Recurrent stroke after transient ischaemic attack or minor ischaemic stroke: does the distinction between small and large vessel disease remain true to type? Dutch TIA Trial Study Group.

The incidence and vascular type of recurrent ischaemic stroke was studied in patients with supratentorial transient ischaemic attacks or non-disabling ischaemic strokes, who were treated with aspirin (30 or 283 mg). Patients were divided into groups with small vessel disease (SVD) (n = 1216) or large vessel disease (LVD) (n = 1221) on the grounds of their clinical features and CT at baseline. Patients with evidence of both SVD and LVD (n = 180) were excluded from further analyses. During follow up (mean 2.6 years) annual stroke rate was 3.6% in both groups. Of the 107 patients with SVD at baseline who had recurrent strokes, 83 proved to have an identifiable infarct: 30 (28%) again had a small vessel infarct, 39 (36%) had a large vessel ischaemic stroke and in 14 (13%) the recurrent ischaemic stroke was in the posterior fossa. Of the 110 patients with LVD at baseline and recurrent stroke, 91 had an identifiable infarct: 67 (61%) again had a large vessel ischaemic stroke, 16 (15%) had a small vessel ischaemic stroke, and eight (7%) had the recurrent ischaemic stroke in the posterior fossa. Thus patients with a transient ischaemic attack or non-disabling ischaemic stroke caused by LVD were more likely to have an ischaemic stroke of the same vessel type during follow up than patients with SVD (relative risk 2.2; 95% confidence interval 1.5-3.4). Possible explanations for this difference are: (1) patients with a small vessel ischaemic stroke at baseline had both SVD and LVD or were misdiagnosed; (2) recurrent small vessel ischaemic stroke may have occurred more often than reported, because they were silent or only minimally disabling; (3) recurring large vessel ischaemic strokes occurring in patients initially diagnosed as having SVD might have been related to potential cardiac sources of emboli that had not been previously recognized; (4) the antiplatelet drug aspirin (30 or 283 mg) prescribed in this patient group may have prevented thrombosis in small vessels better than in large vessels.

Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group.

BACKGROUND AND PURPOSE: The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation (NRAF) varies from 2% to 15% in the first year and is approximately 5% yearly thereafter. Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population. METHODS: We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial. The mean follow-up was 1.6 years. RESULTS: By means of multivariate modeling, six independent variables were identified: history of previous thromboembolism, ischemic heart disease, enlarged cardiothoracic ratio on chest roentgenogram, systolic blood pressure greater than 160 mm Hg at study entry, NRAF for more than 1 year, and presence of an ischemic lesion on CT scan. These variables could also be used to stratify patients in low-, medium-, and high-risk subgroups for the other two arms of the trial, those treated with anticoagulation and aspirin. Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment. CONCLUSIONS: Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke.

Predictive value of clinical history and electrocardiogram in patients with transient ischemic attack or minor ischemic stroke for subsequent cardiac and cerebral ischemic events. The Dutch TIA Trial Study Group.

OBJECTIVE: Patients with cerebral ischemia have a high mortality rate. The most common cause of death is myocardial infarction. We attempted to identify risk factors for subsequent cardiac events in patients with cerebral ischemia by means of the history and electrocardiography performed with the patient at rest. DESIGN: The original inception cohort was entered in a multicenter randomized clinical trial (30 or 283 mg/d of aspirin) and followed up prospectively for a mean period of 2.6 years. SETTING: Patients were admitted to the hospital or seen in outpatient clinics. PATIENTS: Patients with one or more transient ischemic attacks (symptoms completely reversible within 24 hours) and patients with minor ischemic stroke (symptoms persisting for longer than 24 hours) were randomized, provided they were independent in most activities of daily living. Patients with a definite or probable source of embolism in the heart were excluded. A total of 3021 patients were included in the study. Follow-up was performed at 4-month intervals. MAIN OUTCOME MEASURES: Primary cardiac outcome events were defined as nonfatal myocardial infarction and cardiac death. Cardiac death included sudden death, fatal myocardial infarction, or death due to congestive heart failure; 189 patients suffered a cardiac death--82 of which were sudden deaths--or nonfatal myocardial infarction. RESULTS: By means of multivariate analysis, the following independent predictors for cardiac events were identified (hazards ratio/95% confidence limits): age older than 65 years (1.6/1.2 to 2.2), male sex (1.5/1.1 to 2.1), angina pectoris (1.5/1.0 to 2.3), diabetes (1.6/1.1 to 2.5), anterior infarction noted on electrocardiography (1.7/1.1 to 2.7), inverted T wave noted on the electrocardiogram (1.6/1.1 to 2.4), and left ventricular hypertrophy noted on electrocardiography (3.2/2.0 to 4.9). CONCLUSIONS: The history and the electrocardiogram obtained with the patient at rest are valuable tools for cardiac risk assessment in patients with recent cerebral ischemia.

Risk of cardiac events in atypical transient ischaemic attack or minor stroke. The Dutch TIA Study Group.

Proposed guidelines for the diagnosis of transient ischaemic attack (TIA) involve interpretation of symptoms, so it can be very difficult to distinguish a TIA from other disorders, such as migraine, epilepsy, syncope, or neurosis. Atypical cerebral and visual events may be classified as TIA. To see whether TIA or stroke patients with atypical cerebral or visual symptoms are at high or low risk of cardiac complications, we prospectively followed 572 patients (entered into the Dutch multicentre TIA trial) with a diagnosis of TIA or minor ischaemic stroke, but whose symptoms did not fully accord with internationally accepted criteria. We compared their outcome with that of 2555 other TIA or stroke patients in the trial, who had unequivocal symptoms; all patients were treated with aspirin. During mean follow-up of 2.6 years the risk of a major vascular event did not differ between the groups (14.5% in patients with atypical symptoms vs 15.1% of patients with typical attacks). Patients with atypical attacks had a lower risk of stroke (5.6% vs 9.4%, hazard ratio 0.6, 95% confidence interval 0.4-0.9) and a higher risk of a major cardiac event (8.4% vs 5.9%, 1.4, 1.0-2.0) than did patients with typical attacks. These differences could not be explained by differences in cardiac risk factors, and were independent of minor discrepancies in baseline characteristics between the groups. A heavy or tired feeling in one or two limbs was the only atypical symptom associated with cerebral rather than cardiac events (ratio cardiac/cerebral events 0.8). For all other atypical symptoms cardiac events were about twice as common as cerebral events (range 1.3-2.5). Our findings suggest that TIA or minor stroke patients with atypical symptoms may have symptomatic heart disease, especially cardiac arrhythmia.

Hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke: influence on the rate of subsequent stroke. Dutch TIA Trial Study Group.

In a prospective study of 3,017 patients with transient ischemic attack or minor ischemic stroke from the Dutch Transient Ischemic Attack Trial, the presence or absence of diffuse hypodensity of the white matter on a baseline computed tomography (CT) scan of the brain was related to the occurrence of subsequent stroke. On entry, 337 patients were judged to have diffuse hypodensity of the white matter on CT; they were older (71.4 +/- 7.4 years versus 64.4 +/- 9.9 years), more often had hypertension (50% versus 41%), and more often had lacunar infarcts on CT scan (40% versus 26%) than did patients with normal white matter. Strokes, fatal or nonfatal, occurred in 51 (15%) of the patients with diffuse hypodensity of the cerebral white matter, compared to 217 (8%) in the group with normal white matter (crude hazard ratio, 2.0; 95% confidence interval, 1.4-2.7). After adjustment for age and other relevant entry variables, the hazard ratio was 1.6 (95% confidence interval, 1.2-2.2). In patients younger than 70 years the crude hazard ratio was 2.7 (95% confidence interval, 1.7-4.2). The distribution between the main subtypes of stroke was similar for patients with and those without diffuse hypodensity of the cerebral white matter: Intracerebral hemorrhage occurred in 6 and 9%, cortical infarction in 47 and 45%, and lacunar infarction in 34 and 29%, respectively. We conclude that hypodensity of the cerebral white matter in patients with transient ischemic attack or minor stroke is associated with an extra risk of future stroke, from large as well as from small vessels, and particularly in patients under 70 years old; this increase of risk is independent of other risk factors for stroke.

[Interobserver variation in the application of 2 disability scales in heart patients]. / Variatie tussen waarnemers bij de toepassing van twee invaliditeitsschalen bij hartpatiënten.

OBJECTIVE: To examine the use of the Rankin scale for the assessment of disability in patients with ischaemic heart disease. SETTING: University Hospital Utrecht. DESIGN: Prospective interobserver study. PATIENTS AND METHODS: Fifty-two outpatients with heart disease (previous myocardial infarction, angina or both) were separately interviewed by four physicians (residents or specialists), viz., two cardiologists and two neurologists. The degree of disability was recorded by each observer on two different scales: the modified Rankin scale, a six-point scale developed from a neurological background, and the four-point scale developed by the New York Heart Association (NYHA). The agreement rates for the observers (23 in all) were corrected for chance (kappa-statistics; maximum 1.0). RESULTS: Total agreement on both scales was found for six of the participating 51 patients and for 10 and 11 patients when the Rankin scale and the NYHA scale were considered separately. Kappa values were 0.21 for the Rankin scale and 0.24 for the NYHA scale. The weighted kappa values were 0.56 and 0.47, respectively. The agreement among neurologists and cardiologists was comparable. CONCLUSION: The agreement rates of cardiologists and neurologists in the use of the Rankin scale and the NYHA scale in outpatients with heart disease are at best satisfactory. The good results of an earlier study with the Rankin scale in stroke patients were not achieved. This study indicates that the Rankin scale may be useful for the assessment of disability from heart disease particularly in patients with neurological disease, but there is room for further improvement.

Hypertension in the elderly is associated with white matter lesions and cognitive decline.

Forty-two elderly patients (mean age, 66.2 +/- 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 +/- 4.8 yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2-weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi-square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini-Mental State Examination, the Stroop color-word test, Trailmaking test, and the visual subtest of the Wechsler Memory Scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long-standing hypertension in some patients may cause not only strokes but also chronic end-organ damage of the brain in the form of demyelination of the white matter, with cognitive decline.

Transient ischaemic attacks and small-vessel disease. Dutch TIA Study Group.

Histories and computed tomograms of 606 patients with transient cerebral ischaemia were studied. All symptoms and signs had completely resolved within 24 hours, and any episodes suggestive of posterior fossa ischaemia were excluded. Computed tomography, done after the clinical features had resolved, showed 79 relevant infarcts: 46 were small, deep, lacunar infarcts (58%, 95% confidence interval [CI] 47-69%), and 33 were larger cortical infarcts. The histories and the type of infarct in these 79 patients were compared to see whether lacunar infarcts were preceded by a history of unilateral motor or sensory symptoms without features usually attributed to the cerebral cortex. The positive predictive value of such lacunar symptoms was 0.74, with a negative predictive value of 0.61. 11 patients had a cortical infarct despite a history of lacunar TIAs, but only one occurred in the left hemisphere and speech was not affected. Of 527 patients with transient ischaemic attacks without a relevant infarct visible on computed tomography, 335 (64%) had a history suggestive of lacunar ischaemia, whereas in several other studies 20-25% of patients with ischaemic stroke have evidence of lacunar infarcts. Lacunar TIAs may therefore have a better prognosis than cortical TIAs or may often precede cortical infarcts; alternatively, many cortical infarcts may occur without warning.