Citations

Background and Purpose Among patients with spontaneous cervical artery dissections, the risk of recurrent arterial dissection is relatively low at 1% per year, but this risk may be higher for patients with a family history of arterial dissections. We compared the risk of a recurrent arterial dissection in patients with familial versus nonfamilial disease. Methods Long-term follow-up was established in 200 patients (104 women and 96 men with a mean age of 44.9 years) with spontaneous cervical artery dissections evaluated at a single institution between 1970 and 1990. Results Among the 200 patients, 10 (5%) were identified who had a family history of spontaneous arterial dissections. In a multivariate analysis, family history was the only significant variable associated with the risk of recurrent dissection (χ 2 =15.51; P =.0001). A recurrent arterial dissection was identified in 5 (50%) of the 10 patients with familial disease compared with 11 (5.8%) of the 190 patients with nonfamilial disease, with an estimated relative risk of 6.3 (95% confidence interval, 2.2 to 18.3; P =.0007). Conclusions Among patients with spontaneous cervical artery dissections, a family history of arterial dissection is an important risk factor for the development of a recurrent arterial dissection.

Background and Purpose Proto-oncogene activation and induction of heat shock protein (HSP) occur in response to various stimuli to brain, but the role in neuronal survival after cerebral ischemia remains uncertain. We compared the extent of insults and induction of c- fos and c- jun gene products (c-FOS and c-JUN) as well as HSP in ischemic and postischemic gerbil brains immunohistochemically. Methods Common carotid arteries of Mongolian gerbils were occluded for 5 or 15 minutes and recirculated for 0 minutes to 7 days. Antibodies for c-FOS, c-JUN, and HSP 70 were used for immunohistochemistry, and positive reactions were semiquantitatively analyzed. The presence of ischemic and postischemic lesions was ascertained with an antibody for microtubule-associated proteins. Results After ischemia for 15 minutes and reperfusion, c-FOS was induced promptly after 1 to 6 hours in pyramidal cells of the CA3 and CA4 regions, while c-JUN became visible in the same areas after recirculation for 4 to 48 hours. HSP 70 was detected after recirculation for 24 hours in the CA3 region. In layers I and II of the cerebral cortex, c-FOS and c-JUN peaked at 3 hours and HSP 70 at 96 hours. Induction of these proteins was absent or negligible in the areas that developed ischemic or postischemic lesions, including the subiculum-CA1 and CA1 regions of the hippocampus and layers III/IV and Vb/VI of the cerebral cortex. After shorter ischemia for 5 minutes and reperfusion, c-FOS and c-JUN were rapidly induced at 15 minutes to 1 hour except for the subiculum-CA1 and CA1 regions of the hippocampus. Induction of HSP 70 did not occur for 24 hours and was noted only in the hippocampus. Conclusions Induction of c-FOS and c-JUN occurred in the areas surviving after transient cerebral ischemia, but the extent of induction and the latent period varied depending on the duration of the insult and the location. In the areas with ischemic or postischemic damage detected by loss of the reaction for microtubule-associated proteins, the induction of c-FOS and c-JUN was either absent or minimal, suggesting that active induction of those immediate early gene products occurred early in surviving neurons. On the other hand, the induction of HSP 70 did not occur until reperfusion for 24 hours and actively occurred only in the areas with earlier induction of c-FOS and/or c-JUN, suggesting that the induction of HSP 70 occurred in neurons that survived to that point, but it did not participate in early responses for neuronal survival after global cerebral ischemia.

An account of the origin, within the American Heart Association, of a council devoted to vascular disease of the central nervous system, with particular attention to the context in which that occurred, is presented in this article. The forces of a service-charitable organization, political action, medical practice in general, and interested, strong-witted citizens provided the stimuli for the development of the Stroke Council.

Background and Purpose The use of intermittent reperfusion versus straight occlusion during neurovascular procedures is controversial. This experiment studied the effects of intermittent reperfusion and single occlusion on intracellular brain pH (pH i ), regional cerebral or cortical blood flow, and nicotinamide adenine dinucleotide (NADH) fluorescence during temporary focal ischemia. Methods Twenty fasted rabbits under 1.0% halothane anesthesia were divided into four groups: (1) nonischemic controls, (2) 60 minutes of uninterrupted focal ischemia, (3) 2×30-minute periods of focal ischemia separated by a 5-minute reperfusion, and (4) 4×15-minute periods of focal ischemia separated by three 5-minute reperfusion periods. Focal ischemia was produced by occlusion of both the middle cerebral and ipsilateral anterior cerebral arteries. After the final occlusion, there was a 3-hour reperfusion period in all groups. Regional cerebral and cortical blood flow, brain pH i , and NADH fluorescence were measured with in vivo panoramic fluorescence imaging. Results During occlusion, regional cerebral and cortical blood flows and NADH fluorescence values were not different among the groups. Brain pH i was significantly lower in the 4×15-minute group compared with the 1×60-minute group (6.57±0.02 versus 6.73±0.06; P <.03) but not significant when compared with the 2×30-minute group. During the short reperfusion periods, all parameters returned to normal except for NADH fluorescence levels, which remained elevated. During the postischemic final reperfusion period, there was a mild brain alkalosis of approximately 7.1 in all groups. There were no significant differences in NADH fluorescence among groups during the final reperfusion. Regional cerebral and cortical blood flow returned to near normal values in all groups. Conclusions This study demonstrates that intermittent reperfusion during temporary focal ischemia has different effects on the intracytoplasmic and the intramitochondrial compartments: worsening of brain cytoplasmic pH i but no significant differences in the oxidation/reduction level of mitochondrial NADH.

Background and Purpose The present study was conducted to investigate the incidence of stroke and 30-day case-fatality rates for stroke in a defined Russian population. Methods This is a population-based study that was established in 1982. All residents of an administratively defined and typical district of Novosibirsk (approximately 150 000 subjects) who had an incident (first-ever) stroke from January 1, 1982, through December 31, 1992, were registered. Results During an 11-year study period, 3406 incident stroke patients were registered, for an overall crude average annual incidence rate of 202/100 000 population. The rates were higher with increasing age and were significantly higher for men than for women. The age- and sex-adjusted annual incidence rate of stroke declined from 271/100 000 in 1982 to 232/100 000 in 1992. Slowing of the decline in stroke incidence was observed after 1988, and stroke incidence increased slightly in 1992. No significant differences in 30-day stroke case-fatality rates were noted from 1982 through 1992, but a slight trend toward decreasing rates was observed after 1988. There was no major change in patient age at stroke onset. Conclusions Stroke incidence rates in Novosibirsk are among the highest in the world. We observed a decline in stroke incidence but little change in 30-day case-fatality rates in Novosibirsk from 1982 through 1992.

Background and Purpose CGS 19755 is a competitive N -methyl- d -aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. Methods At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. Results Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of ≥70 at the terminal visit. Conclusions We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Background and Purpose Clinical experience has established that intravascularly placed metal coils can be a useful treatment for cerebral vascular aneurysms. However, the mechanism by which the coils induce occlusion of the aneurysm is unclear. Appropriate use of this promising treatment modality requires basic understanding of the occlusive process. We used an animal model system of experimentally induced carotid aneurysms to investigate the initial events induced by Guglielmi detachable coils (GDCs), as well as the subsequent vascular changes induced by the coils over time. Methods We induced 23 aneurysms in the carotid arteries of 16 Japanese monkeys. Nineteen aneurysms were then occluded with GDCs placed via endovascular surgery; 4 aneurysms served as controls. We then used gross and microscopic pathological examination, angiography, and scanning electron microscopy to assess the effects of the GDC. Results In the first few hours after placement of the GDC in the experimental aneurysms, we observed leukocyte attachment and deposition of fibrinlike materials and other proteins. By 4 days after coil placement, leukocytes and fibroblasts were observed in the thrombus. By 2 weeks after coil placement, there was evidence of an endothelial-like covering of the coils. At 3 months after coil placement, we observed development of an arterial media in the occluded aneurysms. Conclusions The GDCs initiated a cellular response within several hours of aneurysm occlusion. By 2 weeks after coil placement, endothelialization was proceeding, and by 3 months after occlusion, remodeling of the aneurysm had progressed to produce a media-like structure in the former aneurysm.

Background A primary arteriopathy is often implicated in the etiology of spontaneous cervicocephalic arterial dissections, but its exact nature usually remains unknown. We describe the familial occurrence of spontaneous arterial dissections and congenitally bicuspid aortic valve (BAV) and propose a common developmental defect in these families. Summary of Report In the first family, a 63-year-old man suffered an extracranial internal carotid artery (ICA) dissection, and his 43-year-old cousin with BAV suffered an intracranial vertebral artery (VA) dissection. Two other family members had pathologically proven BAV. In the second family, a 31-year-old woman suffered bilateral extracranial ICA and VA dissections. Her father, at age 46, suffered an aortic dissection associated with cystic medial necrosis and BAV. Her paternal uncle died from an aortic dissection at age 59. In the third family, a 39-year-old woman suffered extracranial ICA and VA dissections, and her brother died at age 48 from an aortic dissection associated with a BAV. Conclusions The familial occurrence of spontaneous arterial dissections and BAV suggests a common developmental defect. The aortic valvular cusps and the arterial media of the aortic arch and its branches are derived from neural crest cells, suggesting that a neural crest defect may be the underlying abnormality in these families.

Background and Purpose The purpose of this study was to clarify whether mitral valve prolapse increases the subsequent risk of stroke. Methods A historical cohort study was conducted on 1079 residents of Olmsted County, Minnesota, who had an initial echocardiographic diagnosis of mitral valve prolapse between 1975 and 1989 without prior stroke or transient ischemic attack and who were followed up for first stroke occurrence. Results There was an overall twofold increase in the incidence of stroke among individuals with mitral valve prolapse relative to the reference population (standardized morbidity ratio, 2.1; 95% confidence interval, 1.3 to 3.2). Sex, duration of follow-up from the diagnosis of mitral valve prolapse, or calendar year of initial diagnosis did not modify the association. Within the cohort of patients who were at least 35 years old at diagnosis of mitral valve prolapse, a time-dependent proportional-hazards multivariate model and a person-years analysis revealed that age, ischemic heart disease, congestive heart failure, and diabetes mellitus were important determinants for stroke when person-years of observation after mitral valve replacement were excluded. Among seven persons with mitral valve replacement, three strokes occurred in 24 person-years of follow-up. For those with an auscultatory diagnosis of mitral valve prolapse only as the indication for echocardiography (44%), the risk of stroke relative to the population was 1.0 (95% confidence interval, 0.2 to 2.9); for those with another cardiac diagnosis, the standardized morbidity ratio was 2.5 (95% confidence interval, 1.5 to 4.0). Conclusions Individuals with uncomplicated mitral valve prolapse did not have an increased risk of stroke, although a small increase in the risk may not have been detected.

Nonaneurysmal perimesencephalic hemorrhage, a distinct form of subarachnoid hemorrhage, is a recently described variant of intracranial hemorrhage. We describe two patients who presented with unusual features of this type of subarachnoid hemorrhage and also two patients who had a perimesencephalic pattern of hemorrhage due to a ruptured posterior circulation aneurysm. The first patient, a 41-year-old woman with perimesencephalic hemorrhage, underwent an exploratory craniotomy because angiography had suggested an anomaly of the basilar tip. No source of hemorrhage could be identified at the time of surgery. The second patient was a 3-year-old boy who presented with opisthotonos and who was found to have a perimesencephalic hemorrhage. Angiography revealed no source for the hemorrhage. The third patient, a 54-year-old man, had a perimesencephalic pattern of subarachnoid hemorrhage from a vertebrobasilar junction aneurysm associated with a fenestration that was missed on the initial angiographic study. The fourth patient, a 43-year-old man, suffered a perimesencephalic pattern of subarachnoid hemorrhage from a small posterior cerebral artery aneurysm, which had not been recognized on two angiograms. These patients elaborate on the clinical spectrum of subarachnoid hemorrhage with a perimesencephalic pattern. First, a negative exploratory craniotomy suggests that the source of nonaneurysmal perimesencephalic hemorrhage may not be arterial. Second, nonaneurysmal perimesencephalic hemorrhage may also occur in children. Finally, the index of suspicion for a posterior circulation aneurysm should remain high in patients who present with a perimesencephalic pattern of subarachnoid hemorrhage, and these aneurysms may rise from unusual locations.