Nancy Futrell

Frequency, etiology, and prevention of stroke in patients with systemic lupus erythematosus

We retrospectively and prospectively reviewed the incidence of stroke in 105 patients with systemic lupus erythematosus (SLE). Stroke occurred in 14 (15%) of 91 consecutive patients with documented SLE; nine (64%) of the 14 had multiple cerebral infarcts. Factors associated with stroke and the frequency of stroke were systemic thrombosis (30%), elevated partial thromboplastin time (36%), spontaneous abortion (50%), age over 60 years (57%), transient ischemic attacks (57%), previous stroke (64%), and cardiac valvular disease (86%). The major period of risk for the first stroke was during the first 5 years of SLE. The most frequent etiology was a cardiogenic embolus or an antibody-mediated hypercoagulable state, with cerebral vasculitis occurring only in association with infection. Because of the decreased fibrinolysis seen in patients with SLE, anticoagulant therapy may be the most effective preventive treatment currently available. Anticoagulant therapy seemed to prevent recurrent focal cerebral ischemia in our patients and was associated with relatively few and minor complications. Patients with a history of transient ischemic attacks or cardiac valvular lesions are at high (57% and 87%, respectively) risk of stroke. Patients who have had a stroke are at high (64%) risk for a recurrent stroke. Anticoagulant therapy is recommended for all of these patients.

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or “crack” form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Embolic stroke from a carotid arterial source in the rat Pathology and clinical implications

We developed a new animal model of stroke which resembles human stroke more closely than existing models. We described the pathology produced in the brain following platelet embolism, previously described only in the retina. The common carotid artery of the rat was irradiated for 6.5 minutes with an argon laser at 514.5 nm after intravenous injection of a photosensitizing agent, rose bengal. A retinal embolus was seen in 1 rat 5 minutes after irradiation. A nonocclusive platelet thrombus was present in the carotid artery 50 minutes after irradiation, with almost all the platelet thrombus being cleared 24 hours later. Acute (1 to 10 days) changes in the brain included 44 small infarcts in 12/13 rats, cortical arterioles occluded with platelets and thickening of small vessels in normotensive rats. Chronic (4 to 12 weeks) changes included lacunes in the brains of normotensive rats and intimal proliferation of smooth muscle in the carotid artery. This is the 1st animal model of (1) stroke with emboli produced in vivo rather than injected into the carotid, (2) intimal proliferation of smooth muscle without invasion of the vessel, and (3) lacunes. This model provides results important to the laboratory study of stroke.

Lacunar Infarction: Embolism is the Key

Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACEP Section Editors: Lacunes are small deep infarcts which cavitate, producing “lacunes” (French for lake).1 “Lacunar infarcts” have been thought of as strokes caused by intrinsic disease of small vessels called lipohyalinosis, resulting from hypertension2 and diabetes.3 Contrary to this established dogma, the literature demonstrates that emboli are the cause of lacunes. Almost all of the histopathological evaluation of blood vessels associated with lacunes has been done by C. Miller Fisher. In 11 patients with lacunes there was only a single case of lipohyalinosis compared with 2 cases of cerebral emboli.2 Although not commonly cited this way, Fisher’s own writing demonstrates emboli are more common than lipohyalinosis in patients with lacunes. Fisher was also responsible for the hypothesis of hypertension as a cause of lacunes, based on his report of hypertension in 111/114 of his patients with lacunes. This has not been documented by subsequent studies, which showed hypertension in 24% to 73% of patients …

Gender Influences the Magnitude of the Inflammatory Response Within Embolic Cerebral Infarcts in Young Rats

BACKGROUND AND PURPOSE The inflammatory response within cerebral infarcts may have an influence on tissue damage. Since old animals with an impaired immune response have decreased inflammation after experimental cerebral infarction, we postulated that female animals with an increased immune response will have an increased inflammatory response after cerebral infarction. METHODS Embolic cerebral infarcts were produced by photochemical irradiation of the right carotid artery in 12 female Fischer rats. The inflammatory response within 4-day-old infarcts was quantitated by histology with the use of computer-assisted image analysis and compared with that in 12 male rats from a previous series. RESULTS Severe infarcts had the most pronounced inflammatory response. Female rats had an increased inflammatory response in infarcts of all severity, which was statistically significant in severe cerebral infarcts even after adjustment for infarct size. Severe infarcts in males were significantly larger than those in females. CONCLUSIONS Gender influences the outcome of embolic cerebral infarcts after photochemical damage to the carotid artery, both in terms of the magnitude of the inflammatory response and infarct size. There are numerous gender-related differences in neurochemicals, cytokine production, and drug metabolism that may influence tissue damage after stroke and responsiveness to therapeutic intervention. The preponderance of male animals in stroke research may produce results not applicable to female stroke patients. The use of female animals will be required to provide adequate models for the study of stroke in women.