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1.
J Neurol Neurosurg Psychiatry ; 86(12): 1319-23, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25589782

ABSTRACT

BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). CONCLUSIONS: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. TRIAL REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.


Subject(s)
Cerebral Hemorrhage/mortality , Functional Laterality , Aged , Blood Pressure/drug effects , Cause of Death , Cerebral Hemorrhage/physiopathology , Disability Evaluation , Endpoint Determination , Female , Glasgow Coma Scale , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pilot Projects , Prognosis , Survivors , Treatment Outcome
2.
Int J Stroke ; 10(4): 553-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24138577

ABSTRACT

BACKGROUND: Perfusion computed tomography is becoming more widely used as a clinical imaging tool to predict potentially salvageable tissue (ischemic penumbra) after ischemic stroke and guide reperfusion therapies. AIMS: The study aims to determine whether there are important changes in perfusion computed tomography thresholds defining ischemic penumbra and infarct core over time following stroke. METHODS: Permanent middle cerebral artery occlusion was performed in adult outbred Wistar rats (n = 6) and serial perfusion computed tomography scans were taken every 30 mins for 2 h. To define infarction thresholds at 1 h and 2 h post-stroke, separate groups of rats underwent 1 h (n = 6) and 2 h (n = 6) of middle cerebral artery occlusion followed by reperfusion. Infarct volumes were defined by histology at 24 h. Co-registration with perfusion computed tomography maps (cerebral blood flow, cerebral blood volume, and mean transit time) permitted pixel-based analysis of thresholds defining infarction, using receiver operating characteristic curves. RESULTS: Relative cerebral blood flow was the perfusion computed tomography parameter that most accurately predicted penumbra (area under the curve = 0.698) and also infarct core (area under the curve = 0.750). A relative cerebral blood flow threshold of < 75% of mean contralateral cerebral blood flow most accurately predicted penumbral tissue at 0.5 h (area under the curve = 0.660), 1 h (area under the curve = 0.659), 1.5 h (area under the curve = 0.636), and 2 h (area under the curve = 0.664) after stroke onset. A relative cerebral blood flow threshold of < 55% of mean contralateral most accurately predicted infarct core at 1 h (area under the curve = 0.765) and at 2 h (area under the curve = 0.689) after middle cerebral artery occlusion. CONCLUSIONS: The data provide perfusion computed tomography defined relative cerebral blood flow thresholds for infarct core and ischemic penumbra within the first two hours after experimental stroke in rats. These thresholds were shown to be stable to define the volume of infarct core and penumbra within this time window.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain/diagnostic imaging , Perfusion Imaging/methods , Tomography, X-Ray Computed/methods , Animals , Animals, Outbred Strains , Brain/physiopathology , Brain Ischemia/physiopathology , Cerebrovascular Circulation/physiology , Disease Models, Animal , Infarction, Middle Cerebral Artery , ROC Curve , Rats, Wistar , Stroke , Time Factors
3.
Neurology ; 75(12): 1040-7, 2010 Sep 21.
Article in English | MEDLINE | ID: mdl-20720188

ABSTRACT

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.


Subject(s)
Brain Ischemia/drug therapy , Brain/drug effects , Stroke/drug therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Atrophy/drug therapy , Atrophy/pathology , Brain/pathology , Brain Ischemia/pathology , Brain Mapping , Diffusion Magnetic Resonance Imaging , Female , Fibrinolytic Agents/therapeutic use , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Prospective Studies , Stroke/pathology , Time Factors , Treatment Outcome
4.
Lancet ; 375(9727): 1695-703, 2010 May 15.
Article in English | MEDLINE | ID: mdl-20472172

ABSTRACT

BACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. METHODS: We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. FINDINGS: Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. INTERPRETATION: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. FUNDING: None.


Subject(s)
Fibrinolytic Agents/administration & dosage , Stroke/drug therapy , Tissue Plasminogen Activator/administration & dosage , Fibrinolytic Agents/adverse effects , Humans , Infusions, Intravenous , Injections, Intravenous , Intracranial Hemorrhages/chemically induced , Randomized Controlled Trials as Topic , Recombinant Proteins/administration & dosage , Time Factors , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
5.
Article in English | MEDLINE | ID: mdl-20127546

ABSTRACT

Fusarium ear rot, caused by Fusarium verticillioides, is one of the most common diseases of maize, causing yield and quality reductions and contamination of grain by fumonisins and other mycotoxins. Drought stress and various insects have been implicated as factors affecting disease severity. Field studies were conducted to evaluate the interactions and relative influences of drought stress, insect infestation, and planting date upon Fusarium ear rot severity and fumonisin B1 contamination. Three hybrids varying in partial resistance to Fusarium ear rot were sown on three planting dates and subjected to four irrigation regimes to induce differing levels of drought stress. A foliar-spray insecticide treatment was imposed to induce differing levels of insect injury. Populations of thrips (Frankliniella spp.), damage by corn earworm (Helicoverpa zeae), Fusarium ear rot symptoms, and fumonisin B1 levels were assessed. There were significant effects of hybrid, planting date, insecticide treatment, and drought stress on Fusarium ear rot symptoms and fumonisin B1 contamination, and these factors also had significant interacting effects. The most influential factors were hybrid and insecticide treatment, but their effects were influenced by planting date and drought stress. The more resistant hybrids and the insecticide-treated plots consistently had lower Fusarium ear rot severity and fumonisin B1 contamination. Later planting dates typically had higher thrips populations, more Fusarium ear rot, and higher levels of fumonisin B1. Insect activity was significantly correlated with disease severity and fumonisin contamination, and the correlations were strongest for thrips. The results of this study confirm the influence of thrips on Fusarium ear rot severity in California, USA, and also establish a strong association between thrips and fumonisin B1 levels.


Subject(s)
Fumonisins/analysis , Fusarium/isolation & purification , Insecta/growth & development , Plant Diseases/microbiology , Stress, Physiological , Zea mays/chemistry , Zea mays/microbiology , Agriculture/methods , Animals , California , Chimera/microbiology , Chimera/parasitology , Crops, Agricultural/chemistry , Crops, Agricultural/microbiology , Crops, Agricultural/parasitology , Crops, Agricultural/physiology , Droughts , Food Contamination/prevention & control , Fusarium/growth & development , Hybrid Vigor , Insecticides/administration & dosage , Moths/growth & development , Plant Diseases/genetics , Plant Diseases/prevention & control , Seasons , Seeds/microbiology , Severity of Illness Index , Zea mays/parasitology , Zea mays/physiology
6.
Cerebrovasc Dis ; 29(1): 14-21, 2010.
Article in English | MEDLINE | ID: mdl-19893307

ABSTRACT

BACKGROUND: Previous data have suggested that diabetes and hyperglycemia predict poor outcome following stroke. We studied the prognostic impact of diabetes and admission blood glucose in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective randomized placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. A preexisting diagnosis of diabetes was noted and baseline serum glucose was measured. RESULTS: Intravenous tPA attenuated infarct growth in non-diabetics, but not in diabetics (p = 0.029). In the tPA treatment group, admission blood glucose was higher among patients with poor functional outcome (p = 0.002). CONCLUSIONS: Diabetes and hyperglycemia attenuate the effects of tPA on infarct evolution. Future thrombolytic trials should consider randomizing patients by subgroups based on diabetic status and serum glucose levels.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/diagnosis , Fibrinolytic Agents/administration & dosage , Hyperglycemia/diagnosis , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Australia , Diabetes Mellitus/blood , Drug Administration Schedule , Europe , Female , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Infusions, Intravenous , Linear Models , Magnetic Resonance Angiography , Male , Middle Aged , New Zealand , Patient Admission , Patient Selection , Prospective Studies , Recovery of Function , Risk Assessment , Risk Factors , Stroke/blood , Stroke/complications , Stroke/pathology , Stroke/physiopathology , Treatment Outcome
7.
Neurology ; 73(23): 1963-8, 2009 Dec 08.
Article in English | MEDLINE | ID: mdl-19996072

ABSTRACT

BACKGROUND: Uncertainty surrounds the effects of cerebral edema on outcomes in intracerebral hemorrhage (ICH). METHODS: We used data from the INTERACT trial to determine the predictors and prognostic significance of "perihematomal" edema over 72 hours after ICH. INTERACT included 404 patients with CT-confirmed ICH and elevated systolic blood pressure (BP) (150-220 mm Hg) who had the capacity to commence BP lowering treatment within 6 hours of ICH. Baseline and repeat CT (24 and 72 hours) were performed using standardized techniques, with digital images analyzed centrally. Predictors of growth in edema were determined using generalized estimating equations, and its effects on clinical outcomes were estimated using a logistic regression model. RESULTS: Overall, 270 patients had 3 sequential CT scans available for analyses. At baseline, there was a highly significant correlation between hematoma and perihematomal edema volumes (r(2) = 0.45). Lower systolic BP and baseline hematoma volume were independently associated with absolute increase in perihematomal edema volume. History of hypertension, baseline hematoma volume, and earlier time from onset to CT were independently associated with relative increase in edema volume. Both absolute and relative increases in perihematomal edema growth were significantly associated with death or dependency at 90 days after adjustment for age, gender, and randomized treatment, but not when additionally adjusted for baseline hematoma volume. CONCLUSIONS: The degree of, and growth in, perihematomal edema are strongly related to the size of the underlying hematoma of acute intracerebral hemorrhage, and do not appear to have a major independent effect in determining the outcome from this condition.


Subject(s)
Brain Edema/complications , Cerebral Hemorrhage/etiology , Hematoma/complications , Acute Disease , Aged , Brain Edema/pathology , Cerebral Hemorrhage/pathology , Female , Hematoma/pathology , Humans , Internationality , Male , Middle Aged , Pilot Projects , Prospective Studies
8.
J Allied Health ; 38(2): e69-74, 2009.
Article in English | MEDLINE | ID: mdl-19753416

ABSTRACT

Research is often scholarship driven and the findings are then channelled into the practice community on the assumption that it is utilising an evidence-based approach in its service delivery. Because of persisting difficulties in bridging the practice-evidence gap in health care, there has been a call for more active links between researchers and practitioners. The authors were part of an interprofessional research initiative which originated from within an acute stroke clinical community. This research initiative aimed to encourage active participation of health professionals employed in the clinical setting and active collaboration across departments and institutions. On reflection, it appeared that in setting up an interprofessional, practice-driven research collaborative, achievements included the instigation of a community of inquiry and the affording of opportunities for allied health professionals to be actively involved in research projects directly related to their clinical setting. Strategies were put in place to overcome the challenges faced which included managing a demanding and frequently changing workplace, and overcoming differences in professional knowledge, skills and expertise. From our experience, we found that interprofessional, practice-driven research can encourage allied health professionals to bridge the practice-evidence gap, and is a worthwhile experience which we would encourage others to consider.


Subject(s)
Interprofessional Relations , Practice Patterns, Physicians' , Research , Stroke , Cooperative Behavior , Evidence-Based Practice , Health Personnel , Hospitals, Public , Humans , New South Wales , Pilot Projects , Research Personnel
9.
Neurology ; 72(10): 915-21, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19273826

ABSTRACT

BACKGROUND: Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase. METHODS: We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization. RESULTS: Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction > or = 8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours. CONCLUSIONS: Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.


Subject(s)
Brain Ischemia/complications , Plasminogen Activators/therapeutic use , Stroke/drug therapy , Stroke/etiology , Tissue Plasminogen Activator/therapeutic use , Aged , Cerebral Angiography , Cerebrovascular Circulation , Dose-Response Relationship, Drug , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Plasminogen Activators/administration & dosage , Prospective Studies , Regression Analysis , Tenecteplase , Tissue Plasminogen Activator/administration & dosage , Tomography, X-Ray Computed , Treatment Outcome
10.
J Clin Neurosci ; 16(2): 178-87, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19097909

ABSTRACT

The aim of thrombolytic therapy after acute ischemic stroke is salvage of the ischemic penumbra. Several imaging techniques have been used to identify the penumbra in patients who may benefit from reperfusion beyond the currently narrow 3-hour time-window for thrombolysis. We discuss the advantages and disadvantages of positron emission tomography (PET), single photon emission computed tomography (SPECT), MRI and CT scans. We comment on concepts of clinical-imaging mismatch models and we explore the implications for clinical trials.


Subject(s)
Diagnostic Imaging/adverse effects , Diagnostic Imaging/methods , Risk , Stroke/diagnosis , Clinical Trials as Topic , Humans , Reperfusion/methods
11.
Neurology ; 68(10): 730-6, 2007 Mar 06.
Article in English | MEDLINE | ID: mdl-17339580

ABSTRACT

OBJECTIVES: To correlate the two types of early ischemic change on noncontrast CT (NCCT) (parenchymal hypoattenuation [PH] and isolated focal swelling [IFS]) with concurrent assessment of cerebral perfusion and to compare their rates of progression to infarction. METHODS: We assessed cortical regions on NCCT for early ischemic change. Quantitative perfusion values were calculated for cortical regions from acute CT perfusion (CTP) maps of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT). Reperfusion and presence of infarction were determined from follow-up MRI. RESULTS: We studied 40 patients with sub-6 hour anterior circulation ischemic stroke; 19 received IV recombinant tissue plasminogen activator. Of the 202 regions acutely hypoperfused on CTP, 123 were normal on NCCT, 58 had PH, and 21 had IFS. Acute CBV was low in PH regions, and elevated in IFS regions. Acute CBF was reduced in IFS regions, but more so in PH regions. Progression to infarction occurred in virtually all PH regions, but IFS regions had much lower rates of infarction with major reperfusion. Acute CBV in hypoperfused normal NCCT regions ranged from reduced to elevated, with substantially differing risk of infarction. CONCLUSIONS: Isolated focal swelling identifies penumbral tissue and parenchymal hypoattenuation identifies infarct core. Although this has prognostic implications when assessing patient suitability for thrombolytic therapy, the majority of acutely hypoperfused regions appear normal on noncontrast CT. Perfusion CT can stratify the level of risk of subsequent infarction for normal-appearing regions on noncontrast CT.


Subject(s)
Blood Volume , Cerebral Infarction/diagnostic imaging , Cerebrovascular Circulation , Stroke/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Brain Edema/diagnostic imaging , Brain Ischemia/complications , Brain Ischemia/diagnostic imaging , Brain Mapping , Disease Progression , Female , Humans , Logistic Models , Male , Middle Aged , Perfusion , Stroke/etiology
12.
Neurology ; 65(9): 1382-7, 2005 Nov 08.
Article in English | MEDLINE | ID: mdl-16275824

ABSTRACT

BACKGROUND: Elevated hematocrit (Hct) contributes to blood viscosity and has an adverse effect in acute stroke. The authors investigated the influence of Hct on tissue fate using serial MRI in acute stroke patients. METHODS: The effects of Hct on reperfusion, penumbral salvage, and infarct expansion in 64 patients presenting within 24 hours of stroke onset were measured. MRI was performed at baseline (< 24 hours), days 3 to 5, and 90 days from stroke onset. RESULTS: Median Hct was 42% with a bimodal distribution. There was a strong inverse relationship between Hct and reperfusion (Spearman rho = -0.74, p < 0.0001). The odds of major reperfusion (> 50% resolution of the baseline perfusion-weighted imaging deficit) were significantly lower with increasing Hct (odds ratio [OR] = 0.53; 95% CI = 0.97 to 1.00), independent of age, perfusion, and diffusion lesion volumes and recombinant tissue plasminogen activator (rtPA) administration. There was a trend toward reduced penumbral salvage at days 3 to 5 with increasing Hct (p = 0.06, 95% CI = -4.76 to 0.14). An increasing Hct was a significant predictor of infarct growth (OR = 1.26, 95% CI = 1.00 to 1.59), independent of baseline perfusion and diffusion volumes and glucose. The effect of Hct on reperfusion and infarct expansion was similar irrespective of rtPA administration (p = 0.31) and independent of smoking status. CONCLUSIONS: Higher hematocrit (Hct) values have a significant independent association with reduced reperfusion and greater infarct size after ischemic stroke. An elevated Hct may also be a potential physiologic determinant of reduced penumbral salvage.


Subject(s)
Brain Ischemia/physiopathology , Cerebral Infarction/physiopathology , Polycythemia/complications , Reperfusion Injury/physiopathology , Stroke/physiopathology , Adult , Aged , Aged, 80 and over , Blood Viscosity , Brain/blood supply , Brain/pathology , Brain/physiopathology , Causality , Cerebral Arteries/physiopathology , Cerebral Infarction/diagnosis , Cerebrovascular Circulation , Disease Progression , Hematocrit , Humans , Logistic Models , Magnetic Resonance Imaging , Middle Aged , Predictive Value of Tests , Stroke/diagnosis
13.
AJNR Am J Neuroradiol ; 22(7): 1260-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11498412

ABSTRACT

BACKGROUND AND PURPOSE: Prediction of the regions of the ischemic penumbra that are likely to progress to infarction is of great clinical interest. Whether lowered apparent diffusion coefficient (ADC) values were present in the ischemic penumbra of patients presenting with acute ischemic stroke and were specific to regions of the penumbra that proceeded to infarction was investigated. METHODS: Nineteen patients with hemispheric stroke of less than 6 hours' onset and with acute scans showing a perfusion lesion greater than a diffusion lesion (ischemic penumbra) were studied. Scans also were performed subacutely (days 3 to 5) and at outcome (day 90). The outcome scan was used to identify regions of the penumbra that proceeded to infarction. RESULTS: The ADC ratios were significantly reduced (P <.00001) in regions of the penumbra that progressed to infarction on the outcome scan compared with those that remained normal. In regions that showed transition to infarction, the mean ADC ratios were typically 0.75 to 0.90. CONCLUSION: Intermediate ADC values are present in the ischemic penumbra and are indicative of tissue at risk of infarction.


Subject(s)
Brain Ischemia/diagnosis , Cerebral Infarction/diagnosis , Image Enhancement , Magnetic Resonance Imaging , Aged , Aged, 80 and over , Brain/pathology , Brain/physiopathology , Brain Ischemia/physiopathology , Cerebral Infarction/physiopathology , Diffusion , Echo-Planar Imaging , Female , Humans , Male , Middle Aged , Prognosis , Risk , Sensitivity and Specificity , Tissue Survival/physiology
15.
Stroke ; 32(7): 1581-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11441205

ABSTRACT

BACKGROUND AND PURPOSE: In ischemic stroke, perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) provide important pathophysiological information. A PWI>DWI mismatch pattern suggests the presence of salvageable tissue. However, improved methods for distinguishing PWI>DWI mismatch tissue that is critically hypoperfused from benign oligemia are required. METHODS: We investigated the usefulness of maps of relative cerebral blood flow (rCBF), volume (rCBV), and mean transit time (rMTT) to predict transition to infarction in hyperacute (<6 hours) stroke patients with PWI>DWI mismatch patterns. Semiquantitative color-thresholded analysis was used to measure hypoperfusion volumes, including increasing color signal intensity thresholds of rMTT delay, which were compared with infarct expansion, outcome infarct size, and clinical status. RESULTS: Acute rCBF lesion volume had the strongest correlation with final infarct size (r=0.91, P<0.001) and clinical outcome (r=0.67, P<0.01). There was a trend for acute rCBF>DWI mismatch volume to overestimate infarct expansion between the acute and outcome study (P=0.06). Infarct expansion was underestimated by acute rCBV>DWI mismatch (P<0.001). When rMTT lesions included tissue with moderately prolonged transit times (mean delay 4.3 seconds, signal intensity values 50% to 70%), infarct expansion was overestimated. In contrast, when rMTT lesions were restricted to more severely prolonged transit times (mean delay 6.1 seconds, signal intensity >70%), these regions progressed to infarction in all except 1 patient, but infarct expansion was underestimated (P<0.001). CONCLUSIONS: The acute rCBF lesion most accurately identified tissue in the PWI>DWI mismatch region at risk of infarction. Color-thresholded PWI maps show potential for use in an acute clinical setting to prospectively predict tissue outcome.


Subject(s)
Brain Infarction/pathology , Magnetic Resonance Imaging/methods , Perfusion/methods , Stroke/complications , Acute Disease , Aged , Brain/blood supply , Brain/pathology , Brain Infarction/etiology , Cerebrovascular Circulation , Color , Female , Humans , Male , Middle Aged , Stroke/physiopathology
16.
Neuropsychology ; 15(4): 568-75, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11761046

ABSTRACT

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory.


Subject(s)
Attention/physiology , Mental Recall/physiology , Parietal Lobe/physiology , Prefrontal Cortex/physiology , Retention, Psychology/physiology , Verbal Learning/physiology , Adult , Brain Mapping , Dominance, Cerebral/physiology , Female , Hippocampus/physiology , Humans , Image Processing, Computer-Assisted , Male , Reference Values , Tomography, Emission-Computed
18.
Neurology ; 55(4): 498-505, 2000 Aug 22.
Article in English | MEDLINE | ID: mdl-10953180

ABSTRACT

BACKGROUND: The prognostic value of the biochemical changes seen with proton MR spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel localization. METHODS: Nineteen patients had 36 1H MRS studies, 13 patients acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels from the infarct core. Outcome measures were final infarct volume and clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale). RESULTS: Acute lactate/choline ratio correlated more strongly with clinical outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0. 96; p < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of acute lactate/choline ratio with acute DWI lesion volume improved prediction of all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In subacute and chronic infarction, both lactate/choline and NAA/choline ratios continued to correlate with outcome (p < 0.05). At the chronic stage, persistent lactate/choline ratio elevation strongly correlated with outcome measures (r = 0.71 to 0.87). CONCLUSION: Lactate/choline ratio measured in the acute infarct core by 1H MRS improves the prediction of stroke outcome and provides prognostic information complementary to DWI. Lactate/choline ratio could be used as an additional marker to select patients for acute and chronic therapies.


Subject(s)
Aspartic Acid/analogs & derivatives , Stroke/diagnosis , Stroke/pathology , Aged , Aged, 80 and over , Aspartic Acid/metabolism , Brain/metabolism , Brain/pathology , Choline/metabolism , Diffusion , Female , Humans , Infarction, Middle Cerebral Artery/diagnosis , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Linear Models , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Stroke/metabolism , Treatment Outcome
19.
Exp Aging Res ; 23(3): 287-300, 1997.
Article in English | MEDLINE | ID: mdl-9248821

ABSTRACT

Age-related deficits in memory are correlated with deficits in paradoxical sleep and poor glucose tolerance in rats. The present experiment used a longitudinal design to determine whether memory or glucose tolerance in middle-aged rats could predict deficits in memory, sleep, and glucose tolerance in old age. Correlations were obtained between spontaneous alternation scores and glucose tolerance levels in middle age (14 months) and inhibitory avoidance, daytime sleep, and glucose tolerance levels in old age (24 months). Spontaneous alternation scores, but not glucose tolerance levels, predicted performance on all 3 behavioral and biological measures in old age. Measures of functional integrity, such as memory, may be sensitive predictors of subsequent age-related change in specific cognitive and neurobiological systems.


Subject(s)
Aging/physiology , Aging/psychology , Blood Glucose/analysis , Memory Disorders/psychology , Memory , Sleep, REM , Aging/blood , Animals , Behavior, Animal , Forecasting , Male , Rats , Rats, Sprague-Dawley
20.
Behav Neural Biol ; 58(2): 125-30, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1456931

ABSTRACT

The present experiment examined anterograde and retrograde enhancement of memory storage by glucose in elderly humans. Glucose (50 g) or saccharin was administered shortly before or immediately after acquisition of a narrative prose passage. Recall was tested 24 h later. Glucose administration before or after presentation of the material to be learned significantly improved recall 24 h later compared to performance in the saccharin condition. These findings suggest that glucose retroactively enhances memory storage processing in elderly humans and that the enhancement of memory outlasts the transient elevations in blood glucose levels after glucose ingestion.


Subject(s)
Aging/psychology , Glucose/pharmacology , Memory/drug effects , Aged , Aged, 80 and over , Analysis of Variance , Blood Glucose/analysis , Female , Humans , Male , Mental Recall/drug effects , Mental Recall/physiology , Middle Aged , Retention, Psychology/drug effects , Retention, Psychology/physiology , Saccharin/pharmacology , Time Factors
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