Abstracts of Literature
Systemic Administration of Mexiletine for Attenuation of Cerebral Vasospasm Following Experimental Subarachnoid Haemorrhage—Caner H (Baskent Univ. School of Medicine, Dept of Neurosurgery, 12, sokak No: 7 Bahçelievler, Ankara 06490, Turkey), Kwan A-L, Bavbek M, Kilinc K, Durieux M, Lee K, Kassell NF—Acta Neurochir (Wien). 2000;142:455–461. Copyright © Springer-Verlag.
Mexiletine is a class Ib drug that is widely used to treat ventricular arrhythmias. This compound is mainly known as a sodium channel blocker, but studies have demonstrated that it can also activate ATP-sensitive K+ channels and block Ca2+ channels. Recent in vitro data from experiments on liposomes indicate that mexiletine is also a potent antioxidant. The unique activity profile of this drug raised the possibility that it might be of benefit in limiting cerebral vasospasm. Our first series of experiments assessed the effects of mexiletine on transclivally exposed rabbit basilar arteries. The arteries were treated with 50-mM KCl, 20-nM endothelin-1 (ET-1), or 100-μM lyso-phosphatidic acid (LPA) in the presence or absence of 400-mM mexiletine. Vasoconstriction caused by KCl, ET-1, and LPA was inhibited by mexiletine. In a second series of experiments, subarachnoid haemorrhage (SAH) was induced in rabbits by injecting 3-ml of autologous arterial blood into the cisterna magna. Forty-eight hours after SAH induction, transclivally exposed basilar arteries exhibited a spastic constriction that was partially reversed by topical application of 400-μM mexiletine. In a third set of experiments, mexiletine was administered orally at dosages of 80-, 20-, and 5-mg/kg/day t.i.d., beginning 3 hours before SAH to study the prevention of vasospasm. In a separate group of animals, 80- and 20-mg/kg/day t.i.d. of mexiletine was administered 21 hours post-SAH induction, to study the reversal of vasoconstriction. Microscopic analysis of vessels from controls (no SAH), SAH-only, and SAH–mexiletine groups indicated there was −1.43% vascular constriction in the SAH-only group compared with controls. Considerable vaso-relaxation was seen in the prevention study, in which average arterial cross-sectional areas were reduced by only 17.86% and 39.29 in the mexiletine 80- and 20-mg kg/day groups, respectively, compared with controls (p<0.001). Compared with controls, average arterial cross-sectional areas were reduced by 53.58% and 64.29% in the mexiletine 80- and 20-mg/kg/day reversal groups, respectively. Our findings indicate that mexiletine induces potent relaxation in cerebrovascular arteries contracted with various agents, and that it prevents and partially reverses SAH-induced vasoconstriction.
Key Words: subarachnoid hemorrhage, vasospasm
Cerebral Aneurysms Treated by Guglielmi Detachable Coils: Evaluation With Diffusion-Weighted MR Imaging—Biondi A (Dept of Diagnostic and Therapeutic Neuroradiology, Bâtiment Babinski, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l’Hôpital, 75651 Paris, Cedex France), Oppenheim C, Vivas E, Casasco A, Lalam T, Sourour N, Jean LL, Dormont D, Marsault C—AJNR Am J Neuroradiol. 2000;21:957–963. Copyright © American Society of Neuroradiology.
BACKGROUND AND PURPOSE: The most frequent and serious complications of endovascular treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs) are ischemic lesions caused by thromboembolic events. Diffusion-weighted MR imaging appears to be the most sensitive technique for detecting early ischemic phenomena. We evaluated this technique for the detection of brain changes in patients who underwent GDC treatment of aneurysms.
METHODS: Twenty patients with a cerebral aneurysm were studied with diffusion-weighted imaging before and after endovascular treatment with GDCs. Aneurysms were located in the anterior (n=16) or posterior (n=4) circulation. Bleeding had occurred in 11 patients. MR studies, including fast fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted sequences, were scheduled before, 2 to 4 hours after, and 48 hours after treatment. MR images, including apparent diffusion coefficient (ADC) maps, were assessed for the presence of acute ischemic stroke lesions.
RESULTS: In all patients, the aneurysm was excluded without neurologic worsening. In 18 patients, diffusion-weighted and FLAIR images showed no evidence of recent ischemic lesions after treatment. In one patient, an asymptomatic frontobasal hyperintense signal on diffusion-weighted images with a drop of ADC values corresponding to an acute ischemic lesion was observed. In another patient, multiple silent lesions were seen on diffusion-weighted images after embolization. These silent lesions were not all located in the vascular territory of the aneurysm’s parent artery.
CONCLUSION: This preliminary study suggests that diffusion-weighted MR imaging is a potentially useful tool for monitoring patients after endovascular treatment of a cerebral aneurysm. While small asymptomatic lesions can be observed on these images after embolization, their exact prevalence should be evaluated in a larger series.
Key Words: aneurysm, endovascular therapy
The Relation Between Aneurysm Size and Outcome in Patients With Subarachnoid Hemorrhage—Roos EJ, Rinkel GJE (Univ Dept of Neurology, Heidelberglaan 100, 3584 CX Utrecht, Netherlands), Velthuis BK, Algra A—Neurology. 2000;54:2334–2336. Copyright © 2000 by the American Academy of Neurology.
The balance of risks of treatment for unruptured aneurysms might change if the prognosis after rupture depends on the size of the aneurysm. In a prospective series of patients with subarachnoid hemorrhage in whom aneurysmal size was measured by CT angiography performed on admission, poor outcome occurred more often in patients with large (≥10 mm) aneurysms (63%) than in patients with small (<10 mm) aneurysms (41%; RR=1.5; 95% CI 1.0 to 2.2). The relative risk remained essentially the same after adjustment for age, gender, location of the aneurysm, and amount of cisternal blood.
Key Words: aneurysm, subarachnoid hemorrhage
Clinical Features of Intracranial Aneurysms in Siblings—Kasuya H (Dept of Neurosurgery, Tokyo Women’s Medical Univ, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan), Onda H, Takeshita M, Hori T, Takakura K—Neurosurgery. 2000;46:1301–1306.
OBJECTIVE: Among the family members of patients with aneurysmal subarachnoid hemorrhage (SAH), siblings have been documented to be at high risk of SAH and to have a high prevalence of unruptured aneurysms. We studied the distinctive features of aneurysms in siblings and attempted to determine the risk of rupture.
METHODS: We analyzed detailed data on 159 patients with siblings who had ruptured and unruptured aneurysms in 77 families from throughout Japan.
RESULTS: Seventy-three percent of the patients were female, and the mean age at the time of rupture was 55.6 years. In 39 families, two or more siblings had SAH. Eighty of 107 patients with ruptured aneurysms and 28 of 52 with unruptured aneurysms had a family history of SAH in siblings (P=0.0082). Multiple and mirror-image aneurysms were found in 42 and 21 patients, respectively. Among 218 aneurysms, middle cerebral artery aneurysms were the most common type (43%). Anterior communicating artery aneurysms were underrepresented (15%). There were significantly more ruptured than unruptured anterior communicating artery aneurysms, compared with other aneurysms (P=0.01).
CONCLUSION: The clinical features of aneurysms in siblings in this population agreed well with those reported for familial intracranial aneurysms and SAH, except for the age at the time of rupture. It is suggested that the risk of rupture is greater when patients with unruptured aneurysms have siblings with aneurysmal SAH and/or anterior communicating artery aneurysms.
Key Words: aneurysm, hereditary disease
Effect of an Antioxidant, Ebselen, on Development of Chronic Cerebral Vasospasm After Subarachnoid Hemorrhage in Primates—Handa Y (Dept of Neurosurgery, Fukui Medical Univ, Matsuoka, Yoshida-gun, Fukui 910-1193, Japan), Kaneko M, Takeuchi H, Tsuchida A, Kobayashi H, Kubota T—Surg Neurol. 2000;53:323–329. Copyright © 2000 by Elsevier Science Inc.
BACKGROUND Oxidation and/or free radical reactions after subarachnoid hemorrhage (SAH) may be involved in the development of chronic cerebral vasospasm. The inhibition of these reactions is thought to be one of the therapeutic strategies for prevention of cerebral vasospasm. We investigated the effect of Ebselen, a synthetic seleno-organic compound, which exhibits anti-oxidation by glutathione peroxidaselike activity to inhibit free radical reactions by lipid peroxidation on the development of chronic cerebral vasospasm in a primate model.
METHODS Seventeen monkeys were used. SAH was produced by introduction of a blood clot around the right middle cerebral artery and the right side of the circle of Willis in all animals. The monkeys were randomly divided into three groups according to Ebselen dosage: 1) no dosage or non-treated group; 2) high-dose Ebselen group; and 3) low-dose Ebselen group. The drug was administered at 10 mg/Kg in the high-dose group and 5 mg/Kg in the low-dose group twice a day in each group for 7 days after SAH. The vessel diameter was evaluated on angiograms before the induction of SAH and at Day 7 following SAH.
RESULTS In the untreated group, the angiograms showed significant (p<0.05) reductions of the mean vessel caliber of the right internal carotid (ICA) (38±10% reduction) and the middle cerebral artery (MCA) (56±9.7%) compared with the baseline value before SAH. In the high-dose Ebselen-treated group, the mean percent reduction in vessel caliber of the right ICA (16±11%) and MCA (28±9.5%) on Day 7 angiograms were significantly (p<0.05) lower than those in the nontreated group, whereas the mean percent reduction of these vessels in the low-dose Ebselen-treated group showed no significant difference compared with the untreated group.
CONCLUSIONS Chronic cerebral vasospasm was inhibited in the animals in which a relatively large amount of Ebselen was administered for 7 days after SAH. The results suggest that the oxidation or free radical reaction by lipid peroxidation after SAH might be involved in the pathogenesis of vasospasm, and that inhibition of these reactions by drugs, such as Ebselen, may have a promising effect for prevention of vasospasm.
Key Words: vasospasm, subarachnoid hemorrhage
Reliability of Measurements of Muscle Tone and Muscle Power in Stroke Patients—Gregson JM (Aintree Stroke Unit, Dept of Medicine for the Elderly, Univ Hospital, Aintree, Longmoor Lane, Liverpool L9 7AL, UK), Leathley MJ, Moore AP, Smith TL, Sharma AK, Watkins CL—Age Ageing. 2000;29:223–228. Copyright © 2000 British Geriatrics Society.
Objectives: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle: flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists.
Design: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the κ statistic with quadratic weights (Kw).
Setting: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility.
Subjects: people admitted to hospital with an acute stroke—35 patients, median age 73 (interquartile range 65–80), 20 men and 15 women.
Results: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw=0.84–0.96, Kw=0.70–0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw=0.73–0.96, Kw=0.77–0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw=0.45–0.51, Kw=0.59–0.64).
Conclusions: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.
Key Words: stroke outcome, stroke assessment
The Unreliability of Clinical Measures of Muscle Tone: Implications For Stroke Therapy—Pomeroy VM (The Stroke Association’s Therapy Research Unit, Dept of Geriatric Medicine, Clinical Science Bldg, Hope Hospital, Eccles Old Rd, Salford, Manchester M6 8HD, UK), Dean D, Sykes L, Faragher EB, Yates M, Tyrrell PJ, Moss S, Tallis RC—Age Ageing. 2000;29:229–233. Copyright © 2000 British Geriatrics Society.
Background: the central tenet of the neurofacilitatory approach to stroke therapy is that muscle tone needs to be normal before normal movement can occur. A reliable clinical measure of the full spectrum of muscle tone is needed to test: (i) the purported relationship between muscle tone, other motor impairments and disability, and (ii) the effectiveness of stroke therapy to restore movement.
Aim: the purpose of the study was to test the inter-rater reliability of clinical categorization of muscle tone (spastic/normal/flaccid) and also a visual analogue scale with anchor points of lowest tone possible (score 0) and highest tone possible (score 100).
Methods: four independent raters assessed tone of elbow flexors and knee extensors of 14 stroke rehabilitation in patients using the categorical scale. Six independent raters assessed tone of elbow flexors and knee extensors of 25 chronic stroke patients and two healthy volunteers using the visual analogue scale. All assessment orders were randomized.
Results: both scales were unreliable, with κ coefficients for the categorical scale ranging from −0.046 to 0.56 for the categorical scale, and intra-class correlation coefficients for the visual analogue scale of 0.595 for elbow flexors and 0.451 for knee extensors. Assessment order effects for the visual analogue scale were non-significant for elbow flexors (P=0.545) and knee extensors (P=0.911).
Conclusions: these results, and those of earlier studies, suggest that clinical measures of muscle tone are consistently unreliable. Systematic investigation of the therapy rationale for planning and evaluating treatment is required before relevant clinical measures can be developed.
Key Words: stroke assessment, stroke management
Hyperhomocysteinemia: A Risk Factor for Central Retinal Vein Occlusion—Vine AK (Retina Service, Univ of Michigan Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105)—Am J Ophthalmol. 2000;129:640–644. Copyright © 2000 by Elsevier Science Inc.
Purpose: Previous studies have documented that elevated plasma homocysteine level is a risk factor for vascular disease. This study was performed to determine whether hyperhomocysteinemia is a risk factor for central retinal vein occlusion.
METHODS: In a case-control study, data from 74 patients with documented central retinal vein occlusion were reassessed. Control subjects consisted of individuals referred to the same clinic for assessment of a nonretinal vascular disease. Hyperhomocysteinemia was defined as a total plasma homocysteine level above the 95th percentile in the control group.
RESULTS: The mean total plasma homocysteine level was 11.58±4.67 μmol/l (range, 5–26 μmol/l) for cases, and 9.49± 2.65 μmol/l (range, 5–20 μmol/l) for control subjects. Of the 74 patients with a central retinal vein occlusion, 16 (21.6%) had total plasma homocysteine levels above the 95th percentile in the control group (odds ratio, 6.53; 95% confidence interval, 1.81–23.50; P=.003). Hyperhomocysteinemia was present in five (55%) of the nine individuals with bilateral disease, nine (30%) of the 30 patients with ischemic occlusions, and 45 (31%) of the 83 eyes with severe visual loss.
CONCLUSION: Hyperhomocysteinemia is a risk factor for central retinal vein occlusion and may suggest a poor prognosis in patients with central retinal vein occlusion.
Key Words: thrombosis, retina
Do Transient Ischemic Attacks Have a Neuroprotective Effect?—Moncayo J, de Freitas GR, Bogousslavsky J (Dept of Neurology, Centre Hospitalier Universitaire Vaudois [CHUV], CH 1011, Lausanne, Switzerland), Altieri M, van Melle G—Neurology. 2000;54:2089–2094. Copyright © 2000 by the American Academy of Neurology.
Objective: To determine whether TIAs have a neuroprotective effect. Background: Ischemic tolerance or preconditioning, which protects the brain against stroke, has been demonstrated in animal models of cerebral ischemia. Because TIA may represent a clinical model of ischemic tolerance, patients with TIA before cerebral infarction (CI) may therefore have a better outcome than patients without TIA before CI. Methods: A total of 2,490 patients admitted consecutively to a primary care center for first-ever CI in the anterior circulation were divided into two groups on the basis of the presence or absence of prior ipsilateral TIAs. Duration of TIA was classified into three groups (<10 minutes, 10 to 20 minutes, and >20 minutes). The severity of the neurologic picture on admission and functional disability after stroke were compared between patients with and without TIAs. Results: A total of 293 (12%) of the 2,490 patients had prior ipsilateral TIAs before CI. Risk factors did not differ between patients with or without TIAs, whereas the topography and etiology of ischemic stroke did differ (p<0.001). Patients without prior TIAs had a more severe clinical picture on admission, with a greater reduction of consciousness (p=0.009). Patients with previous TIAs had a more favorable outcome than those without TIAs (67% versus 58%, p=0.004). After adjustment for confounding variables, TIAs lasting 10 to 20 minutes were still associated with a favorable outcome (odds ratio, 1.98; 95% confidence interval, 1.27 to 3.08; p=0.002). The interval between TIA and CI influenced the outcome (p=0.007). Conclusions: This study suggests that ischemic tolerance may play a role in patients with ipsilateral TIAs before CI, allowing better recovery from a subsequent ischemic stroke.
Key Words: cerebral ischemia, transient, neuroprotection
Aspirin-Associated Intracerebral Hemorrhage: Clinical and Radiologic Features—Wong KS (Dept of Medicine & Therapeutics, The Chinese Univ of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong), Mok V, Lam WWM, Kay R, Tang A, Chan YL, Woo J—Neurology. 2000;54:2298–2301. Copyright © 2000 by the American Academy of Neurology.
Objective: To identify the clinical and radiologic features of intracerebral hemorrhage (ICH) in aspirin users. Background: Although the benefits of aspirin outweigh its hemorrhagic risks for patients at high risk of vascular diseases, prolonged use of aspirin is associated with an increased risk of ICH. Methods: The authors enrolled consecutive patients with acute stroke who were admitted to a regional hospital from 1993 to 1998 into a stroke registry. From this registry, they identified all stroke patients who had ICH confirmed by CT scan and then selected those taking regular aspirin before ICH as the study group. For each study patient, they selected the immediate next two patients with ICH but not taking aspirin as controls. Results: The authors identified 58 aspirin users and 1193 nonusers among all patients hospitalized for ICH. From the group of nonusers, they selected 116 patients as controls. The locations of the hematoma were different (p=0.002), with more lobar hematoma in the aspirin group (32.8%) than in the control group (10.3%). Prior cerebrovascular disease was the reason for taking aspirin in 37 (64%) patients but five patients had prior ICH. Conclusions: The propensity for lobar hematoma in aspirin-associated ICH suggests its pathology may be somewhat different from spontaneous ICH among nonaspirin users. Further research to examine the risks and benefits of aspirin use in certain subgroups at risk of both thrombotic and hemorrhagic events is needed.
Key Words: aspirin, intracerebral hemorrhage
Apolipoprotein E Polymorphism in Cerebrovascular Disease—Catto AJ (Academic Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds LS1 3EX, UK), McCormack LJ, Mansfield MW, Carter AM, Bamford JM, Robinson P, Grant PJ—Acta Neurol Scand. 2000;101:399–404. Copyright © Munksgaard 2000.
Objectives—The aim of this study was to investigate the relationship between the apo E genotype with acute cerebral infarction and primary intracerebral haemorrhage and to examine the relationship of the apo E genotype with mortality following acute stroke. Materials and methods—We studied 592 cases of acute stroke and 289 healthy control subjects clinically free of cerebrovascular disease. Pathological type of stroke was determined by cranial computed tomography and the subtype of cerebral infarction classified according to the Oxfordshire Community Stroke Project Classification (OCSP). Apo E genotype was determined using polymerase chain reaction. Results—There was no difference in apo E genotype frequency between cases and controls (χ2=3.58, 5 d.f., P=0.60). Apo E genotypes were not related to the pathological type of stroke (cerebral infarction, CI, n=532 and primary intracranial haemorrhage. PICH, n=60, (χ2=3.738, 4 d.f., P=0.44) nor with the Oxfordshire Community Stroke Project Classification subtypes of cerebral infarction, lacunar infarction, LACI (n=169), total anterior circulation infarction, TACI (n=117), partial anterior circulation infarction, PACI (n=173), posterior circulation infarction. POCS (n=54) and including those cerebral infarcts which could not be classified (n=19). χ2=31.1, 20 d.f., P=0.153). At the time of the analysis, 243 cases (41.0%) had died. The median follow-up (including death) was 851 days. There was no relationship between time to death and apo E genotype in cases of either CI or PICH. Conclusion—In this population, there was no relationship between the apolipoprotein E polymorphism and the pathogenesis of cerebral infarction or primary intracerebral haemorrhage. Apo E genotype was not related to all-cause mortality following stroke.
Key Words: apolipoproteins, cerebrovascular disorders
Association Between Severe Cerebral Amyloid Angiopathy and Cerebrovascular Lesions in Alzheimer Disease Is Not a Spurious One Attributable to Apolipoprotein E4—Olichney JM (Neurology Service 127, Veterans Administration Medical Center, 3350 La Jolla Village Dr, San Diego, CA 92161), Hansen LA, Hofstetter R, Lee J-H, Katzman R, Thal LJ—Arch Neurol. 2000;57:869–874.
Background: We have previously reported an association between severe cerebral amyloid angiopathy (CAA) and cerebrovascular lesions in Alzheimer disease (AD), which is particularly strong for microinfarcts, hemorrhages, and multiple lesion types. Cerebral amyloid angiopathy has also been associated with the apolipoprotein E4 (APOE4) genotype, which is in turn associated with premature coronary artery disease and atherosclerosis.
Objective: To test whether severe CAA would be more strongly associated with cerebrovascular lesions than would APOE4 genotype.
Methods: We reviewed 306 cases of autopsy-confirmed AD (from the University of California, San Diego, brain autopsy series) to assess whether APOE genotype and other clinical risk factors were predictive of vascular lesions (VLs) in AD. Cerebral amyloid angiopathy severity was assessed using a semiquantitative scale in 4 brain regions (ie, hippocampus, midfrontal cortex, inferior parietal cortex, and superior temporal cortex) and an average score was computed for each case.
Results: We found that severe CAA was associated with an increased frequency of VLs (33% of the cases of severe CAA had VLs vs 19% of the cases of mild or absent CAA: P=.02). While the APOE4/4 genotype was associated with an increased severity of CAA, there was no significant relationship between APOE genotype and frequency of VLs. Logistic regression models showed that severe CAA, advanced age, atherosclerosis, and Hachinski Ischemia Scale score of 7 or more were all significantly associated with VLs, but the number of APOE4 alleles, history of hypertension, coronary artery disease, sex, and serum cholesterol levels had nonsignificant effects. Within strata of APOE genotype, the presence of severe CAA was associated with increased frequency of VLs (eg, within APOE4/4 homozygotes. VLs were present within 47% of the cases of severe CAA vs 9.5% of the cases of mild or absent CAA: P=.01).
Conclusions: Severe CAA confers a greater risk of VLs in AD, even within strata of APOE genotype. Therefore, the association between severe CAA and VLs in AD is not a spurious one owing to APOE4. Overall, our cases of AD with APOE4 do not seem to be a more “vasculopathic” subtype of AD. The mechanisms by which CAA produces VLs of various types need to be further elucidated, as these are probably important in producing the common entity of “mixed” AD/vascular dementia.
Key Words: apolipoproteins, cerebrovascular disorders
Hypokalemia Associated With Diuretic Use and Cardiovascular Events in the Systolic Hypertension in the Elderly Program—Franse LV, Pahor M (Dept of Internal Medicine, Wake Forest Univ Baptist Medical Center, Medical Center Blvd, Winston-Salem, NC 27157), Di Bari M, Somes GW, Cushman WC, Applegate WB—Hypertension. 2000;35:1025–1030.
The treatment of hypertension with high-dose thiazide diuretics results in potassium depletion and a limited benefit for preventing coronary events. The clinical relevance of hypokalemia associated with low-dose diuretics has not been assessed. To determine whether hypokalemia that occurs with low-dose diuretics is associated with a reduced benefit on cardiovascular events, we analyzed data of 4126 participants in the Systolic Hypertension in the Elderly Program (SHEP), a 5-year randomized, placebo-controlled clinical trial of chlorthalidone-based treatment of isolated systolic hypertension in older persons. After 1 year of treatment, 7.2% of the participants randomized to active treatment had a serum potassium <3.5 mmol/L compared with 1% of the participants randomized to placebo (P<0.001). During the 4 years after the first annual visit, 451 participants experienced a cardiovascular event, 215 experienced a coronary event, 177 experienced stroke, and 323 died. After adjustment for known risk factors and study drug dose, the participants who received active treatment and who experienced hypokalemia had a similar risk of cardiovascular events, coronary events, and stroke as those randomized to placebo. Within the active treatment group, the risk of these events was 51%, 55%, and 72% lower, respectively, among those who had normal serum potassium levels compared with those who experienced hypokalemia (P<0.05). The participants who had hypokalemia after 1 year of treatment with a low-dose diuretic did not experience the reduction in cardiovascular events achieved among those who did not have hypokalemia.
Key Words: hypertension, potassium
A Common Mutation in Lipoprotein Lipase Confers a 2-Fold Increase in Risk of Ischemic Cerebrovascular Disease in Women But Not in Men—Wittrup HH, Nordestgaard BG, Sillesen H, Schnohr P, Tybjaerg-Hansen A (Dept of Clinical Biochemistry, Rigshospitalet 4111, National Univ Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark)—Circulation. 2000;101:2393–2397.
Background—We previously showed that the common Asn291Ser substitution in lipoprotein lipase is associated with elevated plasma triglyceride levels and a 2-fold increase in the risk of ischemic heart disease in women but not men. In this study, we tested the hypothesis that this substitution is also associated with an increased risk of ischemic cerebrovascular disease (ICVD).
Methods and Results—We compared 260 patients who had nonfatal ICVD and carotid stenosis ≥50% with 1560 age-matched controls and also compared 205 Copenhagen City Heart Study cases who had nonfatal ICVD with 1210 age-matched controls. All subjects were white and from Denmark. Overall, no significant difference was observed between carrier frequencies among those with and without ICVD: however, sex interacted with genotype in predicting ICVD in the ICVD and carotid stenosis cases (P=0.02). In Copenhagen City Heart Study cases, sex was not significant (P=0.18). Odds ratios for ICVD in female mutation carriers were 2.9 (95% confidence interval [CI], 1.3 to 6.4) and 1.9 (95% CI, 0.8 to 4.6) in ICVD plus carotid stenosis cases and Copenhagen City Heart Study cases, respectively. Equivalent values in male mutation carriers were 0.8 (95% CI, 0.3 to 1.8) and 0.8 (95% CI, 0.3 to 2.0), respectively. These results were similar in analyses that also allowed for other conventional cardiovascular risk factors.
Conclusions—These results suggest that the Asn291Ser substitution in lipoprotein lipase is not associated with nonfatal ICVD in men but that it possibly confers a 2-fold risk in women.
Key Words: lipoproteins, cerebrovascular disorders
Nitric Oxide Deficiency Contributes to Large Cerebral Infarct Size—Kidd GA, Dobrucki LW, Brovkovych V, Bohr DF (Dept of Physiology, Univ of Michigan Medical School, 7637 Medical Science II, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0622), Malinski T—Hypertension. 2000;35:1111–1118. Copyright © 2000 American Heart Association.
The purpose of this study was to examine the role played by a deficit in nitric oxide (NO) in contributing to the large cerebral infarcts seen in hypertension. Cerebral infarction was produced in rats by occlusion of the middle cerebral artery (MCA). Studies were performed in Sprague-Dawley (SD) rats subjected to NO synthase blockade (NG-nitro-l-arginine [L-NNA], 20 mg · kg−1 · d−1 in drinking water) and in spontaneously hypertensive stroke-prone rats (SHRSP). NO released in the brain in response to MCA occlusion was monitored with a porphyrinic microsensor in Wistar-Kyoto rats. The increment in NO released with MCA occlusion was 1.31±0.05 μmol/L in L-NNA–treated rats, 1.25±0.04 μmol/L in SHRSP, 2.24±0.07 μmol/L in control SD rats, and 2.25±0.06 μmol/L in Wistar-Kyoto rats (P<0.0001 for control versus the other groups). Infarct sizes in the L-NNA–treated and control SD rats were 8.50±0.8% and 5.22±0.7% of the brain weights, respectively (P<0.05). The basilar arterial wall was significantly thicker in L-NNA–treated rats compared with their controls. We conclude that both the deficit in NO and the greater wall thickness contribute to the larger infarct size resulting from MCA occlusion in SHRSP and in L-NNA–treated rats compared with their respective controls.
Key Words: nitric oxide, cerebral infarction
Effect of Lovastatin on Cerebral Circulation in Spontaneously Hypertensive Rats—Régrigny O, Atkinson J (Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, UHP-Nancy 1, 5, rue Albert Lebrun, BP 403, 54000 Nancy, France), Capdeville-Atkinson C, Limiñana P, Chillon J-M—Hypertension. 2000;35:1105–1110. Copyright © 2000 American Heart Association, Inc.
Statins, which are often given to hypertensive patients, reduce the incidence of stroke. However, their effects on the cerebral circulation have been scarcely studied, although lovastatin has been reported to reduce hypertension-induced renal arteriolar hypertrophy. We examined the structure and mechanics of cerebral arterioles and the lower limit of cerebral blood flow (CBF) autoregulation in spontaneously hypertensive rats (SHR) that were untreated (n=9) or treated for 1 month with lovastatin (n=12; 20 mg · kg−1 · d−1) and in untreated Wistar-Kyoto rats (WKY: n=8). We studied the lower limit of CBF autoregulation by repeated measurement of CBF (arbitrary units: laser Doppler) and internal arteriolar diameter (μm; cranial window) at baseline and during stepwise hypotension. Stress-strain relationships were calculated from repeated measurement of internal arteriolar diameter during stepwise hypotension and cross-sectional area (CSA) of the vessel wall in maximally dilated cerebral arterioles (EDTA, 67 mmol/L). Lovastatin slightly reduced mean arterial pressure (treated, 153±3 versus untreated, 171±5 mm Hg, P<0.05; WKY, 106±3 mm Hg) and normalized CSA (treated, 826±52 versus untreated, 1099±16 μm2, P<0.05; WKY, 774±28 μm2). Stress-strain curves show that lovastatin also attenuated the increase in passive distensibility. Lovastatin had no effect on the external diameter of cerebral arterioles or the lower limit of CBF autoregulation. Our results show that although lovastatin has substantial effects on arteriolar mechanics and wall CSA, it has little effect on internal diameter. This phenomenon may explain its lack of effect on CBF autoregulation.
Key Words: cerebral circulation, lipids
Relative Contributions From Neuronal and Endothelial Nitric Oxide Synthases to Regional Cerebral Blood Flow Changes During Forebrain Ischemia in Rats—Santizo R, Baughman VL, Pelligrino DA (Neuroanesthesia Research Laboratory, Univ of Illinois at Chicago, MBRB [M/C 513], 900 S Ashland Ave, Chicago, IL 60607)—Neuroreport. 2000;11:1549–1553. Copyright © 2000 Lippincott Williams & Wilkins.
The principal aim of this study was to examine the relative contributions from the neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively) in their capacity to modulate intra-ischemic cerebral blood flow (CBF) changes, in the ischemically vulnerable hippocampus and striatum. CBF changes were monitored, using laser-Doppler flowmetry, in rats subjected to 30 min of forebrain ischemia (right common carotid occlusion+hemorrhagic hypotension). Rats were pretreated with a selective nNOS inhibitor (ARR 17477), a NOS inhibitor that blocks both eNOS and nNOS (NG-nitro-l-arginine; L-NNA), or saline (control). In initial experiments, where ischemic MABP was targeted to exactly 30 mm Hg, NOS inhibition reduced intra-ischemic cortical CBF from the control level of ∼20% of baseline to 3% (L-NNA) or 6% (ARR 17477) of baseline. The statistically similar effects of the two NOS inhibitors confirmed that nNOS is the predominant NO source supporting intra-ischemic vasodilation in the cortex. In subsequent experiments, CBF was measured in the right hippocampus, and striatum, as well as the cortex, and, to reduce data variability, blood withdrawal was adjusted to achieve an intra-ischemic cortical CBF of 20% (controls) or 5% (NOS inhibited rats) of baseline. In those groups, mean ischemic MABP levels ranged from 28 to 32 mm Hg. In controls, intra-ischemic CBF fell to 20%, 45%, and 47% of baseline in the cortex, hippocampus, and striatum, respectively. With nNOS inhibition, intra-ischemic CBF was further reduced to 5%, 15%, and 18% of baseline, respectively. However, with combined eNOS/nNOS inhibition, the CBF values were 5%, 37%, and 21%, respectively. These results suggest that the nNOS contribution to intra-ischemic vasodilation in vulnerable regions is substantially greater than eNOS. The significantly higher intra-ischemic CBF level in the hippocampus in combined eNOS/nNOS vs nNOS-inhibited rats may relate, in contrast to other regions, to a low eNOS-inhibited rats may relate, in contrast to other regions, to a low eNOS influence on vascular function in that structure and CBF redistribution to the hippocampus when eNOS activity is blocked globally.
Key Words: nitric oxide, cerebral circulation
Physiologic Variations in Dural Venous Sinus Flow on Phase-Contrast MR Imaging—Mehta NR (Boston Univ School of Medicine, 88 E Newton St, Boston, MA 02118), Jones L, Kraut MA, Melhem ER—AJR Am J Roentgenol. 2000;175:221–225. Copyright © American Roentgen Ray Society.
OBJECTIVE. Our study quantifies normal physiologic variations of dural sinus flow using phase-contrast MR imaging.
SUBJECTS AND METHODS. Fifteen volunteers were imaged using nontriggered and triggered phase-contrast MR venography of the superior sagittal and transverse sinuses. Triggered scans were obtained during regular breathing; nontriggered scans were obtained during regular breathing, breath-holding, deep inspiratory breath-holding, and deep expiratory breath-holding. Analysis of variance, Bonferroni method, and Dunn post hoc analysis were used to determine any significant differences in the mean flow and velocity between the different breathing maneuvers. A paired t test was used to compare flow between sinuses during regular breathing.
RESULTS. Deep inspiratory breath-holding and deep expiratory breath-holding resulted in a significant decrease in blood flow and velocity in all dural sinuses compared with regular breathing. During deep inspiratory breath-holding, blood flow decreased 30.8% in the superior sagittal sinus, 19.7% in the left transverse sinus, and 19.1% in the right transverse sinus. Similarly, during deep expiratory breath-holding, blood flow decreased 30.2% in the superior sagittal sinus, 20.8% in the left transverse sinus, and 20.3% in the right transverse sinus. The sum of the flow in the transverse sinuses was significantly greater than in the sagittal sinus. Normal pulsatility of dural sinus blood velocity was also characterized for all measured sinuses.
CONCLUSION. Characterization of variations in dural sinus velocity and flow as a function of the cardiac cycle and breathing maneuvers, using phase-contrast MR imaging, may help separate physiologic from pathologic changes of flow resulting from conditions that influence the cerebrovascular circulation.
Key Words: magnetic resonance imaging, sinus thrombosis
In Vivo Magnetic Resonance Evaluation of Atherosclerotic Plaques in the Human Thoracic Aorta: A Comparison With Transesophageal Echocardiography—Fayad ZA (Mount Sinai School of Medicine, Box 1234, New York, NY 10029), Nahar T, Fallon JT, Goldman M, Aguinaldo JG, Badimon JJ, Shinnar M, Chesebro JH, Fuster V—Circulation. 2000;101:2503–2509. Copyright © 2000 American Heart Association, Inc.
Background—The structure and composition of aortic atherosclerotic plaques are associated with the risk of future cardiovascular events. Magnetic resonance (MR) imaging may allow accurate visualization and characterization of aortic plaques.
Methods and Results—We developed a noninvasive MR method, free of motion and blood flow artifacts, for submillimeter imaging of the thoracic aortic wall. MR imaging was performed on a clinical MR system in 10 patients with aortic plaques identified by transesophageal echocardiography (TEE). Plaque composition, extent, and size were assessed from T1-, proton density-, and T2-weighted images. Comparison of 25 matched MR and TEE cross-sectional aortic plaque images showed a strong correlation for plaque composition (χ2=43.5, P<0.0001; 80% overall agreement; n=25) and mean maximum plaque thickness (r=0.88, n=25; 4.56±0.21 mm by MR and 4.62±0.31 mm by TEE). Overall aortic plaque extent as assessed by TEE and MR was also statistically significant (χ2=61.77, P<0.0001; 80% overall agreement; n=30 regions).
Conclusions—This study demonstrates that noninvasive MR evaluation of the aorta compares well with TEE imaging for the assessment of atherosclerotic plaque thickness, extent, and composition. This MR method may prove useful for the in vivo study of aortic atherosclerosis.
Key Words: magnetic resonance imaging, aortic arch
Gender-Related Differences in Acetazolamide-Induced Cerebral Vasodilatory Response: A Transcranial Doppler Study—Oláh L, Valikovics A, Bereczki D, Fülesdi B, Munkácsy C, Csiba L (Dept of Neurology, Univ Medical School of Debrecen, Nagyerdei krt. 98, H-4012 Debrecen, Hungary)—J Neuroimaging. 2000;10:151–156. Copyright © 2000 by the American Society of Neuroimaging.
Cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration can be easily and reliably assessed by measuring acetazolamide-induced changes using transcranial Doppler. The authors’ aim was to determine whether there are gender-related differences in these parameters. Fifty-six healthy subjects (27 males, 29 females) were examined using transcranial Doppler. Velocities in the middle cerebral artery on both sides were recorded before and at 5, 10, 15, and 20 minutes after intravenous administration of 1 g acetazolamide. The baseline mean flow velocity in the middle cerebral artery was significantly higher in women than in men (p<0.02). After acetazolamide administration, significantly higher cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration were observed in females than in males (p<0.001 in all cases). Subgroup analysis showed that women before menopause responded with higher cerebrovascular reserve capacity and velocity acceleration than age-matched men (p<0.01 and p<0.001, respectively), but no significant difference was found between females after menopause and men of similar age.
Key Words: ultrasonography, vasomotor reactivity
Detection of Stenoses in The Anterior Circulation Using Frequency-Based Transcranial Color-Coded Sonography—Klötzsch C (Dept of Neurology, Universitätsklinikum der Rheinisch-Westfälischen-Technischen Hochschule Aachen, Pauwelsstr. 30, 52057 Aachen, Germany), Popescu O, Sliwka U, Mull M, Noth J—Ultrasound Med Biol. 2000;26:579–584. Copyright © 2000 World Federation for Ultrasound in Medicine & Biology.
Atherosclerotic stenoses of the intracranial vessels are less frequent than those of the extracranial vessels, but they are associated with a considerable annual stroke rate. The aim of the present study was to investigate the usefulness of frequency-based transcranial color-coded sonography (TCCS), transcranial Doppler sonography (TCD) and digital subtraction angiography (DSA) in patients with middle cerebral artery (MCA) and intracranial internal carotid artery (ICA) stenosis. Forty patients presenting with 48 intracranial stenoses of the anterior circulation were involved in the study. The stenoses were detected in the neurovascular laboratory during routine TCD examinations. All patients underwent an additional frequency-based TCCS examination. Both the axial and coronal planes were obtained to allow the exact localization of MCA stenosis and differentiation from intracranial ICA stenosis. Angle-corrected flow velocity measurements were performed if straight vessel compartments were 20 mm or more in length. A total of 18 stenoses (44%) were investigated additionally with DSA. According to the investigation with TCD, 20 (42%) stenoses were low-grade, 12 (25%) were moderate, and the remaining 16 (33%) were severe. Angle-corrected flow velocity measurements obtained with the integrated pulse-wave Doppler device of the TCCS machine were highly correlated (0.912, p<0.001) with those obtained with TCD. TCCS achieved a reliable differentiation of MCA main stem stenosis vs. intracranial ICA stenosis in 7 patients and vs. MCA branch stenosis in 4 patients, but TCD failed in these two subgroups. The agreement between DSA and TCCS to evaluate semiquantitatively 18 intracranial stenoses resulted in a weighted-kappa value of 0.764. The major clinically relevant advantages of TCCS over TCD in MCA stenosis are its ability to differentiate MCA trunk stenosis from terminal ICA or MCA branch stenosis reliably and to perform angle-corrected flow velocity measurements.
Key Words: ultrasonography, arterial occlusive diseases
Prospective Study of the Outcomes of Ambulatory Patients With Excessive Warfarin Anticoagulation—Hylek EM (General Medicine Division/Clinical Epidemiology Unit S50-9, Massachusetts General Hospital, Boston, MA 02114), Chang Y, Skates SJ, Hughes RA, Singer DE—Arch Intern Med. 2000;160:1612–1617.
Background: Warfarin sodium therapy is highly effective in preventing thromboembolism. Its major toxic effect is hemorrhage, the risk of which increases with the international normalized ratio (INR). Data on the rate of major hemorrhage and the rate of INR decay after an episode of excessive anticoagulation therapy would help guide management of elevated INRs in the outpatient setting.
Methods: We prospectively followed up outpatients in an anticoagulant therapy unit from April 24, 1995, through March 1, 1996. Study patients had to be taking warfarin for longer than 1 month and have an INR target range of 2.0 to 3.0. Consecutive outpatients with an INR greater than 6.0 were identified and compared with a randomly selected concurrent set of patients whose INR was in the target range. Major hemorrhage was defined as fatal, intracranial, or requiring hospitalization and transfusion of at least 2 U of blood.
Results: One hundred fourteen patients with INRs greater than 6.0 were identified and compared with 268 patients with INRs in the target range. None of the patients had clinically apparent bleeding at the time of the INR measurement, and none received phytonadione (vitamin K1). Patients did not differ significantly in age, sex, indication, or duration of warfarin therapy. Ten patients with an INR greater than 6.0 (8.8%; 95% confidence interval, 4.3%–15.5%) sought medical attention for abnormal bleeding, and 5 of these experienced a major hemorrhage during 14-day follow-up (4.4%; 95% confidence interval, 1.4%–9.9%) compared with none of the patients with an in-range INR (P<.001). Thirty-three percent of patients with INRs greater than 6.0 had INRs less than 4.0 within 24 hours, 55% within 48 hours, 73% within 72 hours, and nearly 90% within 96 hours of temporary discontinuation of warfarin therapy.
Conclusions: Outpatients with INRs greater than 6.0 face a significant short-term risk of major hemorrhage. Randomized trials are needed to determine the net benefit of preventive treatment with phytonadione.
Key Words: stroke outcome, warfarin
Glycine Antagonist (Gavestinel) in Neuroprotection (GAIN International) in Patients With Acute Stroke: A Randomised Controlled Trial—Lees KR (Univ Dept of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK), Asplund K, Carolei A, Davis SM, Diener H-C, Kaste M, Orgogozo J-M, Whitehead J, for the GAIN International Investigators—Lancet. 2000;355:1949–1954.
Background Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke.
Methods We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional outcome after acute stroke in human beings. Conscious patients with stroke involving limb weakness received either gavestinel at an intravenous loading dose of 800 mg followed by 200 mg every 12 h for five doses, or matching placebo, within 6 h of stroke onset. Stratification variables were age and stroke severity. A computed tomography brain scan within 18 h of stroke onset identified the primary efficacy population with ischaemic stroke. Outcome was assessed by an independent observer with the Barthel index at 3 months. Three outcome categories were applied: good (Barthel index 95–100), moderate (60–90), and poor (0–55 or dead). Analysis was by intention to treat.
Findings Of 1804 patients randomised, 16 received no treatment, and 333 had primary intracranial haemorrhage. 891 patients received gavestinel and 897 received placebo. Outcome in 721 patients who received gavestinel and were analysed for the primary endpoint at 3 months was good in 246 (34.1%), moderate in 136 (18.8%), and poor in 339 (47.0%), compared with 256 (34.9%), 133 (18.1%), and 345 (47.0%), respectively, of 734 patients who received placebo (p=0.8). Mortality at 3 months was 147 (20.4%) in the gavestinel group and 138 (18.8%) in the placebo group. Outcomes within preplanned subgroup and secondary analyses were also neutral. There were no significant differences in serious side-effects between the groups.
Interpretation Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.
Key Words: stroke management, neuroprotection
Postprocedural Hypotension After Carotid Artery Stent Placement: Predictors and Short- and Long-Term Clinical Outcomes—Dangas G, Laird JR Jr, Satler LF, Mehran R, Mintz GS, Larrain G, Lansky AJ, Gruberg L, Parsons EM, Laureno R, Monsein LH, Leon MB (Cardiovascular Research Foundation, 55 E 59th St, 6th Fl, New York, NY 10022)—Radiology. 2000;215:677–683. Copyright © RSNA, 2000.
PURPOSE: To describe the predictors of persistent hypotension after carotid artery stent (CAS) placement and define the clinical outcome of patients with this hemodynamic disturbance.
MATERIALS AND METHODS: One hundred forty CAS procedures were performed in 133 consecutive patients. Post-CAS hypotension—defined as a greater than 40 mm Hg decrease in arterial pressure without evidence of hypovolemia, with a systolic pressure lower than 90 mm Hg at the end of CAS and lasting at least 1 hour—was observed in 25 patients (group 1); 108 patients did not have hypotension (group 2).
RESULTS: Post-CAS hypotension developed in 33.9% of cases after balloon-expandable stent placement versus in 13.6% of cases after self-expanding stent placement (P=.04). In-hospital minor ipsilateral strokes occurred in 16% of cases in group 1 versus in 3% of cases in group 2 (P=.03). There was one (0.9%) major stroke (transient) and three (2.6%) transient ischemic attacks, all of which occurred in group 2 (not significant vs group 1 for both conditions). At 10 months ±4 (SD) of follow-up, there was greater total mortality in group 1 than in group 2 (20% vs 4%, P=.02), whereas neurologic events did not differ significantly between the groups.
CONCLUSION: Hypotension due to carotid sinus stimulation is frequent after CAS with balloon-expandable stents. This phenomenon correlates with increased in-hospital complications and long-term risk of death.
Key Words: carotid endarterectomy, hypotension
A Prospective Controlled Trial Comparing Weekly Self-Testing and Self-Dosing With the Standard Management of Patients on Stable Oral Anticoagulation—Watzke HH (Div of Hematology and Hemostaseology, Wahringer Gürtel 18–20, A-1090 Vienna, Austria), Forberg E, Svolba G, Jimenez-Boj E, Krinninger B—Thromb Haemost. 2000;83:661–665. Copyright © 2000 Schattauer Verlag, Stuttgart.
Oral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events. It is generally assumed, that increasing the frequency of testing would lead to a better control of anticoagulation. We tested this hypothesis in a prospective controlled trial comparing weekly self-testing and self-dosing (self management) with the standard-management of these patients in an anticoagulation clinic. Only patients with stable anticoagulation were included into the study. We recorded 2733 weekly determinations of the intensity of anticoagulation (INR) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on standard-management. Two intensities of anticoagulation were used in each group: a target INR of 3.5 for patients with artificial heart valves (target range: 2.5–4.5) and a target INR 2.5 (target range: 2.0–3.0) for patients with atrial fibrillation or venous thromboembolism. The deviation from the target INR, the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study. The mean deviation from the target INR was smaller in the groups of patients on self-management compared to the patients on standard-management. Individual deviations were significantly (p<0.0001) dependent on the type of management in interaction with the treatment intensity in a general linear model. Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on standard-management (86.2% vs. 80.1% at INR range 2.5–4.5; 82.2 vs. 68.9 at INR range 2.0–3.0). The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly (p<0.005) below the target INR in the high intensity anti-coagulation group on standard-management (target INR: 3.5; achieved mean INR: 3.19; CI 0.95: 3.05–3.34). Our data show, that weekly self-testing and self-dosing leads to a better control of anticoagulation than standard treatment in an anti-coagulation clinic.
Key Words: warfarin, anticoagulants
Attitudes of Canadian and U.S. Neurologists Regarding Carotid Endarterectomy For Asymptomatic Stenosis—Chaturvedi S (Dept of Neurology, Wayne State Univ, 8C-UHC, 4201 St. Antoine, Detroit, MI 48201), Meinke JL, St. Pierre E, Bertasio B—Can J Neurol Sci. 2000;27:116–119.
Background: The American Heart Association carotid endarterectomy (CE) guidelines endorse CE for asymptomatic carotid stenosis if the procedure can be performed with low morbidity. However, the Canadian Stroke Consortium has published a consensus against CE for asymptomatic stenosis. The views of practicing neurologists in the two countries on this subject are unclear. Methods: A survey was undertaken of 270 neurologists from either Florida or Indiana and 180 neurologists from either Ontario or Quebec. Results: The survey was returned by 36% of neurologists. Both Florida (65%) and Indiana neurologists (35%) were significantly more likely than Canadian neurologists (11%) to sometimes often refer patients for surgery (p<0.001). Neurologists from Florida relied more on noninvasive methods of carotid stenosis assessment (36%) than Canadian neurologists (12%, p=0.003), who preferred angiography. Neurologists from Florida more often cited medicolegal concerns as a reason for referring patients for surgery (27%), compared to Canadian neurologists (3%, p=0.0001). Conclusions: Practices pertaining to carotid stenosis evaluation and management differ both regionally and by country. Canadian neurologists refer fewer asymptomatic patients for CE and rely more on angiography as a preoperative diagnostic tool. The potential of medicolegal liability is a greater force in clinical decision-making for certain U.S. neurologists, compared to their Canadian counterparts. These differences may partly explain the variations in CE utilization in the two countries.
Key Words: carotid endarterectomy, surgical treatment
Ultrastructural Pathological Features of Cerebrovascular Malformations: A Preliminary Report—Wong JH, Awad IA (Dept of Neurosurgery, Yale Univ School of Medicine, TMP 403, 333 Cedar St, New Haven, CT 06520), Kim JH—Neurosurgery. 2000;46:1454–1459.
OBJECTIVE: Although cerebrovascular malformations have been characterized histologically, a systematic examination of such lesions by transmission electron microscopy has not been previously published. In this preliminary study, we describe the ultrastructural pathological features of cerebral arteriovenous malformations (AVMs) and cavernous malformations (CMs).
METHODS: Using transmission electron microscopy, we examined three CMs and three AVMs microsurgically harvested from patients, for conventional indications. Normal control cerebral tissue was obtained from two patients undergoing surgery for epilepsy. Specific attention was directed at components of the vascular wall, endothelial cell (EC) morphology, intercellular tight junctions, and the subendothelial layer.
RESULTS: In embolized AVM vessels, ECs were disrupted, with preservation of the underlying subendothelial vessel wall. Nidal vessel walls of AVMs showed disorganized collagen bundles. In CM specimens, ECs lined attenuated cavern walls that were composed of an amorphous material lacking organized collagen. Peripheral to the CMs, capillaries were often surrounded by rings of hemosiderin. Tight junctions between ECs were present in AVMs and control specimens, but substantial inter-EC gaps were found in CMs. Subendothelial smooth muscle cells were present in AVM and control specimens, but they were sparse or poorly characterized in CMs.
CONCLUSION: Surgically resected vascular malformations demonstrate abnormal ultrastructural pathological features. The preoperative embolization of AVMs results in EC denudation, with preservation of vessel wall structural integrity. The thin walls of CMs, lacking significant subendothelial support, along with the rarity of intact tight junctions between ECs, may contribute to the known propensity of CMs for recurrent microhemorrhage.
Key Words: vascular malformations, histology
Items of Interest
MR Perfusion Imaging of the Brain: Techniques and Applications—Petrella JR (Dept of Radiology, Duke Univ Medical Center, Box 3808, Durham, NC 27710), Provenzale JM—AJR Am J Roentgenol. 2000;175:207–219. Copyright © American Roentgen Society.
Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura—Tsai H-M (Div of Hematology, Montefiore Medical Center, 111 E 210th St, Bronx, NY 10467), Rice L, Sarode R, Chow TW, Moake JL—Ann Intern Med. 2000;132:794–799.
Update on Antiplatelet Therapy for Stroke Prevention—Sacco RL (Neurological Institute, 710 W 168th St, Rm 547, Box 6, New York, NY 10032), Elkind MS—Arch Intern Med. 2000;160:1579–1582.
Enhancing Recovery After Stroke With Noradrenergic Pharmacotherapy: A New Frontier?—Gladstone DJ (Cognitive Neurology Unit, Sunnybrook and Women’s College Health Sciences Centre, 2075 Bayview Ave, Rm A421, Toronto, Ontario, Canada M4N 3M5), Black SE—Can J Neurol Sci. 2000;27:97–105.
Building a “Brain Attack” Team to Administer Thrombolytic Therapy for Acute Ischemic Stroke—Hill MD (Stroke Research Office, Foothills Medical Centre, 1403 29th St, NW, Calgary AB T2N 2T9), Barber PA, Demchuk AM, Sevick RJ, Newcommon NJ, Green T, Buchan AM—Can Med Assoc J. 2000;162:1589–1593. Copyright © 2000 Canadian Medical Association.
Recommendations for the Establishment of Primary Stroke Centers—Alberts MJ (Duke Univ Medical Center, Div of Neurology, PO Box 3392 Bryan Research Bldg, Rm 227E, Durham, NC 27710), Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg MR, Starke RD, Todd HW, Viste KM, Girgus M, Shephard T, Emr M, Shwayder P, Walker MD—JAMA. 2000;283:3102–3109.
Stroke Center Guidelines: A Statement of the Working Group on Stroke Centers of the Stork Belt Consortium—Kirshner HS (Dept of Neurology, Vanderbilt Univ School of Medicine, 2100 Pierce Ave, Nashville, TN 37212), for the Working Group—J Stroke Cerebrovasc Dis. 2000;9:144–146. Copyright © 2000 by National Stroke Association.
Stroke—Morgenstern LB, ed—Neurol Clin. 2000;18:273–516.
The Use of Stents in the Management of Neurovascular Disease: A Review of Historical and Present Status—Horowitz MB (Dept of Neurosurgery, Univ of Pittsburgh Medical Center, Suite B-400, 200 Lothrop St, Pittsburgh, PA 15213-2582), Purdy PD—Neurosurgery. 2000;46:1335–1343.
The abstracts in this section have been typeset for consistency with journal format but otherwise appear as in the original articles.
- Copyright © 2000 by American Heart Association