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Background Lipid-lowering medications (LLMs) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment (MCI) at baseline. Methods A longitudinal, observational study was conducted of 3069 cognitively healthy elderly patients (≥75 years of age) who were enrolled in the Ginkgo Evaluation of Memory Study. The primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia (AD). The secondary outcome measure was the change in global cognitive function over time measured by scores from the Modified Mini-Mental State Exam (3MSE) and the cognitive subscale of the AD Assessment Scale (ADAS-Cog). Results Among participants without MCI at baseline, the current use of statins was consistently associated with a reduced risk of all-cause dementia (hazard ratio [HR], 0.79; 95% confidence interval [95% CI], 0.65-0.96; P = .021) and AD (HR, 0.57; 95% CI, 0.39-0.85; P = .005). In participants who initiated statin therapy, lipophilic statins tended to reduce dementia risk more than nonlipophilic agents. In contrast, there was no significant association between LLM use (including statins), dementia onset, or cognitive decline in individuals with baseline MCI. However, in individuals without MCI at baseline, there was a trend for a neuroprotective effect of statins on cognitive decline. Conclusions Statins may slow the rate of cognitive decline and delay the onset of AD and all-cause dementia in cognitively healthy elderly individuals, whereas individuals with MCI may not have comparable cognitive protection from these agents. However, the results from this observational study need to be interpreted with caution and will require confirmation by randomized clinical trials stratifying treatment groups based on MCI status at baseline.

Objective: To delineate factors associated with cognitive function following stroke and test the hypothesis that vascular risk factors associated with oxidative stress impair recovery. Method: We performed a post hoc analysis of the extensive longitudinal database from the 3,680 subjects (over 35 years old) entered between 1996 and 2003 into the Vitamin Intervention for Stroke Prevention trial using a linear mixed effects model. The primary outcome variables were scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS). Results: MMSE and mRS gradually improved during the 2-year follow-up period. Increased age and nonwhite race, recurrent stroke, diabetes mellitus, left hemisphere cortical lesions, and values of high-density lipoprotein and homocysteine were independent predictors of less successful cognitive recovery. A strong interaction between homocysteine and age indicated a threshold effect beginning in the late 50s. No vitamin treatment effects were identified. Similar factors were identified for recovery of disability as assessed by the mRS, although there were qualitative and quantitative differences. Conclusions: The finding that diabetes, high-density lipoprotein, and homocysteine predict poorer cognitive function and greater disability after stroke is consistent with the hypothesis that metabolic stress plays a significant role in the poststroke period.

Ipsilateral transient ischemic attack (TIA) and cerebral infarction (CI) are primary end points of the Asymptomatic Carotid Atherosclerosis Study (ACAS), an ongoing multicenter, prospective, randomized trial designed to assess the effectiveness of carotid endarterectomy for patients with asymptomatic, hemodynamically significant stenosis of the internal or common carotid artery. The evanescent nature and absence of residual physical findings in TIAs pose special difficulties that contribute to interobserver disagreement. A standardized definition was established to be applied accurately and uniformly at the participating centers, including a questionnaire on six cardinal neurological symptoms, a computerized algorithm for characterization of events, and a verification system involving the independent evaluations of three reviewers. Modifications to the end point verification protocol after pilot testing in 115 patients with one or more symptoms enabled the algorithm to distinguish vascular from nonvascular events with a sensitivity of 83%, a specificity of 69%, positive predictive value of 71%, and negative predictive value of 82%. ACAS has developed a system for detecting and diagnosing end points. Using the algorithm as a guideline, consensus between two institutional physicians and a blinded independent reviewer must be made for an end point to be declared. If no consensus can be reached, a panel of two blinded external reviewers confers to arrive at an adjudication of the case. All potential end points are reviewed retrospectively by an end points committee for final adjudication.

We investigated the diagnostic performance of a brief Power Doppler Imaging (PDI) screening examination for carotid artery stenoses using a newly developed portable instrument.A highly experienced sonographer screened in total 152 carotid arteries by either continuous wave (cw) Doppler (n= 50) or a lightweight (2.4 kg) portable duplex device (n= 102) in a prospective study of 76 high-risk patients. The screening protocols included either spectrum analysis and frequency shift measurement in both internal carotid arteries with cw-Doppler or determination of area and diameter ratios in transverse and longitudinal views of both carotid arteries in B-mode and with PDI, but without velocity measurement. Both protocols were evaluated against a complete routine duplex ultrasonography examination.According to the complete examination, stenoses were50% in 73 of 102 (71.6%), 50-75% in 19 of 102 (18.6%), 75-95% in 7 of 102 (6.9%), and occluded in 3 of 102 (2.9%) arteries (PDI cohort), and50% in 39 of 50 (78%), 50-75% in 8 of 50 (16%), 75-95% in 2 of 50 (4%), and occluded in 1 of 50 (2%) artery (cw-Doppler cohort). Mean screening time was 8.8 +/- 2.5 minute (PDI) and 9.4 +/- 2.6 minute (cw-Doppler). For stenoses75%, A(z) values (area under the receiver operating characteristics curve) were 0.897 for area ratios, 0.843 for diameter ratios (PDI protocol) and 1.0 for the cw-Doppler protocol.The diagnostic performance of the cw-Doppler protocol was superior to the PDI protocol. Nevertheless, both protocols appear suitable as inexpensive screening strategies to identify subjects with75% stenosis measured by carotid Doppler ultrasound. However, these preliminary data need further verification.

Folic acid fortification of grain products was mandated in the USA by January 1998 and in Canada by November 1998. It was hypothesized thatscreeningtotal plasma homocysteine levels adjusted for age, sex, race and country that were drawn in stroke patients for the Vitamin Intervention for Stroke Prevention trial from 1997 to 2001 would be steady when fortification was completed. Samples were grouped by years 1997/1998, 1999 and 2000/2001, and adjusted means were calculated using a general linear regression model. In 2,612 US and 1,059 Canadian patients, levels showed no consistent trend in the USA alone, while Canadian levels declined (p = 0.06 overall, 0.0003 in the oldest age group). US levels were 0.39 µmol/l (95% CI: –0.08, 0.85) lower than in Canada. Neither fasting nor time since stroke affected the results.

The authors assessed the increase in the predictivity of ischemic stroke (IS) resulting from the addition of nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors (current smoking, diabetes mellitus, systolic blood pressure, antihypertensive therapy, prior coronary disease, and left ventricular hypertrophy) among 14,685 middle-aged persons in the Atherosclerosis Risk in Communities Study. Participants were recruited from four US communities in 1987-1989. Risk prediction scores for IS through 2000 were estimated from Cox models. The ability to predict which persons would develop IS was assessed by means of the area under the receiver operating characteristic curve-the probability that persons with IS had a higher risk score than those without IS. Among 22 nontraditional factors considered, the joint addition of body mass index, waist:hip ratio, high density lipoprotein cholesterol, albumin, von Willebrand factor, alcohol consumption, peripheral arterial disease, and carotid artery wall thickness modestly and statistically significantly improved prediction of future IS over a risk score that included traditional factors. Further improvement was obtained by adding age and race. For women, the area under the receiver operating characteristic curve went from 0.79 to 0.83 to 0.84; for men, it went from 0.76 to 0.78 to 0.80. These modest improvements are not enough to influence clinical and public health efforts to reduce the community burden of IS.

Neurology in the 1900s: 1900–1909 H. Richard Tyler, MD The first decade of the 20th century (1900–1909) saw dramatic changes and advances in virtually every aspect of neurology. The basic science framework for neurology was solidified by fundamental advances in neurophysiology, led by Sir Charles Sherrington and his collaborators. Equally important advances were made in the study of the histology and pathology of the nervous system by Cajal and others (Tables 1 and 2). The clinical spectrum of neurology was broadened and enriched by many contributions still remembered eponymously today (see Table 1). A very subjective and selective selection of additional landmark contributions in different fields of neurology are listed in Table 2. Prominent among these were the studies that led to Nobel Prizes for Pavlov in 1904 on digestive physiology and to Golgi and Cajal in 1906 for their work on the neuron theory. Few neurodiagnostic tests were available to clinicians in the first decade of the 20th century, with arteriog

Background and Purpose —; Elevated plasma homocyst(e)ine [H(e)] concentration has been associated with an increased risk of stroke. Although the literature suggests that H(e) increases from the acute to the convalescent phase after a stroke, it is not known whether H(e) changes within the acute period. Methods —; A prospective, multicenter study was conducted to examine changes in H(e) during the 2 weeks after an incident stroke. Blood samples were collected at days 1, 3, 5, 7, and between 10 and 14 days after the stroke. Results —; Seventy-six participants (51 men) were enrolled from 9 sites from February 1997 through June 1998. Mean age was 65.6 years, and subjects had at least two H(e) measurements. The estimated mean H(e) level at baseline was 11.3±0.5 μmol/L, which increased consistently to a mean of 12.0±0.05, 12.4±0.5, 13.3±0.5, and 13.7±0.7 μmol/L at days 3, 5, 7, and 10 to 14, respectively. The magnitude of the change in H(e) was not affected by age, sex, smoking status, alcohol use, history of hypertension or diabetes, or Rankin Scale Score. Conclusions —; These data suggest that the clinical interpretation of H(e) after stroke and the eligibility for clinical trials assessing treatment for elevated H(e) levels require an adjustment in time since stroke to properly interpret the observed H(e) levels.

Background and Purpose —The Asymptomatic Carotid Atherosclerosis Study (ACAS) established the effectiveness of prophylactic carotid endarterectomy, for patients in good health who had stenosis ≥60%, if conducted by surgeons with a surgical morbidity and mortality of Methods —One hundred sixty-three participants who had a baseline contralateral occlusion documented by Doppler ultrasound (77 medical, 86 surgical) were compared with 1485 participants with a patent contralateral carotid artery (748 medical, 737 surgical) for the risk of a combined end point of perioperative (30-day) death or stroke or long-term (5-year) ipsilateral stroke. Results —For those without contralateral occlusion, surgery was associated with a 6.7% absolute reduction in the 5-year risk (95% CI, 2.1% to 11.4%), while for those with a contralateral occlusion, surgery was associated with a 2.0% absolute increase in risk (95% CI, −9.3% to 5.2%), which was a statistically significant difference in the effect of surgery ( P =0.047). This difference is primarily attributable to low long-term risk for medically managed patients with contralateral occlusion. Conclusions —While this post hoc analysis should be interpreted with caution, the findings suggest that endarterectomy in asymptomatic subjects with contralateral occlusion provides no long-term benefit (and may be harmful) in preventing stroke and death. These findings were a result of the benign course of medically treated subjects.

Cerebral hypoxia is a major component of immediate and secondary cell damage caused by ischemia. Hyperbaric oxygen (HBO) is a potent means to increase the amount of oxygen dissolved in blood plasma. The effectiveness of HBO in clinical and experimental cerebral ischemia, however, is controversial. We sought to determine whether treatment with HBO initiated early after focal cerebral ischemia-onset protects the brain when experimental conditions such as brain temperature are controlled. Male Wistar rats (n=57) underwent reversible filament occlusion of the right middle cerebral artery (MCA) for 75 min. Animals were awakened after filament introduction and assessed for presence of forelimb paresis. Rats then underwent a 60-min course of either 100% O(2) at 1.0 atmosphere absolute (ata; control group), HBO 1.5 ata, or HBO 2.5 ata in a customized HBO chamber allowing physiological monitoring and pericranial temperature control. The filament was then removed. Seven days after ischemia, rat behavior was scored from 3-18 (18=normal) and brains were removed for histological analysis of infarct volume. Rats treated with HBO 2.5 ata had better mean+/-standard deviation (S.D.) behavioral scores (14+/-2; p0.05) than control (10+/-3) or HBO 1.5-ata-treated animals (11+/-3). Similarly, total infarct volumes (mean+/-S.D.) were smaller in animals receiving HBO at 2.5 ata (76+/-65 mm(3); p0.05) compared to control (129+/-83 mm(3)) and HBO 1.5-ata (119+/-68 mm(3))-treated groups. Cortical infarction occurred less frequently in HBO 2. 5-ata-treated than in control animals (44% vs. 71%; p0.05). We conclude that HBO can improve outcome after temporary focal ischemia when treatment is started early after ischemia-onset but HBO dose appears important. Potential mechanisms include enhanced oxygen supply to marginally perfused cells.

Background and Purpose —Silent cerebral infarctions (SCIs) have a prevalence between 10% and 40% in the transient ischemic attack population and have been associated with increased mortality and morbidity; however, little is known about the prevalence and risk factors for SCI in the general population. This report focuses on the role of cigarette smoking and other risk factors for SCI in the general population. Methods —MRI scans were performed on 1737 participants selected from the general population as part of the Atherosclerosis Risk in Communities Study. Smoking status and other major cerebrovascular risk factors were assessed, and associations between smoking status and SCIs were established with the use of ANCOVA. Results —Overall, the prevalence of SCI in this population aged 55 to 70 years was 11%. Cigarette smoking had an ordered association ( P =0.029) with the presence of SCI, with the odds ratio (OR) of nonsmoking participants exposed to environmental tobacco smoke being 1.06 (95% confidence interval [CI], 0.64 to 1.75) times as great as for nonsmokers not exposed; the OR of past smokers was 1.16 (95% CI, 0.74 to 1.83) times greater, and the OR of current smokers was 1.88 (95% CI, 1.13 to 3.13) times greater. An increased prevalence was also noted among black, older, and hypertensive participants. Conclusions —This report is among the first to examine the risk factors for SCI in the general population and finds a relatively high overall prevalence (11%). There is an ordered relationship between increasing exposure to cigarette smoke and the presence of SCI that parallels the relationship between smoking and carotid atherosclerosis. The magnitude of the association with smoking is substantial compared with the effect of hypertension and other traditional cerebrovascular risk factors. The reduction in prevalence of SCI between current and past smokers and the trend that increased pack-years of smoking is related to increased prevalence of SCI are both additional arguments for smoking avoidance and cessation.

Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis, based on suggestive but inconclusive evidence for its effectiveness. Only during the last 5 years have randomized studies clarified the indications for surgery. In preparing this report, panel members used the same rules of evidence used in the previous report1 2 (Table⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a randomized, prospective manner following carotid endarterectomy. However, a wealth of data are available regarding the general relationship between risk factor control and stroke risk. These data provide some guidance for the care of endarterectomy patients. ### Hypertension Hypertension is the most powerful, prevalent, and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence. Isolated systolic hypertension, which is common in the elderly, also considerably increases risk of stroke. Reduction of elevated blood pressure significantly lowers risk of stroke. Meta-analyses of randomized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42% reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36% without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension (Grade A recommendation for treatment of hypertension in general; Grade C recommendation for postendarterectomy care). Perioperative treatment of hypertension after carotid endarterectomy represents a special situation. Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache, seizures, and occasionally altered mental status or focal neurological signs. Neuroimaging may show intracerebral hemorrhages10 11 12 or white …

White matter lesions (WMLs) detected by cerebral magnetic resonance imaging (MRI) are putatively a consequence of cerebral hypoperfusion or ischemia. We investigated the prevalence, severity and correlates of WMLs in a population-based sample of 1,920 African-American and European-American men and women aged 55-72 years, during the second follow-up examination of the Atherosclerosis Risk in Communities Study. The spin density images from 1.5-tesla MRI scans were used to define WMLs using a 0-9 scale with 0 for normal and 9 for most severe WMLs. Age was positively associated with the prevalence (percent) and severity of WMLs. African-Americans had lower overall prevalence of WMLs, but a higher prevalence of relatively more severe WMLs, than European-Americans. After adjusting for age, sex, and ethnicity, WMLs were significantly associated with smoking, lower education, hypertension, systolic blood pressure, and pulse pressure, and weakly associated with diastolic blood pressure. The associations of smoking, alcohol intake, systolic and diastolic blood pressure, pulse, pressure, and hypertension were stronger in African-Americans than in European-Americans (p < 0.15 for interactions by ethnicity). This population-based MRI study documents significant relationships between several cardiovascular disease risk factors and WMLs. The findings suggest that such factors play a role in the pathogenesis of WMLs, an elements linked to hypoperfusion and/or fluid accumulation, which presumably lead to WMLs. African-Americans exhibited both a higher proportion of normal white matter and a higher proportion of relatively more severe WMLs than European-Americans.

Background and Purpose White matter lesions (WML) may result from cerebral hypoperfusion or ischemia. We investigated the association of WML with blood pressure, hypertension, and its treatment and control. Methods A random sample of 1920 participants aged 55 to 72 years in the Atherosclerosis Risk in Communities Study (ARIC) was examined. Spin-density 1.5-T MRI scan images were coded from 0 for normal to 9 for most severe WML. Hypertension was defined as systolic or diastolic pressure ≥140/90 mm Hg or use of antihypertensive medication. Results The percentages of persons with WML grades 0 through 2 and 3 through 9, respectively, were as follows: normotensive, 92.4% and 7.6%, versus all hypertensive subjects, 83% and 17% ( P P =.003). Multivariable adjusted odds ratios (95% confidence intervals) for WML grade ≥3 relative to normotensive subjects was 2.34 (1.71 to 3.20) for all hypertensives, 1.99 (1.19 to 3.08) for untreated hypertensives, 1.94 (1.32 to 2.85) for treated controlled hypertensives, and 3.40 (2.30 to 5.03) for treated uncontrolled hypertensives. After additional adjustment for hypertension duration, treatment, and control status, the odds ratios (95% confidence intervals) for a 1 SD increase of systolic and diastolic blood pressure were 1.43 (1.11 to 1.85) and 1.16 (0.94 to 1.43), respectively. Conclusions Hypertension is associated with increased odds of WML, and treated uncontrolled hypertensive subjects have greater odds of WML than those with treated controlled hypertension. The data suggest that the level of blood pressure, especially systolic blood pressure, is related to WML, additional to the effects of categorically defined hypertension and its treatment and control status.

Purpose: The selection of surgeons to participate in a prospective randomized trial comparing the efficacy of a surgical method with medical management is critically important because it will have a direct impact on the outcome of the study and the future use of the operation. We report the success of the method used for selecting surgeons who participated in the Asymptomatic Carotid Atherosclerosis Study (ACAS) by examining the surgical morbidity and mortality rates and the outcome of the study.Methods: A Surgical Management Committee established criteria for auditing surgeons who wished to participate in the study. The parameters included a minimum performance of at least 12 carotid endarterectomies (CEA) per year and an audit of each surgeon's last 50 consecutive CEAs with required documentation of a combined neurologic morbidity and mortality rate of

Background and Purpose Indications for carotid endarterectomy have engendered considerable debate among experts and have resulted in publication of retrospective reviews, natural history studies, audits of community practice, position papers, expert opinion statements, and finally prospective randomized trials. The American Heart Association assembled a group of experts in a multidisciplinary consensus conference to develop this statement. Methods A conference was held July 16-18, 1993, in Park City, Utah, that included recognized experts in neurology, neurosurgery, vascular surgery, and healthcare planning. A program of critical topics was developed, and each expert presented a talk and provided the chairman with a summary statement. From these summary statements a document was developed and edited onsite to achieve consensus before final revision. Results The first section of this document reviews the natural history, methods of patient evaluation, options for medical management, results of surgical management, data from position statements, and results to date of prospective randomized trials for symptomatic and asymptomatic patients with carotid artery disease. The second section divides 96 potential indications for carotid endarterectomy, based on surgical risk, into four categories: (1) Proven: This is the strongest indication for carotid endarterectomy; data are supported by results of prospective contemporary randomized trials. (2) Acceptable but not proven: a good indication for operation; supported by promising but not scientifically certain data. (3) Uncertain: Data are insufficient to define the risk/benefit ratio. (4) Proven inappropriate: Current data are adequate to show that the risk of surgery outweighs any benefit. Conclusions Indications for carotid endarterectomy in symptomatic good-risk patients with a surgeon whose surgical morbidity and mortality rate is less than 6% are as follows. (1) Proven : one or more TIAs in the past 6 months and carotid stenosis ≥ 70% or mild stroke within 6 months and a carotid stenosis ≥ 70%; (2) acceptable but not proven : TIAs within the past 6 months and a stenosis 50% to 69%, progressive stroke and a stenosis ≥ 70%, mild or moderate stroke in the past 6 months and a stenosis 50% to 69%, or carotid endarterectomy ipsilateral to TIAs and a stenosis ≥ 70% combined with required coronary artery bypass grafting; (3) uncertain : TIAs with a stenosis proven inappropriate: moderate stroke with stenosis Proven: none. (As this statement went to press, the National Institute of Neurological Disorders and Stroke issued a clinical advisory stating that the Institute has halted the Asymptomatic Carotid Atherosclerosis Study (ACAS) because of a clear benefit in favor of surgery for patients with carotid stenosis ≥60% as measured by diameter reduction. When the ACAS report is published, this indication will be recategorized as proven. (2) acceptable but not proven : stenosis >75% by linear diameter; (3) uncertain : stenosis >75% in a high-risk patient/surgeon (surgical morbidity and mortality rate >3%), combined carotid/coronary operations, or ulcerative lesions without hemodynamically significant stenosis; (4) proven inappropriate : operations with a combined stroke morbidity and mortality >5%.

The methods used for measurement of carotid artery stenosis are not uniform. Witness the chaos that developed when the North American Symptomatic Carotid Endarterectomy Trial (NASCET) group changed its classification system from area to linear measurements only to discover that the European Carotid Stenosis Trial (ECST) used still another angiographic definition of degree of stenosis so that the data from the two studies were not comparable. Fortunately, this has been reconciled by recalculation of the data. In still other studies, using unvalidated ultrasound instruments has made it difficult or impossible to compare results. In part, these problems have been the result of misdirected attempts to amalgamate concepts from Doppler and duplex ultrasound with those of arteriography. The former is more precise and accurate than the latter, yet its methodology is harder to apply and has not been generally distributed. Even such anatomical terms as "carotid bulb" are not standard. Ultrasonographers consider it to be the distal common carotid artery, to vascular surgeons it is the carotid sinus, while still others consider it to be both or neither. The present authors advocate a uniform methodology utilizing duplex ultrasound and predict that it plus magnetic resonance angiography will become the standard by which extracranial carotid artery disease is evaluated in the future.

Although both mean lipoprotein(a) [Lp(a)] concentration and national stroke prevalence estimates are consistently higher in American blacks than in whites, no information exists on the relationship of Lp(a) and stroke prevalence in African-Americans. Associations of Lp(a) with stroke or transient ischemic attack (TIA) are addressed in this report for 15,160 participants--4160 blacks and 11,000 whites--in the Atherosclerosis Risk in Communities (ARIC) Study. Lp(a) was measured in ARIC as its total protein component by double-antibody enzyme-linked immunosorbent assay (ELISA) for apo(a) detection. Self-reported stroke/TIA history was assessed as part of a standardized questionnaire, and resulted in age-adjusted stroke/TIA prevalences of 3.0% in blacks (n = 120) and 2.0% in whites (n = 222). Overall, mean Lp(a) protein levels were markedly higher for blacks than for whites (160.5 versus 81.6 micrograms/mL, respectively), and were statistically significantly higher among individuals reporting stroke/TIA history for both races (191.3 versus 159.6 micrograms/mL in blacks; 100.6 versus 81.2 micrograms/mL in whites). Multivariable logistic regression analysis for the association of Lp(a) protein with stroke/TIA status yielded a prevalence odds ratio (OR) (95% confidence intervals) of 1.17 (1.05, 1.30) overall (based on one standard deviation difference, 108.2 micrograms/mL, in Lp[a] protein). Race-specific ORs, after adjustment for the same covariates, were equivalent for blacks [OR = 1.17 (0.99, 1.39)] and whites [OR = 1.19 (1.04, 1.36)]. These data suggest that Lp(a) is an independent risk factor for stroke/TIA in both blacks and whites, and that the relative risk of stroke/TIA associated with Lp(a) protein does not vary by race.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient ischemic attack (TIA) is generally considered a risk factor for death and cardiovascular events. This assumption is based on comparisons of the survival of the TIA population with that of the general population. Such comparisons may provide biased estimates of the risk associated with TIA because the general population is usually more healthy than TIA patients. Using a prospective case-control study design, we report the comparison of a TIA population (n = 280) and a control group (n = 399) with a comparable cardiovascular risk factor burden. Proportional hazards analysis was used to compare survival time and time to fatal or nonfatal stroke and/or myocardial infarction for the two study groups. Comparisons were made without adjustment for risk factors and after adjustment for age, race, sex, and major cardiovascular risk factors. Before adjustment for age-race-sex or risk factors, TIA proved to be a risk factor for early mortality, stroke, and myocardial infarction (P < .05). Adjustment for age-race-sex disparities between the case and control groups explained much of the differences in mortality, as the hazard ratio was reduced from 2.2 to 1.4. However, adjustment for age-race-sex or age-race-sex and risk factors did not markedly reduce the role of TIA as a risk factor for stroke or myocardial infarction. Although TIA proved to be a risk factor for stroke or myocardial infarction, it apparently plays a smaller role in the risk of death.

The clinical markers for carotid endarterectomy (CE) have traditionally been transient ischemic attack (TIA) or minor stroke. Whether CE should be restricted to this symptomatic category of carotid st

The Atherosclerosis Risk in Communities (ARIC) study is a population-based observational study of randomly sampled, census-based populations in four locations within the United States. The study was designed to determine whether there are regional differences in incidence, prevalence, and mortality rates from cardiovascular and cerebrovascular disease in populations aged 45 to 64 years. Both cohort examinations and community surveillance are included. In addition to a standardized transient ischemic attack (TIA) and stroke questionnaire and algorithm for determination of incidence and prevalence, B-scan ultrasonography is used to quantify the degree of atherosclerotic changes in the carotid artery. Initiated in late 1986, the first cohort evaluation was completed in early 1990. The third, which includes magnetic resonance imaging of the brain, is in progress and will be completed in 1996. Positive responses to the TIA/stroke questionnaire increase by decile of age, are greater in women than men, and are more frequent in African Americans than Caucasians. The baseline study using an algorithm for categorization of patient responses into vascular and other causes of TIA and stroke estimated prevalences of 5.5% in African Americans and 6.3% in Caucasians.

The extent of carotid artery atherosclerosis as measured by B-mode ultrasound has been shown to be strongly and independently correlated with the presence or absence of coronary atherosclerotic disease (CAD), but no studies to date have used carotid B-mode ultrasound to compare the extent of atherosclerotic disease in the two arterial circulations. We used data from a registry of patients undergoing cardiac catheterization and B-mode ultrasound of the carotid arteries to compare the extent of CAD (number of major coronary vessels with 50% or greater stenosis as judged by a consensus interpretation) with the extent of extracranial carotid atherosclerosis. Four hundred thirty-four patients (234 men, 200 women) greater than 40 years of age were stratified by gender and then divided into quartiles on the basis of a B-mode score that was derived by summing arterial wall thickness at nine sites in the left and nine sites in the right carotid arteries. Evaluation of extent of CAD for the four B-mode quartiles showed that men in the lowest B-mode quartile were over six times more likely to have normal coronary arteries than three- to four-vessel CAD, while men in the highest B-mode quartile were over 10 times more likely to have three- to four-vessel CAD than normal coronary arteries. The findings were similar for women but not as dramatic. Gender-specific discriminant function models using traditional risk factors alone or in combination with B-mode score were developed to predict the extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

The establishment of 60% or greater diameter stenosis by Doppler ultrasound is an eligibility requirement of the Asymptomatic Carotid Atherosclerosis Study (ACAS). We used a uniform statistical approach for each of 30 Doppler devices to establish a cutpoint for the peak systolic flow to insure a positive predictive value of 90% in predicting a 60%+ stenosis by angiography. Data were analyzed by device; however, performance relates to the device-sonographer-reader system. For those devices reporting in peak systolic velocity, cutpoints ranged from 151 to 390 cm/s, and for those reporting a peak systolic frequency from 5,400 to 11,250 Hz. Eighteen devices had a sensitivity above 60%, and nine devices had a sensitivity above 80%. However, for six instruments, the relationship between Doppler and angiography was too weak to establish any cutpoint. In addition, for one instrument a value could be established, but the associated sensitivity was only 18%. This remarkable variability in the performance is at odds with the high sensitivity uniformly published in the literature, suggesting (a) that the high reported sensitivity for Doppler may represent an overestimate of average performance, perhaps due to publication bias, (b) the paramount need for documented quality control measures within local laboratories to insure that Doppler examinations are performed reliably, and (c) the need for caution in the generalization of results among laboratories.

Among the 4129 patients of the Community Hospital-based Stroke Program, 30% had an unspecified stroke diagnosis. Since specific diagnosis and, perhaps, eventual treatment, derives in part from diagnostic testing, we examined the effect of clinical condition, geographic and demographic factors on the incidence of certain diagnostic tests after acute stroke. In this multivariable analysis, race, sex, history of hypertension and history of diabetes did not influence the chance of having any test, but older age strongly reduced the chances of receiving extensive evaluation. When CT scanning was available, the utilization of a CT as well as other diagnostic studies including cerebral angiography, radionuclide brain scan, EEG and EKG was increased. The odds of receiving a CT scan increased if the patient was married, and decreased with a history of previous stroke. A history of previous TIA increased the chance of having a cerebral angiogram while a history of cardiac disease decreased the chance. There were striking regional geographic differences in the use of CT, radionuclide brain scanning and cerebral angiography which may, in part, reflect differences between the availability of these technologies in urban and rural hospitals. These results indicate that evaluation of stroke patients remains heterogenous.

We examined the extent of extracranial carotid atherosclerosis as evaluated by a B-mode ultrasound score in four groups of hospitalized patients: hospital controls free of both cerebrovascular symptoms and coronary atherosclerosis (HC, n = 245); patients with coronary atherosclerosis but without cerebrovascular symptoms (CAD, n = 382); patients with transient ischemic attacks but asymptomatic for coronary atherosclerosis (TIA, n = 107); and patients having both transient ischemic attacks and symptomatic coronary events (TIA + CAD, n = 39). The unadjusted B-mode scores were lowest for the HC group, intermediate for the CAD group, and highest for the TIA or TIA + CAD groups (no difference between these two groups). However, after adjustment for age (or age and other risk factors), we could find no significant differences among the CAD, TIA, and TIA + CAD groups, while the HC group had significantly lower adjusted scores. These data suggest that 1) accentuated development of carotid atherosclerosis is associated with both TIA and CAD and 2) the apparent differences in extracranial carotid atherosclerosis between coronary and cerebrovascular patients are partly attributable to differences in risk factor profiles (most notably age). The potentially accentuated rate of development of extracranial atherosclerosis in patients with CAD mandates a low threshold for cerebrovascular evaluation in CAD patients.

We assessed the relationship between characteristics of stroke victims and the risk of early death from coronary or cerebrovascular disease (CCVD) among their children. For each of 55 stroke patients selected from a registry which enrolled patients between 1969 and 1973, an index of their progeny's survival was calculated using the age in 1987 of 197 surviving children, and the age at and cause of death for 55 deceased children. Increased risk of CCVD death within families was significantly related to parental age at the time of first stroke, and with the parental history of diabetes mellitus. No significant relationship was found between the children's risk of CCVD death and the stroke patient/parent's sex, race, history of hypertension or cardiac disease, stroke diagnosis (infarction vs hemorrhage), or severity upon admission. These results suggest that family histories of cerebrovascular disease may impart differential risks, depending upon a family history of diabetes, and perhaps, the ages at which ancestral strokes first occurred.

Objective To determine alternative neural pathways for restitution of piano playing after right hemispheric infarction causing left arm and hand paralysis. Design Case report testing coordinated bimanual skills using structured motor skills tests and neuroimaging. Setting A professional pianist sustained a lacunar infarction in the posterior limb of his right internal capsule, which resulted in left hemiparesis with immobilized left-hand and -finger movements persisting for 13 weeks. After 6 months, he had recovered bimanual coordinated piano skills by “ignoring” his left hand while concentrating or discussing subjects other than music while playing. Patient A 63-year-old, male professional pianist. Intervention Detailed neurological examination including computed cranial tomography, functional magnetic resonance imaging, and positron emission tomography. Results Functional magnetic resonance imaging activation patterns correlated with rapid movements of fingers in each hand separately and together demonstrating that subcortical and cerebellar pathways were activated during skilled motor function of his left hand. Contralateral cerebral and cerebellar activation occurred with both left- and right-hand movements. During tapping of the left fingers, there was bilateral cerebellar, parietal, and left premotor strip and left thalamic activation. Conclusion Patterns of activation relate to task performance and they are not similar to subjects engaged in simpler tasks such as finger opposition.

Objective: To determine if the stroke risk factor profile of participants in a large, multicenter secondary stroke prevention trial changed over the recruitment period. Methods: The 3,680 participants in the Vitamin Intervention for Stroke Prevention (VISP) were categorized into four groups by enrollment date. Baseline patient characteristics and stroke risk factors were compared across groups. Results: Hypertension and hypercholesterolemia management improved but prevalence of three major stroke risk factors did not change. Patients enrolled later had better Mini-Mental State and lower NIH Stroke Scale scores, higher multivitamin use, lower prevalence of cortical infarctions, cardiac symptoms and prior stroke, and lower serum creatinine levels. Conclusions: Those participants enrolled in the later recruitment periods had a different risk factor profile and risk factors were managed differently compared to those enrolled earlier.

Background: To have uniform criteria for evaluating populations for prevalence of transient ischemic attack (TIA)/stroke, validated instruments are necessary for objective assessment and classification. Methods: Patient responses compatible with symptoms of TIA or ischemic stroke, obtained from participants in a substudy of the Asymptomatic Carotid Atherosclerosis Study, were used to program a neural network for each symptom. Models were designed for rapid classification into 1 of 7 outputs: no event, TIA, or stroke (in left carotid, right carotid, or vertebrobasilar). The networks were then tested by comparing decisions with a validated questionnaire used to access an independent data set of 381 patients. Results: There were 144 patients who reported sudden speech change, 89 with sudden vision loss, 67 with double vision, 189 with sudden numbness, 223 with episodic dizziness, and 108 with paralysis, for a total of 820 reported symptoms among the 381 patients tested. For each category, an equal number of individuals reporting "No" to these phenomena were randomly selected and analyzed. Neural network classification correlated with the diagnoses made by specially trained stroke clinicians (e.g., all who responded "No" were correctly classified as having no neurologic event). Ten symptomatic patients were misclassified, with the most common reason being incomplete data. After adjustment of the network logic, these misclassifications did not recur. Conclusion: Computer networks can be trained to produce a rapid and accurate classification of TIA or stroke by vascular distribution, enabling screening of populations for assessment of their incidence and prevalence.

Most (∼70%) of strokes are first-ever strokes, and hence to substantially reduce the neurological burden, primary prevention is crucial. Here, highlights of the National Institute of Neurological Disorders and Stroke workshop ‘Stroke Risk Assessment and Future Stroke Primary Prevention Trials’ held January 12–13, 2004 are summarized. The Workshop discussions focused on stroke risk assessment; the high-risk vs. population-based approaches to primary prevention; desirable characteristics of candidate treatments and potential novel treatments, such as the ‘polypill’; subclinical disease as risk assessment tool and as surrogate outcome, and methodological issues in stroke primary prevention trials. The importance of assessing cognitive decline as an important consequence of covert and overt vascular injury of the brain was emphasized. The scientific or logistic barriers to stroke primary prevention trials are challenging, but are not insurmountable.

The association between computer diagnosis derived from a symptom questionnaire and onset of first hospitalized ischemic stroke during follow-up for up to 11 years has been assessed for 11,804 participants in the Atherosclerosis Risk in Communities Study who had no baseline history of stroke. Of these participants, 578 reported prior positive transient ischemic attack/stroke symptoms, and 265 strokes occurred during the years 1987–1998. Adjusted for age, locale, sex, and race, persons with self-reported baseline symptoms had 2.8 times the hazard rate for incident ischemic stroke of those without symptoms, with 95% confidence interval 1.9–4.1. Greater relative risk was found among younger individuals, women, African-Americans, persons not current smokers, and those with lower white blood cell count.

Objective: We examined the putative relationship between stroke and cognitive function in the population-based prospective cohort of the Cardiovascular Health Study (CHS). Methods: Of the 5888 participants of the CHS aged 65 years or older, there were 5364 with more than one modified mini-mental (3MS) examination between 1992 and 1998. To determine the effect of baseline stroke before first and subsequent (stroke between two consecutive examinations) 3MS examination on cognitive function, linear regression models were computed with potential confounders entered as additional independent variables. Stroke was divided into right and left hemispheres or posterior circulation on the basis of the clinical and/or imaging information by the hospital that treated the event and subsequent adjudication by CHS committee. Results Participants with baseline stroke had an average 3MS decline of 1.2 (95% confidence interval [CI]: −0.7-−1.7) points per year more than those without one. Those with a history of subsequent stroke had an average first year 3MS decline of 6.2 (CI −8.7-−3.7) for left hemisphere, 3.5 (CI −5.3-−1.8) for right hemisphere, and 1.1 (CI −3.9–1.6) for posterior circulation more than those without stroke. The effect of stroke on the rate of cognitive decline appeared to ameliorate after the first year (test for linear trend among those with stroke, P = .003). Conclusion Results from this prospective population-based data study show that stroke in the left hemisphere results in a more pronounced decline in cognition than that in the right hemisphere and that cognitive loss because of stroke appears to attenuate over time, perhaps as a result of relearning.

Periodontitis has been shown to increase the systemic inflammatory response, which has been implicated in atherosclerosis and cerebrovascular events. We hypothesized an association between periodontitis or edentulism and Stroke/TIA in the ARIC Study. Data on 9415 dentate and 1491 edentulous adults included demographics, cardiovascular outcomes, lifestyle, laboratory measures, and, for 6436 of the dentate, a dental examination. The dependent variable was Stroke/TIA, and the exposure was extent (%) of attachment level 3+ millimeters (AL). Quartiles of AL and edentulism were compared for Stroke/TIA using odds ratios (OR) and 95% confidence intervals (CI), and confounders were controlled by logistic regression. Stroke/TIA was prevalent in 13.5% of periodontal examinees, 15.6% of dentate non-examinees, and 22.5% of edentulous persons. The highest quartile of AL (OR 1.3, CI 1.02-1.7) and edentulism (OR 1.4, CI 1.5-2.0) were associated with Stroke/TIA.

To the Editor: Previous studies of therapeutic oxygen in stroke have had conflicting results, and the latest study by Rusyniak et al1 seems to suggest that hyperbaric oxygen therapy (HBO) is harmful in ischemic stroke. The authors have already discussed how several inadequacies in trial design might explain their negative results. We wish to draw attention to additional features in their study that might offer important insights into the design of future studies of oxygen in stroke. The authors evaluated the safety, feasibility, and efficacy of using HBO in a sham-controlled pilot study of 33 patients with acute (

Background and Purpose —The relationship between physical activity and stroke is inconclusive according to the 1996 US Surgeon General’s Report on Physical Activity and Health. Therefore, this study examined the relationship between physical activity and ischemic stroke risk among 14 575 Atherosclerosis Risk in Communities Study participants aged 45 to 64 years free of self-reported stroke and coronary heart disease at baseline. Methods —Eligible potential stroke hospitalizations were identified from ongoing hospital surveillance and from hospitalizations reported by the cohort study participants. All strokes were validated by hospitalization records. Physical activity was measured as sport, leisure (nonsport), and work with the use of the Baecke questionnaire. Multivariable Poisson and Cox proportional hazards models were used to determine the association of differing levels of physical activity with ischemic stroke incidence. Results —During an average of 7.2 years of follow-up, 189 incident ischemic strokes occurred. Ischemic stroke incidence rates were highest in the lowest quartile of sport, leisure, and work scores. The hazard rate ratios with 95% CIs for ischemic stroke for the highest quartile compared with the lowest quartile of activity adjusted for age, sex, race-center, education, and smoking, were sport 0.83 (0.52, 1.32), leisure 0.89 (0.57, 1.37), and work 0.69 (0.47, 1.00). Further adjustment for factors that likely were intermediate variables (hypertension, diabetes, fibrinogen, and body mass index) between physical activity and stroke attenuated the associations. Conclusions —Our findings suggest that physical activity was weakly associated with a reduced risk of ischemic stroke among middle-aged adults. The association may be due to links between physical activity and other risk factors or due to chance.

“Try it or Trial it” is an apt title for a session at this 25th Princeton Stroke Conference because of the pivotal concepts this think tank has initiated in basic and clinical research designed to prevent, treat and rehabilitate stroke victims. Having attended these conferences intermittently since 1961, I suspect I am now the senior attendee. You may not be aware that Irving S. Wright, who founded this conference, was a cardiologist who introduced heparin to the United States from Sweden by studying its safety and efficacy in one of the first randomized trials for patients experiencing myocardial infarction to prevent venous thromboembolism and extension of acute myocardial infarction. In the same context it was he, along with Mrs Mary Lasker, who developed the concept for Princeton Conferences and for a change in national policy regarding research in heart disease and stroke. As Mrs Lasker recalled to me, one of her friends had recently experienced a stroke and she was told there was no treatment other than bed rest. Together they decided to change this sorry state of affairs: Mrs Lasker supplied funds and Dr Wright the impetus for inviting colleagues from many disciplines to …