Charles H. Tegeler

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.Objective:To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods:The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results:TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial

BACKGROUND Patients with mixed dyslipidaemia have raised triglycerides, low high-density lipoprotein (HDL) cholesterol, and high low-density lipoprotein (LDL) cholesterol. Augmentation of HDL cholesterol by inhibition of the cholesteryl ester transfer protein (CETP) could benefit these patients. We aimed to investigate the effect of the CETP inhibitor, torcetrapib, on carotid atherosclerosis progression in patients with mixed dyslipidaemia. METHODS We did a randomised double-blind trial at 64 centres in North America and Europe. 752 eligible participants completed an atorvastatin-only run-in period for dose titration, after which they all continued to receive atorvastatin at the titrated dose. 377 of these patients were randomly assigned to receive 60 mg of torcetrapib per day and 375 to placebo. We made carotid ultrasound images at baseline and at 6-month intervals for 24 months. The primary endpoint was the yearly rate of change in the maximum intima-media thickness of 12 carotid segments. Analysis was restricted to 683 patients who had at least one dose of treatment and had at least one follow-up carotid intima-media measurement; they were analysed as randomised. Mean follow-up for these patients was 22 (SD 4.8) months. This trial is registered with ClinicalTrials.gov, number NCT00134238. FINDINGS The change in maximum carotid intima-media thickness was 0.025 (SD 0.005) mm per year in patients given torcetrapib with atorvastatin and 0.030 (0.005) mm per year in those given atorvastatin alone (difference -0.005 mm per year, 95% CI -0.018 to 0.008, p=0.46). Patients in the combined-treatment group had a 63.4% relative increase in HDL cholesterol (p<0.0001) and an 17.7% relative decrease in LDL cholesterol (p<0.0001), compared with controls. Systolic blood pressure increased by 6.6 mm Hg in the combined-treatment group and 1.5 mm Hg in the atorvastatin-only group (difference 5.4 mm Hg, 95% CI 4.3-6.4, p<0.0001). INTERPRETATION Although torcetrapib substantially raised HDL cholesterol and lowered LDL cholesterol, it also increased systolic blood pressure, and did not affect the yearly rate of change in the maximum intima-media thickness of 12 carotid segments. Torcetrapib showed no clinical benefit in this or other studies, and will not be developed further.

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial

Background: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. Study Design: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. Results: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. Conclusions: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Practice Standards for Transcranial Doppler Ultrasound: Part I—Test Performance

Indications for the clinical use of transcranial Doppler (TCD) continue to expand while scanning protocols and quality of reporting vary between institutions. Based on literature analysis and extensive personal experience, an international expert panel started the development of guidelines for TCD performance, interpretation, and competence. The first part describes complete diagnostic spectral TCD examination for patients with cerebrovascular diseases. Cranial temporal bone windows are used for the detection of the middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA), C1 segment of the internal carotid arteries (ICA), and collateralization of flow via the anterior (AComA) and posterior (PComA) communicating arteries; orbital windows—for the ophthalmic artery (OA) and ICA siphon; the foraminal window—for the terminal vertebral (VA) and basilar (BA) arteries. Although there is a significant individual variability of the circle of Willis with and without disease, the complete diagnostic TCD examination should include bilateral assessment of the M2 (arbitrarily located at 30‐40 mm depth), M1 (40‐65 mm) MCA [with M1 MCA mid‐point at 50 mm (range 45‐55 mm), average length 16 mm (range 5‐24 mm), A1 ACA (60‐75 mm), C1 ICA (60‐70 mm), P1‐P2 PCA (average depth 63 mm (range 55‐75 mm), AComA (70‐80 mm), PComA (58‐65 mm), OA (40‐50 mm), ICA siphons (55‐65 mm), terminal VA (40‐75 mm), proximal (75‐80), mid (80‐90 mm), and distal (90‐110 mm) BA]. The distal ICA on the neck (40‐60 mm) can be located via submandibular windows to calculate the VMCA/VICA index, or the Lindegaard ratio for vasospasm grading after subarachnoid hemorrhage. Performance goals of diagnostic TCD are to detect and optimize arterial segment‐specific spectral waveforms, determine flow direction, measure cerebral blood flow velocities and flow pulsatility in the above‐mentioned arteries. These practice standards will assist laboratory accreditation processes by providing a standard scanning protocol with transducer positioning and orientation, depth selection and vessel identification for ultrasound devices equipped with spectral Doppler and power motion Doppler.

Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology.

The aim of this new statement is to provide comprehensive and timely evidence‐based recommendations on the screening for asymptomatic carotid artery stenosis in the general population and selected subsets of patients. Recommendations are included for high‐risk persons in the general population; patients undergoing open heart surgery including coronary artery bypass surgery; patients with peripheral vascular diseases, abdominal aortic aneurysms, and renal artery stenosis; patients after radiotherapy for head and neck malignancies; patients following carotid endarterectomy, or carotid artery stent placement; patients with retinal ischemic syndromes; patients with syncope, dizziness, vertigo or tinnitus; and patients with a family history of vascular diseases and hyperhomocysteinemia. The recommendations are based on prevalence of disease, anticipated benefit, and concurrent guidelines from other professional organizations in selected populations.

Practice Standards for Transcranial Doppler (TCD) Ultrasound. Part II. Clinical Indications and Expected Outcomes

Transcranial Doppler (TCD) is a physiological ultrasound test with established safety and efficacy. Although imaging devices may be used to depict intracranial flow superimposed on structural visualization, the end‐result provided by imaging duplex or nonimaging TCD is sampling physiological flow variables through the spectral waveform assessment.

Transcranial Doppler Ultrasonography: Year 2000 Update

In this update, the main clinical applications of transcranial Doppler ultrasonography are reassessed. A specific format for technology assessment, personal experience, and an extensive review of the literature form the basis of the evaluation. The document is approved by the American Society of Neuroimaging and the Neurosonology Research Group of the World Federation of Neurology.

Intercenter Agreement in Reading Doppler Embolic Signals A Multicenter International Study

BACKGROUND AND PURPOSE Different frequencies of asymptomatic Doppler embolic signals have been reported in studies. There has been concern that different criteria for identification may account for some of this variation. A previous reproducibility study between two centers found good agreement, but no studies among large numbers of centers have been performed. We performed an international reproducibility study among nine centers, each of which had published recent studies of embolic signal detection in peer-reviewed journals. METHODS Each center performed blinded analysis of a taped audio Doppler signal composed of transcranial Doppler middle cerebral artery recordings from 6 patients with symptomatic carotid artery stenosis. The exact time of any embolic signal was recorded. Six centers also measured the intensity increase of any embolic signals detected. Interobserver agreement was determined by a method based on the proportion of specific agreement. RESULTS Seven centers reported between 39 and 55 signals, but one center reported 142 embolic signals. The probability of agreement between observers was .678, which rose to .791 when the data from the highest reporting center were excluded. Introducing a decibel threshold resulted in a significant increase in the probability of agreement; a decibel threshold of > 7 dB resulted in a probability of agreement of .902. Intensity measurements made by different centers were usually highly correlated, but this was not always the case, and 3 of the 15 correlations were not significant. The absolute values of the intensities measured varied between centers by as much as 40%. CONCLUSIONS Although most centers report similar numbers of embolic signals, some use less specific criteria and report more events. The use of a decibel threshold improves reproducibility. However, intensity thresholds developed by one center cannot be directly transferred without validation to another center; differing methods of measurement are being used, and this results in different intensity values for the same embolic signals, even when the same equipment is used.

Carotid Stenosis in Patients With Atrial Fibrillation: Prevalence, Risk Factors, and Relationship to Stroke in the Stroke Prevention in Atrial Fibrillation Study

BACKGROUND Several mechanisms contribute to the increased stroke rate of patients with atrial fibrillation (AF). We assessed the frequency of carotid artery stenosis in patients with AF and its relationship to stroke during aspirin or warfarin therapy. METHODS Carotid ultrasonography was done in 676 patients with AF enrolled in the Stroke Prevention in Atrial Fibrillation Study to detect cervical carotid stenosis of 50% or more of the luminal diameter. The presence of carotid stenosis was correlated with patient features and subsequent stroke during a mean of 2.6 years of follow-up. RESULTS In patients with AF who were older than 70 years, the frequency of carotid stenosis was 12% in men and 11% in women. Carotid stenosis was independently associated with systolic hypertension (relative risk, 2.4; P = .002), diabetes (relative risk, 1.8; P = .04), and tobacco use (relative risk, 1.8; P = .02). Carotid stenosis did not add significantly to prediction of stroke when analyzed with other clinical risk factors for stroke in patients with AF (relative risk, 1.3; 95% confidence interval, 0.5 to 3.6; P = .55). CONCLUSIONS Carotid artery stenosis of 50% or more occurs in about 12% of elderly patients with AF, reflecting the substantial prevalence of hypertension and diabetes in these patients. Carotid stenosis was not usefully predictive of stroke in patients with AF who were given aspirin or warfarin. Routine ultrasonography to detect carotid stenosis does not appear warranted in patients with AF without previous symptoms of brain ischemia.

Predictors of Time From Hospital Arrival to Initial Brain-Imaging Among Suspected Stroke Patients The North Carolina Collaborative Stroke Registry

Background and Purpose— We examined patient demographic and hospital characteristics and clinical predictors of delay time from hospital arrival until CT among 20 374 patients enrolled in the North Carolina Collaborative Stroke Registry (January 2005 to April 2008). Methods— Delay time was log-transformed in linear regression analyses and dichotomized (≤25 minutes, >25 minutes) in logistic regression analyses to correspond to a 1999 National Institute of Neurological Disorders and Stroke guideline. Results— In multiple linear regression analyses, prehospital delay time, mode of transport, race, gender, presumptive diagnosis, time of day of arrival, weekday versus weekend arrival, and hospital type (defined by Joint Commission Primary Stroke Center certification and teaching status) were significantly associated with CT delay. In analyses of 3549 patients arriving within 2 hours of symptom onset, time of day of arrival and weekday versus weekend arrival were no longer significant. Among patients arriving within 2 hours of symptom onset, the strongest independent predictors of meeting the National Institute of Neurological Disorders and Stroke (NINDS) guideline were arrival by emergency medical services versus other modes of transportation (odds ratio, 95% CI=2.3 [1.9, 2.8]) and a presumptive diagnosis of transient ischemic attack versus unspecified stroke type (odds ratio, 95% CI=0.4 [0.3, 0.5]). Conclusions— Most patients do not arrive to the hospital in a timely manner and cannot be considered for time-dependent therapies. Among those that do, disparities exist in time to receipt of CT scan, suggesting room for improvement in hospital-level stroke systems of care.