Copyright (c) 2009 All rights reserved. http://works.bepress.com/marc_fisher Recent documents in Marc Fisher, MD en-us Sun, 31 May 2009 08:47:07 PDT 3600 http://works.bepress.com/marc_fisher/50 http://works.bepress.com/marc_fisher/50 Thu, 26 Jun 2008 07:17:30 PDT Investigating focal cerebral ischaemia requires animal models that are relevant to human stroke. This study was designed to evaluate the influence of early reperfusion and choice of rat strains on infarct volume and oedema formation. Thirty-six Wistar and Sprague-Dawley rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance imaging (MRI). Impact of rat strains: Reperfusion led to significant larger ischaemic lesion volumes in Wistar rats as compared to Sprague-Dawley rats (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led to significantly larger ischaemic lesion volumes in Sprague-Dawley rats (P<0.05). Oedema formation, however, was significantly more accentuated in Wistar rats (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in ischaemic lesion volume in Wistar rats. Oedema formation, however, was significantly reduced (P<0.0005). In Sprague-Dawley rats, reperfusion caused a significant reduction of ischaemic lesion volume (P<0.00005), but did not modify oedema formation. These findings emphasize the critical importance of rat strain differences in experimental stroke research. Maureen Walberer Animals Brain Edema *Disease Models, Animal Infarction, Middle Cerebral Artery Ischemic Attack, Transient Magnetic Resonance Imaging Rats Rats, Sprague-Dawley Rats, Wistar Reperfusion Injury Species Specificity http://works.bepress.com/marc_fisher/49 http://works.bepress.com/marc_fisher/49 Thu, 26 Jun 2008 07:17:26 PDT BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. METHODS: Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. RESULTS: Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on >15,000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/-12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. CONCLUSIONS: This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. Myzoon Ali Adolescent Adult Aged Aged, 80 and over *Archives Female Humans Internationality Male Middle Aged *Randomized Controlled Trials as Topic Stroke http://works.bepress.com/marc_fisher/48 http://works.bepress.com/marc_fisher/48 Thu, 26 Jun 2008 07:17:22 PDT Partial-volume effects (PVE) in stroke imaging could hinder proper delineation of normal, ischemic, and at-risk tissues. Cerebral-blood-flow (CBF) and apparent diffusion coefficient (ADC) were measured at high and low resolution (HR = 128 x 128, LR = 64 x 64) in focal ischemia in rats during the acute phase. The data were evaluated for PVE on ischemic tissue classification on a pixel-by-pixel basis and the misclassified pixels were quantified as ischemia progressed. The main drawbacks of high-resolution imaging are reduced temporal resolution and/or signal-to-noise ratio. The high- versus low-resolution scatterplots and histograms of pixels along the normal-abnormal boundaries in the ADC and CBF maps showed marked ischemia-related PVE. By comparison with the homologous regions in the contralateral normal hemisphere, the effect of increased noise and intrinsic tissue heterogeneity due to high resolution could be distinguished from ischemia-related PVE. Degrading the high-resolution (128 x 128) data to a 64 x 64 or 32 x 32 matrix increased the severity of PVE. Zero-filling of low-resolution (64 x 64) data to 128 x 128 also increased PVE. It was concluded that PVE: (1) misclassified substantial pixels along the normal-abnormal boundaries, (2) overestimated abnormal volumes at the expense of mostly "at-risk" and some "normal" tissues, (3) were more severe at the early time points postischemia, and (4) confounded the interpretation of the operationally defined ischemic penumbra. Hongxia Ren Animals Brain Ischemia Cerebrovascular Circulation Diffusion Magnetic Resonance Imaging Disease Models, Animal Image Processing, Computer-Assisted Male Rats Rats, Sprague-Dawley Stroke http://works.bepress.com/marc_fisher/47 http://works.bepress.com/marc_fisher/47 Thu, 26 Jun 2008 07:17:18 PDT No abstract provided. Marc Fisher Cerebrovascular Disease http://works.bepress.com/marc_fisher/46 http://works.bepress.com/marc_fisher/46 Thu, 26 Jun 2008 07:17:15 PDT Ischemic brain injury can be anticipated in a number of clinical settings such as procedures associated with a high-risk for stroke, patients with transient ischemic attacks or minor strokes who are at substantial risk for early recurrence and patients with multiple vascular risk factors with an enhanced risk for ischemic stroke over many years. In such high-risk settings, it may be possible to employ neuroprotective drugs prophylactically to reduce the extent and clinical consequences of ischemic events. The concept of prophylactic neuroprotection can be envisioned for varying time periods and with a variety of drug classes depending upon the target population. This review will focus on which target populations should be considered for prophylactic neuroprotection trials and which drugs might be used in such trials. Sean I. Savitz Brain Ischemia Cardiac Surgical Procedures Cardiovascular Diseases Humans Ischemic Attack, Transient Neuroprotective Agents Patient Selection Recurrence Risk Assessment Risk Factors Stroke Vascular Surgical Procedures http://works.bepress.com/marc_fisher/45 http://works.bepress.com/marc_fisher/45 Thu, 26 Jun 2008 07:17:11 PDT Stroke is a major public health concern with few positive phase III clinical trials and a shortage of stroke care expertise. Drug development likely can be enhanced by adapting new outcome measures and following guidelines generated by consensus groups. To enhance rates of drug implementation and to improve stroke care, some states are requiring that acute care hospitals obtain primary stroke center certification, and this mandate necessitates that smaller hospitals join larger ones in stroke care networks. Cutting-edge technology in the form of telemedicine is being implemented in stroke care networks to combat the lack of stroke care expertise by extending the availability of physician stroke expertise. The telemedicine network can be used to transmit real-time data from stroke care-certified community hospitals (spokes) to a tertiary center (hub). Telemedicine can be used to educate physicians in spoke hospitals about new stroke treatments. The advent and development of telemedicine has the potential to ensure that patients with stroke have a greater opportunity to receive the full range of therapeutic options currently available and those that will become available in the future. The implementation of future drug therapies through telemedicine-organized stroke networks will likely substantially influence the future of acute stroke therapy. Marc Fisher Humans Stroke Telemedicine http://works.bepress.com/marc_fisher/44 http://works.bepress.com/marc_fisher/44 Thu, 26 Jun 2008 07:17:06 PDT The current status of thrombolytic therapy approved by the US Food and Drug Administration is intravenous recombinant plasminogen activator given within 3 h of the onset of ischemic stroke. Intra-arterial therapy is possible for up to 6 h but is not Food and Drug Administration-approved for this purpose. Based on current radiologic methods (i.e., magnetic resonance imaging and perfusion computed tomography scans), it is being increasingly realized that the time window for effective thrombolytic therapy is variable, and salvageable tissue in the form of the ischemic penumbra may exist for longer periods of time and could therefore offer a greater time window based on these imaging studies. Development of an effective neuroprotective drug would greatly enhance the stability of the penumbra and offer further opportunities for extending the time window for reperfusion. Vasantha Padma Acute Disease Animals Diffusion Magnetic Resonance Imaging Drug Therapy, Combination Expert Testimony Fibrinolytic Agents Humans Injections, Intravenous Meta-Analysis as Topic Neuroprotective Agents Platelet Glycoprotein GPIIb-IIIa Complex Streptokinase Stroke Thrombolytic Therapy Time Factors Tissue Plasminogen Activator http://works.bepress.com/marc_fisher/43 http://works.bepress.com/marc_fisher/43 Thu, 26 Jun 2008 07:17:03 PDT The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T(2)-weighted (T(2)WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n=6) or sham operation (n=6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T(2) lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 24 h after ischemia. Transient middle cerebral artery occlusion produced lesions on DWI and PWI, which fully recovered by 30 mins after reperfusion. Ipsilesional fMRI responses to hypercapnia and forepaw stimulation were significantly impaired after ischemia and did not fully normalize until 3 and 24 h after tMCAO, respectively. No abnormalities were observed on imaging or TTC at 24 h despite significant behavioral dysfunctions including contralesional forelimb impairment and ipsilesional neglect. No MRI, behavioral, or TTC anomalies were observed in sham-operated rats. There were no significant correlations between MRI parameters, behavior, and TTC in either group. Together, these results suggest that normal findings on diffusion, perfusion, and T(2) imaging shortly after transient ischemia may not indicate normal tissue status as indicated by fMRI and behavior, which may help explain the persistence of neurologic deficits in patients with normal conventional MRI after cerebral ischemia. Kenneth M. Sicard Animals Behavior, Animal Brain Mapping Carbon Dioxide Hypercapnia Ischemic Attack, Transient Magnetic Resonance Imaging Male Motor Activity Nerve Net Oxygen Psychomotor Performance Rats Rats, Sprague-Dawley Sensation http://works.bepress.com/marc_fisher/42 http://works.bepress.com/marc_fisher/42 Thu, 26 Jun 2008 07:16:59 PDT The development of acute stroke therapies has yielded only limited success and many failures in multiple clinical trials. The target of acute stroke therapy is that portion of the ischemic region that is still potentially salvageable, i.e. the ischemic penumbra. Neuroprotective drugs have the potential to prevent a portion of the ischemic penumbra from evolving into infracted tissue and designing trials that target neuroprotective drugs at patients with persistent penumbra should enhance the likelihood of a positive outcome. Currently, diffusion and perfusion MRI has the potential to approximate the location and persistence of the ischemic penumbra and can be used in clinical trials to select appropriate patients for inclusion and to evaluate a meaningful treatment effect. Perfusion CT may also have similar capabilities. Use of these imaging modalities in clinical trials and ultimately in clinical practice will likely help in the development and utilization of novel neuroprotective drugs. Marc Fisher Animals Benzenesulfonates Brain Brain Ischemia Clinical Trials as Topic *Diffusion Magnetic Resonance Imaging Drug Design Humans *Magnetic Resonance Angiography Neuroprotective Agents Patient Selection Recombinant Proteins Stroke Time Factors Tissue Plasminogen Activator *Tomography, X-Ray Computed http://works.bepress.com/marc_fisher/41 http://works.bepress.com/marc_fisher/41 Thu, 26 Jun 2008 07:16:54 PDT The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Atherothrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (P = .24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention. Marc Fisher Brain Ischemia Clinical Trials as Topic Drug Therapy, Combination Humans Platelet Aggregation Inhibitors Randomized Controlled Trials as Topic Risk Factors Thrombosis Ticlopidine *Treatment Outcome