Volume of carotid artery ulceration as a predictor of cardiovascular events.

BACKGROUND AND PURPOSE: Previous studies have shown the presence of ulceration in atherosclerotic plaque either by categorizing the plaque as complex (irregular morphology with ulcers) or smooth or by quantifying the number of ulcers observed in a specific region of interest. The aim of this study was to quantify carotid total ulcer volume by 3-dimensional ultrasound to investigate the relationship of total ulcer volume to vascular events (strokes, transient ischemic attack, myocardial infarction, revascularization, or death because of cardiovascular reasons). METHODS: In total, 349 at-risk subjects provided written informed consent to carotid 3-dimensional ultrasound and were analyzed for ulcerations. Ulcer volume was defined as a distinct discontinuity in an atherosclerotic plaque, with a volume≥1.00 mm3 as measured using manual segmentation. The sum of the volumes of all ulcers seen in both carotids was the total ulcer volume. Participants were monitored for ≤5 years for outcomes, including cardiovascular events and death. RESULTS: Kaplan-Meier survival analysis showed that subjects with total ulcer volume≥5 mm3 experienced a significantly higher risk of developing stroke, transient ischemic attack, or death (P=0.009) and of developing stroke/transient ischemic attack/death/myocardial infarction/revascularization (P=0.017). Lower ulcer volumes did not predict events nor did ulcer depth. CONCLUSIONS: Volume of carotid ulceration on 3-dimensional ultrasound predicts cardiovascular events. In addition to improving risk stratification, ulceration is a potential therapeutic target.

Epilepsy, mental health disorder, or both?

Temporal lobe epilepsy (TLE), a subset of the seizure disorder family, represents a complex neuropsychiatric illness, where the neurological presentation may be complemented by varying severity of affective, behavioral, psychotic, or personality abnormalities, which, in turn, may not only lead to misdiagnosis, but also affect the management. This paper outlines a spectrum of mental health presentations, including psychosis, mood, anxiety, panic, and dissociative states, associated with epilepsy that make the correct diagnosis a challenge.

Analysis of carotid lumen surface morphology using three-dimensional ultrasound imaging.

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this work, our goal was to use both Gaussian and mean curvatures for identifying ulcers from 3D carotid ultrasound (US) images of human subjects. Before performing experiments using patient data, we verified the numerical accuracy of the surface curvature computation method using discrete spheres and tori with different sampling intervals. We also showed that three ulcers of the vascular phantom with 2 mm, 3 mm and 4 mm diameters were associated with high Gaussian and mean curvatures, and thus, were easily detected. Finally, we demonstrated the application of the proposed method for detecting ulcers on luminal surfaces, which were segmented from the 3D US images acquired for two human subjects.

Thrombolysis in patients with marked clinical fluctuations in neurologic status due to cerebral ischemia.

BACKGROUND: It is unclear whether thrombolysis benefits patients with fluctuating neurologic symptoms. OBJECTIVE: To evaluate the clinical course of patients with acute stroke who presented with marked fluctuations in neurologic status and received thrombolytic therapy. DESIGN: Prospective analysis. SETTING: London Health Science Centre University Hospital, London. Patients We prospectively identified patients who were treated with intravenous or intra-arterial recombinant tissue plasminogen activator between January 1, 2004, and January 1, 2006. For this analysis, we chose patients who had marked fluctuation in neurologic status at presentation and who received thrombolytic therapy. Main Outcome Measure Fluctuation of neurologic deficits, defined as a 4-point or greater increase or decrease in the National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: Among 127 patients, 13 (10.2%) had clinical fluctuations. Patients with fluctuations presented with a lower NIHSS score (median, 7; interquartile range, 10-17) compared with patients without fluctuations (median, 12; interquartile range, 10-17) (P < .001). Fluctuation of symptoms or signs ceased after thrombolysis. At 24 hours after stroke, the median NIHSS score was 2 (range, 1-12). All patients had favorable neurologic and functional outcomes at 3 months after thrombolysis (modified Rankin scale score, 0-2). CONCLUSION: Thrombolysis may benefit patients with fluctuating symptoms or signs due to cerebral ischemia.

White matter thresholds for ischemic penumbra and infarct core in patients with acute stroke: CT perfusion study.

PURPOSE: To prospectively determine the parameters derived at admission computed tomographic (CT) perfusion imaging admission that best differentiate ischemic white matter that recovers from that which infarcts, with the latter retrospectively defined at a CT examination performed without contrast material (unenhanced CT) 5-7 days after the event. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Thirty patients with stroke underwent unenhanced CT, CT angiography, and CT perfusion studies at admission. Additionally, CT angiography was performed 24 hours after the stroke, and an unenhanced CT study was performed 5-7 days after the stroke. Five patients were excluded; the remaining patients (10 men, 15 women; mean age, 70 years +/- 13 [standard deviation]) were separated into those with recanalization (n = 16) and those without recanalization (n = 9) at 24 hours. For patients with recanalization, the final infarct was outlined on unenhanced CT images obtained 5-7 days after the event and was superimposed on coregistered maps from the CT perfusion study performed at admission. Ischemic white matter tissue (cerebral blood flow [CBF] < 14 mL/min/100 g) was identified at the admission CT perfusion study, and the penumbra was defined as the difference between the ischemic region and the infarct region. RESULTS: Infarct regions showed a matched decrease in CBF and cerebral blood volume (CBV) at admission, whereas penumbra regions showed a significant (P < .05) decrease in CBF but no change in CBV (P > .05) from contralateral values. A threshold CBF . CBV value of 8.14 was the most sensitive (95%, 20 of 21 regions) and specific (94%, 32 of 34 regions) parameter for differentiating between regions of ischemic white matter that recovered and regions of ischemic white matter that infarcted. CONCLUSION: The product of CBF and CBV derived from CT perfusion data provided the best differentiation between regions of ischemic white matter that infarcted and regions of ischemic white matter that recovered 5-7 days after a stroke.

Cerebrovascular events on awakening, patent foramen ovale and obstructive sleep apnea syndrome.

Patent foramen ovale is a defect in the interatrial septum associated with cryptogenic stroke. The presumed mechanism of cryptogenic stroke due to a patent foramen ovale is the migration of thrombus from the venous side of the circulation to the left atrium with subsequent systematic embolism, called paradoxical embolization. Provacative maneuvers and pre-existing cardiopulmonary disease can cause elevation in right atrial pressure leading to right-to-left shunting through a patent foramen ovale. We report two patients with patent foramen ovale waking up with cryptogenic vascular events and found to have an obstructive sleep apnea syndrome. During nocturnal sleep, obstructive sleep apnea can cause right atrium pressure elevation resulting in right-to-left shunting through patent foramen ovale. The possibility of patent foramen ovale and an obstructive sleep apnea syndrome may be considered in patients with cryptogenic strokes-on-awakening. Further studies are needed to support our observation.

Validation of automatically classified magnetic resonance images for carotid plaque compositional analysis.

BACKGROUND AND PURPOSE: MRI may be used for noninvasive assessment of atherosclerotic lesions; however, MRI evaluation of plaque composition requires validation against an accepted reference standard, such as the American Heart Association (AHA) lesion grade, defined by histopathological examination. METHODS: Forty-eight carotid endarterectomy specimen cross-sections had AHA lesion grade determined histopathologically and were concurrently imaged using combinations of 8 MRI contrast weightings in vitro. A maximum likelihood classification algorithm generated MRI "maps" of plaque components, and an AHA lesion grade was assigned correspondingly. Additional analyses compared classification accuracy obtained with a commonly used set of magnetic resonance contrast weightings [proton density (PDw), T1 (T1w), and partial T2 (T2w)] to accuracy obtained with the combination of PDw, T1w, and diffusion-weighted (Dw) contrast. RESULTS: For the 8-contrast combination, the sensitivities for fibrous tissue, necrotic core, calcification, and hemorrhage detection were 83%, 67%, 86%, and 77%, respectively. The corresponding specificities were 81%, 78%, 99%, and 97%. Good agreement (79%) between magnetic resonance and histopathology for AHA classification was achieved. For the PDw, T1w, and Dw combination, the overall classification accuracy was insignificantly different at 78%, whereas the overall classification accuracy using PDw, T1w, and partial T2w contrast weightings was significantly lower at 67%. CONCLUSIONS: This study provides proof-of-principle that the composition of atherosclerotic plaques determined by automated classification of high-resolution ex vivo MRI accurately reflects lesion composition defined by histopathological examination.

3D ultrasound measurement of change in carotid plaque volume: a tool for rapid evaluation of new therapies.

BACKGROUND AND PURPOSE: New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. METHODS: In 38 patients with carotid stenosis >60%, age+/-SD 69.42+/-7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. RESULTS: There were no significant differences in baseline risk factors. The rate of progression was 16.81+/-74.10 mm3 in patients taking placebo versus regression of -90.25+/-85.12 mm3 in patients taking atorvastatin (P<0.0001). CONCLUSIONS: 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of approximately 20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Lack of improvement in patients with acute stroke after treatment with thrombolytic therapy: predictors and association with outcome.

CONTEXT: The focus of thrombolytic therapy in acute stroke has been on favorable outcome at 3 months. Few studies have analyzed outcome at 24 hours. An early and reliable prediction of poor outcome has implications for clinical management and discharge planning. OBJECTIVE: To evaluate predictors of lack of improvement at 24 hours after receiving alteplase and their relationship with poor outcome at 3 months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of consecutive patients with acute stroke who received alteplase and were admitted to a university hospital from January 1999 to March 2003. Participants were recruited from 2 academic centers in a major city in Ontario and 33 affiliated hospitals from 7 counties. MAIN OUTCOME MEASURES: Lack of improvement defined as a difference between the National Institutes of Health Stroke Scale score at baseline and at 24 hours of 3 points or less. Poor outcome at 3 months defined by a modified Rankin Scale score of 3 to 5 or death. RESULTS: Among 216 patients with acute stroke who were treated with alteplase, 111 (51.4%) had a lack of improvement at 24 hours. After adjusting for age, sex, and stroke severity, baseline glucose level on admission (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.40-5.99 for a glucose level >144 mg/dL [>8 mmol/L]), cortical involvement (OR, 2.66; 95% CI, 1.36-5.20), and time to treatment (OR, 1.01; 95% CI, 1.0-1.02 for each 1 minute increase in time to treatment) were independent predictors of lack of improvement. At 3 months, 43 patients (20.2%) had died; of the 170 survivors, 75 patients (44%) had poor outcomes. After adjusting for age, sex, and stroke severity, lack of improvement at 24 hours was an independent predictor of poor outcome (OR, 12.9; 95%CI, 5.7-29.6) and death (OR, 7.5; 95% CI, 2.9-19.6). Patients with a lack of improvement had longer lengths of hospitalization (14.5 vs 9.6 days; P = .02). CONCLUSIONS: Among patients with acute stroke treated with thrombolytic therapy, lack of improvement at 24 hours is associated with poor outcome and death at 3 months. Elevated glucose level, time to thrombolytic therapy, and cortical involvement were predictors of lack of improvement.

Cervical arterial dissection: time for a therapeutic trial?

BACKGROUND AND PURPOSE: Cervical arterial dissection is a major cause of stroke in young adults, yet despite standard treatment with anticoagulants or antiplatelet drugs, its management remains uncertain. The goal of this study was to assess the natural history of the disorder and to decide on the feasibility of a therapeutic trial. METHODS: Collaborating members of the Canadian Stroke Consortium prospectively enrolled consecutively referred patients with angiographically proven acute vertebral or carotid arterial dissection. Data recorded included clinical and radiological details, recurrence of ischemic cerebral events, and medical or surgical treatment. RESULTS: Of 116 patients, 67 had vertebral and 49 had carotid dissections, with no difference in age or sex. In 68 (59%), trauma occurred at the time of dissection. During the course of a 1-year follow-up, at least 17 patients (15%) had recurrent transient ischemic attacks, stroke, or death, mainly in the weeks immediately after the dissection. In 105 patients with complete follow-up, the event rate in those treated with anticoagulants was 8.3% and in those treated with aspirin was 12.4%, a nonsignificant difference of 4.1%. Using these data, we calculate that for a 2-arm trial (aspirin versus anticoagulants) with 80% power and 5% significance, 913 patients are needed in each group. CONCLUSIONS: From our data indicating an initial relatively high recurrence rate, a multicenter trial of anticoagulants versus aspirin involving a total of 2000 patients is feasible.

Is cerebral microembolism in mechanical prosthetic heart valves clinically relevant?

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) are frequently detected by transcranial Doppler (TCD) ultrasound in patients with mechanical prosthetic heart valves (PHVs), but published data about their clinical relevance are controversial. This study was undertaken to determine the clinical relevance of HITS in patients with mechanical PHVs. METHODS: The authors prospectively studied patients with mechanical PHVs using TCD monitoring for microemboli detection with and without O2 inhalation. The cognitive testing of patients included the Mini-Mental State Examination, the Dementia Rating Scale, and MicroCog. RESULTS: The authors studied 36 patients (20 women, aged 58 +/- 13 years). HITS were detected in 72% of patients, with a nonsignificant increase of HITS rate in the aortic valve group (P = .07). There was no significant difference in HITS rate between asymptomatic and symptomatic patients. In a multiple linear regression model, HITS rate was predicted only by younger age (P = .024). No correlation was found between HITS rate and the cognitive performance of patients. There was a significant decrease in HITS rate after 100% O2 inhalation compared to baseline levels (32.8 +/- 40.2 vs 6.1 +/- 11.3, P = .011). Subgroup analysis in asymptomatic patients confirmed this finding (P = .017), but in symptomatic patients, decreased HITS rate was not statistically significant (P = .18). CONCLUSION: Only age was a significant predictor of HITS in patients with mechanical PHVs. The lack of association between HITS, clinical symptoms, and cognitive functioning suggests that most of these signals represent harmless epiphenomena, and only HITS detected after O2 inhalation have any clinical relevance.

Long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis.

CONTEXT: The annual risk of ischemic stroke in patients with asymptomatic carotid artery stenosis is about 2% during the short-term (2-3 years), but the long-term risks of stroke and other vascular events are unknown, although they may affect surgical decision making. OBJECTIVE: To evaluate the long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis. DESIGN: Cohort study with a median follow-up of 10 years (range, 5-18 years). SETTING: The teaching hospital of the University of Toronto, Toronto, Ontario. PATIENTS: From the initial cohort of 500 patients, 106 patients with asymptomatic carotid artery stenosis were selected because they had completed at least 5 years of follow-up. MAIN OUTCOME MEASURES: Ipsilateral stroke, myocardial infarction, and nonstroke vascular death. RESULTS: The 10- and 15-year actuarial risks of ipsilateral stroke were 5.7% (95% confidence interval [CI], 0%-12%) and 8.7% (95% CI, 1%-17%), respectively, in patients with 0% to 49% internal carotid artery stenosis, and 9.3% (95% CI, 1%-18%) and 16.6% (95% CI, 1%-32%) in patients with 50% to 99% internal carotid artery stenosis. The 10- and 15-year risks of myocardial infarction and nonstroke vascular death were 10.1% (95% CI, 4%-16%) and 24.0% (95% CI, 14%-34%). Age (P =.02), diabetes mellitus (P =.02), and internal carotid artery stenosis of 50% or more (P =.04) were predictive of increased risks of myocardial infarction and nonstroke vascular death. Internal carotid artery stenosis of 50% or more did predict the risk of ipsilateral stroke (P =.003) when all 181 asymptomatic carotid arteries were included. CONCLUSIONS: The annual stroke risk in patients with asymptomatic carotid artery stenosis was low and remained stable during long-term follow-up. Any benefit from carotid surgery is therefore unlikely to increase significantly with long-term follow-up. The high long-term risks of myocardial infarction and nonstroke vascular death suggest that prevention strategies should concentrate on coronary risk more than stroke risk.