Abstracts of Literature
Resumption of Work After Aneurysmal Subarachnoid Hemorrhage in Middle-Aged Japanese Patients—Nishino A (Dept of Neurosurgery, Stroke Center, Sendai National Hospital, 2-8-8 Miyagino, Miyagino-ku, Sendai 983-8520, Japan), Sakurai Y, Tsuji I, Arai H, Uenohara H, Suzuki S, Li JH—J Neurosurg. 1999;90:59–64.
Object. Previous reports on the results of treatment for aneurysmal subarachnoid hemorrhage (SAH) have been based only on activities of daily living after discharge, whereas resumption of work has received insufficient attention. Most Japanese work under a lifetime employment system, and it is best for those who have recovered from SAH to return to work for their previous employer. The present study was conducted to determine the extent to which discharged patients who have suffered an SAH resume their former occupations in Japan, focusing on those between 40 and 49 years of age, who usually have a strong desire to return to work.
Methods. The participants consisted of 193 patients with SAH. Based on the results of telephone interviews or written questionnaires, their work status at 1 year after onset was analyzed.
The work resumption rates for patients with Hunt and Kosnik neurological Grades 1 or 2 on admission were higher than for those with Grades 3 or 4 (p=0.015) and lower for patients with basilar artery aneurysms than for those with aneurysms at other sites (p=0.028). With regard to premorbid occupation, the work resumption rates were high (80%) for professionals and engineers, many of whom were public servants, or teachers at junior or senior high schools. The resumption rates were also high for primary industry workers (80%), but lowest (20%) for professional drivers (p=0.04–0.001). The work resumption rate was lower for women than for men (p=0.01).
Conclusions. These findings indicate that resumption of work is determined not only by medical factors, but also by social factors including gender, type of occupation, employment system, and socioeconomic background.
subarachnoid hemorrhage, stroke outcome
Chronic Shunt-Dependent Hydrocephalus After Early Surgical and Early Endovascular Treatment of Ruptured Intracranial Aneurysms—Gruber A (Dept of Neurosurgery, Univ of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria), Reinprecht A, Bavinzski G, Czech T, Richling B—Neurosurgery. 1999;44:503–512.
OBJECTIVE: The goal of this study was to document the influence of the treatment method (early surgery versus early endovascular treatment) on the development of chronic shunt-dependent hydrocephalus in a series of 242 patients treated within 7 days after aneurysmal subarachnoid hemorrhage (SAH).
METHODS: The following parameters were prospectively recorded in a computerized database and retrospectively analyzed for association with chronic shunt-dependent hydrocephalus: 1) Hunt and Hess grade, 2) Fisher computed tomographic grade, 3) incidence of repeat SAH, 4) aneurysm location, and 5) treatment method (early surgery versus early endovascular treatment).
RESULTS: Forty of 187 patients (21.4%) who survived the SAH and its neurological and/or medical sequelae underwent definitive shunting for treatment of chronic hydrocephalus. The rate of shunt dependency was positively correlated with a higher Hunt and Hess grade (P<0.001), a higher Fisher computed tomographic grade (P=0.003), the occurrence of intraventricular hemorrhage (P<0.001), repeat SAH (P=0.003), and aneurysms arising at the anterior communicating artery (P<0.001).
CONCLUSION: The results of the present study indicate that the treatment method used does not affect the risk of the later development of chronic shunt-dependent hydrocephalus (early surgery, 23.2% [29 of 125]; early endovascular treatment, 17.7% [11 of 62]; P=0.45).
subarachnoid hemorrhage, hydrocephalus
Migraine and Stroke in Young Women: Case-Control Study—Chang CL, Donaghy M, Poulter N (Cardiovascular Studies Unit, Dept of Clinical Pharmacology, Imperial College School of Medicine, London W2 1PG, England), and World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception—BMJ.1999;318:13–18.
Objective To investigate the association between migraine and ischaemic or haemorrhagic stroke in young women.
Design Hospital based case-control study.
Setting Five European centres participating in the World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
Subjects 291 women aged 20–44 years with ischaemic, haemorrhagic, or unclassified arterial stroke compared with 736 age and hospital matched controls.
Main outcome measure Self reported history of headaches.
Results Adjusted odds ratios associated with a personal history of migraine were 1.78 (95% confidence intervals, 1.14 to 2.77), 3.54 (1.30 to 9.61), and 1.10 (0.63 to 1.94) for all stroke, ischaemic stroke, and haemorrhagic stroke respectively. Odds ratios for ischaemic stroke were similar for classical migraine (with aura) (3.81, 1.26 to 11.5) and simple migraine (without aura) (2.97, 0.66 to 13.5). A family history of migraine, irrespective of personal history, was also associated with increased odds ratios, not only for ischaemic stroke but also haemorrhagic stroke. In migrainous women, coexistent use of oral contraceptives or a history of high blood pressure or smoking had greater than multiplicative effects on the odds ratios for ischaemic stroke associated with migraine alone. Change in the frequency or type of migraine on using oral contraceptives did not predict subsequent stroke. Between 20% and 40% of strokes in women with migraine seemed to develop directly from a migraine attack.
Conclusions Migraine in women of childbearing age significantly increases the risk of ischaemic but not haemorrhagic stroke. The coexistence of oral contraceptive use, high blood pressure, or smoking seems to exert a greater than multiplicative effect on the risk of ischaemic stroke associated with migraine.
Small Centrum Ovale Infarcts: A Pathological Study—Lammie GA (Dept of Neuropathology Alexander Donald Building, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, UK), Wardlaw JM—Cerebrovasc Dis. 1999;9:82–90. Copyright © 1999 S. Karger AG, Basel.
There are limited data, mainly clinical and radiological, on small centrum ovale infarcts (SCOIs). From a consecutive series of 159 autopsy brains we identified 12 cases which on gross pathological examination harboured a total of 21 SCOIs. In the majority of lesions histology revealed a significant component of incompletely infarcted brain. Clinicopathological data suggested that the underlying mechanism was likely to have been cardioembolic in 3 cases, and possibly embolic from heart or aortic arch in a further 5. Two cases were due to ipsilateral carotid artery atheroma (i.e. 10 of 12 cases had possible embolic sources). The majority of lesions appeared to lie in arterial borderzones. The combined data suggest that SCOIs are pathologically and pathogenetically heterogeneous, and therefore that the term ’lacune’ is inappropriate because this implies intrinsic small vessel disease as the underlying cause. Clinically, potentially treatable cardiac and large vessel pathology should be excluded.
lacunar infarction, stroke classification
Endogenous Nitric Oxide Synthase Inhibitor: A Novel Marker of Atherosclerosis—Miyazaki H, Matsuoka H (The Cardiovascular Research Institute, Dept of Internal Medicine III, Kurume Univ School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011 Japan), Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T—Circulation. 1999;99:1141–1146. Copyright © 1999 American Heart Association, Inc.
Background—Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans.
Methods and Results—Subjects (n=116; age, 52±1 years; male:female ratio, 100:16) underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and duplex scanning of the carotid arteries. These individuals had no symptoms of coronary or peripheral artery disease and were taking no medications. Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Σ glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise regression analysis revealed that plasma ADMA levels were significantly correlated to the intima-media thickness of the carotid artery (as measured by high-resolution ultrasonography).
Conclusions—This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.
atherosclerosis, nitric oxide
Diabetic Nephropathy Is Associated With an Increased Familial Risk of Stroke—Lindsay RS (Dept of Diabetes, Royal Infirmary of Edinburg NHS Trust, Lauriston Place, Edinburgh EH3 9YW, Scotland, UK), Little J, Jaap AJ, Padfield PL, Walker JD, Hardy KJ—Diabetes Care. 1999;22:422–425.
OBJECTIVE—To test the hypothesis that genetic susceptibility to diabetic nephropathy is associated with an increased familial risk of vascular disease, we have examined the causes and rates of death of parents of individuals with type 1 diabetes complicated by diabetic nephropathy compared with the causes and rates of death of parents of control subjects with diabetes uncomplicated by nephropathy.
RESEARCH DESIGN AND METHODS—Individuals with at least a 14-year duration of type 1 diabetes complicated by diabetic nephropathy were identified and matched for age, sex, and duration of diabetes to control subjects. A total of 118 patients and 118 matched control subjects were identified and approached to obtain information on parental age and cause of death. For parents who had died, the cause of death was ascertained from the death certificate.
RESULTS—Kaplan-Meier curves showed that parents of subjects with nephropathy (PN) had reduced survival compared with parents of diabetic subjects without nephropathy (PC) (log rank test P<0.05). There was an excess of all vascular deaths and, in particular, strokes in the parents of subjects with nephropathy (PN: 20 of 103 deaths, 19% vs. PC: 3 of 66 deaths, 4%; Fisher’s exact test P<0.01).
CONCLUSIONS—Parents of diabetic patients with nephropathy have reduced survival. This seems to be largely explained by an increase in vascular deaths and, in particular, a four-fold increase in the number of strokes. This supports the hypothesis that a common hereditary risk factor predisposes to both vascular death and diabetic renal disease.
diabetes mellitus, risk factors
G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of US Men—Ridker PM (Cardiovascular Div, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115), Hennekens CH, Miletich JP—Circulation. 1999;99:999–1004. Copyright © 1999 American Heart Association, Inc.
Background—A single base pair mutation in the prothrombin gene has recently been identified that is associated with increased prothrombin levels. Whether this mutation increases the risks of arterial and venous thrombosis among healthy individuals is controversial.
Methods and Results—In a prospective cohort of 14 916 men, we determined the prevalence of the G20210A prothrombin gene variant in 833 men who subsequently developed myocardial infarction, stroke, or venous thrombosis (cases) and in 1774 age- and smoking status-matched men who remained free of thrombosis during a 10-year follow-up (control subjects). Gene sequencing was used to confirm mutation status in a subgroup of participants. Overall, carrier rates for the G20210A mutation were similar among case and control subjects; the relative risk of developing any thrombotic event in association with the 20210A allele was 1.05 (95% CI, 0.7 to 1.6; P=0.8). We observed no evidence of association between mutation and myocardial infarction (RR=0.8, P=0.4) or stroke (RR=1.1, P=0.8). For venous thrombosis, a modest nonsignificant increase in risk was observed (RR=1.7, P=0.08) that was smaller in magnitude than that associated with factor V Leiden (RR=3.0, P<0.001). Nine individuals carried both the prothrombin mutation and factor V Leiden (5 controls and 4 cases). One individual, a control subject, was homozygous for the prothrombin mutation.
Conclusions—In a large cohort of US men, the G20210A prothrombin gene variant was not associated with increased risk of myocardial infarction or stroke. For venous thrombosis, risk estimates associated with the G20210A mutation were smaller in magnitude than risk estimates associated with factor V Leiden.
thrombosis, risk factors
Seasonal Variation in Stroke Mortality Rates—Lanska DJ (VA Medical Center, 500 E Veterans St, Tomah, WI 54660), Hoffmann RG—Neurology. 1999;52:984–990. Copyright © 1999 by the American Academy of Neurology.
Objective: To identify possible contributors to the seasonal variation in stroke mortality. Background: Stroke and respiratory disease mortality rates were calculated from vital statistics and census data for the United States from 1938 to 1988. State-specific average temperatures by month were derived from data obtained from the National Climatic Data Center for 1938 to 1987. Methods: Each time series was decomposed into a trend, a seasonal effect, and a residual effect. Multiple regression was used to fit both a trend and a seasonal harmonic series. Cross-correlation was used to assess the relationship between the residual time series. Results: There is a strong and consistent seasonal pattern of high stroke and respiratory disease mortality in the colder winter months. Stroke mortality was significantly and independently both positively associated with respiratory disease mortality and inversely associated with temperature. The sharp initial increases in both respiratory disease and stroke mortality in the late fall and early winter are synchronous, and the amplitudes are strongly associated, except for a saturation effect with extreme respiratory disease amplitudes. Conclusions: Seasonal change in stroke mortality is associated with seasonal variation in both respiratory disease and temperature. Respiratory disease and temperature may influence stroke mortality nonspuriously by affecting stroke case fatality, incidence, or both.
stroke outcome, epidemiology
Nitric Oxide Mediates Neurologic Injury After Hypothermic Circulatory Arrest—Tseng EE, Brock MV, Lange MS, Troncoso JC, Lowenstein CJ, Blue ME, Johnston MV, Baumgartner WA (Div of Cardiac Surgery, Johns Hopkins Hospital, Blalock 618, 600 N Wolfe St, Baltimore, MD 21287)—Ann Thorac Surg. 1999;67:65–71. Copyright © 1999 by The Society of Thoracic Surgeons.
Background. Prolonged hypothermic circulatory arrest (HCA) causes neurologic injury. However, the mechanism of this injury is unknown. We hypothesized that HCA causes nitric oxide production to result in neuronal necrosis. This study was undertaken to determine whether the neuronal nitric oxide synthase inhibitor 17477AR reduces necrosis after HCA.
Methods. Thirty-two dogs underwent 2 hours of HCA at 18°C. Nitric oxide synthase catalytic assay and intracerebral microdialysis for nitric oxide production were performed in acute nonsurvival experiments (n=16). Sixteen animals survived for 72 hours after HCA: Group 1 (n=9) was treated with 17477AR (Astra Arcus), and group 2 (n=7) received vehicle only. Animals were scored from 0 (normal) to 500 (coma) for neurologic function and from 0 (normal) to 100 (severe) for neuronal necrosis.
Results. Administration of 17477AR reduced nitric oxide production in the striatum by 94% (HCA alone), 3.65±2.42 μmol/L; HCA and 17477AR, 0.20±0.14 μmol/L citrulline). Dogs treated with 17477AR after HCA had superior neurologic function (62.22±29.82 for group 1 versus 141.86±61.53 for group 2, p=0.019) and significantly reduced neuronal necrosis (9.33±4.67 for group 1 versus 38.14±2.23 for group 2, p<0.00001) compared with untreated HCA dogs.
Conclusions. Our results provide evidence that neuronal nitric oxide synthase mediates neuronal necrosis after HCA and plays a significant role in HCA-induced neurotoxicity. Pharmacologic strategies to inhibit neuronal nitric oxide synthase after the ischemic period of HCA may be clinically beneficial.
nitric oxide, cerebral ischemia
Pretreatment With Intravenous FGF-13 Reduces Infarct Volume and Ameliorates Neurological Deficits Following Focal Cerebral Ischemia in Rats—Yao DL (Dept of Pharmacology, Human Genome Sciences, 9410 Key West Ave, Rockville, MD 20850), Masonic K, Petullo D, Li YL, Lincoln C, Wibberley L, Alderson RF, Antonaccio M—Brain Res. 1999;818:140–146. Copyright © 1999 Elsevier Science B.V.
Fibroblast growth factor-13 (FGF-13), novel member of FGF family has recently been molecularly cloned as a result of high throughput sequencing of a ovarian cancer cell, hippocampal, and kidney cDNA libraries. The human gene encodes for a protein with a molecular weight of 22 kDa that is most homologous to FGF-8 (70% similarity). In the current study, we tested the effects of intravenously administered FGF-13 in a model of permanent focal cerebral ischemia in Sprague–Dawley rats. FGF-13 or the vehicle was administered systematically via the tail vein 30 min prior, and 30 min and 24 h after the occlusion of the left middle cerebral artery (MCAo). Animals were weighted and evaluated behaviorally prior to and at 24 and 48 h after MCAo. The volume of cerebral infarct and swelling were determined using an image analysis system (BioQuant) and cresyl violet stained sequential sections from the forebrain region. Histopathology was evaluated to compare the therapeutic effects. We found a 63% reduction in infarct volume in FGF-13- vs. vehicle-treated animals (infarct volume was 21.9±3.8% in vehicle- and 8.1±1.6% in FGF-13-treated rats, p=0.0016) and a moderate inhibition of brain swelling by FGF-13. The reduction in infarct volume and brain swelling were associated with improvement of clinical deficits in FGF-13 treated animals (p<0.001). Histopathological examination determined that nervous tissue was better preserved in FGF-13 treated rats than those of controls. These data show that pretreatment with intravenous FGF-13 reduces infarct size and ameliorates neurological deficits following permanent focal cerebral ischemia in rats.
cerebral ischemia, stroke, experimental
A Comparative Study of the Effects of Two Nitric Oxide Synthase Inhibitors and Two Nitric Oxide Donors on Temporary Focal Cerebral Ischemia in the Wistar Rat—Coert BA, Anderson RE, Meyer FB (Dept of Neurosurgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905)—J Neurosurg. 1999;90:332–338.
Object. A critical review of the literature indicates that the effects of nitric oxide synthase (NOS) inhibitors on focal cerebral ischemia are contradictory. In this experiment the authors methodically examined the dose-dependent effects of two NOS inhibitors and two NO donors on cortical infarction volume in an animal model of temporary focal cerebral ischemia simulating potential ischemia during neurovascular interventions.
Methods. Ninety-two Wistar rats underwent 3 hours of combined left middle cerebral artery and bilateral common carotid artery occlusion after having been anesthetized with 1% halothane. A nonselective NOS inhibitor, NG-nitro-l-arginine-methyl-ester (l-NAME), and two NO donors, 3-morpholinosydnonimine hydrochloride and NOC-18, DETA/NO, (Z)-l-[2(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, were administered intravenously 30 minutes before ischemia was induced. A selective neuronal NOS inhibitor, 7-nitroindazole (7-NI), was administered intraperitoneally in dimethyl sulfoxide (DMSO) 60 minutes before ischemia was induced. Two ischemic control groups, to which either saline or DMSO was administered, were also included in this study. Seventy-two hours after flow restoration, the animals were perfused with tetrazolium chloride for histological evaluation.
Cortical infarction volume was significantly reduced by 71% in the group treated with 1 mg/kg l-NAME when compared with the saline-treated ischemic control group (27.1±37 mm3 compared with 92.5±26 mm3, p<0.05). The NOS inhibitor 7-NI significantly reduced cortical infarction volume by 70% and by 92% at doses of 10 and 100 mg/kg: 35.2±32 mm3 (p<0.05) and 9±13 mm3 (p<0.005), respectively, when compared with the DMSO-treated ischemic control group (119±43 mm3). There was no significant difference between the saline-treated and DMSO-treated ischemic control groups. Treatment with NO donors did not significantly alter cortical infarction volume.
Conclusions. These results support an important role for NO in ischemic neurotoxicity and indicate that neuronal NOS inhibition may be valuable in reducing cortical injury in patients suffering temporary focal cerebral ischemia during neurovascular procedures.
nitric oxide, stroke, experimental
Ultra-Early Clot Aspiration After Lysis With Tissue Plasminogen Activator in a Porcine Model of Intracerebral Hemorrhage: Edema Reduction and Blood-Brain Barrier Protection—Wagner KR (Research Service 151, Dept of Veterans Affairs Medical Center, 3200 Vine St, Cincinnati, OH 45220), Xi G, Hua Y, Zuccarello M, de Courten-Myers GM, Broderick JP, Brott TG—J Neurosurg. 1999;90:491–498.
Object. Ultra-early hematoma evacuation (<4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs.
Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0.3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post-ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry.
Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2±1.3 to 2.8±0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40±0.10 compared with 1.26±0.13 cm3, p<0.005) and perihematomal edema volumes (0.28±0.05 compared with 1.46±0.24 cm3, p<0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls.
Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (>70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.
thrombolysis, hemorrhagic stroke
Effect of Cigarette Smoke on Endothelial Regeneration in Vivo and Nitric Oxide Levels—Sarkar R (Sec of Vascular Surgery, UCLA Medical Center, Los Angeles, CA 90095), Gelabert HA, Mohiuddin KR, Thakor DK, Santibanez-Gallerani AS—J Surg Res. 1999;82:43–47. Copyright © 1999 by Academic Press.
Background. Cigarette smoking accelerates atherosclerosis and restenosis after vascular reconstruction. The mechanisms by which smoking alters vessel structure after injury are unclear. This study examined the effects of cigarette smoking on endothelial regeneration, an important component of arterial remodeling.
Materials and methods. Adult male rats were subjected to balloon injury of the thoracic aorta and exposed to mainstream cigarette smoke via a Griffith-type smoking machine for 2 weeks. Control groups included rats which were restrained in the machine but not smoked and a group not utilizing the machine. Aortic reendothelialization was determined using Evan’s blue staining of the arterial surface. Serum levels of nitric oxide were measured to determine if smoke exposure altered this potential endothelial cell mitogen.
Results. Cigarette smoking increased aortic endothelial regeneration (78.4±4.6% vs 59.2±2.1%, P<0.05) and was associated with an increase in serum nitric oxide level (59.9±7.1 μM vs 28.5±1.8 μM, P<0.05). Daily restraint alone in the smoking machine had no effect on endothelial regeneration.
Conclusions. This is the first report on the effects of smoking on endothelial regeneration and demonstrates that smoking increases reendothelialization after large vessel injury and serum levels of nitric oxide, an EC mitogen.
cigarette smoking, endothelium
Correlation Between Symptomatic, Radiological and Etiological Diagnosis in Acute Ischemic Stroke—Tei H (Dept of Neurology, Toda Central General Hospital, 1-19-3 Honcho, Toda City, Saitama 3350023, Japan), Uchiyama S, Koshimizu M, Kobayashi M, Ohara K—Acta Neurol Scand. 1999;99:192–195. Copyright © Munksgaard 1999.
Objectives—The aim of this study was to correlate with the symptomatic, radiological and etiological diagnosis in acute ischemic stroke. Subjects and methods—Two hundred and fifty patients with first-ever ischemic stroke within 24 h of onset were prospectively studied with 3-step diagnoses: 1) symptomatic diagnosis based on the Oxfordshire Community Stroke Project criteria (OCSP), 2) radiological diagnosis (CT or MRI) and 3) etiological diagnosis based on the Lausanne Stroke Registry criteria. Results—Most of the patients with symptoms of total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI) and posterior circulation infarcts (POCI) had corresponding lesions on CT or MRI, while only 68% of lacunar infarcts (LACI) patients had small subcortical infarction (SSI). More than 60% of patients with TACI were classified into cardioembolism in the third diagnosis, while the etiology of PACI was either CE or large-artery atherosclerosis (LAA) in equal numbers. Only 58% of LACI patients were classified into small-artery disease (SAD) and 29% of them (30 cases) into LAA, of which 23 patients had lesions other than SSI. The positive predictive value of SAD in the combination of LACI and SSI was 0.78. The etiology of POCI was variable. Conclusion—Except for LACI, the symptomatic classification by OCSP corresponds well to the radiological diagnosis. The etiological diagnosis can be predicted by OCSP in TACI and PACI, but it is hard in POCI, and a number of LACI are due to LAA.
cerebral infarction, stroke classification
The Relationship Between Cerebral Infarction and Angiographic Characteristics in Childhood Moyamoya Disease—Mugikura S (Dept of Radiology, Hiraka General Hospital, 1-30 Ekimaemachi, Yokote, Akita 013-0036, Japan), Takahashi S, Higano S, Shirane R, Kurihara N, Furuta S, Ezura M, Takahashi A—Am J Neuroradiol. 1999;20:336–343. Copyright © American Society of Neuroradiology.
BACKGROUND AND PURPOSE: In childhood-onset moyamoya disease, the angiographic disease process of stenoocclusive lesions is progressive, and cerebral infarctions often develop as a result of ischemia. Our purpose was to determine how the severity of stenoocclusive lesions in the anterior and posterior circulations affects the distribution of cerebral infarction in patients with childhood-onset moyamoya disease.
METHODS: In 69 patients with childhood-onset moyamoya disease, angiograms were reviewed for stenoocclusive lesions, and CT scans, MR images, or both were reviewed for the sites and extent of cerebral infarction. The relationship between the angiographic and CT/MR findings were examined.
RESULTS: The prevalence and degree of stenoocclusive lesions of the posterior cerebral artery (PCA) significantly correlated with the extent of lesions around the terminal portion of the internal carotid artery (ICA). The prevalence of infarction significantly correlated with the degree of stenoocclusive changes of both the ICA and PCA. Infarctions tended to be distributed in the anterior borderzone in less-advanced cases, while in more advanced cases lesions were additionally found posteriorly in the territory of the middle cerebral artery, the posterior borderzone, and the PCA territory.
CONCLUSION: Our results indicate that progressive changes of the anterior and posterior circulations are associated with the distribution of cerebral infarction, culminating in a patchily disseminated or honeycomb pattern of infarction on CT and MR studies in late stages of the disease.
stroke classification, angiography
MRI Evidence of Past Cerebral Microbleeds in a Health Elderly Population—Roob G, Schmidt R, Kapeller P, Lechner A, Hartung H-P, Fazekas F (Dept of Neurology, Karl-Franzens Univ, Auenbruggerplatz 22, A-8036 Graz, Austria)—Neurology. 1999;52:991–994. Copyright © 1999 by the American Academy of Neurology.
Background: Incidental foci of signal loss suggestive of past microbleeds are a frequent finding on gradient-echo T2*-weighted MRI of patients with nontraumatic intracerebral hemorrhage and have been associated with bleeding-prone microangiopathy. If and to what extent such lesions may also occur in the normal population is unclear. Objective: To determine focal hypointensities in asymptomatic elderly individuals and their relation to other clinical and morphologic variables. Methods: T2*-weighted MRI of the brain was performed in a consecutive series of 280 participants (mean age 60 years, range 44 to 79) of the Austrian Stroke Prevention Study. This cohort consisted of randomly selected individuals without history or signs of neuropsychiatric disorder. Results: Past microbleeds ranging from one to five foci of signal loss were seen in 18 (6.4%) individuals. They were strongly associated with higher age, hypertension, and lacunes (p<0.001), and extensive white matter damage was more frequently noted (p=0.02). Hypertension was present in all individuals with focal hypointensities in the basal ganglia and infratentorially but in only 5 of 10 volunteers with microbleeds limited to cortico-subcortical sites (p=0.04). Conclusions: MRI evidence of past microbleeds may be found even in neurologically normal elderly individuals and is related, but not restricted, to other indicators of small vessel disease. The predictive potential of this finding regarding the risk of intracerebral bleeding requires further investigation.
stroke prevention, cerebral hemorrhage
Cerebral Blood-Flow Responses to Induced Hypotension and to CO2 Inhalation in Patients With Major Cerebral Artery Occlusive Disease: A Positron-Emission Tomography Study—Nishimura S, Suzuki A, Hatazawa J, Nishimura H, Shirane R, Yasui N, Yoshimoto T (Dept of Surgical Neurology, Research Institute of Brain and Blood Vessels–Akita, 6-10 Senshu-Kubota Machi, Akita 010, Japan)—Neuoradiology. 1999;41:73–79. Copyright © Springer-Verlag 1999.
Our aim was to study the relationship between cerebral blood flow (CBF) responses to induced hypotension and to CO2 inhalation in patients with occlusive disease of the carotid or middle cerebral arteries. In 13 patients (8 men, 5 women) aged 31–73 years (mean±1 SD=63.2±10.6), regional CBF values during the resting state (CBFrest), 7% CO2 inhalation (CBFhypercapnia), and hypotension induced by 10–20 μg/kg/min intravenous trimethaphan (CBFhypotension) were measured using positron-emission tomography (PET) with H215O. The % CBF change during induced hypotension (% CBFhypotension) was defined as (CBFhypotension−CBFrest)/CBFrest multiplied by 100. The % CBF change during CO2 inhalation (% CBFhypercapnia) was defined as (CBFhypercapnia−CBFrest)/CBFrest/mm Hg arterial partial pressure of CO2×100. We defined symptomatic hemispheres as those with a stenotic or occlusive lesion with neurological symptoms or signs and asymptomatic hemispheres as those which had a similar lesion and/or were influenced by the collateral flow pattern without neurological symptoms. In the territory of the occlusive lesion, % CBFhypotension correlated significantly with % CBFhypercapnia (r=0.793, P<0.002) in the symptomatic hemispheres. In the brain regions in which trimethaphan did not induce a reduction in CBF, % CBFhypercapnia was 6.13±1.79. In those in which % CBFhypotension ranged from 0 to −5, from −5 to −10, and more than −10%, % CBFhypercapnia was 4.05±1.99, 3.21±1.17, and 1.73±1.61, respectively, with significant differences between each pair of groups. In the asymptomatic hemispheres, % CBFhypotension also correlated with % CBFhypercapnia (r=0.979, P<0.0001). Failure to maintain CBF during induced hypotension was associated with diminished cerebrovascular vasoreactivity to hypercapnia in patients with arterial disease. This may indicate that failure of autoregulation can be assessed by the CBF response to both induced hypotension and CO2 inhalation. From the technical point of view, estimation of the CO2 response may be useful for assessing failure of autoregulation.
cerebrovascular disorders, cerebral blood flow
Pitfalls in The Use of Spiral CT for Identification of Intracranial Aneurysms—Young N, (Dept of Radiology, Westmead Hospital, Darcy Rd, Westmead, NSW 2145 Australia), Dorsch NWC, Kingston RJ—Neuroradiology. 1999;41:93–99. Copyright © Springer-Verlag 1999.
We describe problems encountered in our first 136 patients, with 95 aneurysms, who underwent spiral CT for investigation of possible aneurysms involving the circle of Willis and adjacent major vessels, and who had surgical and/or angiographic confirmation. There were seven false-positive cases, of which the first three could be explained by operator inexperience. There were four false negatives, all small aneurysms; two were not seen because of operator error and two were hidden by an adjacent larger aneurysm. Clip artifacts prevented diagnostic studies in six of 21 postoperative studies. One aneurysm was outside the CT field of view, being on a pericallosal artery. One basilar artery tip aneurysm was excluded from the field of the CT study because of a planning error. Inspection of the axial source images is critical if the diagnosis of small or thrombosed aneurysms is to be made. Close attention to image acquisition and computer modelling is required to reduce errors in spiral CT angiography of intracranial aneurysms.
aneurysm, tomography, x-ray computed
Cerebrovascular Reactivity In Carotid Artery Occlusion: Possible Implications for Surgical Management of Selected Groups of Patients—Silvestrini M (Clinica Neurologica, Univ di Roma “Tor Vergata,” Ospedale S. Eugenio, P le dell’ Umanesimo 10, 00144 Roma, Italy), Vernieri F, Troisi E, Passarelli F, Matteis M, Pasqualetti P, Rossini PM, Caltagirone C—Acta Neurol Scand. 1999;99:187–191. Copyright © Munksgaard 1999.
Objectives—The aim of this study was to use transcranial Doppler ultrasonography to investigate cerebrovascular reactivity to hypercapnia in the middle cerebral arteries of patients with carotid occlusion with different outcomes. Patients and methods—Cerebrovascular reactivity to hypercapnia was calculated with the breath-holding index (BHI). Patients with unilateral carotid occlusion were divided as follows: asymptomatic (20 patients), transient ischemic attack (TIA) (20 patients), minor (20 patients) and major stroke (14 patients). Values of BHI homolateral to the carotid occlusion were compared with those of 25 healthy subjects and 34 stroke patients without significant carotid stenosis. Results—BHI values were comparable in healthy controls, non stenotic stroke patients and asymptomatic occluded patients. BHI values of patients with symptomatic occlusion were significantly lower than those of the above-mentioned groups (P<0.0001). Moreover, the reduction of BHI was significantly associated with the extent of the neurological impairment. In fact, BHI values were significantly higher in TIA than in minor and major stroke (P<0.0001) and in minor than in major stroke patients (P<0.02). Finally, we found that a BHI value homolateral to carotid occlusion of 0.69 can be considered the cut-point for distinguishing between symptomatic and asymptomatic patients. Conclusion—Prospective studies are needed to demonstrate if the presence of this threshold value may help in selecting a subset of patients with asymptomatic carotid occlusion or with transient or mild neurological deficit with the highest probability of benefiting from surgical therapy.
carotid artery diseases, cerebral vessels
Age-Related Transcranial Doppler Findings in the Evaluation of Cerebral Circulation During Postprandial and Postural Test—Poli L (Istituto di Geriatria, Ospedale Molinette, Corso Bramante 88, I-10126 Torino, Italy), Bo M, Secreto P, Zanocchi M, Bottino P—Cerebrovasc Dis. 1999;9:98–101. Copyright © 1999 S. Karger AG, Basel.
We used transcranial Doppler (TCD) to investigate whether there are cerebral circulation differences between young and elderly subjects in response to postprandial postural changes. Preprandial and postprandial systolic and diastolic blood pressure, heart rate, mean middle cerebral artery (MCA) velocity (Vmean MCA), systolic/diastolic MCA velocity ratio (Vs/Vd MCA) and pulsatility index (PI) were determined in 15 healthy elderly subjects (mean age 74.3±6.5 years) and in 10 younger subjects (mean age 31.6±7.2 years) in the supine position and after a postural change. As compared with young subjects, elderly ones showed a greater postprandial systolic pressure decline (p<0.05) associated with a significant decrease of Vmean MCA (p<0.05), and a greater increase of Vs/Vd and PI (p<0.05 both). We conclude that, as compared with young subjects, elderly ones have reduced cerebrovascular adaptive response to pressure modifications induced by postprandial postural changes.
ultrasonography, cerebral vessels
Ebselen in Acute Middle Cerebral Artery Occlusion: A Placebo-Controlled, Double-Blind Clinical Trial—Ogawa A (Dept of Neurosurgery, Iwate Medical Univ 19-1, Uchimaru, Morioka Iwate 020, Japan), Yoshimoto T, Kikuchi H, Sano K, Saito I, Yamaguchi T, Yasuhara H, for the Ebselen Study Group—Cerebrovasc Dis. 1999;9:112–118. Copyright © 1999 S. Karger AG, Basel.
A randomized, double-blind, placebo-controlled trial of ebselen was conducted in patients with complete occlusion of the middle cerebral artery. Ebselen or placebo granules suspended in water (150 mg b.i.d.) were orally administered within 12 h of onset and continued for 2 weeks. The major end points were the maximum volume of cerebral infarct measured on follow-up computed tomography and the Glasgow Outcome Scale score at 1 month. One hundred and five patients were enrolled in this trial. Although the intent-to-treat analysis of 99 patients (43 given ebselen and 56 given placebo) did not reach statistical significance in reduction of the infarct volume (p=0.099), the protocol-compatible analysis of 83 patients with complete occlusion of the middle cerebral artery (34 given ebselen and 49 given placebo) determined a significant reduction using ebselen treatment (p=0.034). A good outcome was seen in approximately 15% more patients from the ebselen group, but the difference between the 2 groups was not significant (p=0.129). There was a corresponding significant reduction in the volume of cerebral infarct and an improvement in the outcome of patients who started treatment within 6 h of onset. These findings may suggest that ebselen protected the brain from ischemic damage in the acute stage.
neuroprotection, neuronal damage
Demonstration of Rapid Onset Vascular Endothelial Dysfunction After Hyperhomocysteinemia: An Effect Reversible With Vitamin C Therapy—Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS (National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK)—Circulation. 1999;99:1156–1160. Copyright © American Heart Association.
Background—Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C.
Methods and Results—We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1 g/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8±1.4; 2 hours, 25.4±2.5; and 4 hours, 31.2±3.1 μmol/l, P<0.001), and flow-mediated dilatation fell (0 hours, 4.3±0.7; 2 hours, 1.1±0.9; and 4 hours, −0.7±0.8%) after oral L-methionine. There was an inverse linear relationship between homocysteine concentration and flow-mediated dilatation (P<0.001). Pretreatment with vitamin C did not affect the rise in homocysteine concentrations after methionine (0 hours, 13.6±1.6; 2 hours, 28.3±2.9; and 4 hours, 33.8±3.7 μmol/l, P=0.27), but did ameliorate the reduction in flow-mediated dilatation (0 hours, 4.0±1.0; 2 hours, 3.5±1.2 and 4 hours, 2.8±0.7%, P=0.02). GTN-induced endothelium independent brachial artery dilatation was not affected after methionine or methionine preceded by vitamin C.
Conclusions—We conclude that an elevation in homocysteine concentration is associated with an acute impairment of vascular endothelial function that can be prevented by pretreatment with vitamin C in healthy subjects. Our results support the hypothesis that the adverse effects of homocysteine on vascular endothelial cells are mediated through oxidative stress mechanisms.
arteriosclerosis, cerebral blood flow
Association of Polymorphisms in the Cytochrome P450 CYP2C9 With Warfarin Dose Requirement and Risk of Bleeding Complications—Aithal GP, Day CP, Kesteven PJL, Daly AK (Dept of Pharmacological Sciences, Univ of Newcastle upon Tyne Medical School, Newcastle upon Tyne NE2 4HH, UK)—Lancet. 1999;353:717–719.
Background The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case. The allelic variants are associated with impaired hydroxylation of S-warfarin in in-vitro expression systems. We have studied the effect of CYP2C9 polymorphism on the in-vivo warfarin dose requirement.
Methods Patients with a daily warfarin dose requirement of 1.5 mg or less (low-dose group, n=36), randomly selected patients with a wide range of dose requirements from an anticoagulant clinic in north-east England (clinic control group, n=52), and 100 healthy controls from the community in the same region were studied. Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis. Case notes were reviewed to assess the difficulties encountered during the induction of warfarin therapy and bleeding complications in the low-dose and clinic control groups.
Findings The odds ratio for individuals with a low warfarin dose requirement having one or more CYP2C9 variant alleles compared with the normal population was 6.21 (95% CI 2.48–15.6). Patients in the low-dose group were more likely to have difficulties at the time of induction of warfarin therapy (5.97 [2.26–15.82]) and have increased risk of major bleeding complications (rate ratio 3.68 [1.43–9.50]) when compared with randomly selected clinic controls.
Interpretation We have shown that there is a strong association between CYP2C9 variant alleles and low warfarin dose requirement. CYP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk of bleeding complications.
Vitamin K Intake and Sensitivity to Warfarin in Patients Consuming Regular Diets—Lubetsky A, Dekel-Stern E, Chetrit A, Lubin F, Halkin H (Dept of Medicine, Sheba Medical Center, Tel-Hashomer, Israel 52621)—Thromb Haemost. 1999;81:396–399. Copyright © 1999 Schattauer Verlag, Stuttgart.
The effect of dietary vitamin K intake on warfarin sensitivity is known only from case reports and few small clinical studies. We followed 50 patients commencing warfarin and consuming their regular diets (for 8 weeks) to study this relationship. A one-week recall dietary questionnaire was completed at weeks 2 and 8. Daily intake of nutrients and vitamin K was calculated from standard tables. Warfarin sensitivity index (WSI) was defined as final INR/final warfarin dose (mg/day/m2 of body surface area) (week 8).
Vitamin K intake was 17–974 (median: 179) μg/day. Median WSI was 0.82 (0.31–4.47). A WSI value of 1.1 significantly separated excess (≥250 μg/day) from normal (<250 μg/day) vitamin K consumers (16/18 vs. 15/32, respectively, p<0.01). The former had lower day 5 INR (median: 1.9 vs. 3.0, p<0.001), needed more warfarin to achieve INR ≥2.0 (32.0±9.2 mg vs. 25.4±6.4 mg, p=0.009) and required a higher maintenance steady state warfarin dose (5.7±1.7 mg/day vs. 3.5±1.0 mg/day, p<0.001).
We conclude that in 32% (16/50) of anticoagulated patients under usual dietary conditions sensitivity to warfarin is decreased by vitamin K intake ≥250 μg/day.
Predictive Factors for Mortality and Cerebral Complications in Arteriosclerotic Aneurysm of the Aortic Arch—Okita Y (Dept of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka, Japan 565), Ando M, Minatoya K, Kitamura S, Takamoto S, Nakajima N—Ann Thorac Surg. 1999;67:72–78. Copyright © 1999 by The Society of Thoracic Surgeons.
Background. The incidence of cerebral complications is high in patients with aortic arch aneurysm.
Methods. Between December 1977 and December 1995, 246 patients with arteriosclerotic arch aneurysm underwent operation. Thirty-nine patients had an aneurysm involving the entire arch, 193 had only distal arch aneurysm, and 14 had arch aneurysm extending to the descending aorta. Eighty-seven patients underwent replacement of the total arch, 85 had replacement of only the distal arch, 14 had simultaneous replacement of the descending aorta, 45 had patch repair, and 15 had thromboexclusion. Selective cerebral perfusion was used in 112 patients and partial bypass in 58 in the earlier series of patients, but deep hypothermic circulatory arrest with retrograde cerebral perfusion technique was exclusively applied in the most recent 76 patients.
Results. There were 50 (20%) early deaths and 37 (19%) late deaths. Postoperative stroke was found in 26 (11%) patients of which 13 (50%) died. Mutual predictive factors for postoperative mortality and stroke were earlier series, preoperative chronic renal failure, ruptured aneurysm, arch clamping during procedure, and using partial cardiopulmonary bypass. Among 129 patients operated on during the most recent 5 years, early mortality and incidence of stroke decreased to 14.7% and 6.9%, respectively.
Conclusions. Results of operations for arteriosclerotic aneurysms of the transverse aortic arch in 246 patients during a period of 17 years have been improving but are still not satisfactory.
cardiovascular disease, cerebral ischemia
Items of Interest
Localization and Characterization of Intracerebral Cavernous Angiomas By Intra-Operative High-Resolution Colour-Duplex-Sonography—Woydt M (Dept of Neurosurgery, Univ of Würzburg, Germany), Horowski A, Krone A, Soerensen N, Roosen K—Acta Neurochir (Wien). 1999;141:143–152. Copyright © Springer-Verlag 1999.
Diagnosis and Treatment of Ischemic Stroke—Alberts MJ (Box 3392, Duke Univ Medical Center, Durham, NC 27710)—Am J Med. 1999;106:211–221. Copyright © 1999 by Excerpta Medica, Inc.
Vasa Vasorum: Another Cause of the Carotid String Sign—Martin MA, Marotta TR (Dept of Neuroradiology, Vancouver General Hospital, 855 W 12th Ave, Vancouver, BC, Canada V5Z 1M9)—Am J Neuroradiol. 1999;20:259–262. Copyright © American Society of Neuroradiology.
Stroke-Like Episodes in Autosomal Recessive Cytochrome Oxidase Deficiency—Morin C, Dubé J, Robinson BH, Lacroix J, Michaud J, De Braekeleer M, Geoffroy G, Lortie A, Blanchette C, Lambert MA, Mitchell GA (Service de génétique médicale, Hôpital Ste-Justine, 3175 Côte Ste-Catherine Rd, Montréal, Québec, Canada H3T 1C5)—Ann Neurol. 1999;45:389–392. Copyright © 1999 by the American Neurological Association.
Recurrence of Bleeding in Patients With Hypertensive Intracerebral Hemorrhage—Bae HG (Dept of Neurosurgery, Soonchunhyang Univ Chonan Hospital 23-20, Bongmyong-dong, Chonan 330-100, South Korea), Jeong DS, Doh JW, Lee KS, Yun IG, Byun BJ—Cerebrovasc Dis. 1999;9:102–108. Copyright © 1999 S. Karger AG, Basel.
Percutaneous Endoscopic Gastrostomy After Acute Stroke: Complications and Outcome—Wijdicks EFM (Dept of Neurology, Mayo Clinic 200 First St SW, Rochester, MN 55905), McMahon MM—Cerebrovasc Dis. 1999;9:109–111. Copyright © 1999 S. Karger AG, Basel.
Imaging Developing Brain Infarction—Baird AE, Warach S (Dept of Neurology, Dana 779, East Campus, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215)—Curr Opin Neurol. 1999;12:65–71. Copyright © Lippincott Williams & Wilkins.
Genetic Susceptibility and Ischaemic Stroke—Elbaz A (INSERM unité 360, Recherches épidémiologiques en Neurologie et Psychopathologie, Hôpital de la Salpêtrière, 47 Blvd de l’hôpital, 75651 Paris CEDEX 13, France), Amarenco P—Curr Opin Neurol. 1999;12:47–55. Copyright © Lippincott Williams & Wilkins.
Performing Cost-Effectiveness Analysis by Integrating Randomized Trial Data With a Comprehensive Decision Model: Application to Treatment of Acute Ischemic Stroke—Samsa GP (Duke Univ Center for Clinical Health Policy Research, First Union Tower, Suite 230, 2200 W Main St, Durham, NC 27705), Reutter RA, Parmigiani G, Ancukiewicz M, Abrahamse P, Lipscomb J, Matchar DB—J Clin Epidemiol. 1999;3:259–271. Copyright © 1999 Elsevier Science Inc.
Gene Therapy for Cerebrovascular Disease—Weihl C, Macdonald RL (Sec of Neurosurgery, MC 3026, Univ of Chicago Medical Center, 5841 S Maryland Ave, Chicago, IL 60037), Stoodley M, Lüders J, Lin G—Neurosurgery. 1999;44:239–253.
The abstracts in this section have been typeset for consistency with journal format but otherwise appear as in the original articles.
- Copyright © 1999 by American Heart Association