A practical stroke severity scale predicts hospital outcomes.

GOAL: To develop a practical severity scale (Wake Forest Stroke Severity Scale [WFSSS]) to predict acute hospital outcomes and resource use after acute ischemic stroke based on the admission neurologic exam. BACKGROUND: A useful scheme enabling physicians and other health care providers to stratify stroke severity on admission to predict acute hospital outcomes and improve efficiency of inpatient care has not been described. METHODS: The study subjects consisted of 271 consecutive acute stroke patients admitted to the neurology department from July 1995 to June 1996 who were prospectively examined and whose stroke severity was classified on the basis of admission neurologic exam (level of consciousness, strength, dysphasia, neglect, and gait) as mild, moderate, or severe, based on the WFSSS. National Institutes of Health stroke scale (NIHSS) was performed early in admission (70% within 24 hours). Discharge disposition (home, inpatient rehabilitation [rehab], skilled nursing facility [SNF], or death); length of stay (LOS); and hospital charges were associated with initial stroke severity ratings using chi-square and Kruskal-Wallis tests. RESULTS: Fifty-percent (136) of strokes were classified as mild, 22% (60) as moderate, and 28% (75) as severe. Initial severity ratings were significantly related to discharge disposition, LOS, and hospital charges (all P values <.001). CONCLUSIONS: A practical clinical severity scale (WFSSS) for acute ischemic stroke patients based on admission neurologic examination predicts hospital disposition, LOS, and hospital charges, and may allow more accurate severity-adjusted comparisons among institutions.

Relationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults.

BACKGROUND: Falling is a major cause of disability and morbidity among older adults. Because poor balance is a major reason for frequent falls, assessment of balance and its risk factors are important. In this study, we postulated that cerebral changes identified on magnetic resonance (MR) imaging are related to balance, and that older adults with balance problems would have significantly greater prevalence of such brain abnormalities than older adults without balance problems. DESIGN AND MEASUREMENTS: Several measures of balance were examined in more than 700 community-dwelling older men and women, blacks and whites. Balance measures included dynamic posturography, functional reach, Romberg and 1-foot stand tests, tandem stand, and 1-foot stand. Cerebral MR imaging assessments included ventricular size, sulcal widening, white matter disease, and ischemic infarctions. Cardiovascular disease and hypertension were determined and controlled for in the analyses. RESULTS: A summary of the balance measures was significantly related to each of the 4 MR imaging measures, with those with poorer balance having more disease. The strongest associations with balance were seen for white matter disease and ventricular size. All but the ischemic infarction variable remained significantly associated with balance after adjustments for sex, race, age, cardiovascular disease, and hypertension. CONCLUSION: Cerebral changes identified by MR imaging are associated with poorer balance among older adults.

Validation of the ACAS TIA/stroke algorithm.

BACKGROUND AND PURPOSE: An easily administered questionnaire and algorithm classifying transient ischemic attacks (TIAs) or strokes, and also their distribution, could be invaluable for identifying endpoints in epidemiologic studies or clinical trials of prevention and therapy of cerebral ischemia. The Asymptomatic Carotid Atherosclerosis Study (ACAS) devised a symptom-based questionnaire and algorithm for detecting events in the trial. The purpose of this study was to determine sensitivity, specificity, and agreement rates of the questionnaire and algorithm against diagnoses of a panel of cerebrovascular disease authorities. METHODS: Three hundred eighty-one men and women at eight medical centers reported symptoms of stroke, TIA, or other neurologic illness. The questionnaire was administered by trained interviewers and the responses were analyzed using the algorithm. A standardized neurologic examination was performed by a neurologist. Data were submitted to two or more external reviewers. Sensitivity, specificity, and the kappa statistic (kappa) were used to evaluate the relationship between the algorithm and the external reviewers' diagnosis. RESULTS: Of the 381 reviews, 196 were diagnosed as TIA or stroke by the external panel. The algorithm's agreement with the diagnosis of TIA or stroke was 80.1%, and kappa was 0.60. Sensitivity was 87.8%, and specificity was 71.9%. CONCLUSION: While statistical agreement rates depend on the method of sample selection, the algorithm has a high agreement with an external panel of experts and is a sensitive tool for event detection. The lower specificity indicates that careful neurologic evaluation may be required to confirm or refute events identified by the screening algorithm.

Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987-1989.

As part of the Atherosclerosis Risk in Communities (ARIC) Study assessment of the etiology and sequelae of atherosclerosis, a standardized questionnaire on transient ischemic attack (TIA) and nonfatal stroke and a computerized diagnostic algorithm simulating clinical reasoning were developed and tested at the four ARIC field centers: Forsyth County, North Carolina; Minneapolis, Minnesota; Jackson, Mississippi; and Washington County, Maryland. The diagnostic algorithm used participant responses to a series of questions about six neurologic trigger symptoms to identify symptoms of TIA or stroke and their vascular distribution. Among 12,205 ARIO participants reporting their lifetime occurrence of one or more symptoms probably due to cerebrovascular causes, nearly half (47%) reported the sudden onset of at least one symptom sometime prior to their ARIC examination. Of those with at least one symptom, only 12.9% were classified by the computer algorithm as having symptoms of TIA or stroke. Dizziness/loss of balance was the most frequently reported symptom (36%); 1.2% of these persons were classified by the algorithm as having a TIA/stroke event. Positive symptoms of speech dysfunction were classified most often (77.%) as being symptoms of TIA or stroke. Symptoms suggesting TIA were reported more frequently than symptoms suggesting stroke by both sexes. TIA or stroke-like phenomena were more frequent (p < 0.001) in females (7%) than in males (5%) and increased with age in both sexes (p = 0.13 for females; p = 0.02 for males). In Forsyth County, TIA and stroke symptoms were greater in African Americans than in Caucasians (p = 0.05, controlling for sex). The association of algorithmically defined symptoms of TIA or stroke with traditional cerebrovascular risk factors is the subject of a companion paper.

Comparison of centralized versus "site-based" measurement of angiographic stenosis for eligibility in the asymptomatic carotid atherosclerosis study.

RATIONALE AND OBJECTIVES: The authors determine the reliability of centralized versus noncentralized (site-based) measurement of angiographic stenosis of patients enrolled into the multicenter, prospective, Asymptomatic Carotid Atherosclerosis Study by angiographic studies. METHODS: Percent agreements and correlations of 244 masked and prospectively interpreted angiograms were calculated for comparison of centralized and noncentralized readers measuring the percent carotid stenosis from the same angiographic studies. Univariate summary statistics for differences in percent stenoses were calculated for these readings. RESULTS: Agreement between readings were 88.5% and 91.8% with kappa statistics of 0.77 and 0.73 for > or = 60% and > or = 80% stenosis, respectively, for comparison of 33 centers to the designated central reader. Comparison between the designated central reader and a second central reader derived percent agreements of 85.0% and 86.5% with kappa statistics of 0.69 and 0.41 for > or = 60% and > or = 80% stenoses, respectively, for arteries selected from the original group. Hence, agreement was slightly better between the enrolling centers and the designated central reader than between the two central readers. CONCLUSIONS: Both centralized and noncentralized (site-based) methods of angiographic measurement of stenosis are equally reliable for large, prospective, masked, multicenter trials when quality control measures are instituted to ensure uniform application of eligibility criteria.

Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.

BACKGROUND: HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease. METHODS AND RESULTS: Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02). CONCLUSIONS: In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.

Demyelinating polyneuropathy in eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a newly recognized disorder, characterized by myalgia, weakness, scleroderma-like changes, and eosinophilia. EMS is associated with lots of L-tryptophan allegedly contaminated with byproducts of the manufacturing process. We describe 3 patients with EMS who presented with a severe demyelinating sensorimotor polyneuropathy. Electrodiagnostic studies revealed multifocal conduction block, slowing and temporal dispersion of motor responses, and prolonged or absent F-responses. Despite plasmapheresis; corticosteroids; and, in 1 patient, cyclophosphamide, 2 patients died and the remaining patient experienced minimal recovery. Pathology revealed patchy perivascular infiltrates and fibrosis in the connective tissue of muscle and nerve. Autopsy of the central nervous system in 2 patients did not reveal changes unique to EMS. In addition to other organ involvement, EMS may manifest as a potentially fatal polyneuropathy, which initially appears to have prominent demyelinating features.

A pilot study of the end point verification system in the asymptomatic carotid atherosclerosis study.

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.

Cerebral vasculitis associated with cocaine abuse.

BACKGROUND: Earlier reports of cocaine-associated cerebral vasculitis have been based primarily on angiographic findings without pathological verification. CASE DESCRIPTION: We present a case of acute encephalopathy following intravenous and intranasal administration of cocaine. Brain biopsy revealed vascular changes involving primarily small arteries. Findings included lymphocytic infiltration, endothelial thickening, and deposition of proteinaceous amorphous material within and around vessel walls. CONCLUSIONS: These abnormalities are consistent with pathological features of arteritis previously reported in association with amphetamine and multiple-drug abuse. Vasospasm-induced changes are an alternative explanation for the vascular picture seen in this case. The patient made modest improvement with high-dose intravenous steroids.

A multicenter validation study of Doppler ultrasound versus angiography.

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.

Implications of the angiographic string sign in carotid atherosclerosis.

We identified 60 patients (42 men and 18 women with an average age of 62.6 years) with angiographically documented carotid stenoses of greater than or equal to 95%; a string sign was demonstrated in 28. Twenty of the 60 patients (33%) were asymptomatic on presentation, 26 (43%) had hemispheric transient ischemic attacks, 21 (35%) had amaurosis fugax, and nine (15%) had previous ipsilateral infarctions. Demographics, mode of presentation, and prevalence of atherosclerotic risk factors were not significantly different between patients with and without a string sign. Doppler frequencies recorded in patients with a string sign were less than 6 or greater than 16 KHz. Real-time ultrasonography imaged a patent lumen in all but three cases with a string sign. Surgery was performed in 26 patients with a string sign and in 21 patients without a string sign. The rate of major perioperative complications was not influenced by the presence of a string sign, contralateral extracranial stenosis, or ipsilateral siphon stenosis. Average lumen size of the endarterectomy specimens was 0.94 mm in those with and 1.7 mm in those without a string sign. We conclude that combined noninvasive testing has a sensitivity of 83% for demonstrating a residual lumen in patients with greater than or equal to 95% carotid stenosis and that the angiographic string sign does not affect the mode of presentation or surgical outcome of these patients.

Pentoxifylline increases cerebral blood flow in patients with cerebrovascular disease.

We determined the immediate effects of pentoxifylline on cerebral blood flow in 10 patients with cerebrovascular disease; four received 400 mg and six received 800 mg pentoxifylline orally. Regional cerebral blood flow was measured before (baseline) and 2, 4, and 6 hours after pentoxifylline administration using the xenon-133 clearance technique with 16 detectors (eight per hemisphere). Global cerebral blood flow as a percentage of the baseline value increased significantly after 800 mg but not 400 mg pentoxifylline (p = 0.017 and p = 0.29, respectively). Regional cerebral blood flow as a percentage of the baseline value at the detector with the lowest baseline value increased significantly 2 hours after both 400 mg and 800 mg pentoxifylline (p = 0.038 and p = 0.010, respectively). Cerebrovascular reactivity to carbon dioxide was preserved despite the increases in cerebral blood flow. Pentoxifylline increases cerebral blood flow and is not associated with "intracerebral steal" in patients with cerebrovascular disease.

Changes in survival following stroke in five North Carolina counties observed during two different periods.

We evaluated survival following stroke for patients from a five-county area of rural North Carolina enrolled in either of two community hospital-based stroke survey programs. In this area, the first program enrolled 843 stroke patients between 1970 and 1973 and the second program enrolled 786 stroke patients between 1979 and 1980. One-year survival increased from 49% in the first program to 62% in the second for all stroke patients, from 54% to 68% for patients with cerebral infarction, and from 18% to 55% for patients with cerebral hemorrhage. While other reports have attributed declining stroke mortality to a decline in the incidence of stroke, our study suggests that increased survival after stroke may account for a large portion of the decrease in stroke mortality.

Treatment of lithium tremor with metoprolol.

Two patients with bipolar affective disorder and a history of bronchospastic phenomena experienced tremor during lithium carbonate therapy. In both, metoprolol produced objective and subjective improvement of the tremor without producing bronchospasm. Objective improvement of tremor after use of metoprolol was documented by accelerometry. The authors discuss the implications of these findings.