We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.
To test interphysician agreement on the diagnosis of subtype of ischemic stroke, we sent subtype definitions and 18 case summaries (clinical features and pertinent laboratory data) to 24 neurologists who have a special interest in stroke, and asked them to determine the most likely subtype diagnosis. The overall agreement was 0.64 (Kappa [K] = 0.54). Interphysician agreement was highest for the diagnoses of stroke secondary to cardioembolism (K = 0.75) or to large-artery atherosclerosis (K = 0.69). Individual physicians varied widely; four agreed with the consensus diagnosis in all 18 cases, while six others disagreed with the consensus diagnosis in three to five cases. Our level of interphysician agreement is greater than that reported in other studies and was substantial. However, despite using subtype definitions and being given extensive information often not available in the acute setting, physicians still disagree about the etiology of stroke, particularly in regard to stroke due to small-artery occlusion or of undetermined etiology. Physicians seem reluctant not to attribute stroke to a specific etiology. The uncertainty about subtype diagnosis will affect interpretation of the results of clinical trials in patients selected by the subtype of ischemic stroke and also suggests that results of treatment as affected by subtype should be cautiously interpreted unless efforts to assure uniformity are included in the trial's operations. Refinement of algorithms for determining subtype of ischemic stroke do improve interphysician agreement. Such criteria should be applied strictly, and trials should include measures to assure the most uniform diagnosis of stroke subtype possible.
To determine the frequency, location, size, and risk factors for silent cerebral infarctions (SCIs) on brain CT, we identified 629 patients without a history of previous stroke who were enrolled in a multicenter clinical trial of therapy for acute ischemic stroke. On the baseline CT, 143 patients (22.7%) had SCIs; 34.3% of the lesions were in the right hemisphere, 38.5% in the left hemisphere, and 27.3% were bilateral. The lesion size was < 1 cm in 65.7%, and the most common site was the basal ganglia (48.3%). Patients with SCI were compared with controls without SCI to determine the odds ratios (ORs) for each risk factor. On univariate analysis, race (black versus white) had an OR of 1.80 (95% confidence interval [CI], 1.14 to 2.85), male sex an OR of 1.68 (95% CI, 1.12 to 2.51), and congestive heart failure an OR of 1.88 (95% CI, 1.07 to 3.31). Significant risk factors on multivariate analysis include age (OR 1.03 per year, p = 0.0070), male sex (OR 1.78, p = 0.0094), and race (OR 2.43, p = 0.0004). After including interaction terms with age and hypertension and age, sex, and race, hypertension was also a significant risk factor.
During the last two years 17 patients of the ENT-Department of the University of Heidelberg suffering from squamous-cell carcinomas of the head and neck underwent a balloon occlusion test of the internal carotid artery (ICA). The investigation was performed because of tumorous infiltration of the large cervical vessels. The balloon occlusion of the ICA was accomplished at the Department of Neuroradiology of the University of Heidelberg. While stopping bloodflow in the ICA of one side for 15-20 min, clinical, electrophysiological and Doppler sonographic monitoring was performed, to detect severe cerebral complications. The specific electrophysiological monitoring contained the detection of MSSEP's (median nerve stimulated somatosensorial evoked potentials) and TCMEP's (transcortical motor evoked potentials) during test occlusion. Balloon occlusion was not possible in three patients because of severe arteriosclerosis. Test occlusion had to be discontinued in three patients because of clinical complications (temporary amaurosis, orthostatic complications). Finally, seven patients showed contraindications during test occlusion for permanent occlusion of the ICA. Four patients had a permanent occlusion of the ICA after tumour resection. In two patients the ICA was removed without problems in test occlusion. The third patient underwent a permanent carotid occlusion because of bleeding complications (in spite of poor clinical tolerance of the test occlusion). In the fourth patient, only intraoperative neuromonitoring with MSSEP's was conducted before permanent carotid occlusion. All four patients did not show any neurological deficits after resection of the ICA. Neurophysiological monitoring played an important role in predicting cerebral complications after permanent occlusion of the ICA.
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