TCD Monitoring of reperfusion therapies in acute ischemic stroke patients with proximal intracranial occlusion

Transcription

1 3 rd Congress of the European Academy of Neurology Amsterdam, The Netherlands, June 24 27, 2017 Teaching Course 5 Advanced neurosonology - Level 3 TCD Monitoring of reperfusion therapies in acute ischemic stroke patients with proximal intracranial occlusion Georgios Tsivgoulis Gerakas, Greece tsivgoulisgiorg@yahoo.gr

2 TCD MONITORING OF REPERFUSION THERAPIES IN AIS PATIENTS WITH PROXIMAL INTRACRANIAL OCCLUSIONS Georgios Tsivgoulis, MD, PhD, MSc, FESO 1,2 1 Second Department of Neurology, School of Medicine, National & Kapodistrian University of Athens, Athens, Greece 2 Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, US Presenter Disclosure Information Georgios Tsivgoulis, MD. Lecture Title: TCD monitoring of reperfusion therapies in AIS patients with proximal intracranial occlusions Financial Disclosure: None Unlabeled/Unapproved Uses Disclosure : None 1

3 OUTLINE Reperfusion therapies for AIS patients with LVO (IVT & ERT) Real-time monitoring of recanalization in IVT Detection of complications of IVT (sich & reocclusion) Prognostication after IVT Detection of complications of ERT Prognostication after ERT Conclusions INTRAVENOUS THROMBOLYSIS: CLOT DISSOLUTION 2

4 SAFETY & EFFICACY OF IVT IN AIS IVT: ONLY APPROVED SYSTEMIC REPERFUSION THERAPY FAVOURABLE FUNCTIONAL OUTCOME (NNT=8), IMPROVEMENT OF NEUROLOGICAL DYSFUNCTION (NNT=4) SICH (6.5%=>2%), DEATH OR SEVERE DISABILITY (NNH: 33) COST EFFECTIVE: 4.000$/PATIENT (1998) Wechsler LR. NEJM 2011;364: Barreto AD. Neurotherapeutics 2011;8: Tsivgoulis et al. Expert Opin Drug Saf 2015;14: TPA-INDUCED RECANALIZATION OF PROXIMAL INTRACRANIAL ARTERIAL OCCLUSION Demchuk et al. Stroke 2001;32:89-93 Alexandrov et al. Circulation 2001; Tsivgoulis et al. Stroke 2008;39:

5 RECANALIZATION: MOST IMPORTANT OUTCOME PREDICTOR IN IVT FFO: 443% Mortality: 76% Rha & Saver. Stroke 2007;38: LIMITATIONS OF IVT FOR AIS NARROW TIME WINDOW ( 4.5hrs) NUMEROUS EXCLUSION CRITERIA (RECENT SURGERY, INTERVENTIONAL PROCEDURES, INR>1.7, NOACs, RECENT AIS/MI) COMPLETE RECANALIZATION : 40% OF PROXIMAL INTRACANIAL ARTERIAL OCCLUSIONS REOCCLUSION (10%-25%) =>DFI LARGE CLOT BURDEN (TICA, TANDEM ICA/MCA): LOW LIKELIHOOD OF RECANALIZATION Wechsler LR. NEJM 2011;364: Barreto AD. Neurotherapeutics 2011;8: Tsivgoulis et al. Expert Opin Drug Saf 2015;14:

6 CLOT BURDEN: STRONGEST PREDICTOR OF TPA FAILURE Riedel et al. Stroke 2011;42: ADVANTAGES OF ENDOVASCULAR REPERFUSION THERAPIES (ERT) EXTENSION OF TIME WINDOW ( 8-12 HRS) APPLICABLE TO PATIENTS WITH CONTRAINDICATIONS TO IVT HIGHER RECANALIZATION RATES (60%-80%) MORE EFFECTIVE THAN IVT IN AMI Broderick JP. Stroke 2013;44:S3-S6 Saver JL.Stroke 2013;44:S13-S15 Hennerici et al. Lancet Neurology 2013;12:

7 MT IS THE NEW STANDARD OF CARE FOR AIS DUE TO LVO IN ANTERIOR CIRCULATION MR CLEAN ESCAPE EXTEND-IA SWIFT PRIME REVASCAT THERAPY THRACE MT IS THE NEW STANDARD OF CARE FOR AIS DUE TO LVO IN ANTERIOR CIRCULATION 6

8 MT FOR AIS DUE TO LVO (7 TRIALS, mrs 0-2) MT: 47% ST: 30% AΒΙ: 17% ΝΝΤ: 6 Tsivgoulis et al. Expert Rev Neurother 2016;16: MT FOR AIS DUE TO LVO (8 TRIALS, mrs 0-2) MT: 47% ST: 30% AΒΙ: 17% ΝΝΤ: 6 MR CLEAN REVASCAT ESCAPE THRACE EXTEND-IA THERAPY SWIFT PISTE Tsivgoulis, Katsanos et al. Unpublished analyses 7

9 MT FOR AIS DUE TO LVO (8 TRIALS, mrs 0-1) MT: 29% ST: 16% AΒΙ: 13% ΝΝΤ: 8 MR CLEAN REVASCAT ESCAPE THRACE EXTEND-IA THERAPY SWIFT PISTE Tsivgoulis, Katsanos et al. Unpublished analyses MT FOR AIS DUE LVO IN ANTERIOR CIRCULATION (8 TRIALS, mortality) MT: 15% ST: 18% ARR: 3% (NS) ΝΝΤ: 33 (NS) MR CLEAN REVASCAT ESCAPE THRACE EXTEND-IA THERAPY SWIFT PISTE Tsivgoulis, Katsanos, et al. Unpublished analyses 8

10 MT FOR AIS DUE TO LVO (3 TRIALS, Recanalization hrs) MT: 79% ST: 35% ΑΒΙ: 44% NNT: 2 Tsivgoulis et al. Brain Behav 2016;6:e00418 MT FOR AIS DUE TO LVO IN ANTERIOR CIRCULATION (AHA/ASA RECOMMENDATIONS) Powers et al. Stroke 2015;46:

11 MT FOR AIS DUE TO LVO IN ANTERIOR CIRCULATION (AHA/ASA RECOMMENDATIONS) Wahlgren et al. Int J Stroke 2016;11: OUTLINE Reperfusion therapies for AIS patients with LVO (IVT & ERT) Real-time monitoring of recanalization in IVT Detection of complications of IVT (sich & reocclusion) Prognostication after IVT Detection of complications of ERT Prognostication after ERT Conclusions 10

12 Bedside evaluation Easily repeatable Non-invasive Inexpensive No radiation TCD IN AIS Can provide diagnostic information (location & degree of occlusion, collateral status, impaired hemodynamics, vascular steal phenomenon in OSAS, real-time embolization, refine CTA/MRA findings) Alexandrov et al. J Neuroimaging 2012;22: Tsivgoulis et al. Curr Neurol Neurosci Report 2009;9:46-54 US SELECTION OF APPROPRIATE CANDIDATES FOR IVT Assist in treatment decisions for patients presenting with mild stroke (NIHSS<4) Assist in treatment decisions in comatose patients (BA occlusion) Assist in differential diagnosis of stroke mimics Assist in timely diagnosis of uncommon causes of AIS with contrandications to IVT (aortic arch dissection, endocarditis, intracranial aneurysm with intraluminal thrombus, vasospasm due to undiagnosed SAH) Fischer et al. Stroke 2005; 36: Tsivgoulis G. et al. Stroke 2007;38: Tsivgoulis G. et al. Stroke 2008;39: Savitz et al. Acad. Emerg. Med 2007;14:

13 CLINICAL PRESENTATION 68 year old man with acute onset of right lid ptosis & sensory deficits in right arm (NIHSS=2) CLINICAL PRESENTATION 37 year old man presenting with acute dysarthria, left hemiparesis & left hemineglect (ΝΙΗSS 14, 160 min) Tsivgoulis, et al. Circulation 2011:124:

14 TCD-MONITORING OF RECANALIZATION TCD-MONITORING OF RECANALIZATION Portable TCD and duplex Fast track protocol Use full power High PRF, gate > 10 mm Occlusion(s) location The worst residual flow Monitoring set Hand-held monitoring in agitated patients 13

15 TCD MONITORING OF RECANALIZATION COMPLETE RECANALIZATION PARTIAL RECANALIZATION Demchuk et al. Stroke 2001;32:89-93 Alexandrov et al. Circulation 2001; Tsivgoulis et al. Stroke 2008;39: ASSESSMENT OF RECANALIZATION: TIBI FLOW GRADES 14

16 PREDICTORS OF RECANALIZATION DURING TCD-MONITORING OF IVT FOR AIS Increase in TIBI flow grading system Increase in EDV Presence of microembolic signal distal to the location of occlusion Presence of flow distal to the location of occlusion Absence of tandem occlusion Good collateral status (flow diversion in ACA/PCA, retroperfusion of distal MCA via leptomeningeal collaterals) Demchuk et al. Stroke 2001;32:89-93 Alexandrov et al. Circulation 2001; Tsivgoulis et al. Stroke 2008;39: RECANALIZATION: MOST IMPORTANT OUTCOME PREDICTOR IN IVT FFO: 443% Mortality: 76% Rha & Saver. Stroke 2007;38:

17 REAL-TIME MONITORING OF RECANALIZATION (CASE EXAMPLE ) 74 year old woman with history of Hypertension & Hypercholesterolemia 8:30 acute onset of dysarthria and right arm weakness 9:10 ER of regional hospital at the state of Alabama NIHSS: 10 Brain CT: No Hemorrhage 16

18 12:46, 4h:16min 12:48, 4h:18min 17

19 12:49, 4h:19min iv tpa bolus 12:50, 4h:20min 18

20 12:51, 4h:21min Beginning of tpa infusion 12:53, 4h:23min 19

21 13:02, 4h:32min (NIHSS 13) 13:16, 4h:46min (NIHSS 14) 20

22 14:57, 6h:27min (NIHSS 5) 24 h, NIHSS 2 21

23 TCD: RELIABLE TOOL IN MONITORING RECANALIZATION 96 time-linked TCD images captured during monitoring of 96 simultaneous DSA runs 62 AIS Median NIHSS 18points Median onset to intra-arterial procedure time 240 min Tsivgoulis et al. Stroke 2013 ;44:

24 Tsivgoulis et al. Stroke 2013 ;44: EARLY NEUROLOGICAL DETERIORATION IN AIS TREATED WITH IVT Seners et al. JNNP 2015;86:

25 EARLY NEUROLOGICAL DETERIORATION IN AIS TREATED WITH IVT sich Malignant Cerebral Edema Failure to recanalize in LVO Extension of ischemic infarct Arterial reocclusion Collateral failure Clot extension Early recurrent ishemic stroke in previous unaffected arterial territory Tisserand et al. Stroke 2014;45: Seners et al. JNNP 2015 ;86:97-94 Seners et al. Stroke 2017; 48: TCCD: Detection of sich Perez et al. Stroke 2009; 40:

26 34 pts with supratentorial acute ICH (<3hrs) Baseline CT/TCCS (TCCS before CT) Repeat CT/TCCS (hematoma expansion) Sonographers blinded to CT Perez et al. Stroke 2009; 40: TCCD: Detection of sich Perez et al. Stroke 2009; 40:

27 TCCD: Detection of sich (Case Description) An 80-year old man present with acute expessive aphasia and mild right hemiparesis (NIHSS-score: 7 points). Admission brain CT disclosed an ASPECTS score of 9/10 The patient received iv-tpa at 4 hours following Sx onset. Post-thrombolysis, the patients blood pressure levels fluctuated with systolic hypertensive picks up to 190 mmhg. Four hours after treatment the patient deteriorated and became non-responsive (NIHSS-score of 19 points). ARTERIAL REOCCLUSION & END IN AIS Arterial reocclusion has increasingly been identified to be causally associated with clinical worsening and poor outcome in AIS pts treated with acute reperfusion therapies Arterial reocclusion accounts for 2/3 of cases experiencing DFI after IVT Early reocclusion occurs in 15%-34% of AIS pts treated with ivtpa achieving any initial recanalization, accounting for up 2/3 of DFI The prevalence of reocclusion among AIS treated with ia-tpa was 17% The prevalence of reocclusion occuring during and within an hour after intra-arterial reperfusion procedures was 19% and 8% respectively Large-vessel atherosclerotic stroke, stroke severity (NIHSS>16) and partial recanalization are independent predictors of reocclusion Burgin& Alexandrov. Neurology 2001;56: Alexandrov&Grotta. Neurology 2002;59: Qureshi et al. AJNR 2004;25: Rubiera et al. Stroke 2005;36: Tsivgoulis et al. Stroke 2009;40:e157-e158 Rubiera et al. Stroke 2010;41:

28 TCD CAN RELIABLY DETECT REOCCLUSION IN REAL-TIME Before tpa-bolus 28 min 42 min 56 min Alexandrov&Grotta. Neurology 2002;59: Rubiera et al. Stroke 2005;36: Tsivgoulis et al, for CLOTBUST Investigators. Stroke 2009;40:e157-e158. ARTERIAL REOCCLUSION IS ASSOCIATED WITH ADVERSE FUNCTIONAL OUTCOMES Variable Reocclusion (+) Reocclusion (-) p Neurological improvement during hospitalization (median NIHSS decrease, IQR) mrs 0-1 at 3 months (%) 3 (7) 7 (10) < % 51% ΔNIHSS at 24 h 3-month mrs Rubiera et al. Stroke 2005;36: Tsivgoulis et al, for CLOTBUST Investigators. Stroke 2009;40:e157-e

29 PROGNOSTIC INFORMATION OF TCD IN IVT Baseline TCD assessment of residual flow may predict the Likelihood of recanalization TCD assessment of recanalization at 2 fours following tpa-bolus is the strongest predictor of FFO at 3 months Persisting occlusion/delayed reperfusion may predict sich following IVT IVT in patients with ICA occlusion may be complicated with malignant cerebral edema Alexandrov et al. J Neuroimaging 2012;22: Tsivgoulis et al. Curr Neurol Neurosci Report 2009;9:46-54 RESIDUAL FLOW AT SITE OF INTRACRANIAL OCCLUSION PREDICTS RESPONSE TO IVT 28

30 RESIDUAL FLOW AT SITE OF INTRACRANIAL OCCLUSION PREDICTS RESPONSE TO IVT RESIDUAL FLOW AT SITE OF INTRACRANIAL OCCLUSION PREDICTS RESPONSE TO IVT 29

31 TCD ASSESMENT OF RECANALIZATION: STRONGER PREDICTOR OF FFO (3 months) TCD ASSESMENT OF RECANALIZATION: STRONGER PREDICTOR OF FFO (3 months) 30

32 DELAYED REPERFUSION/PERISTING OCCLUSION: INDEPENDENT PREDICTOR OF SICH Molina et al. Stroke 2002 ;33: DELAYED REPERFUSION/PERISTING OCCLUSION: INDEPENDENT PREDICTOR OF SICH 31

33 DELAYED REPERFUSION/PERISTING OCCLUSION: INDEPENDENT PREDICTOR OF SICH RISK OF MALIGNANT CEREBRAL INFARCTION IN ICA OCCLUSION TREATED WITH IVT PROSPECTIVE CASE-CONTROL STUDY WITH ADJUSTMENT FOR DEMOGRAPHICS & STROKE SEVERITY(Ν=506) 32

34 ABSOLUTE INCREASE IN FFO (mrs score of 0-2) AT THREE MONTHS: 8% (relative increase 80%) ABSOLUTE INCREASE IN FUNCTIONAL INDEPENDENCE (mrs score of 0-1) AT THREE MONTHS: 10% (relative increase 159%) RISK OF MALIGNANT CEREBRAL INFARCTION IN ICA OCCLUSION TREATED WITH IVT 33

35 TCD MONITORING OF INTRACRANIAL PRESSURE Alexandrov AV. Cerebrovascular Ultrasound in Stroke Prevention and Treatment. 2 nd Edition TCCD MONITORING OF MIDLINE SHIFT MIDLINE SHIFT: [DISTANCE A-DISTANCE B]/2 DISTANCE A: Right transtemporal insonation DISTANCE B: Left transtemporal insonation Motuel et al. Critical Care 2014;18:676 34

36 Motuel et al. Critical Care 2014;18:676 OUTLINE Reperfusion therapies for AIS patients with LVO (IVT & ERT) Real-time monitoring of recanalization in IVT Detection of complications of IVT (sich & reocclusion) Prognostication after IVT Detection of complications of ERT Prognostication after ERT Conclusions 35

37 CLINICAL APPLICATIONS OF DIAGNOSTIC US DURING INTRA-ARTERIAL REPERFUSION PROCEDURES IN AIS Monitor recanalization in real-time (reduce the number of contrast-injections) Provide prognostic information in patients with contraindications to CTA/MRA Detect arterial reoclussion during and shortly after the procedure Detect air embolism in real-time Detect artery-to-artery embolization in real-time Detect hyperperfusion syndrome following IA procedures Rubiera et al. Stroke 2010; 41: Tsivgoulis et al. Stroke 2013 ;44: SELECTION OF PATIENTS FOR RESCUE ENDOVASCULAR REPERFUSION PROCEDURES FOLLOWING IVT 36

38 SELECTION OF PATIENTS FOR RESCUE ENDOVASCULAR REPERFUSION PROCEDURES FOLLOWING IVT DIAGNOSTIC YIELD OF REAL-TIME ULTRASOUND MONITORING OF ENDOVASCULAR REPERFUSION PROCEDURES FOR AIS 37

39 51 AIS Median NIHSS 17points Mean time from onset to ia procedure 289 min IA-TPA, Thrombectomy, Thromboaspiration, Stenting 38

40 39

41 YIELD OF ULTRASOUND MONITORING DURING AND AFTER ENDOVASCULAR PERFUSION PROCEDURES FOR AIS (CASE DESCRIPTION 1) Zhao L. et al. J Neuroimaging 2012;22:92-94 YIELD OF ULTRASOUND MONITORING DURING AND AFTER ENDOVASCULAR PERFUSION PROCEDURES FOR AIS (CASE DESCRIPTION 2) 6 year-old boy with acute left hemiparesis (8:00 am) Past history: mitral valve repair and VSD closure Baseline NIHSS: 15 IV tpa bolus at 78min after Sx onset at outside institution No improvement during 0.9 mg/kg iv tpa infusion, total dose infused 22.5mg Transferred for rescue interventional therapy at UAB 40

42 BASELINE TCD/DSA LMCA, MFV=52cm/sec RTICA Anterior cross-filling MFV=135 cm/sec LACA, MFV=102 cm/sec Interventional Reperfusion Therapies Infusion of IA Reteplase (1.1 U) (12:15-12:45, 4h and 15 min from Sx onset) Failed Thombectomy with MERCI retriever (multiple passes,12:25-12:45, 4h and 45 min from Sx onset) Balloon manipulation of the thrombus to place it into the right A1ACA (13:20, 5 hours and 20 min from Sx onset) Second Infusion of ia Retavase (13:40, 5 h and 40 min from Sx onset) 41

43 A MERCI RETRIEVER C Partial recanalization Pass of retriever coil through the clot B D Reocclusion Retriever coil pulling through the clot TCD/DSA post intervention 42

44 MRI post intervention ADC DWI NIHSS Day 2: 8 NIHSS discharge: 5 NIHSS 3 months: 2 mrs 3 months: 1 43

45 TCD LIMITATIONS IN MONITORING OF SYSTEMIC & ENDOVASCULAR REPERFUSION THERAPIES Absent transtemporal windows (10%-15%) Useful only in the hands of specially trained and experienced operators Stroke team required ( 2 individuals) in order not to use valuable time before tpa infusion or groin puncture The nonradiolucent parts of the head frame can interfere with the lateral projection of the angiography May cause discomfort in agitated patients Can only monitor downstream flow in Vert/Ba occlusions treated with MT Alexandrov et al. J Neuroimaging 2012;22: Tsivgoulis et al. Curr Neurol Neurosci Report 2009;9:46-54 Rubiera et al. Stroke 2010;41: CONCLUSIONS I NVUS IDEAL TOOL FOR OPTIMAL PATIENT SELECTION FOR THROMBOLYSIS (FAST, INEXPENSIVE, EASILY REPEATABLE, PERFORMED AT THE BEDSIDE) TCD/TCCD CAN RELIABLY MONITOR RECANALIZATION IN REAL-TIME DURING IV TPA INFUSION & PROVIDE CRITICAL PROGNOSTIC INFORMATION TCD/TCCD MAY DETECT REOCCLUSION IN AIS PATIENTS WITH DETERIORATION FOLLOWING IMPROVEMENT AFTER TPA INFUSION TCCD MAY DETECT SICH & CEREBRAL EDEMA IN AIS PATIENTS TREATED WITH IVT TCD/TCCD INVALUABLE FOR PATIENTS WHO CANNOT UNDERGO CTA 44

46 CONCLUSIONS II TCD/TCCD MAY DETECT COMPLICATIONS DURING & FOLLOWING ENDOVASCULAR REPERFUSION PROCEDURES: REOCCLUSION, AIR EMBOLISM, HYPERPERFUSION SYNDROME TCD/TCCD: MAY ACCURATELY DETECT RECANALIZATION DURING ENDOVASCULAR REPERFUSION PROCEDURES: LIMIT THE NUMBER OF CONTRAST INJECTIONS & REDUCE THE DURATION OF THE PROCEDURE TCD/TCCD MAY ASSIST INTERVENTIONALISTS IN CLINICAL DECISION MAKING DURING ENDOVASCULAR REPERFUSION PROCEDURES REQUIRES ADEQUATE TRANSTEMPORAL WINDOWS & SKILLED/EXPERIENCED OPERATORS 45