Biomedical subjects
Publications and source records attributed to A J Furlan.
The effect of stroke as a major health issue in the United States is well established. Well-designed epidemiologic studies have contributed important information about the natural history of stroke and its associated risk factors. These cerebrovascular profiles have provided the foundation for many of the current ischemic stroke trials, but the cause and prevention of the hemorrhagic subtypes remain elusive.
We describe the use of abciximab to prevent rethrombosis of the basilar artery after transluminal angioplasty. A 60-year-old patient with vertebral basilar insufficiency and acute occlusion of the basilar artery underwent revascularization with urokinase and angioplasty. Despite the repeated use of urokinase and angioplasty under anticoagulation with heparin, the basilar artery immediately rethrombosed. In a final attempt to prevent rethrombosis, abciximab was administered before the final angioplasty, resulting in a widely patent basilar artery and no rethrombosis.
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The effect of stroke as a major health issue in the United States is well established. Well-designed epidemiologic studies have contributed important information about the natural history of stroke and its associated risk factors. These cerebrovascular profiles have provided the foundation for many of the current ischemic stroke trials, but the cause and prevention of the hemorrhagic subtypes remain elusive.
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Explore the source record for details and available documents.
BACKGROUND AND PURPOSE: Magnetic resonance (MR) diffusion-weighted imaging (DWI), a noninvasive procedure, may play an important role in detecting and accurately localizing the extent of evolving infarction within the period immediately following stroke. We evaluated the sensitivity and specificity of DWI in detecting ischemia and compared a quantitative measure derived from the DWI, the apparent diffusion coefficient (ADC), with autoradiographic cerebral blood flow (CBF) in an experimental model of focal cerebral ischemia in rats. METHODS: MR imaging data were obtained with a General Electric 4.7-T horizontal bore magnet CSI II system with self-shielded gradients. DWI was acquired within 41 +/- 6 minutes (mean +/- SD) after onset of ischemia and repeated at 169 +/- 14 minutes, followed by CBF determination at 237 +/- 21 minutes. DWI, ADC, and CBF images from each animal were then compared. RESULTS: The sensitivities for detecting an abnormality at 1 and 3 hours for DWI were significantly different, and the sensitivity of 3-hour DWI did not differ from the CBF sensitivity of 99%. A mean +/- SD ADC threshold of 460 +/- 95 microns 2/s was defined as 45% higher than the low ADC in the ischemic core compared with the contralateral ADC. Subthreshold ADC area and ischemic area were significantly correlated (r2 = .69, P < .05). In 19 of 48 regions of interest classified as ischemic (< 35 mL.100 g-1.min-1) from both the 3-hour ADC and CBF images, 3-hour ADC correlated significantly with CBF (r2 = .27, n = 19, P < .05), whereas in the nonischemic regions ADC was inversely correlated with CBF. Several ischemic regions showed a sharp drop in ADC to 37% (P < .001, n = 5) compared with all other regions (n = 43) from 1 to 3 hours. CONCLUSIONS: Because of the change in the sensitivity of detecting ischemia with DWI, the difference in correlation of CBF with ADC between ischemic and nonischemic cortex, and the presence of several regions in which ADC dropped to 37% from 1 to 3 hours, our data suggest that ADC values potentially can be used to monitor evolving infarction.
We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetic resonance diffusion-weighted imaging (MR-DWI) is sensitive to the diffusibility of water and may offer characterization and anatomical localization of stroke leading to early tailored therapeutic intervention. We compared DWI, the apparent diffusion constant (ADC), and autoradiographic cerebral blood flow (CBF) in a model of focal cerebral ischemia in the rat. Sprague-Dawley rats were embolized with a single silicone cylinder injected into the internal carotid artery. Both common carotids were permanently ligated. The animals were anesthetized (isoflurane in O2), and paralyzed (gallamine). MR-DWI were obtained with a GE 4.7 T magnet (TE = 3 s, TR = 80 msec, b = 2393.10(-3) mm2/s, slice thickness 3 mm). DWI and CBF autoradiograms were compared visually. ADC was assessed in various regions, including ischemic cortex and a region homologous to ischemic cortex. Imaging times from stroke onset were 50 +/- 6 min (mean +/- SEM) for DWI, 185 +/- 17 min for a second DWI. CBF was determined at 258 +/- 15 min. The specificity was 100% at both 50 min and 185 min, indicating that there were no false positives; in 3 animals ischemia was not present. However, the sensitivity analysis indicated that early DWI yields some false negatives; at 50 min the sensitivity was 60%. We attribute our result of low early sensitivity to small infarcts in relation to the slice thickness. Later, at 185 min, sensitivity was 100%. The first ADCs were higher than the second ADC values in ischemic cortex. For infarcts larger than the slice thickness, early MR-DWI is highly sensitive for imaging evolving ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND AND PURPOSE: Paradoxical embolism through a patent foramen ovale is a recognized cause of stroke, but clinical predictors, recurrence rate, and prevention of brain infarcts in patients with patent foramen ovale have not been determined. We reviewed transesophageal echocardiographic records to ascertain echocardiographic predictors and optimal prophylaxis for patent foramen ovale-related infarcts. METHODS: A patent foramen ovale was identified in 74 patients during 615 transesophageal echocardiograms by color Doppler or saline contrast during a 60-month period. On the basis of final clinical situation, the patients were divided into the following groups: group 1, infarct with patent foramen ovale a likely cause (n = 16); group 2, infarct with patent foramen ovale an unlikely cause (n = 23); and group 3, no infarct (n = 35). Transesophageal echocardiograms were reviewed to assess patent foramen ovale characteristics and associated cardio-embolic sources without knowledge of clinical details or group assignment. Follow-up after a patent foramen ovale-related infarct was obtained by telephone or written correspondence in 15 of 16 group 1 patients. RESULTS: Atrial septal aneurysms were more common in group 1 (38%) compared with group 2 (10%) and group 3 (8%) (P = .02). Contrast right-to-left shunting occurred in 88% of group 1 (P = .06) and 86% of group 2 (P = .07) compared with 60% of group 3. Prevention of recurrence in subjects with presumed patent foramen ovale-related brain infarcts varied. Aspirin was usually chosen after initial brain ischemia. Warfarin and patent foramen ovale closure were usually reserved for subjects with symptoms of brain ischemia while taking aspirin or those who required warfarin or cardiac surgery for other indications. No recurrent infarcts occurred in 15 patients during a mean follow-up period of 28 months. CONCLUSIONS: Atrial septal aneurysm and right-to-left shunt may be predictive of a patent foramen ovale that predisposes a patient to stroke. Aspirin may provide sufficient infarct prophylaxis after initial ischemia. Warfarin and surgical correction should likely be reserved for those in whom aspirin is not effective or those who require warfarin or cardiac surgery for other reasons until prospective studies are available.
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Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.
OBJECTIVE: Primary angiitis of the central nervous system (PACNS) has been considered a rare and highly fatal disorder when untreated. In recent years the disease has been increasingly diagnosed by cerebral angiography, often without histologic confirmation. We have questioned whether cases of PACNS diagnosed on the basis of angiography alone are equivalent to histologically confirmed cases. METHODS: All cases of PACNS reported from 2 sources, including all cases reported in the English medical literature through January of 1990 as well as from the case records of the Cleveland Clinic Foundation were reviewed. Sixty-five variables were analyzed including demographic data, clinical signs and symptoms, treatment, outcome, diagnostic modalities and associated conditions. The cases were divided into 3 groups based on method of diagnosis. Group A referred to those diagnosed by angiography alone, but unconfirmed by histology, Group A & P for those who had positive histologic evidence angiitis confined to the central nervous system and a positive angiogram and Group P containing those diagnosed on the basis of histology who either never underwent angiography or who had angiographic findings other than arteritis. RESULTS: Cases of PACNS defined by angiography alone (Group A) appear often to be clinically distinctive, occurring more frequently in young women, often presenting with the sudden onset of focal neurologic deficit and associated with a relatively benign cerebral spinal fluid analysis. Patients defined in such manner frequently have a self-limited clinical course and may not require combination therapy with corticosteroids and cytotoxic drugs. CONCLUSION: We believe that PACNS is more clinically heterogeneous than is recognized and that a distinct and possibly more benign subset of disease that can be diagnosed on clinical and angiographic grounds has been identified.
We performed postmortem magnetic resonance imaging and pathologic examinations on the brains of seven consecutive patients older than 50 years of age who died of non-neurologic causes. Multiple hyperintense subcortical lesions were identified in each patient, and a total of 29 lesions were examined histologically (eight rims, six caps, six punctate lesions, and nine patches). Rims were characterized by subependymal gliosis and loss of the ependymal lining; caps were associated with myelin pallor, gliosis, and arteriosclerosis; punctate lesions were characterized by dilated perivascular spaces and perivascular gliosis; and patches were associated with myelin pallor and dilated perivascular spaces. The pattern of myelin pallor defined the size and shape of caps and patches. Arteriosclerosis was identified in six of six caps, three of six punctate lesions, and in three of nine patches. These data indicate that (1) each type of hyperintense subcortical lesion has a distinct pathologic correlate; (2) arteriosclerosis is not invariably associated with all types of hyperintense subcortical lesions on magnetic resonance imaging; and (3) myelin pallor appears to contribute to the magnetic resonance imaging signal at 1.5 tesla.
An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.
PURPOSE AND METHODS: We analyzed the clinical, laboratory, and radiologic data in nine patients who sustained an intracranial hemorrhage (ICH) after receiving intravenous recombinant tissue plasminogen activator (rt-PA) and heparin for treatment of acute myocardial infarction (MI). Our purpose was to delineate the clinical and radiologic features of the ICHs, as well as to determine their potential risk factors and mechanisms. RESULTS: Among 1,700 patients with an acute MI treated with an investigational two-chain rt-PA, duteplase (Burroughs Wellcome Co., Research Triangle Park, NC), nine (0.53%) developed symptomatic ICH. Neurologic symptoms occurred between 7 and 96 hours after onset of rt-PA therapy. All patients received heparin concomitantly for prevention of coronary reocclusion. The activated partial thromboplastin times (aPTTs) in five of eight (63%) patients at onset of ICH were excessively prolonged (greater than two times control); hypofibrinogenemia occurred in only one of five (20%) patients tested; and thrombocytopenia was present in only one of the nine (11%) patients. Fibrin degradation products (FDPs) were elevated in all five patients tested. Minor hemorrhage (not requiring transfusion) outside the central nervous system occurred in five of the nine patients with ICH. The ICHs were often of lobar location and of moderate to large size. They occurred at multiple sites in three patients, and were fatal in four instances (44%). CONCLUSIONS: The incidence of ICH in this series was low, and consistent with figures reported from studies with alteplase in patients with acute MI. The mechanisms of these hemorrhages remain unclear; while hypofibrinogenemia was not a uniform finding, excessive prolongation of the aPTT and elevated FDPs may have contributed to the occurrence of ICH in some patients. Still unidentified local cerebrovascular factors may play an additional role in causing ICH. In order to further clarify the mechanisms of ICH in the setting of thrombolytic therapy, prospective data collection on probable risk factors for ICH in patients with acute MI treated with rt-PA will be required.
BACKGROUND AND PURPOSE: We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. METHODS: Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. RESULTS: The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. CONCLUSIONS: These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.