Primary systemic amyloidosis with ischemic stroke as a presenting complication.

BACKGROUND: Amyloidosis is an uncommon disorder that ultimately leads to fatal multiorgan failure. Ischemic strokes have been sporadically described but are not well characterized. The purpose of this study was to review the pathophysiologic relationship between primary systemic amyloidosis and ischemic stroke, and to determine how often stroke is the first defining manifestation. METHODS: Retrospective study of 49 patients with confirmed primary amyloidosis and ischemic stroke. All included patients had biopsy proven amyloidosis. RESULTS: Forty patients were included in the study. Ischemic strokes occurred in 13 patients (32.5%) as the initial presentation of amyloidosis. Patients with initial stroke presentation had the worst outcome, with average survival of 6.9 months after established diagnosis with amyloidosis; strokes developed 9.6 months before diagnosis with primary amyloidosis. Thirty-seven percent experienced recurrent ischemic stroke. The majority (70%) of patients had cardioembolic infarctions. CONCLUSIONS: Ischemic stroke is an underappreciated complication of primary amyloidosis. In the absence of obvious clinical and cardiogenic manifestations, primary amyloidosis should be considered when echocardiography demonstrates thickening of the valves, restrictive pattern, and increased echogenicity. Ischemic strokes as an initial presentation of primary amyloidosis carries a worse prognosis.

Plaque rupture in the carotid artery is localized at the high shear stress region: a case report.

BACKGROUND AND PURPOSE: Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. Summary of Case- We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. CONCLUSIONS: In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.

Correlation between carotid intraplaque hemorrhage and clinical symptoms: systematic review of observational studies.

BACKGROUND AND PURPOSE: We sought to investigate the association between carotid intraplaque hemorrhage (IPH) and ipsilateral symptoms of cerebral ischemia. METHODS: A search was performed for clinical observational studies comparing the incidence of IPH between symptomatic and asymptomatic patients. Odds ratios (ORs) for IPH as a factor in the pathogenesis of neurologic events were calculated and combined by a meta-analysis. Interstudy heterogeneity, estimated effects, and methodologic quality of the studies were assessed. RESULTS: Thirty-one studies were included for analysis. The reported ORs varied widely. Overall, the incidence of IPH in the symptomatic groups was significantly higher than in the asymptomatic group. However, there was an apparent trend for heterogeneity (P<0.00001) between studies. The random-effects summary estimator of ORs was 2.25 (95% CI, 1.57 to 3.22; P<0.00001). To identify potential sources of heterogeneity, subgroup analyses were performed. The pooled ORs varied greatly by stratification. Major heterogeneity was found among studies with low quality, microscopic methods of examination, significant effects, small sizes, early publication, and unequal severity of carotid stenosis in both groups. Large, recent, macroscopic, or high-quality studies, as well as studies with equal degrees of stenosis, tended to yield insignificant associations. The methods in defining and evaluating hemorrhage were very heterogeneous. Characterizations of the age, size, number, and location of hemorrhages were poorly reported and highly variable. In addition, a lack of control of confounders and selection bias were frequently identified among studies. CONCLUSIONS: Statistical inferences have suggested a plausible role in the production of cerebral ischemia; however, reliable interpretation was strongly undermined by poor methodologic quality, substantial heterogeneity, and suspicious publication bias. To preciously estimate the underlying correlation, a well-designed study with uniformity in definition and evaluation for IPH might be warranted.

Cerebral protection during retrograde carotid artery stenting for proximal carotid artery stenosis: technical note.

Carotid artery stenting for carotid bifurcation stenosis usually uses the transfemoral approach. However, in patients with proximal common carotid artery (CCA) stenosis, the guiding catheter is difficult to introduce into the narrow origin of the CCA without risking cerebral embolization before activation of the protection device. A technique of cerebral protection by internal carotid artery (ICA) clamping with or without simultaneous external carotid artery (ECA) clamping was used to treat patients with proximal CCA stenosis by the retrograde direct carotid approach. The carotid bifurcation was surgically exposed and retrograde catheterization was performed to approach the stenosis. The ICA was clamped during angioplasty and stenting to avoid cerebral embolization. The ECA was clamped simultaneously if any extracranial-intracranial anastomosis was present. None of five patients treated with this technique experienced ischemic complications attributable to this technique.

Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy.

BACKGROUND AND PURPOSE: For patients having suffered ischemic stroke, the current diagnostic strategies often fail to detect atrial fibrillation as a potential cause of embolic events. The aim of the study was to identify paroxysmal atrial fibrillation in stroke patients. We hypothesized that patients with frequent atrial premature beats (APBs) recorded in 24-hour ECG will show more often atrial fibrillation when followed by repeated long-term ECG recordings than patients without or infrequent APBs. METHODS: 127 patients with acute ischemic stroke and without known AF were enrolled in a prospective study to detect paroxysmal AF. Patients were stratified according to the number of APBs recorded in a 24-hour ECG (> or =70 APBs versus <70 APBs). Subsequently, they all underwent serial 7-day event-recorder monitoring at 0, 3, and 6 months. RESULTS: Serial extended ECG monitoring identified AF in 26% of patients with frequent APBs but only in 6.5% when APBs were infrequent (P=0.0021). A multivariate analysis showed that the presence of frequent APBs in the initial 24-hour ECG was the only independent predictor of paroxysmal AF during follow-up (odds ratio 6.6, 95% confidence intervals 1.6 to 28.2, P=0.01). CONCLUSIONS: In patients with acute ischemic stroke, frequent APBs (> or = 70/24 hours) are a marker for individuals who are at greater risk to develop or have paroxysmal AF. For such patients, we propose a diagnostic workup with repeated prolonged ECG monitoring to diagnose paroxysmal AF.

Role of elevated alpha2-macroglobulin revisited: results of a case-control study in children with symptomatic thromboembolism.

OBJECTIVE: alpha(2)-Macroglobulin (alpha2MG) is a broad-spectrum protease inhibitor that is known to neutralize alpha-thrombin, plasmin, and activated protein C, which suggests that it has anticoagulant as well as procoagulant properties. The present study was conducted to evaluate the role of alpha2MG in children with venous thromboembolism [VTE: paradoxical embolism causing ischemic stroke (IS) or deep-vein thrombosis (DVT)]. METHODS: alpha2MG levels measured after acute VTE onset in white patients were compared with data obtained from age- and gender-matched healthy controls. In addition, to compare the rate of elevated alpha2MG and prothrombotic risk factors [factor V G1691A, prothrombin G20210A, raised lipoprotein (a)] between patients and controls and to evaluate the interaction between elevated alpha2MG levels and other thrombophilias, odds ratios (ORs) together with 95% confidence intervals (CIs) were estimated using a logistic regression model. The model was adjusted for age and fibrinogen. RESULTS: alpha2MG levels were significantly higher in patients than in controls (320/139-524 vs. 302/109-406; P = 0.005). In the group of patients (IS n = 103; DVT n = 92), the risk of symptomatic thromboembolism was significantly increased with elevated alpha2MG levels, with a gradual increase per mg dL(-1). In addition, when elevated alpha2MG levels > 90th percentile were compared with values below the cut-off, including established prothrombotic risk factors in the multivariate analysis, patients had a significantly increased OR/95% CI for fibrinogen-adjusted alpha2MG levels (IS, 5.9/1.9-18.3; DVT, 7.2/2.1-24.4). CONCLUSIONS: The procoagulant properties of elevated alpha2MG levels independently increase the odds of stroke and DVT in white children.

Brain injury from cardiac bypass procedures.

Patients who undergo coronary artery bypass grafting (CABG) are at increased risk for brain injury. Surgical techniques have advanced so that the risk of neurological sequelae is decreased, but there remains significant morbidity and mortality related to the postoperative period as well as to the surgery itself. In addition, patients who undergo CABG have comorbidities or demographic factors that may increase their likelihood of developing neurological complications. Pathophysiological mechanisms of cerebral injury after CABG range from hemodynamic compromise to embolization, either intraoperatively or postoperatively. Biochemical markers such as S100 and neuron-specific enolase may play a role in the prediction of outcome after CABG, and because of this may help elucidate other potential risk factors. Specific neurological sequelae are discussed, such as stroke, with summaries of the apparent risk factors, as well as encephalopathy, seizure, and both short- and long-term cognitive deficits. Changes in surgical technique have led to some improvements, but there is no definitive information yet as to the role of some of these, such as the use of off-pump CABG. Other techniques such as the use of an arterial filter are discussed, as are their potential benefits in the prevention of neurological complications.

Incidence of new brain lesions after carotid stenting with and without cerebral protection.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) may be a useful tool to evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during carotid angioplasty and stenting (CAS). The goals of this study were (1) to compare the frequency, number, and size of new DWI lesions after unprotected and protected CAS; and (2) to determine the clinical significance of these lesions. METHODS: DWI was performed immediately before and within 48 hours after unprotected or protected CAS. Clinical outcome measures were stroke and death within 30 days. RESULTS: The proportion of patients with any new ipsilateral DWI lesion (49% versus 67%; P<0.05) as well as the number of new ipsilateral DWI lesions (median=0; interquartile range [IQR]=0 to 3 versus median=1; IQR=0 to 4; P<0.05) were significantly lower after protected (n=139) than unprotected (n=67) CAS. The great majority of these lesions were asymptomatic and less than 10 mm in diameter. Although there were no significant differences in clinical outcome between patients treated and not treated with protection devices (7.5% versus 4.3%, not significant), the number of new DWI lesions was significantly higher in patients who developed a stroke (median=7.5; IQR=1.5 to 17) than in patients who did not (median=0; IQR=1 to 3.25; P<0.01). CONCLUSIONS: The use of cerebral protection devices significantly reduces the incidence of new DWI lesions after CAS of which the majority are asymptomatic and less than 10 mm in diameter. The frequent occurrence of these lesions and their close correlation with the clinical outcome indicates that DWI could become a sensitive surrogate end point in future randomized trials of unprotected versus protected CAS.

Endovascular treatment of the carotid stump syndrome.

In patients with an occluded internal carotid artery, the carotid stump syndrome is a potential source of microemboli that pass through the ipsilateral external carotid artery and the ophthalmic artery to the territory of the middle cerebral artery. Thus, the syndrome is associated with carotid territory symptoms although the internal carotid artery is occluded. Surgical exclusion of the internal carotid artery associated with endarterectomy of the external carotid artery has been described as the gold standard of treatment by many authors. This report is the second case, to our knowledge, of endovascular treatment of the carotid stump syndrome with the use of a stent-graft.

Contrast-enhanced transcranial Doppler ultrasound for diagnosis of patent foramen ovale.

The suspected cause of clinical manifestations of patent foramen ovale (PFO) is a transient or a permanent right-to-left shunt (RLS). Contrast-enhanced transcranial Doppler ultrasound (c-TCD) is a reliable alternative to transesophageal echocardiography (TEE) for diagnosis of PFO, and enables also the detection of extracardiac RLS. The air-containing echo contrast agents are injected intravenously and do not pass the pulmonary circulation. In the presence of RLS, the contrast agents bypass the pulmonary circulation and cause microembolic signals (MES) in the basal cerebral arteries, which are detected by TCD. The two main echo contrast agents in use are agitated saline and D-galactose microparticle solutions. At least one middle cerebral artery (MCA) is insonated, and the ultrasound probe is fixed with a headframe. The monitored Doppler spectra are stored for offline analysis (e.g., videotape) of the time of occurrence and number of MES, which are used to assess the size and functional relevance of the RLS. The examination is more sensitive, if both MCAs are investigated. In the case of negative testing, the examination is repeated using the Valsalva maneuver. Compared to TEE, c-TCD is more comfortable for the patient, enables an easier assessment of the size and functional relevance of the RLS, and allows also the detection of extracardiac RLS. However, c-TCD cannot localize the site of the RLS. Therefore, TEE and TCD are complementary methods and should be applied jointly in order to increase the diagnostic accuracy for detecting PFO and other types of RLS.

Cerebral circulation monitoring in carotid endarterectomy and carotid artery stenting.

In the near future it is likely that surgeons, anesthesiologists, and interventional radiologists and cardiologists will care for increasing numbers of patients undergoing carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS). Perhaps the most important factor in assuring technically acceptable interventions is the availability of an experienced team with demonstrable low periprocedural morbidity and mortality and a proper understanding of both vascular principles and cerebral physiology. Although different monitoring techniques have proven successful during both surgical and endovascular carotid interventions, the advantages of periprocedural transcranial Doppler (TCD) monitoring, such as its sensitivity for recording blood flow velocities and microembolism in real-time, are convincing. Because of its high temporal resolution, it provides additional information about the cerebral circulation, especially during cross-clamping, clamp release, and balloon inflation and deflation, respectively. If made audible during the procedure, it also provides unique information concerning cerebral micro-embolization. In CEA, TCD monitoring gives a better understanding of the pathophysiology of complications and makes the operation safer. In CAS, it gives insight into the clinical relevance of cerebral embolism and the possible effects of protection devices.

Detection of cardiac right-to-left shunts by contrast-enhanced harmonic carotid duplex sonography.

OBJECTIVE: Paradoxical embolization by cardiac right-to-left shunts (RLS) is increasingly recognized as an important factor for embolic stroke. Contrast-enhanced transcranial Doppler sonography (ce-TCDS) is an established diagnostic tool for RLS detection but is frequently limited because of an inadequate temporal acoustic bone window. The purpose of this study was to determine whether extracranial sonography (ECS) using harmonic frequencies improves detection of RLS. METHODS: Extracranial color duplex sonography using harmonic frequencies enables visualization of even single ultrasound contrast agent microbubbles because of oscillation. Patients with stroke and positive RLS findings on transesophageal echocardiography underwent a simultaneous extracranial and transcranial sonographic examination of the proximal common carotid artery (CCA) and middle cerebral artery (MCA) on the same side. A Valsalva strain was performed for 10 seconds after intravenous bolus injection of a galactose-based nontranspulmonary contrast agent. The B-mode frame sequences of the transverse plane of the CCA obtained by harmonic ECS and the ce-TCDS recordings of high-intensity transient signals from the MCA were analyzed offline. RESULTS: In all patients with RLS, the shunts could be identified by harmonic ECS. A close correlation could be seen between the count of visualized microbubbles in the CCA and the number of high-intensity transient signals detected on ce-TCDS in the ipsilateral MCA. CONCLUSIONS: The results of this study indicate that contrast-enhanced ultrasound harmonic imaging of the CCA using a Valsalva strain might be an optional screening tool for detection of cardiac RLS in patients with insufficient acoustic bone windows.

Long-term effects of sequential cortical infarcts on scar size, brain volume and cognitive function.

Focal ischemia induces long-term pathophysiological consequences in widespread brain areas. Here we analyzed long-term effects of sequential cortical lesions on brain volume and cognitive function. Rats received either single photothrombotic lesions in the forelimb sensorimotor cortex (SL) or two lesions in sequence either immediately (DL0), 2 days (DL2), 7 days (DL7), or 10 days (DL10) after the first surgery in the homotopic contralateral area. Infarct and global brain volume were measured 7 days (SL and DL2 groups) and one month (all groups) after the last period of ischemia. In the weeks following a stroke, the single lesion shrank considerably. This shrinkage was accentuated by a further lesion received either earlier or later. Thirty-one days after obtaining the second lesion, the lesion scars on both sides had a mean volume of 5.8 +/- 2.3 mm3 in DL2 as compared to 8.5 +/- 3.5 mm3 in SL-animals. In addition, there was a super-additive loss of residual brain volume by 2.2-8.0% in each hemisphere in animals with sequential lesions. In the watermaze, this loss of brain volume corresponded to a slight but significant impairment in performance. The present study revealed a complex interaction of lesions in animals with sequential strokes associated with global reduction of brain volume and cognitive impairment indicating degenerative processes beyond the lesions itself.

Comparison of transesophageal echocardiographic identification of embolic risk markers in patients with lone versus non-lone atrial fibrillation.

Although transesophageal echocardiographically derived parameters, notably spontaneous echocardiographic contrast (SEC) in the left atrium or left atrial appendage (LAA), are known predictors of embolism in atrial fibrillation, their value is less well known in patients who have lone atrial fibrillation (LAF). This study describes transesophageal echocardiographic findings and identifies clinical predictors of SEC in the left atrium or LAA in a cohort of patients who had LAF. Eighty-two patients who had LAF and 289 patients who had non-LAF and underwent transesophageal echocardiography were enrolled from July 1998 to March 2002. LAA abnormality was defined as the presence of an LAA area >5 cm(2), emptying or filling LAA velocities <25 cm/s, or the presence of SEC or thrombus in the left atrium or LAA; LAA abnormalities were significantly less frequent in patients who had LAF than in those who had non-LAF. SEC in the left atrium or LAA was significantly less frequent in patients who had LAF than in those who had non-LAF (29.3% vs 49.8%, respectively, p <0.001). In patients who had LAF, SEC in the left atrium or LAA was significantly (p <0.05) less frequent in patients who were 60 years old (39.5%) and in patients who had paroxysmal LAF (5.9%) than in those who had persistent LAF (45.8%). On multivariate analysis, age and persistent LAF were the only clinical variables independently associated with SEC. Thus, transesophageal echocardiography detects thromboembolism risk markers in patients who have LAF. These abnormalities are less frequent in patients who have LAF than in those who are at low risk and have non-LAF; however, in patients who have LAF, older age and persistent atrial fibrillation are associated with these risk markers.

Interatrial block as a predictor of embolic stroke.

Interatrial block (IAB), defined as a prolonged (>/=110 ms) P wave, is remarkably prevalent in general hospital populations and is associated with an enlarged, poorly contractile left atrium. The investigators sought to determine whether there is an increased incidence of IAB in patients with embolic strokes. Patients' medical records were reviewed for evidence of embolic cerebrovascular events and IAB. One hundred four patients were identified. In 61 patients in normal sinus rhythm, 49 (80%) had IAB. This was almost twice the prevalence of 2 previous studies (41% and 47%). Therefore, IAB may represent a new risk factor for stroke.

Fate of left atrial thrombi in patients with atrial fibrillation determined by transesophageal echocardiography and cerebral magnetic resonance imaging.

Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients receiving continued oral anticoagulation. Forty-three consecutive patients with AF and atrial thrombi were enrolled in the study. Serial and prospective transesophageal echocardiographic studies, cranial magnetic resonance imaging (MRI), and clinical examinations were performed during a period of 12 months. Oral anticoagulation was continued or initiated in all patients. An international normalized ratio of 2.0 to 3.0 was regarded as effective. During follow-up, 56% of the thrombi disappeared (7 [16%] at 1 month, 18 [42%] at 3 months, 21 [49%] at 6 months, and 24 [56%] at 12 months). Patients with the disappearance of thrombi had significantly smaller thrombi compared with patients with persistent thrombi (1.5 +/- 0.8 cm in length and 0.8 +/- 0.5 cm in width vs 1.9 +/- 0.6 cm in length and 1.3 +/- 0.4 cm in width, p = 0.04), reduced echogenicity of thrombi (46% vs 89%, p <0.01), and smaller left atrial (LA) volume (83 +/- 27 vs 116 +/- 55 cm(3)). Seven patients (16%) had embolic lesions during follow-up MRI. Six of these patients (86%) had clinically apparent embolisms, and 1 died from stroke. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (p <0.01) and previous thromboembolic events (p = 0.02). Patients with AF and atrial thrombi have a large likelihood of cerebral embolism (16%) and/or death despite oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.

A model for cardiopulmonary bypass redesign.

INTRODUCTION: A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB. METHODS: We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient's surgical case video. RESULTS: To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels. SUMMARY: Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.

Giant thrombus trapped in foramen ovale with pulmonary embolus and stroke.

We describe the case of a young man who, while he was in coma because of a traffic accident, had first a pulmonary embolus and immediately afterwards had a systemic (cerebral) embolus. A transesophageal echocardiographic image revealed a giant thrombi trapped in foramen ovale protruding in right and left ventricles, diagnosing, thus, a paradoxical embolism. The relationship between patent foramen ovale and pulmonary embolism has been reported in some series. Elevated right-chamber pressure caused by pulmonary hypertension could favor the establishment of a right-to-left shunt, causing, in some cases, paradoxical embolisms. We review the clinical implications.