James Gebel

The Greater Cincinnati/Northern Kentucky Stroke Study Preliminary First-Ever and Total Incidence Rates of Stroke Among Blacks

BACKGROUND AND PURPOSE The Greater Cincinnati/Northern Kentucky Stroke Study was designed to be the first large, population-based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population. METHODS We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack (TIA) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93-6/30/94. We have already prospectively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites, including a random sample of all primary care physicians and nursing homes in the region. We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93-6/30/93 and report preliminary incidence rates for this 6-month period. RESULTS The overall incidence rate for all first-ever hospitalized or autopsied stroke (excluding TIAs) among blacks in the Greater Cincinnati region was 288 per 100000 (95% CI, 250 to 325, age- and sex-adjusted to 1990 US population). The overall incidence rate for first-ever and recurrent stroke (excluding TIAs) was 411 per 100000 (95% CI, 366 to 456). By comparison, the overall incidence rate of first-ever stroke among whites in Rochester, Minn, during the period 1985-1989 was 179 per 100000 (95% CI, 164 to 194, age- and-sex adjusted to 1990 US population). The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester, Minn, for all age categories except ages 75 and older, for which the rates were similar. CONCLUSIONS We conservatively estimate that 731100 first-ever or recurrent strokes occurred in the United States during 1996. Studies of first-ever as well as total stroke among biracial and representative populations are critical for understanding temporal trends in the incidence rate and the burden of stroke in the US population.

Transplantation of cultured human neuronal cells for patients with stroke

Article abstract Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0.046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Stroke in a Biracial Population The Excess Burden of Stroke Among Blacks

Background and Purpose— Excess mortality resulting from stroke is an important reason why blacks have higher age-adjusted mortality rates than whites. This observation has 2 possible explanations: Strokes occur more commonly among blacks or blacks have higher mortality rates after stroke. Our population-based epidemiological study is set in the Greater Cincinnati/Northern Kentucky region of 1.31 million people, which is representative of the US white and black populations with regard to many demographic and socioeconomic characteristics. Methods— Hospitalized cases were ascertained by International Classification of Diseases (ninth revision) discharge codes, prospective screening of emergency department admission logs, and review of coroner’s cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses, followed by physician review. Race-specific incidence and case fatality rates were calculated. Results— We identified 3136 strokes during the study period (January 1, 1993, to June 30, 1994). Stroke incidence rates were higher for blacks at every age, with the greatest risk (2- to 5-fold) seen in young and middle-aged blacks (<65 years of age). Case fatality rates did not differ significantly in blacks compared with whites. Applying the resulting age- and race-specific rates to the US population in 2002, we estimate that 705 000 to 740 000 strokes have occurred in the United States, with a minimum of 616 000 cerebral infarctions, 67 000 intracerebral hemorrhages, and 22 000 subarachnoid hemorrhages. Conclusions— Excess stroke-related mortality in blacks is due to higher stroke incidence rates, particularly in the young and middle-aged. This excess burden of stroke incidence among blacks represents one of the most serious public health problems facing the United States.

Genetic and Environmental Risk Factors for Intracerebral Hemorrhage Preliminary Results of a Population-Based Study

Background and Purpose— Intracerebral hemorrhage (ICH) has a 30-day mortality rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint analysis of the first population-based, case-control study that examines both genetic and environmental risk factors of ICH. Methods— We prospectively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region. All cases underwent medical record and neuroimaging review. Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population-based control subjects by age, race, and sex. Multivariable logistic regression was performed to identify significant independent risk factors. Results— We enrolled 188 cases of ICH (67 lobar, 121 nonlobar) and 366 control subjects in the direct interview arm of the study. Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first-degree relative with ICH. Significant independent risk factors for nonlobar ICH were hypertension, prior stroke, and first-degree relative with ICH. An increasing level of education was associated with a decreased risk of nonlobar ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and the attributable risk of hypertension for nonlobar ICH was 54%. Conclusions— There is significant epidemiological evidence that the pathophysiology of ICH varies by location. We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension.

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: The PROACT II trial

Objective: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. Method: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on “treatment received” and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of ≥4 points) within 36 hours of treatment initiation. Results: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK–treated patients occurred at a mean of 10.2 ± 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK–treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with ≤200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). Conclusions: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Eligibility for Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke: A Population-Based Study

Background and Purpose— Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment. Methods— All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. Results— Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in <3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests. Conclusions— In our population in 1993 to 1994, 8% of all ischemic stroke patients presented to an ED within 3 hours and met other eligibility criteria for rtPA. Even if time were not an exclusion for rtPA, only 29% of all ischemic strokes in our population would have otherwise been eligible for rtPA.

Relative Edema Volume Is a Predictor of Outcome in Patients With Hyperacute Spontaneous Intracerebral Hemorrhage

Background and Purpose— Little is known about the relationship between perihematomal edema in spontaneous intracerebral hemorrhage (ICH) and outcome. The purpose of this study was to determine whether absolute or relative edema volume (edema volume divided by hematoma volume) predicts mortality or functional outcome in patients with hyperacute spontaneous ICH. We hypothesized that increasing baseline relative edema volume is associated with greater probability of poor functional outcome. Methods— This was a secondary analysis of a prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were imaged within 3 hours of onset, then 1 and 20 hours later. Our primary analysis excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), intraventricular extension (n=38), and no consent (n=2). We analyzed whether associations existed between baseline edema volumes or other clinical/radiological variables and either 12-week modified Rankin Scale score >2 or 30-day mortality. Secondary analyses used 20-hour CT scan data, all patients with supratentorial ICH, and 12-week Barthel Index score <85. Results— By multivariable logistic regression analysis, baseline relative edema was the strongest independent predictor of functional outcome and was associated with lesser odds of poor 3-month functional outcome (odds ratio, 0.09 per 1.0-unit [100%] increase; 95% CI, 0.01 to 0.64;P =0.016) and 12-week Barthel Index score <85 (odds ratio, 0.12; 95% CI, 0.02 to 0.91;P =0.039) but did not predict mortality. Secondary analyses confirmed this result. Absolute edema volume predicted neither mortality nor functional outcome. Conclusions— Relative edema is strongly predictive of functional outcome in patients with hyperacute supratentorial spontaneous ICH without intraventricular extension.

Clonal Human (hNT) Neuron Grafts for Stroke Therapy : Neuropathology in a Patient 27 Months after Implantation

Although grafted cells may be promising therapy for stroke, survival of implanted neural cells in the brains of stroke patients has never been documented. Human NT2N (hNT) neurons derived from the NTera2 (NT2) teratocarcinoma cell line were shown to remain postmitotic, retain a neuronal phenotype, survive >1 year in host rodent brains and ameliorate motor and cognitive impairments in animal models of ischemic stroke. Here we report the first postmortem brain findings of a phase I clinical stroke trial patient implanted with human hNT neurons adjacent to a lacunar infarct 27 months after surgery. Neurofilament immunoreactive neurons were identified in the graft site, fluorescent in situ hybridization revealed polyploidy in groups of cells at this site just like polyploid hNT neurons in vitro, and there was no evidence of a neoplasm. These findings indicate that implanted hNT neurons survive for >2 years in the human brain without deleterious effects.

Subarachnoid Hemorrhage A Preventable Disease With a Heritable Component

Background and Purpose— Subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysm affects approximately 16 000 Americans annually, and almost 40% of affected patients die within 30 days despite the best current therapy. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our population-based, case-control study. Methods— Cases were prospectively collected and matched 2:1 by age, race, and gender to controls using random digit dialing. Personal risk factor history, family history, neuroimaging data, and genetic samples were obtained. Univariate and bivariate analyses were performed and population-attributable risks estimated. Multivariable analysis was performed using conditional logistic regression. Results— Between June 1997 and February 2000, 107 cases and 197 controls were enrolled. In bivariate analyses, a large proportion of population-attributable risk for SAH could be explained by modifiable risk factors: smoking, hypertension, and heavy alcohol use. In multivariable analysis, current cigarette smoking, history of hypertension, frequent alcohol use, lower body mass index, and a family history of a relative with SAH or intracranial aneurysm were found to be significant, independent risk factors for SAH. Conclusion— Our data confirm previous reports that SAH clusters within some families independent of environmental risk factors, suggesting that SAH has a significant genetic component. Yet, even among families at increased risk of SAH, smoking cessation, treatment of hypertension, and reduced alcohol intake may substantially decrease SAH risk. The independent associations with heavy alcohol use and low body mass index with SAH may be confounded by smoking and require further study.

Ischemic Stroke Subtypes. A Population-Based Study of Incidence Rates Among Blacks and Whites

Background and Purpose— Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population. Methods— The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by International Classification of Disease (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners’ cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population. Results— Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks. Conclusions— The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.