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.

Ischemic stroke in an adult with glycogen storage disease type I.

Glycogen Storage Disease Type I (GSD-I) is a metabolic disorder characterized by deficiency of glucose-6-phosphatase resulting in ineffective glycogen metabolism to glucose. These patients frequently have hyperlipidemia, among many other metabolic derangements. There is no consensus regarding the risk of developing atherosclerosis. We report an adult male with GSD-I who presented with cerebral infarction and a history of prior ischemic stroke and multiple coronary stent placements. We suggest that patients with GSD-I do have an increased risk of atherosclerosis and its complications and predict that these complications will be seen more frequently since patients with GSD-I are living longer as a result of better treatment.

Has evidence changed practice?: appropriateness of carotid endarterectomy after the clinical trials.

OBJECTIVE: To assess how appropriateness of and indications for carotid endarterectomy (CEA) have changed following the publication of several large international randomized controlled trials (RCTs) designed to rationalize use of CEA. METHODS: The New York Carotid Artery Surgery Study (NYCAS) is a population-based cohort study of all CEAs performed on elderly patients from January 1998 through June 1999 in New York State. Detailed clinical data were abstracted from medical charts to assess indications for and appropriateness of surgery using a list of 1,557 indications for CEA developed by national experts using RAND appropriateness methods. Deaths and strokes within 30 days of surgery were ascertained and confirmed by two physicians. RESULTS: Among the 9,588 patients, the mean age was 74.6 years and 93.6% had 70 to 99% carotid stenosis. Nearly three-quarters of patients (72.3%) underwent CEA for asymptomatic stenosis, 18.6% for TIA, and 9.1% for stroke. Overall, 87.1% of operations were done for appropriate reasons, 4.3% for uncertain reasons, and 8.6% for inappropriate reasons (vs 32% inappropriate before the RCTs, p < 0.0001). Among procedures judged inappropriate, the most common reasons were high comorbidity in asymptomatic patients (62.2%), operating after a major stroke (14.2%), or for minimal stenosis (10.5%). Among asymptomatic patients, those with high comorbidity had over twice the risk of death or stroke compared to those without high comorbidity (7.13% vs 2.69%, p < 0.0001). CONCLUSIONS: Since publication of the randomized controlled trials, there has been a reduction in the proportion of patients undergoing carotid endarterectomy (CEA) for inappropriate reasons. The shift toward many asymptomatic patients undergoing CEA is concerning because the net benefit from surgery for these patients is low and is reduced further for patients with high comorbidity.

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.

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.

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.

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.

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.

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.

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.

Hypertensive cardiovascular damage in patients with primary autonomic failure.

Patients with primary autonomic failure have left-ventricular hypertrophy probably as a result of night-time hypertension.

Treatment of refractory complex-partial status epilepticus with propofol: case report.

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.

Treatment of intraventricular hemorrhage with urokinase : effects on 30-Day survival.

BACKGROUND AND PURPOSE: Intraventricular hemorrhage (IVH) remains associated with high morbidity and mortality. Therapy with external ventricular drainage alone has not modified outcome in these patients. METHODS: Twelve pilot IVH patients who required external ventricular drainage were prospectively treated with intraventricular urokinase followed by the randomized, double-blinded allocation of 8 patients to either treatment or placebo. Observed 30-day mortality was compared with predicted 30-day mortality obtained by use of a previously validated method. RESULTS: Twenty patients were enrolled; admission Glasgow Coma Scale score in 11 patients was

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.

Diffusion-weighted MRI in acute lacunar syndromes. A clinical-radiological correlation study.

BACKGROUND AND PURPOSE: Clinical-radiological correlation studies in lacunar syndromes have been handicapped by the low sensitivity of CT and standard MRI for acute small-vessel infarction and their difficulty in differentiating between acute and chronic lesions. METHODS: We prospectively studied 43 patients presenting with a classic lacunar syndrome using diffusion-weighted MRI, a technique with a high sensitivity and specificity for acute small-vessel infarction. RESULTS: All patients were scanned within 6 days of stroke onset. An acute infarction was identified in all patients. Pure motor stroke was associated with lesions in the posterior limb of the internal capsule (PLIC), pons, corona radiata, and medial medulla; ataxic hemipareses with lesions in the PLIC, corona radiata, pons, and insular cortex; sensorimotor stroke with lesions in the PLIC and lateral medulla; dysarthria-clumsy hand syndrome with lesions in the PLIC and caudate nucleus; and pure sensory stroke with a lesion in the thalamus. Supratentorial lesions extended into neighboring anatomic structures in 48% of the patients. CONCLUSIONS: Lacunar syndromes can be caused by lesions in a variety of locations, and specific locations can cause a variety of lacunar syndromes. Extension of lesions into neighboring structures in patients with lacunar syndromes appears to be more frequent than previously described in studies using CT and standard MRI.

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.

Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity.

BACKGROUND AND PURPOSE: Previous studies have produced conflicting results regarding the putative association between anticardiolipin antibodies (aCL) and infarction in the general stroke population. These inconsistencies may be a function of sample size and methodological differences among the studies. The purpose of the present study, the largest case-control study of this issue to date, was to assess aCL status as an independent risk factor for ischemic stroke in a multiethnic, urban population. METHODS: We obtained aCL titers in 524 hospitalized acute stroke patients and 1020 community controls enrolled in the Minorities Risk Factors and Stroke Study. The results were interpreted as negative (30.0 GPL or 15.0 MPL units). Odds ratios (ORs) were adjusted for age, sex, race/ethnicity, history of diabetes, hypertension, atrial fibrillation, coronary artery disease, and current cigarette smoking. RESULTS: A positive aCL titer was present in 11% (111/1020) of controls and 34% (180/524) of cases. The adjusted OR for any positive aCL titer was 4.0 (95% CI, 3.0 to 5.5). For any positive IgG aCL titer this value was 3.9 (95% CI, 2.8 to 5.5), and for any positive IgM aCL titer it was 3.4 (95% CI, 2.1 to 5.5). There were no significant differences in ORs associated with high- or low-positive IgG or IgM aCL titers. CONCLUSIONS: In the largest study of its kind to date, aCL antibodies were demonstrated to be independent stroke risk factors across the 3 ethnic groups studied, conferring a 4-fold increased risk of ischemic stroke. IgG and for the first time IgM aCL were each shown to be associated with increased stroke risk. The prevalence of these antibodies and the stroke risk associated appear greater than previously reported.