Attitudes and approaches to acute ischemic stroke in Wisconsin hospitals.

Although acute stroke is a common presentation to an emergency room, the presentation of a patient with acute ischemic stroke, within a limited time window as an appropriate candidate for cerebral thrombolysis, is not common. In many of these patients, their candidacy can be improved through community education toward emergent transfer to an emergency room if they manifest symptoms of stroke. This would improve the "symptom-to-door" time. Another goal is to improve the recognition and approach of the hospital itself toward improving the "door-to-drug" time in appropriate patients. The obstacle to this second goal does not seem to be a nihilistic or evasive attitude on the basis of this study. Contrary to what was expected, enthusiasm for the use of cerebral thrombolysis was found in emergency physicians of all hospital categories, particularly of small remote hospitals. Instead, educational initiatives should focus on the facilitation of protocols for present and future ischemic stroke therapy, particularly in larger remote facilities that may be more self-dependent in their approach to acute stroke. An equally important focus should be toward more active participation by local neurologists who may be available for acute stroke care. Further, as this study demonstrates a correlation between the involvement of a local neurologist and the use of a stroke protocol, neurologists of non-tertiary facilities should be recruited to participate in these educational initiatives.

Isolated petrous carotid stenosis and transient ischemic attack.

Although anterior circulation transient ischemic attacks (TIAs) tend to be more common in patients with extra- cranial carotid arterial disease than in those with intracranial carotid or middle cerebral arterial disease, the authors recently encountered 4 patients with both recurrent, stereotypical TIAs as well as isolated stenosis of their petrous internal carotid artery (ICA). While the gold standard for establishing the diagnosis of intracranial large-artery disease has always been conventional angiography, magnetic resonance angiography changes, confirmed with intra-arterial digital subtraction angiography in 2 of these patients, were quite sufficient to define the occlusive disease in each of the cases. Petrous ICA stenosis is not uncommon, but it has often been overshadowed by the search for extracranial ICA disease that might be amenable to surgical reconstruction.

Naratriptan: an alternative for migraine.

OBJECTIVE: To critically evaluate the literature regarding naratriptan's clinical pharmacology, efficacy, safety, and indications. DATA SOURCE: A MEDLINE search was conducted for the period from January 1990 to June 1998. Key words used included naratriptan, triptan, serotonin agonists, migraine, and migraine therapy. In addition, pertinent references cited in articles obtained from MEDLINE and product information for triptans were reviewed. STUDY SELECTION AND DATA EXTRACTION: All original and review articles and abstracts pertaining to naratriptan were reviewed, as were product information extracts. Clinical trials of naratriptan were critically reviewed and compared with pertinent clinical trials of other oral triptans. DATA SYNTHESIS: The treatment of migraine has been dramatically improved with the use of sumatriptan, other triptans, and serotonin-receptor subtype 1B and 1D agonists. Drawbacks to these medications, however, have included poorly tolerated adverse effects and the recurrence of the migraine. Naratriptan has been recently approved for acute oral migraine therapy. In two Phase III trials of naratriptan compared with placebo, relief at four hours was obtained in 60% and 68% of patients using the 2.5-mg dose, with recurrence of headache in 24 hours in 27% and 28% of patients. The data on migraine recurrence were similar to those of other oral triptans; the efficacy of naratriptan at two hours was not specifically analyzed. Adverse effects of naratriptan were similar to placebo, and its tolerability seemed superior compared with studies of other oral triptans. CONCLUSIONS: Naratriptan is a promising new oral therapy for acute migraine; it may successfully treat patients who poorly tolerate other triptan therapies or have longer duration migraine headaches.

Ischemic stroke associated with activated protein C resistance and aortic valvular papillary fibroelastoma.

We report an unusual case of a pontine ischemic stroke associated with activated protein C resistance as well as an embolic source in the form of a cardiac valvular lesion. A 31-year-old man had a sudden onset of right hemiparesis and a severe dysarthria. Cranial magnetic resonance imaging (MRI) showed a nonhemorrhagic pontine lesion with essentially negative craniocervical MR angiography. His transesophageal echocardiogram showed a papillary fibroelastoma on the aortic valve. His laboratory studies showed significant activated protein C resistance at 1.7 (normal, >2.1). Other laboratory parameters, including sedimentation rate, were unremarkable. This case suggests that activated protein C resistance may serve as a cofactor in some cases of ischemic stroke, particularly stroke associated with emboligenic cardiac lesions.

Pulsatile tinnitus in cerebrovascular arterial diseases.

In a prospective study of 100 patients evaluated at the University of Wisconsin Stroke Program, we sought to document cases of incidental pulsatile tinnitus that could be ascribed to stenotic, occluded, ectatic, tortuous, or dissected craniocerebral arteries. Angiographic detail, magnetic resonance angiography, catheter-generated x-ray angiography, or both were necessary for inclusion into either Group 1 (n=29), those with pulsatile tinnitus, or Group 2 (n=71), those without pulsatile tinnitus. Patients did not appear to have head/neck tumors, aneurysms, arteriovenous malformations, transmitted cardiac murmurs, or venous etiologies for their tinnitus. Age, sex, and stroke risk factor profiles did not separate the two groups. Factors that were significantly more common in Group 1 included (1) severe, > or =70% stenosis through complete occlusion, internal carotid artery disease (59% for Group 1 v 21% for Group 2, P<.05); (2) severe, > or =50% stenosis through occlusion, vertebral or basilar disease (38% v 18%, P<.05); (3) tortuosity of at least one carotid, vertebral, or basilar artery (31% v 18%, P<.05); and (4) basilar artery dolichoectasia (14% v 0%, P=.006). We also noted when pulsatile tinnitus was either "objective" (11 of 100, 11%) or "subjective" (18 of 100, 18%), duration of tinnitus, transient versus permanent nature of tinnitus, and reasons seen in consultation by one of us.

Tortuosity of carotid and vertebral arteries: a magnetic resonance angiographic study.

Nine patients (group A) were found on magnetic resonance angiography (MRA) to have excessive carotid artery, vertebral artery, and vertebrobasilar junction tortuosity. A control group (group B) were age- and sex-matched to group A patients, were selected randomly from our MRA or stroke data banks, and had not undergone MRA for evaluation of migraine, "carotidynia," or pulsatile tinnitus. Factors more prevalent in group A patients included migraine, chronic daily headache, carotidynia, pulsatile tinnitus, and a positive family history of headache. Factors more prevalent in group B patients included a positive family history of stroke, large-vessel atherosclerosis, and scan evidence of ischemic infarctions; many group B patients had undergone MRA for stroke or transient ischemic attack evaluation. Men were slightly underrepresented at 44%, and were younger than women (34 +/- 6 years vs. 43 +/- 3 years; p = 0.01). Relationships in this preliminary study between arterial tortuosity and migraine seem evident.

Differing mechanisms between posterior and middle cerebral artery infarctions.

Cardiac embolism has been thought to be one of the principal causes of posterior cerebral artery territory infarction. To determine stroke mechanisms and stroke risk factors in patients with posterior cerebral artery infarction, we studied 23 consecutive patients with recent infarcts in the posterior cerebral artery distribution (PCA infarcts) and compared these with a case-control group of 46 patients with recent infarcts in the middle cerebral artery distribution (MCA infarcts). All patients were similarly studied, including angiography and echocardiography. Case controls were age- and sex-matched and were randomly chosen from the most recent MCA infarcts seen at our institutions. All subjects were white. PCA infarcts had significantly more cardiac-source emboli (P=.01), less evident atherothrombosis (P=.003), multiplicity of infarctions (P=.05), and documented branch occlusions in the vessel involved (P=.05). MCA infarcts had more preinfarction transient ischemic attacks (P=.03) and evident occlusion of the appropriate extracranial vessel (P=.03). Different stroke mechanisms should lead to different diagnostic and therapeutic decisions.

Vasodilatory responses and magnetic resonance angiography. Extracranial and intracranial intravascular flow data.

This study measured the responses of both extracranial (internal carotid arteries) and intracranial (middle cerebral/angular, basilar arteries) intravascular arterial volume flow rates to acetazolamide using phase-contrast magnetic resonance angiography. Twenty-eight newly studied patients were subdivided into four groups: Group I--Nonocclusive, asymptomatic (n = 7, or 14 carotid and middle cerebral/angular artery sides); Group II--unilateral carotid transient ischemic attacks, nonhemodynamic (embolic), varying stenoses (n = 11); Group III--unilateral carotid transient ischemic attacks, hemodynamic, varying stenoses (n = 5); and Group IV--unilateral carotid occlusion, asymptomatic (n = 5). The data were separated into nonischemic and ischemic sides so as to illustrate group differences based on vasodilatory responses to acetazolamide. For example, the percent change in volume flow rates over baseline values for the ischemic-side middle cerebral arteries of Group III was significantly the lowest of all of the vasodilatory responses (-25 +/- 11% vs 40 +/- 14% for group II ischemic middle cerebral/angular artery sides, p = 0.008). Group III patients also had significantly lower standing blood pressures (p = 0.012), higher number of transient ischemic attacks (p = 0.008), and shorter duration of events (p = 0.013). Determinations of volume flow rate continue to assist in determining the degree of hemodynamic compromise of a particular vascular territory.

Relationship between age and mortality due to intracerebral versus subarachnoid hemorrhage.

This cross-sectional study compares trends in mortality by age for intracerebral and subarachnoid hemorrhage. United States mortality data from the Centers for Disease Control from the years 1991 to 1992 are examined with the program CDC Wonder, and mortality rates for 10-year age groups for each disease are compared. As expected, the crude mortality rate attributable to intracerebral hemorrhage, at 7.1 per 100,000, is much greater than that of subarachnoid hemorrhage, at 2.7 per 100,000. However, the age distribution of this mortality is found to be very different in the two conditions (chi(2), P<.0001), with a younger population affected by subarachnoid hemorrhage. This difference is even more pronounced in earlier United States mortality data from 1979 to 1980. This has important implications for epidemiological studies of hemorrhagic stroke as a whole.

Cerebral venous thrombosis and activated protein C resistance.

BACKGROUND: Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT. CASE DESCRIPTIONS: We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons. CONCLUSIONS: Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.

Anticardiolipin antibodies in a university hospital population.

We have retrospectively reviewed data on our university hospital patients who had had at least one anticardiolipin antibody (aCL) titer performed (n = 781) during a 32-month study period between January 1991 and September 1993. We were able to locate clinical data on 95% (741 of 781) of these patients. Women (W) predominated at 70% (513 of 741), with men (M) at 30% (228 of 741). Reasons for ordering this test included brain infarct (M, 16%; W, 9%), multiple brain infarcts (M, 5%; W, 5%), migraine (M, 5%; W, 19%), and excessive clotting tendencies (M, 19%; W, 10%). Overall, aCL positivity was found in 10% of patients (73 of 741), with second-titer-confirmed positivity at 82% (60 of 73), men positive at 8% (18 of 228), and women positive at 11% (55 of 513; M versus W NS). For men, brain infarct (16% of aCL-positive in M versus 5% in W, p = 0.02), and for women, multiple brain infarcts (32% versus 0%, p = 0.01), migraine (10% versus 0%, p = 0.01), and systemic lupus erythematosus (30% versus 14%, p = 0.07) were the evident men-versus-women differences. We further studied stroke risk factors, associated conditions, family history, and laboratory findings relative to both sexes. aCL positivity continues to present differently, based on sex, at our university hospital.

Ischemic stroke in young adults: Results from the university of Wisconsin stroke registry.

We prospectively evaluated 128 consecutive young adults aged 18-50 years who suffered from at least one ischemic stroke. Men (92 of 128, 72%) predominated and had a mean age of 41 ± 8 years. Women (36 of 128, 28%) had a mean age of 40 ± 8 years (ns). Risk factors that separated male and female groups included previous stroke, which as seen overall in 34% (43 of 128; M/F = 38/5, p = 0.002), andstroke in thefamily, which was seen overall in21% (27 of 128;M/F = 22/5, p = 0.005). Thirty-day mortality was seen in 3% (4 of 128), all of whom were men. Stroke causes included atherosclerotic in 22% (28 of 128; M/F = 19/9, ns), cardioembolic in 17% (22 of 128, M/F = 17/5, ns), arteriopathic in 17% (22 of 128, M/F = 11/11, p < 0.002 for female preponderance), and coagulopathic in 15% (19 of 128, M/F = 18/1, p = 0.002 for male preponderance). Stroke causes remained "undetermined, " including small deep stroke and mixed causes, in 16%( 21 of 128; M/F = 17/4, ns), "uncertain, " including migraine-related and mitral valve prolapse, in 9% (11 of 128; M/F = 3/8, p = 0.002 for female preponderance), and "unknown" in 4% (5 of 128; M/F = 5/0, ns). These data, as part of the University of Wisconsin Stroke Registry, compare favorably to similar, previously published series from other institutions. Composite data from several of these series are also included.

Evidence for transhemispheric diaschisis in unilateral stroke.

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.