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Background and Purpose: Interventional Management of Stroke (IMS) III is a randomized, parallel arm trial comparing the approach of intravenous tissue-type plasminogen activator followed by endovascular treatment with intravenous tissue-type plasminogen activator alone in patients with acute ischemic stroke presenting <3 hours of symptom onset. The trial intended to enroll 900 subjects to ensure adequate statistical power to detect an absolute 10% difference in the percentage of subjects with good outcome, defined as modified Rankin Scale score of 0 to 2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the National Institute of Neurological Disorders and Stroke based on the prespecified criterion for futility using conditional power<20%., Methods: Conditional power was defined as the likelihood of finding statistical significance at the end of the study, given the accumulated data to date and with the assumption that a minimum hypothesized difference of 10% truly exists between the 2 groups. The evolution of study data leading to futility determination is described, including the interaction between the unblinded study statisticians and the Data and Safety Monitoring Board in the complex deliberation of analysis results., Results: The futility boundary was crossed at the trial's fourth interim analysis. At this point, based on the conditional power criteria, the Data and Safety Monitoring Board recommended termination of the trial., Conclusions: Even in spite of prespecified interim analysis boundaries, interim looks at data pose challenges in interpretation and decision making, underscoring the importance of objective stopping criteria., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick brain sections can accurately identify early ischemia in the entire monkey brain. Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain. Comparison of adjacent thick and thin sections in a rat brain indicated complete correspondence between ischemic regions (100.4mm(3)+/-1.2%, n=7, p=0.44). Thick sections in monkey brain possessed the increased structural stability necessary for the extensive MAP2 immunostaining procedure permitting quantification of the ischemic region as a percent of total monkey brain, giving infarct volumes of 11.4, 16.3, and 19.0% of total brain. Stacked 2D images of the intact thick brain tissue sections provided a 3D representation for comparison to MRI images. The infarct volume of 16.1cm(3) from the MAP2 sections registered with MRI images agreed well with the volume calculated directly from the stained sections of 16.6 cm(3). Thick brain tissue section MAP2 immunostaining provides a new method for determining infarct volume over the entire brain at early time points in a non-human primate model of ischemic stroke.

Purpose: To demonstrate the use of sodium MRI for measuring the time course of tissue sodium concentration (TSC) in a nonhuman primate model of reversible focal brain ischemia., Materials and Methods: Reversible endovascular focal brain ischemia was induced in nonhuman primates (n = 4), and sodium MRI was performed on a 3 Tesla scanner for monitoring changes in TSC during both the middle cerebral artery (MCA) occlusion and MCA reperfusion portions of the experiment., Results: The TSC increased linearly in the ischemic tissue during MCA occlusion (ranging from a mean TSC increase of 5.44%/h to 7.15%/h across the four subjects), and then there was a statistically significant change from a positive TSC slope during MCA occlusion to a TSC slope after MCA reperfusion that was not statistically different from zero. The linear increase in sodium MRI during brain ischemia was used to estimate the stroke onset time to within 0.45 h in each of the four subjects (with a maximum 95% confidence interval of +/- 1.147 h)., Conclusion: The data indicate that sodium MRI increases linearly during brain ischemia, and that this increase is stopped by tissue reperfusion within 5.4 h after stroke onset., ((c) 2009 Wiley-Liss, Inc.)

Background and Purpose: The aim of acute stroke interventions is to achieve recanalization of the target occluded artery. We sought to determine whether pretreatment cortical cerebral blood flow (CBF) was associated with vessel recanalization in patients undergoing intra-arterial therapy., Methods: This is a retrospective analysis of patients who underwent a quantitative xenon CT blood flow study and were noted to have a documented M1 middle cerebral artery (MCA) or carotid terminus occlusion less than 6 hours from symptom onset between January 1997 and April 2001. Twenty-three patients who underwent intra-arterial thrombolysis were included in the analysis. Univariate and multivariate analyses were performed to determine whether pretherapy CBF was correlated to the likelihood of recanalization., Results: A total of 23 patients were studied in this analysis with a median age of 69 (range 32-81) and median National Institutes of Health Stroke Score of 19 (range, 8-22). Twelve patients (52%) underwent combined intravenous/intra-arterial therapy, and 11 patients (48%) were treated with intra-arterial thrombolytics alone. Successful vessel recanalization (Thrombolysis in Myocardial Infarction classification 2 or 3 flow) occurred in 13 patients (57%). The only variable associated with recanalization in multivariate modeling was mean ipsilateral MCA CBF (odds ratio, 1.25; 95% confidence interval, 1.01-1.54; P = .035). A receiver operating characteristic curve was generated, and a mean ipsilateral MCA CBF threshold of 18 mL/100 g/min was found to be the threshold for successful recanalization., Conclusions: Our study suggests that patients with higher mean ipsilateral MCA CBF are more likely to recanalize. The threshold for successful revascularization may be 18 mL/100 g/min. Further study is required to determine whether pretreatment CBF is related to recanalization success.

Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18-min data acquisition times were demonstrated in vivo in a nonhuman primate model of focal brain ischemia. Focal brain ischemia was induced in four animals using embolization coils to occlude the posterior cerebral artery, and a balloon catheter to occlude the middle cerebral artery. A statistically significant increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic hemisphere relative to the contralateral hemisphere was seen at all time points in all four animals. This increased TQ sodium MRI signal intensity was demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI hyperintensity corresponded to the anatomical location of the ischemic cortex, as indicated by the registration of the TQ imaging data with anatomical proton MRI data. The results demonstrate that early after the onset of ischemia, there was an increase in the TQ signal intensity in the ischemic hemisphere, and a negligible change in the single quantum (SQ) signal intensity.

Background and Purpose: We present the results of endovascular photoacoustic recanalization (EPAR) treatment for acute ischemic stroke from the Safety and Performance Study at 6 centers in Europe and North America. The objectives of mechanical thrombolysis are rapid vessel recanalization and minimal use of chemical thrombolysis., Methods: This study was a prospective, nonrandomized study. The National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score were recorded before treatment. The presence of recanalization was assessed by angiography. To measure outcome, follow-up examinations were performed at 24 hours, 7 days, and 30 days after stroke onset., Results: Thirty-four patients (median NIHSS 19) were enrolled. Ten patients had internal carotid artery occlusion, 12 patients had middle cerebral artery occlusion, 11 patients had vertebrobasilar occlusion, and 1 patient had posterior cerebral artery occlusion. The overall recanalization rate was 41.1% (14/34). Complete EPAR treatment was possible in 18 patients (median NIHSS 18), with vessel recanalization in 11 patients (61.1%) after EPAR. The average lasing time was 9.65 minutes. Incomplete EPAR treatment (16/34, median NIHSS 19) was defined as intention to treat with EPAR and that the EPAR microcatheter entered the patient. Additional treatment with intraarterial application of rTPA occurred in 13 patients. An adverse event associated with use of the device occurred in 1 patient. Symptomatic hemorrhages occurred in 2 patients (5.9%). The mortality rate was 38.2%., Conclusions: This study demonstrates the safety and technical feasibility of EPAR. This new technique may provide another treatment option in the therapeutic armamentarium for patients with acute ischemic stroke.

We have developed a model of reversible cerebral ischemia in a high-level nonhuman primate. By using endovascular techniques, the posterior cerebral artery is permanently occluded with coils, and the ipsilateral middle cerebral artery is temporarily occluded with a balloon. The balloon can be deflated and/or removed to reestablish flow at precise time intervals. Functional imaging of the brain can be performed during occlusion and reperfusion, since the balloon can be deflated or removed in a scanner.

Background and Purpose: Therapeutic internal carotid artery (ICA) occlusion for symptomatic intracavernous artery aneurysms can result in ischemic infarction despite normal clinical balloon test occlusion (BTO). We evaluated outcomes in patients with symptomatic cavernous sinus aneurysms in whom clinical BTO was normal, who underwent carotid occlusion with selective bypass surgery guided by physiologic BTO using quantitative cerebral blood flow (CBF) analysis by means of stable xenon-enhanced CT., Methods: After a normal clinical BTO, 26 consecutive patients with symptomatic cavernous sinus aneurysms underwent a baseline xenon-enhanced CT CBF analysis followed by a second CBF analysis, during which repeat BTO was performed. Patients with a decrease in cortical CBF to below 30 mL/100 g/min were considered moderate risk and those with greater than 30 mL/100 g/min were low risk for developing postocclusion ischemic infarction. Moderate-risk patients underwent cerebral revascularization followed by proximal carotid occlusion. Low-risk patients underwent carotid occlusion alone. Patients were clinically followed up for at least 3 months after carotid occlusion. All patients underwent head CT at least 1 month after carotid occlusion., Results: Eight patients were moderate risk and 18 low risk. Mean follow-up was 15.3 months. Mean CT follow-up was 10.2 months. No low-risk patient developed a postocclusion ischemic deficit by examination or infarct by CT. One patient in the moderate-risk group developed right hemiparesis and a left posterior middle cerebral artery infarction by CT 2 months after carotid occlusion., Conclusion: In this series, BTO combined with quantitative CBF analysis was a safe and reliable technique for identification of patients at risk for ischemic infarction after carotid occlusion, despite a normal clinical BTO.

Two middle-aged patients presented with rapidly progressive dementia and ataxia, nonspecific electroencephalography findings, and negative cerebrospinal fluid (CSF) protein 14-3-3. Both patients underwent brain magnetic resonance imaging (MRI) scans that demonstrated abnormalities on diffusion-weighted imaging (DWI) sequences, and both were later confirmed to have Creutzfeldt-Jakob disease. (CJD) by tissue examination. Because a recent position paper from the American Academy of Neurology characterized CSF protein 14-3-3 as a gold standard for clinically diagnosing CJD, the authors reviewed studies of CJD in which DWI-MRI imaging and CSF protein 14-3-3 studies were both performed. Among 19 reported cases of CJD with DWI-MRI lesions, CSF protein 14-3-3 was negative in 6 cases and positive in 2 others. The authors' findings suggest that multifocal cortical and subcortical hyperintensities confined to gray matter regions in DWI-MRI may be a more useful noninvasive diagnostic marker for CJD than CSF protein 14-3-3. These observations provide a compelling rationale for a prospective comparative study.

Objective and Importance: We describe a case of an unruptured anterior communicating aneurysm that was treated successfully with Guglielmi detachable coils, which subsequently ruptured 23 months after initial therapy. This report discusses only the second published case of an unruptured lesion that was well embolized (>95% occlusion) and stable at 6-month angiographic follow-up that ruptured in a delayed fashion almost 2 years after the primary procedure., Clinical Presentation: An 80-year-old man presented in Hunt and Hess Grade IV as a result of a ruptured anterior communicating artery aneurysm. The patient had undergone endovascular therapy 23 months earlier with documented nearly complete (1-mm residual neck) occlusion at 0 and 6 months., Intervention: The patient underwent diagnostic catheter angiography at the time of admission, which revealed a 10-mm aneurysm adjacent to the previously embolized lesion. No further therapy was administered, and the patient died within 24 hours as a result of ictus. The request for an autopsy was denied., Conclusion: Aneurysm rupture after Guglielmi detachable coil embolization is a rare event. Most cases involve previously ruptured lesions. To the best of our knowledge, only one previous case of delayed rupture of an unruptured aneurysm that was managed endovascularly has been published in the English-language literature. This second case points to the need for vigilance in the follow-up of patients with coiled lesions.

Background and Purpose: Only a small percentage of acute-stroke patients receive thrombolytic therapy because of time constraints and the risks associated with thrombolytic therapy. We sought to determine whether xenon-enhanced CT (XeCT) cerebral blood flow (CBF) and/or CT angiography (CTA) in conjunction with CT can distinguish subgroups of acute ischemic stroke victims and thereby better predict the subgroups most likely to benefit and not to benefit from thrombolytic therapy., Methods: An analysis of 51 patients who had a CT, CTA, and stable XeCT CBF examination within 24 hours of stroke symptom onset was conducted. These initial radiographic studies and National Institutes of Health Stroke Scale score on admission were assessed to determine whether they could predict new infarction on follow-up CT or discharge disposition by use of the Fisher exact test to determine statistical significance., Results: Patients with no infarction on initial CT and normal XeCT CBF had significantly fewer new infarctions and were discharged home more often than those with compromised CBF. The same held true for patients with an open internal carotid artery and middle cerebral artery by CTA and normal CT compared with those with an occluded internal carotid artery and/or middle cerebral artery by CTA. Either was superior to CT and the National Institutes of Health Stroke Scale in prediction of outcome. Both enable the selection of a group of patients not identifiable by CT alone that would do well without being exposed to the risks of thrombolytic therapy. This study included too few patients to statistically assess the role of combining CTA and XeCT CBF information., Conclusions: The combination of CT, CTA, and Xe/CT CBF does define potentially significant subgroups of patients. The utility of this classification is supported by the observation that CTA and XeCT CBF are superior to CT alone in predicting infarction on follow-up CT and clinical outcome. This information may be useful in selecting patients for acute-stroke treatment.

Objective: In this study, the incidence, etiologies, and management with respect to clinical outcome of patients with iatrogenic aneurysmal rupture during attempted coil embolization of intracranial aneurysms are reviewed., Methods: A retrospective analysis was conducted of 274 patients with intracranial aneurysms treated with Guglielmi detachable coils over a 6-year period from 1994 to 2000. Patient medical records were examined for demographic data, aneurysm location, the number of coils deployed preceding and after aneurysmal rupture, the etiology of the rupture, and the clinical status on admission and at the time of discharge., Results: Of 274 patients with intracranial aneurysms treated with coil embolization, six (2%) had an intraprocedural rupture. Of these six, two were women and four were men. The mean age was 67 years (range, 52-85 yr). Mean follow-up time was 8 months (range, 0-25 mo). Aneurysmal rupture resulted from detachment of the last coil in three patients, detachment of the third coil (of four) in one patient, and insertion of the first coil in another patient. In one patient, the aneurysmal rupture was a result of catheter advancement before detachment of the last coil. The Glasgow Outcome Scale score at last follow-up examination was 1 in two patients, 2 in two patients, and 5 in two patients., Conclusion: The rate of rupture of aneurysms during coil embolization is approximately 2 to 4%. The clinical outcome may be related to the timing of the rupture and the number of coils placed before rupture. If extravasation of contrast agent is seen, which suggests intraprocedural rupture, further coil deposition should be attempted if safely possible.

Objective: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis., Subjects and Methods: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations., Results: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected., Conclusions: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.

Stereotactic radiosurgery using the 201 Cobalt-60 source Gamma Knife has been an effective method for obliterating selected cerebral arteriovenous malformations (AVMs). For more than 20,000 patients worldwide, angiography under stereotactic conditions has been the main imaging modality for defining and targeting the AVM nidus. The role of angulation of the X-ray tube for angiographic localization of the AVM during stereotactic Gamma Knife radiosurgery was studied with a phantom. Using current dose-planning software, tube angulation facilitated target visualization, improved three-dimensional dose planning, and has been consistent with the increased probability of complete nidus obliteration., (Copyright 2001 Wiley-Liss, Inc.)

Objective: The purpose of this study was to verify transhemispheric diaschisis in the early hours after an ischemic event., Methods: XeCT cerebral blood flow (CBF) studies within 8 h of stroke were studied in 23 patients. Mean CBF was evaluated in the ischemic area, contralateral hemisphere and ipsilateral cerebellum., Results: A severe CBF reduction was found in the ischemic area (mean 9 +/- 3 ml/100 g/min). The mean CBF in the unaffected hemisphere (33 +/- 10 ml/100 g/min) was 35% less compared to the normal mean value. CBF was decreased in the cerebellum ipsilateral to the stroke (mean 31 +/- 12 ml/100 g/min) suggesting a blood flow depression of the whole brain., Conclusions: During the initial hours of cerebral ischemia, the asymptomatic hemisphere demonstrated CBF depression that was part of the global flow reduction., (Copyright 2000 S. Karger AG, Basel.)

To identify potential risk factors for and clinical manifestations of ventricular and sulcal enlargement on cranial magnetic resonance imaging (MRI), 3,301 community-dwelling people 65 years or older without a history of stroke or transient ischemic attack underwent extensive standardized evaluations and MRI. In the multivariate model, increased age and white matter grade on MRI were the dominant risk factors for ventricular and sulcal grade. For ventricular grade, other than race, for which non-Blacks had higher grades, models for men and women shared no other factors. For sulcal grades, models for men and women shared variables reflecting cigarette smoking and diabetes. Clinical features were correlated more strongly with ventricular than sulcal grade and more strongly for women than men. Significant age-adjusted correlations between ventricular grade and the Digit-Symbol Substitution Test were found for men and women. Prospective studies will be needed to extend findings of this cross-sectional analysis.

Recanalization of acutely occluded arteries in the carotid territory, particularly the middle cerebral artery, by intra-arterial delivery of thrombolytic drugs, has advanced dramatically over the last decade. Randomized prospective studies have begun to show the potential impact of this form of intervention. Still, patient selection, therapeutic window, critical care support, and experience of the management team are clearly the determining features for the success of intra-arterial thrombolysis. The use of thrombolytic agents currently available, and research involving the next generation of these agents, open a field that shows promise for the improvement of outcomes of patients whose typical prognosis is poor.

Objective: To determine whether recanalization, coma at presentation, or clot location in the basilar artery influences the relative mortality risk after intra-arterial thrombolytic therapy for acute vertebrobasilar artery occlusions., Methods: Studies were identified using the MEDLINE database for January 1987 to November 1997. Series were included if they involved 10 or more patients with basilar or vertebrobasilar artery occlusions, used urokinase and/or recombinant tissue plasminogen activator, and were written in English. A fixed-effect meta-analysis approach was used to estimate the risk of death with the aforementioned risk factors. Each study was weighted according to sample size. Relative risks were calculated with 95% confidence intervals., Results: As calculated from peer-reviewed published data, the relative mortality risk for patients for whom recanalization was attempted but not achieved was 2.34 (95% confidence interval, 1.48-3.71; n = 126). Coma at presentation was associated with a relative mortality risk of 1.95 (95% confidence interval, 1.26-2.99; n = 145). Clot locations in the distal one-third of the basilar artery were shown to favor survival, compared with clots located in the proximal and/or middle portions of the basilar artery (relative risk, 0.52; 95% confidence interval, 0.31-0.86; n = 126)., Conclusion: The combined data suggest that coma at presentation has an independent and adverse effect on survival rates. Complete recanalization, distal clot location, and responsiveness at the time of presentation are statistically significant factors for increased patient survival rates.

A rheolytic thrombectomy catheter was used to remove thrombus without thrombolytics from the sigmoid and transverse sinuses of a 34-year-old woman. Using small, high-flow fluid jets and Venturi-effect suction, this catheter allowed mechanical removal of thrombus. This technique may obviate the need for thrombolytic agents and the risks associated with their use.

Computed tomography can provide anatomic and functional information about the brain. The conventional CT of the brain can be coupled with a cerebral blood flow examination using the stable xenon CT technique and with a CT angiography. Distinct subgroups of patients based on variations in cerebral blood flow and vascular pathology have been demonstrated. The addition of the functional information has become extremely important in triaging and determining the appropriate intervention in the patient with an acute neurological deficit.

Acute cerebral ischemia resulting from the occlusion of a large or medium size intracranial artery is a known complication of antiphospholipid antibody syndrome (AAS). Usually these patients are treated by low dose aspirin and anticoagulants to prevent a stroke. We are reporting a case of acute stroke in a patient with AAS in whom combined intravenous and intraarterial thrombolytics were used emergently with an excellent outcome. A 32-year-old woman presented with a left hemispheric stroke of 2.5 hours duration. A computed tomography (CT) study of the brain was normal. The patient was treated with intravenous tissue plasminogen activator but remained aphasic and hemiplegic. Subsequently, the patient had a stable xenon CT cerebral blood flow study demonstrating low flow in the left middle cerebral artery (MCA) territory and an angiogram, which demonstrated occlusion of the left MCA. The patient was then treated with intraarterial urokinase with a rapid and marked improvement in her neurological deficit. The case suggests that stroke patients can be treated safely and effectively with combined thrombolytics.

Background: Cerebral venous thrombosis is a clinical entity which is readily diagnosed with the advent of modern imaging techniques. Anticoagulation is now a standard therapy, but more recent treatment strategies have included endovascular thrombolysis. While the endpoint of this intervention both clinically and radiographically has not been defined, noninvasive monitoring techniques may add further objective measures of treatment response., Clinical Presentation: We present a patient with a four day history of worsening headache and papilledema on exam. Superior sagittal, straight, and bilateral transverse sinus thromboses were identified on computed tomography and angiography., Intervention: Emergent endovascular thrombolysis by a transvenous approach re-established venous patency and resulted in immediate resolution of the patient's symptoms. Cerebral oximetry by near-infrared spectroscopy was utilized during the procedure, and changes in chromophore concentrations correlated directly with angiographic and clinical resolution of the thrombosis., Conclusion: Near-infrared spectroscopy can provide continuous feedback during thrombolytic therapy in cerebral venous thrombosis and may help define endpoints of such intervention.

Objective and Importance: The purpose of this report is to describe the placement and use of a cervical subarachnoid catheter for cerebrospinal fluid diversion. This technique provides an important alternative drainage system for patients whose clinical situations preclude lumbar spinal fluid diversion., Clinical Presentation: Two patients were involved in accidents that resulted in traumatic dural tears. Both patients required thoracolumbar spinal reconstruction with instrumentation. Cerebrospinal fistulae developed, which were refractory to surgical reexploration., Technique: A commercially available catheter was successfully placed in the cervical subarachnoid space under fluoroscopic guidance using a C1-C2 approach in both patients. Spinal fluid drainage was maintained for 5 days via this route, and this proved effective in resolving the cerebrospinal fluid fistula. No complications were observed with the placement or maintenance of the catheter., Conclusion: Cervical spinal fluid drainage is a feasible alternative for patients in whom lumbar access cannot be obtained or is contraindicated.

Background: Intra-arterial papaverine (IAP) has been described as a treatment for cerebral vasospasm refractory to standard therapy., Methods: We report a series of 15 consecutive patients with aneurysmal subarachnoid hemorrhage in which IAP was employed for the treatment of symptomatic vasospasm. All patients exhibited delayed ischemic neurologic deficits, focal cerebral hypoperfusion on stable xenon-enhanced computerized tomography cerebral blood flow studies, and angiographically defined arterial narrowing. Papaverine was infused into 32 arteries on 23 occasions. Six patients required multiple treatments between 1 and 8 days apart. In five instances, IAP was combined with angioplasty., Results: Angiographically defined vasospasm was at least partially reversed immediately following treatment on 18 of 23 occasions. The associated clinical improvement was major on 6 occasions, and either minor or none on 17. Post-treatment cerebral blood flow was assessed on 13 occasions and showed improvement in previously ischemic areas on six occasions and no improvement on seven. Complications were encountered on four occasions. Systemic hypotension and transient brain-stem depression were seen with vertebral artery infusions; a generalized seizure and paradoxical aggravation of vasospasm resulting in hemispheric infarction occurred with internal carotid artery infusions., Conclusions: Intra-arterial papaverine resulted in reversal of arterial narrowing in the majority of cases (78%). However, this angiographic improvement was associated with cerebral blood flow augmentation in only 46% of cases analyzed, and major clinical improvement in 26%.

Objective: To identify risk factors for and functional consequences of lacunar infarct in elderly people., Methods: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings., Results: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts., Conclusions: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.

Object: The purpose of this study was to determine whether cerebral blood flow (CBF) measurements in acute stroke could be correlated with the subsequent development of cerebral edema and life-threatening brain herniation., Methods: Twenty patients with aggressively managed acute middle cerebral artery (MCA) territory strokes who underwent xenon-enhanced computerized tomography (Xe-CT) CBF scanning within 6 hours of onset of symptoms were retrospectively reviewed. The relationship among CBF and follow-up CT evidence of edema and clinical evidence of brain herniation during the 36 to 96 hours following stroke onset was analyzed. Initial CT scans displayed abnormal findings in 11 patients (55%), whereas the Xe-CT CBF scans showed abnormal findings in all patients (100%). The mean CBF in the symptomatic MCA territory was 10.4 ml/100 g/minute in patients who developed severe edema compared with 19 ml/100 g/minute in patients who developed mild edema (p < 0.05). The mean CBF in the symptomatic MCA territory was 8.6 ml/100 g/minute in patients who developed clinical brain herniation compared with 18 ml/100 g/minute in those who did not (p < 0.01). The mean CBF in the symptomatic MCA territory that was 15 ml/100 g/minute or lower was significantly associated with the development of severe edema and herniation (p < 0.05)., Conclusions: Within 6 hours of acute MCA territory stroke, Xe-CT CBF measurements can be used to predict the subsequent development of severe edema and progression to clinical life-threatening brain herniation. Early knowledge of the anatomical and clinical sequelae of stroke in the acute phase may aid in the triage of such patients and alert physicians to the potential need for more aggressive medical or neurosurgical intervention.

Background: Isolated thrombosis of the deep cerebral venous system is very rare and is associated with a poor prognosis. Antithrombin III (AT III) deficiency is a disorder of hypercoagulability associated with deep venous thrombosis and recurrent pulmonary emboli. We report a case of an 18-year-old man who presented with spontaneous thrombosis of the deep cerebral veins and straight dural sinus as the initial presentation of a previously undiagnosed AT III deficiency., Methods: The patient was managed using direct endovascular infusion of the fibrinolytic agent urokinase followed by intravenous heparin., Results: The technique was successful in establishing patency of the deep cerebral venous system. The patient experienced a good clinical outcome., Conclusions: Direct endovascular thrombolysis is a potentially effective management strategy for isolated thrombosis of the deep cerebral venous system.

In this study the authors have examined the effects of transluminal angioplasty on cerebral blood flow (CBF) in the management of intractable vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Fourteen consecutively enrolled patients underwent attempted angioplasty with or without intraarterial infusion of papaverine. Twelve patients underwent pre- and postangioplasty xenon-enhanced computerized tomography (Xe-CT) scanning to measure regional CBF in 55 to 65 regions of interest (ROIs) per patient. Angioplasty was possible in 13 (93%) of 14 patients, with angiographically demonstrated improvement in all 13. Twelve (92%) of the 13 patients were neurologically improved following angioplasty; seven (58%) of the 12 patients who improved had a complete reversal of all delayed ischemic deficits. Angioplasty significantly decreased the mean number of ROIs at risk (11.4 ROIs pre- and 0.9 ROIs postangioplasty) (p < 0.00005, t-test). All patients had a reduction in the number of ROIs at risk after angioplasty; six (50%) of 12 no longer had any ROIs remaining at risk after angioplasty. Angioplasty significantly increased the mean CBF within at-risk ROIs (13 ml/100 g/minute pre- and 44 ml/100 g/minute postangioplasty) (p < 0.00005, t-test). All patients experienced an improvement in mean CBF in at-risk ROIs after angioplasty, with the mean CBF improving to above 20 ml/100 g/minute in all cases. No differences in the degree of improvement were found in patients who received intraarterial papaverine compared with those who did not. In the majority of patients with refractory vasospasm following SAH, angioplasty effectively dilated spastic arteries, reversed delayed neurological deficits, and significantly improved CBF in areas of brain at risk of infarction.

The authors examined the relationship between psychiatric symptoms and the presence of of MR deep white matter lesions (DWMLs) in 28 probable Alzheimer's disease (AD) patients with mild to moderate dementia. The difference in frequency of psychiatric symptoms between patients with and without DWMLs was not statistically significant. However, MR global scores of severity correlated with the presence of ideational disturbances (such as low self-esteem and suicidal ideation). Analysis of specific cerebral regions indicated that the highest correlation occurred in the frontal white matter. Thus, DWMLs are correlated with specific symptoms of depression in AD. Whether DWMLs are etiologically related to these symptoms remains to be determined.

We present two cases of acute thrombosis of the internal cerebral veins, vein of Galen, and straight sinus without sagittal sinus involvement. Both patients had hydrocephalus and severe edema of the basal ganglia and thalami, one with hemorrhagic infarction of the thalamus. Because both patients rapidly deteriorated to a comatose state, endovascular thrombolysis was performed with urokinase infusion of the deep venous structures. Thrombolysis was continued until a patent channel with brisk flow in the venous structures was achieved. Both patients survived with minimal neurologic deficits.

Purpose: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex., Materials and Methods: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex., Results: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race., Conclusion: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

Purpose: To determine the prevalence of clinically serious findings unrelated to stroke on cranial magnetic resonance (MR) images in a population of community-dwelling elderly people., Materials and Methods: Neuroradiologists reviewed MR images of 3,672 people aged 65 years and older who were enrolled in a longitudinal, population-based study of cardiovascular and cerebrovascular disease. The neuroradiologists alerted MR imaging field centers about potentially serious abnormalities. Clinical information was obtained from clinical examinations performed before MR imaging, hospital discharge summaries, and the field centers at which MR imaging was performed., Results: On 3,672 image sets, 64 (1.74%) clinically serious abnormalities were found. Among the presumptive diagnoses were 19 meningiomas (0.52%), six pituitary adenomas (0.16%), five cavernous malformations (0.14%), eight vascular stenoses (0.22%), four aneurysms (0.11%), two intraventricular masses (0.05%), two subdural fluid collections (0.05%), and two other tumors (0.05%). Only nine participants with these abnormalities required surgery. All but one of the meningiomas were in women, and the prevalence of the tumor decreased with increasing age., Conclusion: Physicians should be alert to the possible presence of clinically serious conditions in otherwise asymptomatic elderly individuals.

Purpose: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images., Materials and Methods: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images., Results: Infarctlike lesions were depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1% (86 of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of lesions, respectively., Conclusion: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.

We evaluated the relationship between periventricular white matter lesions (PWMLs) and EEG abnormalities in probable Alzheimer's disease (AD). We visually analyzed the EEG of 27 probable AD patients with mild to moderate degree of cognitive impairment participating in a longitudinal study of dementia. Patients had both CT and MRI scans performed at baseline examination, which also included an EEG. PWMLs were rated in CT and MRI films using a semiquantitative method. The EEGs were classified according to the Mayo Clinic Classification System. Abnormal EEGs correlated with PWMLs rating scores were detected on CT, but not on MRI. These data suggest that the presence of PWMLs contribute to the abnormal EEGs observed in AD patients, and that white matter abnormalities in CT correlate better with both the clinical findings and EEG than does the more sensitive but less specific MRI.

Purpose: To review patients who have presented with acute strokes from a middle cerebral artery occlusion in whom in addition to the middle cerebral artery thromboembolus, an internal carotid artery occlusion has been present, and in whom angioplasty of these totally occluded internal carotid arteries has bee n successful., Methods: We reviewed retrospectively our experience in treating a cute stroke patients with intracranial, intraarterial urokinase. Six of 27 patients had internal carotid artery occlusions in addition to middle cerebral artery occlusions. Two patients presented with spontaneous carotid dissections for wh ich no further intervention from the ipsilateral internal carotid artery was attempted. In the remaining four internal carotid artery occlusions secondary to atherosclerotic disease, standard guide wires and catheters were negotiated across the level of the internal carotid artery occlusion, which expedited intracranial catheterization for thrombolysis. Subsequently, angioplasty of the internal carotid artery was performed., Results: All four occluded internal carotid arteries could be traversed. No new neurologic deficits occurred. No vascular injuries occurred. No deaths occurred. Four- to 6-month follow-up showed all four internal carotid arteries remained patent., Conclusion: In acute occlusions of the internal carotid artery from atherosclerosis, the occluded vessel can sometimes be recanalized with low morbidity. In addition, endovascular access to the intracranial circulation can be expedited by using the recanalized internal carotid artery.

Objective: To examine the clinical consequences of periventricular white-matter lesions on computed tomography (CT) and magnetic resonance imaging (MRI) scans in probable Alzheimer's disease., Design: Case series, 12-month follow-up., Setting: Multidisciplinary behavioral neurology research clinic., Patients: We longitudinally evaluated the clinical characteristics of 27 patients with probable AD for whom both CT and MRI scans had been performed at baseline., Interventions: None., Main Outcome Measure: The presence of abnormal neurological signs was examined at baseline and at a 12-month examination., Results: Periventricular white-matter lesions were observed with CT in 12 patients (44%) and with MRI in 21 patients (78%). Computed tomography did not detect lesions of 1 to 3 mm, as were seen on MRI scans, and CT also did not detect lesions of 4 to 10 mm when they occurred in the deep subcortical white matter and were not part of a greater confluent lesion. There was no relationship between the severity of periventricular white-matter lesions with either neuroimaging method and the presence of abnormal neurological signs. However, there was a greater frequency of periventricular white-matter lesions shown on CT scans than on MRI scans at baseline in patients in whom abnormal neurological signs (eg, abnormal gait, asymmetric deep tendon reflexes, focal motor deficits, abnormal plantar response) developed at 12-month follow-up., Conclusion: Although MRI may be more sensitive in detecting periventricular white-matter lesions, CT is more specific in predicting subsequent symptomatic cerebrovascular disease.

Magnetic resonance angiography is most commonly performed with the three-dimensional (3D) time-of-flight (TOF) technique. As currently practiced, this requires long image acquisition times (5-10 minutes). The authors show that the acquisition time of 3D TOF images can be reduced to less than 1 minute by using a very short TR (< 10 msec). Under normal flow conditions, the major vessels of the circle of Willis were consistently well demonstrated on these fast 3D TOF images. Signal saturation was observed in studies of patients with abnormal blood flow. In those cases, it was demonstrated that serial acquisition of fast 3D TOF data during and after contrast agent administration could be used to overcome the saturation effects. Time-resolved fast 3D TOF imaging during and after contrast agent administration can also provide qualitative assessment of flow and may depict other features that cannot be observed in TOF studies with long imaging times.

Purpose: To describe experience with 500 temporary balloon occlusions of the internal carotid artery, with particular emphasis on the techniques and complications., Methods: Temporary occlusion of the internal carotid artery was accomplished endovascularly using various balloon-catheter combinations. These temporary balloon occlusions were combined, when possible, with cerebral blood flow analysis with stable xenon-enhanced CT., Results: Complications related to this procedure occurred in 16 (3.2%) patients. Eight (1.6%) patients had asymptomatic complications. There were 8 who experienced neurologic changes. Six (1.2%) of these were transient; two (0.4%) were permanent. There were no deaths., Conclusions: Temporary balloon occlusion of the internal carotid artery, believed helpful in identifying patients at risk of stroke during abrupt carotid artery sacrifice, can be performed with an acceptably low complication rate.

This article describes a woman with hemorrhagic telangiectasia, or Osler-Weber-Rendu disease, with recurrent nosebleeds despite prior septal dermoplasty and laser treatments. Telangiectasias were clearly shown at the time of angiography. Embolization of abnormal vessels on both sides resulted in cessation of epistaxis for many months. Bilateral studies are important, even when the epistaxis seems to be unilateral.

Purpose: To evaluate the efficacy of combined particulate embolization and single-stage stereotactic radiosurgery in the treatment of large arteriovenous malformations (AVMs) of the brain., Methods: Twenty-four patients with large brain AVMs (diameter > 3.0 cm; volume > 14 cm3), who had previously undergone particulate embolization and stereotactic radiosurgery, were retrospectively evaluated 2 or more years after radiosurgery., Results: In 12 (50%) of these patients there was complete AVM obliteration, comparing favorably with a 58% obliteration rate in a group of AVMs having a 4- to 10-cm3 volume, treated by radiosurgery alone. Recanalization of embolized, but not radiated, AVM segments was identified in 3 (12%) patients. However, long-term occlusion was demonstrated in the embolized portions of most AVMs subsequently treated by radiosurgery. Complications included 1 (4%) patient with a mild upper extremity paresis after radiosurgery and 2 (8%) patients with transient neurologic deficits after embolization., Conclusion: Combined embolization and stereotactic radiosurgery was more efficacious than radiosurgery alone for large brain AVMs. Recanalization after embolization did occur but was a relatively minor cause of treatment failure.

Purpose: To compare and contrast the physical characteristics of balloon catheter systems used for temporary cerebrovascular occlusion., Method: Commonly used temporary occlusion systems were evaluated to determine: (a) balloon compliance; (b) balloon diameter versus volume; (c) balloon pressure versus volume; (d) simulated vessel wall pressure versus volume; (e) balloon failure volume; and (f) balloon deflation rate. Observations were made concerning construction differences that affect the potential safety of a balloon system or the way it is used., Results: The nondetachable balloon system demonstrating the best compliance characteristics and lowest radial pressure generation was the nondetachable silicone balloon (Interventional Therapeutics Corporation, San Francisco, Calif). Diameter versus volume curves for all systems reveal an initial nonlinear expansion that could contribute to vessel overexpansion during occlusion., Conclusion: Balloon systems vary in construction, method of introduction, and compliance. Knowledge of these characteristics, as well as of nonlinear balloon expansion, should aid balloon selection and appropriate use while helping to minimize complications.

Purpose: A preliminary evaluation of the efficacy and safety of treating patients with acute stroke with intraarterial urokinase infusions was performed., Patients and Methods: Twelve patients with acute stroke were treated within 8 hours of symptom onset (average, 5 hours). Thrombolysis was performed within the middle cerebral (n = 10), internal carotid (n = 1), and basilar (n = 1) arteries. Urokinase (160,000-500,000 IU) was infused through microcatheters placed into or adjacent to the thrombi., Results: Thrombolysis was angiographically successful in nine patients (75%), all of whom had long-term neurologic improvement. No or minimal neurologic deficits were present in six patients (50%). Thrombolysis failed in three patients (25%); one patient died and two developed severe permanent neurologic deficits. No hemorrhagic complications occurred., Conclusion: Preliminary results suggest that intraarterial urokinase infusion may be effective and safe for treating patients with acute stroke. Potentially devastating neurologic damage was averted or lessened in nine patients (75%). No additional neurologic damage was caused by intervention in the remaining three patients (25%).