Abstracts of Literature
Reversal of Cerebral Vasospasm Using an Intrathecally Administered Nitric Oxide Donor—Wolf EW (Dept of Neurosurgery, Univ of Tennessee, 847 Monroe Ave, Suite 427, Memphis, TN 38163), Banerjee A, Soble-Smith J, Dohan FC Jr, White RP, Robertson JT—J Neurosurg. 1998;89:279–288.
Object. Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH).
Methods. The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals): a treatment control group (SAH plus 2 μmol of the inactive drug carrier DETA, eight animals): a low-dose treatment group (SAH plus 0.2 μmol DETA/NO, six animals): or a high-dose treatment group (SAH plus 2 μmol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-μmol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals’ brains were performed after the dogs were killed on Day 8.
The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 μmol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p<0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen.
Conclusions. This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.
Key Words: vasospasm, free radicals
Antioxidant Status and α1-Antiproteinase Activity in Subarachnoid Hemorrhage Patients—Marzatico F (Institue of Pharmacology, Faculty of Sciences, Univ of Pavia, Piazza Botta 11, 27100 Pavia, Italy), Gaetani P, Tartara F, Bertorelli L, Feletti F, Adinolfi D, Tancioni F, Rodriguez y Baena R—Life Sci. 1998;63:821–826. Copyright ® 1998 Elsevier Science Inc.
The antiproteasic activity of alpha1-antitrypsin (α1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; α1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of α1-AT, α1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of α1-AT was not statistically different in controls and in patients with SAH; however, the activity of α1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of α1-AT to oxidative reactions and the activity of α1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.
Key Words: subarachnoid hemorrhage, oxidants
The Management of Patients With Arteriovenous Malformations and Associated Intracranial Aneurysms—Thompson RC, Steinberg GK (Dept of Neurosurgery, R109, Stanford Univ Medical Center, Stanford, CA 94305-5327), Levy RP, Marks MP—Neurosurgery. 1998;43:202–212.
OBJECTIVE: Few published studies have focused specifically on the unique management issues encountered in treating patients with arteriovenous malformations (AVMs) and associated intracranial aneurysms. The primary objective of this study was to retrospectively review the clinical and radiographic features of these patients.
METHODS: Medical records of all patients seen at Stanford University Hospital between 1988 and 1996 with a diagnosis of AVMs were retrospectively reviewed. Aneurysms were identified by conventional angiography and characterized by size, number, and location relative to the AVMs. AVMs were graded according to the Spetzler-Martin scale. Odds ratios were calculated for the risk of intracranial hemorrhage. Variables included age, sex, number of aneurysms, and AVM grade.
RESULTS: Forty-five of 600 patients (7.5%) were identified as having coexisting intracranial aneurysms. All 45 patients had high-flow malformations, and 58% had AVMs of Spetzler-Martin Grade IV or higher. A majority of patients had multiple aneurysms. There was a statistically significant increase in AVM hemorrhage in female patients (odds ratio, 8.53 [1.87–38.98]; P<0.005). There was no statistically significant correlation between the development of hemorrhage and either age, AVM grade, or the number of aneurysms. Twenty-three patients (51%) presented with intracranial hemorrhage: bleeding occurred from the AVMs in 15 and from ruptured aneurysms in 5, and the source of the bleeding could not be determined in 3. Overall, nine patients (20%) bled from ruptured aneurysms: five at presentation, two during or within 3 weeks of AVM treatment, and two from new aneurysms. Two of these nine patients died as a direct result of aneurysmal subarachnoid hemorrhage. Five patients (11%) developed new aneurysms.
CONCLUSION: Aneurysms associated with AVMs are at risk for rupture before, during, and immediately after treatment of the AVMs. New aneurysms may arise in patients with high-flow AVMs. The risk of intracranial hemorrhage from either source is higher in female patients. To reduce the complications of intracranial hemorrhage in these patients, we recommend a management protocol designed to treat the aneurysms by surgical or endovascular means before administering definitive therapy for the AVMs. Meticulous intraoperative blood pressure control and fluid management during aneurysm surgery is critical to avoid hemorrhage from the AVMs.
Key Words: aneurysm, cerebral arteriovenous malformations
Delayed Hospital Arrival for Acute Stroke: The Minnesota Stroke Survey—Smith MA, Doliszny KM, Shahar E, McGovern PG, Arnett DK, Luepker RV (Div of Epidemiology, School of Public Health, Univ of Minnesota, 1300 South Second St, Suite 300, Minneapolis, MN 55454-1015)—Ann Intern Med. 1998;129:190–196. © 1998 American College of Physicians–American Society of Internal Medicine.
Background: Although recent advances have been made in the treatment of acute stroke, patients often arrive at the hospital too late to receive the maximum benefit from these new therapies.
Objective: To investigate characteristics that influence the time from symptom onset to hospital arrival (delay time) for patients with acute stroke.
Design: Retrospective medical record review.
Setting: Minneapolis–St. Paul metropolitan hospitals.
Patients: A 50% random sample of all patients 30 to 79 years of age who were hospitalized with acute stroke from 1991 to 1993.
Measurements: Patients were identified through discharge diagnosis lists by using the International Classification of Diseases, 9th Revision. Trained nurses abstracted the medical records. Stroke events were validated by using neuroimaging reports and additional clinical criteria (1895 patients). An accelerated failure time model was used to identify patient characteristics that independently predicted delay time. For 70% of patients (n=1334), delay time was calculated from the medical record by subtracting the recorded time of symptom onset from the admission time. For the remaining 30% of patients (n=561), the time of symptom onset was not recorded, and an approximate delay time was estimated from all available information.
Results: Among patients with a calculated delay time, half arrived within 3 hours of symptom onset and 90% arrived within 24 hours. Patients with approximated delay times tended to have longer delays, and less than 40% of these patients arrived within 24 hours of symptom onset. Some characteristics associated (P<0.05) with longer delay included Asian/Pacific Islander ethnicity, dependence in any activities of daily living before stroke, and several symptoms at stroke onset. Characteristics associated (P<0.05) with shorter delay included admission through the emergency department, presence of syncope or seizures at stroke onset, previous myocardial infarction, abnormal mental status, and greater disability at presentation (measured by the Rankin scale).
Conclusions: Most patients arrive at the hospital too late to receive the maximum benefit from emerging stroke therapies. Efforts to reduce delays in hospital arrival after acute stroke can maximize the effectiveness of these therapies by specifically targeting persons at risk for longer delay.
Key Words: stroke onset, stroke, acute
Elevated Liver Enzymes After Nontraumatic Intracranial Hemorrhages—Meythaler JM (Univ of Alabama-Birmingham, Dept of Rehabilitation Medicine, Spain Rehabilitation Center, UAB Station, Birmingham, AL 35233-7330), Hazelwood J, DeVivo MJ, Rosner M—Arch Phys Med Rehabil. 1998;79:766–771. © 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.
Objective: To determine the prevalence and possible etiologies of liver enzyme abnormalities in patients with acquired brain injury and to assess the impact of these abnormalities on the rehabilitative process.
Setting: University tertiary care rehabilitation center.
Design: Retrospective study.
Subjects: Fifty-six consecutive patients admitted to a brain injury unit in a 30-month period who had an intracranial hemorrhage without associated head or abdominal trauma.
Main Outcome Measures: Liver function tests, Functional Independence Measure (FIM) scores, exposure to hepatotoxic drugs, antiepileptic medication serum levels, history of alcohol use, medical history, length of stay, and medical costs.
Results: There was an increase (from acute hospital admission to inpatient rehabilitation admission) in gamma-glutamyl-transferase (GGT) levels from 42 to 147U/L (p=.0012). There was an increase in alkaline phosphatase from 83 to 125U/L (p=.0079). There was a significant relationship between the GGT level on rehabilitation admission and exposure to hepatotoxic drugs, particularly phenytoin (n=55, p=.0007). Similar findings were noted between alkaline phosphatase and phenytoin (n=55, p=.0022) and systemic steroids (n=50, p=.0277). History of alcohol use was not predictive of changes in liver function tests (p>.05). Correlation analysis revealed no detrimental effect of the elevated serum liver enzyme levels on the Rasch-converted FIM cognitive or motor admission or discharge scores or change in the scores while on rehabilitation (p>.05). All radiologic testing and hepatitis profiles were negative, and 10 of the 16 patients with follow-up laboratory tests showed improvement in their serum liver enzyme levels.
Conclusions: After nontraumatic brain injury there is a characteristic pattern of enzyme elevation that statistically relates to phenytoin exposure. No additional etiologic abnormalities were found on further workup, suggesting that further evaluation should be guided by the patient’s clinical status, not laboratory value alone.
Key Words: hemorrhagic stroke, blood proteins
Lipid and Lipoprotein Levels Remain Stable in Acute Ischemic Stroke: The Northern Manhattan Stroke Study—Kargman DE (Neurological Insitute, Columbia–Presbyterian Medical Center, 710 W 168 St, New York, NY 10032), Tuck C, Berglund L, Lin I-F, Mukherjee RS, Thompson EV, Jones J, Boden-Albala B, Paik MC, Sacco RL—Atherosclerosis. 1998;139:391–399. © 1998 Elsevier Science Irleand Ltd.
Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0±12.1 years; 32% women) presenting with AIS (evaluated within 9.7±12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225±57.6, 154±56.0, 40±10.4, 181±93.7, 52±28.6, 130±24.6, and 141±46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.
Key Words: stroke, acute, lipids
Validation of Patient Recall of Doctor-Diagnosed Heart Attack and Stroke: A Postal Questionnaire and Record Review Comparison—Walker MK (Dept of Primary Care and Population Sciences, Royal Free Hospital School of Medicine, London, England), Whincup PH, Shaper AG, Lennon LT, Thomson AG—Am J Epidemiol. 1998;148:355–361. Copyright © by the John Hopkins Univ School of Hygiene and Public Health.
Few studies have assessed the accuracy of patient recall of doctor-diagnosed heart attack and stroke on postal questionnaire, yet such data are widely used in epidemiologic studies. In the national prospective British Regional Heart Study of 7,735 men aged 40–59 years, based in general practice and followed up for a mean 13.8 years, a mailed questionnaire was sent to all available survivors in 1992. Patient recall of doctor-diagnosed heart attack and stroke was compared with the 316 new general practice-reported heart attacks and 102 new general practice-reported strokes from the medical record reviews. Both study and general practice records were checked for all discordant findings, and corrections were made to the study database. Patients tended to overrecall major cardiovascular events more than they underrecalled them, 33% versus 6% for heart attacks and 25% versus 11% for strokes. Among overrecalled heart attacks, other circulatory problems were present in 78% of the subjects; transient ischemic attacks accounted for 57% of overrecalled strokes. In contrast, the general practice record review system tended to underreport events rather than to overreport them, 3% versus 0.3% for heart attacks and 23% versus 5% for strokes. Patient recall of doctor-diagnosed heart attack and stroke provides a useful method for estimating prevalence rates and resource needs, but the tendency to overestimation needs to be recognized. In etiologic studies when strict diagnostic case criteria are essential, patient recall should be used to complement rather than to supplant medical record data.
Key Words: cardiovascular diseases, epidemiology
Physical Activity and 10-Year Mortality From Cardiovascular Diseases and All Causes: The Zutphen Elderly Study—Bijnen FCH, Caspersen CJ, Feskens EJM (Dept for Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and the Environment, PO Box 1, NL-3720 BA Bilthoven, Netherlands), Saris WHM, Mosterd WL, Dromhout D—Arch Intern Med. 1998;158:1499–1505.
Background: Little is known about physical activity and mortality risk in the elderly. Therefore, we describe the associations between the physical activity pattern of elderly men and the mortality from cardiovascular diseases (CVDs), particularly coronary heart disease (CHD) and stroke, and all causes.
Methods: Self-reported physical activity was assessed with a validated questionnaire for retired men in a population-based sample of 802 Dutch men, aged 64 to 84 years at baseline. Relative risks were estimated for 10-year mortality from CVD (199 deaths), CHD (90), stroke (47), and all causes (373) for tertiles of time spent on physical activity (reference, lowest tertile). Adjustments were made for baseline age, relevant major chronic diseases, cigarette smoking, and alcohol consumption.
Results: Mortality risks from CVD and all causes decreased with increasing physical activity (P for trend=.04) with adjusted relative risks of 0.70 (95% confidence interval, 0.48–1.01) and 0.77 (95% confidence interval, 0.59–1.00) in the highest tertile of total physical activity, respectively. Except for CHD, time spent in more intense activities (≥4 kcal/kg per hour) was more strongly associated with all mortality outcomes than less intense activities, but no single type of activity was particularly protective. Walking or cycling at least 3 times per week for 20 minutes (our definition of activity based on general health recommendations) was associated with reduced mortality from CVD (adjusted relative risk, 0.69; 95% confidence interval, 0.50–0.88) and all causes (relative risk, 0.71; 95% confidence interval, 0.58–0.88). Additional adjustment for biological cardiovascular risk factors did not affect the strength of any association.
Conclusion: In a general population of elderly men, physical activity may protect against mortality from CVDs and all causes.
Key Words: exercise, mortality
Testosterone Increases and Estradiol Decreases Middle Cerebral Artery Occlusion Lesion Size in Male Rats—Hawk T, Zhang Y-Q, Rajakumar G, Day AL, Simpkins JW (Box 100487, JHMHC, College of Pharmacy, Univ of Florida, Gainesville, FL 32610)—Brain Res. 1998;796:296–298. © 1998 Elsevier Science B.V.
This study was undertaken to determine the effects of estrogen and testosterone on cerebral ischemic lesion size induced by middle cerebral artery (MCA) occlusion in male rats. Rats were gonadectomized and treated with testosterone, estrogen, or testosterone plus estrogen filled Silastic® pellets. The animals were divided into 6 groups: intact, intact+estrogen (E2), castrate, castrate+testosterone (T), castrate+E2, and castrate+T+E2. One week after treatment, cerebral ischemia was induced by MCA occlusion for 40 min, followed by reperfusion. After 24 h, rats were sacrificed and slices were then stained to assess lesion size. The presence of testosterone increased and the removal of testosterone decreased lesion size. A strong positive correlation (r2=0.922) between plasma testosterone concentrations and ischemic lesion size was observed. Estradiol treatment reduced ischemic area. In summary, the present study provides evidence that testosterone exacerbates and estrogens ameliorate ischemic brain damage in an animal model of cerebral ischemia.
Key Words: hormones, middle cerebral artery occlusion
Effects of Mild Hypothermia on the Release of Regional Glutamate and Glycine During Extended Transient Focal Cerebral Ischemia in Rats—Huang F-P, Zhou L-F, Yang G-Y (R5605 Kresge Research I, Univ of Michigan, Ann Arbor, MI 48109-0532)—Neurochem Res. 1998;23:991–996.
The present study is to determine the effect of mild hypothermia (MHT) on the release of glutamate and glycine in rats subjected to middle cerebral artery occlusion and reperfusion. The relationship between amino acid efflux and brain infarct volume was compared in different periods during MHT. Reversible middle cerebral artery occlusion was performed in Sprague-Dawley rats using a suture model. The rats were divided into four groups including (1) MHT during ischemia (MHTi), (2) MHT during reperfusion (MHTr), (3) MHT during ischemia and reperfusion (MHTi+r), and (4) a normothermic group (NT). Extracellular concentrations of glutamate and glycine in the cortex and striatum were monitored using in vivo microdialysis and analyzed using high-performance liquid chromatography. Morphometric measurements for infarct volume were performed using 2,3,5-triphenyltetrazolium chloride staining. The increase of glutamate and glycine in the ischemic cortex of the MHTi and MHTi+r rats during ischemic and reperfusion periods was significantly less than that of the NT rats (p<0.05). However, there was no statistical difference among these groups in the peak of glutamate and glycine release in the striatum. Infarct volume paralleled the release of glutamate and glycine. The protective effect of MHTi and MHTi+r in reducing ischemia and reperfusion brain injury may be due to the attenuation of both glutamate and glycine release during ischemia and reperfusion.
Key Words: hypothermia, cerebral ischemia, focal
Increased Fraction of Circulating Activated Platelets in Acute and Previous Cerebrovascular Ischemia—Grau AJ (Neurology Dept, Univ of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany), Ruf A, Vogt A, Lichy C, Buggle F, Patscheke H, Hacke W—Thromb Haemost. 1998;80:298–301.
Determination of circulating activated platelets may be helpful to estimate the prognosis and to stratify therapies in arterial vascular disorders including stroke. We used flow cytometry and phase contrast microscopy to study whether the fraction of platelets expressing p-selectin and CD63 and the fraction of platelets with shape change are increased in patients with acute and previous cerebrovascular ischemia.
The proportion of platelets expressing activation dependent antigens was higher in patients with acute (n=24; p-selectin: 8.23±4.21%; CD63: 3.53±2.53%) and with previous cerebrovascular ischemia (n=46; 3.86±1.98%; 2.80±1.79%) as compared to age- and sex-matched control subjects (n=35; 2.17±0.96%; 1.79±0.75%; p≤0.005, respectively). In patients with previous ischemia, there was no difference between treatment with aspirin (n=25) or phenprocoumon (n=21). Hypertension, diabetes mellitus and smoking were not associated with increased antigen expression (analysis of variance). The fraction of discoid platelets and platelet counts were not significantly different between groups.
Our results indicate increased expression of platelet neoantigens in acute and to a less degree in previous cerebrovascular ischemia. Ongoing platelet activation after cerebrovascular ischemia despite therapy with aspirin or phenprocoumon indicates that new anti-platelet drugs may be of benefit for these patients. Flow cytometry appears to be a useful tool to assess platelet function in cerebrovascular ischemia.
Key Words: platelet activation, stroke, acute
Cerebral Infarction: Time Course of Signal Intensity Changes on Diffusion-Weighted MR Images—Burdette JH, Ricci PE (Dept of Radiology, Div of Radiologic Sciences, Wake Forest Univ School of Medicine, Bowman Gray Campus, Medical Center Blvd, Winston-Salem, NC 27157-1088), Petitti N, Elster AD—AJR Am J Roentgenol. 1998;171:791–795. © American Roentgen Ray Society.
OBJECTIVE. The objective of this study was to determine the time course of signal intensity changes on diffusion-weighted MR images after cerebral infarction.
MATERIALS AND METHODS. Echoplanar diffusion-weighted MR images were obtained at 1.5 T in 212 patients referred for suspected cerebral infarction over a 6-month period. Of those patients, 85 met strict criteria for inclusion in this study: final clinical diagnosis of stroke, reliable timing of clinical ictus by history, and neurologic symptoms persisting longer than 48 hr after onset. Using adjacent or contralateral normal brain for comparison, diffusion-weighted images were visually analyzed retrospectively to evaluate for abnormalities in signal intensity. Because three patients were scanned on two occasions and five patients had two anatomically separable infarctions, 93 reliably dated brain lesions were analyzed.
RESULTS. Diffusion-weighted images showed abnormal findings in 13 (100%) of 13 lesions less than 1 day old, 46 (96%) of 48 lesions 1–4 days old, 16 (94%) of 17 lesions 5–9 days old, three (60%) of five lesions 10–14 days old, and zero (0%) of 10 lesions more than 14 days old.
CONCLUSION. Abnormal signal intensity was present on all diffusion-weighted MR studies obtained in patients within 24 hr of acute cerebral infarction and in up to 94% of patients scanned during the first 2 weeks after ictus. The percentage of abnormal diffusion studies declined with time, and no signal intensity abnormality was seen in stroke patients scanned more than 2 weeks after symptom onset.
Key Words: magnetic resonance imaging, cerebral infarction
Lacunar Infarcts Defined by Magnetic Resonance Imaging of 3660 Elderly People—Longstreth WT Jr (Dept of Neurology, Box 359775, Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104-2499), Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR—Arch Neurol. 1998;55:1217–1225.
Objective: To identify risk factors for and functional consequences of lacunar infarct in elderly people.
Methods: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings.
Results: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P<.005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P<.005), male sex (OR, 0.74; P<.005), and history of diabetes at entrance into the study (OR, 1.33; P<.05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts.
Conclusions: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.
Key Words: lacunar infarction, magnetic resonance imaging
Evaluation of the Ratio of Cerebral Blood Flow to Cerebral Blood Volume as an Index of Local Cerebral Perfusion Pressure—Schumann P (Université de Caen, CNRS UMR 6551, Cyceron, Bd H. Becquerel, BP2559, F-14074 Caen Cedex, France), Touzani O, Young AR, Baron J-C, Morello R, MacKenzie ET—Brain. 1998;121:1369–1379. © Oxford University Press 1998.
Local cerebral perfusion pressure (CPP), a crucial parameter that should allow a better assessment of the haemodynamic compromise in cerebrovascular diseases, is not currently measurable by non-invasive means. Experimental and clinical studies have suggested that the regional ratio of cerebral blood flow to cerebral blood volume (CBF:CBV), as measured by PET, represents an index of local CPP in focal ischaemia. The present study was designed to evaluate further the reliability of the CBF:CBV ratio during manipulations of CPP by deliberately varying mean arterial pressure (MAP) in the anaesthetized baboon. Cortical CBF, CBV, cerebral metabolic rate for oxygen (CMRO2) and oxygen extraction fraction were measured by PET using the 15O steady-state technique in 10 anaesthetized baboons. Five baboons (Group A) underwent four PET examinations at different levels of MAP: base line (101±6 mm Hg) followed by moderate hypotension (58±3 mm Hg) and, in a separate experiment, minor hypotension (72±3 mm Hg) followed by profound hypotension (34±5 mm Hg). Trimetaphan was used to lower MAP to minor and moderate levels while profound hypotension was achieved by the combined effects of trimetaphan and lower-body negative pressure. Five other baboons (Group B) were subjected to hypertension (121±2 mm Hg) induced by metaraminol and were compared with their base line state (81±10 mm Hg). While CBF displayed significant changes with varying MAP, i.e. decrease and increase with hypotension and hypertension, respectively (−11% from base line to moderate hypotension compared with −20%, from minor to profound hypotension and +31% from base line to hypertension), CBV was more variable and did not significantly change, except with profound hypotension when the increase was significant (+13%). The CBF:CBV ratio decreased significantly at all stages of hypotension (−21 and −31%) and was significantly increased during hypertension (+30%). Importantly, the CBF:CBV ratio demonstrated a significant correlation with MAP (ρ=0.78, Spearman’s rank correlation coefficient, P<0.01). No major changes in CMRO2 were noted during either hypotension or hypertension. Our results demonstrate that, under physiological conditions, cortical CBF:CBV is significantly correlated with CPP, itself a function of MAP. In the investigated range of MAP, the relationships between CBF:CBV and MAP appear to be linear. These findings further argue for the reliability of CBF:CBV as an index of CPP in situations where increases or decreases of MAP without superimposed changes in cerebrovascular tone are encountered, and they confirm the potential usefulness of this regional ratio for clinical investigations and management in cerebrovascular diseases.
Key Words: cerebral blood flow, perfusion
Differentiation Between Transient Ischemic Attack and Ischemic Stroke Within the First Six Hours After Onset of Symptoms by Using 99mTc-ECD-SPECT—Berrouschot J (Dept of Neurology, Univ of Leipzig, Liebigstrasse 22a, 04103 Leipzig, Germany), Barthel H, Hesse S, Köster J, Knapp WH, Schneider D—J Cereb Blood Flow Metab. 1998;18:921–929. © 1998 The International Society of Cerebral Blood Flow and Metabolism. Published by Lippincott-Raven Publishers, Philadelphia.
The aim of this study was to define the accuracy of 99mTc-ethyl cysteinate dimer–single photon emission computed tomography (99mTc-ECD-SPECT) in distinguishing transient ischemic attack from completed ischemic stroke at early stages after the onset of symptoms. In a prospective study we examined 82 patients within 6 hours after the onset of symptoms (neurologic deficit caused by middle cerebral artery ischemia) using both 99mTc-ECD-SPECT and computed tomography (CT). The follow-up was based on Scandinavian Stroke Scale (SSS) 24 hours and 5–7 days, as well as on CT 7 days, after the event. SPECT evaluation was performed both visually and using semiquantitative region-of-interest (ROI) analysis. According to visual SPECT analysis, on admission 59 of 82 patients had activity deficits in the symptomatic hemisphere. After 7 days, all these patients had neurologic symptoms (SSS 28±12 points), caused by a cerebral infarction as evidenced with CT. Twenty-three of 82 patients displayed no early activity deficit despite clinical symptoms. None of these patients had neurologic symptoms after 7 days (indicating transient ischemic attack or prolonged reversible ischemic neurologic deficit). In the semiquantitative SPECT analysis, all patients had abnormal count densities in the respective ROI (activity <90% compared with the contralateral side). All patients with transient ischemia (n=23) had count rate densities more than 70% of the respective contralateral ROI, whereas all patients with subsequent infarction (n=59) had values <70%. Use of 99mTc-ECD-SPECT allows transient ischemia to be distinguished from ischemic infarction using relative regional activity thresholds within the first 6 hours after onset of symptoms.
Key Words: tomography, emission computed, cerebral ischemia, transient
Correlation of Perfusion- and Diffusion-Weighted MRI With NIHSS Score in Acute (<6.5 Hour) Ischemic Stroke—Tong DC (Stanford Stroke Center, 701 Welch Rd, Suite 325B, Palo Alto, CA 94304), Yenari MA, Albers GW, O’Brien M, Marks MP, Moseley ME—Neurology. 1998;50:864–870. Copyright © 1998 by the American Academy of Neurology.
Background: Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome. Objective: The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia. Methods: Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week. Results: There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r=0.96, p<0.001) or DWI (r=0.67, p=0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r=0.99, p<0.00001). Conclusions: Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.
Key Word: stroke, acute, magnetic resonance imaging
Cerebral Hemodynamics in Young Hypertensive Subjects and Effects of Atenolol Treatment—Troisi E, Attanasio A, Matteis M, Bragoni M, Monaldo BC, Caltagirone C, Silvestrini M (tel. +39 6 5914436; fax +39 6 5922086)—J Neurol Sci. 1998;159:115–119. © 1998 Published by Elsevier Science B.V. All rights reserved.
The aim of this study was to evaluate changes in cerebral hemodynamics in young patients with uncomplicated hypertension before and after effective antihypertensive treatment with a beta-blocker drug. Changes in mean flow velocity in the middle cerebral artery from normal condition to hypercapnia were evaluated by means of a transcranial Doppler in 42 hypertensive patients and 21 healthy subjects comparable for age and sex distribution. We obtained hypercapnia with breath-holding and evaluated cerebrovascular reactivity with the breath-holding index (BHI). After a baseline evaluation (time 0), patients were randomly assigned to a placebo (group 1) or atenolol (group 2) therapy. The evaluation was repeated after 30 (time 1) and 60 (time 2) days of treatment. Before treatment, hypertensive patients had significantly lower BHI values (0.96±0.1 group 1 and 0.85±0.3 group 2) than controls (1.69±0.4) (P<0.0001). During treatment, mean blood pressure significantly decreased in group 2 patients. In the same group, BHI values significantly increased with respect to the pre-treatment evaluation: 1.39±0.2 at time 1 and 1.44±0.2 at time 2 (P<0.0001). On the contrary, mean blood pressure and BHI values remained unchanged in the placebo group. Furthermore, BHI values were significantly higher in group 2 than in group 1 patients at times 1 (P<0.001) and 2 (P<0.0001). These findings suggest that hypertension causes reduced capability of cerebral vessels to adapt to functional changes. This condition, which is reversible after treatment, could be implicated in the increased susceptibility to ischemic stroke in hypertension.
Key Words: vasomotor reactivity, hypertension
Use of Hypertonic (3%) Saline/Acetate Infusion in the Treatment of Cerebral Edema: Effect on Intracranial Pressure and Lateral Displacement of the Brain—Qureshi AI (Div of Neurosciences Critical Care, John Hopkins Medical Institution, Baltimore, MD), Suarez JI, Bhardwaj A, Mirski M, Schnitzer MS, Hanley DF, Ulatowski JA—Crit Care Med. 1998;26:440–446. Copyright © 1998 by Williams & Wilkins.
Objective: To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema.
Design: Retrospective chart review.
Settings: Neurocritical care unit of a university hospital.
Patients: Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n=8), postoperative edema (n=5), nontraumatic intracranial hemorrhage (n=8), and cerebral infarction (n=6).
Intervention: Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L.
Measurements and Main Results: A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2=.91, p=.03), and postoperative edema (r2=.82, p=.06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8±1.4 to 1.1±0.9 [SEM]) and in patients with postoperative edema (3.1±1.6 to 1.1±0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus.
Conclusions: Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.
Key Words: brain edema, intracranial pressure
Randomized Study of Carotid Angioplasty and Stenting Versus Carotid Endarterectomy: A Stopped Trial—Naylor AR (Dept of Surgery, Clinical Sciences Bldg, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom), Bolia A, Abbott RJ, Pye IF, Smith J, Lennard N, Lloyd AJ, London NJM, Bell PRF—J Vasc Surg. 1998;28:326–334. Copyright © 1998 by the Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter.
Background: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease.
Methods: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (>70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days.
Results: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days.
Conclusions: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted—even in an amended format—primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.
Key Words: angioplasty, carotid endarterectomy
Provision of Training in Carotid Surgery Does Not Compromise Patient Safety—Naylor AR (Dept of Surgery, Clinical Sciences Bldg, PO Box 65, Leicester Royal Infirmary, Leicester LE2 7LX, UK), Thompson MM, Varty K, Sayers RD, London NJM, Bell PRF—Br J Surg. 1998;85:939–942. © 1998 Blackwell Science Ltd.
Background Vascular surgeons perceive that carotid endarterectomy carries a higher risk of stroke if performed by a surgical trainee. Accordingly, some trainees consider that they receive a less than adequate training in carotid surgery before taking up a consultant position. The aim of this study was to establish whether the stroke rate was adversely affected if carotid endarterectomy was performed by a surgical trainee under consultant supervision.
Methods This was a prospective study of 151 consecutive patients undergoing carotid endarterectomy between 1 January and 31 December 1996 using a standardized technique including intraoperative and postoperative transcranial Doppler monitoring and completion angioscopy.
Results The overall mortality and/or disabling stroke rate was 0.7 per cent (one of 151 patients), whereas the mortality and/or any stroke rate was 1.3 per cent (two of 151). Surgical trainees performed 82 of 151 carotid endarterectomies, with a mortality rate of 1 per cent and a mortality and/or any stroke rate of 2 per cent. There was no significant difference in the incidence of retained thrombus or intimal flaps between trainees and consultants as detected by angioscopy.
Conclusion Vascular surgical trainees can receive a comprehensive training in carotid artery surgery without incurring an unacceptable increase in operative risk.
Key Words: carotid endarterectomy, treatment outcome
Symposium: Controversies in Cerebrovascular Disease 2: Should Patients Be Screened for Asymptomatic Carotid Artery Stenosis?—Hill AB (Dept of Surg, Ottawa General Hospital, University of Ottawa, 501 Smyth Rd, Ottawa, ON K1H 8L6)—Can J Surg. 1998;41:208–213. © 1998 Canadian Medical Association.
Objective: To evaluate, against published guidelines, the potential role of screening to reduce the risk of stroke and death from asymptomatic carotid artery stenosis (ACAS).
Data Sources: Papers selected for review were identified through a GRATEFUL MED literature search, from personal files and from references documented in identified papers.
Study Selection: Population studies concerning disease prevalence, natural history studies related to risk of stroke, randomized controlled trials related to carotid endarterectomy and natural history studies related to the risk of developing ACAS were considered for review.
Data Extraction: An estimate was made of the potential for stroke resulting from ACAS in the general population. This was evaluated against the positive predictive value of duplex scanning, and the number of patients needing to be screened to prevent a stroke was estimated.
Data Synthesis: The prevalence of ACAS in the general population was estimated to range from 2% to 8% for ACAS 50% or greater and to range from 1% to 2% for ACAS 80% or greater. The yearly risk of stroke or death from undetected ACAS was estimated to be 0.16% for ACAS 50% or greater and 0.06% for ACAS 80% or greater. The estimated number of patients needing to be screened to prevent 1 stroke would range from 850 to 1700 (and potentially as high as 8500).
Conclusions: General screening for ACAS to prevent stroke and death cannot be recommended when evaluated against available guidelines. The decision to screen individual patients will require judgment, continued evaluation and surveillance of the results of such screening by the treating physician.
Key Words: carotid stenosis, carotid endarterectomy
Preoperative Volume Expansion Improves Tolerance to Carotid Artery Cross-Clamping During Endarterectomy—Gross CE (Univ of Vermont, College of Medicine, Dept of Surgery, Div of Neurosurgery, Given Building D319, Burlington, VT 05405-0068), Bednar MM, Lew SM, Florman JE, Kohut JJ—Neurosurgery. 1998;43:222–228.
OBJECTIVE: The benefit of carotid endarterectomy for carotid artery stenosis relates to both appropriate patient selection and careful surgical technique. Critical to the latter is the ability to afford intraoperative neuroprotection during carotid cross-clamping, although the optimal strategy to assure this protection remains debated. This report describes the impact of adding preoperative colloid volume expansion to a surgical algorithm that includes electroencephalographic (EEG) monitoring and barbiturate-induced burst suppression for EEG lateralization refractory to hypertension.
METHODS: The incidence of ischemic EEG change during carotid cross-clamping was observed. The results of an initial series of patients (n=45) reported before incorporation of volume expansion were compared with the results of the current series (n=155) of carotid endarterectomies, which included preoperative volume expansion with 6% hetastarch (500 or 1000 cc).
RESULTS: With preoperative volume expansion, there was a 40% decrease in the incidence of EEG lateralization during carotid cross-clamping (17.4 versus 28.9%, P<0.05) and a 63% decrease in the EEG lateralization refractory to induced hypertension (5.8 versus 15.6%, P<0.05). The combined perioperative stroke and death rate was 1.3%.
CONCLUSION: These results support the use of preoperative colloid volume expansion in carotid endarterectomy as a means of increasing the cerebral tolerance to carotid cross-clamping.
Key Words: carotid endarterectomy, cerebral ischemia
Items of Interest
Incomplete Lacunar Infarction (Type I b Lacunes)—Lammie GA (Neuropathology Laboratory, Dept of Pathology, Edinburgh Univ, Alexander Donald Bldg, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, UK), Brannan F, Wardlaw JM—Acta Neuropathol. 1998;96:163–171. © Springer-Verlag 1998.
Time Course of Microglia Activation and Apoptosis in Various Brain Regions After Permanent Focal Cerebral Ischemia in Mice—Rupalla K, Allegrini PR, Sauer D, Wiessner C (Novartis Pharma Inc, K 125 5 15, CH-4002 Basel, Switzerland)—Acta Neuropathol. 1998;96:172–178. © Springer-Vergal 1998.
Predicting Ability to Drive After Stroke—Mazer BL (Jewish Rehabilitation Hospital Research Center, 3205 Place Alton Goldbloom, Laval, Quebec, Canada H7V 1R2), Korner-Bitensky NA, Sofer S—Arch Phys Med Rehabil. 1998;79:743–750. © 1998 by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.
Experimental Models for the Investigation of Brain Ischemia—Hossmann KA (Tel +49 221 4726 211; fax +49 221 4726 325; e-mail firstname.lastname@example.org)—Cardiovasc Res. 1998;39:106–120. © 1998 Elsevier Science B.V. All rights reserved.
Medical, Surgical, and Interventional Treatment for Carotid Artery Disease—Chaturvedi S (6E-UHC, Dept of Neurology, Wayne State Univ, 4201 St Antoine, Detroit, MI 48201)—Clin Neuropharmacol. 1998;21:205–214. © 1998 Lippincott-Raven Publishers, Phaladephia.
Homocysteine as a Risk Factor for Ischemic Stroke: An Epidemiological Story in Evolution—Sacco RL (Neurological Institute, Rm 547, 710 W 168 St, New York, NY 10032), Roberts JK, Jacobs BS—Neuroepidemiology. 1998;17:167–173. © 1998 S. Karger AG, Basel.
Diffusion-weighted Echo-planar MRI of Lacunar Infarcts—Noguchi K (Dept of Radiology, Toyama Medical and Pharmaceutical Univ, 2630 Sugitani, Toyama City, 930-0194 Toyama, Japan), Nagayoshi T, Watanabe N, Kanazawa T, Toyoshima S, Morijiri M, Shojaku H, Shimizu, Seto H—Neuroradiology. 1998;40:448–451. © Springer-Verlag 1998.
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