Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. CONCLUSIONS: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Warfarin use following ischemic stroke among Medicare patients with atrial fibrillation.

BACKGROUND: Elderly patients with ischemic stroke and atrial fibrillation are at especially increased risk for recurrent stroke. Warfarin sodium is highly effective in reducing this risk. OBJECTIVE: To determine the use of warfarin among a population sample of elderly patients with atrial fibrillation hospitalized for ischemic stroke. METHODS: The Connecticut Peer Review Organization conducted a chart review of Medicare patients, aged 65 years or older, hospitalized in 1994 with a diagnosis of atrial fibrillation. Patients with a principal diagnosis of acute myocardial infarction or another indication for anticoagulation were excluded. RESULTS: Among 635 patients (402 women; 585 white; 218 > or =85 years old; 147 with a new diagnosis of atrial fibrillation), 334 had stroke as a principal diagnosis. Among those discharged alive after a stroke, only 147 (53%) of 278 were prescribed warfarin at discharge. Furthermore, among 130 (47%) of 278 patients not prescribed warfarin at discharge, 81 (62%) of 130 were also not prescribed aspirin. Increased potential benefit (additional vascular risk factors) was not associated with a higher rate of warfarin use. Low risk for anticoagulation (lack of risk factors for bleeding) was associated with a slightly higher rate of warfarin use. Among those with an increased risk of stroke and a low risk for bleeding (ideal candidates), 124 (62%) of 278 were discharged on a regimen of warfarin. CONCLUSION: Anticoagulation of elderly stroke patients with atrial fibrillation, even among ideal candidates, is underused. The increased use of warfarin among these patients represents an excellent opportunity for reducing the risk of recurrent stroke in this high-risk population.

Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity.

BACKGROUND AND PURPOSE: We sought to measure the overall rate of usage of tissue-type plasminogen activator (tPA) for ischemic stroke at academic medical centers, and to determine whether ethnicity was associated with usage. METHODS: Between June and December 1999, 42 academic medical centers in the United States each identified 30 consecutive ischemic stroke cases. Medical records were reviewed and information on demographics, medical history, and treatment were abstracted. Rates of tPA use were compared for African Americans and whites in univariate analysis and after adjustment for age, gender, stroke severity, and type of medical insurance with multivariable logistic regression. RESULTS: Complete information was available for 1195 ischemic stroke patients; 788 were whites and 285 were African Americans: Overall, 49 patients (4.1%) received tPA. In the subgroup of 189 patients without a documented contraindication to therapy, 39 (20.6%) received tPA. Ten (20%) of those receiving tPA had documented contraindication. African Americans were one fifth as likely to receive tPA as whites (1.1% African Americans versus 5.3%; P=0.001), and the difference persisted after adjustment (OR 0.21, 95% CI 0.06 to 0.68; P=0.01). When comparison was restricted to those without a documented contraindication to tPA, the difference remained significant (OR 0.24, 95% CI 0.06 to 0.93; P=0.04). Medical insurance type was independently associated with tPA treatment. After adjustment for ethnicity and other demographic characteristics, those with Medicaid or no insurance were one ninth as likely to receive tPA as those with private medical insurance (OR 0.11, 95% CI 0.02 to 0.17; P=0.003). CONCLUSIONS: tPA is used infrequently for ischemic stroke at US academic medical centers, even among qualifying candidates. African Americans are significantly less likely to receive tPA for ischemic stroke. Contraindications to treatment do not appear to account for the difference.

A quality-of-life instrument for young hemorrhagic stroke patients.

BACKGROUND AND PURPOSE: Hemorrhagic stroke has a high initial mortality rate. While survivors often recover motor function, many experience significant changes in their quality of life (QOL). Available outcome measures assess neurological impairment, disability, or handicap, yet often inadequately characterize the full impact of a stroke on patients' lives. In this study, we develop and validate a QOL instrument specific for young patients with hemorrhagic strokes. METHODS: Methodological guidelines for instrument development were initially established. Based on the content of 40 open-ended patient interviews, a 54-item instrument (HSQuale) was developed. The reliability (test-retest and internal consistency) and validity (content and construct) of HSQuale were assessed in another 71 patients (18 to 49 years of age, 63% women, 77% white), at 1 year after their hemorrhagic stroke. Comparisons were made between HSQuale and other commonly used outcome measures. RESULTS: HSQuale demonstrated reproducibility (test-retest kappa, 0.40 to 0.96) and internal consistency (Cronbach alpha >/=0.80 for 5 of 7 domains). HSQuale scores had broad frequency distributions (

The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke.

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Intracranial hemorrhage associated with cocaine abuse: a prospective autopsy study.

OBJECTIVES: To determine the incidence of cocaine abuse in cases of fatal intracranial hemorrhage and to examine potential pathophysiologic mechanisms. DESIGN: Prospective clinical, autopsy, and toxicologic evaluation of all cases of fatal non-traumatic intracranial hemorrhage examined during 1 year (April 11, 1989 to April 10, 1990) at the Connecticut Office of the Chief Medical Examiner. Autopsy examination included exhaustive histologic evaluation of cerebral vessels and parenchyma for vasculitis and other vasculopathies. RESULTS: Ten of 17 (59%) of all non-traumatic intracranial hemorrhages were associated with a positive toxicology for cocaine. Seven (70%) of these were parenchymal hemorrhages, and the remaining three (30%) were subarachnoid hemorrhages (ruptured berry aneurysms). No vasculitis or other vasculopathy was identified. CONCLUSIONS: These findings implicate cocaine use as a significant risk factor for fatal brain hemorrhage and may explain, in part, the increased incidence of hemorrhagic stroke in some drug-using cohorts. The lack of specific pathologic findings suggests that cocaine-associated intracranial hemorrhages are a consequence of the pharmacodynamic effect of cocaine and not a cocaine-induced vasculopathy.

HMG-CoA reductase inhibitors (statins): a promising approach to stroke prevention.

Statins represent a promising class of agents to prevent stroke. In randomized trials of middle-aged patients with coronary artery disease, statins reduce the incidence of stroke. The reduction in stroke may not be solely related to cholesterol or low-density lipoprotein reduction but may involve nonsterol mechanisms effects on endothelial cells, macrophages, platelets, and smooth muscle cells. Statins also reduce the size of cerebral infarction in a murine stroke model, suggesting a neuroprotective effect. The best current evidence for stroke prevention is with pravastatin and simvastatin. Pravastatin reduces the risk of stroke in patients with coronary artery disease and average cholesterol levels; simvastatin reduces the risk of the combined endpoint of stroke and transient ischemic attack in hypercholesterolemic patients with coronary artery disease. Future studies of statins are needed in stroke populations, particularly the elderly.

Brain single-photon emission computed tomography.

Single-photon emission computed tomography (SPECT) provides cost-effective information on regional cerebral perfusion and, indirectly, on regional cerebral metabolism. Its ease of use facilitates the application of SPECT in clinical neurology. SPECT is emerging as a useful tool for the management of patients with stroke, epilepsy, recurrent brain neoplasms, and some forms of dementia. The applications being investigated, such as in vivo receptor labeling for benzodiazepines, serotonin, dopamine, and muscarinic receptors, may expand the clinical usefulness of this technique in the future.

Insulin resistance and risk for stroke.

BACKGROUND AND PURPOSE: Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance. METHODS: The authors searched Medline (1977-2001) and reviewed bibliographies to identify pertinent English-language publications. RESULTS: Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke. CONCLUSION: Insulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes.

Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke.

Stratified randomization for clinical trials.

Trialists argue about the usefulness of stratified randomization. For investigators designing trials and readers who use them, the argument has created uncertainty regarding the importance of stratification. In this paper, we review stratified randomization to summarize its purpose, indications, accomplishments, and alternatives. In order to identify research papers, we performed a Medline search for 1966-1997. The search yielded 33 articles that included original research on stratification or included stratification as the major focus. Additional resources included textbooks. Stratified randomization prevents imbalance between treatment groups for known factors that influence prognosis or treatment responsiveness. As a result, stratification may prevent type I error and improve power for small trials (<400 patients), but only when the stratification factors have a large effect on prognosis. Stratification has an important effect on sample size for active control equivalence trials, but not for superiority trials. Theoretical benefits include facilitation of subgroup analysis and interim analysis. The maximum desirable number of strata is unknown, but experts argue for keeping it small. Stratified randomization is important only for small trials in which treatment outcome may be affected by known clinical factors that have a large effect on prognosis, large trials when interim analyses are planned with small numbers of patients, and trials designed to show the equivalence of two therapies. Once the decision to stratify is made, investigators need to chose factors carefully and account for them in the analysis.

Development of a test battery to identify older drivers at risk for self-reported adverse driving events.

OBJECTIVES: The purposes of this study were (1) to develop a battery of tests that assessed a wide range of functional abilities relevant to driving yet could be performed in a clinician's office and (2) to determine which of these tests were most closely associated with self-reported adverse driving events. DESIGN: A cohort study. SETTING: An urban community. PARTICIPANTS: Participants were drawn from the Project Safety cohort, a probability sample of noninstitutionalized older persons in New Haven, Connecticut, initiated in 1989. The current study included surviving, active drivers in the cohort (N=125). MEASURES: The test battery assessed visual, cognitive, and physical abilities potentially relevant to driving, and was administered in participants' homes by trained interviewers between October 1994 and July 1995. Outcome measures included the self-report of a crash, moving violation, or being stopped by police in any Project Safety interview since the inception of the cohort. Analyses compared performance on the elements of the test battery with participants' histories of adverse driving events. RESULTS: Of the 125 drivers, 50 (40%) had reported an adverse event in a mean period of 5.76 (+/-.25) years before the current interview. The elements of the test battery independently associated with a history of events, adjusting for driving frequency, included near visual acuity worse than 20/40 (adjusted odds ratio 11.90), limited neck rotation (OR 6.10), and poor performance on a test of visual attention, the number cancellation task (OR 3.00). The resulting regression equation yielded a sensitivity of 80%, a specificity of 55%, and an area under the curve of .75 by receiver operating characteristic analysis. CONCLUSION: These findings suggest it may be possible to identify individuals potentially at risk for self-reported adverse driving events using simple tests of functional ability. If validated, such an approach could be used to identify individuals who need a more detailed assessment of functional abilities to determine the severity and etiology of impairments, and their effect on driving performance, as well as possible interventions to correct or compensate for the impairments.

Hyperglycaemia in patients with acute ischaemic stroke: how often do we screen for undiagnosed diabetes?

BACKGROUND: Hyperglycaemia is common among patients with acute ischaemic stroke, and may be due to the physiological stress of the acute stroke event or reflect underlying diabetes mellitus. The under-diagnosis of diabetes in the general population, combined with the association of diabetes and stroke, suggests a rationale for screening for diabetes among hyperglycaemic stroke patients. AIM: To determine how often clinicians screen for diabetes among hyperglycaemic stroke patients without a prior diagnosis of diabetes. DESIGN: Retrospective medical record review. METHODS: We reviewed the records of acute ischaemic stroke patients admitted at any of ten Connecticut hospitals from May 1996 through December 1998. RESULTS: We identified 90 acute stroke patients with no prior history of diabetes. The prevalence of hyperglycaemia varied from 31% down to 6%, depending on the maximum glucose cut-off used to define hyperglycaemia: from > or = 140 mg/dl (7.8 mmol/l) to > or = 200 mg/dl (11.1 mmol/l). Only one of the hyperglycaemic patients (1/90, 1%) had any evidence that a clinician screened or planned to screen for undiagnosed diabetes: one patient had a haemoglobin A1c measured during the hospitalization, none received oral glucose tolerance testing while hospitalized, and no discharge summary included a plan to screen for diabetes as an out-patient. DISCUSSION: Hyperglycaemic stroke patients without a previous diagnosis of diabetes are not routinely screened for diabetes. This situation represents an opportunity, currently unused, to identify an important and modifiable condition.

Lhermitte's sign in a patient with herpes zoster.

A 34-year-old, previously healthy man developed herpes zoster (shingles) involving the C4 dermatome. This was accompanied by Lhermitte's sign, i.e. an electric shock-like sensation radiating from the neck to the sacrum, elicited by flexion of the neck. Lhermitte's sign resolved in this patient after several days, and probably reflected acute inflammation together with changes in sensory axon excitability. This positive manifestation of dorsal column dysfunction can be present in the absence of fixed neurological deficits, and can reflect dorsal column dysfunction caused by a wide spectrum (demyelinating, traumatic, compressive, toxic/deficiency, infectious and inflammatory) of etiologies.

Emotional facial paresis with striatocapsular infarction.

Emotional facial paresis (EFP) refers to hemifacial paresis of emotionally evoked or spontaneous smiling or weeping with preserved volitional movements of the face. The anatomical location for this phenomenon has been controversial. We report a 15-year-old boy with EFP. Follow-up MRI demonstrated infarction limited to the head of the caudate, putamen and anterior limb of the internal capsule on the contralateral side. This case lends support for selective damage at a striatal or capsular site in the production of EFP.

Seasonal fluctuation in the incidence of intracranial aneurysm rupture and its relationship to changing climatic conditions.

Seasonal and climatic variations have been linked to the occurrence of some types of cerebrovascular disease; however, the conditions that lead to intracranial aneurysm rupture are not known. The purpose of the present study was to determine whether seasonal and climatic conditions are related to intracranial aneurysm rupture. Data provided by the Connecticut Health Information Management and Exchange were analyzed for all patients with a primary diagnosis of aneurysmal subarachnoid hemorrhage (SAH) for the fiscal years 1981, 1983, 1985, 1987, 1988, and 1989. Patient records were correlated with climatic conditions for the years 1981 to 1989 obtained from the National Climatic Data Center, National Oceanic and Atmospheric Administration, National Environmental Satellite Data, and Information Service. During the time periods studied, 1487 patients with a primary diagnosis of aneurysmal SAH were treated by reporting hospitals. Seasonal variation in the incidence of aneurysmal SAH and admission clustering were observed but differed significantly between men and women. Men showed a single large peak in late fall (Roger's r = 11.5, p < 0.005), whereas women had an annual peak occurring in late spring (Roger's r = 10.3, p < 0.01). Substantial climatic change occurred during the 72 hours prior to 10 of the 14 clusters of men who were admitted (p < 0.01, Yates' corrected chi-square 7.33, df = 1). In contrast, clusters of women admitted were not related to preceding climatic change (p > 0.25, Yates' corrected chi-square 0.06, df = 1). Hospital admissions for aneurysmal SAH display seasonal fluctuation, with women showing a different seasonal pattern from men. Changing climatic conditions precede aneurysm rupture in men but not in women, which suggests that weather is causally related to aneurysm rupture in men, and that factors that lead to aneurysm rupture in women may be different from those in men. These data do not explain why weather fronts or gradients are associated with aneurysm rupture in men.

SPECT imaging of stroke.

Single-photon emission computed tomography (SPECT) is a helpful tool for the management of stroke patients. Brain perfusion SPECT can help differentiate an ischemic event from peri-ictal phenomena such as Todd's paresis. Initial data suggest that SPECT may be useful in prognosticating the likelihood of an early stroke after a transient ischemic attack and in distinguishing lacunar from cortical stroke. After an acute stroke, early SPECT depicts the area of ischemia with greater accuracy than either computed tomography or magnetic resonance imaging. When the perfusion defect is large, the likelihood of hemorrhagic complications or herniation increases. Reperfusion of an arterial territory after thrombolysis can be documented more conveniently with SPECT than with angiography. SPECT before and after the injection of acetazolamide has been used to assess the vascular reserve in patients with severe stenosis of the proximal vessels of the cerebrovascular tree. Combined with transcranial Doppler studies, SPECT is used to document ischemia after subarachnoid hemorrhage. It has also been used to assess the effect of arterial ligation intended to treat arteriovenous malformations or aneurysms on brain perfusion and to evaluate ischemia secondary to pressure from an intracranial hemorrhage.

Single-photon emission computed tomography in distal field hypoperfusion.

To assess the ability of technetium-99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) imaging to differentiate distal field hypoperfusion from other stroke mechanisms, 24 patients with acute cerebral ischemia were studied. SPECT scans were read by two physicians according to a preestablished set of criteria for distal field hypoperfusion. SPECT patterns read as "probable" or "definite" for distal field hypoperfusion were found in 42% (10/24); of these, 80% (8/10) had ipsilateral carotid occlusion or high-grade stenosis. Severe carotid stenosis was found in 43% (6/14) with SPECT scans negative for distal field hypoperfusion (Fisher exact test [1-tailed] p = 0.0796). The results suggest that a distal field hypoperfusion pattern on SPECT may identify patients with hemodynamically significant large vessel disease.

The transcranial Doppler standardization project. Phase 1 results. The TCD Study Group, American Society of Neuroimaging.

A project to pursue standardization of the performance and interpretation of transcranial Doppler studies was designed. Phase I consisted of a national survey of the current practice of transcranial Doppler in the United States. From 200 ultrasound laboratories surveyed about the use of transcranial Doppler, 60 completed questionnaires were returned. The results show that further standardization of transcranial Doppler performance and interpretation is necessary, and provide the foundation for phases II and III of the project.