John E. Castaldo

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke The CLEAR Stroke Trial

Background and Purpose— Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. Methods— The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke–funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 &mgr;g/kg bolus followed by 0.75 &mgr;g/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Results— Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA–only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. Conclusions— The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

Internal carotid artery redundancy is significantly associated with dissection.

Background and Purpose Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated. Methods We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies. Results Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P=.0019 and P=.0001, respectively). Conclusions We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally.

Spectrum and Potential Pathogenesis of Reversible Posterior Leukoencephalopathy Syndrome

BACKGROUND Controversy still exists over the etiology and pathophysiology of reversible posterior leukoencephalopathy syndrome (RPLS). This large single-center case series aims to describe the clinical and imaging features of RPLS in an attempt to deduce the etiology of the disorder and the mechanisms of brain injury. METHODS A retrospective chart and imaging review was conducted on 59 cases of RPLS in 55 patients. RESULTS Five RPLS imaging patterns were observed: posterior predominant (n = 40), anterior predominant (n = 7), diffuse lesion (n = 7), basal ganglia predominant (n = 3), and brainstem/cerebellum predominant patterns (n = 2). RPLS resulted in permanent neurologic deficits in 14 patients and death in 4 patients. Hypertension was seen in 57 (97%) cases, and mean arterial blood pressure exceeded 140 mm Hg in 30 (51%) cases. Follow-up magnetic resonance imaging scans revealed a significant worsening of vasogenic edema in 2 cases, both with persistent hypertension. Magnetic resonance imaging scans revealed areas of ischemia in 14 cases, all within or at areas closely adjacent to vasogenic edema. Diffuse vasculopathy was seen in 8 cases. There was a lack of correlation between the presence of vasculopathy and the degree of vasogenic edema (P = .62), but a correlation was suggested between ischemia and vasculopathy (P = .02). CONCLUSIONS This study strongly suggests that hypertension-induced vasodilation rather than vasoconstriction-mediated hypoxia is likely the major mechanism responsible for the development of vasogenic edema, and that vasoconstriction may contribute to the development of ischemia in RPLS.

Hemiplegic migraine during pregnancy : Unusual magnetic resonance appearance with SPECT scan correlation

Objective.—This article discusses the pathophysiology and implications for treatment of hemiplegic migraine within a case study presentation.

The impact of cardiac index on cerebral hemodynamics.

Background and Purpose Current noninvasive testing allows accurate assessment of cerebrovascular hemodynamics. The cardiovascular influence on the noninvasive assessment of cerebrovascular studies has not been defined. This study was designed to determine the effect of cardiac index (CI) on cerebral blood flow velocities, ocular pulse amplitude, ophthalmic systolic pressure, and ocular blood flow (OBF) as currently estimated by noninvasive laboratories. Methods Based on a retrospective study of 181 patients, we prospectively evaluated 45 patients undergoing right heart catheterization for hemodynamic monitoring to correlate the relation between CI, transcranial Doppler sonography, and ocular pneumoplethysmography. Patients with hemodynamic instability, severe carotid stenoses, massive cerebral infarct, or sepsis were ineligible for the study. Simultaneous recordings of systemic blood pressure, ophthalmic systolic pressure, heart rate, ocular pulse amplitude, middle cerebral artery blood flow velocities, and cardiac output were obtained on all patients. OBF was calculated from the heart rate and ocular pulse amplitude. Results The relation between OBF and CI is expressed by the equation CI=2.36+0.61xOBF (r=.47, P=.0010). The middle cerebral artery peak systolic velocities and CI had a correlation of .36 (P=.0181). The equation, derived from the linear relation between OBF and CI, was then validated on a sample of 15 patients. With the apparent linear relation between OBF and CI, we used the derived equation to predict CI from OBF. The OBF determination predicted CI within 30% in all patients and within 20% in 53.3% of the patients. Conclusions We demonstrated that OBF and middle cerebral artery systolic velocity decrease with diminishing CI. Our findings suggest that CI may be potentially estimated in selected patients by noninvasive assessment of OBF using ocular pneumoplethysmography. (Stroke. 1993;24:1686-1690.)

Posterior Reversible Encephalopathy Syndrome: Clinicoradiological Spectrum and Therapeutic Strategies

Abstract Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance, and seizures. In most cases, symptoms present acutely or subacutely in the setting of accelerated hypertension, eclampsia, autoimmune disease, immunosuppressive treatment, or cancer chemotherapy. One essential feature of PRES is the presence of reversible cerebral vasogenic edema that has a predominantly posterior distribution on brain imaging. Atypical imaging features are commonly described, including involvement of the anterior brain or brainstem and the coexistence of ischemia or hemorrhage. In most cases, both clinical and radiological findings are reversible, although permanent imaging abnormalities and residual neurological sequelae can be seen in a minority of patients. The syndrome is thought to be caused by a breakdown of the blood–brain barrier and an extravasation of the intravascular fluid. Treatment of hypertension and seizures, and withdrawal of causative agents are the mainstays of therapy in PRES.

Is carotid artery disease responsible for perioperative strokes after coronary artery bypass surgery

The coronary and extracranial carotid vascular beds are often simultaneously affected by significant atherosclerotic disease, and stroke is one of the potential major complications of coronary artery surgery. As a result, there is no shortage of reports in the vascular surgery literature describing simultaneous coronary and carotid artery revascularizations. Generally, these reports have found this combination of operations safe, but have stopped short of proving that it is necessary. Intuitively, simultaneous carotid endarterectomy and coronary artery bypass surgery could be justified if most perioperative strokes were the result of a significant carotid stenosis, either directly or indirectly. At first glance this appears to be a fairly straightforward issue; however, much of the evidence on both sides of the argument is circumstantial. One significant problem in analyzing outcome by choice of treatment in patients presenting with both coronary and carotid disease is the multiple potential causes of stroke in coronary bypass patients, which include hemorrhage and atheroemboli from aortic atheromas during clamping. But this controversial subject is now open to discussion, and our debaters have been given the challenge to clarify the evidence to justify their claims.

Sulcal artery syndrome after vertebral artery dissection.

Sulcal artery syndrome is a rare cause of spinal cord infarction. We describe a case of sulcal artery syndrome due to traumatic vertebral artery dissection and review the known literature on this rare syndrome.

Reversible Confluent Deep White Matter Abnormalities: A New Variant of Posterior Reversible Encephalopathy Syndrome

We describe a confluent deep white matter abnormalities variant of PRES, further strengthening the notion that PRES is a disorder of radiological heterogeneity. We present 2 cases of PRES with findings of diffuse but reversible vasogenic edema located in the deep periventricular white matter regions of bilateral hemispheres without a clearly posterior distribution. We feel that this represents a rare variant of PRES on imaging, thus adding to the existing radiological spectrum for this entity. Both of our patients presented with malignant hypertension (mean arterial blood pressure of 200 mmHg) and developed neurological symptoms that included encephalopathy, seizure, headache, and vision changes. Additionally, both patients presented with significant subcortical white matter edema that improved dramatically on follow-up imaging. The clinical and radiological improvement in both patients occurred following successful blood pressure management. It is possible that the deep white matter changes of PRES are seen exclusively in the setting of severe accelerated hypertension. Our case reports reveal that, in patients with hypertensive encephalopathy, a deep white matter pattern of diffuse signal changes may not necessarily indicate chronic ischemic changes and follow-up imaging studies are essential to rule out a diagnosis of PRES.

The Lowering of Vascular Atherosclerotic Risk (LOVAR) Program: An Approach to Modifying Cerebral, Cardiac, and Peripheral Vascular Disease

More than 1 million US citizens die of cerebral, cardiac, and peripheral vascular disease (collectively, CVD) each year. Basic science and clinical outcome research aimed at reducing the burden of this illness is widespread, but the knowledge gleaned from controlled trials has not fully translated into everyday clinical practice and care of patients with CVD and their inherent risk factors. The Lowering of Vascular Atherosclerotic Risk (LOVAR) program was a 5-year observational study that evaluated the feasibility of a high-intensity multidisciplinary program of risk factor reduction in a population with known symptoms of CVD. The population comprised patients with documented clinically symptomatic cerebral, cardiac, or peripheral vascular disease and at least two modifiable risk factors for stroke, myocardial infarction, or peripheral vascular occlusive disease. Final outcomes were evaluated by comparing primary and secondary end points and quality of life. A total of 271 patients were enrolled in the intervention group, and 242 were enrolled in the standard care group (control). At 3 years, significant improvements in several risk factors were seen in the intervention group, with no significant improvements for the control group. The rate of patient retention was 95% at 3 years, and overall rates of physician and patient satisfaction were high. We believe that the Lowering of Vascular Atherosclerotic Risk program is generalizable to a sufficiently motivated population targeted as high risk for vascular disease.