Defining Ischemic Core in Acute Ischemic Stroke Using CT Perfusion: A Multiparametric Bayesian-Based Model.

BACKGROUND AND PURPOSE: The Bayesian probabilistic method has shown promising results to offset noise-related variability in perfusion analysis. Using CTP, we aimed to find optimal Bayesian-estimated thresholds based on multiparametric voxel-level models to estimate the ischemic core in patients with acute ischemic stroke. MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke who had baseline CTP and achieved successful recanalization were included. In a subset of patients, multiparametric voxel-based models were constructed between Bayesian-processed CTP maps and follow-up MRIs to identify pretreatment CTP parameters that were predictive of infarction using robust logistic regression. Subsequently CTP-estimated ischemic core volumes from our Bayesian model were compared against routine clinical practice oscillation singular value decomposition-relative cerebral blood flow <30%, and the volumetric accuracy was assessed against final infarct volume. RESULTS: In the constructed multivariate voxel-based model, 4 variables were identified as independent predictors of infarction: TTP, relative CBF, differential arterial tissue delay, and differential mean transit time. At an optimal cutoff point of 0.109, this model identified infarcted voxels with nearly 80% accuracy. The limits of agreement between CTP-estimated ischemic core and final infarct volume ranged from -25 to 27 mL for the Bayesian model, compared with -61 to 52 mL for oscillation singular value decomposition-relative CBF. CONCLUSIONS: We established thresholds for the Bayesian model to estimate the ischemic core. The described multiparametric Bayesian-based model improved consistency in CTP estimation of the ischemic core compared with the methodology used in current clinical routine.

Seasonal distribution of antiphospholipid antibodies.

BACKGROUND AND PURPOSE: The purpose of this study was to determine if there was a seasonal variation in antiphospholipid antibody (aPL) titers and whether this variation differed between stroke cases and control subjects. METHODS: IgG and IgM anticardiolipin and antiphosphatidyl serine antibody titers were obtained on serum samples from 884 stroke patients and 1024 control subjects over a 7-year period. Temporal distributions by month of blood draw were evaluated. RESULTS: Marked seasonal differences in the proportion of positive titers were found for control subjects, but no seasonal variability among patients was noted. In control subjects, positive titers occurred less frequently in the summer months, mirroring the seasonal trends seen in respiratory track infections and rheumatic fever. CONCLUSIONS: Our data suggest some aPL antibodies arise from different origins in patients and control subjects. The seasonality observed in the apparently normal population may be related to antibodies of infectious origin and is consistent with the reported lack of association with thrombosis of infection-related antibodies.

Stroke mechanisms and clinical presentation in large subcortical infarctions.

Large subcortical infarctions may be due to cerebral embolism and cause cortical signs more frequently than small subcortical infarctions, which usually result from small-vessel disease and are not associated with cortical findings. We evaluated 51 consecutive patients with a subcortical infarct on CT that was 1.5 cm or larger for a potential carotid or cardiac source of embolism and determined how frequently aphasia, hemineglect, or gaze paresis occurred. A carotid or cardiac embolic source was identified in 63% of the total population with a carotid source occurring in 23% and a cardiac source occurring in 49%. More than one-half of the patients with hypertension or diabetes mellitus had an embolic source, whereas all patients without these risk factors had a possible carotid or cardiac source of embolism. Aphasia or hemineglect occurred in 39% of patients and gaze paresis occurred in 41%. Large subcortical strokes frequently result in a different clinical syndrome and from a different mechanism than small subcortical strokes.

Aortic plaque in patients with brain ischemia: diagnosis by transesophageal echocardiography.

We evaluated 183 patients with brain ischemia for an embolic source, using transesophageal echocardiography with extensive imaging of the thoracic aorta. There were mobile, frond-like projections of aortic plaque in seven (4%) patients. The plaque originated on a wide base on the posterior aspect of the ascending aorta at its junction with the transverse arch in six patients, and on the aortic root in one. The acute event was a cerebral infarction in five patients, and a transient ischemic attack in two. This type of aortic plaque could be a previously underdiagnosed source of cerebral embolism that is now easily visualized by transesophageal echocardiography.

Antiphosphatidyl serine antibodies are independently associated with ischemic stroke.

OBJECTIVE: To determine whether elevated titers of antiphosphatidyl serine antibodies (aPS) are associated with an increased risk of ischemic stroke in a general stroke population. BACKGROUND: aPS are members of the family of antiphospholipid antibodies that has been associated with increased stroke risk. Although aPS have been demonstrated to occur in 18% of a group of young patients with cerebrovascular symptoms, their prevalence in the general stroke population is unknown, and no controlled study to assess the strength of their association with ischemic stroke has been undertaken previously. METHODS: A case-control study comparing 267 acute ischemic stroke patients and 653 community controls. Sera were obtained immediately after acute stroke in patients. Titers of IgG aPS >16 IgG phospholipid units or IgM aPS >22 IgM phospholipid units were considered positive. Odds ratios (ORs) were obtained by logistic regression, adjusting for age, gender, race/ethnicity, history of hypertension, diabetes mellitus, cardiovascular disease, and cigarette smoking. RESULTS: The adjusted OR was 5.6 (95% confidence interval [CI] 1.8, 18.0) for IgG aPS and 2.9 (95% CI 1.6, 5.3) for IgM aPS. The adjusted OR for either an elevated IgG or IgM aPS was 3.2 (95% CI 1.8, 5.5). CONCLUSIONS: This study demonstrates that elevated IgG and IgM antiphosphatidyl serine antibodies titers are associated with increased risk of ischemic stroke. The prevalence of these antibodies is lower, but the associated stroke risk is comparable with that of anticardiolipin antibodies.

Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features.

To gain insight into the historical features relevant to the diagnosis of cardiac embolic strokes, we studied the 1,290 patients with cerebral infarcts in the NINCDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we divided the patients into groups of high (n = 250), medium (n = 166), and low (n = 874) risk of a cardiogenic mechanism for their stroke. There was a highly significant graded relationship between increasing risk of a cardiac source and a history, or presence of, systemic embolism, abrupt onset, and diminished level of consciousness at onset. These clinical features may be useful for assessing the likelihood of a cardiac embolic mechanism in patients with cerebral infarcts.

Infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank: neurologic examination.

To gain insight into neurologic signs relevant to the diagnosis of cardiogenic embolism, we analyzed data from 1,290 patients with cerebral infarcts in the NINDS Stroke Data Bank. Based solely on the presence of potential cardiac sources of embolism, we divided patients into groups of high (N = 250), medium (N = 167), and low (N = 873) risk of a cardiogenic mechanism for their stroke. Diminished level of consciousness was highly associated with the presence of a cardiac source of embolism. Of the four primarily cortical deficits assessed, three (visual field abnormalities, neglect, and aphasia) showed a highly significant graded relationship to the cardiac risk groups. For the fourth cortical deficit (other nonlanguage cognitive functions), this relationship did not attain statistical significance. Conversely, hemiparesis without sensory or cortical deficits had a strong inverse association to the presence of a cardiac source of embolism. This inverse association was weaker for sensorimotor strokes and nonexistent for pure sensory strokes. Although some neurologic findings had highly significant associations with the presence of a cardiac source of embolism, their predictive value for an embolic source was low.

Intracranial metastases in the initial staging of bronchogenic carcinoma.

We evaluated the effectiveness of neurologic examination, electroencephalography (EEG), and computed tomography (CT) in the initial staging of patients with nonsmall cell carcinoma. Eight of 66 patients had evidence of intracranial metastases. Three of these had no other metastases and would otherwise have been surgical candidates. Thus, thorough investigation for evidence of intracranial metastases is warranted at the time of initial staging. The CT proved to be more effective than clinical evaluation or EEG, alone or in combination, in detecting intracranial metastases. The CT screening of patients prior to curative resection should increase the success rate for such procedures by eliminating patients with preexisting metastases.

Dipping is superior to cusums analysis in assessment of the risk of stroke in a case-control study.

BACKGROUND: Blunted nocturnal decline in blood pressure (BP) is associated with increased risk of stroke. Mean day-night BP difference (dipping) and cusums-derived circadian alteration magnitude (CDCAM) of BP are the common measures of diurnal BP variation. Although a significant number of clinical trials have demonstrated that dipping is associated with a lower risk of cardiovascular events, the clinical value of CDCAM of BP is unknown. We evaluated the association between dipping and CDCAM of BP and the risk of stroke. METHODS: We analyzed 24-h ambulatory BP recordings of 110 control subjects and 91 stroke survivors enrolled in a case-control stroke study. Nondipping was defined as nocturnal drop of < 10 mm Hg in systolic BP. The associations between nondipping, CDCAM of BP, and risk of stroke were calculated in the same sample. RESULTS: There were significantly fewer nondippers in the control group as compared with those among the stroke survivors. The odds ratio for stroke of nondippers was 2.3. By contrast, there was no significant difference in CDCAM of systolic BP between the control and stroke survivor groups. This finding could not be explained by the presence of reverse dippers in both groups. CONCLUSIONS: In this case-control study, classification of subjects into dippers and nondippers was found to be more clinically useful than cusums analysis of BP profile. Analysis of prospective data is needed to determine the clinical value of the cusums analysis of BP profile.

The association of blunted nocturnal blood pressure dip and stroke in a multiethnic population.

Nondipping has been defined as a reduction in the mean systolic and diastolic blood pressure (BP) of <10% from awake to sleep. We hypothesized that nondipping might be associated with stroke in minority populations. We monitored BP over a 24 h period with an ambulatory device in 166 cases from a multiethnic population of stroke survivors (63 blacks, 61 non-Hispanic whites, and 42 Caribbean Hispanics, aged 69.5 +/- 11 years) and 217 community control subjects (73 blacks, 107 non-Hispanic whites, and 67 Caribbean Hispanics, aged 69 +/- 9 years). Prevalence of nondipping was significantly greater among cases than among control subjects (64% v. 37%, P < .001). In a multiple logistic regression model adjusted for traditional risk factors for stroke, nondipping conferred an increased risk for stroke. Probability of stroke associated with nondipping (odds ratio (OR) 2.5, confidence interval (CI) 1.6 to 4.0) was equal to that of traditional risk factors. Nondipping increased the chance of having a stroke in both non-Hispanic whites (OR 4.2, P < .001) and blacks/Caribbean Hispanics (OR 1.9, P = .03). The strength of the contribution of nondipping to stroke risk was similar in all ethnic groups. Nondipping was associated with stroke in both men and women. Given the previous reports that nondipping contributes to stroke risk in European and Asian populations, these data suggest that nondipping may be universally associated with risk for stroke.

Diffusion-weighted MR of acute cerebral infarction: comparison of data processing methods.

BACKGROUND AND PURPOSE: Some investigators have proposed that either calculated diffusion trace images or apparent diffusion coefficient (ADC) maps, which require imaging with multiple diffusion sensitivities and/or postacquisition image processing, are essential for the accurate interpretation of diffusion-weighted images in acute stroke because of the possible pitfalls of regional diffusion anisotropy, magnetic susceptibility artifacts, and confounding T2 effects, all of which alter signal on diffusion-weighted MR images. The purpose of our study was to compare the sensitivity, specificity, and accuracy of simple, orthogonal-axis diffusion-weighted imaging for the diagnosis of early cerebral infarction with three other sets of postacquisition-processed images: isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace images. METHODS: Twenty-six consecutive adult patients with signs and symptoms consistent with a clinical diagnosis of early cortical and/or subcortical cerebral infarction and 17 control subjects were studied with multisection, single-shot, spin-echo echo-planar diffusion-weighted imaging at 1.5 T to generate a set of three orthogonal-axis diffusion-weighted images. Isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace (mean ADC) images were then generated off-line and all four sets of images were interpreted blindly by two neuroradiologists. RESULTS: The average sensitivity, specificity, and accuracy for the orthogonal-axis diffusion-weighted images were 98.1%, 97.1%, and 97.7%, respectively. The average sensitivity, specificity, and accuracy for isotropic diffusion-weighted images were 88.5%, 100%, and 93% respectively. The average sensitivity, specificity, and accuracy for diffusion trace-weighted images were 82.7%, 73.6%, and 79.1%, respectively. The average sensitivity, specificity, and accuracy for diffusion trace images were 50.0%, 85.3%, and 64.0%, respectively. CONCLUSION: Orthogonal-axis diffusion-weighted images have the highest sensitivity and accuracy and very high specificity for early cerebral infarction. Our data contradict the contention that quantitative diffusion maps, requiring imaging with multiple diffusion sensitivities and/or subsequent image processing, are necessary for clinical stroke imaging.

Vertebral artery dissection in Turner's syndrome: diagnosis by magnetic resonance imaging.

Aortic artery dissection is a rare but well-recognized complication of Turner's syndrome. Isolated carotid or vertebral artery dissection has not previously been reported. The authors report the clinical and magnetic resonance imaging findings in a 30-year-old woman with Turner's syndrome who developed a high cervical spinal cord infarction with a Brown-Sequard syndrome owing to bilateral vertebral artery dissection. The diagnosis and management of the case is reviewed.

Feasibility of physician-developed expert systems.

The authors developed an experimental domain-independent "expert system generator" intended for direct use by physicians. They then undertook a four-year study to determine whether physicians could use such a system effectively. During this period they taught the use of the expert system generator to 70 medical students, who utilized it to build two small medical expert systems. At the conclusion of the course, students were examined on decision-making concepts and completed anonymous questionnaires. Performance scores, a composite of test and project grades, were calculated for each student. There was no significant association between previous computer experience and performance score. Thirty-two of 47 students responding felt the expert system generator was easy to use; 15 felt it was of moderate difficulty. Forty-three of 47 thought it a useful teaching aid. These data support the conclusion that physicians can learn to use domain-independent software to implement medical expert systems directly, without a knowledge engineer as an intermediary.

Stroke risk factors.

Despite advances in the treatment of acute cerebral infarction, the most effective method of reducing stroke morbidity and mortality is the identification and modification of stroke risk factors. Modifiable stroke risk factors include hypertension, atrial fibrillation, hypercholesterolemia, cigarette smoking, hyperhomocystinemia, and carotid stenosis. Improved identification of individuals at increased stroke risk due to these factors can reduce individual risk and the cost to society of the consequences of stroke.

Frontiers in the treatment of ischemic stroke.

Advances in the understanding of the pathophysiology of ischemic neuronal death have led to the development of new approaches to treating acute stroke. Concurrently technologic advances have permitted application of older approaches in a more sophisticated manner. These advances herald an era in which rapid, precise evaluation and treatment of the patient with acute stroke may dramatically alter prognosis. This article reviews some of these advances.

High-specificity neurological localization using a connectionist model.

Most previous connectionist models for diagnosis have been developed using error backpropagation. While these systems function reasonably well, they have been limited by their need for a large database of test cases, to situations where a single disorder is present, and by the large number of connections required between fully-connected sets of processing units. Here we describe a recently developed connectionist model that overcomes these limitations. This approach can reuse existing causal knowledge bases, works well in situations where multiple disorders can occur simultaneously, and does not require fully-connected sets of processing units. We demonstrate that the accuracy of this model is comparable to that of more conventional AI programs using the same knowledge base in determining precisely the site of brain damage in a group of 50 stroke patients. These results support the conclusion that connectionist models can effectively use pre-existing causal knowledge bases from AI systems, and that they can function accurately when handling actual clinical problems.

The effects of various definitions of dipping and daytime and night-time on the characterization of 24 h profiles of blood pressure.

BACKGROUND: Ambulatory blood pressure monitoring allows characterization of the patient's average blood pressure load as well as various profiles of blood pressure. Results from clinical studies suggest that dippers (patients whose blood pressures decrease during night-time) have a lower risk of cardiovascular events than do nondippers with similar daytime blood pressures. However, the definitions of dipping as well as of daytime and night-time vary among clinical studies. OBJECTIVE: To determine whether various definitions lead to markedly different classifications of dipper status. DESIGN AND METHODS: We analyzed 894 24 h ambulatory blood pressure recordings that had been performed at our institution according to three previously published definitions of daytime and night-time and five definitions of dipping. RESULTS: There were small but statistically significant differences among the mean daytime and night-time blood pressures determined using the various definitions. Likewise, the proportions of dippers varied significantly with definitions of dipping and of daytime and night-time. CONCLUSIONS: Differences among definitions of dipping as well as of daytime and night-time lead to significant variations in the characterization of patients' 24 h blood blood pressure profiles. The results of this analysis can be used when comparing the results of clinical studies as well as in their design.

Thyrocervical to vertebral artery transposition and ipsilateral carotid endarterectomy.

BACKGROUND: We report a new method for treating patients with symptomatic high-grade stenosis of the proximal vertebral artery associated with high-grade stenosis of the ipsilateral carotid artery. METHODS: Our patient had high-grade stenosis of the proximal right vertebral artery as well as high-grade stenosis of the ipsilateral carotid artery and suffered continued posterior circulation ischemic neurological deficits despite anticoagulation. RESULTS: The patient was successfully treated with a carotid endarterectomy and thyrocervical-to-vertebral artery transposition in a single operation. CONCLUSION: This procedure has the advantage in this setting of avoiding additional cross clamping on the diseased carotid artery that would normally be required for the vertebral-to-carotid artery transposition with carotid endarterectomy. Also, thrombosis at one anastamosis site would not endanger the other site as well.

Delayed signal detection by diffusion-weighted imaging in brainstem infarction.

Diffusion-weighted magnetic resonance imaging (DW MRI) is a sensitive and specific technique for imaging acute hemispheric infarction. Its utility in the diagnosis of acute brainstem infarction has not been well studied. We present 3 cases of brainstem infarction in which DW MRI performed 5 to 15 hours after symptom onset failed to reveal any abnormality. Repeat diffusion-weighted imaging (DWI) 2 to 5 days later did demonstrate an abnormality in the clinically appropriate region in each instance. This suggests that the time course to the development of abnormalities detectable by DWI may be longer in brainstem than in hemispheric infarctions. Therefore, repeat studies after initially negative DWI might be useful in the diagnosis of brainstem infarctions.

Clinical improvement related to thrombolysis of third ventricular blood clot in a patient with thalamic hemorrhage.

Intraventricular extension of hemorrhage after intraparenchymal hemorrhage is associated with significant morbidity and mortality. Clinical improvement is reported in a patient with thalamic hemorrhage with intraventricular extension after third and fourth ventricular blood clot resolution with instillation of urokinase intraventricularly. A 49-year-old man with hypertension collapsed while at work. A computed tomography (CT) scan of the head revealed a left thalamic hemorrhage with extension into the lateral, third, and fourth ventricles and associated hydrocephalus. A left frontal intraventricular catheter (IVC) was placed and intraventricular urokinase was administered at a dose of 25,000 U every 12 hours. The CT scan revealed resolution of the lateral ventricular dilatation and blood clot but no decrease in third or fourth ventricular hemorrhage. No clinical improvement was noted. The IVC was reinserted on the right side with the catheter tip placed through the foramen of Monroe into the third ventricle. Twelve hours after receiving the first dose of urokinase through the new catheter, the patient's condition improved. The CT scan showed a reduction in the volume of blood of the third and fourth ventricles. This case report shows that treatment of hydrocephalus with an IVC was not sufficient to provide a therapeutic effect. Substantial clinical improvement occurred only after the blood clot was cleared from the third and fourth ventricles.