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Microemboli: revisione

Microemboli: revisione. M. Del Sette Dipartimento di Neuroscienze Università di Genova. IPOTESI CLINICA. GLI EVENTI CEREBROVASCOLARI SONO IN MAGGIOR PARTE DI ORIGINE EMBOLICA IL DOPPLER TRANSCRANICO PUO’ RILEVARE MICROEMBOLI ( M.E.S.) 3. LA MICROEMBOLIA E’ CORRELATA ALLA MACROEMBOLIA.

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Microemboli: revisione

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  1. Microemboli: revisione M. Del Sette Dipartimento di Neuroscienze Università di Genova

  2. IPOTESI CLINICA • GLI EVENTI CEREBROVASCOLARI SONO IN MAGGIOR PARTE DI ORIGINE EMBOLICA • IL DOPPLER TRANSCRANICO PUO’ RILEVARE MICROEMBOLI ( M.E.S.) 3. LA MICROEMBOLIA E’ CORRELATA ALLA MACROEMBOLIA

  3. SOMMARIO • COME SI FA LA DIAGNOSI DI M.E.S.? • IN QUALI CONDIZIONI CLINICHE SI POSSONO RILEVARE? • SONO INFLUENZATI DA TERAPIE? • DI COSA SONO COMPOSTI?

  4. DIAGNOSI DI M.E.S. • Durata < 300 msec. • Ampiezza > 3 dB • Unidirezionalità • Suono tipico • Monitoraggio prolungato (Consensus Committee, Stroke’95 and ‘98)

  5. CONDIZIONI CLINICHE CON PRESENZA DI M.E.S. • 1. STENOSI CAROTIDEA • 2. PATOLOGIE CARDIACHE EMBOLIGENE • 3. ICTUS ISCHEMICO ACUTO • 4. INTERVENTI DI ENDOARTERIECTOMIA CAROTIDEA - ANGIOPLASTICA E STENT • 5. CHIRURGIA CARDIACA

  6. MES SONO MARKER SURROGATO DI EVENTI?

  7. FATTORI DI RISCHIO PER:ICTUS M.E.S. • entità della stenosi carotidea • placca ulcerata • pregresso TIA • sintomi recenti • presenza di M.E.S.? • entità della stenosi carotidea • placca ulcerata • pregresso TIA • sintomi recenti

  8. M.E.S. E STENOSI CAROTIDEA (Siebler et al., ’94)

  9. Valore predittivo dei M.E.S. • 111 PAZIENTI STENOSI >60% • MES: 41 (36.9%) • STENOSI: • <70: 22% • 70-90: 48% • >90: 21% • RECIDIVA PIU’ FREQUENTE IN STENOSI CON M.E.S: O.R. 8.10 (Molloy and Markus, 1999)

  10. M.E.S.: marker di eventi clinici nella stenosi carotidea>60% MES criteria Patients Risk of Stroke/TIA* MES positive Symptomatic1 X 8 With >1 MES per hour Symptomatic and asymptomatic2 X 9 Symptomatic3 X 31 With >2 MES per hour • 1.Siebler M et al. Stroke 1995; 26: 21842186. • 2. Valton L et al. Stroke 1998; 29: 21252128. • 3. Molloy J et al. Stroke 1999; 30: 14401443.

  11. Stenosi asintomatiche senza MES sono a basso rischio • 319 stenosi asintomatiche > 60% • Monitoraggio per 1 ora in 2 occasioni • MES in 32 (10%) • A 1 anno: rischio di ictus 15.6% vs. 1% (p<.0001) (Spence et al., Stroke 2005;36:2373-8)

  12. Significato prognostico dei M.E.S. nell’ictus acuto • Nessuna relazione con prognosi funzionale • Possibile significato predittivo sulla probabilità di recidiva precoce (Valton et al., ‘97; Babikian et al., ‘97) • Correlati con deterioramento cognitivo (Russell, ’92)

  13. MES POSSONO ESSERE USATI PER STUDIARE L’EFFETTO DI FARMACI?

  14. Cardioembolie • Nessuna correlazione tra MES e terapie (anticoagulanti o antiaggreganti) • Georgiadis et al., Anticoagulation monitoring with transcranial Doppler.Lancet. 1994 12;344(8933):1373-4 • Sturzenegger et al., Monitoring Combined Antithrombotic Treatments in Patients With Prosthetic Heart Valves Using Transcranial Doppler and Coagulation Markers Stroke. 1995;26:63-69 • Sliwka et al., Occurrence of Transcranial Doppler High-Intensity Transient Signals in Patients With Potential Cardiac Sources of EmbolismStroke. 1995;26:2067-2070 ‘98, • Del Sette et al., Warfarin, aspirin and microembolic signals in the acute phase of stroke in a patient with mechanical heart valves. Cerebrovasc Dis . 1998 8(3):182-3

  15. Ictus acuto • No correlazione tra MES e ASA, eparina o warfarin • Georgiadis et al., Anticoagulation monitoring with transcranial Doppler.Lancet. 1994 12;344(8933):1373-4 • Tong et al., Transcranial Doppler–Detected Microemboli in Patients With Acute Stroke. Stroke. 1995;26:1588-1592. • Del Sette et al. Microembolic Signals With Serial Transcranial Doppler Monitoring in Acute Focal Ischemic Deficit A Local Phenomenon? Stroke.1997;28:1311-1313 • Poppert et al.Embolic signals in unselected stroke patients Stroke 2006;37:2039-43)

  16. Sliwka et al. Prevalence and Time Course of Microembolic Signals in Patients With Acute Stroke (Stroke. 1997;28:358-363.)

  17. ICTUS ACUTO: ANEDDOTICA • 1 case of MCA stenosis: disappearance of after Warfarin + ticlopidine (Segura et al., ’98) • 1 case of PCA infarction: MES disappearance after Warfarin + ASA (Behrens et al., ’99) • 1 case of basilar stenosis: reduction of MES after warfarin (Kassnasrallah et al., ’99) • 2 reports: decline of MES after heparine (Dinia et al. Cerebrovasc Dis. 2006; Marinoni et al., Eur Neurol ‘06)

  18. STENOSI CAROTIDEA • 9 pt. with recently symptomatic ICA stenosis: ASA i.v. (500 mg): significant reduction of ipsilateral MES in 7 after 30 minutes • no ischemic event was observed within a 90-day follow-up after the initiation of ASA prevention compared with 2.3 events in the month before. (Goertler et al.,Stroke. 1999;30:66-69.)

  19. STENOSI CAROTIDEA • 74 pt., 1 hour monitoring • 26 without ASA: 73% MES • 48 with ASA: 40% • Predictors of MES: • Absence of ASA (OR 7.1; 95% CI 1.6-31.4) • Recurrent events (OR 3.8; 95% CI 1.1-13.2) (Goertler et al., Cerebrovasc Dis ’01) (p=0.023)

  20. STENOSI ACI O ACM • 8 pt.with recent (7 days) TIA and ASA therapy • Addition of clopidogrel and MES monitoring from 3rd to 7th days • Significant decrease of MES (cessation in 4) (Esagunde et al., Cerebrovasc Dis, 2006)

  21. CARESS Randomized, controlled, double blind (n=107) D1 D2 D7 ± 1 D-1 Clopidogrel 75 mg o.d. Clopidogrel 300 mg Clopidogrel n = 50 R ASA 75 mg o.d. to all patients from D1 to D7±1 Placebo n = 50 Placebo Placebo o.d. MES detection MES detection MES detection (Markus et al., Circulation, 2005)

  22. CARESS: Results Primary Endpoint Results: Number of MES+ Patients at D7** RRR 25.2% p = 0.078 RRR 37.3% p = 0.011 100% 100% 100 76.0% 80 72.5% 56.8% 60 %of Patients 45.5% 40 Placebo* Clopidogrel* 20 0 Baseline Day 1 Day 7 (Markus et al., Circulation, 2005)

  23. ASA + CLOPIDOGRELCHE FARE? MATCH • N= 7599 • TIA (21%) or stroke (79%) + 1 RF • Distance from symptoms: 3 months • F.U.: 18 months • many lacunar stroke CARESS • N= 107 • TIA (63%) or stroke (37%) • Distance from symptoms: 3 months • F.U.: 7 days • all > 50% carotid stenosis

  24. NATURA DEI M.E.S. • Gassosa • Particolata (piastrine, trombo)

  25. NATURA DEI M.E.S. • Inalazione ossigeno • Rete neurale • Analisi multifrequenza: • 2 MHz riflette gas • 2.5 MHz riflette particelle solide • Analisi “time frequency” (wavelet transform)

  26. CONCLUSIONI - I • M.E.S. INDICANO LA PRESENZA NEL VASO DI MATERIALE A IMPEDENZA DIFFERENTE DAL SANGUE • COMPOSTI DA GAS O PARTICELLE • MARKER DI EVENTI CLINICI, SPECIE IN STENOSI CAROTIDEA

  27. CONCLUSIONI - II • NECESSITANO DI TECNICHE DI MONITORAGGIO PROLUNGATO (60’) • ICTUS ACUTO: predittori di recidiva e deterioramento cognitivo • MONITORAGGIO ENDOARTERIECTOMIA E STENTING

  28. GRAZIE

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