Setor de Doenças Cerebrovasculares, Serviço de Neurologia do Departamento de Clínica Médica do Hospital de Clinícas da UFPR - Curitiba, PR
Os primeiros estudos clínicos com o uso do Doppler transcraniano (DTC) durante a fase aguda do acidente vascular cerebral isquêmico (AVCi) foram realizados ainda no período pré-trombólise. Velocidade média de fluxo (VM) na artéria cerebral média (ACM) menor que 20 cm/seg ou 50% abaixo da ACM contralateral, nas primeiras 24 horas, traduz fator de pior prognóstico1. A trombólise endovenosa no tratamento do AVCi possibilitou uma utilização ainda maior do DTC na fase aguda, complementando a avaliação emergencial, possibilitando a identificação da oclusão intracraniana e configurando-se em ferramenta única na monitoração contínua da abertura do vaso – recanalização2. Desenhos de estudos mais recentes propõem que as alterações encontradas no DTC façam parte dos critérios de inclusão no uso do trombolítico endovenoso, uma vez que esse esquema terapêutico é potencialmente indicado e benéfico nos casos de isquemia encefálica com oclusão de ramo arterial intracraniano3-5.
O DTC vem sendo absorvido pelos principais serviços universitários do nosso país e também por hospitais que realizam atendimento de pacientes com doenças cerebrovasculares6. Além da não-invasibilidade, o DTC apresenta como principais vantagens o baixo custo, o dinamismo, a rapidez em casos direcionados e a portabilidade. Pode ser realizado e repetido inúmeras vezes, à beira de leito, podendo ainda apresentar potencial terapêutico7-9. As principais dificuldades do método são a de pertencer ao grupo de exames complementares operador-dependente e a falta de estudos para estabelecimento de critérios de interpretação uniformemente aceitos7. Na situação do AVCi agudo, em paralelo aos exames de imagem, como a tomografia axial computadorizada (TAC) e a ressonância nuclear magnética (RNM), o DTC vem inovando conceitos e tratamentos permitindo melhor atendimento aos pacientes candidatos e não-candidatos à trombólise. A pesquisa de microembolias – ferramenta única – e a alta sensibilidade para detecção e seguimento de estenoses intracranianas fazem do DTC um exame de rotina no paciente com doença cerebrovascular (DCV)3,10. Limitaremos essa revisão em situação de atendimento agudo da DCV.
É importante ressaltarmos que os principais estudos estão relacionados com a análise da ACM, cuja topografia corresponde à maioria dos eventos isquêmicos cerebrais. Sugerimos, sempre que possível, a investigação extracraniana não-invasiva com ultra-sonografia dos vasos cervicais – artérias carótidas, vertebrais e subclávias – para o auxílio na interpretação e conseqüente aumento da acurácia do DTC11.
Embora ainda sejam poucos os serviços que disponibilizam tratamento trombolítico aos pacientes com AVCi agudo em nosso país, a tendência em aprimorar essa terapêutica é imperativa e promissora. Estudos
Utilizando essa classificação como modelo, Demchuk e cols.4, em 2001, descreveram uma análise sistemática da ACM por meio do DTC no AVCi agudo denominada TIBI (
Vários estudos experimentais já demonstraram que o ultra-som facilita a atividade de agentes fibrinolíticos em razão da melhora no transporte da medicação, alteração da estrutura da fibrina e aumento da ligação tPA-fibrina8. O estudo CLOTBUST demonstrou uma possível potencialização da trombólise quando utilizada concomitantemente com o DTC, nos casos de documentação de oclusão de ACM com menos de três horas de evolução. O grupo monitorado continuamente durante a infusão endovenosa do trombolítico apresentou um maior índice de recanalização e melhora da independência funcional, quando comparado aos pacientes que não foram monitorados continuamente com o DTC5. Entretanto, estudo recente, denominado TRUMBI, onde os autores analisaram a relação da baixa intensidade do ultra-som (300 Khz) com o potencial de trombólise, foi interrompido precocemente pela maior incidência de hemorragia intraparenquimatosa sintomática no grupo de estudo16. Outros estudos serão necessários para a fundamentação desse método. A utilização de solução de microbolhas endovenosa tem demonstrado aumentar ainda mais o efeito obtido pela associação do DTC com o trombolítico17.
Entre as informações obtidas pelo método, o DTC também possibilita o reconhecimento da recanalização precoce na ACM ocluída após a infusão do trombolítico, independente da recuperação clínica, conhecido como cérebro hibernado15,18. O padrão de recanalização, quando espontânea, deve sempre ser diferenciado de estenose intracraniana, a qual pode apresentar-se com achados similares no exame inicial. Os exames seqüenciais serão fundamentais para definição, uma vez que na recanalização as velocidades de fluxo retornam a valores próximos à normalidade em um período variável de tempo.
O DTC possibilita a identificação de sinais de microembolia, do inglês "
A embolia pode originar-se de fontes cardíacas, das grandes artérias – aorta, carótidas e vertebrais –, artérias intracranianas, e paradoxalmente alcança a circulação cerebral por meio da presença de
A metodologia inclui a monitoração simultânea de ambas as ACM por um período mínimo de 30 minutos, estando os transdutores fixados para diminuir artefatos de movimento. Na presença de duas possíveis fontes embólicas, cardiogênica e placa carotídea, a identificação de MES permite um aumento da acurácia diagnóstica e um auxílio na decisão terapêutica, além de sua detecção – MES – ser um fator preditor na recorrência de um novo evento isquêmico cerebral20,22-24.
Linhas de pesquisa com a monitoração de procedimentos cirúrgicos e endovasculares vêm sendo estabelecidas, correlacionando a presença de MES e alterações neurológicas no pós-operatório25-29. Esse procedimento poderá, futuramente, reconhecer pontos cruciais na manipulação cirúrgica das estenoses carotídeas.
O avanço técnico do DTC propiciará melhor conhecimento da fisiopatologia do fenômeno embólico, e provavelmente será de grande auxílio guiando a terapêutica mais adequada. Nesse momento, podemos considerar que o estudo para pesquisa de microembolia é útil em pacientes com AVCi indefinido de provável etiologia cardioembólica e em portadores de aterosclerose de grandes vasos30,31.
A doença intracraniana corresponde a aproximadamente 8% dos AVCi, dependendo do sexo e da raça32,33. O diagnóstico é freqüentemente realizado por arteriografia, exame padrão de referência, cujos riscos e invasibilidade do procedimento não permitem sua utilização em grande escala, provavelmente subestimando esses números. Avanços de técnicas diagnósticas como a angioressonância, a angiotomografia e o DTC tendem a confirmar a importância dessa etiologia como fator de risco independente para o AVC, embora ainda careçam de critérios validados na literatura34,35.
O DTC configura uma ferramenta auxiliar nesse diagnóstico apresentando sensibilidade e especificidade elevados quando são seguidos critérios rigorosos36. A sensibilidade é de 70% a 90%, e a especificidade de 90% a 95% para as artérias da circulação anterior e um pouco menor para as artérias da circulação posterior; nesse território a sensibilidade de 50% a 80%, e a especificidade é de 80% a 96%37. É importante ressaltar que, na prática, a análise da VM na identificação das estenoses intracranianas não é suficiente, sendo necessária combinação dessa com outros parâmetros, como assimetria, elevações segmentares, análise espectral e conhecimento da circulação extracraniana.
O principal fator confusional na interpretação das velocidades é a presença de circulação colateral ou de vasodilatação como mecanismos compensatórios nos casos associados com estenoses extracranianas38. O achado compatível com estenose intracraniana na fase aguda do AVCi deve ser diferenciado da "estenose evanescente". Essa terminologia define o processo de recanalização do vaso ocluído, que se comporta, hemodinamicamente, como uma estenose. Há necessidade de exames evolutivos para diferenciação diagnóstica10,39.
O DTC, quando comparado a outros métodos não-invasivos emergentes, traz a vantagem de também monitorar microêmbolos no sítio da estenose, o que é freqüentemente observado na nossa experiência, podendo influenciar na decisão terapêutica40.
O uso do DTC na fase aguda do AVCi propicia, portanto, uma complementação diagnóstica de valor ainda subestimado na prática, auxiliando os exames de imagem na etiologia e fisiopatologia, guiando o neurologista na conduta terapêutica e provavelmente estimando o prognóstico desses pacientes.
Declaro não haver conflitos de interesses pertinentes.
1. Halsey Jr JH, Tan MJ. Evaluation of acute stroke. In: Newell DW, Aaslid R (eds). Transcranial Doppler. New York: Raven Press; 1992. p. 145-51.
2. Baruzzi AC, Knobel E, Cirenza C, Kihara EN, Souza VC, Massaro A, et al. Use of tissue plasminogen activator factor for acute ischemic stroke. Arq Bras Cardiol. 1997; 68: 347-51.
3. Arenillas JF, Molina CA, Montaner J, Abilleira S, González-Sánchez MA, Álvarez-Sabín J. Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial Doppler ultrasound study. Stroke. 2001; 32: 2898-904.
4. Demchuk AM, Burgin WS, Christou I, Felberg RA, Barber PA, Hill MD, et al. Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator. Stroke. 2001; 32: 89-93.
5. Alexandrov AV, Molina CA, Grotta J, Garami Z, Ford SR, Alvarez-Sabin J, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004; 351: 2170-8.
6. Zétola VF, Lange MC, Muzzio JA, Marchioro I, Nóvak EM, Werneck LC. Doppler transcraniano na prática neurológica. Arq Neuropsiquiatr. 2006; 64: 100-3.
7. Demchuk AM, Alexandrov AV. Acute ischemic stroke. In: Alexandrov A (ed). Cerebrovascular ultrasound in stroke prevention and treatment. New York: Blackwell Publishing/Futura; 2004. p. 170-80.
8. Francis CW. Ultrasound-enhanced thrombolysis. Echocardiography. 2001; 18: 239-46.
9. Egido JA, Sánchez C. Neurosonology in cerebral ischemia: future application of transcranial Doppler in acute stroke. Cerebrovasc Dis. 2001; 11(suppl 1): 15-9.
10. Segura T, Serena J, Castellanos M, Teruel J, Vilar C, Dávalos A. Embolism in acute middle cerebral artery stenosis. Neurology. 2001; 56: 497-501.
11. Chernyshev OY, Garami Z, Calleja S, Song J, Campbell MS, Noser CA, et al. Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia. Stroke. 2005; 36: 32-7.
12. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992; 32: 78-86.
13. Caplan LR, Mohr JP, Kistler JP, Koroshetz W. Should thrombolytic therapy be the first-line treatment for acute ischemic stroke? N Engl J Med. 1997; 337: 1309-13.
14. Hackworthy RA, Sorensen SG, Fitzpatrick PG, Barry WH, Menlove RL, Rothbard RL, et al. Dependence of assessment of coronary artery reperfusion during acute myocardial infarction on angiographic criteria and interobserver variability. Am J Cardiol. 1988; 62: 538-42.
15. Alexandrov A. Ultrasound identification and lysis of clots. Stroke. 2004; 35(Suppl 1): 2722-5.
16. Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, et al. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005; 36: 1441-6.
17. Molina CA, Ribo M, Rubiera M, et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke. 2006; 37: 425-9.
18. Alexandrov AV, Hall CE, Labiche LA, Wojner AW, Grotta JC. Ischemic stunning of the brain. Early recanalization without immediate clinical improvement in acute ischemic stroke. Stroke. 2004; 35: 449-52.
19. Segura T, Serena J. Detección de microembolias mediante DTC. In: Molina CA, Serena J, Alvarez Sabín J (eds). Manual de Doppler transcraneal. Madrid: Aula Medica Ediciones; 2000. p. 51-60.
20. Markus H. Microembolic signal detection in cerebrovascular disease. In: Babikian VL, Wechsler LR, Toole JF (eds). Transcanial Doppler ultrasonography. 2nd edition. Woburn: Butterworth-Heinemann; 1999. p. 167-74.
21. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24: 35-41.
22. Batista P, Oliveira V, Ferro JM. The detection of microembolic signals in patients at risk of recurrent cardioembolic stroke: possible therapeutic relevance. Cerebrovasc Dis. 1999; 9: 314-9.
23. Markus HS, MacKinnon A. Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis. Stroke. 2005; 36: 971-5.
24. Valton L, Larrue V, le Traon AP, Massabuau P, Geraud G. Microembolic signals and risk of early recurrence in patients with stroke or transient ischemic attack. Stroke. 1998; 29: 2125-8.
25. Spencer MP, Thomas GI, Nicholls SC, Sauvage LR. Detection of middle cerebral artery emboli during carotid endarterectomy using transcranial Doppler ultrasonography. Stroke. 1990; 21: 415-23.
26. Siebler M, Sitzer M, Rose G, Bendfeldt D, Steinmetz H. Silent cerebral embolism caused by neurologically symptomatic high-grade carotid stenosis. Event rates before and after carotid endarterectomy. Brain. 1993; 116 (Pt 5): 1005-15.
27. Markus HS, Thomson N, Brown MM, Thomson ND. Asymptomatic cerebral embolic signals in symptomatic and asymptomatic carotid artery disease. Brain. 1995; 118: 1005-11.
28. Siebler M, Nachtmann A, Sitzer M, Rose G, Kleinschmidt A, Rademacher J, et al. Cerebral microembolism and the risk of ischaemia in asymptomatic high-grade internal carotid artery ischaemia. Stroke. 1995; 26: 2184-6.
29. Malheiros SM, Massaro AR, Gabbai AA, Pessa CJ, Gerola LR, Branco JN, et al. Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery? Arq Neuropsiquiatr. 2001; 59: 1-5.
30. Alexandrov AV, Neumyer MM. Diagnostic criteria for cerebrovascular ultrasound. In: Alexandrov A, ed. Cerebrovascular ultrasound in stroke prevention and treatment. New York: Blackwell Publishing/Futura; 2004. p. 107-8.
31. Ringelstein EB, Droste DW, Babikian VL, Evans DH Grosset DG, Kaps M, et al. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke. 1998; 29: 725-9.
32. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Rate-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. Stroke. 1995; 26: 14-20.
33. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke. 1996; 27: 1974-80.
34. Wong KS, Li H, Chan YL, Ahuja A, Lam WWM, Wong A, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease. Stroke. 2000; 31: 2641-7.
35. Chimowitz MI, Kokkinos J, Strong J, Brown MB, Levine SR, Silliman S, et al. The Warfarin-Aspirin symptomatic in,tracranial disease study. Neurology. 1995; 45: 1488-93.
36. Felberg RA, Christou I, Demchuk AM, Malkoff M, Alexandrov AV. Screening for intracranial stenosis with transcranial Doppler: the accuracy of mean flow velocity tresholds. J Neuroimaging. 2002; 12: 1-6.
37. Sloan MA, Alexandrov AV, Tegeler CH, Spencer MP, Caplan LR, Feldman E, et al. Assessment transcranial Doppler ultrasonography report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2004; 62: 1468-81.
38. Rorick MB, Nichols FT, Adams RJ. Transcranial Doppler correlation with angiography in detection of intracranial stenosis. Stroke. 1994; 25: 1931-4.
39. Diehl RR, Samii C, Diehl A. Dynamics and embolic activity of symptomatic intra-cranial cerebral artery stenoses. Acta Neurol Scand. 2002; 106: 173-81.
40. Gao S, Wong KS, Hansberg T, Lam WW, Droste DW, Ringelstein EB. Microembolic signal predicts recurrent cerebral ischemic events in acute stroke patients with middle cerebral artery stenosis. Stroke. 2004; 35: 2832-6.
Viviane Flumignan Zétola Rua General Carneiro, 181 – sala 1236 80060-900 – Curitiba, PR E-mail:
Artigo recebido em 05/03/06; revisado recebido em 13/04/06; aceito em 09/05/06.
Internal Medicine Department, Neurology Service - Cerebrovascular Diseases, Paraná State Federal University (UFPR) - Curitiba, PR, Brazil
The first clinical trials on the utility of Transcranial Doppler (TCD) in acute ischemic stroke (AIS) were conducted still in the pre-thrombolysis stage. Middle cerebral artery (MCA) mean flow velocity (MV) below 20 cm/sec or 50% below contralateral MCA within 24 hours translates worse prognostics factors1. Intravenous thrombolysis in the management of AIS brought forth an even higher utility of TCD in the acute phase – to add to emergency evaluation – thus allowing the identification of intracranial occlusion and acting as a unique tool for continuous monitoring of vessel recanalization2. More recent study designs suggest that changes found in TCD should be added to inclusion criteria for the use of intravenous thrombolytic, since that therapeutic regimen is potentially indicated and beneficial in cases of encephalic ischemia with intracranial artery branch occlusion3-5.
TCD has been absorbed by major university services in our country, as well as by hospitals that assist patients with cerebrovascular diseases6. In addition to being non-invasive, TDC has other major advantages: it is low-cost, dynamic, fast for specific cases, and portability. It may be carried out and repeated many times, by the bed side, and may also stand for therapeutic potential7-9. Major difficulties posed by the method are: it belongs to the group of operator-dependent complementary exams, and the lack of studies on interpretation criteria that can be uniformly accepted7. In regard to acute AIS – concurrently to imaging exams such as computed axial tomography (CAT Scan) and nuclear magnetic resonance (NMR) – TCD has been innovating concepts and treatments, contributing for better assistance to patients who are thrombolysis candidates and non-candidates. Research on micro emboli – a unique tool – and high sensitivity for the detection and follow-up of intracranial stenoses have turned TCD into a routine exam for cerebrovascular disease patients3,10. The present review will focus on the assistance for acute cerebrovascular diseases (CVD). It is important to point out that major studies are related to the analysis of MCA, whose topography corresponds to most ischemic cerebral events. Whenever possible, non-invasive extracranial investigation should be carried out with ultrasound of cervical vessels – carotid, vertebral and subclavian arteries – to help interpret and therefore increase accuracy of TCD11.
Although patients with acute AIS can still count on few services for treatment in our country, the tendency for therapy improvement is imperative and promising. '
A number of experimental studies have already demonstrated that ultrasound makes fibrinolytic agents activities easier due to improvement in medication transportation, change in fibrin structure, and higher tPA-fibrin binding8. The 'CLOTBUST' study has demonstrated a possible potentialization of thrombolysis when concurrent to TCD in cases where MCA occlusion evolution is recorded as under 3 hours. The group under constant monitoring of IV thrombolytic infusion reported higher recanalization and improvement of functional independence when compared to patients not constantly monitored through TCD5. On the other hand, a recent study - 'TRUMBI' – where authors reviewed the correlation between ultrasound low intensity (300Khz) and potential thrombolysis had early discontinuation due to higher incidence of symptomatic intraparenchymatose haemorrhage in the study group16. Further studies are required for method validation. The IV microbubbles solution has demonstrated to even increase the effect obtained from the association of TCD and the thrombolytic17.
From all the information provided by the method, TCD also allows recognizing early recanalization of MCA occluded after thrombolytic infusion irrespective of clinical recovery, a condition known as stunned brain15,18. The pattern of recanalization – if spontaneous – must also be distinguished from intracranial stenosis, which may be presented with similar findings at first exam. Sequential exams are crucial for definition, since in recanalization flow velocities return to values close to normal within variable time frame.
TCD identifies microembolic signs (MES) in intracranial circulation. Such study is possible, since ultrasound distinguishes signal characteristics through embolyc materials – solid or gaseous – from erythocyte flow velocity. Those differences are present in the wave spectrum – intensity and frequency – and in sonority emission19.
Embolism may result from cardiac sources, from major arteries – aorta, carotids and vertebral arteries -, intracranial arteries, and paradoxically reach cerebral circulation through a venous-arterial shunt – patent oval foramen or arteriovenous fistula20. The cardioembolic source stands for 20 to 30% of all AISs, with most patients presumptively identified following TOAST criteria, through the combination of clinical symptomatology associated to mid and high risk factors from complementary cardiovascular exams findings - ECG, transthoracic or transaesophagic ECG – and imaging exams – cranial CAT Scan and NMR21. However, none of those methods allows direct identification of the active embolic phenomenon as TCD does. Methodology includes simultaneous monitoring of both MCAs for at least 30 minutes, with fixed transducers in order to reduce movement artifacts. With two possible embolic sources – cardiogenic and carotid plaque – the identification of MES contributes with higher diagnosis accuracy and support for therapy decision making. MES detection, in addition, acts as a predictor for new cerebral ischemic event recurrence20,22-24.
Research lines have been established with monitoring of surgical and endovascular procedures to correlate the presence of MES and post-surgery neurologic changes25-29. Such procedure may in the future identify crucial sites for surgical manipulation in carotid stenoses.
TCD technical advance will contribute for deeper knowledge of embolic phenomenon pathosphysiology, and will most likely be of great help in showing the most appropriate therapy. At this point in time we could say that studies on micro embolism are useful for patients with non-defined AIS, and which is of probable cardioembolic etiology, as well as for carriers of atheroscleroses of large vessels30,31.
Intracranial disease corresponds to approximately 8% of AISs, depending on gender and race32,33. Diagnosis is frequently reached through arteriography, the gold standard, whose risks and invasive procedure do not allow large scale use, therefore, with figures probably underestimated. Advances in diagnosis techniques – as angioresonance, angiotomography and TCD – tend to confirm the relevance of that etiology as an independent risk for CVA, although literature still needs validated criteria34,35.
TCD stands as an ancillary diagnosis tool with increased sensitivity and specificity when strict criteria are complied with36. Sensitivity lies between 70 and 90%, and specificity between 90 and 95% for arteries in the anterior circulation, and a little lower for arteries in posterior circulation, where sensitivity is between 50 and 80%, and specificity is between 80 and 96%37. It is important to point out that in practice, mean velocity analysis to identify intracranial analysis is not enough. It must be combined with other parameters such as asymmetry, segmental elevations, spectral analysis, and knowledge on extracranial circulation. Major confusion factor in interpreting velocities is collateral or vasodilation circulation as compensatory mechanisms in cases associated to extracranial stenoses38. A finding compatible with intracranial stenosis in AIS acute phase must be distinguished from 'vanishing stenosis'. The term defines the process of recanalization of an occluded vessel that behaves as stenosis hemodynamically speaking. Evolution exams are required for diagnosis differentiation10,39.
When compared to other emergent, non-invasive methods, TCD contributes with the advantage of also monitoring micro emboli at stenosis site, frequently been observed in our practice, and which may influence therapy decision making40.
Therefore, the use of TCD in AIS acute phase allows complementary diagnosis – still underestimated in practice – as support to imaging exams in etiology and pathophysiology, therefore guiding neurologists in their therapy conduct, and most likely estimating prognosis for those patients.
No potential conflict of interest relevant to this article was reported.
1. Halsey Jr JH, Tan MJ. Evaluation of acute stroke. In: Newell DW, Aaslid R (eds). Transcranial Doppler. New York: Raven Press; 1992. p. 145-51.
2. Baruzzi AC, Knobel E, Cirenza C, Kihara EN, Souza VC, Massaro A, et al. Use of tissue plasminogen activator factor for acute ischemic stroke. Arq Bras Cardiol. 1997; 68: 347-51.
3. Arenillas JF, Molina CA, Montaner J, Abilleira S, González-Sánchez MA, Álvarez-Sabín J. Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial Doppler ultrasound study. Stroke. 2001; 32: 2898-904.
4. Demchuk AM, Burgin WS, Christou I, Felberg RA, Barber PA, Hill MD, et al. Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator. Stroke. 2001; 32: 89-93.
5. Alexandrov AV, Molina CA, Grotta J, Garami Z, Ford SR, Alvarez-Sabin J, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004; 351: 2170-8.
6. Zétola VF, Lange MC, Muzzio JA, Marchioro I, Nóvak EM, Werneck LC. Doppler transcraniano na prática neurológica. Arq Neuropsiquiatr. 2006; 64: 100-3.
7. Demchuk AM, Alexandrov AV. Acute ischemic stroke. In: Alexandrov A (ed). Cerebrovascular ultrasound in stroke prevention and treatment. New York: Blackwell Publishing/Futura; 2004. p. 170-80.
8. Francis CW. Ultrasound-enhanced thrombolysis. Echocardiography. 2001; 18: 239-46.
9. Egido JA, Sánchez C. Neurosonology in cerebral ischemia: future application of transcranial Doppler in acute stroke. Cerebrovasc Dis. 2001; 11(suppl 1): 15-9.
10. Segura T, Serena J, Castellanos M, Teruel J, Vilar C, Dávalos A. Embolism in acute middle cerebral artery stenosis. Neurology. 2001; 56: 497-501.
11. Chernyshev OY, Garami Z, Calleja S, Song J, Campbell MS, Noser CA, et al. Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia. Stroke. 2005; 36: 32-7.
12. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992; 32: 78-86.
13. Caplan LR, Mohr JP, Kistler JP, Koroshetz W. Should thrombolytic therapy be the first-line treatment for acute ischemic stroke? N Engl J Med. 1997; 337: 1309-13.
14. Hackworthy RA, Sorensen SG, Fitzpatrick PG, Barry WH, Menlove RL, Rothbard RL, et al. Dependence of assessment of coronary artery reperfusion during acute myocardial infarction on angiographic criteria and interobserver variability. Am J Cardiol. 1988; 62: 538-42.
15. Alexandrov A. Ultrasound identification and lysis of clots. Stroke. 2004; 35(Suppl 1): 2722-5.
16. Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, et al. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005; 36: 1441-6.
17. Molina CA, Ribo M, Rubiera M, et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke. 2006; 37: 425-9.
18. Alexandrov AV, Hall CE, Labiche LA, Wojner AW, Grotta JC. Ischemic stunning of the brain. Early recanalization without immediate clinical improvement in acute ischemic stroke. Stroke. 2004; 35: 449-52.
19. Segura T, Serena J. Detección de microembolias mediante DTC. In: Molina CA, Serena J, Alvarez Sabín J (eds). Manual de Doppler transcraneal. Madrid: Aula Medica Ediciones; 2000. p. 51-60.
20. Markus H. Microembolic signal detection in cerebrovascular disease. In: Babikian VL, Wechsler LR, Toole JF (eds). Transcanial Doppler ultrasonography. 2nd edition. Woburn: Butterworth-Heinemann; 1999. p. 167-74.
21. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24: 35-41.
22. Batista P, Oliveira V, Ferro JM. The detection of microembolic signals in patients at risk of recurrent cardioembolic stroke: possible therapeutic relevance. Cerebrovasc Dis. 1999; 9: 314-9.
23. Markus HS, MacKinnon A. Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis. Stroke. 2005; 36: 971-5.
24. Valton L, Larrue V, le Traon AP, Massabuau P, Geraud G. Microembolic signals and risk of early recurrence in patients with stroke or transient ischemic attack. Stroke. 1998; 29: 2125-8.
25. Spencer MP, Thomas GI, Nicholls SC, Sauvage LR. Detection of middle cerebral artery emboli during carotid endarterectomy using transcranial Doppler ultrasonography. Stroke. 1990; 21: 415-23.
26. Siebler M, Sitzer M, Rose G, Bendfeldt D, Steinmetz H. Silent cerebral embolism caused by neurologically symptomatic high-grade carotid stenosis. Event rates before and after carotid endarterectomy. Brain. 1993; 116 (Pt 5): 1005-15.
27. Markus HS, Thomson N, Brown MM, Thomson ND. Asymptomatic cerebral embolic signals in symptomatic and asymptomatic carotid artery disease. Brain. 1995; 118: 1005-11.
28. Siebler M, Nachtmann A, Sitzer M, Rose G, Kleinschmidt A, Rademacher J, et al. Cerebral microembolism and the risk of ischaemia in asymptomatic high-grade internal carotid artery ischaemia. Stroke. 1995; 26: 2184-6.
29. Malheiros SM, Massaro AR, Gabbai AA, Pessa CJ, Gerola LR, Branco JN, et al. Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery? Arq Neuropsiquiatr. 2001; 59: 1-5.
30. Alexandrov AV, Neumyer MM. Diagnostic criteria for cerebrovascular ultrasound. In: Alexandrov A, ed. Cerebrovascular ultrasound in stroke prevention and treatment. New York: Blackwell Publishing/Futura; 2004. p. 107-8.
31. Ringelstein EB, Droste DW, Babikian VL, Evans DH Grosset DG, Kaps M, et al. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke. 1998; 29: 725-9.
32. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Rate-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. Stroke. 1995; 26: 14-20.
33. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke. 1996; 27: 1974-80.
34. Wong KS, Li H, Chan YL, Ahuja A, Lam WWM, Wong A, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease. Stroke. 2000; 31: 2641-7.
35. Chimowitz MI, Kokkinos J, Strong J, Brown MB, Levine SR, Silliman S, et al. The Warfarin-Aspirin symptomatic in,tracranial disease study. Neurology. 1995; 45: 1488-93.
36. Felberg RA, Christou I, Demchuk AM, Malkoff M, Alexandrov AV. Screening for intracranial stenosis with transcranial Doppler: the accuracy of mean flow velocity tresholds. J Neuroimaging. 2002; 12: 1-6.
37. Sloan MA, Alexandrov AV, Tegeler CH, Spencer MP, Caplan LR, Feldman E, et al. Assessment transcranial Doppler ultrasonography report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2004; 62: 1468-81.
38. Rorick MB, Nichols FT, Adams RJ. Transcranial Doppler correlation with angiography in detection of intracranial stenosis. Stroke. 1994; 25: 1931-4.
39. Diehl RR, Samii C, Diehl A. Dynamics and embolic activity of symptomatic intra-cranial cerebral artery stenoses. Acta Neurol Scand. 2002; 106: 173-81.
40. Gao S, Wong KS, Hansberg T, Lam WW, Droste DW, Ringelstein EB. Microembolic signal predicts recurrent cerebral ischemic events in acute stroke patients with middle cerebral artery stenosis. Stroke. 2004; 35: 2832-6.
Viviane Flumignan Zétola Rua General Carneiro, 181 – sala 1236 80060-900 – Curitiba, PR E-mail:
Manuscript received March 5, 2006; revised manuscript received April 13, 2006; accepted May 9, 2006.
28. Siebler M, Nachtmann A, Sitzer M, Rose G, Kleinschmidt A, Rademacher J, et al. Cerebral microembolism and the risk of ischaemia in asymptomatic high-grade internal carotid artery ischaemia. Stroke. 1995; 26: 2184-6.