Chronic Kidney Disease as Risk Factor for Enlarged Perivascular Spaces in Patients With Stroke and Relation to Racial Group.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) are considered subclinical markers of small vessel disease, associated with increased risk of stroke and dementia. Increasing evidence links chronic kidney disease (CKD) to small vessel disease. We explored the relationship between CKD and EPVS burden and the influence of racial group in this relation. METHODS: Consecutive patients with stroke who underwent brain magnetic resonance imaging were included (n=894). Racial group was categorized as White, Black, or other (other racial groups). CKD was defined by glomerular filtration rate <60 mL/minute per 1.73 m2 for >3 months. EPVS were rated following a standardized method, dichotomized for analyses (mild [<20] versus severe [≥20]), and stratified by brain region (basal ganglia and centrum semiovale). RESULTS: In multivariable-adjusted analysis, the association of CKD with severe EPVS varied across racial groups. Comparing patients with and without CKD within racial groups, we found that Whites with CKD had higher odds of severe centrum semiovale EPVS (odds ratio [OR], 2.41 [95% CI, 0.98-5.88]). Among patients with CKD, Black patients had higher odds of severe EPVS in the basal ganglia and centrum semiovale compared with Whites (OR, 1.93 [95% CI, 1.18-3.16] and OR, 1.90 [95% CI, 1.16-3.11], respectively) and other racial groups (OR, 2.03 [95% CI, 1.23-3.36] and OR, 2.02 [95% CI, 1.22-3.34], respectively). CONCLUSIONS: CKD was more prevalent in our sample of patients with stroke with severe EPVS in the centrum semiovale. The relation differed when stratified by racial group and brain topography. Further studies are needed to confirm that CKD may relate differently to subclinical measures of small vessel disease according to race.

High Prevalence of Cerebral Microbleeds in Inner City Young Stroke Patients.

BACKGROUND: Data on cerebral microbleeds (CMBs) in younger populations are lacking, particularly in young stroke patients. We sought to characterize CMBs in an inner city cohort of young adults with stroke. METHODS: CMB presence, count, and topography were assessed on magnetic resonance imaging (MRI) scans of 104 young stroke patients (≤49 years) presenting to Boston Medical Center between January 2006 and February 2010. Subsequent MRIs were assessed for the occurrence of new microbleeds in 29 patients. We performed cross-sectional analysis comparing baseline characteristics between patients with and without microbleeds, and between predefined microbleed burden and topography categories. We performed additional analysis to assess the determinants of new microbleeds on repeat MRI. RESULTS: Microbleeds were present in 17% of the sample. Male sex (odds ratio [OR] 5.7, 95% confidence interval [CI] 1.0-32.6, P = .049), hypertension (OR 6.2, 95% CI 1.2-32, P = .03), moderate-severe white matter hyperintensities on MRI (OR 5.8, 95% CI 1.6-29.0, P = .01), and intracerebral hemorrhage (ICH; OR 5.0, 95% CI 1.2-20, P = .03) were over-represented in patients with microbleeds. Patients who developed new microbleeds on repeat MRI (14%) had higher microbleed counts on baseline MRI (50% versus 0% ≥ 3 CMBs, P = .02), history of illicit drug use (75% versus 24%, P = .08), positive serum toxicology for cocaine (67% versus 13%, P = .11), ICH as their presenting stroke subtype (50% versus 8%, P = .08), and over-representation of moderate-severe white matter hyperintensities (75% versus 20%, P = .05). CONCLUSIONS: Results from this inner city cohort suggest that microbleeds are prevalent in young stroke patients and are largely associated with modifiable risk factors.

Larger A1/M1 diameter ratio predicts embolic anterior cerebral artery territorial stroke.

BACKGROUND AND PURPOSE: In contrast to middle cerebral artery territory strokes, anterior cerebral artery strokes (ACAS) occur rarely. The low frequency of ACAS, in relation to middle cerebral artery territory strokes, may be explained by differences in ACA and middle cerebral artery anatomy influencing their respective flow-directed embolism rates. We aimed to determine whether variability in ACA anatomy, and in particular A1 segment diameter, is associated with embolic ACAS. METHODS: Consecutive patients admitted to Boston Medical Center with embolic ACAS were reviewed. Ipsilateral and contralateral A1 diameters, M1 diameters, and terminal internal carotid artery bifurcation angles were measured from computed tomographic angiography and MRI angiography images. We compared these measurements between cases of ACAS and consecutive cases of embolic middle cerebral artery territory strokes. RESULTS: The study comprised 55 individuals (27 ACAS, 28 middle cerebral artery territory strokes) with mean age of 69 years. In multivariate regression analysis, larger ipsilateral A1 diameters (odds ratio per 1 mm increment: 8.5; 95% confidence interval, 1.4-53.3) and ipsilateral A1/M1 diameter ratio (odds ratio per 10% increment: 1.8; 95% confidence interval, 1.2-2.9) were associated with ACAS, whereas larger ipsilateral M1 diameters was protective for ACAS (odds ratio per 1 mm increment: 0.8; 95% confidence interval, 0.0-0.9). CONCLUSIONS: Larger ipsilateral A1 diameters and A1/M1 diameter ratio are associated with embolic ACAS. These findings suggest that A1 diameters and M1 diameters are important in determining the path of emboli that reach the terminal internal carotid artery.

Stroke care in Armenia: Recent developments.

Introduction: Armenia is an upper-middle-income country with a population of nearly 3 million. Stroke is one of its major public health problems and ranks as the sixth leading cause of death, with a mortality of 75.5 per 100,000. Methods and results: Until recently, modern stroke care was not available in Armenia. During the past 8 years substantial advances have been made in building medical infrastructure and delivering acute stroke care. This manuscript describes contributors to this progress, including extensive and long-term collaboration with international stroke experts, the development of hospital-based stroke teams, and a funding commitment for stroke care by the government. Conclusion: The results of acute stroke revascularization procedures during the past 3 years are reviewed and found to meet international standards. Future directions are discussed including the immediate need to expand acute stroke care to underserved parts of the country by adding primary and comprehensive stroke centers. An active educational program for nurses and physicians and the TeleStroke system development will help support this expansion.

Cerebral ischemic events associated with 'bubble study' for identification of right to left shunts.

BACKGROUND AND PURPOSE: Detection of an intracardiac shunt is frequently sought during the evaluation of patients with cryptogenic ischemic stroke and agitated saline intravenous injection, or "bubble study" (BS), is performed in most cases. We present the first attempt to identify the clinical features in patients who had cerebral ischemic events with BS. METHODS: Using a list serve established by the American Academy of Neurology, a member posted a question regarding the safety of BS in patients with patent foramen ovale. A standardized questionnaire was used to gather data about patients with cerebral ischemic events, details of each case were reviewed, and the findings pooled. RESULTS: Five patients with ischemic complications of BS (all female, aged 42 to 90 years) were identified from 4 institutions, 3 ischemic strokes and 2 transient ischemic attacks. Events occurred either during or within 5 minutes of BS. Early brain MRIs confirmed acute infarction in 3, including one who had transient symptoms. MRI infarct volumes were small, and deficits were mild in those who developed stroke. Diagnostic evaluation revealed a patent foramen ovale alone in one case, a pulmonary arteriovenous malformation in one case, and a patent foramen ovale and/or pulmonary shunt in 3 cases. CONCLUSIONS: Ischemic cerebrovascular complications can occur in patients who undergo BS and are associated with the presence of cardiac or pulmonary shunts. The true incidence and degree of disability remains unknown, and further study is indicated to assess the impact of technical differences in BS methodology. Novel methods to promote physician communication such as the use of electronic list serves may reduce barriers to reporting of drug, technique, or device complications and should be explored to identify rare complications that otherwise will likely go unappreciated.

Microemboli are not associated with delirium after coronary artery bypass graft surgery.

Delirium is an acute change in cognition which occurs frequently after coronary artery bypass graft (CABG) surgery. Cerebral microemboli, from plaque, air, or thrombus, have been hypothesized to contribute to delirium and cognitive decline after CABG. The purpose of this study was to determine if there was an association between cerebral microemboli and delirium after cardiac surgery. Non-delirious patients (n=68) were prospectively enrolled and underwent intraoperative monitoring of the middle cerebral arteries with transcranial Doppler (TCD). TCD signals were saved and analyzed postoperatively for microemboli manually, according to established criteria. Postoperatively, patients were assessed for delirium with a standardized battery. Thirty-three patients (48.5%) developed delirium after surgery. Microemboli counts (mean + or - SD) were not significantly different in those with and without delirium (303 + or - 449 vs. 299 + or - 350; p=0.97). While intraoperative microemboli were not associated with delirium after CABG, further investigation into the source and composition of microemboli can further elucidate the long-term clinical impact of microemboli.

Intracranial hemorrhage sparing meningioma in an anticoagulated patient.

BACKGROUND AND PURPOSE: The risk of intracerebral hemorrhage (ICH) in patients receiving antithrombotic therapy is well known. However, there is sparse literature regarding the risk of intracerebral hemorrhage in patients receiving warfarin, who have an intracranial meningioma. METHODS AND RESULTS: We report a case of a 66-year-old man who developed multifocal ICHs in the context of supratherapeutic anticoagulation. There was sparing of the intracranial meningioma despite the development and growth of multiple intraparenchymal hemorrhages that resulted in death. We also review the literature evaluating the risk of ICH in anticoagulated patients with an intracranial meningioma. CONCLUSIONS: The findings of this case lend further support to the gradually developing notion of relative safety of anticoagulation in patients with meningioma. They also underscore the importance of close monitoring of the INR.

Direct Visualization of Arterial Emboli in Moyamoya Syndrome.

BACKGROUND: Hemodynamic insufficiency is often considered the cause of ischemic stroke in patients with moyamoya syndrome. While high-intensity transient signals (HITS) on transcranial Doppler (TCD) have been reported in this population, the relationship between these signals and ischemic symptoms is not clearly established. Accordingly, current treatment is directed at improving perfusion. CLINICAL PRESENTATION: We present two patients with symptoms of cerebral ischemia and angiographic findings of moyamoya syndrome. In each case, ischemia may have been caused by either hypoperfusion or embolization. Patient A presented with multifocal right middle cerebral artery (MCA) territory infarctions and angiographic findings consistent with moyamoya disease. She underwent right superficial temporal artery-MCA bypass. Intra-operatively, embolic material was observed and recorded traveling through the recipient MCA branch artery on two occasions. Postoperative TCD demonstrated HITS that resolved with uptitration of antiplatelet therapy. Patient B presented with multifocal, embolic-appearing left MCA infarctions, and unilateral angiographic moyamoya syndrome. She was found to have HITS in the left MCA, which eventually resolved with a combination of antiplatelets and anticoagulation. CONCLUSION: Hemodynamic compromise may not be the only cause of brain infarction in patients with moyamoya syndrome. Observations from these two patients provide both direct visualization and TCD evidence of embolization as a potential etiology for brain ischemia. Future investigations into the role of antithrombotic agents should be considered.

Neuroprotection and stroke rehabilitation: modulation and enhancement of recovery.

Recent advances in research are modifying our view of recovery after nervous system damage. New findings are changing previously held concepts and providing promising avenues for treatment of patients after stroke. This review discusses mechanisms of neuronal injury after brain ischemia and the attempts to study neuroprotection options based on such mechanisms. It also considers measures available at present to improve outcome after stroke and presents new areas of research, particularly stimulation techniques, neurogenesis and trophic factors to enhance recovery. In order to improve outcomes, medications that may be detrimental to recovery should be avoided, while symptomatic therapy of problems such as depression, pain syndromes and spasticity may contribute to better results. Continued surveillance and early treatment of complications associated with acute stroke, along with supportive care remain the mainstay of treatment for stroke patients in the recovery phase. Present research on limiting brain damage and improving recovery and plasticity enhance the prospects for better clinical treatments to improve recovery after stroke.

Atherosclerosis is associated with delirium after coronary artery bypass graft surgery.

OBJECTIVES: To investigate whether atherosclerosis of the ascending aorta, internal carotid arteries, and coronary arteries is predictive of postoperative delirium in subjects undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: Boston Veterans Affairs Healthcare System. PARTICIPANTS: Thirty-six male veterans undergoing primary CABG surgery. MEASUREMENTS: Subjects underwent Duplex ultrasound to assess stenosis in the internal carotid arteries. Information on the ascending aortic plaque, as assessed by transesophageal echocardiogram, and the number of coronary vessels bypassed was collected. To create an atherosclerosis score, the number of atherosclerotic areas was added. A validated delirium battery was administered to the subjects preoperatively and on postoperative Days 2 and 5. RESULTS: Fifteen subjects (41.7%) developed delirium postoperatively. In bivariate analysis, carotid stenosis of 50% or more (relative risk (RR)=3.5, 95% confidence interval (CI)=1.5-8.1) and moderate-severe ascending aortic plaque (RR=2.9, 95% CI=1.0-8.5) were significantly associated with the development of delirium. There was a trend toward a significant association for three or more vessels bypassed (RR=9.6, 95% CI=0.6-145.3). After controlling for age, baseline cognition, and medical comorbidity, the atherosclerosis score was significantly associated with postoperative delirium (adjusted RR=2.7, 95% CI=1.1-6.8). CONCLUSION: In this preliminary report, atherosclerosis in the carotid arteries, aorta, and coronary circulation is associated with the development of delirium after CABG surgery. Further investigation into atherosclerosis as a risk factor for delirium is warranted.

Symptomatic and asymptomatic retinal embolism have different mechanisms.

PURPOSE: To investigate differences between symptomatic and asymptomatic retinal embolism regarding the frequency and source of cerebral microemboli. METHODS: Thirty-seven patients with transient monocular blindness or retinal infarction and 27 patients (29 eyes) with asymptomatic retinal embolism were prospectively enrolled. Patients underwent a transcranial Doppler study and noninvasive imaging of the cervical internal carotid arteries (ICA). The middle cerebral artery (MCA) ipsilateral to the affected eye was monitored for 30 minutes for microembolic signals (MES), which were saved and analyzed offline. Age-matched controls (n=15) had no history of retinal or brain ischemia, <50% ICA stenosis, and normal ophthalmologic examinations. RESULTS: MES were detected in 0/15 (0%) controls, 11/37 (30%) MCAs in the symptomatic group (P=0.02), and 3/29 (10%) MCAs in the asymptomatic group (P=0.54). Nine of 11 (82%) symptomatic eyes with MES had ipsilateral ICA stenosis of > or =50%, as compared with 0/3 (0%) eyes in the asymptomatic group with MES (P=0.03). Both MES and ICA stenosis of >50% were present in 9/37 (24%) cases in the symptomatic and in 0/29 (0%) cases of the asymptomatic group (P=0.0036). CONCLUSIONS: The frequency and potential source of cerebral microemboli in symptomatic and asymptomatic retinal embolism are different. Cerebral microemboli are more frequent in symptomatic patients and are associated with ICA stenosis.

Influence of 17-beta-estradiol on cerebrovascular impedance during menstrual cycle in women.

Numerous experimental studies showed that estrogen alters diameters of cerebral arteries by modifying production of vasoactive substances. In this study, we address a question whether increased concentration of 17-beta-estradiol (E2) during a typical menstrual cycle of young, healthy women influences cerebrovascular impedance, as measured with Doppler pulsatility index (PI) in the common (CCA), internal (ICA), and external (ECA) carotid arteries using duplex Doppler sonography. PI was determined and correlated with plasma E2 concentration in 14 women (ages 23-25) throughout their menstrual cycle. The concentration of E2 increased in the follicular phase of the cycle and reached a peak of 140-300 pg/ml on days 13 and 14, whereas concentration of progesterone remained low (<1 ng/ml). Along with an increase in E2 concentration, the ICA PI decreased from its initial level on average by 11% on day 13 and by 7% on day 14 (r=-0.41, P<0.05). In contrast, the value of the ECA PI showed an increasing trend during the peak of E2 concentration. There were no significant changes in the CCA PI as well as in the systolic blood pressure, heart rate, hematocrit, and hemoglobin concentration during the menstrual cycle. Cerebral vascular impedance in young women is modulated by concentration of E2 throughout the menstrual cycle. The decrease in the ICA PI during the late follicular phase seems to be attributed to a decrease in cerebrovascular resistance.

Detection of microemboli by transcranial Doppler ultrasonography in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the frequency and characteristics of microembolic signals (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the presence of MES and vasospasm. Each middle cerebral artery was monitored for 30 minutes three times each week. Patients were excluded if they had traumatic SAH or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1-16 d) after SAH and lasted 6.6 days (1-13 d). Eleven individuals without SAH or other cerebrovascular diseases who were treated in the same unit served as control subjects. Each patient underwent monitoring of both middle cerebral arteries a mean of three times; therefore, 46 vessels were studied (a total of 138 observations). Control subjects underwent assessment of each middle cerebral artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16 of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with 2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P < 0.05). MES were observed for 83% of patients with clinical vasospasm and 54% of those without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138 vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of those without vasospasm. Aneurysms proximal to the monitored artery were identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were common in SAH, occurring in 70% of cases of SAH and one-third of all vessels monitored. Although MES were more frequent among patients with clinical vasospasm, this difference did not reach statistical significance. We were unable to demonstrate a relationship between ultrasonographic vasospasm and MES, and the presence of a proximal secured or unsecured aneurysm did not alter the chance of detection of MES. Further studies are required to determine the origin and clinical relevance of MES in SAH.

Brain microembolism.

PURPOSE: To alert clinicians about the occurrence of a subtype of brain infarction, its suspected etiology, and its detection by specific neuroimaging techniques. METHODS: The article presents 5 nonconsecutive patients admitted to the stroke services of 2 tertiary care hospitals, who presented with acute or subacute symptoms suspicious, but at times atypical, of brain ischemia. FINDINGS: Each patient had evidence of 3 to > 20 small areas of recent brain infarction detected by diffusion-weighted imaging (DWI). When available, brain computerized tomography images were not helpful for the diagnosis of these recent infarcts. Most lesions were present on magnetic resonance imaging fluid-attenuated inversion recovery sequences, but the diffusion-weighted images allowed the determination of their acuity. Further evaluation revealed a potential source of embolism in each patient. Brain microembolism was suspected in all cases. CONCLUSION: Small and multiple areas of acute or subacute brain infarction occasionally present with clinical features atypical for brain embolism. They can be detected by magnetic resonance DWI studies.

Echocardiographic findings of patients with retinal ischemia or embolism.

BACKGROUND AND PURPOSE: A potential source of emboli is not detected in more than 50% of patients with retinal arterial occlusive events. Echocardiographic studies are not always included in the diagnostic workup of these patients. The authors studied the diagnostic yield of transthoracic (TTE) and/or transesophageal (TEE) echocardiography in identifying potential sources of emboli in patients with retinal ischemia or embolism. METHODS: In a prospective study, 73 consecutive patients with clinically diagnosed retinal ischemia or embolism received a standardized diagnostic workup including retinal photography, echocardiography, and imaging studies of the internal carotid arteries. TTE was performed in 83.6% of patients, TEE was performed in 5.5% of patients, and both TTE and TEE were performed in 11.0% of patients. Ophthalmological diagnoses consisted of amaurosis fugax (n = 28), asymptomatic cholesterol embolism to the retina (n = 34), and branch or central retinal artery occlusion (n = 11). RESULTS: Echocardiography identified a potential cardiac or proximal aortic source for embolism in 16 of 73 (21.9%) patients, including 8 who also had either atrial fibrillation or internal carotid artery stenosis of more than 50% on the side of interest. Thus, 8 of 73 (11.0%) patients had lesions detected only by echocardiography. The most commonly identified lesions were proximal aortic plaque of more than 4 mm thickness (n = 7, 9.6%) and left ventricular ejection fraction of less than 30% (n = 6, 8.2%). TEE was particularly helpful in identifying prominent aortic plaques. CONCLUSION: Echocardiography frequently identifies lesions of the heart or aortic arch that can act as potential sources for retinal ischemia or embolism. Further studies are needed to evaluate the prognostic and therapeutic relevance of these findings.

Acute stroke, catheter related venous thrombosis, and paradoxical cerebral embolism: report of two cases.

BACKGROUND: Patent foramen ovale (PFO) has been associated with cryptogenic stroke, particularly in young adults. However, the source of particles leading to cerebral embolism remains frequently unknown despite comprehensive evaluation. OBJECTIVE: To report and comment on therapeutic options for 2 patients with acute ischemic strokes, PFO, and venous access related thrombosis, sources of paradoxical embolism, from Boston Medical Center stroke database. CASE DESCRIPTIONS: Case 1. A 71-year-old man presented with brain magnetic resonance imaging (MRI) confirmed acute cerebellar infarction. Echocardiography showed a PFO and thrombotic material at the tip of a peripherally inserted central catheter (PICC) line in the superior vena cava (SVC) prolapsing into the right atrium (RA). Case 2. A 64-year-old woman with end-stage renal disease and PFO presented with brain MRI confirmed acute parietal lobe infarction. Three days prior to her stroke, she had thrombectomy and venoplasty of an arterio-venous (AV) dialysis graft followed by a post-thrombectomy fistulogram that showed persistent thrombotic material at the venous site. CONCLUSIONS: PFO associated with large venous access site thrombosis was the most likely mechanism of stroke in both cases. Local thrombosis at sites of large venous access may be an overlooked source of paradoxical embolism in patients with PFO as well as a preventable cause of stroke in critically ill patients.

Intra-arterial treatment methods in acute stroke therapy.

Acute revascularization is associated with improved outcomes in ischemic stroke patients. It is unclear which method of intra-arterial intervention, if any, is ideal. Promising approaches in acute stroke treatment are likely a combination of intravenous and endovascular revascularization efforts, combining early treatment initiation with direct clot manipulation and/or PTA/stenting. In this review, we will discuss available thrombolytic therapies and endovascular recanalization techniques, beginning with chemical thrombolytic agents, followed by mechanical devices, and a review of ongoing trials. Further randomized studies comparing medical therapy, intravenous and endovascular treatments are essential, and their implementation will require the wide support and enthusiasm from the neurologic, neuroradiologic, and neurosurgical stroke communities.

Balloon angioplasty of the A2 segment of the anterior cerebral artery for recurrent, symptomatic atherosclerotic disease.

Intracranial atherosclerotic disease accounts for 5-10% of ischemic strokes in the US. Lesions located in the anterior cerebral artery territory are infrequently reported. Patients in whom medical therapy fails are at a high risk for recurrent ischemic events, in which case intracranial angioplasty or stenting may be a reasonable therapy. There is a paucity of literature describing angioplasty of fixed atherosclerotic lesions affecting the anterior cerebral artery territory, and especially the A(2) segment. This case illustrates that this vessel segment may be treated with balloon angioplasty.