Viken L. Babikian

Consensus on Microembolus Detection by TCD

Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

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.

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.

Cerebellar infarction. Clinical and anatomic observations in 66 cases.

Background and Purpose Cerebellar infarction displays different clinical features, depending on the vascular territory involved. We studied patients with infarcts in the territories of the posterior inferior cerebellar artery or the superior cerebellar artery to compare their clinical presentation, course, and prognosis. Methods We retrospectively analyzed the clinical features, laboratory data, and imaging studies of 66 patients with cerebellar infarction collected consecutively at five institutions. All the cerebellar infarcts were documented on computed tomographic scan or magnetic resonance imaging. Results Two distinct profiles emerged, depending on the vascular territory involved. In 36 patients with posterior inferior cerebellar artery territory infarcts, a triad of vertigo, headache, and gait imbalance predominated at stroke onset. Computed tomography showed severe cerebellar mass effect in 11 cases (30%), with associated hydrocephalus in seven. In these seven patients (19%), postinfarct swelling led to brain stem compression that resulted in four deaths. In 30 patients with superior cerebellar artery infarcts, gait disturbance predominated at onset; vertigo and headache were significantly less common. The clinical course was usually benign. Computed tomography showed marked cerebellar mass effect, hydrocephalus, and brain stem compression in only two instances (7%). Presumed cerebral embolism was the predominant stroke mechanism in patients with superior cerebellar artery distribution infarcts, whereas in those with posterior inferior cerebellar artery distribution infarcts, the stroke mechanism was equally divided between cardiogenic embolism and posterior circulation arterial disease. Conclusions Cerebellar infarcts in the posterior inferior cerebellar artery and superior cerebellar artery distribution have distinct differences in clinical presentation, course, and prognosis. These differences should help in the selection of appropriate monitoring and treatment strategies.

Occlusive disease of the middle cerebral artery

We studied 20 patients with severe occlusive disease of the mainstem middle cerebral artery (MCA) or its major division branches, and 25 patients with internal carotid artery (ICA) disease. MCA disease patients were more often black, female, younger, and had fewer TIAs than the ICA disease patients. Neurologic signs in patients with MCA disease evolved progressively during days to weeks, whereas ICA disease patients more often had an acute onset of nonprogressive deficits. CT commonly showed restricted subcortical or wedge-shaped infarcts in MCA disease patients. All MCA disease patients had stroke, but 40% of ICA disease patients had no infarction. MCA lesions usually affected the mainstem MCA or its major superior division. Patients with MCA disease seldom had recurrent ischemia in the same vascular territory as the stroke and had a low incidence of subsequent cardiac death.

Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia

We reviewed the clinical and laboratory data of 128 patients with cerebrovascular disease and antiphospholipid antibodies. Cases were evenly divided between men and women, and the mean age of the study group was 46 years. Cerebral infarction occurred in 97 patients, and transient hemispheric ischemic attacks without stroke were recorded in 19; 12 suffered ocular ischemia. Systemic lupus erythematosus was diagnosed in 16% of all cases. Histories of systemic thromboembolic events and recurrent miscarriages were noted in 14% of the patients and in 19% of the women, respectively. Evidence of cerebral infarction preceding the index event was present in 30% of cases. During a mean follow-up of 16 months, nine of 96 (9%) patients sustained new cerebral infarctions. Of 72 echocardiographic studies, 16 (22%) showed valvular abnormalities. Cerebral angiography detected intracranial lesions in 24 of 49 patients (49%). These data indicate that antiphospholipid antibodies can be identified in stroke patients without known autoimmune disorders. They also suggest that antiphospholipid antibody-associated cerebrovascular ischemia may be recurrent and often occurs in patients with systemic thromboembolic events. Our findings should help design a prospective clinical trial that will assess the risk of recurrent thromboembolism in this population, identify stroke risk factors, and address therapy.

Clinical correlates of high-intensity transient signals detected on transcranial Doppler sonography in patients with cerebrovascular disease.

Background and Purpose High-intensity transient signals detected by transcranial Doppler sonography have been associated with particulate cerebral emboli. Their clinical correlates are poorly understood. This study was undertaken to assess their relation to cerebral ischemia and to determine whether the severity of cerebral arterial stenosis has an impact on their occurrence. Methods We studied 96 arteries in 75 consecutive patients with extracranial or intracranial arterial lesions or potential cardiac sources of cerebral embolism. Sixty patients had histories of cerebral or retinal transient ischemic attacks or infarcts, and 15 were asymptomatic. The diagnosis of ischemia was based on the clinical presentation and was supported by extensive laboratory testing. A transcranial Doppler sonography unit equipped with special software for emboli detection was used. Signals were selected based on criteria established a priori. Results Signals were detected in the territories of 28.3% of symptomatic and 11.6% of asymptomatic arteries. The difference was significant (P=.045). When patients with suspected cardiac embolic sources were excluded, the difference between symptomatic (27.9%) and asymptomatic (2.9%) arteries remained significant (P=.003), and signals were more frequent distal to arteries with more than 50% area stenosis (23.5%) than arteries with stenoses equal to or less than 50% (3.7%) (P=.028). In patients with only extracranial internal carotid artery stenoses, the difference between these degrees of stenosis remained significant (P=.043). Conclusions We conclude that high-intensity transient signals are significantly more common in the territories of symptomatic arteries and distal to lesions causing more than 50% stenosis. These findings may have diagnostic and therapeutic applications.

Risk Factor Modification in Stroke Prevention The Experience of a Stroke Clinic

BACKGROUND AND PURPOSE [corrected] We reviewed Stroke Clinic data to determine the extent of risk factor modification achieved in patients with cerebrovascular disease over 2 years. METHODS Visits to the Stroke Clinic of a tertiary medical center from July 1, 1994, through June 30, 1996, were reviewed. Obesity, smoking, hypertension, hyperlipidemia, hyperglycemia, and lifestyle changes were noted in patients with >/=2 visits (n=61) and measures (number varied) of these parameters. RESULTS Fifty-six patients (92%) had primary care physicians. In the 49 patients with >/=2 weight measurements, 33 (67%) were moderately or severely overweight by weight-height correlation. Forty-four patients (90%) remained in the same weight category. Of the 60 patients with available blood pressure data, 50 (83%) were hypertensive. At their last visits, 43 of the 50 (86%) were receiving medications, and 22 of the 43 treated (51%) were controlled. Serum glucose remained elevated in 14 of 47 patients (30%) and in 11 of 16 diabetic patients (69%). Thirty-six of 47 patients (55%) had elevated lipid measurements. None of the 21 smokers quit during the study period. Few patients modified dietary and exercise practices. Of 61 patients, 29 (48%) sustained vascular events during the study, with 17 of these 29 patients (59%) having strokes or transient ischemic attacks. CONCLUSIONS Although most patients were asked to quit smoking, received advice regarding diet and exercise, and were medicated for hypertension, elevated glucose, and cholesterol levels, their risk factor profiles showed little improvement during the 2-year period. More effective methods of controlling stroke risk factors are needed.

Effect of Anticoagulation Protocol on Outcome in Patients Undergoing CABG With Heparin-Bonded Cardiopulmonary Bypass Circuits

BACKGROUND We have demonstrated that the use of heparin-bonded cardiopulmonary bypass circuits (HBCs) combined with a lower anticoagulation protocol as an adjunct to an integrated blood conservation strategy decreases the incidence and magnitude of homologous transfusion and improves clinical outcome in patients undergoing primary coronary artery bypass grafting. It is not known whether it is the lower anticoagulation protocol that influences outcome in patients treated with HBCs. Furthermore, the thrombogenic risk of using lower anticoagulation with HBCs still is debated. METHODS To answer these questions, a prospective randomized study was conducted in which 244 patients undergoing primary coronary artery bypass grafting were treated with HBCs and randomized to undergo either a full (activated clotting time, > 450 seconds) or a lower (activated clotting time, > 250 seconds) anticoagulation protocol. In addition to clinical outcome, levels of thrombin generation markers during and after cardiopulmonary bypass were assessed in a consecutive subset of 58 patients (full anticoagulation profile = 28, lower anticoagulation profile = 30) by measuring thrombin-antithrombin complexes and prothrombin fragment 1.2. Levels of these markers also were correlated with the activated clotting time during cardiopulmonary bypass. RESULTS Preoperative and intraoperative risk profiles and other characteristics were similar in both groups, with more than 60% of patients undergoing nonelective operation. Compared with the full anticoagulation protocol group, patients in the lower anticoagulation protocol group were less likely to require blood products (24.2% versus 35.8%, respectively; p = 0.047) and received substantially fewer homologous donor units (0.50 +/- 0.92 versus 1.08 +/- 2.10 U, respectively; p = 0.005). Clinical outcomes were uniformly outstanding (but similar) in both treatment groups, with a modest reduction in the length of the hospital stay in the lower anticoagulation protocol group (5.26 +/- 1.23 versus 5.63 +/- 1.73 days, respectively; p = 0.05). The use of HBCs with a lower anticoagulation protocol was not associated with any adverse clinical events. Thrombin generation increased during cardiopulmonary bypass in both treatment groups, but was unrelated to the anticoagulation protocol or the activated clotting time (r2 = 0.03). No differences between the full and lower anticoagulation protocol groups were noted in the number of microemboli detected by transcranial Doppler analyses during cardiopulmonary bypass (n = 40) or in the postoperative neurologic and neuropsychologic outcomes (n = 30). CONCLUSIONS This study definitively demonstrates that, when used appropriately, patients who are treated with HBCs and a lower anticoagulation protocol have a lower incidence and magnitude of homologous transfusion and are not at any added risk for clinical, hematologic (thrombin-antithrombin complex and fragment 1.2 measurements), or microscopic (transcranial Doppler analyses) thromboembolic complications or for neurologic or neuropsychologic deficits.

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.