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Biomedical subjects

A V Alexandrov

Publications and source records attributed to A V Alexandrov.

At least 19 recordsLinked to original sources

Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy.

Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke.

Aged↗

Feedback equilibrium control during human standing.

Equilibrium maintenance during standing in humans was investigated with a 3-joint (ankle, knee and hip) sagittal model of body movement. The experimental paradigm consisted of sudden perturbations of humans in quiet stance by backward displacements of the support platform. Data analysis was performed using eigenvectors of motion equation. The results supported three conclusions. First, independent feedback control of movements along eigenvectors (eigenmovements) can adequately describe human postural responses to stance perturbations. This conclusion is consistent with previous observations (Alexandrov et al., 2001b) that these same eigenmovements are also independently controlled in a feed-forward manner during voluntary upper-trunk bending. Second, independent feedback control of each eigenmovement is sufficient to provide its stability. Third, the feedback loop in each eigenmovement can be modeled as a linear visco-elastic spring with delay. Visco-elastic parameters and time-delay values result from the combined contribution of passive visco-elastic mechanisms and sensory systems of different modalities.

Adult↗

Postpartum cerebral angiopathy: atypical features and treatment with intracranial balloon angioplasty.

Postpartum cerebral angiopathy (PCA) is an uncommon cause of ischemic and hemorrhagic stroke in young women. It is usually clinically benign and not relapsing. We describe a patient with nonhemorrhagic PCA who had an atypical progressive neurological deficit from bilateral hemisphere watershed ischemia despite treatment with aggressive medical therapy and intracranial balloon angioplasty.

Adult↗

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.

Adolescent↗

Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement.

BACKGROUND: Arterial recanalization precedes clinical improvement or may lead to hemorrhage or reperfusion injury. Speed of clot lysis was not previously measured in human stroke. METHODS AND RESULTS: Transcranial Doppler (TCD) and the National Institutes of Health Stroke Scale (NIHSS) were used to monitor consecutive patients receiving intravenous tissue plasminogen activator (tPA), before tPA bolus and at 24 hours. Patients with complete or partial recanalization of the middle cerebral or basilar artery on TCD were studied. Recanalization was classified a priori as sudden (abrupt appearance of a normal or stenotic low-resistance signal), stepwise (flow improvement over 1 to 29 minutes), or slow (>/=30 minutes). Recanalization was documented in 43 tPA-treated patients (age 68+/-17 years; NIHSS score 16.8+/-6, median 15 points). tPA bolus was given at a mean of 135+/-61 minutes after symptom onset. Recanalization began at a median of 17 minutes and was completed at 35 minutes after tPA bolus, with mean duration of recanalization of 23+/-16 minutes. Recanalization was sudden in 5, stepwise in 23, and slow in 15 patients. Faster recanalization predicted better short-term improvement (P=0.03). At 24 hours, 80%, 30%, and 13% of patients in these respective recanalization groups had NIHSS scores of 0 to 3. Symptomatic hemorrhage occurred in only 1 patient, who had stepwise recanalization 5.5 hours after stroke onset. Slow or partial recanalization with dampened flow signal was found in 53% of patients with total NIHSS scores >10 points at 24 hours (P=0.01). Complete recanalization (n=25) occurred faster (median 10 minutes) than partial recanalization (n=18; median 30 minutes; P=0.0001). CONCLUSIONS: Rapid arterial recanalization is associated with better short-term improvement, mostly likely because of faster and more complete clot breakup with low resistance of the distal circulatory bed. Slow (>/=30 minutes) flow improvement and dampened flow signal are less favorable prognostic signs. These findings may be evaluated to assist with selection of patients for additional pharmacological or interventional treatment.

Aged↗

Intravenous tissue-type plasminogen activator therapy for ischemic stroke: Houston experience 1996 to 2000.

CONTEXT: Intravenous tissue-type plasminogen activator (tPA) therapy using the National Institute of Neurological Disorders and Stroke criteria has been given with variable safety to less than 5% of the patients who have ischemic strokes nationwide. Our center is experienced in treating large numbers of stroke patients with intravenous tPA. OBJECTIVE: To report our total 4-year experience in the treatment of consecutive patients who had an ischemic stroke. DESIGN: Prospective inception cohort registry of all patients seen by our stroke team and an additional retrospective medical record review of all patients treated between January 1, 1996, and June 1, 2000. SETTING: A veteran stroke team composed of fellows and stroke-specialty faculty servicing 1 university and 3 community hospitals in a large urban setting. PATIENTS: Consecutive patients with ischemic stroke treated within the first 3 hours of symptom onset. INTERVENTION: According to the National Institute of Neurological Disorders and Stroke protocol, 0.9 mg/kg of intravenous tissue-type plasminogen activator was administered. MAIN OUTCOME MEASURES: Number and proportion treated, patient demographics, time to treatment, hemorrhage rates, and clinical outcome. RESULTS: A total of 269 patients were treated between January 1, 1996, and June 1, 2000. Their mean age was 68 years (age range, 24-93 years); 48% were women. This represented 9% of all patients admitted with symptoms of cerebral ischemia at our most active hospital (over the final 6 months, 13% of all patients with symptoms of cerebral ischemia and 15% of all acute ischemic stroke patients). Before treatment the mean +/- SD National Institutes of Health Stroke Scale (NIHSS) score was 14.4 +/- 6.1 points (median, 14 points; range, 4-33 points). A tPA bolus was given at 137 minutes (range, 30-180 minutes); 28% of the patients were treated within 2 hours. The mean door-to-needle time was 70 minutes (range, 10-129 minutes). The symptomatic intracerebral hemorrhage rate was 5.6% of those patients with a second set of brain scans (4.5% of all patients), with a declining trend from 1996 to 2000. Protocol violations were found in 13% of all patients; the symptomatic intracerebral hemorrhage rate in these patients was 15%. At 24 hours, the NIHSS score was 10 +/- 8 points (median, 8 points; range, 0-36 points). In-hospital mortality was 15% and the patients' discharge NIHSS scores were 7 +/- 7 points (median, 3 points; range, 0-35 points). CONCLUSIONS: Intravenous tPA therapy can be given to up to 15% of the patients with acute ischemic stroke with a low risk of symptomatic intracerebral hemorrhage. Successful experience with intravenous tPA therapy depends on the experience and organization of the treating team and adherence to published guidelines.

Adult↗

Biomechanical analysis of movement strategies in human forward trunk bending. I. Modeling.

Two behavioral goals are achieved simultaneously during forward trunk bending in humans: the bending movement per se and equilibrium maintenance. The objective of the present study was to understand how the two goals are achieved by using a biomechanical model of this task. Since keeping the center of pressure inside the support area is a crucial condition for equilibrium maintenance during the movement, we decided to model an extreme case, called "optimal bending", in which the movement is performed without any center of pressure displacement at all, as if standing on an extremely narrow support. The "optimal bending" is used as a reference in the analysis of experimental data in a companion paper. The study is based on a three-joint (ankle, knee, and hip) model of the human body and is performed in terms of "eigenmovements", i.e., the movements along eigenvectors of the motion equation. They are termed "ankle", "hip", and "knee" eigenmovements according to the dominant joint that provides the largest contribution to the corresponding eigenmovement. The advantage of the eigenmovement approach is the presentation of the coupled system of dynamic equations in the form of three independent motion equations. Each of these equations is equivalent to the motion equation for an inverted pendulum. Optimal bending is constructed as a superposition of two (hip and ankle) eigenmovements. The hip eigenmovement contributes the most to the movement kinematics, whereas the contributions of both eigenmovements into the movement dynamics are comparable. The ankle eigenmovement moves the center of gravity forward and compensates for the backward center of gravity shift that is provoked by trunk bending as a result of dynamic interactions between body segments. An important characteristic of the optimal bending is the timing of the onset of each eigenmovement: the ankle eigenmovement onset precedes that of the hip eigenmovement. Without an earlier onset of the ankle eigenmovement, forward bending on the extremely narrow support results in falling backward. This modeling approach suggests that during trunk bending, two motion units--the hip and ankle eigenmovements--are responsible for the movement and for equilibrium maintenance, respectively.

Biomechanical Phenomena↗

Biomechanical analysis of movement strategies in human forward trunk bending. II. Experimental study.

The large mass of the human upper trunk, its elevated position during erect stance, and the small area limited by the size of the feet, stress the importance of equilibrium control during trunk movements. The objective of the present study was to perform a biomechanical analysis of fast forward trunk movements in order to understand the coordination between movement and posture. The analysis is based on a comparison between experimentally observed bending and hypothetical "optimal bending" performed on an infinitely narrow support, as presented in a companion paper. The experimental data were obtained from 16 subjects who performed fast forward bending while standing on a wide platform or on a narrow beam. The analysis is performed by decomposition of the movement into three dynamically independent components, each representing a movement along one of the three eigenvectors of the motion equation. The eigenmovements are termed "hip", "ankle", and "knee" eigenmovements, according to the dominant joint. The experimentally observed movement is characterized mainly by the hip and ankle eigenmovements, whereas the knee eigenmovement is negligible. Similarly to the "optimal bending" the ankle eigenmovement starts earlier and lasts longer than the hip eigenmovement. An early forward acceleration of the center of gravity in the ankle eigenmovement is caused by anticipatory changes in the ankle joint torque. This clarifies the role of the early tibialis anterior burst and/or soleus inhibition usually observed in electromyographic recordings during forward bending. The results suggest that the hip and the ankle eigenmovements can be treated as independently controlled motion units aimed at functionally different behavioral goals: the bending per se and postural adjustment. It is proposed that the central nervous system has to control these motion units sequentially in order to perform the movement and maintain equilibrium. It is also suggested that the hip and ankle eigenmovements can be regarded as a biomechanical background for the hip and ankle strategies introduced by Horak and Nashner (1986) on the basis of electromyographic recordings and kinematic patterns in response to postural perturbations.

Adult↗

A broad diagnostic battery for bedside transcranial Doppler to detect flow changes with internal carotid artery stenosis or occlusion.

BACKGROUND AND PURPOSE: The authors establish accuracy parameters of a broad diagnostic battery for bedside transcranial Doppler (TCD) to detect flow changes due to internal carotid artery (ICA) stenosis or occlusion. METHODS: The authors prospectively studied consecutive patients with stroke or transient ischemic attack referred for TCD. TCD was performed and interpreted at bedside using a standard insonation protocol. A broad diagnostic battery included major criteria: collateral flow signals, abnormal siphon or terminal carotid signals, and delayed systolic flow acceleration in the middle cerebral artery. Minor criteria included a unilateral decrease in pulsatility index (< or = 0.6 or < or = 70% of contralateral side), flow diversion signs, and compensatory velocity increase. Angiography or carotid duplex ultrasound (CDU) was used to grade the degree of carotid stenosis using North American criteria. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD findings were determined. RESULTS: Seven hundred and twenty patients underwent TCD, of whom 517 (256 men and 261 women) had angiography and/or CDU within 8.8 +/- 0.9 days. Age was 63.1 +/- 15.7 years. For a 70% to 99% carotid stenosis or occlusion, TCD had sensitivity of 79.4%, specificity of 86.2%, PPV of 57.0%, NPV of 94.8%, and accuracy of 84.7%. For a 50% to 99% carotid stenosis or occlusion, TCD had sensitivity of 67.5%, specificity of 83.9%, PPV of 54.5%, NPV of 90.0%, and accuracy of 81.6%. TCD detected intracranial carotid lesions with 84.9% accuracy and extracranial carotid lesions with 84.4% accuracy (sensitivity of 88% and 79%, specificity of 85% and 86%, PPV of 24% and 54%, and NPV of 99% and 95%, respectively). The prevalence of the ophthalmic artery flow reversal was 36.4% in patients with > or = 70% stenosis or occlusion. If present, this finding indicated a proximal ICA lesion location in 97% of these patients. CONCLUSIONS: In symptomatic patients, bedside TCD can accurately detect flow changes consistent with hemodynamically significant ICA obstruction; however, TCD should not be a substitute for direct carotid evaluation. Because TCD is sensitive and specific for a > or = 70% carotid stenosis or occlusion in both extracranial and intracranial carotid segments, it can be used as a complementary test to refine other imaging findings and detect tandem lesions.

Angiography↗

Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: TIMI angiographic classification measures coronary residual flow and recanalization. We developed a Thrombolysis in Brain Ischemia (TIBI) classification by using transcranial Doppler (TCD) to noninvasively monitor intracranial vessel residual flow signals. We examined whether the emergent TCD TIBI classification correlated with stroke severity and outcome in patients treated with intravenously administered tPA (IV-tPA). METHODS: TCD examination occurred acutely and on day 2. TIBI flows were determined at distal MCA and basilar artery depths, depending on occlusion site. TIBI waveforms were graded as follows: 0, absent; 1, minimal; 2, blunted; 3, dampened; 4, stenotic; and 5, normal. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours after administration of tPA. RESULTS: One hundred nine IV tPA patients were studied. Mean+/-SD age was 68+/-16 years; median NIHSS score before administration of tPA (pre-tPA) was 17.5. The tPA bolus was administered 143+/-58 minutes and the TCD examination 141+/-57 minutes after symptom onset. Pre-tPA NIHSS scores were higher in patients with TIBI grade 0 than TIBI grade 4 or 5 flow. TIBI flow improvement to grade 4 or 5 occurred in 35% of patients (19/54) with an initial grade of 0 or 1 and in 52% (12/23) with initial grade 2 or 3. The 24-hour NIHSS scores were higher in follow-up in patients with TIBI grade 0 or 1 than those with TIBI grade 4 or 5 flow. TIBI flow recovery correlated with NIHSS score improvement. Lack of flow recovery predicted worsening or no improvement. In-hospital mortality was 71% (5/7) for patients with posterior circulation occlusions; it was 22% (11/51) for patients with pre-tPA TIBI 0 or 1 compared with 5% (1/19) for those with pre-tPA TIBI 2 or 3 anterior circulation occlusions. CONCLUSIONS: Emergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPA-treated stroke patients. A flow-grade improvement correlated with clinical improvement.

Aged↗

Thrombolytic therapy in an adolescent ischemic stroke.

We report the case of a 16-year-old Caucasian girl who developed acute onset of left hemiplegia, left hemisensory deficit, and dysarthria. After a negative computed tomographic scan of the brain, the patient was given intravenous recombinant tissue plasminogen activator according to established adult guidelines. The patient experienced a marked improvement within 24 hours. Stroke etiology was determined to be a paradoxical embolus via a patent foramen ovale associated with pelvic vein thrombosis. This case illustrates the importance of early recognition of stroke and the utility of thrombolytics in treating ischemic infarcts in the adolescent population.

Adolescent↗

Arterial status after intravenous TPA therapy for ischaemic stroke. A need for further interventions.

BACKGROUND: Intravenous tissue plasminogen activator (TPA) is an approved therapy for acute ischaemic stroke in the United States. We aimed to noninvasively monitor the therapy to determine arterial recanalisation and persisting vascular abnormalities. METHODS: We prospectively studied consecutive patients with symptoms of ischaemic stroke who received intravenous TPA and were monitored by 2 MHz transcranial Doppler (TCD) to determine occlusion and recanalisation (TIMI grades equivalent). For outcome assessment we used the National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: Sixty patients were studied (age 71+/-15 years, pre-TPA NIHSS 18+/-6.1, TPA bolus at 141+/-68 min after stroke onset). The internal carotid artery (ICA) was occluded in 25%, middle cerebral artery (MCA) in 80%; combined (ICA+MCA) occlusion was found in 19%; and basilar artery (BA) was occluded in 7%. Also, 2% had normal TCD and 8% of patients had no temporal windows. Complete recanalisation on TCD of all insonated arteries was found in 19 patients (32%) at 44+/-22 min after a TPA bolus. However, 67% of MCA, 25% of BA, and all ICA occlusions did not completely recanalise (TIMI grades 0-2). If flow impairment persisted for more than two hours after a TPA bolus, these patients continued to have significant neurological deficits at 24 hours (15.0+/-8.2 vs 6.3+/-7.3 NIHSS points, p<0.001 in non-parametric statistics). High-grade residual stenoses with microembolic signals were seen on TCD in the MCA and BA (n=3) suggesting continuing clot dissolution. In patients without complete recanalisation (n=36, or 60%), TCD identified lesions potentially amenable to further interventions. CONCLUSIONS: Persisting arterial occlusion after intravenous TPA therapy leads to poor short-term outcome. Noninvasive monitoring of TPA therapy with TCD can identify these high-risk patients for combined interventions such as intra-arterial thrombolysis, mechanical clot disruption, stenting or anticoagulation.

Aged↗

Citicoline. Ferrer Internacional.

Citicoline was originally developed and launched by Ferrer for the treatment of stroke, and is now also being investigated for the potential treatment of Alzheimer's disease (AD). In the US, the compound is being developed by Interneuron for the treatment of stroke. A US launch had been rescheduled for 2002 although a decision on future US development of citicoline was intended to be made in conjunction with Takeda, Interneuron's US licensee. Takeda had decided not to pursue development by December 2000 and was in negotiations with Interneuron for another product candidate. Interneuron stated at this time that it would explore other partnership opportunities for citicoline. In 1993, Interneuron licensed exclusive marketing and manufacturing rights to citicoline in the US and Canada from Ferrer. By September 1997, a patent application had been filed worldwide by Interneuron for the use of citicoline in the reduction of cerebral infarct volume, and in September 1998, US-05801160 was issued for citicoline relating to the protection of brain tissue from cerebral infarction following ischemic stroke. In December 1999, US rights to the commercialization of citicoline were licensed to Takeda.

Alzheimer Disease↗

Seizures after stroke: a prospective multicenter study.

BACKGROUND: Studies of seizures after stroke have largely been retrospective, with small patient numbers and limited statistical analysis. Much of the doctrine about seizures after stroke is not evidenced based. OBJECTIVE: To determine the incidence, outcome, and risk factors for seizures after stroke. DESIGN: International, multicenter, prospective, analytic inception cohort study conducted for 34 months. PATIENTS AND SETTING: There were 2021 consecutive patients with acute stroke admitted to university teaching hospitals with established stroke units. After exclusion of 124 patients with previous epilepsy or without computed tomographic diagnosis, 1897 were available for analysis. Mean follow-up was 9 months. MAIN OUTCOME MEASURES: Occurrence of 1 or more seizures after stroke, stroke disability, and death after stroke. RESULTS: Seizures occurred in 168 (8.9%) of 1897 patients with stroke (28 [10.6%] of 265 with hemorrhagic and 140 [8.6%] of 1632 with ischemic stroke). On Kaplan-Meier survival analysis, patients with hemorrhagic stroke were at significantly greater risk of seizures (P =.002), with an almost 2-fold increase in risk of seizure after stroke (hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.26-2.73; P =.002). On multivariate analysis, risk factors for seizures after ischemic stroke were cortical location of infarction (HR, 2.09; 95% CI, 1. 19-3.68; P<.01) and stroke disability (HR, 2.10; 95% CI, 1.16-3.82; P<.02). The only risk factor for seizures after hemorrhagic stroke was cortical location (HR, 3.16; 95% CI, 1.35-7.40; P<.008). Recurrent seizures (epilepsy) occurred in 47 (2.5%) of 1897 patients. Late onset of the first seizure was an independent risk factor for epilepsy after ischemic stroke (HR, 12.37; 95% CI, 4.74-32.32; P<. 001) but not after hemorrhagic stroke. CONCLUSIONS: Seizures occur more commonly with hemorrhagic stroke than with ischemic stroke. Only a small minority later develop epilepsy. Patients with a disabling cortical infarct or a cortical hemorrhage are more likely to have seizures after stroke; those with late-onset seizures are at greater risk of epilepsy.

Aged↗

Predictors of tube feeding in acute stroke patients with dysphagia.

Stroke is the third leading cause of death and the leading cause of disability in adults. Dysphagia, or difficulty with swallowing, is an untoward outcome of stroke occurring in as many as 71% of stroke survivors. This study sought to identify characteristics in stroke patients predictive of tube feeding dependency during acute care secondary to neurogenic oropharyngeal dysphagia. Significant differences in age, stroke severity scores, length of stay, and cost per case were measured between the tube feeding and control group patients. Univariate analysis identified the existence of seven dependent risk factors, of which four were found to be independent risk factors for the outcome of interest: wet voice after swallowing water, hypoglossal nerve dysfunction, National Institutes of Health Stroke Scale score, and incomplete oral labial closure. Findings from this study may assist healthcare providers in the early identification of stroke patients at risk for clinically significant neurogenic oropharyngeal dysphagia, facilitating reduction of untoward outcomes.

Acute Disease↗

Accuracy and criteria for localizing arterial occlusion with transcranial Doppler.

The authors determined transcranial Doppler (TCD) accuracy for the proximal internal carotid artery (ICA), distal ICA, proximal middle cerebral artery (MCA), distal MCA, anterior cerebral artery (ACA), posterior cerebral artery (PCA), terminal vertebral artery (tVA), and basilar artery (BA) occlusion in cerebral ischemia patients. Detailed diagnostic criteria were prospectively applied for TCD interpretation independent of angiographic findings. Of 320 consecutive patients referred to the neurosonology service with symptoms of cerebral ischemia, 190 (59%) patients also underwent angiography (MRA or DSA). 48 of those 190 patients had angiographic occlusion and 12 of those 48 patients had involvement of multiple vessels. Median time from TCD until angiography was performed was 1 hour (41 patients had angiography before TCD). TCD showed 40 true positive, 8 false negative, 8 false positive, and 134 true negative studies with sensitivity 83.0%, specificity 94.4%, positive predictive value 83.0%, negative predictive value 94.4%, and accuracy 91.6% to determine all sites of occlusion. Sensitivity for each individual occlusion site was: proximal ICA 94%, distal ICA 81%, MCA 93% tVA 56%, BA 60%. Specificity ranged from 96% to 98%. TCD is sensitive and specific in determining the site of the arterial occlusion using detailed diagnostic criteria, including proximal ICA and distal MCA lesions. TCD has the highest accuracy for ICA and MCA occlusions. If the results of TCD are normal, there is at least a 94% chance that angiographic studies will be negative.

Arterial Occlusive Diseases↗