Abstracts of Literature
Timing of Surgery in Patients With Aneurysmal Subarachnoid Haemorrhage: Rebleeding is Still the Major Cause of Poor Outcome in Neurosurgical Units That Aim at Early Surgery—Roos YBWEM (Dept of Neurology, Academic Medical Centre [AMC], Meibergdreef 9, 1105 AZ Amsterdam-Zuidoost, Netherlands), Beenen LFM, Groen RJM, Albrecht KW, Vermeulen M—J Neurol Neurosurg Psychiatry. 1997;63:490–493.
Objective—To investigate prospectively the proportion of patients actually operated on early in units that aim at surgery in the acute phase of aneurysmal subarachnoid haemorrhage (SAH) and what is the main current determinant of poor outcome.
Methods—A prospective analysis of all SAH patients admitted during a one year period at three neurosurgical units that aim at early surgery. The following clinical details were recorded: age, sex, date of SAH, date of admission to the neurosurgical centre, whether a patient was referred by a regional hospital or a general practitioner, Glasgow coma scale and grade of SAH (World Federation of Neurological Surgeons (WFNS) score) on admission at the neurosurgical unit, results of CT and CSF examination, the presence of an aneurysm on angiography, details of treatment with nimodipine or antifibrinolytic agents, and the date of surgery to clip the aneurysm. At follow up at three months, the patients’ clinical outcome was determined with the Glasgow outcome scale and in cases of poor outcome the cause for this was recorded.
Results—The proportion of patients that was operated on early—that is, within three days after SAH—was 55%. Thirty seven of all 102 admitted patients had a poor outcome. Rebleeding and the initial bleeding were the main causes of this in 35% and 32% respectively of all patients with poor outcome.
Conclusions—In neurosurgical units with what has been termed “modern management” including early surgery, about half of the patients are operated on early. Rebleeding is still the major cause of poor outcome.
Key Words: aneurysm, subarachnoid hemorrhage
Experience With Computed Tomographic Angiography for the Detection of Intracranial Aneurysms in the Setting of Acute Subarachnoid Hemorrhage—Anderson GB, Findlay JM (Division of Neurosurgery, 2D1.02 W.C. Mackenzie Health Sciences Centre, 8440 112th St, Edmonton, Alberta, Canada T6G 2B7), Steinke DE, Ashforth R—Neurosurgery. 1997;41:522–528.
Objective—To objectively compare computed tomographic angiography (CTA) with selective digital subtraction angiography (DSA) in the detection and anatomic definition of intracranial aneurysms, particularly in the setting of acute subarachnoid hemorrhage (SAH).
Methods—In a blinded prospective study, 40 patients with known or suspected intracranial saccular aneurysms underwent both CTA and DSA, including 32 consecutive patients with SAH in whom CTA was performed after CT images were obtained diagnostic for SAH. The CT angiograms were interpreted for the presence, location, and size of the aneurysms, and anatomic features, such as the number of aneurysm lobes, aneurysm neck size (≤4 mm), and the number of adjacent arterial branches were assessed. The images obtained with CTA were then compared with the images obtained with DSA, with the latter images serving as controls.
Results—DSA revealed 43 aneurysms in 30 patients and ruled out intracranial aneurysms in the remaining 10 patients. For aneurysm presence alone, the sensitivity and specificity for CTA was 86 and 90%, respectively. For the presence of an aneurysm, six CT angiograms showed false negative results and one CT angiogram showed a false positive result. False negative results were usually caused by technical problems with the image, tiny aneurysm domes (<3 mm), and unusual aneurysm locations (i.e., intracavernous carotid or posterior inferior cerebellar artery aneurysms). The results obtained with CTA were, compared with the results obtained with DSA, more than 95% accurate in determining dome and neck size of aneurysm, aneurysm lobularity, and the presence and number of adjacent arterial branches. In addition, CTA provided a three-dimensional representation of the aneurysmal lesion, which was considered useful for surgical planning.
Conclusion—CTA is useful for rapid and relatively noninvasive detection of aneurysms in common locations, and the anatomic information provided in images showing positive results is at least equivalent to that provided by DSA. In cases of SAH in which the nonaugmented CT and CTA results indicate a clear source of bleeding and provide adequate anatomic detail, we think it is possible to forego DSA before urgent early aneurysm surgery. In all other cases, DSA is indicated.
Key Words: tomography, x-ray computed, subarachnoid hemorrhage
Screening for Ocular Hemorrhages in Patients With Ruptured Cerebral Aneurysms: A Prospective Study of 99 Patients—Frizzell RT, Kuhn F, Morris R, Quinn C, Fisher WS III (Division of Neurosurgery, 514 Medical Education Bldg, 1813 Sixth Ave S, University of Alabama at Birmingham Station, Birmingham, AL 35294-3295)—Neurosurgery. 1997;41:529–534.
Background—Terson’s syndrome (vitreous hemorrhage) and other ocular hemorrhages (retinal hemorrhages) have been reported to occur in up to 40% of patients with ruptured cerebral aneurysms. Because microsurgical vitrectomy can safely restore vision in patients with visual loss secondary to Terson’s syndrome, we hypothesized that prospectively screening a selected group of patients with aneurysms would result in a higher rate of vitrectomy in patients with more extensive subarachnoid hemorrhage.
Methods—Ninety-nine patients with ruptured cerebral aneurysms were prospectively screened for Terson’s syndrome and other forms of ocular hemorrhage by an ophthalmologist. Follow-up data were obtained for seven of eight cases of Terson’s syndrome, and vitrectomy was performed for visual restoration when indicated.
Results—Ocular hemorrhages were present in 17% of patients with ruptured cerebral aneurysms, and Terson’s syndrome was present in 8% of patients. Screening of patients with histories of transient or prolonged comas sensitively identified patients with ocular hemorrhages in 100% of the patients with Terson’s syndrome and 89% of the patients with other ocular hemorrhages. Fifty-five percent of the patients in the overall series had histories of transient or prolonged comas, and 53% (specificity) of those patients had ocular hemorrhages. Two of the eight patients with Terson’s syndrome underwent vitrectomy, with dramatic improvement in vision. No other ocular hemorrhages required surgery.
Conclusions—Ophthalmological screening of patients with histories of transient or prolonged comas after ruptured cerebral aneurysms very sensitively identifies patients with ocular hemorrhages, which are relatively common in patients with subarachnoid hemorrhage treated in an academic neurosurgical practice. The present study underestimates the true incidence of Terson’s syndrome in that patients who died shortly after their subarachnoid hemorrhage were not included. Vitrectomy for patients who do not exhibit spontaneous improvement in vision results in a dramatic reversal of blindness.
Key Words: ocular disease, aneurysm
Matrix Metalloproteinase-9 in Cerebral Aneurysms—Kim SC, Singh M, Huang J, Prestigiacomo CJ, Winfree CJ, Solomon RA, Connolly ES Jr (710 W 168th St, Box 72, New York, NY 10032)—Neurosurgery. 1997;41:642–647.
Objective—Generalized disruption of arterial wall morphological changes in patients harboring cerebral aneurysms has been documented; however, little is known regarding the pathogenesis of these changes. To explore the role of the elastolytic gelatinase, matrix metalloproteinase-9 (MMP-9), levels of this enzyme in the wall of intracranial aneurysms were compared with those in both intracranial and extracranial arteries. The tissue levels of its major inhibitor, tissue inhibitor of metalloproteinase (TIMP), were measured in these tissues as well. The activity of MMP-9 in plasma was also evaluated.
Methods—The aneurysm wall was excised from three of six patients undergoing craniotomies for aneurysm clipping. A 1-cm segment of superficial temporal artery (STA) was obtained from each of six patients. Additional STAs were obtained from six patients in the control group who were undergoing craniotomies for nonvascular disease. An intracranial artery was also obtained from the anterior temporal neocortical resection of a patient undergoing a craniotomy for mesial temporal sclerosis. MMP-9 and TIMP levels were determined via Western blot analysis. Using substrate gel zymography, MMP-9 plasma activity was determined for a separate cohort of patients with aneurysms (n=6) and patients in the control group (n=6).
Results—MMP-9 and TIMP levels in the aneurysm wall were markedly increased beyond levels in both extracranial arteries (STAs from patients with aneurysms and patients in the control group) and the intracranial artery. There were no differences in the levels of MMP-9 in the STAs of patients harboring aneurysms when compared with patients in the control group. Also, no differences were noted in plasma MMP-9 activity.
Conclusion—Local rather than systemic perturbations in MMP-9 levels may contribute to the matrix disruption associated with cerebral aneurysms. This local up-regulation is not the result of TIMP down-regulation. The lack of increased systemic metalloproteinase activity precludes the use of plasma MMP-9 activity as a screening tool for presymptomatic aneurysms. However, local therapeutic modulation of MMP-9 activity may help arrest aneurysm progression.
Key Words: arterial wall, aneurysm
Intracranial Aneurysms in Marfan’s Syndrome: An Autopsy Study—Schievink WI (Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013), Parisi JE, Piepgras DG, Michels VV—Neurosurgery. 1997;41:866–871.
Objective—Marfan’s syndrome is a heritable connective tissue disorder that has been associated with intracranial aneurysms. However, the prevalence of intracranial aneurysms in Marfan’s syndrome is unknown and pathological studies of affected vessels have not been reported. We therefore examined the neuropathological findings in a group of patients with Marfan’s syndrome.
Methods—We identified all patients with Marfan’s syndrome in whom postmortem examination had been performed at the Mayo Clinic between 1969 and 1993.
Results—Autopsy included examination of the brain in seven patients with Marfan’s syndrome (five men and two women with a mean age of 28 yr). Each of two patients had one or more intracranial aneurysms. The first patient, a 32-year-old man who died as a result of aortic dissection, was observed to have an incidental saccular supraclinoid carotid artery aneurysm (7 mm). Microscopic examination of the remainder of the cerebral arteries revealed duplication and fragmentation of the internal elastic lamina. The second patient, a 20-year-old man who died as a result of a subarachnoid hemorrhage, had ruptured saccular supraclinoid carotid artery (3 mm) and anterior cerebral artery (20 mm) aneurysms as well as unruptured fusiform middle cerebral artery (18 mm) and posterior cerebral artery (13 mm) aneurysms. Microscopic examination of the cerebral arteries revealed widespread changes consisting of intimal proliferation, medial degeneration, and fragmentation of the internal elastic lamina.
Conclusion—These findings confirm an association between Marfan’s syndrome and intracranial aneurysms. Microscopic involvement of cerebral arteries in Marfan’s syndrome may be variable, even among those with intracranial aneurysms.
Key Words: Marfan syndrome, aneurysm
Homocysteine in Sickle Cell Disease: Relationship to Stroke—Houston PE, Rana S (Dept of Pediatrics, 2041 Georgia Ave NW, Washington, DC 20060), Sekhsaria S, Perlin E, Kim KS, Castro OL—Am J Med. 1997;103:192–196.
Purpose—The risk factors and pathophysiology of stroke and other serious complications of sickle cell disease (SCD) are poorly defined. Hyperhomocysteinemia has recently been identified as a risk factor for stroke and other vascular diseases in the general population, however its role in SCD has not been investigated.
Patients and methods—We measured serum homocysteine and red cell folate levels in 100 patients with SCD, including 16 patients with stroke. A disease severity score was determined for all patients and those without stroke were classified into mild (44 patients) or severe (40 patients) disease groups.
Results—Homocysteine levels for the stroke group (median 13.3 μmol/L, mean 13.1±4.3 μmol/L) were significantly higher than those in patients without stroke (median 9.7 μmol/L, mean 10.7 μmol/L) (P<0.02), and on multiple regression analysis homocysteine level was independently correlated with stroke (P<0.026). Homocysteine and folate levels were inversely correlated (r=−0.41, P<0.00005). Using logistic regression, the odds ratio for stroke in patients with homocysteine levels above the median (10.1 μmol/L) was 3.5 in this group of patients (95% confidence interval 1.1 to 11.9).
Conclusion—High homocysteine levels may be a risk factor for development of stroke in SCD patients. The role of homocysteine in the pathogenesis of stroke in SCD needs to be examined in a longitudinal, prospective study. @ 1997 by Excerpta Medica, Inc.
Key Words: homocyst(e)ine, anemia, sickle cell
Human Immunodeficiency Virus Infection and Stroke in Young Patients—Qureshi AI, Janssen RS, Karon JM, Weissman JP, Akbar MS, Safdar K, Frankel MR (Dept of Neurology, Grady Memorial Hospital, BG007, 80 Butler St, Atlanta, GA 30335)—Arch Neurol. 1997;54:1150–1153.
Objective—To determine the association between human immunodeficiency virus (HIV) infection and stroke among young persons.
Design—Retrospective case-control study.
Setting—Large, inner-city public hospital.
Participants—All patients aged 19 to 44 years with a diagnosis of stroke, whose HIV status was determined, admitted from January 1990 through June 1994. Controls matched for age and sex were selected from patients who were admitted during the same period for status asthmaticus whose HIV status was known.
Main Outcome Measure—The associations of HIV infection with all strokes and with cerebral infarction, after adjustment for other cerebrovascular risk factors, were evaluated by Mantel-Haenszel stratified analyses. The subtypes and causes of stroke in HIV-infected patients were compared with HIV-seronegative patients.
Results—The HIV infection was associated with stroke (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0–5.3) and cerebral infarction (OR, 3.4; 95% CI, 1.1–8.9), after adjustment for other cerebrovascular risk factors. Among patients with stroke, cerebral infarction was more frequent in HIV-infected patients than in HIV-seronegative patients (20 [80%] of 25 vs 48 [56%] of 88, P=.04). The frequency of cerebral infarctions associated with meningitis (P<.001) and protein S deficiency (P=.06) was higher in HIV-infected patients than in seronegative patients.
Conclusions—Our study suggests that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency.
Key Words: young adults, acquired immunodeficiency syndrome
Aphasia Type, Age and Cerebral Infarct Localisation—Ferro JM (Serviço de Neurologia, Hospital de Santa Maria, Centro de Estudos Egas Moniz, P-1600 Lisboa, Portugal), Madureira S—J Neurol. 1997;244:505–509.
Stroke patients with nonfluent aphasia tend to be younger than fluent aphasics. We investigated whether this difference was due to an age-related change in the anatomico-functional organisation of language areas or to an age-dependent variation on the distribution of infarct localisation. From a hospital prospective stroke database we selected those patients who suffered an ischaemic stroke with at least one non-lacunar infarct demonstrated by computed tomography (n=423 patients). We retrieved information on language disturbance in the acute phase (no aphasia, non-fluent aphasia, fluent aphasia) and on infarct localisation by CT. Non-fluent aphasia predominated in young (aged <51 years) patients while in elderly patients (aged >70 years) the opposite was found (χ2=8.03; P=0.005). Posterior infarcts were also more frequent in elderly patients (χ2=9.9; P=0.002). There were 27 atypical cases (patients with lesions on language areas without aphasia) and 14 aphasics with atypical infarct localisation (9 fluent aphasics with anterior lesions and 5 non-fluent aphasics with posterior lesions). The proportions of atypical cases, their infarct location or fluency type were not influenced by age. It was concluded that the predominance of fluent aphasia in older patients was related to the higher proportion of posterior infarcts in these patients. The hypothesis of age-related changes in the anatomico-functional organisation of language areas was not supported by the present data.
Key Words: aphasia, cerebral infarction
The Effect of Treating People With Reversible Ischaemic Attacks of the Brain and Eye on the Incidence of Stroke in Australia—Hankey GJ (Stroke Unit, Dept of Neurology, Royal Perth Hospital, GPO Box X2213, Perth, W Australia 6001)—Aust NZ J Med. 1997;27:420–430.
Background—Reversible ischaemic attacks of the brain or eye (RIA) are a risk factor for stroke. Strategies of stroke prevention include vascular risk factor control, antithrombotic therapy, and carotid surgery.
Aims—To determine the effectiveness, risks and costs of each stroke prevention strategy for patients with RIA and the Australian community, and the effect of treating people with RIA on the incidence of stroke in Australia.
Methods—Review of data from prospective community-based studies to determine the prevalence of RIA, the incidence of stroke, and the proportion of stroke patients who report a RIA before their stroke; and data from randomised trials to determine the effectiveness, risks and costs of treatments for RIA.
Results—About 111,000 Australians have had a prior RIA. Each year, about 37,000 Australians suffer a stroke, of whom up to 8000 (22%) have had a prior (‘warning’) RIA. Targeting effective stroke prevention strategies to RIA patients with relevant treatable conditions may reduce the individual’s stroke risk by two-thirds (individual strategies) and possibly further (combination strategies). However, because the attributable risk of RIA for stroke is only about 22% (and may be less, given the role of other causal risk factors for stroke), strategies of stroke prevention in RIA patients can only reduce stroke incidence by up to 15% (from 22% to 7%).
Conclusions—The potential benefits of the ‘high’ approach to stroke prevention appear to be less than the ‘population’ approach, but both approaches are necessary and complementary. Indeed, the cost of implementing the ‘high risk’ approach may be less than the cost of the strokes prevented ($255 million; i.e. 15% of $1.7 billion).
Key Words: cerebral ischemia, transient, incidence
Common Carotid Intima-Media Thickness and Risk of Stroke and Myocardial Infarction: The Rotterdam Study—Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (Dept of Epidemiology and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, Netherlands)—Circulation. 1997;96:1432–1437.
Background—Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction.
Methods and Results—We used a nested case-control approach among 7983 subjects aged ≥55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively.
Conclusions:—The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.
Key Words: carotid arteries, risk factors
Predictive Value of Electrophoretically Detected Lipoprotein(a) for Coronary Heart Disease and Cerebrovascular Disease in a Community-Based Cohort of 9936 Men and Women—Nguyen TT (Division of Endocrinology, Mayo Clinic, 200 First St SW, Rochester, MN 55905), Elefson RD, Hodge DO, Bailey KR, Kottke TE, Abu-Lebdeh HS—Circulation. 1997;96:1390–1397.
Background—Elevated lipoprotein(a) [Lp(a)] levels have been associated with the presence of atherosclerotic disease. However, the results of prospective studies of Lp(a) and cardiovascular disease have been contradictory.
Methods and Results—From 1968 through 1982, lipoprotein analysis was performed in 11 335 Olmsted County residents. Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a) levels based on electrophoretic pattern. Lp(a) bands were scored from 0 (absent) to 3 (increased). A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a) determinations were followed up for 14 years for development of coronary artery disease (CAD) and cerebrovascular disease (CVD). During 131 330 person-years of follow-up, there were 1848 CAD events and 841 CVD events. Age, diabetes, hypertension, cholesterol, and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women. There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a) levels for men and women. For Lp(a) level 3, the hazard ratio was 1.9 (range, 1.3 to 2.9) in women and 1.6 (range, 1.0 to 2.5) in men. The adjusted hazard ratio for CVD showed an irregular association with Lp(a) levels in men and no association in women.
Conclusions—In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years, Lp(a) was a significant predictor of risk of future CAD. Lp(a) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women.
Key Words: lipoproteins, risk factors
Morphological Investigation of the Neuroprotective Effects of Graded Hypothermia After Diverse Periods of Global Cerebral Ischemia in Gerbils—Nakajima Y (Dept of Second Surgery, Shiga University of Medical Science, Seta, Otsu, Shiga 520-21, Japan), Fujimiya M, Maeda T, Mori A—Brain Res. 1997;765:113–121.
Hypothermia is known to be the most effective method to protect the neuronal damage induced by ischemia. In the present study, we investigated the histopathological consequences of hippocampal CA1 pyramidal neurons as well as the glial reactions in the hippocampus, after diverse periods of ischemic insult at graded intra-ischemic hypothermia ranging from 32 to 20°C. Gerbils were exposed to forebrain ischemia by clamping the bilateral common carotid arteries for 5–120 min depending upon the temperatures. The morphological study was performed 7 days after ischemia or sham-operation. Histopathological evaluation of delayed neuronal death (DND) was performed by Cresyl violet (CV) staining and MAP2 immunoreactivity. Glial reactions were examined by GFAP immunostaining and isolectin B4 histochemistry, corresponding to astrocytes and microglia, respectively. The forebrain ischemia at 32°C for 10 min and at 28°C for 20 min did not induce DND in the CA1 region. However, the ischemia at 32°C for 20 min and at 28°C for 30 min caused extensive degeneration of CA1 pyramidal neurons as observed in normothermic ischemic animals. Under the condition of deep hypothermia, the ischemia for 60 min at 24°C and for 120 min at 20°C which were the longest durations of each temperature within the limitation of the animal survival following 7 days, induced no DND in CA1 pyramidal neurons. The reactive changes of astrocytes were observed not only in ischemic animals with DND, but also in ischemic animals without DND. Computer image analysis showed that the area fraction of GFAP-positive structures in the CA1 region was significantly increased in both ischemic cases with and without DND compared with each sham group. In contrast, the distribution of activated microglia was much more restricted to the CA1 region and they were always accompanied by DND at 7 days postischemia. The present results demonstrate the remarkable neuroprotective effect of deep hypothermia that has been widely used in cardiovascular surgeries as the cerebroprotective strategy during total circulatory cessation. The findings also suggest that even under the condition of hypothermia, glial reactions may play an important role in neuronal survival and death after ischemia. @ 1997 Elsevier Science B.V.
Key Words: hypothermia, cerebral ischemia
Increased Susceptibility to Ischemic Brain Damage in Transgenic Mice Overexpressing the Amyloid Precursor Protein—Zhang F, Eckman C, Younkin S, Hsiao KK, Iadecola C (Dept of Neurology, University of Minnesota, Box 295 UMHC, 420 Delaware St SE, Minneapolis, MN 55455)—J Neurosci. 1997;17:7655–7661.
We studied the role of the amyloid precursor protein (APP) in ischemic brain damage using transgenic mice overexpressing APP. The middle cerebral artery (MCA) was occluded in FVB/N mice expressing APP695. SWE (Swedish mutation) and in non-transgenic littermates. Infarct volume (cubic millimeters) was assessed 24 hr later in thionin-stained brain sections. The infarct produced by MCA occlusion was enlarged in the transgenics (+32±6%; n=12; p<0.05; t test). Measurement of APP by ELISA revealed that, although relatively high levels of Aβ were present in the brain of the transgenics (Aβ1–40=80±19 pmol/g; n=6), there were no differences between ischemic and nonischemic hemispheres (p>0.05). The reduction in cerebral blood flow produced by MCA occlusion at the periphery of the ischemic territory was more pronounced in APP transgenics (−42±8%; n=9) than in controls (−20±8%; n=9). Furthermore, the vasodilatation produced by neocortical application of the endothelium-dependent vasodilator acetyl-choline (10 μm) was reduced by 82±5% (n=8; p<0.05) in APP transgenics. The data demonstrate that APP overexpression increases the susceptibility of the brain to ischemic injury. The effect is likely to involve the Aβ-induced disturbance in endothelium-dependent vascular reactivity that leads to more severe ischemia in regions at risk for infarction. The cerebral vascular actions of peptides deriving from APP metabolism may play a role in the pathogenic effects of APP.
Key Words: cerebral ischemia, amyloid
Effect of Delayed Albumin Hemodilution on Infarction Volume and Brain Edema After Transient Middle Cerebral Artery Occlusion in Rats—Belayev L, Busto R, Zhao W, Clemens JA, Ginsberg MD (Dept of Neurology [D4-5], University of Miami School of Medicine, PO Box 016960, Miami, FL 33101)—J Neurosurg. 1997;87:595–601.
The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague-Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-l-lysine–coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals’ neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p<0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p<0.0002).
These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke.
Key Words: cerebral ischemia, focal, hemodilution
A Theoretical Model of Cerebral Hemodynamics: Application to the Study of Arteriovenous Malformations—Gao E, Young WL (PO Box 46, Columbia University College of Physicians and Surgeons, 630 West 168th St, New York, NY 10032), Ornstein E, Pile-Spellman J, Ma Q—J Cereb Blood Flow Metab. 1997;17:905–918.
A comprehensive computer model of the cerebral circulation, based on both hydrodynamics and electrical network analysis, was used to investigate the influences of arteriovenous malformations (AVM) on regional cerebral hemodynamics. The basic model contained 114 normal compartments: 55 arteries, 37 veins, 20 microvessel groups (MVG), one compartment representing systemic and extracranial vascular resistance, and one representing the heart. Each microvessel group, which represented the arteriolar bed, consisted of 5000 microvessels. Cerebral blood flow autoregulation was simulated by a formula that determined the resistance and therefore the flow rate of the microvessel groups (arterioles) as a function of perfusion pressure. Elasticity was introduced to describe the compliance of each vessel. Flow rate was made a controlling factor for the positive regulation of the diameters of conductance vessels by calculation of shear stress on the vessel wall (vessel dilation). Models containing an AVM were constructed by adding an AVM compartment and its feeding arteries and draining veins. In addition to the basic model, AVM models were simulated with and without autoregulation and flow-induced conductance vessel dilation to evaluate the contributions of these factors on cerebral hemodynamics. Results for the model with vessel dilation were more similar to clinical observations than those without vessel dilation. Even in the presence of total vasoparalysis of the arteriolar bed equivalent, obliteration of a large (1000 mL/min) shunt flow AVM resulted in a near-field CBF increase from a baseline of 21 to a post-occlusion value of no more than 74 mL/100 g/min, casting doubt on a purely hemodynamic basis for severe hyperemia after treatment. The results of the simulations suggest that our model may be a useful tool to study hemodynamic problems of the cerebral circulation.
Key Words: cerebral arteriovenous malformations, hemodynamics
Metabolic and Neurological Patterns in Chronic Cerebral Infarction: A Single-Voxel 1H-MR Spectroscopy Study—Kamada K (Institute for Cognitive and Computational Science, Georgetown University, Research Building 3970, Research Rd NW, Washington, DC 20007-9197), Houkin K, Iwasaki Y, Abe H, Kashiwaba T—Neuroradiology. 1997;39:560–565.
The details of brain metabolism in chronic cerebral infarcts have not been clarified. Using proton MR spectroscopy (1H-MRS) at 1.5 T, we measured biochemical changes in 16 patients with large infarcts involving the motor cortex in the chronic phase (median 293.9 days) and related the findings to clinical data. Localised spectra were obtained using point-resolved spectroscopy, with an echo time of 270 ms. Regions of interest were placed on the frontal lobe, including the precentral gyrus and central sulcus. Motor function was assessed by the manual muscle power test at the time of the 1H-MRS study. Only three patients with severe paresis had no signal in the lesions and a lactate signal was obtained in 13 cases. N-acetyl aspartate (NAA) was observed in 4 cases with recanalisation of an occluded vessel. Motor function correlated strongly with the NAA/choline-containing compounds (Cho) ratio (P<0.01) and lactate/Cho ratio (P<0.01). We found various metabolic patterns, reflecting residual neurological function.
Key Words: cerebral infarction, spectroscopy, nuclear magnetic resonance
The Importance of Pulsatile Components of Hypertension in Predicting Carotid Stenosis in Older Adults—Franklin SS (Veterans Affairs Medical Center, Hypertens Ctr E109, 5901 E 7th St, Long Beach, CA 90822), Sutton-Tyrrell K, Belle SH, Weber MA, Kuller LH—J Hypertens. 1997;15:1143–1150.
Objective:—To evaluate pulsatile components of the blood pressure as risk markers for carotid stenosis in isolated systolic hypertension.
Design:—Duplex scans with Doppler measures of the blood flow velocity were used to diagnose carotid stenosis in 187 participants in the Systolic Hypertension in the Elderly Program and in 187 normotensive and mildly hypertensive control subjects.
Methods:—The systolic blood pressure (SEP), diastolic blood pressure (DBP), pulse pressure, and mean arterial pressure (MAP) were selected as independent variables. A logistic regression model for carotid stenosis was used to adjust for potentially confounding risk factors. Serial models, each containing single or double blood pressure variables, were run to compare risk markers for carotid stenosis. Receiver operating characteristic curves were compared to assess the predictive value of each model.
Results:—In the multivariate analysis, both the SEP (P=0.005) and the pulse pressure (P<0.001) were predictive of carotid stenosis, but the DBP and MAP were not. However, when either the SEP or the pulse pressure was included in the model, the DBP was associated negatively with carotid stenosis (P<0.001 and P=0.023, respectively). An increased pulse pressure and a decreased DBP were independent risk markers for carotid stenosis. Comparison of receiver operating characteristic curves indicated that the pulse pressure had superior predictive value to the SEP (P=0.034).
Conclusions:—The pulse pressure is the single best predictor of carotid stenosis. There is a negative correlation between the DBP and carotid stenosis for subjects with isolated systolic hypertension, but this can be demonstrated only after one has stratified for the SEP or for the pulse pressure. Thus, the pulsatile components of the blood pressure, increased pulse pressure and decreased DBP, are the most sensitive risk markers for the diagnosis of carotid stenosis.
Key Words: hypertension, carotid artery diseases
Prevention of Arterial Thrombosis Using a Novel Heparin With Enhanced Antiplatelet Activity and Reduced Anticoagulant Activity—Poletti LF, Bird K, Harris RB, Marques D, Sobel M (Medical College of Virginia, Box 980108, Richmond, VA 23298)—J Vasc Surg. 1997;26:366–372.
Purpose:—Thrombosis after arterial injury is often initiated by von Willebrand factor (vWF)-dependent platelet accumulation. A promising antithrombotic strategy is the interruption of platelet/vWF interactions. Previously, we demonstrated how chemical and affinity modification can enhance heparin’s anti-vWF activity while reducing conventional anticoagulation. Here, we investigated whether a modified heparin can block platelet-dominated arterial thrombosis.
Methods:—Standard heparin was oxidized with periodate, refined to have high vWF affinity and inhibitory potency, and tested in a guinea pig model of platelet-dependent arterial thrombosis. In this model, a controlled mechanical arterial injury yields cyclic flow variations (CFVs) caused by recurrent accumulation of platelet thrombi.
Results:—All six control animals developed CFVs (mean, 10.4±2.6 CFVs), and six of seven animals treated with standard heparin also developed CFVs (mean, 7.6±4.6). Only one of six animals treated with the anti-vWF heparin and one of six treated with AJvW-2 (an anti-vWF antibody) developed CFVs (mean, 2.0±4.9 and 0.5±1.2, respectively). Thus both the modified heparin and AJvW-2 were more effective than standard heparin (p<0.03). Bleeding times and platelet counts were unaffected. A modified activated partial thromboplastin time was less prolonged by the modified high-affinity heparin (91±17 seconds) than by standard heparin (144±30 seconds; p<0.01).
Conclusions:—The modified heparin with high vWF affinity was a more effective arterial antithrombotic agent, with fewer conventional anticoagulant effects than standard heparin. Interruption of the vWF/platelet interaction is a promising antithrombotic strategy that may be met by novel heparin-based antithrombotic drugs.
Key Words: thrombosis, antithrombotic therapy
Effect of the Asymptomatic Carotid Atherosclerosis Study on Carotid Endarterectomy in Veterans Affairs Medical Centers—Huber TS (Section of Vascular Surgery, Dept of Surgery, PO Box 100286, University of Florida College of Medicine, Gainesville, FL 32610-0286), Durance PW, Kazmers A, Jacobs LA—Arch Surg. 1997;132:1134–1139.
Objective:—To examine the effect of the Asymptomatic Carotid Atherosclerosis Study on the volume of carotid endarterectomies (CEAs) performed in Veterans Affairs medical centers.
Design:—The data were retrospectively extracted from the Veterans Affairs Patient Treatment File for all patients undergoing CEA using the International Classification of Diseases, Ninth Revision, Clinical Modification procedural code 38.12. Data were classified into patient management categories to identify complications and to quantify the severity of illnesses and comorbidities.
Setting:—All 172 US Veterans Affairs medical centers.
Patients:—Veterans undergoing CEA during fiscal years 1993 through 1995.
Main Outcome Measures:—Procedural volume, mortality, and morbidity.
Results:—There was a 43.4% increase in the volume of CEAs performed in fiscal year 1995 despite a 4.6% decrease in the served inpatients and an 8.8% decrease in the inpatient surgical procedures. The monthly volume of CEAs increased (P<.001, r2=0.78) at the onset of the fiscal year (October 1994) immediately after the Asymptomatic Carotid Atherosclerosis Study clinical advisory. The volume of CEAs increased in every region of the country for all nonpsychiatric hospital classifications and for almost every surgeon subspecialty. Despite the increased volume, the operative mortality rate, the International Classification of Diseases, Ninth Revision, Clinical Modification—and patient management categories-based complication rates, and the patients’ comorbidity and severity of illness indexes all remained unchanged.
Conclusion:—The dramatic increase in CEAs following the Asymptomatic Carotid Atherosclerosis Study clinical advisory suggests that the conclusions of the trial have been accepted by the medical community throughout the Veterans Affairs medical centers.
Key Words: carotid endarterectomy, carotid stenosis
Carotid Endarterectomy in Patients Less Than 50 Years Old—Martin GH, Allen RC (712 N Washington #509, Dallas, TX 75246), Noel BL, Talkington CM, Garrett WV, Smith BL, Pearl GJ, Thompson JE—J Vasc Surg. 1997;26:447–455.
Purpose:—The purpose of this study was to compare the results of carotid endarterectomy (CEA) in a young population with premature atherosclerosis with the results of an older control group, examining perioperative morbidity and mortality data, recurrent stenosis and symptoms, late stroke, and survival data.
Methods:—We retrospectively studied 26 patients less than 50 years old (mean, 43.2±3.8 years) and 30 patients greater than 55 years old (mean, 69.1±7.4 years) who underwent CEA during the same time period. Data were obtained regarding demographics, atherosclerotic risk factors, indication for CEA, perioperative complications, recurrent stenosis and symptoms, late stroke, and survival.
Results:—Smoking was more prevalent among young patients who underwent CEA (92% vs 70%; p=0.036). Young patients were also more likely to be symptomatic at presentation (92% vs 57%; p=0.003). The perioperative mortality rate (0% vs 0%) and neurologic morbidity rate (0% vs 3%; p=1.000) were low for the study patients. During a mean follow-up of 67±42.7 months, there was no significant difference in survival rate (5-year survival rate, 93% vs 81%; p=0.373), rate of late ipsilateral (4% vs 3%) and contralateral (4% vs 3%) stroke, restenosis and occlusion (26.9% vs 14.3%), recurrent symptoms (22% vs 17%), reoperation (11.5% vs 5.7%), or contralateral disease (17% vs 23%) development that required surgery for the study or the control cohorts.
Conclusions:—Our data show that there is a high incidence of smoking and symptomatic presentation among young patients in whom carotid occlusive disease develops. CEA may be performed in young patients with low perioperative morbidity and mortality rates. Recurrent disease, late stroke, and survival rates are not significantly different than for older patients. Follow-up with serial duplex ultrasound and reoperation for symptomatic and high-grade asymptomatic restenosis may decrease the risk of late stroke.
Key Words: carotid endarterectomy, young adults
Risk of Spontaneous Haemorrhage After Diagnosis of Cerebral Arteriovenous Malformation—Mast H (Stroke Unit, Neurological Institute, 710 West 168th St, New York, NY 10032), Young WL, Koennecke H-C, Sciacca RR, Osipov A, Pile-Spellman J, Hacein-Bey L, Duong H, Stein BM, Mohr JP—Lancet. 1997;350:1065–1068.
Background:—A small proportion of strokes are caused by cerebral arteriovenous malformations (AVM). Treatment to prevent intracranial haemorrhage itself carries risks, and untreated AVM may in many cases have a good prognosis. We investigated the risk of subsequent symptomatic bleeding in the clinical course of AVM in patients with and without an initial haemorrhage.
Methods:—281 unselected, consecutive, prospectively enrolled patients with cerebral AVM were grouped according to their initial clinical presentation—142 presented with and 139 without haemorrhage. The frequency of AVM haemorrhages during the subsequent clinical course (before the start of endovascular, surgical, or radiation treatment) in the two groups was compared by means of Kaplan-Meier life-tables, log-rank test, and multivariate proportional-hazards regression models. Haemorrhage was defined as a clinically symptomatic event with signs of acute bleeding on computed tomography or magnetic resonance brain imaging.
Findings:—During mean follow-up of 8.5 months for the haemorrhage group and 11.9 months for the non-haemorrhage group, haemorrhages occurred in 18 (13%) of the former patients and in three (2%) of the latter (p=0.0002). The annual risk of haemorrhage was 17.8% and 2.2%, respectively. In the multivariate regression model, the adjusted hazard ratio for haemorrhage at initial presentation was 13.9 (95% CI 2.6–73.8; p=0.002). Deep venous drainage (hazard ratio 4.1 [1.2–14.9], p=0.029) and male sex (9.2 [2.1–41.3], p=0.004) were also significantly associated with subsequent haemorrhage, but no significant association was found for age or AVM size. The annual rate of spontaneous haemorrhage was 32.6% for men and 10.4% for women in the haemorrhage group compared with 3.3% for men and 1.3% for women in the non-haemorrhage group. Among patients with haemorrhage at initial presentation, the risk of haemorrhage fell from 32.9% in year 1 to 11.3% in subsequent years (34.2% to 31.0% in men; 31.1% to 5.5% in women).
Interpretation:—In AVM, patients initially presenting with haemorrhage have a higher risk of subsequent bleeding than those presenting with other symptoms. The risk is higher in men than in women.
Key Words: cerebral arteriovenous malformations, intracerebral hemorrhage
Surgery Versus Stereotactic Radiosurgery for Small, Operable Cerebral Arteriovenous Malformations: A Clinical and Cost Comparison—Porter PJ (c/o Christopher Wallace, MD, Division of Neurosurgery, The Toronto Hospital, Western Division, Suite 2-427, McLaughlin Pavilion, 399 Bathurst St, Toronto, Ontario, Canada, M5T 2S8), Shin AY, Detsky AS, Lefaive L, Wallace MC—Neurosurgery. 1997;41:751–766.
Objective:—Cerebral arteriovenous malformations (AVMs) may cause stroke and death in young patients. For small AVMs, the major curative treatment options are surgery and stereotactic radiosurgery (SR). Although the initial costs and risks of SR are less, there is a latency to cure and ultimately the success rate is lower than with surgery. Thus, these two treatment modalities were compared with respect to clinical outcomes and associated costs by means of a cost-effectiveness analysis.
Methods:—A decision analysis model was developed using Smitree software (J.P. Hollenberg, Roslyn, NY). Probability estimates for cure and complications for both therapies were derived from the literature. Utility values for minor and major stroke were measured in patients with AVMs who were treated at the University of Toronto clinic, using the standard gamble technique. Costs were obtained from several sources, including the case costing systems of several hospitals in Ontario, Canada.
Results:—Surgery confers a 0.98 quality-adjusted life year (QALY) advantage over SR, at an additional cost of $6937 per patient. Thus, from a societal perspective, the incremental cost-effectiveness ratio is $7100 per QALY for a patient treated surgically. The result is sensitive to only two variables: surgical morbidity and surgical mortality. However, the preferred treatment strategy changes to favor SR only at the extreme high end of the possible range for these variables, when the rate of permanent neurological morbidity resulting from surgery exceeds 12% or the surgical mortality rate exceeds 4%.
Conclusions:—In the treatment of small AVMs, surgery confers a large clinical benefit over SR. The reason is that surgery protects the patient from hemorrhage earlier and with greater success than does SR. The associated cost-effectiveness ratio, $7100/QALY, is highly economically attractive. Therefore, surgery achieves important improvements in clinical outcomes and is associated with an excellent ratio of incremental costs per QALY gained.
Key Words: cerebral arteriovenous malformations, radiosurgery
Items of Interest
The New Language of Cerebral Ischemia—Ginsberg MD (Dept of Neurology [D4-5], University of Miami School of Medicine, PO Box 016960, Miami, FL 33101)—AJNR Am J Neuroradiol. 1997;18:1435–1445.
Gene Expression Induced by Cerebral Ischemia: An Apoptotic Perspective—MacManus JP, Linnik MD (Hoescht Marion Roussel Inc, 2110 E Galbraith Rd, Cincinnati, OH 45215-6300)—J Cereb Blood Flow Metab. 1997;17:815–832.
CADASIL: Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy—Ruchoux M-M (Laboratory of Neuropathology, Hopital Roger Salengro, CHRU 59037 Lille, France), Maurage C-A—J Neuropathol Exp Neurol. 1997;56:947–964.
Clinical Implications of Poststroke Hypothalamo-Pituitary Adrenal Axis Dysfunction: A Critical Literature Review—Mitchell AJ (Dept of Psychiatry, Box 175, Addenbrooke’s Hospital, Cambridge, UK CB2 2QQ)—J Stroke Cerebrovasc Dis. 1997;6:377–388.
Stroke Prevention: Windows of Opportunity and Failed Expectations? A Discussion of Modifiable Cardiovascular Risk Factors and a Prevention Proposal—Gorelick PB (Center for Stroke Research, 1645 West Jackson, Suite 400, Chicago, IL 60612)—Neuroepidemiology. 1997;16:163–173.
The abstracts in this section have been typeset for consistency with journal format but otherwise appear as in the original articles.
- Copyright © 1998 by American Heart Association