CT Perfusion Maps Improve Detection of M2-MCA Occlusions in Acute Ischemic Stroke

ObjectivesMiddle cerebral artery occlusions, particularly M2 branch occlusions are challenging to identify on CTA. We hypothesized that additional review of the CTP maps will increase large vessel occlusion (LVO) detection accuracy on CTA and reduce interpretation time.Materials and MethodsTwo readers (R1 and R2) retrospectively reviewed the CT studies in 99 patients (27 normal, 26 M1-MCA, 46 M2-MCA occlusions) who presented with suspected acute ischemic stroke (AIS). The time of interpretation and final diagnosis were recorded for the CTA images (derived from CTP data), both without and with the CTP maps. The time for analysis for all vascular occlusions was compared using McNemar tests. ROC curve analysis and McNemar tests were performed to assess changes in diagnostic performance with the addition of CTP maps.ResultsWith the addition of the CTP maps, both readers showed increased sensitivity (p = 0.01 for R1 and p = 0.04 for R2), and accuracy (p = 0.02 for R1 and p = 0.004 for R2) for M2-MCA occlusions. There was a significant improvement in diagnostic performance for both readers for detection of M2-MCA occlusions (AUC R1 = 0.86 to 0.95, R2 = 0.84 to 0.95; p < 0.05). Both readers showed reduced interpretation time for all cases combined, as well as for normal studies (p < 0.001) when CTP images were reviewed along with CTA. Both readers also showed reduced interpretation time for M2-MCA occlusions, which was significant for one of the readers (p < 0.02).ConclusionThe addition of CTP maps improves accuracy and reduces interpretation time for detecting LVO and M2-MCA occlusions in AIS. Incorporation of CTP in acute stroke imaging protocols may improve detection of more distal occlusions.     

Whole brain CT perfusion combined with CT angiography in patients with subarachnoid hemorrhage and cerebral vasospasm

Objective

To assess cerebral vasospasm (CVS) and monitor cerebral microcirculatory changes in patients with acute subarachnoid hemorrhage (SAH) via CT angiography (CTA) combined with whole-brain CT perfusion (CTP) techniques.

Methods

Sixty patients with SAH (SAH group) and 10 patients without SAH (control group) were selected for a prospective study. CTP combined with CTA and digital subtraction angiography (DSA) studies were performed on patients with initial onset of SAH less than three days. CTA and DSA as well as the CTP parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) were acquired and analyzed. The relationship of CTA and CTP measurements was assessed in these acute SAH patients.

Results

CTP techniques were used to achieve the perfusion maps of the whole brain in patients with acute SAH. Compared to the control group, mean CBF value was significantly lower while both MTT and TTP values were significantly higher in SAH group (all p < 0.05). Further analysis revealed that mean CBF in patients with CVS, sCVS, Fisher III–IV and Hunt–Hess III–V significantly decreased when compared to patients with nCVS, asCVS, Fisher I–II and Hunt–Hess I–II (p < 0.05). Furthermore both MTT and TTP values were also significantly reduced in patient with CVS, sCVS, Fisher III–IV and Hunt–Hess III–V (p < 0.05).

Conclusion

The study demonstrated that changes of microcirculation in patients with SAH could be assessed by whole-brain CTP. CTP combined with CTA could detect both macroscopic evident vasospasm on CTA and alterations of microcirculation on CTP. Mean CBF was significantly lower in patients with SAH.     

Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients

The clinical importance of asymptomatic proximal and distal deep vein thrombosis (DVT) remains uncertain and controversial. The aim of this retrospective, post-hoc analysis was to examine mortality and risk factors for development of proximal DVT in hospitalized patients with acute medical illness who were recruited into a randomized, prospective clinical trial of thromboprophylaxis with dalteparin (PREVENT). We analyzed 1738 patients who had not sustained a symptomatic venous thromboembolic event by Day 21 and who had a complete compression ultrasound of the proximal and distal leg veins on Day 21. We examined the 90-day mortality rates in patients with asymptomatic proximal DVT (Group I, N=80), asymptomatic distal DVT (Group II, N=118) or no DVT (Group III, N=1540). The 90-day mortality rates were 13.75%, 3.39%, and 1.92% for Groups I-III, respectively. The difference in mortality between Group I and Group III was significant (hazard ratio 7.63, 95% CI=3.8-15.3; p <0.0001), whereas the difference between Groups II and III did not reach significance (hazard ratio 1.36, 95% CI=0.41-4.45). The association of asymptomatic proximal DVT with increased mortality remained highly significant after adjusting for differences in baseline demographics and clinical variables. Risk factors significantly associated with the development of proximal DVT included advanced age (p=0.0005), prior DVT (p=0.001), and varicose veins (p=0.04). In conclusion, the high mortality rate in patients with asymptomatic proximal DVT underscores its clinical relevance and supports targeting of asymptomatic proximal DVT as an appropriate endpoint in clinical trials of thromboprophylaxis.     

Effect of indomethacin on edema following single and repetitive cerebral ischemia in the gerbil

BACKGROUND AND PURPOSE: Repetitive periods of cerebral ischemia result in more severe injury than a single period of ischemia of similar total duration. We investigated the possibility of prostaglandin mediation of this increased injury by attempting to modify brain edema formation with indomethacin pretreatment. METHODS: Under halothane/N2O anesthesia, groups of gerbils underwent bilateral carotid occlusion to induce forebrain ischemia. Group I underwent a single 15-minute period of carotid occlusion. Group II underwent three 5-minute periods of occlusion at hourly intervals. Groups III and IV were similar to groups I and II, respectively, but received 0.2 mg/kg indomethacin before carotid occlusion. Cortical and cerebellar water and sodium contents were determined in control animals (n = 6) at time zero and in experimental animals 24, 48, and 72 hours after ischemia (n = 6-10 gerbils/group at each time point). RESULTS: Cortical water and sodium contents in group II peaked 48 hours after insult (82.15 +/- 0.31% and 420 +/- 14 meq/kg dry wt, respectively) and were significantly higher than control and group I values at both 24 and 48 hours. Cortical water did not change from control in group I animals. Indomethacin pretreatment significantly attenuated increases in water and sodium content seen at 48 hours in gerbils undergoing repetitive ischemia (peak 80.02 +/- 0.45% and 300 +/- 39 meq/kg dry wt), but did not affect mortality. CONCLUSIONS: Indomethacin lessens edema after repetitive cerebral ischemia, suggesting that elevations of cyclooxygenase products are responsible, at least in part, for severe brain edema following repetitive ischemia.     

Association Between CT Angiogram Collaterals and CT Perfusion in Delayed Time Windows for Large Vessel Occlusion Ischemic Strokes

ObjectivesRecent endovascular trials have established the use of CT perfusion (CTP) in endovascular treatment selection for patients with large vessel occlusions (LVO). However, the relationship between CTP and collateral circulation is unclear in delayed time windows. We explored the relationship between CT Angiogram (CTA) collaterals and CTP parameters in delayed time windows (6-24 hours).Materials and MethodsWe utilized a single institutional, retrospective stroke registry of consecutive patients between May 2016 and May 2018 with anterior LVO with CTA and CTP imaging within 6-24 hours of stroke onset. We graded baseline collaterals on single phase CTA using modified Tan collateral score (0-3) and dichotomized into good (2-3) and poor (0-1) collaterals. We recorded automated CTP parameters, including estimated ischemic core (cerebral blood flow (CBF)<30%), penumbra (T_max>6 s), and mismatch ratio. We used Mann-Whitney test and linear regression to assess associations.ResultsWe included 48 patients with median age of 62 years (IQR= 52-72), median core of 17.5 mL (IQR=0-47), and median penumbra of 117.5 mL (IQR= 62-163.5). Patients with good collaterals had smaller median core (0 mL, IQR=0-12 mL vs. 40.5 mL, IQR=15-60 mL) (p < 0.001), smaller median penumbra (83.5 mL, IQR=43-135 mL vs. 142.5 mL, IQR=77-190 mL) (p = 0.04), larger median mismatch ratio (13.7, IQR=5.7-58.0 vs. 3.1, IQR=2.1-5.0) (p < 0.001), and lower median hypoperfusion intensity ratio (0.23, IQR=0-0.44 vs. 0.52, IQR=0.45-0.63) (p < 0.001) than patients with poor collaterals.ConclusionsIn delayed time window LVO patients, good CTA collaterals are significantly associated with smaller CTP core, smaller penumbra, larger mismatch ratio, and lower hypoperfusion intensity ratio. CTA collateral assessment could be a potential valuable surrogate to perfusion imaging, particularly in stroke centers where CTP is unavailable.     

Brain CT perfusion improves intracranial vessel occlusion detection on CT angiography

Background and purpose

To evaluate whether brain CT perfusion (CTP) aids in the detection of intracranial vessel occlusion on CT angiography (CTA) in acute ischemic stroke.

Fluctuations in plasma levels of thrombomodulin in patients with DIC.

Plasma thrombomodulin (TM) has attracted considerable attention as a marker of endothelial cell membrane injury. We examined fluctuations in plasma TM levels in patients receiving therapy for the disseminated intravascular coagulation syndrome (DIC) using an enzyme immunoassay. Sixty healthy controls and 18 patients with DIC were studied. The mean +/- SD of the TM values initially measured immediately after the onset of DIC was 42.00 +/- 20.85 ng/ml, which was markedly increased as compared with the control value of 15.36 +/- 4.85 ng/ml (p < 0.001). Fluctuations in the TM levels over time were studied after dividing the patients according to the presence or absence of improvement in the underlying disease and improvement or lack thereof in the coagulation findings. Group I showed improvement in both categories, Group II showed improvement only in the latter, and Group III showed no improvement in either category. In Group I, the mean +/- SD of initial measured TM levels was 37.02 +/- 10.12 ng/ml and the mean of final values decreased to 58.9% of the initial value. This decrease was significant by paired Student's t-test (p < 0.01). The initial value in Group II was 45.86 +/- 18.86 ng/ml and the final values increased to 117.0% of the initial values, this difference was not significant. The initial value in Group III was 44.48 +/- 21.53 ng/ml and the final values increased to 143.4% of the former. This increase was significant by paired Student's t-test (p < 0.05). The difference in % fluctuations between Group I and Group III was significant by Wilcoxon's test (p < 0.01). These results suggest that the measurement of plasma TM can be useful in the management of DIC.     

Bleeding risk of tirofiban, a nonpeptide GPIIb/IIIa platelet receptor antagonist in progressive stroke: an open pilot study.

BACKGROUND: Glycoprotein (gp) IIb/IIIa-receptor antagonists are highly effective antiplatelet agents with proven efficacy in the treatment of acute coronary and experimental cerebral ischemia. In this study we examined the rate of hemorrhagic transformation and major bleedings in patients with acute stroke treated with tirofiban, a nonpeptide gpIIb/IIIa antagonist. METHODS: Eighteen patients with progressively deteriorating acute ischemic stroke were treated with body-weight adjusted intravenous tirofiban for a mean period of 46 h and compared with a matched group of 17 acute ischemic clinically stable stroke patients. Cerebral hemorrhage was assessed by cranial imaging 6-10 days after symptom onset. RESULTS: No major intracranial hemorrhage was observed in either group. Clinically asymptomatic hemorrhagic infarctions type I/II/III were detected in 4/2/0 controls and in 4/1/1 patients of the tirofiban group, respectively (OR = 0.92; 95% CI 0.4-2.5). Clinical outcome scores were not different in both groups (p = 0.18). CONCLUSIONS: Tirofiban was not associated with a significantly increased cerebral bleeding rate in acute ischemic stroke. Randomized multicenter studies are needed to further evaluate the safety and efficacy of tirofiban in the treatment of acute stroke.     

大脑中动脉狭窄或闭塞患者侧支循环320排计算机断层扫描血管成像联合脑灌注成像研究

目的   利用320排计算机断层扫描血管成像（computed tomography angiography,CTA）及脑灌注成像（computed tomography perfusion imaging,CTP）探讨单侧大脑中动脉（middle cerebral artery,MCA）重度狭窄或闭塞的急性缺血性卒中患者侧支循环与脑灌注的关系。 方法  对72例单侧MCA重度狭窄或闭塞的急性缺血性卒中患者行头部320排CTA及CTP检查,根据有无侧支循环分为2组,对2组CTA和CTP情况进行分析比较。 结果  共入组72例患者,有侧支循环组58例,无侧支循环组14例。有侧支循环组38例（65.52%）MCA闭塞,无侧支循环组中5例（35.71%）MCA闭塞,两组差异有显著性（P=0.041）。有侧支循环组脑灌注代偿率高于无侧支循环组（68.97% vs 21.43%,χ2＝10.595,P＝0.001）;在CTP异常的68例患者中,有侧支循环者54例,无侧支循环者14例,有侧支循环组患侧的脑血容量［35.00（29.92,41.13）ml/100?g vs 26.25（18.23,37.18）ml/100?g］及脑血流量［（2.39±0.73）ml/100?g·min vs （1.75±0.72）ml/100?g·min］高于无侧支循环组,P分别为0.007和0.040。但2组患侧平均通过时间（mean transit time,MTT）及平均达峰时间（time to peak,TTP）差异无显著性。 结论  320排CTA联合CTP检查显示急性缺血性卒中患者中有侧支循环者脑灌注代偿率高,而且其脑血容量和脑血流量均高于无侧支循环者。     

Dynamic tracking of acute ischemic tissue fates using improved unsupervised ISODATA analysis of high-resolution quantitative perfusion and diffusion data.

High-resolution (200 x 200 x 1,500 microm3) imaging was performed to derive quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps in stroke rats (permanent occlusion) every 30 minutes up to 3 hours after occlusion onset, followed by histology at 24 hours. An improved automated iterative-self-organizing-data-analysis-algorithm (ISODATA) was developed to dynamically track ischemic tissue fate on a pixel-by-pixel basis during the acute phase. ISODATA-resolved clusters were overlaid on the CBF-ADC scatterplots and image spaces. Tissue volume ADC, and CBF of each ISODATA cluster were derived. In contrast to the single-cluster normal left hemisphere (ADC = 0.74 +/- 0.02 x 10(-3) mm2/s, CBF = 1.36 +/- 0.22 mL g(-1)min(-1), mean +/- SD, n = 8), the right ischemic hemisphere exhibited three ISODATA clusters, namely: "normal" (normal ADC and CBF), "ischemic core" (low CBF and ADC), and at-risk "perfusion-diffusion mismatch" (low CBF but normal ADC). At 180 minutes, the mismatch disappeared in five rats (Group I, 180-minute "core" lesion volume = 255 +/- 62 mm3 and 24-hour infarct volume = 253 +/- 55 mm3, P > 0.05), while a substantial mismatch persisted in three rats (Group II, 180-minute CBF-abnormal volume = 198 +/- 7 mm3 and 24-hour infarct volume 148 +/- 18 mm3, P < 0.05). The CBF (0.3 +/- 0.09 mL g(-1)min(-1)) of the "persistent mismatch" (Group II, 0.3 +/- 0.09 mL g(-1)min(-1)) was above the CBF viability threshold (0.2 to 0.3 mL g(-1)min(-1)) throughout and its ADC (0.70 +/- 0.03 x 10(-3) mm2/s) did not decrease as ischemia progressed. In contrast, the CBF (0.08 +/- 0.03 mL g(-1)min(-1)) of the analogous brain region in Group I was below the CBF viability threshold, and its ADC gradually decreased from 0.63 +/- 0.05 to 0.43 +/- 0.03 x 10(-3) mm2/s (ADC viability threshold = 0.53 +/- 0.02 x 10(-3) mm2/s). The modified ISODATA analysis of the ADC and CBF tissue characteristics during the acute phase could provide a useful and unbiased means to characterize and predict tissue fates in ischemic brain injury and to monitor therapeutic intervention.     

Feasibility of deconvolution-based multiphase CT angiography perfusion maps in acute ischemic stroke: Simulation and concordance with CT perfusion

ObjectivesIntegration of CT perfusion (CTP) with requisite non-contrast CT and CT angiography (CTA) stroke imaging may allow efficient stroke lesion volume measurement. Using surrogate images from CTP, we simulated the feasibility of using multiphase CTA (mCTA) to generate perfusion maps and assess target mismatch profiles.Materials and methodsPatients with acute ischemic stroke who received admission CTP were included in this study. Four CTP images (surrogate mCTA, one pre-contrast and three post-contrast, starting at the arterial peak then at 8 s intervals) were selected according to the CTP arterial time-density curve to simulate non-contrast CT and mCTA images. Cerebral blood flow (CBF) and Tmax maps were calculated using the same model-based deconvolution algorithm for the standard CTP and surrogate mCTA studies. Infarct and penumbra were delineated with CBF < 20% and Tmax > 6 s threshold, respectively. Classification accuracy of surrogate mCTA target mismatch (infarct <70 ml; penumbra ≥15 ml; mismatch ratio ≥1.8) with respect to standard CTP was assessed. Agreement between infarct and penumbra volumes from standard CTP and surrogate mCTA maps were evaluated by Bland-Altman analysis.ResultsOf 34 included patients, 28 had target mismatch and 6 did not by standard CTP. Accuracy of classifying target mismatch profiles with surrogate mCTA was 79% with respect to that from standard CTP. Mean  ±  standard deviation of differences (standard CTP minus surrogate mCTA) of infarct and penumbra volumes were 9.8 ± 14.8 ml and 20.1 ± 45.4 ml, respectively.ConclusionsSurrogate mCTA ischemic lesion volumes agreed with those from standard CTP and may be an efficient alternative when CTP is not practical.     

Assessment of ophthalmic artery collateral pathway in the hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis

The role of ophthalmic artery collateral pathway in hemispheric hemodynamics in patients with severe carotid stenosis is controversial. The aim of the present study was to address this question comparing the asymmetry of the velocity in middle and anterior cerebral arteries (MCAs and ACAs) and cerebrovascular reactivity (CVR) in MCA on stenotic side in the patients with unilateral severe stenosis of internal carotid artery (ICA) in patients with and without ophthalmic artery collateral pathway. The cohort of 118 patients with carotid stenosis was prospectively assembled. Fifty patients who had severe unilateral ICA stenosis (71%-99%) by Duplex Ultrasound (DUS) were observed by transcranial Doppler (TCD). Cerebral blood flow velocity in MCA and ACA in both sides, direction of blood flow in ophthalmic artery (OA) and CVR on the side of stenosis were determined. There were 14 patients with retrograde blood flow in OA (Group I). The remaining 36 patients with anterograde flow in OA composed Group II. The degree of interarterial asymmetry of peak and mean velocity (Vpeak and Vmean) in MCA and ACA and CVR in MCA were compared in both groups. The degree of ACA asymmetry by Vpeak was 44.0% +/- 6.9% in Group I and 38.3% +/- 3.9% in Group II (p = 0.49), by Vmean 40.3% +/- 6.7% and 36.6% +/- 3.8% (p = 0.63) respectively. The degree of MCA asymmetry by Vpeak was 24.2% +/- 2.8% in Group I and 19.5% +/- 5.0% in Group II (p = 0.42), by Vmean 23.5% +/- 2.9% and 20.6% +/- 5.1% (p = 0.63) respectively. CVR in Group I was 26.1% +/- 6.1%, in Group II 29.0% +/- 6.7% (p = 0.65). The ophthalmic collateral pathway has no influence on hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis.     

Correlation between cerebral blood flow, somatosensory evoked potentials, CT scan grade and neurological grade in patients with subarachnoid hemorrhage.

Cerebral blood flow (CBF) and central conduction time (CCT) were recorded from 58 subarachnoid hemorrhage patients and from 49 age-matched controls. CBF was calculated following Xenon inhalation and CCT was determined from somatosensory evoked potentials (SSEP's) following median nerve stimulation. Each patient had a CT scan on the day of admission which was graded from I-IV. CBF, CCT and neurological grade (Hunt and Hess classification) were concomitantly recorded 1, 4, 7 and 14 days after subarachnoid hemorrhage. Mean CBF was highest in patients with neurological grades I and II (48.6 +/- 12.3 and 48.1 +/- 10.3 ml/100gm/min respectively) and lowest in patients with neurological grade IV (37.3 +/- 9.6 ml/100gm/min). Patients in neurological grade I or II had mean CBF and CCT measurements that were significantly different from those obtained from patients in neurological grade IV (P less than 0.05). Neurological grade and CT scan grade correlated with CBF (P less than 0.0001) better than CCT (P = 0.015). Unexpectedly low CBF's from patients in neurological grades II and III (less than 37 and less than 31 ml/100gm/min respectively) failed to significantly prolong CCT suggesting CCT is unable to detect marginal ischemia. A significant correlation between CBF and CCT occurred only when CBF was less than 30 ml/100gm/min (R = 0.75, P = 0.05). It appears that prolonged CCT is associated with a drop in CBF only when CBF drops below a certain threshold.     

Effect of olanzapine on cognition during treatment of behavioral and psychiatric symptoms in patients with dementia: a post-hoc analysis

OBJECTIVE: This study was conducted to determine the effect of olanzapine treatment on cognition in elderly patients with behavioral and psychiatric symptoms (BPSD) associated with dementia. METHODS: This was a post-hoc analysis of three randomized double-blind, clinical trials of olanzapine (n = 682) vs placebo (n = 257) in dementia patients with BPSD in long-term or continuing-care settings. One study was 6 weeks long; the other two were 10 weeks duration, and their data were combined. Patients were subgrouped according to baseline Mini Mental State Examination (MMSE) scores: Group I = 23-26; Group II = 19-22; Group III = 14-18; Group IV = 7-13; Group V = 1-6. BPSD was assessed by the Neuropsychiatric Inventory (NPI). RESULTS: Within-treatment group cognitive decline in patients was significant in the combined studies, but not in the 6-week study. Between-treatment cognitive changes were non-significant in the 6-week study, but showed a statistical trend in the combined studies (olanzapine, -0.78 +/- 0.19 vs placebo, -0.32 +/- 0.25; p = 0.06). In the subgroup analysis, there was a significant between-treatment difference in cognitive changes in MMSE subgroup IV in the combined studies (olanzapine, -0.63 +/- 0.26 vs placebo, 0.27 +/- 0.41, p = 0.04). Improvement in BPSD was correlated with better cognitive outcome (r = -0.2; p < 0.01). CONCLUSIONS: Although the overall differences in cognitive changes in patients treated with olanzapine vs placebo were small and non-significant, negative effects on cognition in some patients cannot be excluded, especially in patients with more pronounced cognitive decline or whose behavioral and psychiatric symptoms are not responding to treatment.     

The influence of nifedipine on blood-brain barrier permeability during bicuculline-induced seizures.

The influence of the calcium channel blocker nifedipine plus bicuculline-induced seizures on the permeability of the blood-brain barrier to protein was studied in rats. Evans-blue was used as a blood-brain barrier tracer. Four groups of rats were studied. Group I: control, Group II: Nifedipine, Group III: bicuculline-induced seizure, Group IV: Nifedipine + seizure. The mean value for Evans-blue dye in the brain was found to be 0.23+/-0.03 mg/g in control animals and 0.32+/-0.06 mg/g in the group of all rats during nifedipine-induced hypotension. This difference between control and hypotensive animals was not statistically significant (p < 0.5). Mean value for Evans-blue dye in the brain was found to be 1.4+/-0.3 mg/g in bicuculline-induced seizure, and 0.73+/-40.2 mg/g in the group of nifedipine plus bicuculline-induced seizures. This difference between Group III and Group IV was found statistically significant (p < .01). The calcium channel blocker nifedipine significantly prevents the blood brain barrier disruption during bicuculline-induced seizure.     

The early protective effects of L-arginine and Ng-nitro-L-arginine methyl ester after experimental acute spinal cord injury. A light and electron microscopic study.

The purpose of this study was to investigate the early protective effects of L-arginine and Ng-nitro-L-arginine methyl ester (L-NAME) after acute spinal cord injury. Acute spinal cord injury was performed by epidural application of an aneurysm clip at thoracic (T) 7 - 11 level. L-arginine at a dose of 750 microg/kg/min was administered 10 min before acute spinal cord injury and continued for 30 min to 10 animals (Group II). L-NAME at a dose of 250 microg/kg/min was administered 10 min before acute spinal cord injury and continued for 30 min to 10 animals (Group III). No drug was administered to 10 animals after acute spinal cord injury (Group I). Light and electron microscopic analysis were performed in all of the groups. Oedema of perineural, axoplasm or white matter in the L-arginine-treated group was less than in Group I and Group III. Thickening in the walls of the arterioles and venules in the L-arginine-treated group was much milder than in Group I and Group III. Degeneration of myelinated axons in the L-arginine-treated group was milder than in the control group. But there was no different between Group II and Group III.     

Hypertension with or without hemodilution after cardiac arrest in dogs

We studied blood flow-promoting therapies after cardiac arrest in 18 dogs. Our model consisted of ventricular fibrillation (no blood flow) lasting 12.5 minutes, controlled reperfusion with cardiopulmonary bypass and defibrillation within 5 minutes, controlled intermittent positive-pressure ventilation to 20 hours, and intensive care to 96 hours. Group I (control, n = 6) dogs were reperfused under conditions of normotension (mean arterial blood pressure 100 mm Hg) and normal hematocrit (greater than or equal to 35%). Group II (n = 6) and III (n = 6) dogs were treated with norepinephrine at the beginning of reperfusion to induce hypertension for 4 hours. In addition, group III dogs received hypervolemic hemodilution to a hematocrit of 20% using dextran 40. There were no differences in the time to recovery of electroencephalographic activity among groups. All six group I dogs remained severely disabled; in groups II and III combined, six of the 12 dogs achieved good outcome (p less than 0.01). Some regional histopathologic damage scores at 96 hours were better in groups II and/or III than in group I (neocortex: p less than 0.05 group II different from group I; hippocampus: p less than 0.01 both groups II and III different from group I). Total histopathologic damage scores were similar among the groups. A hypertensive bout with a peak mean arterial blood pressure of greater than or equal to 200 mm Hg beginning 1-5 minutes after the start of reperfusion was correlated with good outcome (p less than 0.01). Our results support the use of an initial bout of severe hypertension, but not the use of delayed hemodilution.     

Benefits of a prehospital stroke code system. Feasibility and efficacy in the first year of clinical practice in Barcelona, Spain

BACKGROUND AND OBJECTIVES: Hospital admission delay is a main limiting factor for effective thrombolytic therapy in stroke patients. We developed a stroke code system for rapid request of emergency transportation to the hospital and a priority availability of the attending neurologist on the patient's arrival at the Emergency Department (ED). METHODS: Over a 1-year period, a 24-hour telephone hotline between the attending neurologist and the Barcelona public emergency coordination service was established. Priority 1 (P1) was defined as a patient with symptoms suggestive of acute stroke with onset of less than 3 h, in which case immediate transportation service and rapid ED reception was organized. Data from patients in the P1 group (n = 39) and patients without activation of the stroke code (P0) (n = 181) were compared. RESULTS: There were significant differences between P1 and P0 groups in mean time from ED arrival to request for neurologic assessment (4.4 +/- 19.5 vs. 194.7 +/- 244.9 min, p < 0.001), from arrival to neurologic examination (12.6 +/- 21.1 vs. 225.3 +/- 258.2 min, p < 0.005), and from arrival to performance of brain CT scan (35.5 +/- 34.9 vs.120.3 +/- 143.2 min, p < 0.001), and also in the number of patients treated with thrombolytic agents (19 vs. 4.5%, p < 0.003). There were no differences between groups in the time elapsed from stroke onset to ED arrival. CONCLUSIONS: Activation of the stroke code was effective in increasing the percentage of patients treated with thrombolytic drugs and also in shortening the delay from ED arrival until neurologic assessment and from ED arrival until brain CT.     

Carbamazepine/valproic acid interaction in man and rhesus monkey

Sodium valproate (VPA) was administered for 1 week (1 g b.i.d.) to seven epileptic patients receiving chronic carbamazepine (CBZ) therapy. Steady-state CBZ levels determined before and after VPA therapy were reduced by 3-59% in six patients and were unchanged in one patient. The plasma concentration ratio of carbamazepine-10,11-epoxide ( CBZE ) to CBZ increased in all patients by 11-500%. The plasma binding of CBZ was determined in six healthy volunteers given a single 400 mg CBZ dose with and without the coadministration of 1 g VPA in a cross-over design. The mean CBZ free-fraction was increased in three of the subjects (p = 0.008-0.031), decreased in one subject (p less than 0.002), and remained unchanged in two subjects when VPA was administered. Four male rhesus monkeys were infused intravenously with CBZ (15 mg h-1) for 5 days and then three consecutive 24-h infusions were given: I, CBZ alone; II, CBZ with 75 mg h-1 VPA; III, CBZ with 150 mg h-1 VPA. The mean free-fraction of CBZ and CBZE increased during infusions II and III from 31.5 +/- 2.7% to 33.6 +/- 2.6% (p less than 0.05) and 37.7 +/- 1.3% (p less than 0.01) for CBZ and from 46.9 +/- 9.2% to 53.6 +/- 5.7% (p greater than 0.05) and 60.1 +/- 4.0% (p less than 0.01) for CBZE . The clearance of free CBZ declined from 7.96 +/- 1.75 to 4.84 +/- 1.26 (p less than 0.01) and 4.12 +/- 1.75 (p less than 0.01) 1 kg-1h-1 during infusions II and III, respectively. The mean free CBZE /CBZ ratio increased from 0.12 +/- 0.03 to 0.24 +/- 0.03 and 0.36 +/- 0.04 during infusions II and III, respectively (p less than 0.001). These findings indicate a decrease in the elimination clearance of CBZE possibly coupled with a decrease in its formation clearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic perfusion imaging

BACKGROUND: Stroke management would benefit from a broadly available imaging tool that detects perfusion deficits in patients with acute stroke. OBJECTIVE: To determine the role of dynamic, single-slice computed tomographic (CT) perfusion imaging (CTP) in the assessment of acute middle cerebral artery stroke. DESIGN AND PATIENTS: Imaging with CTP and CT within the first 6 hours of symptom onset and before the start of treatment in a consecutive clinical series of 22 patients (mean age, 68.3 years; 14 women; studied within 143 +/- 96 minutes of stroke onset). SETTING: A stroke unit in a university hospital. MAIN OUTCOME MEASURES: Area of the perfusion deficit (nAP(0)) from time-to-peak maps, hemispheric lesion area from follow-up CT (HLA(F)), final infarct volume, and stroke recovery (National Institutes of Health Stroke Scale scores). RESULTS: Eighteen patients had perfusion deficits in the middle cerebral artery territory and corresponding hypoattenuation in follow-up CT. Three patients with normal CTP findings showed lacunar infarctions or normal findings on follow-up CT. In 1 patient, CTP did not reveal a territorial deficit above the imaging slice. The overall sensitivity and specificity of CTP for the detection of perfusion deficits in patients with proven territorial infarction (n = 18) on follow-up CT were 95% and 100%, respectively. The nAP(0) was significantly correlated with the National Institutes of Health Stroke Scale score at admission (P<.003) and the HLA(F) (P<.001). Different stroke patterns were identified in patients with follow-up CTP (n = 10): (1) initial perfusion deficit and partial nutritional reperfusion (nAP(0)>HLA(F); n = 6), (2) initial perfusion deficit and nonnutritional reperfusion (nAP( 0)>/=HLA(F); n = 2), and (3) initial perfusion deficit without reperfusion (nAP(0)>/=HLA(F); n = 2). CONCLUSIONS: Computed tomographic perfusion imaging detects major perfusion deficits in the middle cerebral artery territory. Because CTP is broadly available, it may play a role in acute stroke management. Arch Neurol. 2000;57:1161-1166