Montpellier University Hospital, Montpellier, FranceDepartment of Interventional Neuroradiology Department of NeurologyDepartment of Intensive Care and AnesthesiologyEmergency Department – Head&Neck Unit

FIBRINOLYSE IV

• Intérêt rt-PA IV dans les 3H (NINDS,1995)

mRs 0 &1:50% vs 38% (12% bénéfice absolu ou 30% bénéfice relatif)

• Extension de la fenêtre thérapeutique :4H30 (ECASS3, 2008) mais avec un bénéfice relatif plus faible

• Fibrinolyse IV associée à une augmentation significative du risque HIC

ECASS 3W.Hacke, N.Engl J Med,2008;259:1317

Randomisée, multicentrique,rt-PA entre 3H et 4H30 contre placebo, outcome à J90

Efficacité marginale, bénéfice absolu du rt-PA 7.2%( p=0.04)

Hemorragies IC rt-PA: 27% vs17.6% (p=0.001)

NNT=17

52.4%

45.2%

FIBRINOLYSE IVAnalyse critique

• Selon la severité de l’AVCI– Infarctus etendu :ECASS I& II– NIHSS> 20– RISQUE HEMORRAGIQUE ACCRU

• Selon le siège de l’occlusion:taux recanalisation– 8.7% ACI– 35.2% M1-ACM– 53.8% M2-ACM– 65.9% M3-ACM Del Zoppo,ann.neurol.1992;1:78-86

SCANNER C-/ AVC PHASE AIGUE

• Signes précoces ACM avant 3H(+75% des cas)– Hypodensite NGC– Effacement ruban cortical insulaire– Augmentation de la teneur en H2O (hypodensité

corrélée à l’infarctus final; œdème sans hypoattenuation corrélé à rVSC=tissu viable) (von Kummer, Radiology, 2001)

– Accord inter-observateur médiocre– Score ASPECTS/ Thrombolyse IV(Dzialowski, Stroke 2006)

7 favorable; 2 risque hémorragique

• Signe ACM hyperdense= thrombus– Sensibilité faible (27-34%), sans valeur pronostique

SELECTION DES PATIENTS SCANNER DE PERFUSION

• Couverture anatomique restreinte:20mm• irradiation non négligeable ( 3mSev)• Tracking de bolus• Infarctus : rCBV cartographie (< 2.5ml/100mg)• Pénombre : MTT. cartographie (>145%)

• Neurotherapeutics. 2011;8(1):19-27 Neuroimaging Clin N Am. 2011;21(2):215-38

RadioGraphics 2006; 26:S75-S95

↓CBV ↑MTT↓ CBF

PPPENOMBREINFARCTUS

SELECTION DES PATIENTS IRM DWI/FLAIR MISMATCH

• Circulation antérieure:– Score ASPECTS:>7 (facteur de bon pronostic)

A.Demchuk, Stroke, 2005;36:2110

– Transposition cartographie ADCP.Barber ,J Neurol Neurosurg Psychiatry.2005;76:1528K.Kimura, Stroke, 2008;39:2388 (mauvais pronostic si ≤ 5)T.Nezu, Neurology 2010 (aspects DWI≤ 5corrélé à une augmentation

du taux sICH( OR 4.7); ≤ 4 corrélé au taux de morbidité(OR 3.6)

– volume: DWI lesion vol facteur prédictif HICM.Lansberg, Stroke, 2007;38:2275 (OR 1.42 pour 10ml DWI)

• Circulation postérieure:pc-ASPECTS ≥8 V.Puetz, Stroke.2008;39:2485

Score ASPECTS (0-10) : étendue AVCI territoire ACM.Coter 1 point = normal; Coter 0= ischémie

régions corticale (M1, M2, M3, M4, M5, M6 et I) sous corticale (C, CI et L).M1: cortex antérieur ACM, M2: cortex latéral ACM, M3: cortex postérieur ACM,

M4, M5 et M6 sont les points respectivement au dessus de M1, M2 et M3 ; I: cortex insulaire

C: tête noyau caudé, L: noyau lentiforme et CI: genou capsule interne.

M1

IM2

M3

M4

M5

M6

CL

CI

Time from Symptom Onset in Acute Stroke Petkova et al

Radiology: : December 2010

Bar.Ch,58ans,hémiplegie g masive, NHISS=20, <3H, ASPECTS =5

DIFFUSION/PERFUSION MISMATCH

Wardlaw, jnnp,2007;78:405

ASPECTS =2,deficit BF gauche, 4H30

VOLUME INFARCTUS CEREBRAL

Cartographie du TTP

Nécrose (ADC)pénombre

Parenchyme sain

AVC

Volume(cm3) TTM TTPCerebral

Blood Volume

Index of Cerebral

Blood Flow

nécrose 102,013 30,05 21,21 72,2451 4,24971

parenchyme sain 721,531 10,6 19,44 114,16 19,0266

pénombre 69,213 15,9 22,97 116,551 12,9501

Imagerie de diffusion b=10000i : phase aigue

Imagerie FLAIR : 5 jours après AVC

ASPECTS FOSSE POST

Pc-ASPECTS=3

Pc-ASPECTS=2

Thrombectomie mécanique

CATCHMERCI

PENUMBRASOLITAIRE

Technical considerations

General Anesthesia & Femoral Approach Guiding catheter: 6F for VA; 8F or 9F balloon guiding catheter for ICA (aspiration during system pull-back)Microcatheter at least .021 in of IDMicroguidewire .014-.016 in Bolus of heparine IV (1000 IU after femoral puncture plus 1000 IU at the end

of first hour), no antiplatelet agents

Solitaire FR eV3

After the procedure: no anticoagulation therapy at least for 24 hours, CT after the procedure and CT or MRI the day after.

Protocol for acute stroke intervention

•Rescue (failed IV Fibrinolysis/MCA)–IV Fibrinolysis 0.9 mg/kg (IV bolus 10%)–Clinical Revaluation at 60 minutes

• If NIHSS > 7 Thrombectomy

•Combined/Bridging (ICA-MCA Tandem, Carotid ‘T’, BA)

–IV Fibrinolysis 0.9 mg/kg (IV bolus 10%) –Thrombectomy under GA

•Mechanical thrombectomy alone (MTB)–After 4h30

Inclusion/Exclusion:

Inclusion- A stroke with relevant deficit- Between 0 and 6H in the anterior circulation OR unknown onset of symptoms (but +ve FLAIR and –ve T2)- No time limit in the posterior circulation- Presence of arterial vascular occlusion on MRA (ICA-M1 TANDEM or M1-M2 or CAROTID ‘T’ or BA)

Exclusion- ASPECT score < 5 for the MCA territory (on b1000)- Extensive brainstem lesions- Spontaneous improvement of the NIHSS (NIHSS < 7)

- High degree of deficit prior to insult

Aspect=7

68years old womenSymptoms onset= H+2H35Admission NIHSS = 17

before

before after

Solitaire FR

Thrombolysis IV = (H+3h20)Reevaluation + 60 mm = NIH 18Rescue : Solitaire FR thrombectomy(+6h20)

Control CT day 1

Hospital discharge D10 NIHSS= 10 mRS =1 D90

Recanalization rate

TICI 3 42 cases, 84%

TICI 2B + 3 44 cases, 88%

n %TICI 3 42 84%TICI 2B 2 4%TICI 2A 2 4%TICI 1 0 0%TICI 0 4 8%Total 50 100% 

Procedure Time

All Procedures Mean time (min)

Onset - Admission 171

Admission - MRI 51

MRI - Puncture 101

Puncture - Recanalization 53

All Proceduresexcluding « Rescue » Mean time (min)

Onset - Admission 188

Admission - MRI 53

MRI - Puncture 95

Puncture - Recanalization 60

Procedural results by location

TICI 3 Procedure time (Puncture to

Recanalization)

Onset to recanalizatio

n time

Number of Device passes

NeurologicalComplicati

on rates

MCA 19/20 (86%)

40 min 296 min 1.5 2/20(10%)

BA 13/16 (81%)

55 min 506 min 2.1 3/16(19%)

ICA 10/14 (71%)

56 min 271 min 2.4 0(0%)

Overall 42/50(84%)

54 min 358 min 2.0 5/50(10%)

Immediate clinical results

Complications

MCA BA ICA

IMMEDIATE N (%)5 (10%)

Asymptomatic SAH 1 (2%)A2 embolism 1 (2%)PICA embolism (+ dissection) 1 (2%)Asymptomatic HSA 1 (2%)Hemorrhagic transformation 1 (2%)

EXTENSION OF INFARCTION AT 24H 6/50 (12%)Failed thrombectomy 1Successful thrombectomy 4Successful thrombectomy and procedural complication 1

PH-1: hematoma ≤30% of the infarcted area with slight space-occupying effect PH-2: dense hematoma >30% of the infarcted area with substantial space- occupying effect or any hemorrhagic lesion outside the infarcted area Pessin et al, 1990; Wolpert et al, 1993; Berger et al, 2001.

Procedure-related mortality: 0

Total complications N (%)10 (20%)

Asymptomatic SAH 1 (2%)PH1 1 (2%)A2 embolism 1 (2%)M1 dissection (+ occlusion) 1 (2%)PH2 1 (2%)PICA embolism 1 (2%)PICA embolism (+ dissection) 1 (2%)Asymptomatic SAH 1 (2%)PH1 1 (2%)Asymptomatic PCA embolism 1 (2%)

Symptomatic complications N (%)5 (10%)

A2 embolism 1 (2%)M1 dissection (+ occlusion) 1 (2%)PH2 1 (2%)PICA embolism 1 (2%)PICA embolism (+ dissection) 1 (2%)

PATIENT 12:NHISS WORSENING FROM 10 IN ADMISSION TO 16 AT DISCHARGE ACA OCCLUSION AFTER T REVASCULARIZATION DURING A COMBINED

PROCEDURE

efore efore AfterBefore

After

3-months outcome

Thombectomy/stroke studies

STUDY Patients NIHSSLocatio

nTime Passes TICI 2+3

Embol

isICH Mortality mRS ≤2

Montpellier 50 15 A + P 377 28 + 84 =

92%8% 2% 12% 54%

POST Penumbra 157 16 A + P 311 n/a54 + 33 =

87% (TIMI)n/a 6% 20% 41%

Multi MERCI 164 19 A + P 354 2.9 68% (TIMI) n/a 10% 34% 36%

iv rt-PA 1391 11 A + P n/a n/a n/a n/a 9% 13% 49%

Thombectomy/stroke studies

STUDY Patients NIHSSLocatio

nTime Passes TICI 2+3

Embol

isICH Mortality mRS ≤2

Montpellier 20 15 MCA 294 1.55 + 95 =

100%5% 0% 0% 70%

Castano et al. 20 19 MCA 359 1.45 + 85 =

90%10% 10% 20% 45%

Roth et al. 8 18 MCA n/a 1.863 + 37 =

100% n/a 0% 0% 75%

PROACT II 121 17 MCA 359 1.4 66% (TIMI) n/a 10% 25% 40%

PROACT II (c) 59 17 MCA 359 1.4 18% (TIMI) n/a 2% 27% 25%

HISTORICAL COMPARISON OF 2 STRATEGIES:IV Rt-pa(2007-2009) VS RESCUE THROMBECTOMY

ALL CASES MCA OCCLUSION (MRA)

Rescue thrombectomyn=24

IV Rt- Pan=32

Recanalization 94%

NIHSS 24H

81% 52%

P=0.01

9% 11%HIC

71% 36%

DC 1 1

IValonen=7

IV+thrombectomyn=17

mRS 90 d P<0.01

SUBMITED IN CEREBROVASCLAR DISEASES

†adjOR(IC95%)

*p

Rescue thrombectomy 11.9 (1.6-89.1) 0.02

Initial NIHSS < 15 12.5 (1.8-87.0) 0.01

MRI ASPECTS > 7 4.9 (0.8-31.0) 0.09

Table 3: Multivariate analysis of favorable clinical outcome at 3 months

Data are adjusted odd ratio (95% CI). Adj OR=adjusted odd ratio. NIHSS=national institute health stroke scale. MRI=magnetic resonnance imaging. ASPECT=alberta stroke program early computed tomography score. *p for comparison between IVT and Rescue therapy (χ² test or Fisher’s exact test). †Odd ratio value comparing the 3 months clinical outcome between IVT and Rescue therapy, after adjustment for confounding factors.

Inclusion per site

Country Center Lead Physician

# of Ptsn = 141

Spain Hospital Germans Trias i Pujol de Badalona, Barcelona C. Castano 45 (32%)

Switzerland

Hôpitaux Universitaires de Genève, Geneva

V. Mendes Pereira

29 (20.5%)

Germany AKK Hospital, Essen R. Chapot 25 (18%)

France Hôpital Gui de Chauliac, Montpellier A. Bonafé 20(14%)

Sweden Karolinska sjukhuset, Stockholm T. Andersson 15 (10.5%)

Switzerland

Inselspital University Hospital of Bern J. Gralla 7 (5%)

Patient and Stroke Characteristics

• Mean age: 66.3 [20-89]• Female: 62 (44%)• Median NIHSS score: 18 [1-32]• IV-tPA administered: 74 (52%)

• 0.6mg/kg: 11 - 0.9 mg/kg: 49 - Dose not specified: 14

– Failed IV-tPA: 46 (32%)– Bridging: 28 (20%)

• No IV-tPA administered: 67 (48%)– Contraindication to IV-tPA: 56 (40%)– Direct to IA with no contraindication to IV-tPA: 11 (8%)

Occlusion site - CoreLab

Localisation N (%)ICA 6 (4%)

Carotid T 33 (23%)M1 66 (46%)M2 19 (13%)VB 16 (11%)

PCA 2 (1%)SCA 1 (1%)

• N= 143 occlusion sites over 138 patients analyzed*

*: 2 patients not evaluable: Angiopplasty/ stent proxy carotid. Not clear distal clot removal performed Stent left ICA origin. Stenosis 70%. No intracranial occlusion treated.

1 patient not evaluated due to missing imaging (pt 10-035).

Solitaire outcomes compared to Merci and Penumbra historical outcomes data

Revascularization rates: TIMI ≥ 2 Scores 90 days F/U: modified Rankin Scores

References: 1.Mechanical thrombectomy for Acute ischemic stroke,WS Smith et al Stroke 2008; 39:1205-12122.The penumbra pivotal stroke trial: Stroke, 2009; 40: 2761-2768

mRS grade at 90 days (site evaluation)

Patient Outcome at 90 days

mRS N (%)0 27 (19%)1 25 (18%)2 25 (18%)3 13 (9%)4 17 (12%)5 4 (3%)6 26 (18%)

mRS ≤ 2: 55%

Morbidity (mRS>2): 34/141 (24%)

Mortality : 29/141 (20.5%)3 patients lost to Follow-up considered as worst outcome

CONCLUSIONS

• Validity of patient selection based on DWI derived ASPECT Score ≥5 and clinical mismatch,

• Safety of bridging strategy combining IV lytics and mechanical thrombectomy ( low rate of symptomatic IC hemorragic complications),

• Significant 3 months improvment of clinical outcome in MCA occlusion (70% mRS ≤2).