ASSESSMENT: TRANSCRANIAL DOPPLER ULTRASONOGRAPHY

Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
Neurology 2004;62(9):1468

Authors
Michael A. Sloan, MD, MS; Andrei V. Alexandrov, MD, RVT; Charles H. Tegeler, MD; Merrill P. Spencer, MD; Louis R. Caplan, MD; Edward Feldmann, MD; Lawrence R. Wechsler, MD; David W. Newell, MD; Camilo R. Gomez, MD; Viken L. Babikian, MD; David Lefkowitz, MD; Robert S. Goldman, MD; Carmel Armon, MD; Chung Y. Hsu, MD, PhD; and Douglas S. Goodin, MD
2 Copyright 2004 American Academy of Neurology

Objective of the guideline
To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis.

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Copyright 2004 American Academy of Neurology

Methods of evidence review
‡ Panel reviewed summary statements and other articles, based upon selection of relevant publications cited in these new articles and additional MEDLINE search through June, 2003 using the AAN rating system, ‡ Articles reviewed and cited contain a mixture of diagnostic, therapeutic or prognostic information used as the reference standard in individual studies. ‡ Sensitivity and specificity reflect the ability of a diagnostic test to detect disease. Reviewed for TCD and TCCS.
4 Copyright 2004 American Academy of Neurology

Methods of evidence review
‡ Sensitivity and specificity were operationally defined as excellent (>/= 90%), good (80-89%), fair (60-79%) and poor (<60%). ‡ The clinical utility of a diagnostic test was operationally defined as the value of the test result to the clinician caring for the individual patient. ‡ Panel summarized the clinical utility of TCD/TCCS and focus on the clinical indications for which conclusions can be drawn.

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Copyright 2004 American Academy of Neurology

Study measures predictive ability using independent gold standard to define cases. Outcome is measured in evaluation masked to presence of predictor. Predictor is measured in evaluation masked to clinical presentation. Copyright 2004 American Academy of Neurology Class II: 6 . Study measures prognostic accuracy of risk factor using acceptable independent gold standard to define cases. Risk factor is measured in evaluation masked to the outcome. Evidence provided by prospective study of narrow spectrum of persons who may be at risk for having the condition. retrospective study of broad spectrum of persons with condition compared to broad spectrum of controls. work status).AAN¶s Class of evidence for determining the yield of established diagnostic and screening tests Class I: Evidence provided by prospective study in broad spectrum of persons who may be at risk of outcome (target disease.

Risk factor measured in evaluation masked to outcome. 7 Copyright 2004 American Academy of Neurology .AAN¶s Class of evidence for determining the yield of established diagnostic and screening tests Class III: Evidence provided by retrospective study where persons with condition or controls are of narrow spectrum. Study measures predictive ability using independent gold standard to define cases. case series. Class IV: Any design where predictor is not applied in masked evaluation OR evidence by expert opinion.

"/= 1 convincing Class I or "/=2 consistent.AAN¶s Recommendation levels Level A: Established as useful/ predictive or not useful/ predictive for the given condition in the specified population. Level B: Probably useful/ predictive or not useful/ predictive for the given condition in the specified populations. convincing Class II studies. "/= 1 convincing Class II or "/=3 consistent Class III studies 8 Copyright 2004 American Academy of Neurology .

test/predictor unproven.AAN¶s Recommendation levels Level C: Possibly useful/ predictive or not useful/ predictive for the given condition in the specified population. Given current knowledge. "/=2 convincing and consistent Class III studies Level U: Data inadequate or conflicting. 9 Copyright 2004 American Academy of Neurology .

10 Copyright 2004 American Academy of Neurology . ‡ TCD¶s principal use is in the evaluation and management of patients with cerebrovascular disease.Introduction ‡ TCD is a non-invasive ultrasonic technique measuring local blood flow velocity and direction in the proximal portions of large intracranial arteries.

Introduction ‡ Advantages of TCD: ± non-invasive ± can be performed at the bedside ± easily repeated or used for continuous monitoring ± is generally less expensive than other techniques ± contrast agents are not used avoiding allergic reactions and decreasing risk to the patient 11 Copyright 2004 American Academy of Neurology .

Introduction ‡ Limitation of TCD: ± examination of cerebral blood flow velocities in certain segments of large intracranial vessels ± detects indirect effects (abnormal waveform characteristics) suggesting of proximal hemodynamic or distal obstructive lesions ± more valuable in specific conditions 12 Copyright 2004 American Academy of Neurology .

Conventional or Non-imaging TCD .

14 Copyright 2004 American Academy of Neurology . although the optimal frequency of testing is unknown (Type U). Class I evidence).Summary of findings Sickle Cell Disease INDICATION Sickle Cell Disease SENSITIVITY (%) 86 SPECIFICITY (%) 91 REFERENCE STANDARD Conventional angiography Recommendation: TCD screening of children with SCD between the ages of 2 and 16 years is effective for assessing stroke risk (Type A.

TEE is superior than contrast TCD since it provides direct anatomic information regarding the site and nature of the shunt or presence of an ASA. Class II evidence).Summary of findings Right to Left Cardiac Shunts INDICATION Right to Left Cardiac Shunts SENSITIVITY (%) 70-100 SPECIFICITY (%) "95 REFERENCE STANDARD Transesophageal echocardiography Recommendation: Contrast TCD is comparable to contrast TEE for detecting right to left shunts due to PFO (Type A. While the number of microbubbles reaching the brain can be quantified by TCD. the therapeutic impact of this additional information is unknown (Type U). 15 Copyright 2004 American Academy of Neurology .

Summary of findings Intracranial Steno-Occlusive Disease INDICATION Intracranial Steno-Occlusive Disease: Anterior Circulation Posterior Circulation Occlusion 70-90 50-80 90-95 80-96 SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Conventional angiography 16 Copyright 2004 American Academy of Neurology .

VA. 17 Copyright 2004 American Academy of Neurology . BA SENSITIVITY (%) 85-95 55-81 SPECIFICITY (%) 90-98 96 REFERENCE STANDARD Recommendation: Data are insufficient to establish TCD criteria for greater than 50% stenosis or for progression of stenosis in intracranial arteries (Type U).Summary of findings Intracranial Steno-Occlusive Disease (Continued ) INDICATION MCA ICA.

Data are insufficient to give a recommendation regarding replacing conventional angiography with TCD (Type U). The relative value of TCD compared with MRA or CTA remains to be determined (Type U). Class II evidence). 18 Copyright 2004 American Academy of Neurology . particularly in the ICA siphon and MCA (Type B.Summary of findings Acute cerebral infarction INDICATION Acute cerebral infarction SENSITIVITY (%) 85-95 SPECIFICITY (%) 90-98 REFERENCE STANDARD Recommendation: TCD is probably useful for the evaluation of patients with suspected intracranial steno-occlusive disease.

Summary of findings Extracranial ICA Stenosis INDICATION Extracranial ICA Stenosis: Single TCD variable TCD Battery TCD Battery & Carotid Duplex 3-78 49-95 89 60-100 42-100 100 SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Conventional angiography Recommendation:TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion (Type C. Class IIIII 19 evidence). Copyright 2004 American Academy of Neurology .

clinical outcomes 20 Copyright 2004 American Academy of Neurology .Summary of findings Vasomotor Reactivity (VMR) Testing INDICATION Vasomotor Reactivity (VMR) Testing "/= 70% extracranial ICA stenosis / occlusion SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Conventional angiography.

21 Copyright 2004 American Academy of Neurology . Class II-III evidence).Summary of findings Vasomotor Reactivity (VMR) Testing (continued) Recommendation: TCD vasomotor reactivity testing is considered probably useful for ±the detection of impaired cerebral hemodynamics in patients with asymptomatic severe (>70%) stenosis of the extracranial ICA ±patients with symptomatic or asymptomatic extracranial ICA occlusion and patients with cerebral small artery disease (Type B. How the results from these techniques should be used to influence therapy and affect patient outcomes remains to be determined (Type U).

magnetic resonance imaging. neuropsychological tests Recommendation: TCD is probably useful to detect cerebral microembolic signals in a wide variety of cardiovascular/ cerebrovascular disorders/procedures (Type B. However. pathology.Summary of findings Detection of Cerebral Microemboli INDICATION Cerebral Microembolization SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Experimental model. data at present do not support the use of TCD for diagnosis or for monitoring response to antithrombotic therapy in 22 Copyright 2004 American Academy of Neurology ischemic cerebrovascular disease in these settings(Type U). Class II-IV evidence). .

Perioperative and Periprocedural Monitoring .

TCD monitoring is probably useful during and after CEA in circumstances where monitoring is felt to be necessary (Type B. clinical outcomes Recommendation: CEA monitoring with TCD can provide important feedback pertaining to hemodynamic and embolic events during and after surgery that may help the surgeon take appropriate measures at all stages of the operation to reduce the risk of perioperative stroke. 24 Class II-III evidence). Copyright 2004 American Academy of Neurology .Summary of findings Carotid Endarterectomy (CEA) INDICATION Carotid Endarterectomy (CEA): SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD EEG. magnetic resonance imaging.

Summary of findings Coronary Artery Bypass Graft (CABG) Surgery INDICATION Coronary Artery Bypass Graft (CABG) Surgery SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Recommendation: TCD is possibly effective in documenting changes in flow velocities and CO2 reactivity in patients who undergo CABG (Type C. TCD is probably useful for the detection and monitoring of cerebral microemboli in patients undergoing CABG (Type B. Class III evidence). 25 Copyright 2004 American Academy of Neurology . Data are presently insufficient regarding the clinical utility of this information (Type U). Class II-III evidence).

magnetic resonance angiography.Summary of findings Cerebral Thrombolysis INDICATION Cerebral Thrombolysis SENSITIVITY (%) SPECIFICITY (%) REFERENCE STANDARD Conventional angiography. clinical outcome 50 100 91 100 76 93 Copyright 2004 American Academy of Neurology Complete Occlusion Partial Occlusion Recanalization 26 .

Present data are insufficient to either define the optimal frequency of TCD monitoring for clot dissolution and enhanced recanalization or to influence therapy (Type U). Class II-III evidence). 27 Copyright 2004 American Academy of Neurology .Summary of findings Cerebral Thrombolysis (continued) Recommendation: TCD is probably useful for monitoring thrombolysis of acute MCA occlusions (Type B.

Monitoring in the Neurology/ Neurosurgery Intensive Care Unit .

Summary of findings Subarachnoid Hemorrhage (SAH): INDICATION Vasospasm after Spontaneous Subarachnoid Hemorrhage Intracranial ICA MCA ACA VA 29 SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Conventional angiography 25-30 39-94 13-71 44-100 83-91 70-100 65-100 82-88 Copyright 2004 American Academy of Neurology .

Class I-II evidence). 30 Copyright 2004 American Academy of Neurology . More data are needed to show if TCD affects clinical outcomes in this setting (Type U). especially the MCA and BA. following sSAH (Type A.Summary of findings Subarachnoid Hemorrhage (SAH) (continued) INDICATION BA PCA SENSITIVITY SPECIFICITY (%) (%) 77-100 48-60 42-79 78-87 REFERENCE STANDARD Recommendations: TCD is useful for the detection and monitoring of angiographic VSP in the basal segments of the intracranial arteries.

31 Copyright 2004 American Academy of Neurology . Class I-III evidence). specificity and predictive value of TCD for VSP after tSAH are needed.Summary of findings Traumatic SAH (tSAH) INDICATION Vasospasm after Traumatic Subarachnoid Hemorrhage SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Conventional angiography Recommendation: TCD is probably useful for the detection of VSP and cerebral hemodynamic impairment following tSAH (Type B. Data on sensitivity. Data are insufficient regarding how use of TCD affects clinical outcomes after tSAH (Type U).

EEG. Class II evidence). 32 Copyright 2004 American Academy of Neurology . clinical outcome Recommendation: TCD is a useful adjunct test for the evaluation of cerebral circulatory arrest associated with brain death (Type A.Summary of findings Increased Intracranial Pressure (ICP) and Cerebral Circulatory Arrest INDICATION Cerebral Circulatory Arrest and Brain Death SENSITIVITY SPECIFICITY (%) (%) 91-100 97-100 REFERENCE STANDARD Conventional angiography.

Transcranial Color-Coded Sonography (TCCS) or Imaging TCD .

with/without contrast enhancement 34 Copyright 2004 American Academy of Neurology .Transcranial Color-Coded Sonography (TCCS) INDICATION SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Conventional angiography. pathology Transcranial Color-Coded Sonography (TCCS).

Summary of findings Ischemic Cerebrovascular Disease INDICATION ACoA Collateral Flow PCoA Collateral Flow SENSITIVITY SPECIFICITY (%) (%) 100 100 REFERENCE STANDARD 85 98 35 Copyright 2004 American Academy of Neurology .

Summary of findings Ischemic Cerebrovascular Disease (Continued) INDICATION SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD Intracranial StenoOcclusive Lesions Any Up to 100 Up to 83 36 Copyright 2004 American Academy of Neurology .

Summary of findings Ischemic Cerebrovascular Disease (Continued) INDICATION SENSITIVITY SPECIFICITY (%) (%) REFERENCE STANDARD "/= 50% Stenosis MCA ACA VA BA PCA 37 100 100 100 100 100 100 100 100 100 100 Copyright 2004 American Academy of Neurology .

Summary of findings Ischemic Cerebrovascular Disease (Continued) Recommendation: (CE)-TCCS is probably useful in the evaluation and monitoring of patients with ischemic cerebrovascular disease (Type B. Class II-IV evidence). 38 Copyright 2004 American Academy of Neurology .

Summary of findings Hemorrhagic Cerebrovascular Disease INDICATION Parenchymal Hypoechogenicity in MCA Distribution SENSITIVITY SPECIFICITY (%) (%) 69 83 REFERENCE STANDARD Computed tomographic scan Recommendation: (CE-) TCCS is probably useful in the evaluation and monitoring of patients with aneurysmal SAH or intracranial ICA/MCA VSP following SAH (Type B. Class II-III evidence). 39 Copyright 2004 American Academy of Neurology . Data are insufficient regarding the use of TCCS to replace CT for diagnosis of ICH (Type U).

Summary of findings Vasospasm after Spontaneous Subarachnoid Hemorrhage INDICATION Vasospasm after Spontaneous Subarachnoid Hemorrhage Intracranial ICA MCA ACA 40 SENSITIVITY SPECIFICITY (%) (%) 69 83 REFERENCE STANDARD Conventional angiography 100 100 71 97 93 85 Copyright 2004 American Academy of Neurology .

evaluation of cerebral autoregulation in other settings (Type U recommendation). evaluation of arteriovenous malformations.Summary of findings Intracerebral Hemorrhage INDICATION Intracerebral Hemorrhage SENSITIVITY SPECIFICITY (%) (%) 94 95 REFERENCE STANDARD Computed tomographic scan Recommendation:There are insufficient data to support the routine clinical use of TCD/TCCS for other indications including: migraine. 41 Copyright 2004 American Academy of Neurology . monitoring during cerebral angiography. cerebral venous thrombosis.

‡ Detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A. 42 Copyright 2004 American Academy of Neurology . Class I-II).Summary of TCD recommendations Settings in which TCD is able to provide information and in which its clinical utility is established ‡ Screening of children aged 2-16 years with sickle cell disease for assessing stroke risk (Type A. More data are needed to show if its use affects clinical outcomes (Type U). although the optimal frequency of testing is unknown (Type U). Class I).

Summary of TCD recommendations Settings in which TCD is able to provide information. but in which its clinical utility remains to be determined ‡ Cerebral Thrombolysis: TCD is probably useful for monitoring thrombolysis of acute MCA occlusions (Type B. Data do not support the use of this TCD technique for diagnosis or monitoring response to antithrombotic therapy in ischemic cerebrovascular disease (Type U). Class II-III). 43 Copyright 2004 American Academy of Neurology . More data are needed to assess the frequency of monitoring for clot dissolution and enhanced recanalization and to influence therapy (Type U). ‡ Cerebral Microembolism Detection: TCD monitoring is probably useful for the detection of cerebral microembolic signals in a variety of cardiovascular/ cerebrovascular disorders/procedures (Type B. Class II-IV).

but in which its clinical utility remains to be determined ‡ Carotid Endarterectomy: TCD monitoring is probably useful to detect hemodynamic and embolic events that may result in perioperative stroke during and after CEA in settings where monitoring is felt to be necessary (Type B. Data are insufficient regarding the clinical impact of this information (Type U). ‡ Coronary Artery Bypass Graft (CABG) Surgery: TCD monitoring is probably useful (Type B. 44 Copyright 2004 American Academy of Neurology .Summary of TCD recommendations Settings in which TCD is able to provide information. Class II-III). Class III). TCD is possibly useful to document changes in flow velocities and CO2 reactivity during CABG surgery (Type C. Class II-III) during CABG for detection of cerebral microemboli.

but data are needed to show its accuracy and clinical impact in this setting (Type U). but in which its clinical utility remains to be determined ‡ Vasomotor Reactivity Testing: TCD is probably useful (Type B. Class III). 45 Copyright 2004 American Academy of Neurology . symptomatic or asymptomatic extracranial ICA occlusion and cerebral small artery disease.Summary of TCD recommendations Settings in which TCD is able to provide information. ‡ Vasospasm after traumatic subarachnoid hemorrhage: TCD is probably useful for the detection of VSP following traumatic SAH (Type B. Whether these techniques should be used to influence therapy and improve patient outcomes remains to be determined (Type U). Class II-III) for the detection of impaired cerebral hemodynamics in patients with severe (>70%) asymptomatic extracranial ICA stenosis.

Class III) for the evaluation and monitoring of space-occupying ischemic MCA infarctions. but in which its clinical utility remains to be determined ‡ Transcranial Color-Coded Sonography: TCCS is possibly useful (Type C. CT and MRI scanning and if its use affects clinical outcomes (Type U).Summary of TCD recommendations Settings in which TCD is able to provide information. More data are needed to show if it has value vs. 46 Copyright 2004 American Academy of Neurology .

as it can provide direct information regarding the anatomic site and nature of the shunt. TEE is superior. in general. Class II-IV). but in which other diagnostic tests are typically preferable ‡ Right-to-left cardiac shunts: While TCD is useful for detection of right-to-left cardiac and extracardiac shunts (Type A.Summary of TCD recommendations Settings in which TCD is able to provide information. ‡ Extracranial ICA Stenosis: TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion (Type C. ‡ Contrast-Enhanced Transcranial Color-Coded Sonography: (CE)-TCCS may provide information in patients with ischemic cerebrovascular disease and aneurysmal SAH (Type B. Its clinical utility vs. Class II-III) but. is unclear (Type U). conventional angiography or non-imaging TCD. 47 Copyright 2004 American Academy of Neurology . CT scanning. Class II). carotid duplex or MRA are the diagnostic tests of choice.

48 Copyright 2004 American Academy of Neurology . Data are needed to assess the value of TCD in the evaluation of adults with sickle cell disease and its impact. on selection of treatment and prognosis.Recommendations for future research Ischemic Cerebrovascular Disease ‡ Sickle Cell Disease: The optimal frequency for screening children between the ages of 2 and 16 years needs to be determined. if any.

49 Copyright 2004 American Academy of Neurology . if any. the determination of the relative value of each technique for specific vascular lesions which may influence patient management. requires study. The ability of TCD to predict outcome in vertebrobasilar distribution stroke. Once MRA and CTA are validated. The value of TCD in the prediction of hemorrhagic transformation of ischemic infarction needs confirmation in well designed studies of patients who do and do not receive anticoagulation or thrombolysis.Recommendations for future research ‡ Intracranial Steno-Occlusive Disease: More data are needed to define the ability of TCD to detect >/= 50% stenosis of major basal intracranial arteries vs. MRA and CTA.

it would be useful to directly compare TCD/vasomotor reactivity testing with PET to see if TCD would be valuable to select and serially monitor patients for extracranial to intracranial bypass surgery. In patients with symptomatic ICA occlusion. 50 Copyright 2004 American Academy of Neurology . In patients with asymptomatic high grade ICA stenosis.Recommendations for future research ‡ Extracranial ICA Stenosis: The clinical utility of TCD¶s ability to detect impaired cerebral hemodynamics distal to high grade extracranial ICA stenosis or occlusion and assist with stroke risk assessment needs confirmation and evaluation in randomized clinical trials. it would be useful to learn if TCD assessment of vasomotor reactivity or microembolic signal detection can improve selection of patients for CEA or angioplasty.

cerebral blood flow) needs further study. 51 Copyright 2004 American Academy of Neurology . stump pressures. evoked potentials. ‡ Carotid Endarterectomy: The incremental value of TCD monitoring compared with other intraoperative monitoring procedures (EEG. Clinical utility in specific disease states should be defined.Recommendations for future research Perioperative and Periprocedural Monitoring ‡ Cerebral Microembolization: The ability of TCD to better distinguish between the various types of microembolic signals needs to be enhanced.

52 Copyright 2004 American Academy of Neurology . Data from such studies might help in determining the need for further interventions and predicting the outcome of treated and non-treated patients. In addition.Recommendations for future research Perioperative and Periprocedural Monitoring ‡ Coronary Artery Bypass Graft (CABG) Surgery: More data are needed to show if TCD predicts the occurrence of stroke or neurocognitive impairment following CABG or be useful as a biomarker or surrogate endpoint for clinical trials of neuroprotective agents or new surgical techniques. ‡ Cerebral Thrombolysis: The value of TCD in monitoring thrombolytic therapy (intravenous and intra-arterial) and other recanalizing techniques needs to be shown in clinical trials. studies should be done to determine if thrombolysis can be enhanced with specific frequency(ies) of transcranial ultrasound.

More data are needed to show the clinical utility and predictive power of TCD in this setting. ‡ Traumatic Subarachnoid Hemorrhage: Data on the sensitivity and specificity of TCD for detection of angiographic VSP in this setting are needed. The ability of specific TCD measurements to predict long term outcome from SAH requires study. 53 Copyright 2004 American Academy of Neurology .Recommendations for future research Monitoring in the Neurology / Neurosurgery Intensive Care Unit ‡ Spontaneous Subarachnoid Hemorrhage: More data are needed on the sensitivity and specificity of TCD in the detection of angiographic VSP in different age groups. since diagnostic criteria (like normative data) may vary with age. It remains to be shown how use of TCD affects clinical outcomes.

MRA and conventional angiography. Whether (CE)-TCCS can assist stroke and NeuroICU clinicians in the monitoring of reperfusion techniques or selection of patients with severe MCA territory infarction for clinical trials of aggressive. 54 Copyright 2004 American Academy of Neurology . in comparison to TCD.Recommendations for future research Monitoring in the Neurology/Neurosurgery Intensive Care Unit ‡ Contrast-Enhanced Transcranial Color-Coded Sonography: The incremental value of (CE)-TCCS in diverse settings of ischemic and hemorrhagic cerebrovascular disease. needs to be confirmed. CT. CTA. MRI. putative beneficial or life-saving therapies remains to be determined.

aan.To view the entire guideline and additional AAN guidelines visit: www.com/professionals/practice/index.62(9):1468 55 Copyright 2004 American Academy of Neurology .cfm Neurology 2004.

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