Lee R. Guterman

Prevention and Treatment of Thromboembolic and Ischemic Complications Associated with Endovascular Procedures: Part II—Clinical Aspects and Recommendations

We reviewed the incidence, risk factors, and clinical features of thromboembolic and ischemic events associated with diagnostic cerebral angiography, endovascular treatment of aneurysms using coils or balloons, angioplasty and stent placement to treat extracranial carotid artery stenosis, and embolization of arteriovenous malformations using glue or other embolic agents. We performed a cumulative analysis to determine the frequency and characteristics of these events and a subset analysis (whenever possible) to determine the benefits of various strategies for complication avoidance. Of the 1,547 patients who underwent Guglielmi detachable coil treatment, thromboembolic events were observed for 127 (8.2%), consisting of asymptomatic events for 12 patients, transient ischemic attacks for 29, and strokes for 86. The outcomes for the 86 patients with strokes were categorized as full recovery for 15, good recovery for 27, partial recovery for 19, no recovery for 11, death for 12, and undetermined outcome for 2. Of the 834 patients who underwent carotid angioplasty and stent placement, thromboembolic events were observed for 73 (8.8%), consisting of transient ischemic attacks for 26 patients and strokes for 47. The outcomes for the patients with strokes were categorized as full recovery for 20, good recovery for 15, partial recovery for 6, no recovery for 2, and death for 4. High rates of thromboembolic events were also observed with balloon occlusion of aneurysms (11%) or parent arteries (19%) and carotid angioplasty alone (5.9%). Arteriovenous malformation embolization was associated with an ischemic event/procedure rate of 9.4%. High rates of thromboembolic and ischemic complications, with subsequent morbidity and death, are associated with most endovascular procedures. Further research and the formulation of standard preventive guidelines may help to reduce these risks and improve the overall success of these procedures.

Frequency and determinants of postprocedural hemodynamic instability after carotid angioplasty and stenting.

BACKGROUND AND PURPOSE Hemodynamic instability can occur acutely after carotid angioplasty and stent placement (CAS). We performed this study to determine the frequency of hemodynamic instability in a series of patients who underwent CAS and to analyze factors associated with development of postprocedural hemodynamic events. METHODS We reviewed medical records and angiograms in a series of 51 patients (mean age 68.3+/-8.9 years) who underwent CAS for symptomatic (n=29) or asymptomatic (n=22) carotid artery stenosis. Any episodes of hypotension (systolic blood pressure <90 mm Hg), hypertension (systolic blood pressure >160 mm Hg), or bradycardia (heart rate <60 bpm) that occurred in the acute postprocedural period were recorded. The effect of demographic, clinical, intraprocedural, and angiographic factors on subsequent development of hemodynamic instability was analyzed by logistic regression. RESULTS The frequency of postprocedural hemodynamic complications in our patient series was as follows: hypotension, 22.4%; hypertension, 38.8%; and bradycardia, 27.5%. Intraprocedural hypotension (odds ratio [OR] 14.6, P=0.024) and history of myocardial infarction (OR 14.1, P=0.04) independently predicted postprocedural hypotension. Postprocedural hypertension was predicted by intraprocedural hypertension (OR 7.6, P=0.01) and previous ipsilateral carotid endarterectomy (OR 7.6, P=0.02). Postprocedural bradycardia was associated with intraprocedural hypotension (OR 74, P=0.001) and intraprocedural bradycardia (OR 12, P=0.008). All events had resolved at the conclusion of the intensive care unit monitoring period (mean 25.7 hours, range 18 to 43 hours). CONCLUSIONS Postprocedural hemodynamic instability is frequent after CAS and supports the need for monitoring in settings suited to expeditious management of cardiovascular emergencies. Patients who have evidence of hemodynamic instability during the procedure are at highest risk.

Stenting and secondary coiling of intracranial internal carotid artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE Endovascular stents have been successfully used in the treatment of fusiform and dissecting aneurysms of the peripheral circulation and extracranial carotid and vertebral arteries. Technical limitations related to the inability to navigate the stent and the delivery system through tortuous vascular segments has limited their application with intracranial lesions. Availability of new flexible and pliable stent systems might overcome these difficulties. CLINICAL PRESENTATION A 49-year-old woman presented with a dissecting pseudoaneurysm of the horizontal portion of the petrous internal carotid artery that increased in size, as revealed by serial angiographic studies. INTERVENTION The aneurysm was treated by deploying a new flexible stent across the aneurysm neck and by then packing the aneurysm sac with Guglielmi detachable coils that were delivered by a microcatheter positioned through the stent struts into the aneurysm lumen. CONCLUSION New flexible stents can be used to treat intracranial internal carotid artery aneurysms in difficult-to-access areas, such as the horizontal petrous segment. The stent may disrupt the aneurysm inflow tract, thereby inducing stasis and facilitating intra-aneurysmal thrombosis. In addition, the stent acts as an endoluminal scaffold to prevent coil herniation into the parent artery, which allows tight packing of even wide-necked and irregularly shaped aneurysms. The stent may also serve as a matrix for endothelial growth. We think this new generation of flexible stents and the use of this described technique will usher in the next era of endovascular management of intracranial aneurysms.

Cocaine Use and the Likelihood of Nonfatal Myocardial Infarction and Stroke Data From the Third National Health and Nutrition Examination Survey

Background —Numerous case series have implicated cocaine use as a cause of both myocardial infarction (MI) and stroke on the basis of the temporal relationship between drug use and event onset. Increasing cocaine use in the US population, especially in younger individuals, mandates a more extensive investigation of this relationship. Methods and Results —We determined the association of cocaine use with self-reported physician diagnosis of MI or stroke in a nationally representative sample of 10 085 US adults aged 18 to 45 years who participated in the Third National Health and Nutrition Examination Survey. A total of 46 nonfatal MIs and 33 nonfatal strokes were reported. After adjusting for differences in age, sex, race/ethnicity, education, hypertension, diabetes mellitus, cholesterol level, body mass index, and cigarette smoking, persons who reported frequent lifetime cocaine use had a significantly higher likelihood of nonfatal MI than nonusers (odds ratio, 6.9; 95% confidence interval, 1.3 to 58) but not stroke. In this age group, the population-attributable risk percent of frequent cocaine for nonfatal MI was estimated as 25%. Conclusion —Regular cocaine use was associated with an increased likelihood of MI in younger patients. Approximately 1 of every 4 nonfatal MIs in persons aged 18 to 45 years was attributable to frequent cocaine use in this survey. Behavior modification by public awareness and education may reduce the cardiovascular morbidity associated with cocaine use.

Aggressive mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic agent for ischemic stroke: a prospective study.

OBJECTIVE We prospectively evaluated the safety and effectiveness of aggressive mechanical disruption of clot in conjunction with intra-arterial administration of a low-dose third-generation thrombolytic agent (reteplase) to treat ischemic stroke in patients who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis. Mechanical clot disruption was used if low-dose pharmacological thrombolysis was ineffective. This strategy was adopted to increase the recanalization rate without increasing the risk of intracerebral hemorrhage. METHODS Patients were considered poor candidates for intravenous therapy because of severity of neurological deficits, interval from symptom onset to presentation of at least 3 hours, or recent major surgery. We administered a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. After the initial doses were administered, we performed mechanical angioplasty (for proximal occlusion) or snare manipulation (for distal occlusion) at the occlusion site if recanalization had not occurred. The remaining doses of thrombolytics were subsequently administered if required for further recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical evaluations were performed before and 24 hours, 7 to 10 days, and 1 to 3 months after treatment. RESULTS Nineteen consecutive patients were treated (mean age, 64.3 ± 16.2 yr; 10 were men). Initial National Institutes of Health Stroke Scale scores ranged from 11 to 42. Time from onset to treatment ranged from 1 to 9 hours. Occlusion sites were in the following arteries: cervical internal carotid (n = 7), intracranial internal carotid (n = 1), middle cerebral (n = 9), and basilar (n = 2). Of the 19 patients, thrombolysis alone was used in 5 patients, angioplasty was performed in 11 patients, and snare maneuvers were used in 5 patients. Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, near-complete restoration of flow (modified TIMI Grade 3) in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0). Neurological improvement at 24 hours (decline of at least 4 points in National Institutes of Health Stroke Scale score) was observed in seven patients. Five other patients experienced further improvement in National Institutes of Health Stroke Scale score at 7 to 10 days. No vessel rupture, dissection, or symptomatic intracranial hemorrhages were observed. At the time of follow-up evaluation, 7 of 19 patients were functionally independent. CONCLUSION A high rate of recanalization and clinical improvement can be observed in patients with ischemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot. Moreover, this strategy may reduce the risk of intracerebral hemorrhage observed with thrombolytics.

Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part I--Pathophysiological and pharmacological features.

Thromboembolic and ischemic complications frequently occur during and after endovascular procedures, because of associated arterial injury and the thrombogenic characteristics of arterial catheters, contrast agents, and implanted devices such as coils and stents. Platelet adhesion, activation, and aggregation occurring at the site of arterial injury are mediated by local factors, including thromboxane A2 (inhibited by aspirin) and adenosine diphosphate (inhibited by ticlopidine and clopidogrel). Concomitantly, thrombin is formed by serial activation of clotting factors via contact with subendothelial tissue factor. Thrombin cleaves fibrinogen into fibrin. Thrombin activation is indirectly blocked by heparin and its analogs. However, after thrombin is clot-bound (with fibrin), it is relatively protected from heparin and is effectively blocked only by direct thrombin inhibitors (hirudin and its analogs). The final common pathway in clot formation is the binding of fibrinogen to platelets via platelet glycoprotein IIb/IIIa receptors, which is inhibited by antibodies to platelet IIb/IIIa receptors. New treatment modalities, such as the use of direct thrombin inhibitors and antibodies to platelet glycoprotein IIb/IIIa, seem to be more effective for prophylaxis and treatment than conventional anticoagulation and antiplatelet therapies.

Stent-assisted intracranial recanalization for acute stroke: early results.

OBJECTIVE: In patients who are not candidates for intravenous tissue plasminogen activator, intra-arterial (IA) therapy is an alternative. Current recanalization rates are 50 to 60% for IA thrombolysis. Stent-assisted recanalization in the setting of acute stroke after failed thrombolysis may improve recanalization rates. METHODS: A retrospective analysis was performed of 19 patients treated at two institutions between July 2001 and March, 2005 with intracranial stenting of a vessel resistant to standard thrombolytic techniques. Demographics, clinical, and radiographic presentation and outcomes were studied. RESULTS: Thirteen men and six women with a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 16 (range, 15-22) were included. Eight lesions were located at the internal carotid artery terminus, seven in the M1/M2 segment, and four in the basilar artery. Average time-to-treatment was 210 ± 160 minutes. Overall recanalization rate (Thrombolysis in Cerebral Infarction Grade 2 or 3) was 79%. There were six deaths: five due to progression of stroke and withdrawal of care at the family’s request and one as the result of a delayed carotid injury after tracheostomy. One postoperative asymptomatic intracranial hemorrhage occurred without adverse affect on outcome. Median discharge NIHSS score of surviving patients was 5 (range, 2.5-11.5). Lesions at the internal carotid artery terminus (P < 0.009), older age (P < 0.003), and higher baseline NIHSS score (P < 0.009) were significant negative outcome predictors, as measured by >3 modified Rankin scale score at discharge. CONCLUSION: Stent-assisted recanalization for acute stroke resulting from intracranial thrombotic occlusion is associated with a high recanalization rate and low intracranial hemorrhage rate. These initial results suggest that stenting may be an option for recalcitrant cerebral arterial occlusions.

Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE Abnormal serum sodium levels (hyponatremia and hypernatremia) are frequently observed during the acute period after aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema and mass effect. We performed this study to determine the prognostic significance of serum sodium concentration abnormalities. METHODS We analyzed prospectively collected data for the placebo treatment group in a clinical trial conducted at 54 neurosurgical centers in North America. The presence of hypernatremia (serum sodium concentration of >145 mmol/L) and hyponatremia (serum sodium concentration of <135 mmol/L) was determined with serum sodium measurements obtained at admission and 3, 6, and 9 days after SAH. The effects of hypernatremia and hyponatremia on the risk of symptomatic vasospasm and on 3-month outcomes were analyzed after adjustment for the following potential confounding factors: age, sex, preexisting hypertension, admission Glasgow Coma Scale score, initial mean arterial pressure, subarachnoid clot thickness, intraventricular blood or intraparenchymal hematoma, ventricular dilation, and aneurysm size and location. RESULTS Of 298 patients in the analysis, 58 (19%) developed hypernatremia and 88 (30%) developed hyponatremia. Hypernatremia was significantly associated with poor outcomes (odds ratio, 2.7; 95% confidence interval, 1.2–6.1). A positive correlation was observed between the highest sodium values recorded and Glasgow Outcome Scale scores at 3 months (P < 0.0001 by analysis of variance). Hyponatremia was not associated with 3-month outcomes (odds ratio, 1.9; 95% confidence interval, 0.9–4.3). Neither hypernatremia nor hyponatremia was associated with the risk of symptomatic vasospasm. CONCLUSION Hyponatremia seems to be more common than hypernatremia after SAH. However, hypernatremia after SAH is independently associated with poor outcomes, and this association is independent of previously identified outcome predictors, including age and admission Glasgow Coma Scale scores. Further studies are needed to define the underlying mechanism of this association.

Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: An in vivo microdialysis study

ObjectiveTo determine whether extracellular concentrations of glutamate and other amino acids are significantly elevated after intracerebral hemorrhage and, if so, the temporal characteristics of these changes. Although the role of excitotoxic amino acids, particularly that of glutamate, has been described in ischemic stroke and head trauma, no information exists regarding their possible contribution to the pathogenesis of neuronal injury in intracerebral hemorrhage. DesignProspective, controlled, laboratory trial. SettingsAnimal research laboratory. SubjectsSixteen anesthetized New Zealand rabbits. InterventionWe introduced intracerebral hemorrhage in each of eight anesthetized New Zealand rabbits by injecting 0.4 mL of autologous blood under arterial pressure into the deep gray matter of the cerebrum. Measurements and Main ResultsExtracellular fluid samples were collected from the perihematoma region and contralateral (right) hemisphere by in vivo microdialysis at 30-min intervals for 6 hrs. Corresponding samples were similarly collected from both hemispheres in each of eight control animals that underwent needle placement without introduction of a hematoma. Concentrations of amino acids (glutamate, aspartate, asparagine, glycine, taurine, and &ggr;-aminobutyric acid) in the samples were measured by use of high-pressure liquid chromatography with fluorescence detection. Glutamate concentrations (mean ± sem) were significantly higher in the hemisphere ipsilateral to the hematoma than in the contralateral hemisphere (92 ± 22 pg/&mgr;L vs. 22 ± 6 pg/&mgr;L) at 30 mins after hematoma creation. A significant increase was observed at 30 mins posthematoma creation in the hemisphere ipsilateral to the hematoma compared with the baseline value. A nonsignificant increase in glutamate concentration persisted in the hemisphere ipsilateral to the hematoma, ranging from 134% to 187% of baseline value between 1 and 5 hrs after hematoma creation. In the hemisphere ipsilateral to the hematoma, a three-fold increase in the concentration of glycine was observed at 30 mins after hematoma creation compared with the baseline level (890 ± 251 pg/&mgr;L vs. 291 ± 73 pg/&mgr;L). There was a significant difference between the hemisphere ipsilateral to the hematoma compared with the ipsilateral (corresponding) hemisphere of the control group at 30 mins posthematoma (890 ± 251 pg/&mgr;L vs. 248 ± 66 pg/&mgr;L). A similar transient increase was observed in taurine and asparagine concentrations at 30 mins after hematoma creation, compared with baseline measurements. Taurine concentrations in the hemisphere ipsilateral to the hematoma were significantly higher than the ipsilateral hemisphere of the control group (622 ± 180 pg/&mgr;L vs. 202 ± 64 pg/&mgr;L) at 30 mins after hematoma creation. ConclusionsThe present study suggests that glutamate and other amino acids accumulate transiently in extracellular fluids in the perihematoma region during the early period of intracerebral hemorrhage. The exact role of these amino acids in the pathogenesis of neuronal injury observed in intracerebral hemorrhage needs to be defined.

Angioplasty of intracranial occlusion resistant to thrombolysis in acute ischemic stroke.

OBJECTIVEThrombolysis has been demonstrated to improve revascularization and outcome in patients with acute ischemic stroke. Many centers now apply thrombolytic therapy locally via intra-arterial infusion. One therapeutic benefit is the ability to cross soft clots with a guidewire and to perform mechanical thrombolysis. In some instances, reopened arteries reocclude as a result of either thrombosis or vasospasm. We report the use of balloon angioplasty during thrombolysis for acute stroke. METHODSFrom June 1995 through June 1999, 49 patients underwent intra-arterial therapy for acute stroke. In this group, nine patients (seven men and two women) were treated with balloon angioplasty after inadequate recanalization with thrombolytic infusion. The mean age of these patients was 67.9 years. Nine matched control patients who underwent thrombolysis alone without angioplasty were chosen for comparison. RESULTSIn the group of nine patients who had angioplasty, the mean National Institutes of Health Stroke Scale score at presentation was 21.8 ± 5.4. Four patients had residual distal occlusion after angioplasty, and one patient had a hemorrhagic conversion. Of the five patients in which recanalization was successful, none had reocclusion of the balloon-dilated vessel. The mean score at 30 days for the five survivors was 12.6 ± 14.9, for an improvement of 7.0 ± 14.2. Among the nine control patients, the mean score at presentation was 20.3 ± 5.2; the mean score at 30 days for the five survivors was 19.4 ± 7.7, for an improvement of 4.2 ± 7.8. CONCLUSIONIn our experience, balloon angioplasty is a safe, effective adjuvant therapy in patients who are resistant to intra-arterial thrombolysis. The use of balloon angioplasty may prevent reocclusion in a stenotic artery and permit distal infusion of thrombolytic agents.