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.

Oscillations of cerebrovascular resistance throughout the menstrual cycle in healthy women.

OBJECTIVES: Increased concentration of endogenous estrogen during a typical menstrual cycle has been shown to correlate with augmentation of blood flow through the internal carotid arteries (ICAs), which may be related to changes in vascular resistance within the brain. In this study we investigated the effects of endogenous estrogen and progesterone on cerebrovascular impedance in young healthy women. METHODS: The blood flow in the ICA and the common (CCA) and external (ECA) carotid arteries was studied with duplex Doppler sonography. The resistance index (RI) was determined and correlated with plasma 17beta-estradiol concentration in 14 young healthy women throughout their menstrual cycle. RESULTS: The concentration of 17beta-estradiol increased in the follicular phase of the cycle and reached a peak on day 14, whereas concentration of progesterone remained low. Along with an increase in estrogen concentration, the ICA RI had decreased from its initial level on average by 9.2% on day 13 and by 6.7% on day 14 (P < 0.05). In contrast, the trend of the ECA RI was to increase during the peak of estrogen concentration. There were no significant changes in the CCA RI or in the systolic blood pressure, heart rate, hematocrit and hemoglobin concentration through the menstrual cycle. CONCLUSIONS: Estrogen-related augmentation of blood flow through the ICA is caused mainly by decreased cerebrovascular impedance, as shown by a decrease in the ICA RI. These changes in RI suggest that estrogen influences cerebral impedance mainly by altering the resistance of cerebral microvasculature.

[Overestimation of the degree of stenosis in the intracranial internal carotid artery determined by magnetic resonance angiography compared to conventional arteriography]. / Sobreestimación del grado de estenosis de la arteria carótida interna intracraneal por la angiorresonancia respecto a la arteriografía convencional.

INTRODUCTION: In the evaluation of stenoses of the extracranial internal carotid artery (ICA), there are studies that suggest that magnetic resonance angiography (MRA) can be a substitute for conventional arteriography (CA), although it seems it has a tendency to overestimate the degree of stenosis. No similar comparison of the two techniques has been conducted in intracranial ICA. We report the case of a patient suffering from an acute ischemic stroke and symptomatic intracranial stenosis that was overestimated when MRA was used, compared to the results obtained using CA. CASE REPORT: We report the case of a 64-year-old male with a history of arterial hypertension, hypercholesterolemia and intermittent claudication who visited the emergency department because of the sudden onset of paresthesias in the left hemiface and hand. The cranial tomography scan performed in the emergency unit ruled out any acute bleeding or early signs of a stroke. Magnetic resonance (MR) diffusion imaging showed an acute ischemic stroke in the right parietal cortex. Extracranial MRA was normal and in the intracranial area a 73% stenosis was detected in the cavernous segment of the right ICA, whereas the use of CA showed the stenosis to be only 55%. On repeating the MRA to rule out a possible rechanneling of the ICA, the image obtained was exactly the same as the earlier one. CONCLUSIONS: Our observations suggest that, as occurs with the extracranial part, MRA tends to magnify the degree of stenosis in the intracranial vessels, and this technique would therefore appear to be less efficient than CA in the evaluation of intracranial stenoses.

Occurrence of hemispheric and retinal ischemia in atrial fibrillation compared with carotid stenosis.

BACKGROUND AND PURPOSE: The goal of this study was to examine the hypotheses that retinal ischemia is caused more often by carotid atherosclerosis than by atrial fibrillation and that the odds of retinal events compared with hemispheric events increase with worsening carotid stenosis. METHODS: We used data from the Stroke Prevention in Atrial Fibrillation (SPAF) I through III trials and North American Symptomatic Carotid Endarterectomy Trial (NASCET), calculating hemispheric:retinal (H:R) odds for the territory of ischemic events during follow-up in patients with atrial fibrillation and medically treated 50% to 99% carotid stenosis or occlusion in the respective trials. RESULTS: The H:R odds were 25:1 in the SPAF aspirin-assigned patients and 2:1 for NASCET vessels. In NASCET patients, the H:R odds of recurrent ischemic events were 1:4 for vessels randomized initially for retinal symptoms compared with 6:1 for those randomized for hemispheric events (significant difference; P<0.001). Moreover, the H:R odds of first events in the territory of the contralateral asymptomatic artery were 1:1 if the randomized vessel had retinal symptoms compared with 4:1 if the randomized vessel had hemispheric symptoms (significant difference; P<0.01). Increasing carotid stenosis in the 50% to 99% range had no effect on H:R odds (P=0.8). CONCLUSIONS: These findings confirm that retinal symptoms are more typical of carotid stenosis. Hemodynamic effects do not appear to be more important in the pathogenesis of retinal events than hemispheric ones in carotid stenosis. The retinal versus hemispheric location of initial symptoms is strongly predictive of the location of subsequent events in patients with carotid stenosis, even when new symptoms are contralateral to the original ones.

Importance of angle correction in the measurement of blood flow velocity with transcranial Doppler sonography.

BACKGROUND AND PURPOSE: The angle of insonation cannot be assessed with conventional transcranial Doppler sonography. Findings in healthy control subjects suggest that the angle is relatively small in routine clinical practice. Data regarding the angle in middle cerebral artery (MCA) stenosis are scarce. In this study, the angle and its effect on flow velocity measurements were assessed with transcranial color Doppler sonography in patients with MCA stenosis. METHODS: Eighteen patients (median age, 53 y; age range, 22-72 y) who satisfied qualifying criteria (eg, angiographically revealed unilateral MCA stenosis of > or =50%) were selected from 149 consecutive patients enrolled in a prospective study of transcranial color Doppler sonography and cerebral digital subtraction angiography. All had active neurologic symptoms. The angle of insonation and peak systolic and mean flow velocities in both MCAs were measured from videotapes generated at sonography. RESULTS: The mean angle of insonation was 47 +/- 11 degrees (range, 19-64 degrees ) on the stenotic side and 34 +/- 18 degrees on the contralateral side (P <.05). Angle-corrected velocities were higher than uncorrected ones. Differences between angle-corrected and uncorrected peak systolic and mean flow velocities on the stenotic side were 46.6% and 45.9%, respectively, of uncorrected values. Differences between corrected and uncorrected peak systolic and mean velocities were larger on the stenotic side compared with those on the contralateral side (P <.05). CONCLUSION: In patients with moderate or severe MCA stenosis, the angle of insonation can be substantial and cause large errors when flow velocities are measured without angle correction.

Retinal ischemia and embolism. Etiologies and outcomes based on a prospective study.

OBJECTIVES: To identify the most likely mechanisms of retinal ischemia and embolism in a hospital-referred population, and to determine the frequency of recurrent vascular events during the 3-month period following initial presentation. METHODS: Consecutive patients presenting to 2 tertiary medical centers and their outpatient clinics were prospectively enrolled over a 22-month period. Eligible patients presented with histories of transient or permanent monocular visual loss, or had evidence of asymptomatic retinal embolism on routine ophthalmological examination. They underwent a rapid and standardized evaluation that included imaging studies as well as blood tests, and follow-up was obtained at 1 and 3 months. RESULTS: Seventy-seven patients were enrolled. Enrollment diagnoses consisted of amaurosis fugax (n = 32), asymptomatic retinal embolism (n = 34), and central or branch retinal artery occlusion (n = 11). Eight different presumed etiologies of retinal artery distribution embolism or hypoperfusion were identified. Extracranial internal carotid artery occlusion or more than 50% stenosis was observed in 17/77 (22.1%) cases, making it the largest etiologic subgroup. Uncommon but treatable conditions were identified in 8/77 (10.4%) patients, and an etiologic diagnosis could not be made in 35/77 (45.5%) patients. Recurrent events occurred in, respectively, 14/77 (18.2%) and 6/73 (8.2%) patients at the 1- and 3-month follow-ups. They included 2 infarcts and 2 deaths; ischemic events of the retina were more common than those involving the brain. CONCLUSION: Severe stenosis of the extracranial internal carotid artery is the most common identified condition associated with retinal ischemia and embolism, but a variety of other, potentially treatable, conditions can be diagnosed if appropriate and specific evaluations are conducted. The frequency of recurrent vascular ischemic events is highest during the 1st month of follow-up and decreases during the 2nd and 3rd months. Recurrences range from relatively innocuous episodes of amaurosis fugax to vascular death.

Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. CONCLUSIONS: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Diagnosis of hyperlipidemia and treatment with a statin in the outpatient stroke clinic.

The aim of this study was to assess a stroke clinic's performance in the diagnosis of hyperlipidemia and more specifically to evaluate the effectiveness of statins in patients with cerebrovascular disease not enrolled in a research study. The records of 370 consecutive patients seen at a stroke clinic over a 4-year period were reviewed, and information regarding neurologic diagnosis, lipid profile, and use and type of cholesterol-lowering medication was abstracted. Hyperlipidemia was defined as a total cholesterol level equal to or more than 200 mg/dL. Forty-eight patients meeting specific criteria were further analyzed to monitor the effects of statins. Cholesterol testing was obtained in 324 patients (88%) and 178 (55%) were hyperlipidemic, but only 86 (48%) patients received treatment. The mean cholesterol level of the 48 patients dropped from 246.2 mg/dL to 197.1 mg/dL (P < .0001) after the initiation of statin therapy, and significant reductions were present in subgroups with pretreatment levels of 200 to 249 mg/dL and 250 to 299 mg/dL. Of the 21 patients with repeated cholesterol testing more than 6 months after the first posttreatment test, only 11 (52%) maintained a level below 200 mg/dL. Effective control of hyperlipidemia can be achieved in patients with cerebrovascular disease, but not all are adequately tested or treated. Improved physician awareness and more effective health care delivery systems are needed.

Ophthalmic artery microembolism in giant cell arteritis.

A 70-year-old man presented with a history of headache and sudden loss of vision of the left eye. Funduscopic examination showed sector retinal edema and hemorrhage as well as optic disc swelling consistent with anterior ischemic optic neuropathy. The Westergren sedimentation rate was 66 mm/h. Temporal artery biopsy was consistent with giant cell arteritis. Routine transcranial Doppler testing performed on a Pioneer 2020 instrument (Nicolet Vascular, Inc., Golden, CO) equipped with special software for microembolus detection showed a microembolic signal in the left ophthalmic artery. During a subsequent monitoring study, microembolic signals were detected in the anterior and middle cerebral arteries, bilaterally. Microembolism can occur in giant cell arteritis. Ophthalmic artery microembolism can be detected in vivo by transcranial Doppler ultrasonography. This new imaging capability can potentially be useful when evaluating patients with vascular disorders of the eye.

Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension.

BACKGROUND AND PURPOSE: Although aging and hypertension may predispose hypertensive elderly subjects to cerebral hypoperfusion during orthostatic stress, their effects on the acute cerebral autoregulatory response to hypotension are not known. METHODS: Continuous middle cerebral artery blood flow velocity (BFV) (transcranial Doppler ultrasound) and mean arterial pressure (MAP, Finapres) were measured in response to (1) acute hypotension during standing, (2) steady-state sitting and standing, and (3) hypercarbia during CO(2) rebreathing in 10 healthy young subjects (age 24+/-1 years), 10 healthy elderly subjects (age 72+/-3 years), and 10 previously treated hypertensive elderly (age 72+/-2 years) subjects. CO(2) reactivity was computed as the slope of cerebrovascular conductance (CVC=BFV/MAP) versus end-expiratory CO(2). Coherence, transfer magnitudes, and phases between low-frequency MAP and BFV signals were computed from their autospectra during 5 minutes of sitting and standing. RESULTS: MAP fell to a similar extent in all groups by an average of 21 to 26 mm Hg (22% to 26%) within 30 seconds of standing. Mean BFV also fell in all subjects but significantly less in the older subjects (-4.7+/-0. 7 cm/s in hypertensives and -5.3+/-1.2 cm/s in normotensives, P=NS) compared with younger subjects (-10.1+/-1.1 cm/s, P<0.05). CO(2) reactivity was greater in the young subjects (0.19+/-0.01) compared with normotensive (0.14+/-0.01, P<0.05) and hypertensive elderly subjects (0.11+/-0.02, P<0.05) (P=NS between elderly groups). Fewer hypertensive subjects had coherence between MAP and BFV signals; for subjects with coherence, there were no significant group differences in phase or transfer magnitudes in either sitting or standing positions. CONCLUSIONS: Despite reduced CO(2) reactivity, elderly normotensive and previously treated hypertensive subjects retain cerebral autoregulatory capacity in response to acute orthostatic hypotension.

Evaluation of new online automated embolic signal detection algorithm, including comparison with panel of international experts.

BACKGROUND AND PURPOSE: The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. METHODS: In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. RESULTS: In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of > or =7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity >95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of > or =7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give P=0.84, which was similar to that of the software. CONCLUSIONS: By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts

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.

Distribution of cerebral microembolism in the anterior and middle cerebral arteries.

BACKGROUND AND PURPOSE: Cerebral infarcts occur more frequently along the middle (MCA) than the anterior cerebral artery (ACA) territory. The reason(s) for this difference remains speculative. The objective of this study was to investigate the distribution of cerebral microemboli as detected by transcranial Doppler ultrasound (TCD) along the MCA and ACA territories. METHODS: Records of consecutive patients examined for the presence of cerebral microembolism during a 32-month period at the Neurovascular Laboratory were reviewed. Of the original 375 TCD studies in 268 patients, 28 studies in 24 patients demonstrated microembolic signals (MES) and monitored the MCA and ACA on the same side. TCD studies were performed on TC-2000 or TC-2020 instruments. MES positive studies were saved and off-line reviewed. MES satisfied previously established criteria. RESULTS: MES were more frequent in the MCA than the ACA in 85.7% (24/28) of studies (P < 0.01). Of the total number of MES (n = 979), 29.6% (n = 290) were detected in the ACA and 70.4% (n=689) in the MCA (P<0.01). The mean (+/- SD) intensity of MCA MES of 12.2 (+/- 2.4) dB was significantly lower than that of ACA MES of 14.8 (+/-3.2) dB (P=0.05). The mean (+/-SD) duration of MCA MES of 38.1 (+/- 45.3) ms was longer than that of ACA MES of 30.7 (+/-34.0) ms (P=0.05). CONCLUSIONS: Cerebral microembolism occurs more frequently in the MCA than the ACA, which may explain the uneven distribution of cerebral infarcts along these arterial territories. Furthermore, there are significant differences in the characteristics of ACA and MCA MES.

[Detection of microembolus with transcranial doppler]. / Detección de microémbolos con Doppler transcraneal.

OBJECTIVES: To review techniques and the most important clinical applications of microembolus detection with transcranial Doppler. DEVELOPMENT: Technical aspects of microembolus detection are discussed initially; clinical circumstances in which embolus detection is currently used follow, such as carotid stenosis, cardiac pathology, monitoring during neuroangiography, coronary revascularization surgery and endarterectomy. Lastly, the potential clinical applications of this technique are reviewed: localization of an embolic source, risk of recurrent ischemia in patients with unstable atherosclerotic plaques, intraoperative monitoring and potential surgical technique modifications based on this information, contributions to the understanding of the pathophysiology of the fat embolism syndrome, and monitoring therapeutic efficacy of antithrombotics and thrombolytics. CONCLUSIONS: The ability to detect cerebral emboli with transcranial ultrasound has increased significantly our understanding about the pathogenesis of cerebral ischemia. Microembolus detection with transcranial Doppler is a powerful and novel diagnostic technique that allows to study the embolic process in vivo and in real time, instead of using indirect indicators of embolism (clinical and radiological features, possible embolic sources, etc.).

Transcranial doppler detection of fat emboli.

BACKGROUND AND PURPOSE: The fat embolism syndrome (FES) is characterized by the simultaneous occurrence of pulmonary and neurological symptoms as well as skin and mucosal petechiae in the setting of long-bone fractures or their surgical repair. Its pathophysiology is poorly understood, and effective treatments are lacking. We present 5 patients with long-bone fractures in whom in vivo microembolism was detected by transcranial Doppler. METHODS: Five patients with long-bone fractures were monitored with transcranial Doppler for microembolic signals (MESs) after trauma. Two patients also had intraoperative monitoring. A TC-2020 instrument equipped with MES detection software was used. Detected signals were saved for subsequent review. Selected signals satisfied criteria defined previously and were categorized as large or small. RESULTS: Cerebral microembolism was detected in all 5 patients and was transient, resolving within 4 days of injury. Intraoperative monitoring revealed an increase in MESs during intramedullary nail insertion. The characteristics of MESs after injury varied among patients, with large signals being more frequent in the only patient with a patent foramen ovale. CONCLUSIONS: Cerebral microembolism after long-bone fractures can be detected in vivo and monitored over time. These findings may have potential diagnostic and therapeutic implications.