset. (Brott T. Thrombolytic therapy. In: Neurologic clinics; 1992:219-32.)
  • 21. PROACT 1 • 40 patients were randomized for treatment of acute ischemic stroke within 6 hours of symptom onset • Cerebral angiography was performed, and M1 or M2 occlusions were treated with 6 mg of rpro-UK (n=26) or placebo (n=14). • Results: Rpro-UK treated patients had higher vessel recanalization rates compared to placebo (57.7% versus 14.3%). The incidence of ICH was higher in the rpro-UK group (15.4% versus 7.1%) (del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: aphase II randomized trial of recombinant pro-urokinase by direct arterial delivery)
  • 22. PROACT 2 • This randomized, controlled clinical trial treated patients with MCA occlusion within 6 hours of symptom onset with either 9 mg of IA rpro-UK and heparin infusion (n=121) or heparin infusion alone (n-59). • Results: • Patients who received IA rpro-UK had significantly lower Rankin scores at the 90-day endpoint compared to heparin only treated patients. The MCA racanalization and mortality rates favored the rpro-UK group as opposed to the control group (66% versus 18%) (Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. In: JAMA; 1999:2003-11.)
  • 23. Theron et al Study • Investigated the efficacy of IA thrombolysis in patients who had acute internal carotid artery (ICA) with MCA occlusion. (Theron J, Courtheoux P, Casasco A, et al. Local intraarterial fibrinolysis in the carotid territory. In: AJNR American journal of neuroradiology; 1989:753-65). Results: 1. IA fibrinolysis of the MCA should be performed within 6 hours from ischemia onset, when the occlusion involves the horizontal segment of the MCA extending into the lenticulostriate arteries. 2. If the occlusion does not involve the horizontal MCA segment and the lenticulostriate arteries, then the treatment window can be extended to 12 hours following symptoms.
  • 24.
  • 25. Acute right MCA occlusion Mid-arterial digital subtraction angiogram of right ICA shows complete MCA occlusion at the level of the bifurcation, frontal and lateral views
  • 26. Mechanical thrombolysis with Penumbra device showing recanalization of the superior M2 division in a frontal high magnification view
  • 27. Frontal and lateral views of right ICA angiograms following MCA mechanical recanalization.
  • 28.
  • 29. Internal carotid artery • Occlusions of the proximal ICA (extra-cranial) generally have a better prognosis than intracranial occlusions • Patients with insufficient extracranial-intracranial anastomoses or an incomplete circle of Willis may be predisposed to developing significant neurological symptoms. These patients are potential candidates for IA intervention. • Mechanical thrombolysis, in addition to pharmacological thrombolysis, is of paramount importance for recanalization. • Negative prognostic factors include distal ICA distribution involving the M1 and A1 segments (“T” occlusion) and poor neurological presentation . In a 25-patient series, Jovi and colleagues demonstrated successful revascularization in 92 % of patients followingthrombolysis and ICA stenting.
  • 30. • Bhatia et al, recanalization following IV r-tPA in patients with T occlusion is the lowest at 4.4%.( Bhatia R, Hill MD, Shobha N, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. In: Stroke; 2010:2254-8). • Arnold and colleagues presented a series of 24 patients with distal ICA occlusions treated with IA urokinase. Favorable 3- month functional outcome was present in only 16% of patients, and the mortality rate was approximately 42%. (Arnold M, Nedeltchev K, Mattle HP, et al. Intra-arterial thrombolysis in 24 consecutive patients with internal carotid artery T occlusions. In: J Neurol Neurosurg Psychiatr; 2003:739-42.) • Flint et al published a series of 80 patients with ICA occlusion who were treated with combinations of the Merci retriever with or without andjunctive endovascular therapy. Recanalization rates were higher in the combination group (63%) as opposed to the Merci group (53%). Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS, Committee MaMMW. Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. In: Stroke; 2007:1274-80. Adjuvant mechanical assistance with devices for balloon angioplasty, clot retrieval, and vessel stenting enhance the probability of vessel recanalization
  • 31. Case • Acute left ICA occlusion. The patient presented 6 hours following onset of global aphasia and R hemiplegia
  • 32. A-B. Mid-arterial digital subtraction angiogram of left ICA artery showing complete occlusion of the distal ICA (T occlusion), frontal and lateral views.
  • 33. C. Frontal view of balloon angioplasty and recanalization of the distal left ICA.
  • 34. D-E. Frontal and lateral views of left ICA angiograms following mechanical and chemical recanalization with balloon angioplasty, Merci device, and administration of of Urokinase.
  • 35. Central retinal artery • Occlusion of the Central Retinal Artery (CRA) is an ophthalmologic emergency with natural history that leads to loss of vision. • Conventional medical therapy have limited efficacy. • In most studies, IA alteplase is most commonly used within 4- 6 hours from symptom onset. • Padolecchia and colleagues showed that intervention within 4.5 hours of ischemic onset leads to visual improvement in all patients. (Padolecchia R, Puglioli M, Ragone MC, Romani A, Collavoli PL. Superselective intraarterial fibrinolysis in central retinal artery occlusion. In: AJNR American journal of neuroradiology; 1999:565-7.)
  • 36. Posterior circulation • Acute basilar artery (BA) occlusion is a life-threatening event with untreated BA occlusion having mortality rates ranging from 86% to 100%. • In a series of nearly 300 patients, Furlan and Higashida reported an IA recanalization rate of 60%, and mortality rates of 31% in at least partially recanalized patients as opposed to 90% in nonrecanalized patients. (Furlan A, Higashida, R. Intra-arterial thrombolysis in acute ischemic stroke. In: Stroke: Pathophysiology, Diagnosis, and Management. 4th ed. Philadelphia: Churchill Livingstone; 2004:943-51.)
  • 37. IA Vs IV • Lindsberg and Mattle compared BA occlusion treatment with IV or IA thrombolysis. • Results: They found that although recanalization rates were higher with IA treatement (65% versus 53%), dependency or death rates were equal between the two groups (76-78%). • Conclusion: Emergent thrombolysis via either technique is of paramount importance to the survival of this patient population.
  • 38. BASICS STUDY • Basilar Artery International Cooporation Study (BASICS), 624 patients with radiographically confirmed occlusion of the BA were enrolled in nearly 50 centers over a 5-year period. • Results: All patients (n=41) treated with IA or IV thrombolytics beyond 9 hours from symptom onset had a poor reported outcome. • Conclusion: The therapeutic window can be successfully extended upto 6-9 hours but not more than 9 hours. Schonewille WJ, Wijman CA, Michel P, Algra A, Kappelle LJ, Group BS. The basilar artery international cooperation study (BASICS). In: International journal of stroke : official journal of the International Stroke Society; 2007:220-3.
  • 39. LEVY et al study • In a metaanalysis of 164 patients with BA occlusion over a 10- year period • Factors with a negative prognostic value were 1. Coma at initial presentation 2. Failure of vessel recanalization 3. Proximal vessel occlusion. • Distal BA occlusions are more commonly embolic in nature and therefore have a better response to thrombolytic agents. (Levy EI, Firlik AD, Wisniewski S, et al. Factors affecting survival rates for acute vertebrobasilar artery occlusions treated with intra-arterial thrombolytic therapy: a meta-analytical approach. In: Neurosurgery; 1999:539-45; discussion 45-8.)
  • 40. Normal angiographic picture of posterior circulation
  • 41. A-B. Mid-arterial digital subtraction angiogram of the right vertebral artery (dominant) showing complete occlusion with no distal filling of the basilar artery, frontal and lateral views
  • 42. C. Frontal view of balloon angioplasty of the right vertebro-basilar junction
  • 43. Road map during deployment of Wingspan stent at the vertebro-basilar level
  • 44. E-F. Frontal and lateral views of right vertebral artery mid-arterial angiograms depicting vessel recanalization following mechanical thrombolysis.
  • 45. Intra-arterial mechanical thrombolysis Broadly categorized into the following categories: • thrombectomy, • thromboaspiration, • thrombus disruption, • augmented fibrinolysis, • thrombus entrapment.
  • 46. 1) Endovascular thrombectomy • Devices under this category apply a constant force to the clot material at its proximal or distal end and facilitate clot removal. Proximal end forces are applied through grasp-like attachments, whereas distal end forces are applied via basket-like devices. • The advantage of these devices is their decreased association with embolic material since there is no attempt for mechanical clot disruption. • Some of the most widely used examples are the Merci retriever (Concentric Medical, Mountain View, California), the Neuronet device (Guidant, Santa Clara, California), the Phenox clot retriever (Phenox, Bochum, Germany), the Catch thrombectomy device (Balt Extrusion, Montmorency, France), and the Alligator retrieval device (Chestnut Medical Technologies, Menlo Park, California).
  • 47. • FDA approved in August 2004 • Flexible nitinol wire with coil loops that is used in conjunction with a microcatheter and an 8-Fr or 9-Fr balloon guide catheter Recent analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi Merci trials showed that patients with M2 occlusions had higher recanalization rates, decreased procedure duration and similar complication rates with M1 occlusion patients Shi Z-S, Loh Y, Walker G, Duckwiler GR, Investigators MaM-M. Clinical outcomes in middle cerebral artery trunk occlusions versus secondary division occlusions afte mechanical thrombectomy: pooled analysis of the Mechanical Embolus Removal I Cerebral Ischemia (MERCI) and Multi MERCI trials In: Stroke; 2010:953-60.
  • 48. 2) Endovascular thromboaspiration • The functioning mechanism in this category utilizes an aspiration technique, which is suited for fresh non-adhesive clots. These devices also have the advantage of fewer embolic material and decreased vasospasm. • Some examples in this category are the Penumbra system (Penumbra, Alameda, California) and the AngioJet system (Possis Medical, Minneapolis, Minnesota). • The Penumbra stroke system (Penumbra, Inc, Alameda, CA) is increasingly popular and uses 2 types of devices to remove occlusive thromboembolus in acute ischemic stroke.
  • 49. •FDA approved in January 2008 •The Penumbra devices act on the proximal face of the occlusion without traversing the occluded artery. • An aspiration device is used to debulk and extract the clot. •A second retriever device resembling a stent attached to a guidewire is used to remove resistant clot. ENDOVASCULAR THROMBOASPIRATION CAUSE FEWER EMBOLIC EVENTS AND VASOSPASM R.G. Nogueira, L.H. Schwamm, and J.A. Hirsch Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and Data AJNR Am J Neuroradiol April 2009 30: 649-661
  • 50. 3) MECHANICAL THROMBUS DISRUPTION - PTA - Microwire/microcatheter fragmentation R.G. Nogueira, L.H. Schwamm, and J.A. Hirsch Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and Data AJNR Am J Neuroradiol April 2009 30: 649-661 In this category, mechanical disruption of the clot is accomplished via a microguidewire or a snare. Some devices utilizing this mechanism are the EPAR (Endovasix, Belmont, California) and the LaTIS laser device (LaTIS, Minneapolis, Minnesota). Risks of vessel rupture and distal embolization (generally reserved as salvage therapy)
  • 51. 4) Augmented fibrinolysis • These devices, such as the MicroLysUS infusion catheter (EKOS, Bothell, Washington), utilize a sonographic micro-tip to facilitate thrombolysis through ultrasonic vibration. • The clot removal is augmented without any additional fragment embolization to the distal circulation.
  • 52. 5) Thrombus entrapment • The underlying mechanism of these devices utilizes a stent to recanalize the occluded vessel and therefore trap the clot between the stent and vessel wall. • Stents can be deployed via a balloon mechanism or could be self- expandable. The latter are becoming increasingly popular due to their flexibility and ease of navigation
  • 53. Solitaire & Trevo “Stentriever“: •Self-expandable •Retrievable •Dual functionality: •1) Acts as a temporary intracranial bypass providing immediate flow restoration through the thrombus •2) Acts as a clot retriever, trapping thrombus into its cells allowing for clot removal •The first 4 stents are utilized in stent-assisted coiling of wide-neck aneuryms, whereas the Wingspan is the only stent approved for intracranial treatment of atherosclerotic disease Machi et al. Solitaire FR thrombectomy system: immediate results in 56 consecutive acute ischemic stroke patients. J NeuroIntervent Surg 2012;4:62-66 NEUROFORM STENT (BOSTON SCIENTIFIC) ENTERPRISE STENT (CORDIS, MIAMI LAKES, FLA) LEO STENT (BALT EXTRUSION, MONTMORENCY, FRANCE) SOLITAIRE/SOLO STENT (EV3) WINGSPAN STENT (BOSTON SCIENTIFIC)
  • 54. Illustration depicting the major steps in evolution of thrombectomy devices, beginning from the first-generation concept to state-of-the-art approaches.
  • 55. Advantages of intra-arterial mechanical thrombolysis • In their multi-center review, Gupta and colleagues have demonstrated that multimodality approach with chemical and mechanical thrombolysis leads to higher recanalization rates. (Gupta R, Tayal AH, Levy EI, et al. Intra-arterial thrombolysis or Stent Placement during Endovascular Treatment for Acute Ischemic Stroke Leads to the Highest Recanalization Rate: Results of a Multi-center Retrospective Study. In: Neurosurgery; 2011.) • The mechanical disruption of the arterial clot has several advantages to IA management of acute stroke. 1. First, it increases the working surface area for thrombolytic agents thereby enhancing their efficacy. 2. Even partial removal of clot via retrieval or thromboaspiration techniques lessens the concentration of IA agent required to dissolve the remainder pieces and risk of ICH is reduced. 3. Provides patients with contraindications to anticoagulation with a reasonable alternative to endovascular therapy.
  • 56. Risk • The use of mechanical thrombolysis is associated with several associated risks. 1. The endovascular trauma to the blood vessel could cause endothelial damage, permanent vascular injury, and ultimately vessel rupture, especially in old friable vessels. 2. The technical skills needed for the endovascular navigation of such devices, especially through severely occluded segments, are substantial, and require rigorous training. 3. Finally, the dislodged clot material could become an embolic source, exposing the already compromised distal circulation to additional ischemic risks.
  • 57. REPERFUSION STRATEGIES1 • Recanalization or antegrade reperfusion • Global reperfusion (flow augmentation or transarterial retrograde reperfusion) • Transvenous retrograde reperfusion (flow reversal)
  • 58. GLOBAL REPERFUSION / FLOW AUGMENTATION • Cerebral reperfusion during acute ischemic stroke can be augmented via alternative strategies that utilize an anterograde or retrograde route. • Anterograde reperfusion can be facilitated systemically with vasopressors leading to global reperfusion by increasing the mean arterial blood pressure. • Retrograde reperfusion can be facilitated with a trans-arterial or trans-venous approach.
  • 59. • The transarterial approach involves the endovascular deployment of the NeuroFlo device (CoAxia, Maple Grove, Minnesota). This dual balloon catheter allows for partial occlusion of the aorta above and below the level of the renal arteries, therefore diverting flow away from the systemic and toward the cerebral circulation (Lylyk P, Vila JF, Miranda C, Ferrario A, Romero R, Cohen JE. Partial aortic obstruction improves cerebral perfusion and clinical symptoms in patients with symptomatic vasospasm)
  • 60. REPERFUSION STRATEGIES1 • Recanalization or antegrade reperfusion • Global reperfusion (flow augmentation or transarterial retrograde reperfusion) • Transvenous retrograde reperfusion (flow reversal)
  • 61. COMPLETE ARTERIO-VENOUS FLOW REVERSAL Frazee JG, Luo X, Luan G, et al. Retrograde transvenous neuroperfusion: a back doortreatment for stroke. In: Stroke; 1998:1912-6. •Transvenous retrograde reperfusion is an experimental technique with potential benefit in acute ischemic stroke. •Animal studies suggest that diversion of blood from the femoral artery into the transverse venous sinuses via transvenous catheters could lower infarction size and improve neurological outcome in the setting of acute cerebrovascular ischemia.
  • 62. Complications of Endovascular Treatment • Morbidity and Mortality of endovascular treatment- 5- 10%. • Cerebral Infarction • Cerebral Hemorrhage • Cerebral Edema
  • 63. Cerebral Infarction • Thrombus formation – Intra procedure – Post procedure • Parent artery dissection • Parent artery occlusion – Coil migration – Stent migration • Cerebral vasospasm • Vessel Re-stenosis
  • 64. Cerebral Hemorrhage • Aneurysm rupture • AVM rupture • Ischemic reperfusion injury – Hemorrhage – Contrast extravasations • Parent artery perforation
  • 65. Cerebral Edema • Peaks 3 to 5 days following injury • Increased risk with large hemorrhage or hemispheric infarcts • Increased risk of brain herniation.
  • 66. RECANALIZATION SCORING TICI (Thrombolysis In Cerebral Infarction) 0 No perfusion 1 Penetration, but no distal branch filling 2a Perfusion with incomplete (<50%) distal branch filling 2b Perfusion with incomplete (>50%) distal branch filling 3 Full perfusion with filling of all distal branches
  • 67. CLINICAL OUTCOME MEASURE / FUNCTIONAL INDEPENDENCE Modified Rankin Score (MRS) 0 No symptoms at all 1 No significant disability despite symptoms; able to carry out all usual duties and activities 2 Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3 Moderate disability; requiring some help, but able to walk without assistance 4 Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5 Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6 Dead
  • 68. SUMMARY OF PROSPECTIVE AIS TRIAL DATA
  • 69. Conclusion • Current recommendation of 120 mins from door-to-treatment is too long • Relatively rapid rate of infarct growth and the dramatic effect of infarct volume on clinical outcome • In order to achieve optimal outcomes in ischemic stroke, door-to-puncture times will ultimately need to be shorter than the 60-min benchmark for tx of AMI • Should be dispatched to the highest level of care available in the shortest time possible (Mehta et al. J Am Heart Assoc.2014; 3: e000963originally published November 11, 2014doi: 10.1161/JAHA.114.000963 ) ~12% decline in outcomes for q 30 min delay to puncture
  • 70. VIDEO
  • 71. References • Endovascular Management of Acute Ischemic Stroke (Stavropoula I. Tjoumakaris,Pascal M. Jabbour, Aaron S. Dumont, L. Fernando Gonzalez and Robert H. Rosenwasser Thomas Jefferson University, Philadelphia, USA) • Mechanical Thrombectomy in Acute Stroke: Prospective Pilot Trial of the Solitaire FR Device while Under Conscious Sedation (S. Soize, K. Kadziolka, L. Estrade, I. Serre, S. Bakchine, and L. Pierot) • ENDOVASCULAR TREATMENT IN ACUTE ISCHEMIC STROKE (Silva Andonova1, Zvetomila Dimitrova1, Еvgenia Кalevska1, Мarina Petkova1, Vania Аrgirova1, Penka Кirilova1, Zvetan Zvetkov1, Мarianna Novakova2, Radoslav Georgiev) • ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE (Biraj M. Patel, MD)
  • 72.
  • 73. • The MCA is divided into four segments: • M1: from the origin to bifurcation/trifurcation (the limen insulae); also known as horizontal or sphenoidal segment • M2: also known as insular segment, from bi(tri)furcation to circular sulcus of insula where it makes hairpin bend to continue as M3 • M3: opercular branches (those within the Sylvian fissure); also known as opercular segment • M4: branches emerging from the Sylvian fissure onto the convex surface of the hemisphere; also known as cortical segment
  • 74. • Branches • M1 • medial lenticulostriate penetrating arteries • lateral lenticulostriate penetrating arteries • anterior temporal artery • polar temporal artery • uncal artery (which may branch from the anterior choroidal artery) • M2 • Division of the MCA is variable after the horizontal segment, although most commonly, it divides into two trunks-superior and inferior: • 78% bifurcate into superior and inferior divisions • 12% trifucate into superior, middle and inferior divisions • 10% branch into many smaller branches
  • 75. • Superior terminal branch • lateral frontobasal artery • prefrontal sulcal artery • pre-Rolandic (precentral) and Rolandic (central) sulcal arteries • Inferior terminal branch • three temporal branches (anterior, middle, posterior) • branch to the angular gyrus • two parietal branches (anterior, posterior) • Supply • The middle cerebral arteries supply the majority of the lateral surface of the hemisphere, except the superior portion of the parietal lobe (via ACA) and the inferior portion of the temporal lobe and occipital lobe (via PCA). In addition, they supply part of the internal capsule and basal ganglia. • In its territory lie the motor and sensory areas excluding leg and perineum and auditory and speech areas.

Editor's Notes

  1. Every second saved is around thousnads of neurons saved. So it can easily stated that in stroke time is very precious.
  2. The clinical consequences of vascular disease in the cerebral circulation is depend upon which vessels or combinations of vessels are involved.
  3. By crossing the siteof occlusion, this corkscrew-shaped device pulls the occlusive thromboembolus into an extracranial guide catheterunder active suction. Successive generations of the MERCI device have been reported in 3 prospective, single-arm, nonrandomized, multicenter feasibility, and safety studies (Table 2). Patients enrolled in these studies were ineligible for intravenous fibrinolysis or had failed to respond to intravenous fibrinolysis. Enrolled patients were treated within 8 hours of stroke onset. On average, treatment began 4.3 hours after stroke onset. Recanalization, if achieved, occurred by 5.9 hours. Primary outcome measures included partial or complete recanalization of the occlusion