Age at intracranial aneurysm rupture among generations: Familial Intracranial Aneurysm Study.

BACKGROUND: Previous studies have reported intracranial aneurysm (IA) occurring at young ages in subsequent generations. These studies did not correct for duration of follow-up. Second-generation members who would have their ruptured IA late in life may not be detected due to shorter follow-up time than the first generation. We examined families in which ruptured IA occurred in two consecutive generations for the hypothesis that the second generation (F1) was more likely to have a rupture at a younger age than the older generation (F0). METHODS: The Familial Intracranial Aneurysm (FIA) Study is a multicenter, international study recruiting families of ruptured and unruptured IA. All available family members are interviewed. Cox proportional hazards regression models and Kaplan-Meier curves were used to examine differences by generation. RESULTS: Although we found that the F1 generation was more likely to have an aneurysm rupture at a younger age than the F0 generation, we found that this was largely because of a lack of follow-up time in the F1 generation. The F1 generation had 50% the rupture rate of the prior generation. When analyzed by Kaplan-Meier curves, we found a tendency to have a slightly later rupture rate in the F1 generation once time to follow-up was included in the analysis model. CONCLUSIONS: Families of ruptured intracranial aneurysm (IA) do not appear to demonstrate "anticipation." Our finding suggests that genetic epidemiology of ruptured IA should examine all types of variations such as single base-pair changes, deletions, insertions, and other variations that do not demonstrate anticipation.

Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.

BACKGROUND: The management of unruptured intracranial aneurysms is controversial. Investigators from the International Study of Unruptured Intracranial Aneurysms aimed to assess the natural history of unruptured intracranial aneurysms and to measure the risk associated with their repair. METHODS: Centres in the USA, Canada, and Europe enrolled patients for prospective assessment of unruptured aneurysms. Investigators recorded the natural history in patients who did not have surgery, and assessed morbidity and mortality associated with repair of unruptured aneurysms by either open surgery or endovascular procedures. FINDINGS: 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms. These rates were often equalled or exceeded by the risks associated with surgical or endovascular repair of comparable lesions. Patients' age was a strong predictor of surgical outcome, and the size and location of an aneurysm predict both surgical and endovascular outcomes. INTERPRETATION: Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient.

Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

OBJECTIVES: The aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population. BACKGROUND: Clinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined. RESULTS: Age, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

Fatal progression of posttraumatic dural arteriovenous fistulas refractory to multimodal therapy. Case report.

The authors report the case of a man who suffered from progressive, disseminated posttraumatic dural arteriovenous fistulas (DAVFs) resulting in death, despite aggressive endovascular, surgical, and radiosurgical treatment. This 31-year-old man was struck on the head while playing basketball. Two weeks later a soft, pulsatile mass developed at his vertex, and the man began to experience pulsatile tinnitus and progressive headaches. Magnetic resonance imaging and subsequent angiography revealed multiple AVFs in the scalp, calvaria, and dura, with drainage into the superior sagittal sinus. The patient was treated initially with transarterial embolization in five stages, followed by vertex craniotomy and surgical resection of the AVFs. However, multiple additional DAVFs developed over the bilateral convexities, the falx, and the tentorium. Subsequent treatment entailed 15 stages of transarterial embolization; seven stages of transvenous embolization, including complete occlusion of the sagittal sinus and partial occlusion of the straight sinus; three stages of stereotactic radiosurgery; and a second craniotomy with aggressive disconnection of the DAVFs. Unfortunately, the fistulas continued to progress, resulting in diffuse venous hypertension, multiple intracerebral hemorrhages in both hemispheres, and, ultimately, death nearly 5 years after the initial trauma. Endovascular, surgical, and radiosurgical treatments are successful in curing most patients with DAVFs. The failure of multimodal therapy and the fulminant progression and disseminated nature of this patient's disease are unique.

Association of atrial fibrillation and aortic atherosclerosis: a population-based study.

OBJECTIVE: To examine the association between atrial fibrillation (AF) and aortic atherosclerosis in the general population. SUBJECTS AND METHODS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the adult Olmsted County, Minnesota, population (45 years of age or older) participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency of aortic atherosclerosis was determined in 42 subjects with AF and compared with that in 539 subjects without AF (non-AF group). RESULTS: Subjects with AF were significantly older than non-AF subjects (mean +/- SD age, 82+/-10 vs 66+/-13 years, respectively; P<.001) and more commonly had hypertension (28 [66.7%] vs 288 [53.4%], respectively; P=.10). The 2 groups were similar in sex and frequency of diabetes mellitus, hyperlipidemia, or smoking history (P>.10). The odds of aortic atherosclerosis (of any degree) were 2.87 times greater (95% confidence interval [CI], 1.41-5.83; P=.004) and the odds of complex atherosclerosis (protruding atheroma >4 mm thick, mobile debris, or plaque ulceration) were 2.71 times greater (CI, 1.13-6.53; P=.03) in the AF group than in the non-AF group. Age was a significant predictor of aortic atherosclerosis (P<.001). After adjusting for age, the odds of atherosclerosis and complex atherosclerosis were not significantly different between the 2 groups (P=.13 and P=.75, respectively). CONCLUSIONS: In the general population, AF is associated with aortic atherosclerosis, including complex atherosclerosis. This association is related to age since both AF and aortic atherosclerosis are more frequent in the elderly population.

Development of a rapid, quantitative method for LDL subfractionation with use of the Quantimetrix Lipoprint LDL System.

BACKGROUND: Recent evidence suggests that the presence of small, dense LDL is independently associated with increased risk of developing coronary artery disease. Current methods to subfractionate LDL are time-consuming and/or technically demanding. Therefore, we have sought the development of a less complex LDL subfractionation procedure. METHODS: LDL subfractions were separated using the Quantimetrix Lipoprint(TM) LDL System. High-resolution 3% polyacrylamide gel tubes were scanned densitometrically (610 nm) with a Helena EDC system. A computerized method to identify and quantitatively score the resolved LDL subfractions was developed. Results from the Quantimetrix method were compared using 51 plasma samples with values obtained by nondenaturing gradient gel electrophoresis (NDGGE) and nuclear magnetic resonance (NMR) spectroscopy. RESULTS: LDL subfractionation scores correlated significantly (P <0.05) with triglyceride, HDL-cholesterol, apolipoprotein B100, and LDL-cholesterol/apolipoprotein B100 (r = 0.591, -0.392, 0.454, and -0.411, respectively). For 51 samples, the Quantimetrix method classified 21 with small, 14 with intermediate, and 16 with large LDL. Of the 21 samples classified as small by Quantimetrix, 20 (95%) were classified as small (n = 18) or intermediate (n = 2) by NDGGE. All of the 16 specimens classified as large by Quantimetrix were either large (n = 14) or intermediate (n = 2) by NDGGE. LDL score was inversely correlated (r = -0.674; P <0.0001) with LDL particle size determined by NMR spectroscopy. CONCLUSIONS: A quantitative method for the assessment of LDL particle size phenotype was developed using the Quantimetrix Lipoprint LDL System. The method can be performed in less than 3 h in batch mode and is suitable for routine use in clinical laboratories.

Left atrial appendage flow velocities in subjects with normal left ventricular function.

The objectives of this study were to establish reference values and define the determinants of left atrial appendage (LAA) flow velocities in the general population. LAA flow velocities (contraction and filling velocities) were assessed by transesophageal echocardiography in 310 subjects aged > or = 45 years, sampled from the population-based Stroke Prevention: Assessment of Risk in a Community study. All subjects were in sinus rhythm, with preserved left ventricular systolic function (ejection fraction > or = 50%), and without valvular disease. Values of LAA contraction and filling velocities were established for various age groups in the population. Age was negatively associated with LAA contraction and filling velocities, which decreased by 4.1 cm/s (p < 0.001) and 2.0 cm/s (p < 0.01) for every 10 years of age, respectively. Contraction velocities were 5 cm/s higher in men than in women (p < 0.05). After adjusting for age and sex, heart rate was independently associated with LAA contraction velocities (p < 0.001; nonlinear association). Body surface area, left atrial size, left ventricular mass index, and a history of previous cardiac disease or hypertension showed no significant association with LAA flow velocities (p > 0.05). Furthermore, detailed analysis of 24-hour ambulatory blood pressure data (available in 253 subjects) showed no association between various blood pressure parameters (systolic and diastolic blood pressure, out-of-bed and in-bed measurements) and LAA flow velocities (all p > 0.05). In summary, the present study establishes the reference values for LAA flow velocities in a large sample of the general population. LAA flow velocities progressively decline with age in subjects with preserved left ventricular systolic function.

Independent association of high blood pressure and aortic atherosclerosis: A population-based study.

BACKGROUND: Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. METHODS AND RESULTS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques >/=4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree (P:

Verifying the stroke-free phenotype by structured telephone interview.

BACKGROUND AND PURPOSE: Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. METHODS: A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). RESULTS: Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke (P<0.001), TIA (P<0.001), or either stroke or TIA (P<0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). CONCLUSIONS: Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.

Detection and control of high blood pressure in the community : Do we need a wake-up call?

At the community level, the effect of national programs in increasing hypertension awareness, prevention, treatment, and control is unclear. This study evaluated the degree of detection and control of high blood pressure in a random population-based sample of Olmsted County, Minnesota, residents >/=45 years old, of whom 636 subjects among 1245 eligible residents agreed to participate. Home interview and home and office measurements of blood pressure were used to estimate awareness, treatment, and control rates for hypertension in the community. Mean blood pressures (+/-SD) were 138/80+/-20/12 mm Hg for men and 137/76+/-23/11 mm Hg for women. The overall prevalence of hypertension was 53%. The percentage of subjects with treated and controlled hypertension was 16.6%. Thirty-nine percent of subjects were unaware of their hypertension. Despite clinical trial evidence of reduced morbidity and mortality with antihypertensive therapy, recently reported national data suggest a leveling-off trend for treatment and control of hypertension. This population-based study supports these observations and suggests that at a community level, hypertension awareness and blood pressure control rates are suboptimal, presumably because of decreased attention to the detection and control of hypertension.

Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke Prevention: Assessment of Risk in a Community.

OBJECTIVE: The SPARC (Stroke Prevention: Assessment of Risk in a Community) study was designed to identify risk factors for stroke and cardiovascular disease using transesophageal echocardiography and carotid ultrasonography. This protocol was undertaken to establish a cohort in which putative risk factors for stroke were identified so that subsequent follow-up could discern the roles these risk factors play in stroke incidence. SUBJECTS AND METHODS: This was a prospective, population-based study. A randomly selected cohort comprised 1475 Olmsted County, Minnesota, residents aged 45 years or older, of whom 588 agreed to participate. Transesophageal echocardiography and carotid ultrasonography were used for evaluation of the subjects. Prevalences of various cardiovascular and cerebrovascular conditions were determined. RESULTS: Transesophageal echocardiography was successfully completed in 581 subjects. The prevalence (+/-SE) of patent foramen ovale was 25.6% (+/-1.9%), and that of atrial septal aneurysm was 2.2% (+/-0.6%). The prevalence of aortic atherosclerosis increased with age and was most common in the descending aorta, particularly in subjects 75 to 84 years old. The prevalence of strands on native valve was 46.4% (+/-2.2%). Carotid ultrasonography data for 567 participants revealed minimal atherosclerotic disease. Most subjects had minimal or mild carotid occlusive disease. The prevalence of moderate (50%-79%) and severe (80%-99%) stenosis was 7.7% (+/-1.1%) and 0.3% (+/-0.2 %), respectively. CONCLUSIONS: This prospective study defines the prevalence of multiple potential cardiovascular and cerebrovascular risk factors, providing population-based data for ongoing follow-up of the risk of stroke.

Frequency of atrial septal aneurysms in patients with cerebral ischemic events.

BACKGROUND: Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. METHODS AND RESULTS: The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. CONCLUSIONS: The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

Functional organization of the Golgi apparatus in glycosphingolipid biosynthesis. Lactosylceramide and subsequent glycosphingolipids are formed in the lumen of the late Golgi.

Biosynthesis of plasma membrane sphingolipids involves the coordinate action of enzymes localized to individual compartments of the biosynthetic secretory pathway of proteins. These stations include the endoplasmic reticulum and the Golgi apparatus. Although a precise localization of all the enzymes that synthesize glycosphingolipids has not been achieved to date, it is assumed that the sequence of events in glycosphingolipid biosynthesis resembles that in glycoprotein biosynthesis, i.e. that early reactions occur in early stations (endoplasmic reticulum and cis/medial Golgi) of the pathway, and late reactions occur in late stations (trans Golgi/trans Golgi network). Using truncated analogues of ceramide and glucosylceramide that allow measurement of enzyme activities in intact membrane fractions, we have reinvestigated the localization of individual enzymes involved in glycosphingolipid biosynthesis and for the first time studied the localization of lactosylceramide synthase after partial separation of Golgi membranes as previously described (Trinchera, M., and Ghidoni, R. (1989) J. Biol. Chem. 264, 15766-15769). Here, we show that the reactions involved in higher glycosphingolipid biosynthesis, including lactosylceramide synthesis, all reside in the lumen of the late Golgi compartments from rat liver.

Intra-arterial thrombolysis in acute basilar artery thromboembolism: the initial Mayo Clinic experience.

OBJECTIVE: To investigate the feasibility of intra-arterial thrombolysis in acute basilar artery thrombosis. DESIGN: We reviewed a consecutive series of patients in whom intra-arterial thrombolysis was performed during the period from 1994 to 1996. MATERIAL AND METHODS: Intra-arterial thrombolysis with urokinase was done in an attempt to recanalize the basilar artery in a series of nine patients with basilar artery thrombosis admitted to the neurologic intensive care unit. At the time of initial assessment, all nine patients had major neurologic deficits attributable to brain-stem ischemia, including two patients with locked-in syndrome. RESULTS: Recanalization of the basilar artery system was successful in seven of the nine patients (a range of 2 to 13 hours after the ictus). Failure to recanalize the basilar artery occurred in two patients, who died after progressing to coma. Complete recovery or only minimal neurologic deficits were demonstrated in five of the nine patients. Despite recanalization of the basilar artery, two patients had no major change in their neurologic function, and both ultimately had severe ataxia and were fully dependent on others. A cerebellar hemorrhage occurred in one patient but without clinical worsening. Two patients had a retroperitoneal hematoma. CONCLUSION: Intra-arterial thrombolysis with urokinase in acute basilar artery occlusion resulted in recanalization in seven of the nine patients (78%). Five of the nine patients recovered fully, including two patients who had had locked-in syndrome. In light of the devastating natural course of acute basilar artery occlusion, these initial results are encouraging and indicate that intra-arterial thrombolysis may be a useful emergency treatment, even in patients with prolonged symptoms of ischemia (up to 12 hours).

Oculopneumoplethysmography.

Oculopneumoplethysmography is an indirect noninvasive technique to assess the presence of a critical or pressure-significant stenosis in the internal carotid system. Its accuracy, reproducibility, and cost-effectiveness make it a useful tool for evaluating both symptomatic and asymptomatic subjects with carotid occlusive disease.

Clinical implications from studies of HLA antigens in idiopathic nephrotic syndrome in children.

HLA class I and II antigen frequencies were determined in two large cohorts of children with idiopathic nephrotic syndrome (NS) from Southwest France (n = 199) and Southwest Germany (n = 152) and compared with unrelated healthy individuals from the same geographical areas. Strength of HLA association was expressed by the relative risk (RR) estimated by Odd's ratio. We examined 105 steroid-resistant and 242 steroid-sensitive NS patients who were subdivided in non-relapsers, infrequent relapsers and frequent relapsers or steroid-dependent patients. In steroid-sensitive patients significant associations were found with HLA-DR7 (RR 5.1 in French, 3.2 in Germans), -DQ2 (RR 4.7/2.3) and with the phenotypic combination HLA-DR3/DR7 (RR 5.6/7.7). Significant negative associations were encountered with HLA-DR2, -DR6 and -DQ1. The associations were stronger in frequent relapsers/steroid-dependent patients than in infrequent relapsers and were not significant in non-relapsers. In steroid-resistant patients the only significant association found was with the combined occurrence of HLA-DR3/DR7. We propose that in childhood NS tissue typing for selected HLA class II antigens is helpful in prediciting the clinical course.

Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.

BACKGROUND AND PURPOSE: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. METHODS: At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee-evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. RESULTS: Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of > or = 70 at the terminal visit. CONCLUSIONS: We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Transient ischemic attack and minor ischemic stroke: an algorithm for evaluation and treatment. Mayo Clinic Division of Cerebrovascular Diseases.

OBJECTIVE: To report a cost-effective and scientifically based algorithm for the clinical assessment and treatment of patients with transient ischemic attack (TIA) or minor ischemic stroke. DESIGN: We comprehensively reviewed the literature on the epidemiologic features, assessment approaches, and treatment recommendations for ischemic cerebrovascular disease and developed an algorithm by using the available clinical and research data to support all decision-making steps. MATERIAL AND METHODS: For patients with TIA or minor ischemic stroke, the appropriate setting for investigation (inpatient or outpatient), suggested diagnostic tests, use of anticoagulants and antiplatelet agents, and indications for surgical treatment are reviewed. RESULTS: Although stroke is a common cause of death and lost productivity in the United States, the clinical assessment of patients with TIA or minor ischemic stroke has lacked consistency. The simplified algorithm clarifies patients who may be candidates for hospitalization and possible anticoagulation therapy. Initial diagnostic studies should include computed tomography of the head without use of a contrast agent, which quickly distinguishes nonhemorrhagic from hemorrhagic cerebrovascular disease. Evolving noninvasive studies of the cerebral vasculature are providing increasingly sensitive means of detecting stenoses, yet cerebral angiography remains the "gold standard." Treatment options depend on the pathophysiologic findings on diagnostic evaluation. CONCLUSION: The assessment of patients with ischemic cerebrovascular disease is complex. The simplified algorithmic approach reported herein necessitates entry of appropriate patients into the algorithm. Because of clinical heterogeneity, an algorithm may apply to a wide spectrum of patients but will not cover every situation; hence, evaluation must be guided by a patient's unique history and findings on examination and by the physician's clinical experience.